WorldWideScience

Sample records for bioclim deliverable d1

  1. Bioclim Deliverable D1: environmental change analysis

    International Nuclear Information System (INIS)

    The BIOCLIM project on modelling sequential Biosphere systems under Climate change for radioactive waste disposal is part of the EURATOM fifth European framework programme. The project was launched in October 2000 for a three-year period. The project aims at providing a scientific basis and practical methodology for assessing the possible long term impacts on the safety of radioactive waste repositories in deep formations due to climate and environmental change. The project brings together a number of representatives from both European radioactive waste management organisations which have national responsibilities for the safe disposal of radioactive waste, either as disposers or regulators, and several highly experienced climate research teams. In particular, BIOCLIM aims to address the important objective of how to represent the development of future biosphere systems by addressing both how to model long-term climate change, the relevant environmental consequences of such changes and the implementation of a sequential approach to such changes. The results from the development of this sophisticated approach will be of great benefit for improving long term radiological impact calculations and the information presented in a safety case. Simulations will be conducted to represent the time series of long-term climate in three European areas within which disposal sites may be established (i.e. Central/Southern Spain, Northeast of France and Central Britain). Two complementary strategies will provide representations of future climate predictions together with associated vegetation patterns using either an analysis of distinct climate states or a continuous climate simulation over at least one glacial-interglacial cycle and possibly for other selected periods over the next 1,000,000 years. These results will be used to derive the characteristics of possible future human environments (i.e. biosphere systems) through which radionuclides, emerging from the repository, may

  2. Bioclim Deliverable D7: continuous climate evolution scenarios over western Europe (1000 km scale)

    International Nuclear Information System (INIS)

    The overall aim of BIOCLIM is to assess the possible long term impacts due to climate change on the safety of radioactive waste repositories in deep formations. This aim is addressed through the following specific objectives: - Development of practical and innovative strategies for representing sequential climatic changes to the geosphere-biosphere system for existing sites over central Europe, addressing the timescale of one million years, which is relevant to the geological disposal of radioactive waste. - Exploration and evaluation of the potential effects of climate change on the nature of the biosphere systems used to assess the environmental impact. - Dissemination of information on the new methodologies and the results obtained from the project among the international waste management community for use in performance assessments of potential or planned radioactive waste repositories. A key point of the project is therefore to develop strategies for representing sequential long-term climatic changes by addressing time scales of relevance to geological disposal of solid radioactive wastes. The integrated strategy, which first step is described in this deliverable (D7), consists of building an integrated, dynamic climate model, to represent all the known important mechanisms for long term climatic variations. The time-dependent results will then be interpreted in terms of regional climate using rule-based and statistical down-scaling approaches. Therefore, the continuous simulation of the climate evolution of the next 200 000 years selected for study is a major objective of the BIOCLIM project. This requires models that account for the simultaneous evolution of the atmosphere, biosphere, land-ice and the ocean. To be able to perform several 200 000-yearlong transient climate simulations, the models have to include all these components, but also need to be simple enough to run fast. Therefore, climate models of intermediate complexity have been chosen to

  3. Bioclim Deliverable D6b: application of statistical down-scaling within the BIOCLIM hierarchical strategy: methods, data requirements and underlying assumptions

    International Nuclear Information System (INIS)

    identified, together with the additional issues which arise in applying these techniques to output from the BIOCLIM simulations. This preliminary work is described in this BIOCLIM technical note. It provides an overview of statistical down-scaling methods, together with their underlying assumptions and advantages/disadvantages. Specific issues relating to their application within the BIOCLIM context (i.e., application to the IPSLCM4D snapshot simulations) are identified, for example, the stationarity issue. The predictor and predictand data sets that would be required to implement these methods within the BIOCLIM hierarchical strategy are also outlined, together with the methodological steps involved. Implementation of these techniques was delayed in order to give priority to the application of the rule-based down-scaling method developed in WP3 to WP2 EMIC output (see Deliverable D8a). This task was not originally planned, but has allowed more comprehensive comparison and evaluation of the BIOCLIM scenarios and down-scaling methods to be undertaken

  4. 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.

  5. Bioclim Deliverable D4/5: global climatic characteristics, including vegetation and seasonal cycles over Europe, for snapshots over the next 200,000 years

    International Nuclear Information System (INIS)

    The aim of the BIOCLIM project is to develop and present techniques that can be used to develop self-consistent patterns of possible future climate changes over the next million years (climate scenarios), and to demonstrate how these climate scenarios can be used in assessments of the long-term safety of nuclear waste repository sites. Within the project, two strategies are implemented to predict climate change. The first is the hierarchical strategy, in which a hierarchy of climate models is used to investigate the evolution of climate over the period of interest. These models vary from very simple 2-D and threshold models, which simulate interactions between only a few aspects of the earth system, through general circulation models (GCMs) and vegetation models, which simulate in great detail the dynamics and physics of the atmosphere, ocean, and biosphere, to regional models, which focus in particular on the European region and the specific areas of interest. The second strategy is the integrated strategy, in which intermediate complexity climate models are developed, and used to consecutively simulate the development of the earth system over many millennia. Although these models are relatively simple compared to a GCM, they are more advanced than 2D models, and do include physical descriptions of the biosphere, cryo-sphere, atmosphere and ocean. This deliverable, D4/5, focuses on the hierarchical strategy, and in particular the GCM and vegetation model simulation of possible future climates. Deliverable D3 documented the first step in this strategy. The Louvain-la-Neuve 2-D climate model (LLN-2D) was used to estimate (among other variables) annual mean temperatures and ice volume in the Northern Hemisphere over the next 1 million years. It was driven by the calculated evolution of orbital parameters, and plausible scenarios of CO2 concentration. From the results, 3 future time periods within the next 200,000 years were identified as being extreme, that is either

  6. Bioclim Deliverable D2: consolidation of needs of the European waste management agencies and the regulator of the consortium

    International Nuclear Information System (INIS)

    period, with particular emphasis on the last glacial cycle. The data and information collated in this report for three of these countries (France, Spain and the United Kingdom) will be used within BIOCLIM to guide the development of down-scaling rules for regional climate characteristics and thereby to provide a basis for linking climate model output to system descriptions required for the purposes long-term safety assessment. In each case, the description begins with a summary of the present-day characteristics of the regions/sites of interest, categorized under the following headings: site location and the geology of the region; human communities and land use; topography; climate; litho-stratigraphy; surface water bodies; and biota These site descriptions are then followed by a detailed presentation of the information base that has enabled palaeo-reconstructions of environmental change to be made within each country. The intention is that, by correlating these reconstructions with the global climate record, it will be possible to develop down-scaling procedures that allow the projected effects of future global climate change to be reflected in assumptions about biosphere conditions relevant to long-term radiological safety assessments. Key outputs from the palaeo-environmental analysis for each selected region include: - a narrative description of the sequence of climate change at a regional scale, expressed in terms of simple climate parameters, such as the estimated mean annual temperature, associated with defined time periods. - associated descriptions of environmental change, taking into account the effects on hydrology, soils and vegetation. - identification of key environmental properties associated with a range of 'typical' conditions that have prevailed in different regions of Europe during the last glacial-interglacial cycle. Additional information for the Czech Republic has also been summarised for interest and comparison. Because the information described

  7. Deliverable D1.1 Go-Lab learning spaces specification

    OpenAIRE

    De Jong, Ton

    2013-01-01

    The current deliverable presents a set of initial specifications of the Go-Lab learning spaces, which is the interface that students see and use when learning with a Go-Lab online lab. These specifications are based on an overview of the literature on the use of cycles in inquiry learning and of the guidance that can be given to students involved in an inquiry process with online labs. The current deliverable is organized as follows: We start with summarizing the main learning goals for learn...

  8. Bioclim Deliverable D10 - 12: development and application of a methodology for taking climate-driven environmental change into account in performance assessments

    International Nuclear Information System (INIS)

    The BIOCLIM project on modelling sequential Biosphere systems under Climate change for radioactive waste disposal is part of the EURATOM fifth European framework programme. The project was launched in October 2000 for a three-year period. The project aims at providing a scientific basis and practical methodology for assessing the possible long term impacts on the safety of radioactive waste repositories in deep formations due to climate and environmental change. Five work packages have been identified to fulfill the project objectives: - Work package 1 will consolidate the needs of the European agencies of the consortium and summarize how environmental change has been treated to date in performance assessments. - Work packages 2 and 3 will develop two innovative and complementary strategies for representing time series of long term climate change using different methods to analyse extreme climate conditions (the hierarchical strategy) and a continuous climate simulation over more than the next glacial-interglacial cycle (the integrated strategy). - Work package 4 will explore and evaluate the potential effects of climate change on the nature of the biosphere systems. - Work package 5 will disseminate information on the results obtained from the three year project among the international community for further use. The output from the climate models developed and applied in WP2 and WP3 has been interpreted in WP4 ('Biosphere system description') in terms of model requirements for the post-closure radiological performance assessment of deep geological repositories for radioactive wastes, in order to develop a methodology to demonstrate how biosphere systems can be represented in the long-term. The work undertaken in WP4 is described in this report. This report describes the methodology used for identification and characterisation of specific climate states and transitions between those climate states. It also covers the application of those methods in the context of

  9. Bioclimate and city planning - open space planning

    Science.gov (United States)

    Mertens, Elke

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

  10. Wavetrain 2 : Deliverable 19

    DEFF Research Database (Denmark)

    Chozas, Julia Fernandez; Raventos, Alex

    in these areas in order to propose specific policies in case the impacts are negative or to increase their visibility in case they are positive and, of course, to monitor its development. This deliverable focuses on tools and methodologies that have been used or developed by Wavetrain2 fellows Alex Raventos (Wav...

  11. 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...

  12. Wavetrain 2 : Deliverable 28

    DEFF Research Database (Denmark)

    Chozas, Julia Fernandez

    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......9 and D19. The first case study looks into the impact of integrating of wave energy into electricity markets. From the results it is expected that the costs of balancing wave power are smaller than those faced currently by wind power, and that any combination of wave technologies and wave and wind...... 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...

  13. 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...

  14. Bioclimate analysis of Mountain Bjelašnica

    Directory of Open Access Journals (Sweden)

    Šušnjar Sanda

    2014-01-01

    Full Text Available The main task of this paper was to assess weather suitability on Bjelasnica Mountain for optimal function of a human organism. Also, this paper represents weather classification for certain types of recreation and sport's activities. For the purpose of bioclimate analyses it has been used Model “MENEX”. This paper deals with the assessment of heat exchange between man and its environment. Research is based on a meteorological data from 2000 to 2010. The aim of a research was to determine periods in year on mountain Bjelasnica with optimal climate conditions for recreation and living but also to define periods with mostly unsuitable weather conditions, except for healthy and well adapted persons and specific type of activities.

  15. 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.

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

    NARCIS (Netherlands)

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

    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

  17. [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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

    2015-12-01

    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.

  3. 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 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...... Framework forms the common structure for the work and results of this deliverable. The deliverable furthermore discusses work preparation as an important activity in extended enterprise planning. In this relation different forms of work preparation are introduced and discussed leading to a specific...

  4. 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. PMID:26694490

  5. Instruments for evaluating inquiry experiences, skills and societal responsibility - initial : Deliverable No. D1.2

    NARCIS (Netherlands)

    Vries, Bregje de

    2015-01-01

    The Ark of Inquiry project aims to build a scientifically literate and responsible society through inquiry-based science education. The project seeks to expand young people's awareness of Responsible Research and Innovation (RRI) by disseminating engaging inquiry activities across Europe. Teachers a

  6. Instruments for evaluating inquiry experiences, skills and societal responsibility - initial: Deliverable No. D1.2

    OpenAIRE

    Vries, Bregje de

    2015-01-01

    The Ark of Inquiry project aims to build a scientifically literate and responsible society through inquiry-based science education. The project seeks to expand young people's awareness of Responsible Research and Innovation (RRI) by disseminating engaging inquiry activities across Europe. Teachers are trained to motivate and support their pupils in doing inquiry.

  7. Specification of support systems in Ark of Inquiry - initial: Deliverable D1.4

    OpenAIRE

    Siiman, Leo; Mäeots, Mario; Vries, Bregje de; Veermans, Koen

    2015-01-01

    The Ark of Inquiry project aims to build a scientifically literate and responsible society through inquiry-based science education. The project seeks to expand young people's awareness of Responsible Research and Innovation (RRI) by disseminating engaging inquiry activities across Europe. Teachers are trained to motivate and support their pupils in doing inquiry.

  8. 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...

  9. 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.

  10. Disseny i optimització d'una casa bioclimàtica alpina

    OpenAIRE

    Llovera Massana, Jordi

    2009-01-01

    La present tesi doctoral correspon a l'estudi i optimització energètica d'una casa solar i bioclimàtica situada en una zona amb clima alpí, on la temperatura mínima exterior és de -12ºC. Es tracta d'un habitatge unifamiliar, situat a la població d'Engordany, al Principat d'Andorra, a 1260 metres sobre el nivell del mar.L'habitatge es va construir els anys 1999 - 2000 amb tots els critèris de sostenibilitat del moment, i s'ha habitat des de llavors.Es tracta d'un edifici solar passiu i actiu, ...

  11. 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

  12. QUEST2: Release 1: Project plan deliverable set

    Energy Technology Data Exchange (ETDEWEB)

    Braaten, F.D.

    1995-02-10

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

  13. QUEST2: Release 1: Project plan deliverable set

    International Nuclear Information System (INIS)

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

  14. Leveraging the Deliverance Phenomenon: Penteco/Charismatic Vista.

    Science.gov (United States)

    Asamoah, Moses Kumi

    2016-10-01

    This article reflects on the deliverance concept within Classical Pentecostalism and Neo-Pentecostalism against historical and contemporary considerations. The research design combined ethnography and case study. Participant observation and in-depth interviews were used for data collection. Findings include: overstretched demonic mentality; the notion that the Penteco/Charismatic believer cannot be possessed but could be harassed by demons; and dehumanizing situations inherent in deliverance practice. It is recommended that sanity, care and collaboration be established amongst deliverance practitioners, psychologists, psychiatrists, professional counsellors as well as other business experts to ensure a holistic deliverance practice and also to enhance the dignity and value of the deliverance ministry in Ghana and Africa at large. PMID:26912091

  15. Vegetation-Soil-Active Layer Relationships Along a Low-Arctic Bioclimate Gradient, Alaska

    Science.gov (United States)

    Walker, D. A.; Jia, G. J.; Epstein, H. E.; Shiklomanov, N.; Nelson, F.; Hinzman, L. D.; Romanovsky, V. E.

    2002-12-01

    Northern Alaska has three of five Arctic bioclimate subzones, which are representative of the circumpolar Low Arctic. This portion of the Arctic has more or less continuous tundra plant cover and well-developed moss canopies. We examined the biomass and remotely sensed spectral properties of the vegetation canopy, active-layer thickness, and the soil properties at 21 sites on the Arctic Slope and Seward Peninsula of Alaska. The sites were grouped into three bioclimate subzones according the summer warmth at the sites. The summer warmth index (SWI) is the sum of the mean monthly temperatures greater than 0 degrees C. Subzone C, the coldest subzone, occurs in a narrow strip along the northern coast of the Alaska. Subzone D covers most of the Arctic Coastal Plain and the northwest portion of the Seward Peninsula, and Subzone E covers most of the Foothills and most of the unforested portion of the Seward Peninsula. The SWIs in Subzones C, D, and E are generally less than 10-15 degrees C, 15-25 degrees C, and 25-35 degrees C respectively. The average active layer depths were 44, 55, and 47 cm respectively The shallow active layer in Subzone E is to a large degree a response to the denser vegetation canopies in Subzone E. Total plant biomass in Subzone C, D, and E averaged 421 g m-2, 503 g m-2, and 1178 g m-2 respectively. The much higher biomass in Subzone E was due primarily to woody shrubs (40 g m-2 in Subzone C, 51 g m-2 in Subzone D, and 730 g m-2 in Subzone E). The normalized difference vegetation index (NDVI) is one measure of greenness. Highest NDVI values were obtained from acidic tundra regions in Subzone E, and the lowest NDVI values were obtained in the nonacidic areas of Subzone C. In summary, the insulative properties of the vegetation play a very important role controlling the thickness of the active layer, and the amount of vegetation biomass differs according to summer warmth and soil properties. Acidic soils in the warmest parts of the Arctic (Subzone E

  16. The EC BIOCLIM Project (2000-2003), 5. Euratom Framework Programme - Modelling sequential biosphere systems under climate change for radioactive waste disposal

    International Nuclear Information System (INIS)

    Marianne Calvez (ANDRA, France) presented the new EC BIOCLIM project that started in 2001. Its main objective is to provide a scientific basis and practical methodology for assessing the possible long-term impacts on the safety of radioactive waste repositories in deep formations due to climate driven changes. She explained that BIOCLIM objective is not to predict what will be the future but will correspond to an illustration of how people could use the knowledge. The BIOCLIM project will use the outcomes from the Biomass project. Where Biomass considered discrete biospheres, the BIOCLIM project will consider the evolution of climate with a focus on the European climate for three regions in the United Kingdom, France and Spain. The consortium of BIOCLIM participants consists of various experts in climate modelling and various experts and organisations in performance assessment. The intent is to build an integrated dynamic climate model that represents all the important mechanisms for long-term climate evolution. The modelling will primarily address the next 200000 years. The final outcome will be an enhancement of the state-of-the-art treatment of biosphere system change over long periods of time through the use of a number of innovative climate modelling approaches and the application of the climate model outputs in performance assessments

  17. Influences Determining European Coal Seam Gas Deliverability

    Science.gov (United States)

    Clark, G.

    2009-04-01

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

  18. 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.

  19. Deliverable 3.2. EU Project Open Science Link

    OpenAIRE

    Hugelier, Sara; Janssens, Marie-Christine; Van den Boom, Freya; Verhenneman, Griet

    2015-01-01

    The objective of this deliverable is to clarify the legal state of the art and rules applicable to the OpenScienceLink project and to ensure that the development and workings of the OpenScienceLink platform are compatible with the different regulatory frameworks This deliverable should provide a clear description and explanation of the applicable legal framework to the OpenScienceLink platform, and more in general, the legal aspects of open access to research data.

  20. Actualización del Atlas Bioclimático del estado de Jalisco

    Directory of Open Access Journals (Sweden)

    Hermes Ulises Ramírez Sánchez

    2013-01-01

    Full Text Available En esta nueva versión del Atlas Bioclimático del estado de Jalisco, se hace una descripción más detallada de las condiciones climáticas por municipios del estado, ob- tenidas a partir de una metodología más actualizada y con una mayor base de datos meteorológicos, que en la versión anterior, realizada por Gómez Amador en SEMADES (2009. Se utilizaron los datos procesados de las Normales Clima- tológicas de 1971-2000 del Servicio Meteorologico Nacional (SMN de la Comisión Nacional del Agua (CONAGUA. Los mapas fueron elaborados en el sistema de información geográfica (SIG ArcGis 9.3, con temporalidad mensual y anual. Se observa que en los meses de enero a mayo el bioclima predominante en la mayoría del estado es el seco extremoso, seguido del templado y frío, pero a partir del mes de junio el dominante cambia a cálido, seguido del templado. El mes de julio vuelve a cambiar predominando el templado, seguido de los cálidos, y agosto se caracteriza por tener bioclimas cálidos; posteriormente, de septiembre a octubre se vuelven a presentar los templados seguidos de los cálidos. Finalmente en noviembre y diciembre reaparece el seco extremoso como dominante y resurgen los templados y frío. En cuanto a la distribución anual, dado que los promedios equilibran los valores extremos, la mayoría del estado presenta bioclima templado.

  1. Diseño bioclimático en Galicia : ahorro energético y confort

    OpenAIRE

    Pena Gayo, Katia

    2016-01-01

    El objeto de estudio de la presente disertación es la arquitectura bioclimática en Galicia, comunidad situada al noroeste de la península ibérica. La investigación surge fruto de una manera de entender la arquitectura como un elemento que debe relacionarse con el entorno en el que se ubica, aprovechando las condiciones del medio a su favor para generar ahorro energético y un mayor confort a sus ocupantes. El carácter limitado de recursos energéticos, junto con los problemas act...

  2. Bioconstrucción y arquitectura bioclimática para la ejecución de vivienda unifamiliar

    OpenAIRE

    LÓPEZ GARRIDO, DANIEL

    2016-01-01

    [ES] Este trabajo final de grado, estudia diferentes formas de construir una vivienda aplicando criterios de bioconstrucción y arquitectura bioclimática. Para ello se realizó la búsqueda de un solar cuya ubicación y características cumplieran los requisitos para la construcción de una vivienda de este tipo. Para el diseño de la vivienda se utilizan el mayor número de elementos naturales, reciclados o que sean altamente reutilizables y reciclables. Otro de los puntos que se ha estudiado en pro...

  3. 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.

  4. Deliverable 2.2.1 Use Scenarios in the Pilot Services

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth

    2010-01-01

    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...... 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...... the services look like and shall work at runtime. The integration work is now in progress and during the next months the design, workflow, GUI etc. for each service will be fully integrated, tested and evaluated in cooperation with the regions according to the project plan...

  5. Deliverable D1.1: Definition of boundaries and requirements for the common scale for harmonisation of skid resistance measurements

    OpenAIRE

    GREENE, Martin; VINER, Helen; Cerezo, Véronique; Kokot, Darko; Schmidt, Bjarne

    2014-01-01

    The main objective of ROSANNE is the harmonisation and standardisation of the measurement of skid resistance, noise emission and rolling resistance of road pavements. The ROSANNE project proposed that a possible way to achieve an acceptable accuracy is to restrict the range and type of devices, including operating principle and condition. In this way, different measurement classes can be introduced, associated with achieving different levels of accuracy, and where restrictions on the type of...

  6. State-of-the-art of screening methods for the rapid identification of chemicals in drinking water Deliverable D1

    OpenAIRE

    Llorca, Marta; Rodríguez-Mozaz, Sara

    2013-01-01

    The contamination of drinking water is potentially harmful and poses a risk to public health. If any observation suggests a potential contamination of drinking water, such as consumer complaints about the alteration of the water’s organoleptic properties, the appearance of health problems or an alarm triggered by sensors, a rapid identification of the hazard causing the problem is necessary. With regards to chemical contamination, EU Member States have several strategies to deal with the pres...

  7. Project management support tool implementation. DynaLearn, EC FP7 STREP project 231526, Deliverable D1.1

    NARCIS (Netherlands)

    B. Bredeweg; J. Liem

    2009-01-01

    Different project management tools have been evaluated. We have chosen several well-known, flexible and mature tools to support management activities and communication between the DynaLearn project participants. We have created a DynaLearn website for stakeholders outside the DynaLearn website. An i

  8. 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

  9. Zoneamento bioclimático da ovinocultura no Estado do Paraná

    Directory of Open Access Journals (Sweden)

    Barbosa Orlando Rus

    2001-01-01

    Full Text Available Utilizaram-se 45 fêmeas ovinas adultas (15 Hampshire Down [HD], 15 Texel [TE] e 15 Ile de France [IF], para propor um zoneamento bioclimático da ovinocultura no Estado do Paraná. Mediram-se a temperatura retal (Tr, da epiderme (Te, do interior do velo (Tiv e da superfície do velo (Tsv; a frequência respiratória (Fr; a temperatura do ar (Ta, pressão de vapor (e, velocidade do vento (v e carga térmica radiante (CTR. O Índice de Conforto Térmico utilizado foi ICT= 0,6678Ta + 0,4969e + 0,5444Tg + 0,1038v. A regressão do ICT sobre Tr mostrou efeito quadrático para as três raças. Para ICT=24,3, 27,3 e 20,6, os valores de Tr foram respectivamente: 39,10ºC para a raça HD, 39,05ºC para TE e 39,09ºC para IF, atingindo 40,40; 40,50; e 40,28ºC, respectivamente, para ICT=58. As três raças aumentaram sua Tr a partir de ICT=26, com a TE apresentando menor Tr até o valor ICT=46; neste ponto, as três raças foram semelhantes, tendo a TE apresentado maiores valores. Para ICT igual a 27,6; 29,7; e 27,0, os valores de Fr foram, respectivamente, 89,63; 77,08; e 78,77 resp./min., para as raças HD, TE e IF. A raça TE apresentou menor Fr (77,08 resp./min., para ICT=29,7 e para ICT=48, valores semelhantes aos da IF (181,96 resp./min.; a partir deste índice, passou a ser maior que as demais raças, atingindo valores de 288,66 resp./min. no ICT=56, porém inferior à HD (289,01 resp./min.. Neste índice, a raça IF foi a que apresentou a menor Fr (275,72 resp./min.. Uma extensa faixa ao longo do litoral do Estado, entrando cerca de 200 km para o interior até os limites das cidades de Castro, Telêmaco Borba, Laranjeiras do Sul e Pato Branco, permite a criação das três raças, sem exigir grandes esforços de termorregulação.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. EMGWS, D1 projectile tests

    International Nuclear Information System (INIS)

    This paper reports on the 90 mm EMGWS D1 Projectile which is an unguided projectile that is designed for launch from an Electromagnetic gun to achieve significant armor penetration. It is being developed under the broader program called Electromagnetic Gun Weapon System (EMGWS) which is sponsored by DARPA, DNA, and the U.S. Army. The 90 mm D1 Type II 'workhorse' Projectile is used to prove out material strength, fabrication techniques, and projectile structural integrity. The type II flight projectile is designed to allow maximum stress levels of 100-ksi when launched at 100-kilogees peak acceleration. The total weight of the projectile is 2.0 kg to attain a muzzle velocity of 3.0 km/s from a 9-Megajoule EM Gun. The Type II projectile configuration employs a tungsten nosetip plus 12 segmented tungsten penetrators, a two-piece aluminum discarding sabot, an aluminum pusher plate, and a nylon obturator. The pusher plate can incorporate either a solid or plasma armature

  15. 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.

  16. 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....

  17. Evaluating the Effects of Façade Greening on Human Bioclimate in a Complex Urban Environment

    Directory of Open Access Journals (Sweden)

    Britta Jänicke

    2015-01-01

    Full Text Available The evaluation of the effectiveness of countermeasures for a reduction of urban heat stress, such as façade greening, is challenging due to lacking transferability of results from one location to another. Furthermore, complex variables such as the mean radiant temperature (Tmrt are necessary to assess outdoor human bioclimate. We observed Tmrt in front of a building façade in Berlin, Germany, which is half-greened while the other part is bare. Tmrt was reduced (mean 2 K in front of the greened compared to the bare façade. To overcome observational shortcomings, we applied the microscale models ENVI-met, RayMan, and SOLWEIG. We evaluated these models based on observations. Our results show that Tmrt (MD = −1.93 K and downward short-wave radiation (MD = 14.39 W/m2 were sufficiently simulated in contrast to upward short-wave and long-wave radiation. Finally, we compare the simulated reduction of Tmrt with the observed one in front of the façade greening, showing that the models were not able to simulate the effects of façade greening with the applied settings. Our results reveal that façade greening contributes only slightly to a reduction of heat stress in front of building façades.

  18. La arquitectura popular como base de una arquitectura bioclimática. Aplicación al enfriamiento pasivo

    Directory of Open Access Journals (Sweden)

    Esteban Sáiz, José Luis

    1986-11-01

    Full Text Available In this work it is described de diversity of popular architectures that can be found in Spain due to the strong climatological influence in the different zones of the country. It is also pointed out their similarity with the architecture of other countries, independently of the connexions existing between their dwellers. The rise of new tendencies in construction has brought the need to investigate on new architectural design adapted to ambient conditions considering thermophysical conceipts, which till now were not used, since a so called bioclimatic architecture woulbe be reached.En este artículo se describe la diversidad arquitectónica popular que puede apreciarse en España debido, en parte, a la gran influencia climatológica de las diferentes regiones. Se hace resaltar la indudable similitud con otros países, de condiciones ambientales análogas, independientemente de las relaciones que hayan existido entre sus moradores. La entrada de tendencias innovadoras en la edificación ha requerido investigar sobre nuevos diseños constructivos adecuados a las condiciones ambientales y considerando conceptos termofísicos, que hasta el momento actual no se utilizaban, hasta llegar a una arquitectura que pudiéramos llamar bioclimática.

  19. Deliverable 1.2 Road safety management investigation model and questionnaire

    OpenAIRE

    Dupont, Emmanuelle; Martensen, Heike; PAPADIMITRIOU, Eleonora; YANNIS, George; MUHLRAD, Nicole; JAHI, Heikki; VALLET, Gilles; Giustiniani, Gabriele; PERSIA, Luca; BAX, Charlotte; WIJNEN, Wim; MACHATA, Klaus; BUTLER, Ilona; ZYSINSKA, Malgorzata; BARNES, Jo

    2011-01-01

    The aim of the DaCoTA Work Package 1 is to investigate road safety policy-making and management processes in Europe. In the Deliverables released previously, the Work Package 1 assessed the experts' needs in terms of road safety knowledge, data and decision support tools (Deliverable 1.1/4.1), as well as the road safety stakeholders' views (Deliverable 1.3). These two Deliverables contain information on the present and future needs and the actual availability of various types of road safety d...

  20. Natural Gas Deliverability Task Force report: A joint FERC/DOE project

    International Nuclear Information System (INIS)

    The purpose of the FERC/DOE Natural Gas Deliverability Task Force Report was threefold: (1) to review current deliverability data for utility, accuracy, and timeliness; (2) to identify mechanisms for closing significant gaps in information resulting from changing market structures; and (3) to ensure that technologies are available to meet the needs of the emerging, competitive natural gas industry

  1. 20 CFR 638.812 - State and local taxation of Job Corps deliverers.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false State and local taxation of Job Corps deliverers. 638.812 Section 638.812 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... § 638.812 State and local taxation of Job Corps deliverers. The Act provides that transactions...

  2. 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 projec&tacute;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.

  3. Contribución para la caracterización bioclimática del Norte de Portugal. La transición florística atlántico-mediterránea.

    OpenAIRE

    Martins, Alvaro R.; Crespí, Antonio L.; Castro, Adriano; Fernandes, Claúdia P.; Rocha, Joao; de Castro, Carlos; Bernardos, Sonia; Amich García, Francisco

    2008-01-01

    Contribución para la caracterización bioclimática del norte de Portugal. La transición florística atlántico-mediterránea. Este trabajo se incluye en la serie de trabajos ya iniciados por Crespí et al. (2001), con el objetivo de contribuir al conocimiento bioclimático del Norte de Portugal, a través de la información florística presente. En este sentido, y para proceder a una posible cartografia de las áreas biogeográficas naturales desde una perspectiva termopluviométrica, son ahora introduci...

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

    Science.gov (United States)

    Craft, David; Richter, Christian

    2013-01-01

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

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

    CERN Document Server

    Craft, David

    2012-01-01

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

  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. 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.

  8. Analysis within the systems development life-cycle data analysis, the deliverables

    CERN Document Server

    Rock-Evans, Rosemary

    1987-01-01

    Analysis within the Systems Development Life-Cycle: Book 1, Data Analysis-The Deliverables provides a comprehensive treatment of data analysis within the systems development life-cycle and all the deliverables that need to be collected in analysis. The purpose of deliverables is explained and a number of alternative ways of collecting them are discussed. This book is comprised of five chapters and begins with an overview of what """"analysis"""" actually means, with particular reference to tasks such as hardware planning and software evaluation and where they fit into the overall cycle. The ne

  9. 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

  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

    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....... 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...

  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. (d,1)-total labelling of graphs

    OpenAIRE

    Havet, Frédéric; Yu, Min-Li

    2002-01-01

    A $(d,1)$-total labelling of a graph $G$ is an assignment of integers to $V(G)\\cup E(G)$ such that: (i) any two adjacent vertices of $G$ receive distinct integers, (ii) any two adjacent edges of $G$ receive distinct integers, and (iii) a vertex and its incident edge receive integers that differ by at least $d$ in absolute value. The {\\it span} of a $(d,1)$-total labelling is the maximum difference between two labels. The minimum span of a $(d,1)$-total labelling of $G$ is denoted by $\\lambda_...

  13. Deliverable 4.3 Decision support guideline based on LCA and cost/efficiency assessment

    OpenAIRE

    Larsen, Henrik Fred; Hansen, Peter Augusto; Boyer-Souchet, Florence

    2010-01-01

    The environmental sustainability assessments described in this report is based on life cycle assessments (LCA) of selected waste water treatment technology (WWTT) cases included in NEPTUNE. The basic approach in these assessments (avoided against induced impacts) is described in Deliverable 4.1 (Larsen et al. 2007) and other methodological issues (e.g. normalization and weighting) in Deliverable 4.2 (Larsen et al. 2009). The basic approach is illustrated in a simplified way for the case ozona...

  14. 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

  15. 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 ...

  16. Evolution and development of a deliverability improvement program for gas storage

    International Nuclear Information System (INIS)

    With the implementation in November 1993 of FERC Order 636, the responsibilities and contractual obligations for a Gas Transmission Company operating Gas Storage have changed. Among these responsibilities is the ability to deliver gas from storage in a timely manner as specified by gas storage contracts. To ensure that their deliverability obligations are met, a program has been implemented to review well performance and to re-work wells where deliverability can economically be improved. This program is aimed at maintaining or improving deliverability from wells and monitoring their future performance. Re-working existing wells has proven to be an economically successful method of maintaining deliverability compared to drilling new wells to meet this purpose. Re-working can be broken into two groups of wells: wells that have mechanical problems that need to be corrected or wells that need some type of stimulation treatment. In developing a rework program, several things need to be addressed such as: a candidate recognition program, the design of the work to be performed, execution of that work, and the evaluation of the results obtained along with the economics. The Deliverability Improvement Program is in its third year. It has developed from a small pilot program to a substantial part of normal storage activities. The purpose of this paper is to review the processes used to find candidates to work on and an evaluation of work performed

  17. Deliverable navigation for multicriteria IMRT treatment planning by combining shared and individual apertures

    Science.gov (United States)

    Fredriksson, Albin; Bokrantz, Rasmus

    2013-11-01

    We consider the problem of deliverable Pareto surface navigation for step-and-shoot intensity-modulated radiation therapy. This problem amounts to calculation of a collection of treatment plans with the property that convex combinations of plans are directly deliverable. Previous methods for deliverable navigation impose restrictions on the number of apertures of the individual plans, or require that all treatment plans have identical apertures. We introduce simultaneous direct step-and-shoot optimization of multiple plans subject to constraints that some of the apertures must be identical across all plans. This method generalizes previous methods for deliverable navigation to allow for treatment plans with some apertures from a collective pool and some apertures that are individual. The method can also be used as a post-processing step to previous methods for deliverable navigation in order to improve upon their plans. By applying the method to subsets of plans in the collection representing the Pareto set, we show how it can enable convergence toward the unrestricted (non-navigable) Pareto set where all apertures are individual.

  18. 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...

  19. 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

  20. 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.

  1. Prediction of mass deliverability from a single wellhead measurement and geothermal inflow performance reference curves

    Energy Technology Data Exchange (ETDEWEB)

    Moya, Sara L.; Aragon, Alfonso; Iglesias, Eduardo R.; Santoyo, Edgar [Instituto de Investigaciones Electricas, Dept. de Geotermia, Temixo, Morelos (Mexico)

    1998-06-01

    We propose a method to estimate mass deliverability curves for geothermal wells from a single wellhead measurement of pressure, mass flowrate and enthalpy (P,W,h){sub wh} and the known reservoir pressure. This method takes advantage of dimensionless Geothermal Inflow Performance Relationships (Dimensionless GIPRs), which we introduced in earlier papers. One advantage of the proposed method is that it would significantly shorten flow tests needed to obtain deliverability curves. Shorter flow test would lessen costs and greatly reduce the volume of disposal fluids, with obvious ecological advantages; in some cases they could be the only economic option. We tested our method with data from a commercial geothermal well. The resulting estimated deliverability curves are well within the errors of the method used to measured the input wellhead parameters, which suggests that our method could be generally applicable. Further studies, already underway, are necessary to confirm this. (Author)

  2. Deliverable D1.2: Analysis of data from the first round of tests and initial development of the common scale

    OpenAIRE

    GREENE, Martin; VINER, Helen; Cerezo, Véronique; Schmidt, Bjarne; SCHARNIGG, Karen

    2015-01-01

    The main objective of ROSANNE is the harmonisation and standardisation of the measurement of skid resistance, noise emission and rolling resistance of road pavements. The ROSANNE project proposed that a possible way to achieve an acceptable accuracy is to restrict the range and type of devices, including operating principle and condition. In this way, different measurement classes can be introduced, associated with achieving different levels of accuracy, and where restrictions on the type of...

  3. Estimation real number of road accident casualties. SafetyNet, Building the European Road Safety Observatory, Deliverable D.1.15 : final report on task 1.5.

    NARCIS (Netherlands)

    Broughton, J. Amoros, E. Bos, N.M. Evgenikos, P. Hoeglinger, S. Holló, P. Pérez, C. & Tecl, J.

    2009-01-01

    The objective of Task 1.5 of the SafetyNet IP has been to estimate the actual numbers of road accident casualties in Europe from the CARE database by addressing two issues: • the under-reporting in national accident databases and • the differences between countries of the definitions used to classif

  4. 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...

  5. D1.1 Stakeholders Needs Regarding EA

    DEFF Research Database (Denmark)

    Ryberg, Thomas; Eleftheriou, Paraskevi; Maglavera, Stavroula;

    2009-01-01

    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...

  6. OPTIMISE - Deliverable D4.2 Deliver optimised samples made by two axis rolling to UNIVERSITY OF TWENTE, month 11

    DEFF Research Database (Denmark)

    Eriksen, Morten

    This report explains why the deliverables of optimised samples made by two axis rolling was not send to UNIVERSITY OF TWENTE.......This report explains why the deliverables of optimised samples made by two axis rolling was not send to UNIVERSITY OF TWENTE....

  7. Outlook for Alberta production and deliverability in relation to domestic and export markets of natural gas

    International Nuclear Information System (INIS)

    Cautious optimism about the deliverability of Alberta natural gas during the 1993/1994 heating season is justified. There are not likely to be the shortages of the previous winter. These predictions are based on favourable reserve and production figures together with an increase in drilling activity. There are also more disciplined contracting practices and a positive outlook for available pipeline capacity. (author)

  8. 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.

  9. Test results evaluation: Pilot evaluations Deliverable no D6.5. Final draft

    NARCIS (Netherlands)

    Hoedemaeker, D.M.; Dangelmaier, M.; Gelau, C.; Mattes, S.; Montanari, R.

    2003-01-01

    This deliverable describes the User Centred Design approach that has been adopted within the COMUNICAR project. In this design approach several iterative steps were taken to design and evaluate the multimedia Human Machine Interface that is able to manage all the information exchanges between the dr

  10. Deliverable 3.3.2 Specification of tests and test groups

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  11. 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

  12. 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...

  13. Privacy and Security Framework. OpenIoT Deliverable D522

    OpenAIRE

    Calbimonte, Jean-Paul; Riahi, Mehdi; Zaslavsky, Arkady

    2014-01-01

    This deliverable describes the Security and Privacy Framework of the OpenIoT platform, including details about its design and implementation. The aim of this framework is to ensure that Internet-Connected Objects (ICOs) contributing to the OpenIoT platform, its internal modules and external applications will communicate through secured IoT data interfaces (according to the target security/confidentiality level specified by the user). Moreover we show the feasibility of this security module ...

  14. Specification of the Legal Knowledge Interchange Format: Deliverable 1.1

    OpenAIRE

    Boer, A. de; Di Bello, M.; Berg, van den, W.; Gordon, T; Förhécz, A.; Vas, R.

    2007-01-01

    The main technical objectives of work package 1 are to develop a first version of a Legal Knowledge Interchange Format (LKIF), building upon emerging XML-based standards of the Semantic Web, including RDF and OWL, and Application Program Interfaces (APIs) for interacting with legal knowledge systems. The LKIF will apply the state of the art in the field of Artificial Intelligence and Law, taking into account business and application requirements. This deliverable reports on the specification ...

  15. OPTIMISE - Deliverable D4.3 Report on two axis rolling, month 12

    DEFF Research Database (Denmark)

    Eriksen, Morten

    This report is one of two reports which describe de deliverables on two axis rolling in the OPTIMISE project. Most of the work in this report has also been described in the sub work package reports produced during the project. The sub work package reports are WP4.1 Two axis rolling and WP4.3 Fini...... Element Modelling of two axis rolling....

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

    OpenAIRE

    Zia Haque

    2010-01-01

    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 univers...

  17. Deliverable D21.11 - Results of model tests on optimised configurations

    OpenAIRE

    Falchi, Massimo; Bugalsky, Tomasz Bugalsky; Di Felice, Fabio; Aloisio, Giovanni; Pereira, Francisco; Franchi, Stefano Ildebrando; Costanzo, Marcello; Pecoraro, Andrea; Salvatore, Francesco; Grizzi, Silvano; Nicolai, Claudia, Dr.

    2013-01-01

    Results of experimental work to evaluate design solutions aimed at improving the hydrodynamic performance of state-of-art screw propeller systems are presented. The report is written in fulfilment of the STREAMLINE Project Deliverable D21.11 `Results of model tests on optimised configurations.' The work documented herein is performed in the framework of Work Package 21, Task 21.6 in which propulsion efficiency enhancements deriving from the application of CFD- based design and numerical optim...

  18. 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.

  19. 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...

  20. 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...

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

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  2. 26 CFR 1.509(d)-1 - Definition of support

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Definition of support 1.509(d)-1 Section 1.509(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(d)-1 Definition of support For purposes...

  3. 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.

  4. 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.

  5. 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.

  6. Self-management and Optimization Framework. OpenIoT Deliverable D512

    OpenAIRE

    Calbimonte, Jean-Paul; Riahi, Mehdi; Gwadera, Robert; Guo, Tian; Podnar Zarko, Ivana; Georgoulis, Chris

    2013-01-01

    This deliverable describes the OpenIoT self-management and optimization framework, in terms of algorithms and mechanisms that it comprises as well as in terms of their implementation over the OpenIoT platform and associated cloud infrastructure. As a first step the main operations and functionalities of the OpenIoT self-management and optimization infrastructure are described and related to the structure of management operations defined in state-of-the-art frameworks for autonomic computing a...

  7. 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.

  8. Road Safety Data, Collection, Transfer and Analysis DaCoTa. Deliverable 1.2: Road safety management investigation model and questionnaire.

    OpenAIRE

    Dupont, H. Martensen, H. Papadimitriou, E. Yannis, G. Muhlrad, N. Jähi, H. Vallet, G. Giustiniani, G. Tripodi, A. Usami, D. Bax, C. Wijnen, W. Schöne, M.-L. Machata, K. Buttler, I. Zysinska, M. Talbot, R. Gitelman, V. & Hakkert, S. & Muhlrad, N. & Dupont, E. (Eds.)

    2012-01-01

    The aim of the DaCoTA Work Package 1 is to investigate road safety policy-making and management processes in Europe. In the Deliverables released previously, the Work Package 1 assessed the experts’ needs in terms of road safety knowledge, data and decision support tools (Deliverable 1.1/4.1), as well as the road safety stakeholders’ views (Deliverable 1.3). These two Deliverables contain information on the present and future needs and the actual availability of various types of road safety d...

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Temple, Brian Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Armstrong, Jerawan Chudoung [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-04-14

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

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

    International Nuclear Information System (INIS)

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

  12. Protein Kinase D1-Dependent Phosphorylation of Dopamine D1 Receptor Regulates Cocaine-Induced Behavioral Responses

    Science.gov (United States)

    Wang, Ning; Su, Ping; Zhang, Ying; Lu, Jie; Xing, Baoming; Kang, Kai; Li, Wenqi; Wang, Yun

    2014-01-01

    The dopamine (DA) D1 receptor (D1R) is critically involved in reward and drug addiction. Phosphorylation-mediated desensitization or internalization of D1R has been extensively investigated. However, the potential for upregulation of D1R function through phosphorylation remains to be determined. Here we report that acute cocaine exposure induces protein kinase D1 (PKD1) activation in the rat striatum, and knockdown of PKD1 in the rat dorsal striatum attenuates cocaine-induced locomotor hyperactivity. Moreover, PKD1-mediated phosphorylation of serine 421 (S421) of D1R promotes surface localization of D1R and enhances downstream extracellular signal-regulated kinase signaling in D1R-transfected HEK 293 cells. Importantly, injection of the peptide Tat-S421, an engineered Tat fusion-peptide targeting S421 (Tat-S421), into the rat dorsal striatum inhibits cocaine-induced locomotor hyperactivity and injection of Tat-S421 into the rat hippocampus or the shell of the nucleus accumbens (NAc) also inhibits cocaine-induced conditioned place preference (CPP). However, injection of Tat-S421 into the rat NAc shell does not establish CPP by itself and injection of Tat-S421 into the hippocampus does not influence spatial learning and memory. Thus, targeting S421 of D1R represents a promising strategy for the development of pharmacotherapeutic treatments for drug addiction and other disorders that result from DA imbalances. PMID:24362306

  13. 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)

  14. 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.

  15. Paradoxical roles of cyclin D1 in DNA stability.

    Science.gov (United States)

    Jirawatnotai, Siwanon; Sittithumcharee, Gunya

    2016-06-01

    Maintenance of DNA integrity is vital for all of the living organisms. Consequence of DNA damaging ranges from, introducing harmless synonymous mutations, to causing disease-associated mutations, genome instability, and cell death. A cell cycle protein cyclin D1 is an established cancer-driving protein. However, contribution of cyclin D1 to cancer formation and cancer survival is not entirely known. In cancer tissues, overexpression of cyclin D1 is associated with both cancer genome instability, and resistance to DNA-damaging cancer drugs. Emerging evidence indicated that cyclin D1 may play novel direct roles in regulating DNA repair. Here we provide an insight how cyclin D1 expression may contribute to DNA repair and chromosome instability, and how these functions may facilitate cancer formation, and drug resistance. PMID:27155130

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

    International Nuclear Information System (INIS)

    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. 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

  18. Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases.

    Science.gov (United States)

    Kairn, Tanya; Papworth, Daniel; Crowe, Scott B; Anderson, Jennifer; Christie, David R H

    2016-01-01

    Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beam complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging-based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor

  19. Deliverable 4.2: Methodology for including specific biological effects and pathogen aspects into LCA

    DEFF Research Database (Denmark)

    Larsen, Henrik Fred; Olsen, Stig Irving; Hauschild, Michael Zwicky;

    2009-01-01

    As described in deliverable 4.1 (Larsen et al. 2007) NEPTUNE is using two main types of life cycle impact assessment (LCIA) methodologies when doing LCA studies on the waste water treatment technologies included. The basic methodology is the well known existing EDIP97 methodology (Wenzel et al....... 1997, Hauschild and Wenzel 1998) for which the impact assessment on toxicity is PNEC based. However, in order to include the newest development on especially best available practice as regards ecotoxicity a new revised and updated EDIP 200X LCIA methodology has been developed. A first draft...... of this methodology is presented here. Furthermore, special issues related to waste water have been addressed by including novel development on LCIA methodology for possible impact from pathogens and whole effluent toxicity. Special focus is also allocated to micropollutants with specific toxic mode of action (i...

  20. SOFTWARE PROJECT SCOPE VERIFICATION THROUGH DELIVERABLE-ORIENTED WORK BREAKDOWN STRUCTURE

    Directory of Open Access Journals (Sweden)

    Robert T. Hans

    2013-02-01

    Full Text Available Software project scope verification is a very important process in project scope management and it needs to be performed properly so as to avoid project rework and to promote better project scope control. Moreover, software scope verification is crucial in the process of delivering exactly what the customer requested and minimizing project scope changes. Well defined software scope eases the process of scope verification and contributes to project success. Furthermore, a deliverable-oriented WBS provides a road map to a well defined software scope of work. It is on the basis of this that this paper extends the use of deliverableoriented WBS to that of scope verification process. This paper argues that a deliverableoriented WBS is a tool for software scope verification

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

    DEFF Research Database (Denmark)

    Tølle, Martin; Vesterager, Johan

    2002-01-01

    (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...... 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...... envision to do business in the future. This is followed by a description of the current business environment the company is facing, intended to give an insight in the motivation for why the enterprise pursues the vision described. This chapter concludes with a more detailed description of a vision...

  2. 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 ...

  3. 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....... The principles are also applicable for other queueing systems...

  4. A pseudoCoulombian potential in D=1 dimensional space

    International Nuclear Information System (INIS)

    In the D=1 dimensional space, we study the bound state solutions of the potential V(x)=-c/x+b/x2 (e, b>0). They occur on the right half-plane xin[0, ∞[. In the limit b→0, we recover the spectrum of the D=1 Coulomb potential. Supersymmetric properties are briefly discussed. The model is extended by considering complex coupling constants. Nonlinear effects are also treated by considering a linear energy dependence of the e coupling constant.

  5. L(d1, d2,..., dt)-Number λ(Cn; d1, d2,...,dt) of Cycles

    Institute of Scientific and Technical Information of China (English)

    GAO Zhen Bin; ZHANG Xiao Dong

    2009-01-01

    An L(d1,d2,...,dt)-labeling of a graph G is a function f from its vertex set V(G) to the set {0, 1,..., k} for some positive integer k such that {f(x) - f(y)| ≥ di, if the distance between vertices x and y in G is equal to i for i = 1,2,...,t. The L(d1,d2,...,dt)-number λ(G;d1,d2,... ,dt) of G is the smallest integer number k such that G has an L(d1,d2,... ,dt)labeling with max{f(x)|x ∈ V(G)} = k. In this paper, we obtain the exact values for λ(Cn; 2, 2,1) and λ(Cn; 3, 2, 1), and present lower and upper bounds for λ(Cn; 2,..., 2,1,..., 1)

  6. Cyclin D1, Id1 and EMT in breast cancer

    Directory of Open Access Journals (Sweden)

    Lehn Sophie

    2011-09-01

    Full Text Available Abstract Background Cyclin D1 is a well-characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in 'inhibitor of differentiation 1' (ID1 gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT. Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. Methods Protein and gene expression of ID1, CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western blot and qPCR. Cell migration and promoter occupancy were monitored by transwell and ChIP assays, respectively. Gene expression was analysed from publicly available datasets. Results The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1low/ID1high tumours displayed increased expression of EMT markers and were associated with reduced recurrence free survival. Finally, a greater percentage of CCND1low/ID1high tumours were found in the EMT-like 'claudin-low' subtype of breast cancer than in other subtypes. Conclusions These results indicate that increased migration of MDA-MB-231 cells following

  7. Geoscience for Alaska's D-1 Lands: A preliminary report

    Science.gov (United States)

    Schmidt, Jeanine M.; Gamble, B.M.; Labay, K.A.

    2007-01-01

    Purpose of This Report This interim report follows from the June 2006 recommendations to Congress by the BLM concerning disposition of the d-1 lands. That report recommended lifting of a significant number of d-1 PLOs, through the ongoing land management process within the BLM (e.g. resource management planning areas), or through Congressional action. The strategic actions outlined in this document refer only to Federal lands under US Bureau of Land Management (BLM) jurisdiction that 1) are affected by temporary withdrawals from mineral entry and mineral leasing by PLOs made pursuant to the Section 17(d)(1) of the ANCSA; 2) have been identified by the BLM as candidates for possible lifting of these PLOs and restrictions (U.S. Bureau of Land Management, 2006); and 3) lie outside of current Federal parks, preserves, monuments, refuges, reserves, wilderness areas and military installations that are closed to mineral entry, because within those areas the potential lifting of the d-1 restrictions has no practical effect. The resulting lands discussed here comprise approximately 121,000 km2 (29.9 million acres) of Alaska (Table 1) that, pending final resolution of Native and State land claims, will or may remain under Federal (BLM) control, and could be opened to mineral entry. For the purposes of this report, only these 29.9 million acres will hereafter be referred to as 'd-1' lands. This report gives a brief overview of the spatial distribution and physiographic setting, mineral occurrences, and mineral resource potential of the d-1lands. It outlines further geoscience information which could be compiled, collected, and evaluated in order to make a more accurate and comprehensive examination of the potential for undiscovered, locatable mineral resources on these Federal lands. This information is intended to provide guidance to USGS program managers and Federal land managers on matters of future exploration, access needs, and consequences of land status changes.

  8. A pseudoCoulombian potential in D=1 dimensional space

    Energy Technology Data Exchange (ETDEWEB)

    Lombard, R J [Groupe de Physique theorique, Institut de Physique Nucleaire, 91406 Orsay Cedex (France); Mezhoud, R [Faculty of Sciences, Boumerdes University, 35000 Boumerdes (Algeria); Yekken, R [Institut de Physique, USTHB Bab Ezzouar, Alger (Algeria)], E-mail: lombard@ipno.in2p3.fr, E-mail: mezhoudreda@yahoo.fr, E-mail: rabia_yek@yahoo.fr

    2009-12-15

    In the D=1 dimensional space, we study the bound state solutions of the potential V(x)=-c/x+b/x{sup 2} (e, b>0). They occur on the right half-plane xin[0, {infinity}[. In the limit b{yields}0, we recover the spectrum of the D=1 Coulomb potential. Supersymmetric properties are briefly discussed. The model is extended by considering complex coupling constants. Nonlinear effects are also treated by considering a linear energy dependence of the e coupling constant.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  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. JPI Oceans Concerted support action deliverable 5.1 'Mapping and preliminary analysis of policy needs for evidence'

    OpenAIRE

    Redd, Thomas; Wood, Jacky; Foden, Jo; Mills, David; Bonne, Wendy

    2014-01-01

    CSA Oceans preliminary analysis of policy needs CSA Oceans has completed its preliminary analysis of policy needs. The public deliverable reports on the current status of marine and maritime policies relevant to JPI Oceans and identifies examples of science to policy mechanisms. The report uses stakeholder input to identify the needs of different policies to fulfil their objectives. One of the underlying issues is thought to be a lack of integration between marine and maritime activi...

  17. 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.

  18. 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)1 requirements. The FCT-QAPD interfaces with SNL approved Quality Assurance Program Description (SNL-QAPD)2 as explained in the Sandia National Laboratories QA Program Interface Document for FCT Activities3 (Interface Document). As part of the annual work planning process, FCT work package managers designate a Quality Rigor Level (QRL) for each work package. This designation is concurred in by the SNL FCT QA Point of Contact (POC). The QRLs (QRL 1, 2, 3, and Lab/Participant), and the review requirements for each QRL are specified in the FCT-QAPD and the Interface Document section 10. Sections 11 and 12 of the Interface Document specify a milestone deliverable review and submittal requirements. Upon completion, SNL FCT milestone deliverables are uploaded to the Performance Information Collection System-Nuclear Energy (PICS:NE). Deliverables uploaded to PICS:NE are automatically copied to the FCT Document Management System (FCT-DMS) in conformance with the FCT Records Management Plan4, because PICS:NE is not intended for document management. Note that Sandia’s Enterprise Information Management Services (EIMS), is the records management system for SNL documents, not FCT-DMS.

  19. D1 dopamine receptor activity of anti-parkinsonian drugs.

    Science.gov (United States)

    Fici, G J; Wu, H; VonVoigtlander, P F; Sethy, V H

    1997-01-01

    Clinical and preclinical investigations suggest that stimulation of D1 dopamine receptors may be responsible for dyskinesias induced by dopamine agonist treatment of Parkinson's Disease (PD), and that these dyskinesias may be decreased by treatment with a D1 antagonist (clozapine). Therefore, the effects of dopamine agonists and antagonists have been investigated in a primary cerebellar granule cell model of cAMP formation that seems to be highly responsive to the D1 receptors. SKF 38393, lisuride, apomorphine, pergolide, dopamine, bromocriptine and 7-OH-DPAT showed concentration-dependent increases in cAMP formation, with EC50s (in microM) of 0.013, 0.053, 0.25, 1.04, 2.18, 50.9 and 54.4, respectively. SKF 38393, apomorphine, dopamine and pergolide had similar intrinsic activity (100%), while the intrinsic activities of 7-OH-DPAT, bromocriptine and lisuride were 28.0%, 20.7% and 17.2%, respectively. SCH 23390, a selective D1 dopamine receptor antagonist, blocked an increase in cAMP formation produced by EC50 concentrations of all of the dopamine agonists investigated in this study. Clozapine concentration-dependently blocked pergolide-induced increases in cAMP and was approximately 1700-fold less potent than SCH 23390 (IC50: 0.97 microM and 0.56 nM, respectively). U-95666A (1-1000 microM), selective for the D2 receptors, showed no significant effect on cAMP, while pramipexole (0.1-100 microM), a D3 preferring agonist, did not elevate cAMP. These data suggest that primary cerebellar granule cell cultures are an excellent model for measuring D1 dopamine receptor-mediated changes in cellular cAMP. The results are discussed with reference to the relationship between the D1 receptor-stimulated increase in cAMP formation and the induction of dyskinesia in humans by these anti-parkinsonian drugs. PMID:9126882

  20. 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.

  1. 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.

  2. Redesign of Glenn Research Center D1 Flywheel Module

    Science.gov (United States)

    Jansen, Ralph H.; Wagner, Robert C.; Duffy, Kirsten P.; Hervol, David S.; Storozuk, Ronald J.; Dever, Timothy P.; Anzalone, Salvatore M.; Trudell, Jeffrey J.; Konno, Kevin E.; Kenny, Andrew

    2002-01-01

    Glenn Research Center has completed the redesign of the D1 flywheel module. The redesign includes a new rotor with a composite rim, motor/generator, touchdown bearings, sensors, and a magnetic actuator. The purpose of the relatively low cost module upgrade is to enable it to continuously operate throughout its speed range of 0 to 60,000 RPM. The module will be used as part of a combined attitude control and bus regulation experiment.

  3. Underground storage tank 431-D1U1, Closure Plan

    Energy Technology Data Exchange (ETDEWEB)

    Mancieri, S.

    1993-09-01

    This document contains information about the decommissioning of Tank 431-D1U1. This tank was installed in 1965 for diesel fuel storage. This tank will remain in active usage until closure procedures begin. Soils and ground water around the tank will be sampled to check for leakage. Appendices include; proof of proper training for workers, health and safety briefing record, task hazard analysis summary, and emergency plans.

  4. Conclusions and summaries of feed-back comments from participating countries. Deliverable D18

    International Nuclear Information System (INIS)

    Deliverable 18 is focused on the principal components of risk communication strategies and based on actual experiences from different cultural settings in relation to nuclear waste management (NWM) issues. Essentially it describes how the ideas were presented and developed within the 3rd year of the ARGONA project, in sub-workpackage 4.1. The intention of this work was to delineate good risk communication approaches across national borders, as well as to specify the circumstances that require more specific and unique national or group considerations. Our aim was to provide an in-depth analysis of societal patterns and trends regarding the management of nuclear wastes on the basis of a number of individual participants' understanding and open discussion of the issue between themselves and across the heterogeneous groups represented. To meet these goals we involved a number of stakeholders from ARGONA participating countries (UK, Sweden, Slovakia, Czech Republic) in a one-day focus group in September 2009. Their task was to provide comments on the strategies for risk communication that have emanated from the various interest groups within the different countries. Another reason for their engagement was to elicit their comments on the central features of existing materials and thus point to any strengths and weaknesses associated with various risk communication techniques and more composite risk communication strategies. The results obtained reflect the opinions and sentiments related to risks and safety of various groups in civil society within the participating countries. We also believe that the work performed in D18 fits well into the transparency framework provided in the RISCOM model. This model was successfully used in Sweden and has actually also been applied in the Czech Republic within the ARGONA project. It was shown that if applied in practice this model has a high potential for improving transparency related to consensus building in the NWM area

  5. 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.

  6. EINS D1.2 Roadmap for an economic theory for information networks

    NARCIS (Netherlands)

    Cave, J; Salamatian, Kave; Antoniadis, Panos; Dini, Paolo; Griffiths, Frances; Hutchinson, David; Papadimitriou, Dimitri; Tiropanis, Thanassis; Papaioannou, Thanassis; Scharnhorst, Andrea; Akdag Salah, A.

    2015-01-01

    This Deliverable collects a series of research perspectives on the economic analysis of Internet-related phenomena. In the spirit of multidisciplinarity that pervades the project, many of these contributions reflect the disciplinary perspectives of consortium members. They illustrate the two-way rel

  7. Areas of interest of potential users for naturalistic observation studies. PROmoting real Life Observations for Gaining Understanding of road user behaviour in Europe PROLOGUE, Deliverable D1.2.

    NARCIS (Netherlands)

    Schagen, I.N.L.G. van Craen, S. de Nes, N. van & Eenink, R.

    2010-01-01

    Identification of the interests of potential users is crucial for setting up a useful and broadly supported large-scale naturalistic driving (ND) study. This report describes the results of a survey amongst 72 road transport professionals in Europe from different organisation types that aimed at ide

  8. 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.

  9. SiteChar. Characterisation of European CO2 storage. Deliverable D8.1. Qualitative and quantitative social site characterisations

    Energy Technology Data Exchange (ETDEWEB)

    Brunsting, S.; Pol, M.; Paukovic, M. [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. [Scottish Carbon Capture and Storage SCCS, Edinburg, Scotland (United Kingdom); Hepplewhite, F.; Loveridge, R. [Energy Markets Unit, Scottish Government, Edinburg, Scotland (United Kingdom); Mazurowski, M.; Polak-Osiniak, D. [Polish Oil and Gas Company PGNiG, Warszawa (Poland); Rybicki, C. [AGH University of Science and Technology, Krakow (Poland)

    2012-10-15

    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 engagement process does increase the likelihood thereof. Social site characterisation can be used as an instrument to explore, plan and evaluate a process of active and constructive local stakeholder engagement in a prospective CCS project as a parallel activity to technical site characterisation. It roughly consists of a formative research phase to get acquainted with the area followed by a series of public information and engagement activities. This deliverable presents results from the first phase for the social site characterisations of a prospective CCS site in Poland (onshore) and the UK (offshore), using qualitative as well as quantitative research methods, as a first step to planning of local public engagement activities and evaluation of these activities that will be undertaken by this consortium at both sites in the near future. Although the term social site characterisation actually refers to the entire process of formative research and subsequent public outreach, and hence to the complete package of awareness work undertaken as part of SiteChar, in the present deliverable the term only refers to the formative research activities as undertaken up to now and as described in this deliverable. The qualitative part of the social site characterisation consisted of (1) a description of relevant social site characteristics such as local history; (2) interviews with relevant local stakeholders; (3) a media analysis of local newspapers. The quantitative part of the social site characterisation consisted of surveys using representative samples to characterise the local population in terms of awareness, knowledge and perceptions of CCS, felt involvement in decision making, extent of local activism, level of trust in representatives and

  10. 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...

  11. 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.

  12. The embedding of $\\mathcal{O}_{d_1d_2}$ into $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$

    OpenAIRE

    Chambers, Amy B.

    2014-01-01

    As a particular example of a general theorem presented in \\cite{me}, there is a conditional expectation from the tensor product of Cuntz algebras, $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$, onto the Cuntz algebra $\\mathcal{O}_{d_1d_2}$. Motivated by this example, we examine the embedding of $\\mathcal{O}_{d_1d_2}$ in $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$, first by examining the index of the conditional expectation mentioned, and then by expressing $\\mathcal{O}_{d_1}\\otimes\\mathcal{O...

  13. 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.

  14. D1.3. Report on the role of main stakeholders in crisis situations

    OpenAIRE

    Blaha, Manfred; Bonnamour, Marie-Christine; Miskuf, Robert; De Vries, David; Groenendaal, Jelle; Helsloot, Ira

    2015-01-01

    EXECUTIVE SUMMARY The purpose of deliverable 1.3 “Report on the role of main stakeholders in crisis situations” is for COSMIC to examine the role of the different emergency response agencies before and during crisis situations, and to focus on the communication challenges they face during those situations. The presentation of two case studies illustrates the differences between various services throughout the European Union and identifies common challenges. This is followed by ...

  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. Plasticity in D1-like receptor expression is associated with different components of cognitive processes.

    Directory of Open Access Journals (Sweden)

    Christina Herold

    Full Text Available Dopamine D1-like receptors consist of D1 (D1A and D5 (D1B receptors and play a key role in working memory. However, their possibly differential contribution to working memory is unclear. We combined a working memory training protocol with a stepwise increase of cognitive subcomponents and real-time RT-PCR analysis of dopamine receptor expression in pigeons to identify molecular changes that accompany training of isolated cognitive subfunctions. In birds, the D1-like receptor family is extended and consists of the D1A, D1B, and D1D receptors. Our data show that D1B receptor plasticity follows a training that includes active mental maintenance of information, whereas D1A and D1D receptor plasticity in addition accompanies learning of stimulus-response associations. Plasticity of D1-like receptors plays no role for processes like response selection and stimulus discrimination. None of the tasks altered D2 receptor expression. Our study shows that different cognitive components of working memory training have distinguishable effects on D1-like receptor expression.

  17. 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

  18. 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

  19. Synthesis gas demonstration plant, Phase I. Deliverable No. 7C: current working estimates for Phases II and III allowing 7% annual escalation

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    The Current Working Estimates for Phases II and III, as described in the Statement of Work for Contract No. ET-77-C-01-2577, were submitted to DOE on October 31, 1979, as Deliverable No. 23. These estimates were presented as fully forward priced based on best estimate escalation assumptions developed by Grace and exhibited in detail in an appendix to Deliverable No. 23. At the request of DOE, the estimate of capital and operating costs applicable to Phases II and III have been recalculated using a seven percent annual escalation factor for all categories of cost. Utilizing the base dollar (February 15, 1979) estimates in accordance with Deliverable No. 23 and allowing the requested seven percent escalation, the Phases II and III costs are summarized. While details of the forward pricing, allocation and cost sharing estimates are presented herein, it should be noted that data supportive of the base capital and operating costs, together with the approved Allocation Method, were presented in Deliverable No. 23 and are not repeated here. Any review of this document should recognize that the seven percent escalation which serves as the basis is as directed by DOE and does not represent Grace's best estimate of the expected costs of Phases II and III. (LTN)

  20. 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.

  1. Data of evolutionary structure change: 1D1SB-1QLJA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D1SB-1QLJA 1D1S 1QLJ B A GTAGKVIKCKAAVLWEQKQPFSIEEIEVAPPKTKEVRIK...EMTGNNVGYTFEVIGHLETMIDALASCHMNYGTSVVVGVPPSAKMLTYDPMLLFTGRTWKGCVFGGLKSRDDVPKLVTEFLAKKFDLDQL...ne>GLY CA 380 VAL CA 377 1QL...J A 1QLJA LKNDLSMPRGT

  2. Data of evolutionary structure change: 1AP2D-1QLRD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AP2D-1QLRD 1AP2 1QLR D D EVQLQQSGAELVRPGASVKLSCTASGFNIKDDFMHWVKQ...RPEQGLEWIGRIDPANDNTKYAPKFQDKATIIADTSSNTAYLQLSSLTSEDTAVYYCARREVYSYYSPLDVWGAGTTVTVPSGS------------------------...--------------------------------------------------------------- EVQLQQWGAGLLKPSETLSLTCAVYGGSFSD...EEE EEEEE 0 1QLR D 1QLRD GEINH-SGST

  3. Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis

    OpenAIRE

    Xiong, Jin; Bauer, Carl E.; Pancholy, Anjly

    2007-01-01

    Haem d1 is a unique tetrapyrrole molecule that serves as a prosthetic group of cytochrome cd1, which reduces nitrite to nitric oxide during the process of denitrification. Very little information is available regarding the biosynthesis of haem d1. The extreme difficulty in studying the haem d1 biosynthetic pathway can be partly attributed to the lack of a theoretical basis for experimental investigation. We report here a gene cluster encoding enzymes involved in the biosynthesis of haem d1 in...

  4. 26 CFR 1.45D-1 - New markets tax credit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true New markets tax credit. 1.45D-1 Section 1.45D-1... Computing Credit for Investment in Certain Depreciable Property § 1.45D-1 New markets tax credit. (a) Table...) Allowance of credit (1) In general (2) Credit allowance date (3) Applicable percentage (4) Amount paid...

  5. 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...

  6. Effects of D1 receptor knockout on fear and reward learning.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2016-09-01

    Dopamine signaling is involved in a variety of neurobiological processes that contribute to learning and memory. D1-like dopamine receptors (including D1 and D5 receptors) are thought to be involved in memory and reward processes, but pharmacological approaches have been limited in their ability to distinguish between D1 and D5 receptors. Here, we examine the effects of a specific knockout of D1 receptors in associative learning tasks involving aversive (shock) or appetitive (cocaine) unconditioned stimuli. We find that D1 knockout mice show similar levels of cued and contextual fear conditioning to WT controls following conditioning protocols involving one, two, or four shocks. D1 knockout mice show increased generalization of fear conditioning and extinction across contexts, revealed as increased freezing to a novel context following conditioning and decreased freezing to an extinguished cue during a contextual renewal test. Further, D1 knockout mice show mild enhancements in extinction following an injection of SKF81297, a D1/D5 receptor agonist, suggesting a role for D5 receptors in extinction enhancements induced by nonspecific pharmacological agonists. Finally, although D1 knockout mice show decreased locomotion induced by cocaine, they are able to form a cocaine-induced conditioned place preference. We discuss these findings in terms of the role of dopamine D1 receptors in general learning and memory processes. PMID:27423521

  7. 关于图的L(d1,d2)-标号问题%The L(d1, d2)-Labeling Problem on Graphs

    Institute of Scientific and Technical Information of China (English)

    邵振东; 刘家壮

    2006-01-01

    The L(2, 1)-labeling is formulated from the frequency assignment problem. We study the L(d1, d2)- labeling which is a generalization of the L(2, 1)-labeling. Vertex 2-coloring, 2-chromatic number and other related concepts are firstly defined, and the upper bound for 2-chromatic number is given; a very general relationship between λd1 ,d2 (G) and minimum degree δ(G) and maximum degree △(G) is then derived; finally, the upper bounds of L(d1, d2)-labelings of general and planar graphs are given.%图的L(2,1)-标号问题是由频率分配问题归结而来,本文研究作为L(2,1)-标号问题的推广的L(d1,d2)-标号问题.首先定义了顶点2-着色,2-色数及其它有关概念,给出了2-色数的上界.然后得出了λd1,d2(G)与δ(G)和△(G)的一般关系.最后得出了一般图与平面图的λd1,d2(G)的上界.

  8. 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

    2014-01-01

    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. PMID:24599455

  9. Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas

    International Nuclear Information System (INIS)

    Purpose: We recently reported that overexpression of epidermal growth factor receptor (EGFR) positively correlated with radioresistance of murine carcinomas. Because cyclin D1 is a downstream sensor of EGFR activation, the present study investigated whether a relationship exists between the extent of cyclin D1 expression and in vivo radiocurability of murine tumors. We further investigated the influence of radiation on cyclin D1 expression and the expression of p27, an inhibitor of the cyclin D1 downstream pathway, as well as the relationship of these molecular determinants to cell proliferation and induced apoptosis in tumors exposed to radiation. Methods and Materials: Cyclin D1 expression was assayed in nine carcinomas syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse as assessed by TCD50. The expression of cyclin D1 and p27 proteins was determined by Western blotting. Cell proliferative activity in tumors was determined by proliferating cell nuclear antigen (PCNA) immunochemistry. The effect of irradiation on the expression of cyclin D1 or p27 proteins and on PCNA positivity was determined in the radiosensitive OCa-I and in the radioresistant SCC-VII tumors. Results: Cyclin D1 expression varied among tumors by 40-fold, and its magnitude positively correlated with poorer tumor radioresponse (higher TCD50 values). The level of cyclin D1 expression paralleled that of EGFR. A 15-Gy dose reduced constitutive expression of cyclin D1 in the radiosensitive OCa-I tumors, but had no influence on expression of cyclin D1 in the radioresistant SCC-VII tumors. In contrast, 15 Gy increased the expression of p27 in radiosensitive tumors and reduced it in radioresistant tumors. Radiation induced no significant apoptosis or change in the percentage of PCNA-positive (proliferating) cells in SCC-VII tumors with high cyclin D1 levels, but it induced significant apoptosis and a decrease in the percentage of proliferating

  10. Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

    Institute of Scientific and Technical Information of China (English)

    Peng Gao; Geng-Yin Zhou; Yuan Liu; Jin-Song Li; Jun-Hui Zhen; Yin-Ping Yuan

    2004-01-01

    AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma.METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma.RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively.The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples.There was no significant correlation between cyclin D1protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (x2= 0.038,0.059,0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (x2 = 3.92, P<0.05).CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.

  11. 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.

  12. 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...

  13. Overview of resulting tools, guidelines, and instruments. IN-SAFETY Workpackage 3: New models, tools and guidelines for road safety assessment, Deliverable 3.4.

    OpenAIRE

    Dijkstra, A. Bald, S. Benz, T. & Gaitanidou, E. (eds.)

    2009-01-01

    Road safety will most probably be influenced by introducing Advanced Driver Assistance Systems (ADAS) or Intelligent Vehicle Safety Systems (IVSS). The effects of these systems on road safety can be assessed in different ways. This document gives a short overview of methodologies which allow for assessing road safety effects (Chapter 2), This Deliverable gives an overview of the outcome of work package 3 of IN-SAFETY. Two methodologies have basically been applied: • simulation model • risk an...

  14. 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.

  15. 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.

  16. 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.

  17. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Science.gov (United States)

    2010-04-01

    ... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund shares... issued by a money market fund; and (2) A money market fund, any principal underwriter thereof, and...

  18. Cyclin D1 Gene Expression in Oral Mucosa of Tobacco Chewers”–An Immunohistochemical Study

    OpenAIRE

    Basnaker, Maharudrappa; SP, Srikala; BNVS, Satish

    2014-01-01

    Objective: The objective of the present study was to evaluate the expression of cyclin D1 in normal oral mucosa of both non tobacco habituated and tobacco habituated individuals histologically and also compare and correlate cyclin D1 expression with histopathologically confirmed cases of oral squamous cell carcinomas.

  19. Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Huang Shiang-Fu

    2012-02-01

    Full Text Available Abstract Background Cyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC is inconclusive. Methods A total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC. The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity. Results Overexpression of cyclin D1 was found in 97 (36.7% OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002, tumor cell differentiation (P = 0.031 and tumor stage (P = 0.051, but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002 and overall survival (OS, P Conclusion Cyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.

  20. Effect of postharvest storage on the expression of the apple allergen Mal d 1

    NARCIS (Netherlands)

    A.I. Sancho; R. Foxall; T. Browne; R. dey; L. Zuidmeer; G. Marzban; K.W. Waldron; R. van Ree; K. Hoffmann-Sommergruber; M. Laimer; E.N.C. Mills

    2006-01-01

    Consumption of fresh apples can cause allergy in susceptible individuals. A competitive enzyme-linked immunosorbent assay ( ELISA) has been developed to determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1). The ELISA was able to rank ten cultivars according to their Mal d 1 con

  1. 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...

  2. 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.

  3. 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)...

  4. 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...

  5. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Science.gov (United States)

    2010-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Destruction or disposition of livestock because of disease. (a) The destruction occurring in a taxable year to which the Internal Revenue Code of 1954 applies, of livestock by, or on account of, disease, or the...

  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. Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1.

    Science.gov (United States)

    Ito, Hidenori; Morishita, Rika; Nagata, Koh-Ichi

    2016-08-01

    Dysbindin-1 (dystrobrevin binding protein-1, DTNBP1) is now widely accepted as a potential schizophrenia susceptibility gene and accumulating evidence indicates its functions in the neural development. In this study, we tried to identify new binding partners for dysbindin-1 to clarify the novel function of this molecule. When consulted with BioGRID protein interaction database, cyclin D3 was found to be a possible binding partner for dysbindin-1. We then examined the interaction between various dysbindin-1 isoforms (dysbindin-1A, -1B and -1C) and all three D-type cyclins (cyclin D1, D2, and D3) by immunoprecipitation with the COS7 cell expression system, and found that dysbindin-1A preferentially interacts with cyclin D1. The mode of interaction between these molecules was considered as direct binding since recombinant dysbindin-1A and cyclin D1 formed a complex in vitro. Mapping analyses revealed that the C-terminal region of dysbindin-1A binds to the C-terminal of cyclin D1. Consistent with the results of the biochemical analyses, endogenous dysbindin-1was partially colocalized with cyclin D1 in NIH3T3 fibroblast cells and in neuronal stem and/or progenitor cells in embryonic mouse brain. While co-expression of dysbindin-1A with cyclin D1 changed the localization of the latter from the nucleus to cytosol, cyclin D1-binding partner CDK4 inhibited the dysbindin-cyclin D1 interaction. Meanwhile, depletion of endogenous dysbindin-1A increased cyclin D1 expression. These results indicate that dysbindin-1A may control the cyclin D1 function spatiotemporally and might contribute to better understanding of the pathophysiology of dysbindin-1-associated disorders. PMID:27130439

  8. Galectin-3 and cyclin D1 expression in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gołecki Marcin

    2011-10-01

    Full Text Available Abstract Introduction Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC. We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue. Materials and methods We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90. years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA. Results Galectin-3 expression was positive in 18 cases (38.29% and cyclin D1 in 39 (82.97%. We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07 and cyclin D1 expression was higher in this group (p = 0.080. We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061 and we revealed negative

  9. 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.

  10. 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.

  11. Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL

    Directory of Open Access Journals (Sweden)

    Yonggang Yao

    2016-01-01

    Full Text Available Background/Aims: Oxidized low-density lipoprotein (Ox-LDL induces macrophage proliferation, a key physiological process which leads to atherosclerosis. The aim of this study was to determine the effects of dopamine D1-like receptors on macrophage proliferation induced by Ox-LDL. Methods: The expression of dopamine D1-like receptors was determined by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR and immunoblotting. The effect of D1-like receptors on macrophage proliferation induced by Ox-LDL was measured by 3[H]-thymidine incorporation and cell number count. Results: Dopamine D1-like receptors were present in macrophages as determined by immunohistochemistry, RT-PCR and immunoblotting. A D1-like receptor agonist, fenoldopam, which by itself had no effect on macrophage proliferation, inhibited the stimulatory effect of Ox-LDL on macrophage proliferation. This was further confirmed by the D1-like receptor antagonist SCH 23390 blocking the effect of fenoldopam, thereby indicating that the fenoldopam action was receptor specific. Phosphatidylinositol 3-kinase (PI3K/Akt and mitogen-activated protein kinase (MAPK/ERK pathways were also involved in the proliferative effect of Ox-LDL because in the presence of PI3K/Akt or MAPK/ERK inhibitors, LY294002 or PD98059, the stimulatory effects of Ox-LDL were blocked. Moreover, the stimulatory effect of Ox-LDL on the phosphorylation of ERK and Akt was significantly reduced by fenoldopam in macrophages. Additional experiments found that both D1 and D5 receptor expression was lower in the peritoneal macrophages from Apolipoprotein E-deficient mice compared to the control C57Bl/6J mice. Conclusions: Macrophages express D1-like receptors. The activation of the D1-like receptors significantly inhibits Ox-LDL-induced macrophage proliferation, possibly through the inhibition of the PI3K/Akt and MAPK/ERK signaling pathways.

  12. 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.

  13. The expression of MIF and Cyclin D1 in hepatocellular carcinoma%MIF和Cyclin D1在肝细胞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    夏金堂; 伍兆锋; 李雯; 赖越元; 赵杰; 徐晨; 王花; 滕元; 李瑜元

    2009-01-01

    Objective To investigate the expression of macrophage migration inhibition factor (MIF) and cell cycle regulating factor Cyclin D1 in hepatocellular carcinoma tissue and the interaction between MIF and Cyclin D1 in hepatocellular carcinoma cell cycle controlling. Methods Using quantitative real-time PCR and Western blotting to detect mRNA and protein expression of MIF and Cyelin DI in HCC tissues and tumor adjacent tissues. Specific small interfering RNA(siRNA) targeting MIF gene was transfccted at doses of 50 nmol/L and 100 nmoL/L into HCC cell lines of PLC and HepG2 with lipofeetamine 2000 methods to knockdown the expression of M1F gene and to investigare the the interaction between M1F and Cyclin D1. Results MIF and Cyclin D1 protein and mRNA were overexpressed in HCC tumor tissues. The relative expression of MIF,Cyclin D1 protein and mRNA were 0.825±0.13,0.843± 0.104 and 7.31±1.85 folds、4.27±1.05 folds, compared with the tumor adjacent tissues (FMIF= 15.5, P<0.01;FCyclin D1=87.5,P <0.01). In MIF siRNA treated PLC and HepG2 cells, MIF mRNA down regulation 71.2%±7.2%, 87.4%±2.9% ,74.3%±8.9% and 88.4%±4.6% respectively (FPLC = 315.5 ,P < 0.01 ; FHepG2= 201.2 P < 0.01). While MIF protein expression were significandy reduced to 0.33±0.03,0.11±0.02, 0.81±0.08 and 0.36±0.02 in a dose-dependent manner (FPLC= 43.9, P <0.01 ;FHepG2 = 133.4 P <0.01). Cyclin D1 mRNA was significantly down-regnlated in MIF siRNA treated PLC and HepG2 cell lines when compared with control group(P <0.01). In 50 nmol/L and 100 nmol/L groups, Cyclin DI mRNA levels were respectively decreased by 68.2%±3% and 78.1%±1.4% in PLC cell, 65.8%±4.7% and 77.3%±2.6% in HepG2 cell (FPLC= 1569, P < 0.01 ; FHepG2= 480.4, P <0.01). Compared with control groups, Cyclin D1 protein levels significantly reduced to 0.28±0.06、0.15±0.03 and 0.44 ±0.04、0.13±0.02 in the PLC and HepG2 after M IF siRNA treatment(FPLC= 35.5, P < 0.01 ; FHepG2 = 114.7, P < 0.01). Conclusions MIF and Cyclin D1 m

  14. 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.

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

    International Nuclear Information System (INIS)

    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

  16. 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.

  17. Origin of the Scaling Constant "d" = 1.7 in Item Response Theory.

    Science.gov (United States)

    Camilli, Gregory

    1994-01-01

    Describes the scaling constant "d" = 1.702, used in Item Response Theory, which minimizes the maximum difference between the normal and logistic distribution functions. Recapitulates the theoretical and numerical derivation of "d" given by D. Haley (1952). (SLD)

  18. 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。

  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 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.

  1. Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats

    OpenAIRE

    Fu, Jinjuan; Han, Yu; Wang, Hongyong; Wang, Zhen; Liu, Yukai; Chen, Xingjian; Cai, Yue; Guan, Weiwei; Yang, Di; Asico, Laureano D.; ZHOU, Lin; Jose, Pedro A; Zeng, Chunyu

    2014-01-01

    Background Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear. Methods Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myog...

  2. 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.

  3. Effect of postharvest storage on the expression of the apple allergen Mal d 1.

    Science.gov (United States)

    Sancho, Ana I; Foxall, Robert; Browne, Tom; Dey, Rickmer; Zuidmeer, Laurian; Marzban, Gorji; Waldron, Keith W; van Ree, Ronald; Hoffmann-Sommergruber, Karin; Laimer, Margit; Mills, E N Clare

    2006-08-01

    Consumption of fresh apples can cause allergy in susceptible individuals. A competitive enzyme-linked immunosorbent assay (ELISA) has been developed to determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1). The ELISA was able to rank ten cultivars according to their Mal d 1 content (between 3.8 and 72.5 mug/g pulp). For the first time, it has been demonstrated that growing conditions and postharvest storage, using three different treatments over a 5 month period in 2 consecutive years, increase Mal d 1 expression at a translational and transcriptional level (3.5- and 8.5-fold under controlled atmosphere storage). Expression of three major Mal d 1 isoforms was observed by real-time polymerase chain reaction over the 5 month storage period, and Mal d 1.02 was the most highly expressed isoform. In conclusion, Mal d 1 gene expression was significantly increased during modified atmosphere storage. Individuals suffering from birch pollen-apple allergy syndrome might experience fewer problems consuming freshly picked apples.

  4. Coexpression of cyclin D1 and alpha-internexin in oligodendroglial tumors.

    Science.gov (United States)

    Matsumura, Nozomi; Nobusawa, Sumihito; Ikota, Hayato; Hirato, Junko; Hirose, Takanori; Yokoo, Hideaki; Nakazato, Yoichi

    2015-10-01

    Oligodendroglial tumors with neuronal differentiation cases have been reported in recent studies. Oligodendrocyte precursor cells (OPCs) give rise to both oligodendrocytes and neurons; however, little is known about the association between OPCs and oligodendroglial tumors with neuronal differentiation. Previously, we observed the coexpression of cyclin D1, one of the OPC markers, and alpha-internexin (INA) in oligodendroglial tumor cells. INA is a neuronal marker, and has been indicated as an immunohistochemical surrogate of chromosome 1p/19q co-deletion in oligodendroglial tumors. In this study, we investigated the expression status in 83 gliomas immunohistochemically, and found that cyclin D1-positive cells were commonly detected in gliomas. There was no correlation between the cyclin D1 and Ki-67 labeling indices, suggesting an unrecognized role of cyclin D1 other than a cell cycle regulator in gliomas. Cyclin D1/INA double-positive cells were consistently observed in oligodendroglial tumors regardless of histological grade. In 2 cases of oligodendroglioma with neuronal differentiation, the tumor cells of neuronal morphology showed higher expression of INA, suggesting INA expression may be associated with a bona fide neuronal phenotype. The prevalence of cyclin D1/INA double-positive cells is a distinct feature of oligodendroglial tumors. This new characteristic finding may have practical utility in glioma classification. PMID:26233522

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer.

    Science.gov (United States)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing; Sun, Shiqin; Chen, Xiangmei; Lu, Fengmin

    2014-04-25

    Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168-245 nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers. PMID:24704453

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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...

  19. Reappraising striatal D1- and D2-neurons in reward and aversion.

    Science.gov (United States)

    Soares-Cunha, Carina; Coimbra, Barbara; Sousa, Nuno; Rodrigues, Ana J

    2016-09-01

    The striatum has been involved in complex behaviors such as motor control, learning, decision-making, reward and aversion. The striatum is mainly composed of medium spiny neurons (MSNs), typically divided into those expressing dopamine receptor D1, forming the so-called direct pathway, and those expressing D2 receptor (indirect pathway). For decades it has been proposed that these two populations exhibit opposing control over motor output, and recently, the same dichotomy has been proposed for valenced behaviors. Whereas D1-MSNs mediate reinforcement and reward, D2-MSNs have been associated with punishment and aversion. In this review we will discuss pharmacological, genetic and optogenetic studies that indicate that there is still controversy to what concerns the role of striatal D1- and D2-MSNs in this type of behaviors, highlighting the need to reconsider the early view that they mediate solely opposing aspects of valenced behaviour. PMID:27235078

  20. 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 .

  1. Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingjie [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Li, Xuejun, E-mail: xjli@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Huang, Chuanshu, E-mail: chuanshu.huang@nyumc.org [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States)

    2012-09-01

    Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. -- Highlights: ► SAHA inhibits cell transformation in Cl41 cells. ► SAHA suppresses Cyclin D1 protein expression. ► SAHA decreases cyclin D1 mRNA stability.

  2. 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.

  3. 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.

  4. 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

  5. D1/D5 system and Wilson Loops in (Non-)commutative Gauge Theories

    OpenAIRE

    Takahashi, Hidenori; Nakajima, Tadahito; Suzuki, Kenji

    2002-01-01

    We study the behavior of the Wilson loop in the (5+1)-dimensional supersymmetric Yang-Mills theory with the presence of the solitonic object. Using the dual string description of the Yang-Mills theory that is given by the D1/D5 system, we estimate the Wilson loops both in the temporal and spatial cases. For the case of the temporal loop, we obtain the velocity dependent potential. For the spatial loop, we find that the area law is emerged due to the effect of the D1-branes. Further, we consid...

  6. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Sun, Shiqin [College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319 (China); Chen, Xiangmei, E-mail: xm_chen6176@bjmu.edu.cn [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Fengmin [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-04-25

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  7. 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。

  8. c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

    Institute of Scientific and Technical Information of China (English)

    Meryem G(u)ller; Kahina Toualbi-Abed; Agnès Legrand; Laurence Michel; Alain Mauviel; Dominique Bernuau; Fanny Daniel

    2008-01-01

    AIM: To investigate the effect of stable c-Fos over-expression on immortalized human hepatocyte (IHH) proliferation. METHODS: IHHs Stably transfected with c-Fos (IHH-Fos) or an empty "vector (IHH-C) were grown in me-dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, to-tal and phosphorylated GSK-3?and epidermal growth factor receptor (EGF-R) were assayed by Western blot-ting. Analysis of Cyclin D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction (PCR) analysis. Stability of Cyclin D1 was studied by cycloheximide blockade experiments. RESULTS: Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora-tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress-ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK-3? A kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com-pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH-Fos by treatment with AG1478, a specific EGF-R tyro-sine kinase inhibitor, prevented the phosphorylation of GSK-3?induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION: Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new

  9. The elements of human cyclin D1 promoter and regulation involved

    OpenAIRE

    Guo, Zhi-yi; Hao, Xiao-hui; Tan, Fei-Fei; Pei, Xin; Shang, Li-Mei; Jiang, Xue-lian; Yang, Fang

    2011-01-01

    Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the pr...

  10. The panel of egg allergens, Gal d 1-Gal d 5: Their improved purification and characterization

    DEFF Research Database (Denmark)

    Jacobsen, B.; Hoffmann-Sommergruber, K.; Have, T. T.;

    2008-01-01

    Egg proteins represent one of the most important sources evoking food allergic reactions. In order to improve allergy diagnosis, purified and well-characterized proteins are needed. Although the egg white allergens Gal d 1, 2, 3 and 4 (ovomucoid, ovalbumin, ovotransferrin, and lysozyme) are comme......Egg proteins represent one of the most important sources evoking food allergic reactions. In order to improve allergy diagnosis, purified and well-characterized proteins are needed. Although the egg white allergens Gal d 1, 2, 3 and 4 (ovomucoid, ovalbumin, ovotransferrin, and lysozyme...

  11. A Note on the Generalized Ramanujan-Nagell Equation D1x2 + D2=Pn%关于广义Ramanujan-Nagell方程D1 x2+D2=pn的一点注记

    Institute of Scientific and Technical Information of China (English)

    乐茂华; 陈锡庚

    2001-01-01

    设r,D1,D2是适合gcd(D1,D2)=1的正整数,又设p是适合p| D1D2的奇素数.本文证明了:如果D1+D2=4Pr且方程D1x2+D2=Pn有正整数解(x,n),则3pr-D2=±2,而且此时该方程仅有解(x,n)=(|pr-D2|/2,3r).

  12. 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

  13. Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Michael eAvery

    2015-03-01

    Full Text Available The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC.

  14. 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"

  15. Path Integral Evaluation of the Free Propagator on the (D-1)-dimensional Pseudosphere

    OpenAIRE

    Wospakrik, Hans J.

    1999-01-01

    We present an explicit path integral evaluation of the free Hamiltonian propagator on the (D-1)-dimensional pseudosphere, in the horicyclic coordinates, using the integral equation method. This method consists in deriving an integral equation for the propagator that turns out to be of Abel's type.

  16. 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.

  17. Data of evolutionary structure change: 1BU1D-1QLYA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BU1D-1QLYA 1BU1 1QLY D A -IIVVALYDYEAIHHEDLSFQKGDQMVVLEESG-EWWKA...RSLATRKEGYIPSNYVARV- LKKVVALYDYMPMNANDLQLRKGDEYFILEESNLPWWRARDK-NGQEGYIPSNYVTEAE -...A 277 TRP CA 316 LYS CA 330 ALA CA 359 1QL...Y A 1QLYA LEESNLPWW...21347046 2.311821937561035 1 1QL

  18. Frontal-subcortical circuits in obsessive-compulsive disorder: role of the dopamine D1 receptor

    International Nuclear Information System (INIS)

    Full text: Obsessive-Compulsive Disorder (OCD) is an anxiety disorder which is increasingly being recognised as a neurobiological disorder. While serotonergic mechanisms have been proposed, the major competing theory in the pathophysiology of OCD involves the neurotransmitter dopamine. The Dopamine D1 receptor is implicated in OCD following the finding of specific spatial working memory abnormalities in a series of neuropsychological studies. Spatial working memory is known to depend on the integrity of D1 receptor function in the Dorso-lateral Prefrontal Cortex (DLPFC) of primates. This study aims to examine the role of dopamine in patients with OCD and in particular to test the hypothesis that there is an upregulation of dopamine D1 receptors in the DLPFC which correlates with spatial working memory deficits in OCD. Three OCD patients and three normal controls underwent Positron Emission Tomography (PET) following intravenous injection of the D1 antagonist PET ligand SCH23390. Reconstructed PET images were co registered with subject Magnetic Resonance Images (MRI) and regions of interest drawn manually. We will present the analysis of the Binding Potentials of SCH23390 in the regions of interest of the first three OCD patients and compare them with three normal control patients. In conclusion Dopamine-Serotonergic interactions are involved in the pathophysiology of OCD. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. The dopamine D1 receptor agonist SKF-82958 effectively increases eye blinking count in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Kiyoshi, Akihiko; Murai, Takeshi; Nakako, Tomokazu; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Ogi, Yuji; Ikeda, Kazuhito

    2016-03-01

    Eye blinking is a spontaneous behavior observed in all mammals, and has been used as a well-established clinical indicator for dopamine production in neuropsychiatric disorders, including Parkinson's disease and Tourette syndrome [1,2]. Pharmacological studies in humans and non-human primates have shown that dopamine agonists/antagonists increase/decrease eye blinking rate. Common marmosets (Callithrix jacchus) have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field due to their more developed prefrontal cortex than rodents, easy handling compare to other non-human primates, and requirement for small amounts of test drugs. In this study, we evaluated the effects of dopamine D1-4 receptors agonists on eye blinking in common marmosets. Our results show that the dopamine D1 receptor agonist SKF-82958 and the non-selective dopamine receptor agonist apomorphine significantly increased common marmosets eye blinking count, whereas the dopamine D2 agonist (+)-PHNO and the dopamine D3 receptor agonist (+)-PD-128907 produced somnolence in common marmosets resulting in a decrease in eye blinking count. The dopamine D4 receptor agonists PD-168077 and A-41297 had no effect on common marmosets' eye blinking count. Finally, the dopamine D1 receptor antagonist SCH 39166 completely blocked apomorphine-induced increase in eye blinking count. These results indicate that eye blinking in common marmosets may be a useful tool for in vivo screening of novel dopamine D1 receptor agonists as antipsychotics. PMID:26675887

  20. ( sup 125 I)(+)FISCH: A new CNS D-1 dopamine receptor imaging ligand

    Energy Technology Data Exchange (ETDEWEB)

    Billings, J.; Kung, M.P.; Chumpradit, S.; Pan, S.; Kung, H.F. (Univ. of Pennsylvania, Philadelphia (USA))

    1989-01-01

    Radiolabeling and in vitro and in vivo evaluation of an iodinated benzazepine: ({sup 125}I)FISCH 7-Chloro-8-hydroxy-1-(4{prime}-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, as a potential imaging agent for CNS D-1 dopamine receptors in animals, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats. The striatum/cerebellum ratio was 2.50 at 60 min after the injection. The regional distribution in rat brain, as measured by ex vivo autoradiography, displayed highest uptake in the regions of the striatal complex and the substantia nigra, regions known to have a high concentration of D-1 dopamine receptors. Furthermore, this localized regional cerebral distribution was blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist. The in vitro binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 {plus minus} 0.15 nM. Competition data (in vitro) showed the following rank order of potency: SCH-23390 > ({plus minus})IBZP >> apomorphine > WB 4101 > ketanserin {approximately} spiperone. The preliminary data suggest that this analog of SCH-23390 shows similar selectivity for the CNS D-1 receptor.

  1. 26 CFR 7.57(d)-1 - Election with respect to straight line recovery of intangibles.

    Science.gov (United States)

    2010-04-01

    ... THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1976 § 7.57(d)-1 Election with respect to straight line recovery of intangibles. (a) Purpose... Tax Reform Act of 1976. Under this election taxpayers may use cost depletion to compute straight...

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Cocaine Seeking and Taking: Role of Hippocampal Dopamine D1-like Receptors

    Science.gov (United States)

    Xie, Xiaohu; Wells, Audrey M.; Fuchs, Rita A.

    2015-01-01

    Despite the well-documented involvement of dopamine D1-like receptor stimulation in cocaine-induced goal-directed behaviors, little is known about the specific contribution of D1-like receptor populations in the dorsal hippocampus (DH) to drug context-induced cocaine-seeking or drug-reinforced instrumental behaviors. To investigate this question, rats were trained to lever press for un-signaled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behavior (non-reinforced lever responding) was then assessed in the previously cocaine-paired and extinction contexts. SCH23390-induced D1-like receptor antagonism in the DH, but not the overlying trunk region of the somatosensory cortex, dose-dependently inhibited drug context-induced cocaine-seeking behavior, without altering cocaine-reinforced instrumental responding, cocaine intake, food-reinforced instrumental responding, or general motor activity, relative to vehicle treatment. These findings suggest that D1-like receptor stimulation in the DH is critical for the incentive motivational effects and/or memory of cocaine-paired contextual stimuli that contribute to drug-seeking behavior. PMID:24655895

  7. 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. PMID:25135633

  8. 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.

  9. Resolvin D1 protects the liver from ischemia/reperfusion injury by enhancing M2 macrophage polarization and efferocytosis.

    Science.gov (United States)

    Kang, Jung-Woo; Lee, Sun-Mee

    2016-09-01

    Resolution of inflammation is an active process involving a novel category of lipid factors known as specialized pro-resolving lipid mediators, which includes Resolvin D1 (RvD1). While accumulating evidence suggests that RvD1 counteracts proinflammatory signaling and promotes resolution, the specific cellular targets and mechanisms of action of RvD1 remain largely unknown. In the present study, we investigated the role and molecular mechanisms of RvD1 in ischemia/reperfusion (IR)-induced sterile liver inflammation. Male C57BL/6 mice underwent 70% hepatic ischemia for 60min, followed by reperfusion. RvD1 (5, 10, and 15μg/kg, i.p.) was administered to the mice 1h before ischemia and then immediately prior to reperfusion. RvD1 attenuated IR-induced hepatocellular damage and the proinflammatory response. In purified Kupffer cells (KCs) from mice exposed to IR, the levels of M1 marker genes (Nos2a and Cd40) increased, while those of M2 marker genes (Arg1, Cd206, and Mst1r) decreased, demonstrating a proinflammatory shift. RvD1 markedly attenuated these changes. Depletion of KCs by liposome clodronate abrogated the effects of RvD1 on proinflammatory mediators and macrophage polarization. In addition, RvD1 attenuated increases in myeloperoxidase activity and Cxcl1 and Cxcl2 mRNA expression. RvD1 markedly augmented the efferocytic activity of KCs, as indicated by increases in F4/80(+)Gr-1(+) cells in the liver. However, antagonist pretreatment or gene silencing of the RvD1 receptor, ALX/FPR2, abrogated the anti-inflammatory and pro-resolving actions of RvD1. These data indicate that RvD1 ameliorates IR-induced liver injury, and this protection is associated with enhancement of M2 polarization and efferocytosis via ALX/FPR2 activation. PMID:27317426

  10. Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D1 over D2 Receptor Signaling

    Science.gov (United States)

    Park, Kicheon; Pan, Yingtian

    2013-01-01

    Dopamine increases triggered by cocaine and consequent stimulation of dopamine receptors (including D1 and D2) are associated with its rewarding effects. However, while facilitation of D1 receptor (D1R) signaling enhances the rewarding effects of cocaine, facilitation of D2R signaling decreases it, which indicates that for cocaine to be rewarding it must result in a predominance of D1R over D2R signaling. Moreover, the transition to compulsive cocaine intake might result from an imbalance between D1R and D2R signaling. To test the hypothesis that chronic cocaine use unbalances D1R over D2R signaling during cocaine intoxication, we used microprobe optical imaging to compare dynamic changes in intracellular calcium ([Ca2+]i, marker of neuronal activation) to acute cocaine in striatal D1R-EGFP and D2R-EGFP-expressing neurons between control and chronically treated mice. Chronic cocaine attenuated responses to acute cocaine in D1R (blunting Ca2+ increases by 67 ± 16%) and D2R (blunting Ca2+ decrease by 72 ± 17%) neurons in most D1R and D2R neurons (∼75%). However, the dynamics of this attenuation during cocaine intoxication was longer lasting for D2R than for D1R. Thus, whereas control mice showed a fast but short-lasting predominance of D1R over D2R signaling (peaking at ∼8 min) during acute cocaine intoxication, in chronically treated mice D1R predominance was sustained for >30 min (throughout the measurement period). Thus, chronic cocaine use dramatically reduced cocaine-induced DA signaling, shifting the balance between D1R and D2R signaling during intoxication to a predominance of D1R (stimulatory) over D2R (inhibitory) signaling, which might facilitate compulsive intake in addiction. PMID:24089490

  11. 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.

  12. 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

  13. The Mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, Function in the Endocytic Pathway, but Their Individual Loss of Function Does Not Affect Notch Signalling.

    Directory of Open Access Journals (Sweden)

    Nadja Drusenheimer

    2015-12-01

    Full Text Available CC2D1A and CC2D1B belong to the evolutionary conserved Lgd protein family with members in all multi-cellular animals. Several functions such as centrosomal cleavage, involvement in signalling pathways, immune response and synapse maturation have been described for CC2D1A. Moreover, the Drosophila melanogaster ortholog Lgd was shown to be involved in the endosomal trafficking of the Notch receptor and other transmembrane receptors and physically interacts with the ESCRT-III component Shrub/CHMP4. To determine if this function is conserved in mammals we generated and characterized Cc2d1a and Cc2d1b conditional knockout mice. While Cc2d1b deficient mice displayed no obvious phenotype, we found that Cc2d1a deficient mice as well as conditional mutants that lack CC2D1A only in the nervous system die shortly after birth due to respiratory distress. This finding confirms the suspicion that the breathing defect is caused by the central nervous system. However, an involvement in centrosomal function could not be confirmed in Cc2d1a deficient MEF cells. To analyse an influence on Notch signalling, we generated intestine specific Cc2d1a mutant mice. These mice did not display any alterations in goblet cell number, proliferating cell number or expression of the Notch reporter Hes1-emGFP, suggesting that CC2D1A is not required for Notch signalling. However, our EM analysis revealed that the average size of endosomes of Cc2d1a mutant cells, but not Cc2d1b mutant cells, is increased, indicating a defect in endosomal morphogenesis. We could show that CC2D1A and its interaction partner CHMP4B are localised on endosomes in MEF cells, when the activity of the endosomal protein VPS4 is reduced. This indicates that CC2D1A cycles between the cytosol and the endosomal membrane. Additionally, in rescue experiments in D. melanogaster, CC2D1A and CC2D1B were able to functionally replace Lgd. Altogether our data suggest a functional conservation of the Lgd protein family

  14. 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.

  15. (d,4)-DOMINATING NUMBER OF THE TOROIDAL MESH C(d1,d2)%Toroidal网格C(d1,d2)的(d,4)-控制数

    Institute of Scientific and Technical Information of China (English)

    邵汝军; 吕长虹; 姚天行

    2000-01-01

    Motivated by some models of transmitting messages in interconnection networks,we studied a new parameter, named (d,4)-dominating number,in 2-dimensional toroidal mesh C(d1,d2).We show that the (d,4)-dominating number of C(d1,d2)(d1≥3,d2≥3) is 2 for d=diam(G) or diam(G)+1.%本文讨论二维Toroidal网格的(d,4)-控制数,得到如下结果:(1)如果,m≥2,G=C(2m+1)或G=C(2m+2,3),当d=diam(G)+1时,Rd,4(G)=2;(2)如果G=C(d1,4)(d1≥3)或G=C(d15)(d1≥9),当d=diam(G)时,Rd,4(G)=2.

  16. 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.

  17. 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. PMID:25900179

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report

    Directory of Open Access Journals (Sweden)

    Aquino Gabriella

    2012-07-01

    Full Text Available Abstract Peripheral T-cell lymphomas not otherwise specified are generally considered aggressive non-Hodgkin lymphomas, because of poor natural outcome and response to therapy. They show a complex karyotype without any specific genetic hallmark. We report a case of peripheral T-cell lymphoma not otherwise specified with heterogeneous nuclear Cyclin D1 immunohistochemical overexpression, due to gene copy gain, a phenomenon similar to that observed in Mantle Cell Lymphoma characterized by t(11;14(q13;q32. In this case report we underline the diagnostic pitfall rapresented by Cyclin D1 immunoistochemical overexpression in a T-cell lymphoma. Several pitfalls could lead to misinterpretation of diagnosis, therefore, we underlined the need to integrate the classical histology and immunohistochemistry with molecular tests as clonality or Fluorescence in situ hybridization. Virtual slide The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1117747619703769

  3. 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.

  4. 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.

  5. Model Magnet Development of D1 Beam Separation Dipole for the HL-LHC Upgrade

    CERN Document Server

    Nakamoto, T; Kawamata, H; Enomoto, S; Higashi, N; Idesaki, A; Iio, M; Ikemoto, Y; Iwasaki, R; Kimura, N; Ogitsu, T; Okada, N; Sasaki, K I; Yoshida, M; Todesco, E

    2015-01-01

    KEK has been conducting the design study of the beam separation dipole magnet, D1, for the High Luminosity LHC (HL-LHC) upgrade within a framework of the CERN-KEK collaboration. The D1 magnet has a coil aperture of 150 mm using Nb-Ti superconducting cable and the nominal dipole field of 5.6 T can be generated at 12 kA and 1.9 K. A field integral of 35 T·m is required. The development of the 2-m-long model magnet has been started since May 2013. This paper describes the development status of the short model magnet as well as advancement of the fundamental design studies.

  6. Multi-centered D1-D5 solutions at finite B-moduli

    International Nuclear Information System (INIS)

    We study the fate of two-centered D1-D5 systems on T4 away from the singular supergravity point in the moduli space. We do this by considering a background D1-D5 black hole with a self-dual B-field moduli turned on and treating the second center in the probe limit in this background. We find that in general marginal bound states at zero moduli become metastable at finite B-moduli, demonstrating a breaking of supersymmetry. However, we also find evidence that when the charges of both centers are comparable, the effects of supersymmetry breaking become negligible. We show that this effect is independent of string coupling and thus it should be possible to reproduce this in the CFT at weak coupling. We comment on the implications for the fuzzball proposal

  7. Towards the D1 protein application for the development of sensors specific for herbicides

    Energy Technology Data Exchange (ETDEWEB)

    Piletskaya, E. [Academy Agrarian Sciences of Ukraine, Kiev (Ukraine). Inst. of Agroecology and Biotechnology; Piletsky, S.; Lavrik, N. [Academy of Sciences of Ukraine, Kiev (Ukraine). Inst. of Molecular Biology and Genetics; Masuchi, Y.; Karube, I. [Univ. of Tokyo (Japan). Research Center for Advanced Science and Technology

    1998-12-01

    One of the most widespread groups of pesticides are the triazine herbicides. These substances inhibit photosynthesis by blocking electron transport in plant chloroplasts. The possibility of the chloroplast D1 protein application for determination of the herbicide concentration in solution was investigated. Potentiometry and cyclic voltammetry have been selected to monitor specific interaction between the D1 protein and herbicide. It was found that membranes with well-defined structure, like Langmuir-Blongett film are more suitable for sensitive sensor construction than cross-linked membranes. After addition of atrazine, the current through these multilayers appeared to increase 5 fold. The effect was found to be fast and irreversible. It has been proposed that the toxic action of herbicides on chloroplasts, traditionally interpreted by inhibition of electron flow along the chloroplast membrane, may also be the result of the thylakoid membrane depolarization.

  8. 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.

  9. 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.)

  10. Repeated apomorphine administration alters dopamine D1 and D2 receptor densities in pigeon basal telencephalon

    OpenAIRE

    Acerbo, Martin J.; Výboh, Pavel; Košťál, Ľubor; Kubíková, Ľubica; Delius, Juan

    2005-01-01

    When pigeons are repeatedly administered a dose of apomorphine they show an increasing behavioral response, much as rodents do. In birds this expresses itself in an augmented pecking response. This sensitization is assumed to be largely due to a conditioning process. Here we present evidence that sensitization is accompanied by an alteration of the D1 to D2 dopamine receptor densities. An experimental group of pigeons was repeatedly injected with apomorphine, and a control group with saline. ...

  11. 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....

  12. 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.

  13. Phospholipase D1 facilitates second-phase myoblast fusion and skeletal muscle regeneration

    OpenAIRE

    Teng, Shuzhi; Stegner, David; Qin CHEN; Hongu, Tsunaki; Hasegawa, Hiroshi; Li CHEN; Kanaho, Yasunori; Nieswandt, Bernhard; Frohman, Michael A.; Huang, Ping

    2015-01-01

    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 tha...

  14. CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects

    Directory of Open Access Journals (Sweden)

    Ainhoa eBilbao

    2014-06-01

    Full Text Available IIt is suggested that striatal cAMP responsive element binding protein (CREB regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. Drug-naïve mutants showed moderate alterations in gene expression, most prominently a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2, when compared to wild-type controls. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB.

  15. CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects.

    Science.gov (United States)

    Bilbao, Ainhoa; Rieker, Claus; Cannella, Nazzareno; Parlato, Rosanna; Golda, Slawomir; Piechota, Marcin; Korostynski, Michal; Engblom, David; Przewlocki, Ryszard; Schütz, Günther; Spanagel, Rainer; Parkitna, Jan R

    2014-01-01

    It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB. PMID:24966820

  16. 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

  17. Radial-build design and support system for the helical DEMO reactor FFHR-d1

    International Nuclear Information System (INIS)

    Highlights: ► A conceptual design study for the helical DEMO reactor FFHR-d1 is conducted. ► A radial-build design concept is proposed, which ensures constant geometric positions of the components. ► A structural design procedure for the coil support structure with large apertures is presented and FEM analysis is performed. -- Abstract: A conceptual design for the helical DEMO reactor FFHR-d1 is under development at the National Institute for Fusion Science. In the large helical device (LHD)-type configuration of FFHR-d1, the space between the plasma boundary and the helical coil is limited. Many components are required to be installed at definite geometric positions within this space. The position of each component changes owing to variations in the surrounding conditions, such as temperature, electromagnetic forces, and support methods. This paper proposes a radial-build design concept; the application of this concept ensures constant geometric positions of the components and the gaps between them during normal operation and the construction/maintenance phase. On the other hand, large apertures are required for the coil support structure for the maintenance of blanket and divertor systems. This paper presents a structural design procedure for the coil support structure with large apertures and an LHD-type gravity support post. The analytic results show that the stress level of the structure is lower than the permissible limit

  18. 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.

  19. Design of structural components for the helical reactor FFHR-d1A

    International Nuclear Information System (INIS)

    Highlights: •A design for the helical reactor FFHR-d1A is conducted. Stress analysis of the coil support structure is performed. •Fundamental design for the vacuum vessel and access ports is presented. •A concept of the gravity support is shown. -- Abstract: FFHR-d1 is a conceptual design of the helical reactor being developed at the National Institute for Fusion Science. The maintenance of in-vessel components is very important for the fusion demo reactor. In addition, sufficient pathways are needed for the divertor exhaust. To implement these, the vacuum vessel, coil support structure, and cryostat require large apertures. However, the coil support structure has to be sufficiently rigid to remain within soundness and deformation limits. A design combining the structural components in the FFHR-d1A was developed from mechanical and thermal viewpoints. Consequently, components having a sufficiently large port area were provided. An investigation of the maintenance and exhaust schemes has been planned on the basis of this fundamental design

  20. A merger in the dusty, $z=7.5$ galaxy A1689-zD1?

    CERN Document Server

    Knudsen, Kirsten K; Frayer, David; Christensen, Lise; Gallazzi, Anna; Michalowski, Michal J; Richard, Johan; Zavala, Jesus

    2016-01-01

    The gravitationally-lensed galaxy A1689-zD1 is one of the most distant spectroscopically confirmed sources ($z=7.5$). It is the earliest known galaxy where the interstellar medium (ISM) has been detected; dust emission was detected with the Atacama Large Millimetre Array (ALMA). A1689-zD1 is also unusual among high-redshift dust emitters as it is a sub-L* galaxy and is therefore a good prospect for the detection of gaseous ISM in a more typical galaxy at this redshift. We observed A1689-zD1 with ALMA in bands 6 and 7 and with the Green Bank Telescope (GBT) in band Q. We map the mm thermal dust emission, confirming the large dust emission found before, and finding two spatial components with sizes about 0.4-1.7 kpc (lensing-corrected). The rough spatial morphology is similar to what is observed in the near-infrared with HST and points to a perturbed dynamical state, perhaps indicative of a major merger or a disc in early formation. The ALMA photometry is used to constrain the far-infrared spectral energy distr...

  1. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

    Science.gov (United States)

    Long, Jonathan Z; Svensson, Katrin J; Bateman, Leslie A; Lin, Hua; Kamenecka, Theodore; Lokurkar, Isha A; Lou, Jesse; Rao, Rajesh R; Chang, Mi Ra; Jedrychowski, Mark P; Paulo, Joao A; Gygi, Steven P; Griffin, Patrick R; Nomura, Daniel K; Spiegelman, Bruce M

    2016-07-14

    Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders. PMID:27374330

  2. Production of the excited charm mesons D1 and D*2 at HERA

    International Nuclear Information System (INIS)

    The production of the excited charm mesons D1(2420) and D*2(2460) in ep collisions has been measured with the ZEUS detector at HERA using an integrated luminosity of 373 pb-1. The masses of the neutral and charged states, the widths of the neutral states, and the helicity parameter of D1(2420)0 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameter of the D01 allows for some mixing of S- and D-waves in its decay to D*±π-+. The result is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D*2(2460)0 and D*2(2460)± states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D1 and D*2 were measured and are consistent with those obtained in e+e- annihilations.

  3. Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes.

    Science.gov (United States)

    Cox, Sylvia M L; Frank, Michael J; Larcher, Kevin; Fellows, Lesley K; Clark, Crystal A; Leyton, Marco; Dagher, Alain

    2015-04-01

    The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways.

  4. 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...

  5. 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.

  6. A study of Magnetic Bright Points in the Na I D1 line

    CERN Document Server

    Jess, D B; Christian, D J; Crockett, P J; Keenan, F P

    2010-01-01

    High cadence, multiwavelength, optical observations of solar magnetic bright points, captured at disk center using the ROSA and IBIS imaging systems on the Dunn Solar Telescope, are presented. Magnetic bright points manifesting in the Na I D1 core are found to preferentially exist in regions containing strong downflows, in addition to co-spatial underlying photospheric magnetic field concentrations. Downdrafts within Na I D1 bright points exhibit speeds of up to 7km/s, with preferred structural symmetry in intensity, magnetic field and velocity profiles about the bright point center. Excess intensities associated with G-band and Ca II K observations of magnetic bright points reveal a power-law trend when plotted as a function of magnetic flux density. However, Na I D1 observations of the same magnetic features indicate an intensity plateau at weak magnetic field strengths below ~150G, suggesting the presence of a two-component heating process; one which is primarily acoustic, the other predominantly magnetic....

  7. 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.

  8. A tandem segmental duplication (TSD) in the green revolution gene Rht-D1b region underlies plant height variation

    Science.gov (United States)

    Semi-dwarfing genes Rht-B1b (Rht1) and Rht-D1b (Rht2), known as the “Green revolution” genes, have made a significant contribution to wheat production worldwide. Rht-D1c (Rht10) carried by Chinese wheat line Aibian 1 is an allele at the Rht-D1 locus. It has the strongest effect among all dwarfing...

  9. The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Coombes R Charles

    2006-02-01

    Full Text Available Abstract Background The cyclin D1 proto-oncogene is an important regulator of G1 to S-phase transition and an important cofactor for several transcription factors in numerous cell types. Studies on neonatal cardiomyocytes and postmitotic neurons indicate that the activity of cyclin D1 may be regulated through its cytoplasmic sequestration. We have demonstrated previously, that TSA induces the ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells. Additional studies were initiated in order to further investigate the effect of TSA on cyclin D1 regulation using sub-cellular fractionation techniques. Results Our studies revealed cyclin D1 to be localized predominantly within the cytoplasmic fraction of all cell lines tested. These observations were confirmed by confocal microscopy. GSK3β was found to be localized within both the nucleus and cytoplasm throughout the cell cycle. Inhibition of GSK3β or CRM1-dependent nuclear export resulted in only modest nuclear accumulation, suggesting that the cytoplasmic localization of cyclin D1 results from the inhibition of its nuclear import. Conclusion We have shown by several different experimental approaches, that cyclin D1 is in fact a predominantly cytoplasmic protein in mammalian cancer cell lines. Recent studies have shown that the cytoplasmic sequestration of cyclin D1 prevents apoptosis in neuronal cells. Our results suggest that cytoplasmic sequestration may additionally serve to regulate cyclin D1 activity in mammalian cancer cells.

  10. NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition

    OpenAIRE

    Osborne, J K; Larsen, J E; Gonzales, J X; Shames, D S; Sato, M.; Wistuba, I. I.; Girard, L; Minna, J D; Cobb, M H

    2013-01-01

    The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pi...

  11. 大鼠海马tau蛋白过度磷酸化时细胞周期蛋白cyclin D1的表达%Expression of mitotic protein cyclin D1 during tau hyperphosphorylation in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    李妍; 董为人; 王海红; 刘忠英; 晏芳

    2011-01-01

    目的:探讨大鼠海马tau蛋白过度磷酸化时细胞周期蛋白cyclin D1的表达.方法:用cAMP-依赖性蛋白激酶 A (PKA) 的激动剂Forskolin注射大鼠侧脑室,免疫印迹和免疫组织化学技术检测大鼠海马tau蛋白的磷酸化水平,同时采用免疫印迹、免疫组织化学和RT-PCR方法检测海马cyclin D1和cyclin D1 mRNA.结果:侧脑室注射Forskolin 48h,大鼠海马tau蛋白Ser214、Ser396和Ser202/Thr205位点的磷酸化水平升高,同时检测到细胞周期蛋白cyclin D1和cyclin D1 mRNA.结论:侧脑室注射Forskolin诱导大鼠海马 tau蛋白过度磷酸化的同时,大鼠海马出现细胞周期蛋白cyclin D1的表达,提示了tau蛋白过度磷酸化与细胞周期相关蛋白cyclin D1之间可能的内在联系.%Objective: To investigate the expression of mitotic protein cyclin D1 during tau hyperphosphorylation. Methods: Forskolin (80 μmol/L, 40μl) was injected into the lateral ventricle by stereotaxic injection. Tau phosphorylation in the hippocampus of rats was measured by Western blot and immunohistochemistry. The expression of cyclin D1 protein and the level of cyclin D1 mRNA in the hippocampus of rats were detected by Western blot, irnmunohistochemistry and RT-PCR technique. Results: The level of tau phosphorylation at Ser214, Ser396 and Ser202/Thr205 sites was significantly elevated at 48 h after administration of Forskolin. Meanwhile cyclin D1 protein and cyclin D1 mRNA were detected in Forskolin injection group. Conclusion: Mitotic protein cyclin D1 expressed in the hippocampus of rats during tau hyperphosphorylation induced by injection of Forskolin into the lateral ventricle of the rats. Present results suggest a positive correlation between tau hyperphosphorylation and the mitotic protein cyclin D1.

  12. 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.

  13. Write-up for the Diffractometer D1 at Risø

    DEFF Research Database (Denmark)

    Bundgaard, Jørgen; Krebs Larsen, F.; Lebech, Bente;

    Manual for the crystallographic program system used to control the 4-circle neutron diffractometer D1/TASII at DR3, Risø. The mechanical part of the diffractometer consists of a monochromator part which allows an easy change of incident neutron wavelength and a four-circle HUBER goniostate...... consisting of an Euler cradle (HUBER 512) and two horizontal goniometers (HUBER 440 and HUBER 430). The goniostate is computer controlled by a PDP-11/34 interfaced via CAMAC modules. The PDD-11/34 computer has a 128 k byte memory, two hard magnetic disc stations, a fast DEC-writer terminal and a screen...

  14. 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.

  15. 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.

  16. Characterization of the Mycobacterial NER System Reveals Novel Functions of the uvrD1 Helicase

    OpenAIRE

    Guthlein, C.; Wanner, R M; Sander, P; Davis, E O; Bosshard, M.; Jiricny, J; Bottger, E. C.; Springer, B.

    2008-01-01

    In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB or the helicase uvrD1 gene and a double knockout lacking both genes were constructed, and their sensitivities to a series of DNA-damaging agents were analyzed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and interstrand cross-links. In addition, i...

  17. Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase

    OpenAIRE

    Güthlein, C; Wanner, R M; Sander, P; Davis, E O; Bosshard, M.; Jiricny, J; Böttger, E C; Springer, B.

    2009-01-01

    In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB, the helicase uvrD1 and a double knock-out lacking both proteins were constructed and their sensitivity to a series of DNA damaging agents wa analysed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and inter-strand cross-links. In addition, it coul...

  18. Absolute Frequency Measurements of the D1 and D2 Transitions in Aatomic Li

    Science.gov (United States)

    Sheets, Donal; Almaguer, Jose; Baron, Jacob; Elgee, Peter; Rowan, Michael; Stalnaker, Jason

    2014-05-01

    We present preliminary results from our measurements of the D1 and D2 transitions in Li. The data were obtained from a collimated atomic beam excited by light from an extended cavity diode laser. The frequency of the diode laser was stabilized to an optical frequency comb, providing absolute frequency measurement and control of the excitation laser frequency. These measurements will provide a stringent test of atomic structure calculations and yield information about the nuclear structure. We also discuss plans to extend the technique to other high-lying states in lithium. Funded by the NIST Precision Measurements Grant and NSF Award #1305591.

  19. Design Window Analysis for the Helical DEMO Reactor FFHR-d1

    OpenAIRE

    Goto, Takuya; MIYAZAWA, Junichi; TAMURA, Hitoshi; TANAKA, Teruya; Hamaguchi, Shinji; Yanagi, Nagato; SAGARA, Akio; the FFHR Design Group

    2012-01-01

    Conceptual design activity for the LHD-type helical DEMO reactor FFHR-d1 has been conducted at the National Institute for Fusion Science under the Fusion Engineering Research Project since FY2010. In the first step of the conceptual design process, design window analysis was conducted using the system design code HELIOSCOPE by the “Design Integration Task Group”. On the basis of a parametric scan with the core plasma design based on the DPE (Direct Profile Extrapolation) method, a design poin...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Sensitivities of dopamine D1 and D2 receptor radioligands to changes in synaptic dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Gifford, A.N.; Gatley, S.J.; Shea, C. [Brookhaven National Lab., Upton, NY (United States)

    1996-05-01

    Prior studies have shown that the in vivo binding of D2 radioligands such as raclopride and IBZM is subject to competition with synaptic DA. D2 radioligands can thus be used to evaluate both direct effects of drugs at DAergic synapses, and indirect effects at these synapses mediated via neurotransmitter interactions. Competition with DA must also be a potential confounding factor in studies designed to evaluate changes in D2 receptor number. We evaluated the sensitivity of the D1 radioligands for susceptibility to alterations in synaptic DA. We evaluated the sensitivity of the D1 radioligand SCH 23390 using three different models: rat brain slices in which DA release is controlled by electrically simulation, ex vivo mouse brain uptake, and PET in the baboon brain. In slices, the order of sensitivity of DA system radioligands to synaptic DA was D1>D2>DA transporter, and the sensitivity of the low affinity (Kd = 1 nM) D2 ligand, [H-3]raclopride, was greater than that of the high affinity (Kd = 0.05 nM) D2 ligand, [I-123]epidepride (Gifford et al., Synapse, in press). In mice, striatal [H-3]SCH 23390 was decreased after administration of the DA transporter blocker RTI-55 ({beta}-CIT, 0.5 mg/kg, i/v), to a similar extent as that of co-administered [I-123]epidepride. In these experiments RTI-55 was given four hours after injection of radiotracers, after peak striatal radioactivity, to avoid the effects of the increase in delivery of radiotracer to the brain caused by RTI-55. In PET experiments, striatal binding of the D1 radioligand [C-11]SCH23390 was less sensitive to challenge with the DA transporter blocker methylphenidate (0.5 mg/kg, 7-10 min before radiotracer) than is [C-11]raclopride. Our results together indicate that SCH 23390 is not very sensitive to pharmacological challenges which decrease the in vivo binding of labeled raclopride.

  5. 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.

  6. 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

    BACKGROUND: Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS: The authors reviewed 143...

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

    International Nuclear Information System (INIS)

    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

  8. Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice.

    Science.gov (United States)

    Zhang, Ying; Wang, Ning; Su, Ping; Lu, Jie; Wang, Yun

    2014-12-01

    Dopamine D1 receptors (D1Rs) play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1R in the forebrain. These transgenic mice showed reduced phospho-D1R (S421) and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These findings provide in vivo evidence for the critical role of S421 phosphorylation of the D1R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders. PMID:25304015

  9. The Protein Elicitor PevD1 Enhances Resistance to Pathogens and Promotes Growth in Arabidopsis.

    Science.gov (United States)

    Liu, Mengjie; Khan, Najeeb Ullah; Wang, Ningbo; Yang, Xiufen; Qiu, Dewen

    2016-01-01

    The protein elicitor PevD1, isolated from Verticillium dahlia, could enhance resistance to TMV in tobacco and Verticillium wilt in cotton. Here, the pevd1 gene was over-expressed in wild type (WT) Arabidopsis, and its biological functions were investigated. Our results showed that the transgenic lines were more resistant to Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 than the WT line was. In transgenic plants, both the germination time and bolting time required were significantly shorter and fresh weights and plant heights were significantly higher than those in the WT line. A transcriptomics study using digital gene expression profiling (DGE) was performed in transgenic and WT Arabidopsis. One hundred and thirty-six differentially expressed genes were identified. In transgenic Arabidopsis, three critical regulators of JA biosynthesis were up-regulated and JA levels were slightly increased. Three important repressors of the ABA-responsive pathway were up-regulated, indicating that ABA signal transduction may be suppressed. One CML and two WRKY TFs involved in Ca(2+)-responsive pathways were up-regulated, indicating that this pathway may have been triggered. In conclusion, we show that PevD1 is involved in regulating several plant endogenous signal transduction pathways and regulatory networks to enhance resistance and promote growth and development in Arabidopsis. PMID:27489497

  10. Intense ionizing radiation from laser-induced processes in ultra-dense deuterium D(-1)

    International Nuclear Information System (INIS)

    Nuclear fusion in ultra-dense deuterium D(-1) has been reported from our laboratory in a few studies using pulsed lasers with energy < 0.2 J. The direct observation of massive particles with energy 1–20 MeV u-1 is conclusive proof for fusion processes, either as a cause or as a result. Continuing the step-wise approach necessary for untangling a complex problem, the high-energy photons from the laser-induced plasma are now studied. The focus is here on the photoelectrons formed. The photons penetrating a copper foil have energy > 80 keV. The total charge created is up to 2 μC or 1 × 1013 photoelectrons per laser shot at 0.13 J pulse energy, assuming isotropic photon emission. The variation of the photoelectron current with laser intensity is faster than linear for some systems, which indicates rapid approach to volume ignition. On a permanent magnet at approximately 1 T, a laser pulse-energy threshold exists for the laser-induced processes probably due to the floating of most clusters of D(-1) in the magnetic field. This Meissner effect was reported previously. (author)

  11. 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.

  12. 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...

  13. External corrosion of tanks 8D-1 and 8D-2. Final report

    International Nuclear Information System (INIS)

    Tanks 8D-1 and 8D-2 at the West Valley Nuclear Services (WVNS) site, West Valley, New York, rest on layers of perlite brick contained within steel pans. The pans tend to collect water, which can contact the tanks directly and which also can be ''wicked'' to the external surfaces of the tank through the perlite brick. The presence of air in the tank vault is conducive to the formation of oxygen concentration cells, which can promote localized corrosion of the carbon steel tank wall. Pacific Northwest Laboratory conducted an experiment to estimate the extent to which the external surfaces of the tanks could have corroded in the 30 years since their construction. Specimens of carbon steel, similar to that used in the tank construction, were partially embedded in an upright position in particulate perlite in closed containers. The water line in the containers.was maintained at two levels: above the perlite level (high water level tests) and below the bottoms of the specimens (low water level tests). The water used in the tests was obtained from the pan of tank 8D-1. The containers were maintained in an aerated condition. Specimens were examined after 3-, 6-, 12-, 18-, 24-, and 30-month exposures

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. COMPARISON OF THE THERAPEUTIC EFFECTS OF D1 TO D2 OPERATIVE METHODS IN GASTRIC CANCER%胃癌D1和D2术式的疗效比较

    Institute of Scientific and Technical Information of China (English)

    刘金炎; 许国平; 庄丹; 谢昭雄; 洪建文; 林建群; 黄鑫

    2001-01-01

    目的评价进展期胃癌D1和D2术式的疗效。方法前瞻性收集1996年6月至2000年5月60例可切除性远侧胃癌,将患者随机分为D1组30例和D2组30例,分别由两组年资相当的医生进行手术操作。结果两组患者无手术死亡。经统计,术后转移复发率1年D1组40.0%、D2组3.3%; 2年D1组53.3%、D2组10.0%; 3年D1组56.6%、D2组13.3%; 4年D1组60.0%、D2组16.7%。提示D2与D1比较差异有极显著性意义(P<0.01);术后生存率1年D1组73.3%、D2组96.7%; 2年D1组59.3%、D2组96.5%; 3年D1组53.6%、D2组83.3%; 4年D1组44.5%、D2组80.0%(P<0.05)。结论 D2术式在减少胃癌术后转移复发率及提高生存率方面,效果明显优于D1术式,可作为进展期胃癌的首选术式。%Objective To evaluate the therapeutic effects of D1 and D2 operative methods for advanced gastric carcinoma. Methods  60 cases of the resectably distal gastric cancer were colleted prospectively and they were randomly divided into group D1 (30 cases) and group D2 (30 cases). They were operated respectively by the doctors with equivalent grade in two groups. Results No patients in the two groups died from the operation. The rate of recurrence and metastasis in group D1 and D2 was 40.0% and 3.3% (P<0.01) respectively in a year, 53.3% and 10.0%(P<0.01) in two years, 56.6% and 13.3% (P<0.01) in three years, 60.0% and 16.7% (P<0.01) in four years; The survival rates in group D1 and D2 were 73.3% and 96.7%(P<0.05) in a year, 59.3% and 96.5% (P<0.01) in two years, 53.6% and 83.3% (P<0.05) in three years, 44.4% and 80.0% (P>0.05) in four years, respectively. Conclusion In reducing the recurrent rate of gastric cancer and increasing the postopertive survival rate, the D2 operative method is much better than the D1 operative method, and it can be the first choice for advanced gastric carcinoma.

  19. 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.

  20. 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.

  1. Resolvin D1, a Metabolite of Omega-3 Polyunsaturated Fatty Acid, Decreases Post-Myocardial Infarct Depression

    Directory of Open Access Journals (Sweden)

    Kim Gilbert

    2014-11-01

    Full Text Available We hypothesized that inflammation induced by myocardial ischemia plays a central role in depression-like behavior after myocardial infarction (MI. Several experimental approaches that reduce inflammation also result in attenuation of depressive symptoms. We have demonstrated that Resolvin D1 (RvD1, a metabolite of omega-3 polyunsaturated fatty acids (PUFA derived from docosahexaenoic acid, diminishes infarct size and neutrophil accumulation in the ischemic myocardium. The aim of this study is to determine if a single RvD1 injection could alleviate depressive symptoms in a rat model of MI. MI was induced in rats by occlusion of the left anterior descending coronary artery for 40 min. Five minutes before ischemia or after reperfusion, 0.1 μg of RvD1 or vehicle was injected in the left ventricle cavity. Fourteen days after MI, behavioral tests (forced swim test and socialization were conducted to evaluate depression-like symptoms. RvD1 reduced infarct size in the treated vs. the vehicle group. Animals receiving RvD1 also showed better performance in the forced swim and social interaction tests vs. vehicle controls. These results indicate that a single RvD1 dose, given 5 min before occlusion or 5 min after the onset of reperfusion, decreases infarct size and attenuates depression-like symptoms.

  2. Pharmacological and biochemical characterization of the D-1 dopamine receptor mediating acetylcholine release in rabbit retina

    Energy Technology Data Exchange (ETDEWEB)

    Hensler, J.G.; Cotterell, D.J.; Dubocovich, M.L.

    1987-12-01

    Superfusion with dopamine (0.1 microM-10 mM) evokes calcium-dependent (/sup 3/H)acetylcholine release from rabbit retina labeled in vitro with (/sup 3/H)choline. This effect is antagonized by the D-1 dopamine receptor antagonist SCH 23390. Activation or blockade of D-2 dopamine, alpha-2 or beta receptors did not stimulate or attenuate the release of (/sup 3/H)acetylcholine from rabbit retina. Dopamine receptor agonists evoke the release of (/sup 3/H)acetylcholine with the following order of potency: apomorphine less than or equal to SKF(R)82526 < SKF 85174 < SKF(R)38393 less than or equal to pergolide less than or equal to dopamine (EC50 = 4.5 microM) < SKF(S)82526 less than or equal to SKF(S)38393. Dopamine receptor antagonists inhibited the dopamine-evoked release of (/sup 3/H)acetylcholine: SCH 23390 (IC50 = 1 nM) < (+)-butaclamol less than or equal to cis-flupenthixol < fluphenazine < perphenazine < trans-flupenthixol < R-sulpiride. The potencies of dopamine receptor agonists and antagonists at the dopamine receptor mediating (/sup 3/H)acetylcholine release is characteristic of the D-1 dopamine receptor. These potencies were correlated with the potencies of dopamine receptor agonists and antagonists at the D-1 dopamine receptor in rabbit retina as labeled by (/sup 3/H)SCH 23390, or as determined by adenylate cyclase activity. (/sup 3/H)SCH 23390 binding in rabbit retinal membranes was stable, saturable and reversible. Scatchard analysis of (/sup 3/H)SCH 23390 saturation data revealed a single high affinity binding site (Kd = 0.175 +/- 0.002 nM) with a maximum binding of 482 +/- 12 fmol/mg of protein. The potencies of dopamine receptor agonists to stimulate (/sup 3/H)acetylcholine release were correlated with their potencies to stimulate adenylate cyclase (r = 0.784, P less than .05, n = 7) and with their affinities at (/sup 3/H)SCH 23390 binding sites (r = 0.755, P < .05, n = 8).

  3. 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.

  4. 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

  5. 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.

  6. Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical coupling

    OpenAIRE

    Sinha, Krishna Murari; Glickman, Michael S.; Shuman, Stewart

    2009-01-01

    Mycobacterial UvrD1 is a DNA-dependent ATPase and a Ku-dependent 3’ to 5’ DNA helicase. The UvrD1 motor domain resembles that of the prototypal superfamily I helicases UvrD and PcrA. Here we performed a mutational analysis of UvrD1 guided by the crystal structure of a DNA-bound E. coli UvrD-ADP-MgF3 transition state mimetic. Alanine scanning and conservative substitutions identified five amino acids essential for both ATP hydrolysis and duplex unwinding, including those implicated in phosphoh...

  7. Mapping of the spontaneous deletion in the Ap3d1 gene of mocha mice: fast and reliable genotyping

    OpenAIRE

    Delenclos Marion; Holm Mai; Drasbek Kim; Jensen Kimmo

    2008-01-01

    Abstract Background The mocha mouse carries a spontaneous deletion in the Ap3d1 gene, encoding the delta 1 subunit of the adaptor related protein complex 3, (Ap3d1), and subsequently lack the expression of functional AP-3. This leads to a deficiency in vesicle transport and storage, which affects neurotransmitter vesicle turnover and release in the central nervous system. Since the genomic sequence of the Ap3d1 gene of mocha mouse is not known, precise mapping of the deletion as well as relia...

  8. 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. PMID:26208915

  9. 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.

  10. 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.

  11. Some Developments of the Casimir Effect in $p$-Cavity of $(D+1)$-Dimensional Spacetime

    CERN Document Server

    Zhai, Xiang-Hua; Feng, Chao-Jun; Li, Xin-Zhou

    2014-01-01

    The Casimir effect for rectangular boxes has been studied for several decades. But there are still some points unclear. Recently, there are new developments related to this topic, including the demonstration of the equivalence of the regularization methods and the clarification of the ambiguity in the regularization of the temperature-dependent free energy. Also, the interesting quantum spring was raised stemming from the topological Casimir effect of the helix boundary conditions. We review these developments together with the general derivation of the Casimir energy of the $p$-dimensional cavity in ($D+1$)-dimensional spacetime, paying special attention to the sign of the Casimir force in a cavity with unequal edges. In addition, we also review the Casimir piston, which is a configuration related to rectangular cavity.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. Protein kinase D1 (PKD1) influences androgen receptor (AR) function in prostate cancer cells

    International Nuclear Information System (INIS)

    Protein kinase D1 (PKD1), founding member of PKD protein family, is down-regulated in advanced prostate cancer (PCa). We demonstrate that PKD1 and androgen receptor (AR) are present as a protein complex in PCa cells. PKD1 is associated with a transcriptional complex which contains AR and promoter sequence of the Prostate Specific Antigen (PSA) gene. Ectopic expression of wild type PKD1 and the kinase dead mutant PKD1 (K628W) attenuated the ligand-dependent transcriptional activation of AR in prostate cancer cells and yeast cells indicating that PKD1 can affect AR transcription activity, whereas knocking down PKD1 enhanced the ligand-dependent transcriptional activation of AR. Co-expression of kinase dead mutant with AR significantly inhibited androgen-mediated cell proliferation in both LNCaP and DU145 PC cells. Our data demonstrate for the first time that PKD1 can influence AR function in PCa cells

  20. Iterative 2-D/1-D methods for the 3-D neutron diffusion calculation

    International Nuclear Information System (INIS)

    To remedy the problems arising from assembly homogenization and de-homogenization, several efforts have been made to solve directly the heterogeneous problem with a fine mesh and to reduce the computational burden by coupling 2-D planar with 1-D axial solutions using a Transverse Leakage (TL) coupling. However, the potential for a numerical instability at a small axial mesh size has been observed. Lee et al. showed that one of the two existing methods, method A, is mathematically unstable at a small mesh size while the other, method B, is always stable. They also proposed a new method for a 2-D/1-D coupling, method C, and they showed that it is always stable and it provides the best performance in terms of the convergence rate. In this paper another algorithm, method D, is proposed and its stability is also investigated

  1. 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.

  2. Design window analysis for the helical DEMO reactor FFHR-d1

    International Nuclear Information System (INIS)

    Conceptual design activity for the LHD-type helical DEMO reactor FFHR-d1 has been conducted at the National Institute for Fusion Science under the Fusion Engineering Research Project since FY2010. In the first step of the conceptual design process, design window analysis was conducted using the system design code HELIOSCOPE by the “Design Integration Task Group”. On the basis of a parametric scan with the core plasma design based on the DPE (Direct Profile Extrapolation) method, a design point having a major radius of 15.6 m and averaged magnetic field strength at the helical coil winding center of 4.7 T was selected as a candidate. The validity of the design was confirmed through the analysis by the related task groups (in-vessel component, blanket, and superconducting magnet). (author)

  3. Geochemistry areas and sample sites, and multielement and single element geochemistry maps of Mauritania (phase V, deliverable 58): Chapter D1 in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

    Science.gov (United States)

    Giles, Stuart A.; Eppinger, Robert G.

    2015-01-01

    In 1996, at the request of the Government of the Islamic Republic of Mauritania, a team of U.S. Geological Survey (USGS) scientists produced a strategic plan for the acquisition, improvement and modernization of multidisciplinary sets of data to support the growth of the Mauritanian minerals sector and to highlight the geological and mineral exploration potential of the country. In 1999, the Ministry of Petroleum, Energy, and Mines of the Islamic Republic of Mauritania implemented a program for the acquisition of the recommended basic geoscientific information, termed the first Projet de Renforcement Institutionnel du Secteur Minier (Project for Institutional Capacity Building in the Mining Sector, PRISM-I). As a result of the PRISM-I efforts, a great deal of new geological, geophysical, geochemical, remote sensing, and hydrological data became available for evaluation and synthesis. However, the Ministry of Petroleum, Energy, and Mines recognized that additional work was required to extract the full benefit of the data before it could be of greatest use to the international community and of benefit to the Mauritanian minerals and development sector.

  4. 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

  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. Glucocorticoid receptor mediated the propofol self-administration by dopamine D1 receptor in nucleus accumbens.

    Science.gov (United States)

    Wu, Binbin; Liang, Yuyuan; Dong, Zhanglei; Chen, Zhichuan; Zhang, Gaolong; Lin, Wenxuan; Wang, Sicong; Wang, Benfu; Ge, Ren-Shan; Lian, Qingquan

    2016-07-22

    Propofol, a widely used anesthetic, can cause addictive behaviors in both human and experimental animals. In the present study, we examined the involvement of glucocorticoid receptor (GR) signaling in the molecular process by which propofol may cause addiction. The propofol self-administration model was established by a fixed ratio 1 (FR1) schedule of reinforced dosing over successive 14days in rats. On day 15, the rats were treated with dexamethasone, a GR agonist (10-100μg/kg), or RU486, a GR antagonist (10-100μg/kg) at 1h prior to the last training. The animal behaviors were recorded automatically by the computer. The expression of dopamine D1 receptor in the nucleus accumbens (NAc) was examined by Western blot and the concentrations of plasma corticosterone were measured by enzyme-linked immunosorbent assay (ELISA). To further examine the specificity of GR in the process, mineralocorticoid receptor (MR) antagonist, spironolactone, and dexamethasone plus MR agonist, aldosterone, were also tested. Administration of dexamethasone (100μg/kg) or RU486 (⩾10mg/kg) significantly attenuated the rate of propofol maintained active nose-poke responses and infusions, which were accompanied by reductions in both plasma corticosterone level and the expression of D1 receptor in the NAc. Neither spironolactone alone nor dexamethasone combined with aldosterone affected the propofol-maintaining self-administrative behavior, indicating GR, but not MR, modulates the propofol reward in rats. In addition, neither the food-maintaining sucrose responses under FR1 schedule nor the locomotor activity was affected by any doses of dexamethasone or RU486 tested. These findings provide evidence that GR signaling may play an important role in propofol reward. PMID:27126557

  7. 关于丢番图方程x3±1=pD1 y2%On the Diophantine equation x3±1=pD1 y2

    Institute of Scientific and Technical Information of China (English)

    杜先存; 万飞; 赵金娥

    2014-01-01

    D1是无平方因子的正整数,p以1(mod 6)为素数,运用Pell方程px2-3y2=1的最小解、同余式、平方剩余、勒让德符号的性质等初等方法,证明了:当 D1是不能被3或6k +1型的素数整除的正整数、p =3n(n +1)+1时,丢番图方程x3±1= pD1 y2无正整数解。%Let D1 be an non-square positive integer, p=1(mod 6), and p be an odd prime. By using the minimal solution to the Pell equation px2-3y2=1, congruent formula, quadratic residue, and the properties of Legendre symbol, the sufficient conditions were obtained that the Diophantine equation x3±1=pD1 y2 has no integer solutions, where D1 could not be exactly divided by the prime number 3 or 6k+1, p=3n(n+1)+1.

  8. 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.

  9. 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.

  10. The Calcium Goes Meow: Effects of Ions and Glycosylation on Fel d 1, the Major Cat Allergen.

    Directory of Open Access Journals (Sweden)

    Rodrigo Ligabue-Braun

    Full Text Available The major cat allergen, Fel d 1, is a structurally complex protein with two N-glycosylation sites that may be filled by different glycoforms. In addition, the protein contains three putative Ca2+ binding sites. Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues. While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity. As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy.

  11. Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

    Science.gov (United States)

    Sathler, Matheus Figueiredo; Stutz, Bernardo; Martins, Robertta Silva; Dos Santos Pereira, Maurício; Pecinalli, Ney Roner; Santos, Luis E; Taveira-da-Silva, Rosilane; Lowe, Jennifer; de Freitas, Isis Grigorio; de Melo Reis, Ricardo Augusto; Manhães, Alex C; Kubrusly, Regina C C

    2016-08-01

    Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC. PMID:27208619

  12. The human collagen beta(1-Ogalactosyltransferase, GLT25D1, is a soluble endoplasmic reticulum localized protein

    Directory of Open Access Journals (Sweden)

    Spaan Willy JM

    2010-05-01

    Full Text Available Abstract Background Glycosyl transferases transfer glycosyl groups onto their substrate. Localization partially defines their function. Glycosyl transferase 25 domain 1 (GLT25D1 was recently shown to have galactosyltransferase activity towards collagens and another well known substrate, mannose binding lectin (MBL. To gain more insight in the role of galactosylation of lysines in the Gly-X-Lys repeats of collagenous proteins, we investigated the subcellular localization of GLT25D1. Results Immunofluorescence analysis of GLT25D1 expressed in the human hepatoma cell line (Huh7, revealed a perinuclear lattice like staining, resembling localization to the endoplasmic reticulum (ER. Possible targeting signals, an N-terminal signal sequence and a C-terminal ER-retention signal, were identified using prediction programs. These signals were then investigated by constructing a series of epitope-tagged forms of GLT25D1 that were analyzed by immunofluorescence and western blotting. In agreement with the predictions our results show that GLT25D1 is directed to the ER lumen as a soluble protein and retained there. Moreover, using two endoglycosidase enzymes EndoH and EndoF, we demonstrate that the putative bi-functional glycosyl transferase itself is a glycoprotein. Additionally we examined co-localization of GLT25D1 with MBL and lysyl hydroxylase 3 (LH3, PLOD3, which is a protein able to catalyze hydroxylation of lysine residues before they can be glycosylated. We demonstrate overlapping localization patterns of GLT25D1, MBL and LH3. Conclusions Taken together our data indicate that galactosylation of collagenous proteins by the soluble GLT25D1 occurs in the early secretory pathway.

  13. The human collagen beta(1-O)galactosyltransferase, GLT25D1, is a soluble endoplasmic reticulum localized protein

    OpenAIRE

    Spaan Willy JM; Punt Simone; Liefhebber Jolanda MP; van Leeuwen Hans C

    2010-01-01

    Abstract Background Glycosyl transferases transfer glycosyl groups onto their substrate. Localization partially defines their function. Glycosyl transferase 25 domain 1 (GLT25D1) was recently shown to have galactosyltransferase activity towards collagens and another well known substrate, mannose binding lectin (MBL). To gain more insight in the role of galactosylation of lysines in the Gly-X-Lys repeats of collagenous proteins, we investigated the subcellular localization of GLT25D1. Results ...

  14. Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to normal common marmosets

    OpenAIRE

    Löschmann, P A; Smith, L A; Klaus W. Lange; Jaehnig, P.; Jenner, P.; Marsden, C. D.

    1991-01-01

    In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2 agonist quinpirole caused a dose-dependent increase in motor activity and induced stereotyped behaviour. Both the selective D-2 antagonist raclopride and the selective D-1 antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy. Quinpirole- and apomorphine-induced motor activity were potently inhibited by pretreatment with raclopride. The effects of quinpirole, but not apom...

  15. Finite temperature Casimir effect on spherical shells in (D+1)-dimensional spacetime and its high temperature limit

    OpenAIRE

    Teo, L. P.

    2013-01-01

    We consider the finite temperature Casimir free energy acting on a spherical shell in (D+1)-dimensional Minkowski spacetime due to the vacuum fluctuations of scalar and electromagnetic fields. Dirichlet, Neumann, perfectly conducting and infinitely permeable boundary conditions are considered. The Casimir free energy is regularized using zeta functional regularization technique. To renormalize the Casimir free energy, we compute the heat kernel coefficients $c_n$, $0\\leq n\\leq D+1$, from the ...

  16. Enhanced Resolution of Hyperoxic Acute Lung Injury as a result of Aspirin Triggered Resolvin D1 Treatment.

    Science.gov (United States)

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Arias, Stephen; Cho, Young; Lockey, Richard F; Kolliputi, Narasaiah

    2015-09-01

    Acute lung injury (ALI), which presents as acute respiratory failure, is a major clinical problem that requires aggressive care, and patients who require prolonged oxygen exposure are at risk of developing this disease. Although molecular determinants of ALI have been reported, the molecules involved in disease catabasis associated with oxygen toxicity have not been well studied. It has been reported that lung mucosa is rich in omega-3 fatty acid dicosahexanoic acid (DHA), which has antiinflammatory properties. Aspirin-triggered resolvin D1 (AT-RvD1) is a potent proresolution metabolite of DHA that can curb the inflammatory effects in various acute injuries, yet the effect of AT-RvD1 on hyperoxic acute lung injury (HALI) or in the oxygen toxicity setting in general has not been investigated. The effects of AT-RvD1 on HALI were determined for the first time in 8- to 10-week-old C57BL/6 mice that were exposed to hyperoxia (≥95% O2) for 48 hours. Mice were given AT-RvD1 (100 ng) in saline or a saline vehicle for 24 hours in normoxic (≈21% O2) conditions after hyperoxia. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analysis associated with proinflammatory signaling and lung inflammation. AT-RvD1 treatment resulted in reduced oxidative stress, increased glutathione production, and significantly decreased tissue inflammation. AT-RvD1 treatment also significantly reduced the lung wet/dry ratio, protein in BAL fluid, and decreased apoptotic and NF-κB signaling. These results show that AT-RvD1 curbs oxygen-induced lung edema, permeability, inflammation, and apoptosis and is thus an effective therapy for prolonged hyperoxia exposure in this murine model. PMID:25647402

  17. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.

    Science.gov (United States)

    Calipari, Erin S; Bagot, Rosemary C; Purushothaman, Immanuel; Davidson, Thomas J; Yorgason, Jordan T; Peña, Catherine J; Walker, Deena M; Pirpinias, Stephen T; Guise, Kevin G; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J

    2016-03-01

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse. PMID:26831103

  18. 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.

  19. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.

    Science.gov (United States)

    Calipari, Erin S; Bagot, Rosemary C; Purushothaman, Immanuel; Davidson, Thomas J; Yorgason, Jordan T; Peña, Catherine J; Walker, Deena M; Pirpinias, Stephen T; Guise, Kevin G; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J

    2016-03-01

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse.

  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. 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.

  2. Effects of Chronic REM Sleep Restriction on D1 Receptor and Related Signal Pathways in Rat Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Yan Han

    2015-01-01

    Full Text Available The prefrontal cortex (PFC mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR, particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR on the D1 receptor (D1R and key molecules in D1R’ signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P<0.01, P<0.05; the expression of phosphor-PKAcα was significantly lowered in CSR rats (P<0.05. The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

  3. 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.

  4. 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.

  5. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake.

    Science.gov (United States)

    Zhu, Xianglong; Ottenheimer, David; DiLeone, Ralph J

    2016-01-01

    While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The nucleus accumbens (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 designer receptors exclusively activated by designer drugs (DREADD) 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 NAc D1 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. PMID:27147989

  6. 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.

  7. 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

  8. 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.

  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. 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. PMID:25428992

  11. Structure detection in the D1 CFHTLS deep field using accurate photometric redshifts: a benchmark

    CERN Document Server

    Mazure, A; Pierre, M; Lefèvre, O; Arnouts, S; Duc, P A; Ilbert, O; Le Brun, V; Meneux, B; Pacaud, F; Surdej, J; Valtchanov, I

    2007-01-01

    We investigate structures in the D1 CFHTLS deep field in order to test the method that will be applied to generate homogeneous samples of clusters and groups of galaxies in order to constrain cosmology and detailed physics of groups and clusters. Adaptive kernel technique is applied on galaxy catalogues. This technique needs none of the usual a-priori assumptions (luminosity function, density profile, colour of galaxies) made with other methods. Its main drawback (decrease of efficiency with increasing background) is overcame by the use of narrow slices in photometric redshift space. There are two main concerns in structure detection. One is false detection and the second, the evaluation of the selection function in particular if one wants "complete" samples. We deal here with the first concern using random distributions. For the second, comparison with detailed simulations is foreseen but we use here a pragmatic approach with comparing our results to GalICS simulations to check that our detection number is n...

  12. 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.

  13. 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.

  14. 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...

  15. Increased hydrogen photoproduction by means of a sulfur-deprived chlamydomonas reinhardtii D1 protein mutant

    Energy Technology Data Exchange (ETDEWEB)

    Torzillo, Giuseppe; Scoma, Alberto; Faraloni, Cecilia; Ena, Alba [Istituto per lo Studio degli Ecosistemi (ISE), CNR, via Madonna del Piano 10, 50019 Sesto Fiorentino (FI) (Italy); Johanningmeier, Udo [Martin-Luther-Universitaet Halle-Wittenberg, Institut fuer Pflanzenphysiologie, Halle-Saale (Germany)

    2009-05-15

    The photoproduction of H{sub 2} was studied in a sulfur-deprived Chlamydomonas reinhardtii D1 mutant that carried a double amino acid substitution. The leucine residue L159 was replaced by isoleucine, and the asparagine N230 was replaced by tyrosine (L159I-N230Y). Phenotypic characterization of the mutant showed some interesting features compared to its wild type, namely: (1) a lower chlorophyll content; (2) a higher photosynthetic capacity and higher relative quantum yield of photosynthesis; (3) a higher respiration rate; (4) a very high conversion of violaxanthin to zeaxanthin during H{sub 2} production; (5) a prolonged period of H{sub 2} production. In standard conditions, the mutant produced more than 500 ml of H{sub 2}, that is, more than one order of magnitude greater than its wild type, and about 5-times greater than the CC124 strain that was used for comparison. The better performance of the mutant was mainly the result of a longer production period. Biogas produced contained up to 99.5% H{sub 2}. (author)

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. \\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.

  1. Λ-enhanced sub-Doppler cooling of lithium atoms in D1 gray molasses

    Science.gov (United States)

    Grier, Andrew T.; Ferrier-Barbut, Igor; Rem, Benno S.; Delehaye, Marion; Khaykovich, Lev; Chevy, Frédéric; Salomon, Christophe

    2013-06-01

    Following the bichromatic sub-Doppler cooling scheme on the D1 line of 40K recently demonstrated in Fernandes [Europhys. Lett.EULEEJ0295-507510.1209/0295-5075/100/63001 100, 63001 (2012)], we introduce a similar technique for 7Li atoms and obtain temperatures of 60μK while capturing all of the 5×108 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 Λ-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.

  2. 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...

  3. 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.

  4. 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.

  5. Fel d 1-airway inflammation prevention and treatment by co-immunization vaccine via induction of CD4+CD25-Foxp3+ Treg cells

    OpenAIRE

    Pei, Yechun; Geng, Shuang; Liu, Lin; Yan, Fengxiang; Hong GUAN; Hou, Jian; Chen, Yongfu; Wang, Bin; An, Xiaorong

    2013-01-01

    Pet allergens are major causes for asthma and allergic rhinitis. Fel d 1 protein, a key pet allergen from domestic cat, can sensitize host and trigger asthma attack. In this study, we report that co-immunization with recombinant Fel d 1 protein (rFel d 1) plus plasmid DNA that contains Fe1 d 1 gene was effective in preventing and treating the natural Fel d 1 (nFel d 1) induced allergic airway inflammation in mice. A population of T regulatory cells (iTreg) exhibiting a CD4+CD25-Foxp3+ phenoty...

  6. RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Hoban PR

    2006-06-01

    Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. Methods Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. Results Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p Conclusion These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.

  7. 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.

  8. 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.

  9. Prognostic significance of cyclin D1 expression in colorectal cancer: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available OBJECTIVE: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC. However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance. METHODS: A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR with 95% confidence intervals (CI was used to estimate the effects. RESULTS: 22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS, disease-free survival (DFS and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63-0.85, P<0.001 and DFS (HR = 0.60, 95% CI: 0.44-0.82, P = 0.001. Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥ 60 years (OR 0.62, 95% CI 0.44-0.89, P = 0.009, T3,4 tumor invasion (OR 0.70, 95% CI 0.57-0.85, P<0.001, N positive (OR 0.75, 95% CI 0.60-0.95, P = 0.016 and distant metastasis (OR 0.60, 95% CI 0.36-0.99, P = 0.047 of CRC. CONCLUSION: The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients.

  10. 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.

  11. 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.

  12. 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%.

  13. Cigarette smoke extract promotes proliferation of airway smooth muscle cells in asthmatic rats via regulating cyclin D1 expression

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-yu; XU Yong-jian; LIU Xian-sheng; ZHANG Zhen-xiang

    2010-01-01

    Background Increased proliferation of airway smooth muscle cells (ASMCs) are observed in asthmatic patients and smoking can accelerate proliferation of ASMCs in asthma. To elucidate the molecular mechanisms leading to these changes, we studied in vitro the effect of cigarette smoke extract (CSE) on the proliferation of ASMCs and the expression of cyclin D1, an important regulatory protein implicated in cell cycle.Methods ASMCs cultured from 8 asthmatic Brown Norway rats were studied. Cells between passage 3 and 6 were used in the study and were divided into control group, pcDNA3.1 group, pcDNA3.1-antisense cyclin D1 (ascyclin D1) group, CSE group, CSE+pcDNA3.1 group and CSE+pcDNA3.1-ascyclin D1 group based on the conditions for intervention. The proliferation of ASMCs was examined with cell cycle analysis, MTT colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemical staining. The expression of cyclin D1 was detected by reverse transcriptase-PCR (RT-PCR) and Western blotting.Results (1) The percentage of S+G2M phase, absorbance value at 490 nm wavelength (A490) and the expression rate of PCNA protein in CSE group were (31.22 1.17)%, 0.782 0.221, (90.2 7.0)% respectively, which were significantly increased compared with those of control group ((18.36 1.02)%, 0.521 0.109, and (54.1 3.5)%, respectively) (P<0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours, the percentage of S+G2M phase, A490 and the expression rate of PCNA protein in ASMCs were much lower than in untreated cells (P <0.01). (2) The ratios of A490 of cyclin D1 mRNA in CSE group was 0.288 0.034, which was significantly increased compared with that of control group (0.158 0.006) (P<0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours, the ratios of A490 of cyclin D1 mRNA in ASMCs was much lower than in untreated cells (P <0.01). (3) The ratios of A490 of cyclin D1 protein expression in CSE group was 0.375 0.008, which was

  14. Cyclin D1 expression in ductal carcinoma of the breast and its correlation with other prognostic parameters

    Directory of Open Access Journals (Sweden)

    Gayatri Ravikumar

    2014-01-01

    Full Text Available Purpose: Cyclin D1 is a cell cycle regulatory gene emerging as a potentially significant oncogene in invasive breast cancers. In this study, we attempted to see the expression of Cyclin D1 in invasive ductal carcinomas of the breast in our population and correlate its expression with other known prognostic parameters. Materials and Methods: A total of 39 cases were selected from our case files from January 2011. Immunohistochemistry for Cyclin D1 was performed and interpreted as positive when >10% of the tumor cells expressed the marker with a moderate to strong intensity of staining. Clinicopathological parameters such as laterality, focality, tumor size, grade, ductal carcinoma in situ (DCIS, axillary lymph node (ALN metastasis, hormone receptor status and human epidermal growth factor receptor 2 status were analyzed and correlated with Cyclin D1 expression. Results: The patients′ age ranged from 30 to 76 years (mean = 53.18. The tumors were unilateral and unifocal in 38 cases; one patient had bilateral synchronous tumors. The majority were grade2 (67.5% and tumor size T2 (57.5%. Nearly 35% were associated with DCIS and 57.5% had ALN metastasis. Estrogen receptors (ER and progesterone receptor (PgR positivity was seen in 65% of the cases and 25% was triple negative. Cyclin D1 expression was seen in 67.5% of the cases in our study. Among the ER, PgR positive and Her-2 negative tumors, Cyclin D1 expression was seen in the majority of cases (92% cases, whereas none of the triple negative tumors showed Cyclin D1 expression. The other prognostic parameters such as tumor size, grade and lymph node status did not show any association with Cyclin D 1 positivity. Conclusions: Cyclin D1 expression was seen in 67.5% of ductal carcinoma and it showed a significant correlation with ER, PgR expression (92% in this study, which is in concordance with other similar studies in literature.

  15. Variational dynamics of the sub-Ohmic spin-boson model on the basis of multiple Davydov D1 states.

    Science.gov (United States)

    Wang, Lu; Chen, Lipeng; Zhou, Nengji; Zhao, Yang

    2016-01-14

    Dynamics of the sub-Ohmic spin-boson model is investigated by employing a multitude of the Davydov D1 trial states, also known as the multi-D1 Ansatz. Accuracy in dynamics simulations is improved significantly over the single D1 Ansatz, especially in the weak system-bath coupling regime. The reliability of the multi-D1 Ansatz for various coupling strengths and initial conditions is also systematically examined, with results compared closely with those of the hierarchy equations of motion and the path integral Monte Carlo approaches. In addition, a coherent-incoherent phase crossover in the nonequilibrium dynamics is studied through the multi-D1 Ansatz. The phase diagram is obtained with a critical point sc = 0.4. For sc < s < 1, the coherent-to-incoherent crossover occurs at a certain coupling strength, while the coherent state recurs at a much larger coupling strength. For s < sc, only the coherent phase exists. PMID:26772548

  16. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi.

    Science.gov (United States)

    Dracatos, Peter M; Payne, Jennifer; Di Pietro, Antonio; Anderson, Marilyn A; Plummer, Kim M

    2016-01-01

    Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. PMID:27598152

  17. Neurogenin2 directs granule neuroblast production and amplification while NeuroD1 specifies neuronal fate during hippocampal neurogenesis.

    Directory of Open Access Journals (Sweden)

    Laurent Roybon

    Full Text Available The specification and differentiation of dentate gyrus granule neurons in the hippocampus require temporally and spatially coordinated actions of both intrinsic and extrinsic molecules. The basic helix-loop-helix transcription factor Neurogenin2 (Ngn2 and NeuroD1 are key regulators in these processes. Based on existing classification, we analyzed the molecular events occurring during hippocampal neurogenesis, primarily focusing on juvenile animals. We found that Ngn2 is transiently expressed by late type-2a amplifying progenitors. The Ngn2 progenies mature into hippocampal granule neurons. Interestingly, the loss of Ngn2 at early stages of development leads to a robust reduction in neurogenesis, but does not disturb granule neuron maturation per se. We found that the role of Ngn2 is to maintain progenitors in an undifferentiated state, allowing them to amplify prior to their maturation into granule neurons upon NeuroD1 induction. When we overexpressed Ngn2 and NeuroD1 in vivo, we found NeuroD1 to exhibit a more pronounced neuron-inductive effect, leading to granule neuron commitment, than that displayed by Ngn2. Finally, we observed that all markers expressed during the transcriptional control of hippocampal neurogenesis in rodents are also present in the human hippocampus. Taken together, we demonstrate a critical role of for Ngn2 and NeuroD1 in controlling neuronal commitment and hippocampal granule neuroblast formation, both during embryonic development and in post-natal hippocampal granule neurogenesis.

  18. 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.

  19. 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.

  20. Dopamine D1 and D3 receptors mediate reconsolidation of cocaine memories in mouse models of drug self-administration.

    Science.gov (United States)

    Yan, Y; Newman, A H; Xu, M

    2014-10-10

    Memories of drug experience and drug-associated environmental cues can elicit drug-seeking and taking behaviors in humans. Disruption of reconsolidation of drug memories dampens previous memories and therefore may provide a useful way to treat drug abuse. We and others previously demonstrated that dopamine D1 and D3 receptors play differential roles in acquiring cocaine-induced behaviors. Moreover, D3 receptors contribute to the reconsolidation of cocaine-induced conditioned place preference. In the present study, we examined effects of manipulating D1 or D3 receptors on reconsolidation of cocaine memories in mouse models of drug self-administration. We found that pharmacological blockade of D1 receptors or a genetic mutation of the D3 receptor gene attenuated reconsolidation that lasted for at least 1week after the memory retrieval. In contrast, with no memory retrieval, pharmacological antagonism of D1 receptors or the D3 receptor gene mutation did not significantly affect reconsolidation of cocaine memories. Pharmacological blockade of D3 receptors also attenuated reconsolidation in wild-type mice that lasted for at least 1week after the memory retrieval. These results suggest that D1 and D3 receptors and related signaling mechanisms play key roles in reconsolidation of cocaine memories in mice, and that these receptors may serve as novel targets for the treatment of cocaine abuse in humans. PMID:25149631

  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. 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.

  3. 增益可控BTL D类音频功率放大器TPA3007D1及其应用%Gain Controllabe BTL Class- D Audio Power Amplifier TPA3007D1 and Its Application

    Institute of Scientific and Technical Information of China (English)

    祝大卫

    2004-01-01

    TI公司新推出的6.5W单声道桥接负载(BTL)D类音频功率放大器芯片TPA3007D1采用第三代调制技术,增益可通过两个输入端(GAIN0和GAIN1)设定.文中介绍了TPA3007D1的内部结构、引脚功能、新一代调制技术及应用电路.

  4. Espacio Residencial y Racionalidad Bioclimática.

    OpenAIRE

    Luxan Garcia de Diego, Margarita de

    2008-01-01

    Como es una especie de introducción, que entiendo que debe ser cortita, he escogido que en vez de hablar de mis obras, voy a hablar de mis preocupaciones. Entre otras razones porque creo que casi es más interesante hacer público señalar cosas que hacen falta tanto de investigación, como de análisis y de elementos de trabajo. Y en ese sentido voy a hablar sobre todo de mis dudas en ese límite entre los que hacen los urbanistas y lo que hacen los arquitectos; porque cada vez veo más imposible d...

  5. Intangible assets for intangible deliverables

    DEFF Research Database (Denmark)

    Elsmore, Matthew J.

    2008-01-01

    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....

  6. 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)

  7. APPLICATION OF BAYES DISCRIMINATING METHOD IN THE DELIVERABILITY PREDICTION%贝叶斯判别方法在产能预测中的应用

    Institute of Scientific and Technical Information of China (English)

    张姮好; 刘江; 邓廷勇

    2011-01-01

    油层产能评价是油田勘探开发过程中的重要环节,也是测井评价技术的难题之一.在常规产能预测分析的基础上,提出按物性分类进行贝叶斯判别,使每一子类具有相近的油气渗流特性和油层污染状况,既减轻了采用测井资料难以确定表皮系数、微裂缝带来的影响,又减小了油相渗透率求取不准带来的误差.结合庆新油田储层泥质含量、孔渗变化大的特点,将油层分为纯砂岩、低含泥砂岩、高含泥或泥质砂岩3类油层,分别给出贝叶斯判别模型并按原油产量划分为4个级别,判别符合率达到80.1%,应用效果良好.%Reservoir deliverability prediction is a key step in oilfield exploration and development, and a difficult issue in logging evaluation as well. Therefore, Bayes discrimination based on property classification is proposed on the foundation of conventional performance prediction analysis. Every property subclass has similar hydrocarbon seepage properties and reservoir pollution, which reduces not only the influence of uncertainty in skin factor and micro-fracture predicted by logging data, but also the error due to inaccurate calculation of oil-phase permeability. Considering the characteristics of shale content in reservoir and great variation of porosity and permeability of Qingx-in Oilfield, formations are categorized into 3 types: pure sandstone, low shale content sandstone, and high shale content or argillaceous sandstone. Bayes discrimination models are established respectively and divided into 4 classes according to oil production. The matching rate of discrimination is 80. 1% , which means the effect is favorable.

  8. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    International Nuclear Information System (INIS)

    Introduction: R-[11C]-SKF 82957 is a high-affinity and potent dopamine D1 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, facilitating the use of R-[11C]-SKF 82957 to image the high-affinity state of the dopamine D1 receptor with PET. Methods: R-[11C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D1 binding of R-[11C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor α-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[11C]-SKF 82957 dopamine D1 binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC90 5.3±4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[11C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D1 antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[11C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[11C]SKF 82957. Under such conditions, R-[11C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D1 receptor by PET.

  9. 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.

  10. 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.

  11. Combined effect of cyclin D3 expression and abrogation of cyclin D1 prevent mouse skin tumor development

    Science.gov (United States)

    Wang, Xian; Sistrunk, Christopher; Miliani de Marval, Paula L; Kim, Yongbaek

    2012-01-01

    We have previously demonstrated that ras-mediated skin tumorigenesis depends on signaling pathways that act preferentially through cyclin D1 and D2. Interestingly, the expression of cyclin D3 inhibits skin tumor development, an observation that conflicts with the oncogenic role of D-type cyclins in the mouse epidermis. Here, we show that simultaneous up and downregulation of particular members of the D-type cyclin family is a valuable approach to reduce skin tumorigenesis. We developed the K5D3/cyclin D1−/− compound mouse, which overexpresses cyclin D3 but lacks expression of cyclin D1 in the skin. Similar to K5D3 transgenic mice, keratinocytes from K5D3/cyclin D1−/− compound mice show a significant reduction of cyclin D2 levels. Therefore, this model allows us to determine the effect of cyclin D3 expression when combined with reduced or absent expression of the remaining two members of the D-type cyclin family in mouse epidermis. Our data show that induced expression of cyclin D3 compensates for the reduced level of cyclin D1 and D2, resulting in normal keratinocyte proliferation. However, simultaneous ablation of cyclin D1 and downregulation of cyclin D2 via cyclin D3 expression resulted in a robust reduction in ras-mediated skin tumorigenesis. We conclude that modulation of the levels of particular members of the D-type cyclin family could be useful to inhibit tumor development and, in particular, ras-mediated tumorigenesis. PMID:22214766

  12. Estrogen induction of the cyclin D1 promoter: Involvement of a cAMP response-like element

    OpenAIRE

    Sabbah, Michele; Courilleau, Delphine; Mester, Jan; Redeuilh, Gerard

    1999-01-01

    Estrogens induce cell proliferation in target tissues by stimulating progression through the G1 phase of the cell cycle. Induction of cyclin D1 expression is a critical feature of the mitogenic action of estrogen. We have determined a region between −96 and −29 in the cyclin D1 promoter that confers regulation by estrogens in the human mammary carcinoma cells MCF-7. This region encompasses a unique known transcription factor binding site with a sequence of a potential cAMP response element (C...

  13. 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.

  14. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system.

    OpenAIRE

    Resnitzky, D; Gossen, M; Bujard, H; Reed, S I

    1994-01-01

    Conditional overexpression of human cyclins B1, D1, and E was accomplished by using a synthetic cDNA expression system based on the Escherichia coli tetracycline repressor. After induction of these cyclins in asynchronous Rat-1 fibroblasts, a decrease in the length of the G1 interval was observed for cyclins D1 and E, consistent with an acceleration of the G1/S phase transition. We observed, in addition, a compensatory lengthening of S phase and G2 so that the mean cell cycle length in popula...

  15. Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine

    OpenAIRE

    Martinez, Diana; Slifstein, Mark; Narendran, Rajesh; Foltin, Richard W.; Broft, Allegra; Hwang, Dah-Ren; Perez, Audrey; Abi-Dargham, Anissa; Fischman, Marian W.; Kleber, Herbert D.; Laruelle, Marc

    2009-01-01

    Objective The goal of this study was to determine D1 receptor availability in human cocaine dependent (CD) subjects and matched healthy controls (HC). In addition, the cocaine dependent subjects performed cocaine self-administration sessions in order to explore the association between D1 receptor availability and cocaine seeking behavior. Methods 25 cocaine dependent subjects (40 ±4 yrs, 19M/6 F) and 23 matched healthy controls (38 ±4 yrs, 19M/4F) were scanned with PET and the radiotracer [11...

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Association of cyclin D1 genotype with breast cancer risk and survival.

    Science.gov (United States)

    Shu, Xiao Ou; Moore, Derek B; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Pierce, Larry; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G(1) to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction < 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis. PMID:15668481

  4. Final repository for spent nuclear fuel. Underground design Forsmark, Layout D1

    International Nuclear Information System (INIS)

    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 to the applied

  5. 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

  6. Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation.

    Science.gov (United States)

    Karasinska, Joanna M; George, Susan R; Cheng, Regina; O'Dowd, Brian F

    2005-10-01

    Co-localization of dopamine D1 and D3 receptors in striatal neurons suggests that these two receptors interact at a cellular level in mediating dopaminergic function including psychostimulant-induced behaviour. To study D1 and D3 receptor interactions in cocaine-mediated effects, cocaine-induced locomotion and reward in mice lacking either D1, D3 or both receptors were analysed. Spontaneous locomotor activity was increased in D1-/- and D1-/-D3-/- mice and D1-/-D3-/- mice did not exhibit habituation of spontaneous rearing activity. Cocaine (20 mg/kg) increased locomotor activity in wild-type and D3-/- mice, failed to stimulate activity in D1-/- mice and reduced activity in D1-/-D3-/- mice. In the conditioned place preference, all groups exhibited reward at 5, 10 and 20 mg/kg of cocaine. D1-/-D3-/- mice did not demonstrate preference at 2.5 mg/kg of cocaine although preference was observed in wild-type, D1-/- and D3-/- mice. The transcription factor cAMP-responsive element binding protein (CREB) is activated by phosphorylation in striatal regions following dopamine receptor activation. Striatal pCREB levels following acute cocaine were increased in wild-type and D3-/- mice and decreased in D1-/- and D1-/-D3-/- mice. After repeated administration of 2.5 mg/kg of cocaine, D1-/- mice had lower pCREB levels in caudate-putamen and nucleus accumbens. Our findings suggest that, although spontaneous and cocaine-induced horizontal activity depended mainly on the presence of the D1 receptor, there may be crosstalk between D1 and D3 receptors in rearing habituation and the perception of cocaine reward at low doses of the drug. Furthermore, alterations in pCREB levels were associated with changes in cocaine-induced locomotor activity but not reward. PMID:16197514

  7. On the number of solutions of the generalized Ramanujan-Nagell equation $D_{1}x^2+D_{2}^{m}=2^{n+2}$}

    OpenAIRE

    Jianghua, Li

    2013-01-01

    Let $D_{1}$, $D_{2}$ be coprime odd integers with min$(D_{1},D_{2})>1$, and let $N(D_{1},D_{2})$ denote the number of positive integer solutions $(x, m, n)$ of the equation $D_{1}x^2+D_{2}^{m}=2^{n+2}$. In this paper, we prove that $N(D_{1},D_{2})\\leq 2$ except for $N(3,5)=N(5,3)=4$ and $N(13,3)=N(31,97)=3$.

  8. D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.

    Science.gov (United States)

    Krawczyk, Michal; Mason, Xenos; DeBacker, Julian; Sharma, Robyn; Normandeau, Catherine P; Hawken, Emily R; Di Prospero, Cynthia; Chiang, Cindy; Martinez, Audrey; Jones, Andrea A; Doudnikoff, Évelyne; Caille, Stephanie; Bézard, Erwan; Georges, François; Dumont, Éric C

    2013-07-17

    Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. PMID:23864683

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 26 CFR 1.691(d)-1 - Amounts received by surviving annuitant under joint and survivor annuity contract.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Amounts received by surviving annuitant under... Decedents § 1.691(d)-1 Amounts received by surviving annuitant under joint and survivor annuity contract. (a) In general. Under section 691(d), annuity payments received by a surviving annuitant under a...

  15. 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

    2016-04-01

    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. PMID:26874213

  16. D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats

    Science.gov (United States)

    Krawczyk, Michal; Mason, Xenos; DeBacker, Julian; Sharma, Robyn; Normandeau, Catherine P.; Hawken, Emily R.; Di Prospero, Cynthia; Chiang, Cindy; Martinez, Audrey; Jones, Andrea A.; Doudnikoff, Évelyne; Caille, Stephanie; Bézard, Erwan; Georges, François; Dumont, Éric C.

    2014-01-01

    Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. PMID:23864683

  17. 26 CFR 1.924(d)-1 - Requirement that economic processes take place outside the United States.

    Science.gov (United States)

    2010-04-01

    ... addresses the customer's attention to the product or service which is the subject of the transaction. For... customers. Through its existing agreements with a domestic unrelated person, the related supplier... requirements of section 924(d)(1)(A). For example, if a FSC sells a product to a foreign customer by...

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Stöckli, Jacqueline; Meoli, Christopher C; Hoffman, Nolan J;

    2015-01-01

    Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated...... in this process: AS160 for insulin stimulation and its homolog, TBC1D1, are suggested to regulate exercise-mediated glucose uptake into muscle. TBC1D1 has also been implicated in obesity in humans and mice. We investigated the role of TBC1D1 in glucose metabolism by generating TBC1D1(-/-) mice and...... analyzing body weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise...

  6. 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.

  7. 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.

  8. Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer

    International Nuclear Information System (INIS)

    Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer. The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments. In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass. The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA

  9. 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.

  10. 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.

  11. The neurosteroidogenic enzyme 5α-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating.

    Science.gov (United States)

    Frau, Roberto; Mosher, Laura J; Bini, Valentina; Pillolla, Giuliano; Pes, Romina; Saba, Pierluigi; Fanni, Silvia; Devoto, Paola; Bortolato, Marco

    2016-01-01

    Neurosteroids exert diverse modulatory actions on dopamine neurotransmission and signaling. We previously documented that the enzyme 5α-reductase, which catalyzes the main rate-limiting step in neurosteroid synthesis, is required for the behavioral responses of Sprague-Dawley rats to non-selective dopaminergic agonists, such as the D1-D2 receptor agonist apomorphine. Specifically, systemic and intra-accumbal administrations of the 5α-reductase inhibitor finasteride countered apomorphine-induced deficits of sensorimotor gating, as measured by the prepulse inhibition (PPI) of the startle reflex; the classes of dopamine receptors involved in these effects, however, remain unknown. Prior rodent studies have revealed that the contributions of dopamine receptors to PPI regulation vary depending on the genetic background; thus, we analyzed the effect of finasteride on the PPI deficits induced by selective dopamine receptor agonists in Long-Evans (a strain exhibiting PPI deficits in response to both D1 and D2 receptor agonists) and Sprague-Dawley rats (which display PPI reductions following treatment with D2, and D3, but not D1 receptor agonists). In Long-Evans rats, finasteride opposed the PPI deficits induced by activation of D1, but not D2 receptors; conversely, in Sprague-Dawley rats, finasteride prevented the reductions in %PPI and accumbal dopamine extracellular levels caused by selective stimulation of D3, but not D2 receptors; however, the effects on %PPI were not confirmed by analyses on absolute PPI values. Our findings suggest that 5α-reductase modulates the effects of D1, but not D2 receptor agonists on sensorimotor gating. These data may help elucidate the role of neurosteroids in neuropsychiatric disorders featuring PPI deficits, including schizophrenia and Tourette syndrome. PMID:26415119

  12. Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical coupling.

    Science.gov (United States)

    Sinha, Krishna Murari; Glickman, Michael S; Shuman, Stewart

    2009-05-19

    Mycobacterial UvrD1 is a DNA-dependent ATPase and a Ku-dependent 3' to 5' DNA helicase. The UvrD1 motor domain resembles that of the prototypal superfamily I helicases UvrD and PcrA. Here we performed a mutational analysis of UvrD1 guided by the crystal structure of a DNA-bound Escherichia coli UvrD-ADP-MgF(3) transition state mimetic. Alanine scanning and conservative substitutions identified amino acids essential for both ATP hydrolysis and duplex unwinding, including those implicated in phosphohydrolase chemistry via transition state stabilization (Arg308, Arg648, Gln275), divalent cation coordination (Glu236), or activation of the nucleophilic water (Glu236, Gln275). Other residues important for ATPase/helicase activity include Phe280 and Phe72, which interact with the DNA 3' single strand tail. ATP hydrolysis was uncoupled from duplex unwinding by mutations at Glu609 (in helicase motif V), which contacts the ATP ribose sugar. Introducing alanine in lieu of the adenine-binding "Q motif" glutamine (Gln24) relaxed the substrate specificity in NTP hydrolysis, e.g., eliciting a gain of function as a UTPase/TTPase, although the Q24A mutant still relied on ATP/dATP for duplex unwinding. Our studies highlight the role of the Q motif as a substrate filter and the contributions of adenosine-binding residues as couplers of NTP hydrolysis to motor activity. The Ku-binding function of UvrD1 lies within its C-terminal 270 amino acid segment. Here we found that deleting the 90 amino acid C-terminal domain, which is structurally uncharacterized, diminished DNA unwinding, without affecting ATP hydrolysis or binding to the DNA helicase substrate, apparently by affecting the strength of the UvrD1-Ku interaction. PMID:19317511

  13. Mapping of the spontaneous deletion in the Ap3d1 gene of mocha mice: fast and reliable genotyping

    Directory of Open Access Journals (Sweden)

    Delenclos Marion

    2008-11-01

    Full Text Available Abstract Background The mocha mouse carries a spontaneous deletion in the Ap3d1 gene, encoding the delta 1 subunit of the adaptor related protein complex 3, (Ap3d1, and subsequently lack the expression of functional AP-3. This leads to a deficiency in vesicle transport and storage, which affects neurotransmitter vesicle turnover and release in the central nervous system. Since the genomic sequence of the Ap3d1 gene of mocha mouse is not known, precise mapping of the deletion as well as reliable genotyping protocols are lacking. Findings We sequenced the Ap3d1 gene (HGNC GeneID: 8943 around the deletion site in the mocha mouse and revealed a 10639 bp deletion covering exon 2 to 6. Subsequently, new PCR primers were designed yielding a reliable genotyping protocol of both newborn and adult tissue. To examine the genotypes further, hippocampal neurons were cultured from mocha and control mice. Patch-clamp recordings showed that mocha neurons had a higher input resistance, and that autaptic EPSC in mocha cultures depressed faster and stronger as compared with control cultures. Conclusion Our study reports the sequence of the deleted part of the Ap3d1 gene in mocha mice, as well as a reliable PCR-based genotyping protocol. We cultured hippocampal neurons from control and mocha mice, and found a difference in input resistance of the neurons, and in the synaptic short-term plasticity of glutamatergic autapses showing a larger synaptic depression than controls. The described procedures may be useful for the future utilization of the mocha mouse as a model of defective vesicle biogenesis. Importantly, as genotyping by eye color is complicated in newborn mice, the designed protocol is so fast and reliable that newborn mice could rapidly be genotyped and hippocampal neurons dissociated and cultured, which is normally best done at P0-P2.

  14. Opposing effects of dopamine D1- and D2-like agonists on intracranial self-stimulation in male rats.

    Science.gov (United States)

    Lazenka, Matthew F; Legakis, Luke P; Negus, S Stevens

    2016-06-01

    Dopamine acts through dopamine Type I receptors (comprising D1 and D5 subtypes) and dopamine Type II receptors (comprising D2, D3, and D4 subtypes). Intracranial self-stimulation (ICSS) is 1 experimental procedure that can be used to evaluate abuse-related effects of drugs targeting dopamine receptors. This study evaluated effects of dopamine receptor ligands on ICSS in rats using experimental procedures that have been used previously to examine abused indirect dopamine agonists such as cocaine and amphetamine. Male Sprague-Dawley rats responded under a fixed-ratio 1 schedule for electrical stimulation of the medial forebrain bundle, and frequency of stimulation varied from 56-158 Hz in 0.05 log increments during each experimental session. Drug potency and time course were determined for the D1 ligands A77636, SKF82958, SKF38393, fenoldopam, and SCH39166 and the D2/3 ligands sumanirole, apomorphine, quinpirole, PD128907, pramipexole, aripiprazole, eticlopride, and PG01037. The high-efficacy D1 agonists A77636 and SKF82958 produced dose-dependent, time-dependent, and abuse-related facilitation of ICSS. Lower efficacy D1 ligands and all D2/3 ligands failed to facilitate ICSS at any dose or pretreatment time. A mixture of SKF82958 and quinpirole produced a mixture of effects produced by each drug alone. Quinpirole also failed to facilitate ICSS after regimens of repeated treatment with either quinpirole or cocaine. These studies provide more evidence for divergent effects of dopamine D1- and D2-family agonists on ICSS procedure in rats and suggest that ICSS may be a useful complement to other approaches for preclinical abuse potential assessment, in part because of the reproducibility of results. (PsycINFO Database Record PMID:26987070

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Role of cyclin D1 in differentiation of thymocytes induced by rentinoids in mice%Cyclin D1在视黄酸诱导胸腺细胞分化中的作用研究

    Institute of Scientific and Technical Information of China (English)

    杨志祥; 糜漫天; 张乾勇; 郎海滨; 韦娜

    1999-01-01

    目的:探讨视黄醇类化合物促胸腺细胞分化的分子机制.方法:选择幼年小鼠胸腺细胞为研究对象,采用免疫组化染色、Western blot、流式细胞分析等实验方法,观察全反式视黄酸(ATRA)或视黄醇(Retinol)灌胃给药后对胸腺细胞分化成熟的影响,同时检测周期调控蛋白cyclinD1及相应基因表达变化情况.结果:ATRA和Retinol均可抑制胸腺细胞增殖活性,使胸腺组织中成熟功能T细胞比例增大;胸腺细胞cyclinD1、CDK4和RB基因表达呈时间剂量依赖性下调,而P16、P21蛋白表达上调,且ATRA作用优于Retinol.结论:RA可能经PRb、P16等多因素反馈调节cyclinD1和CDK4表达,抑或直接同其发生作用,进而影响胸腺细胞增殖分化的变化.

  2. Correlation of antiaging effects of Fructus Corni Polysaccharides with cyclinD1 expression%山茱萸多糖抗HDF衰老与cyclinD1表达的关系

    Institute of Scientific and Technical Information of China (English)

    欧芹; 葛堂栋; 王迪迪; 王跃新

    2008-01-01

    目的:探讨山茱萸多糖对抗HDF细胞衰老作用及对细胞周期蛋白的作用.方法:体外培养HDF细胞,实验组从40代开始加多糖含药血清.在培养至43代、47代和50代采用MTT法检测细胞活力,RT-PCR法检测cyclinD1的mRNA表达,并与30代时进行比较.结果:衰老组细胞活力下降,cyclinD1 mRNA表达升高;山茱萸多糖血清可提高细胞活力,降低HDF细胞cyclinD1 mRNA含量表达. 结论:山茱萸多糖可能通过改变细胞周期调控因子的表达而发挥其抗HDF细胞衰老作用.

  3. D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses.

    Science.gov (United States)

    Cahill, E; Pascoli, V; Trifilieff, P; Savoldi, D; Kappès, V; Lüscher, C; Caboche, J; Vanhoutte, P

    2014-12-01

    Convergent dopamine and glutamate signalling onto the extracellular signal-regulated kinase (ERK) pathway in medium spiny neurons (MSNs) of the striatum controls psychostimulant-initiated adaptive processes underlying long-lasting behavioural changes. We hypothesised that the physical proximity of dopamine D1 (D1R) and glutamate NMDA (NMDAR) receptors, achieved through the formation of D1R/NMDAR complexes, may act as a molecular bridge that controls the synergistic action of dopamine and glutamate on striatal plasticity and behavioural responses to drugs of abuse. We found that concomitant stimulation of D1R and NMDAR drove complex formation between endogenous D1R and the GluN1 subunit of NMDAR. Conversely, preventing D1R/GluN1 association with a cell-permeable peptide (TAT-GluN1C1) left individual D1R and NMDAR-dependent signalling intact, but prevented D1R-mediated facilitation of NMDAR-calcium influx and subsequent ERK activation. Electrophysiological recordings in striatal slices from mice revealed that D1R/GluN1 complexes control the D1R-dependent enhancement of NMDAR currents and long-term potentiation in D1R-MSN. Finally, intra-striatal delivery of TAT-GluN1C1 did not affect acute responses to cocaine but reduced behavioural sensitization. Our findings uncover D1R/GluN1 complexes as a major substrate for the dopamine-glutamate interaction in MSN that is usurped by addictive drugs to elicit persistent behavioural alterations. They also identify D1R/GluN1 complexes as molecular targets with a therapeutic potential for the vast spectrum of psychiatric diseases associated with an imbalance between dopamine and glutamate transmission. PMID:25070539

  4. 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.

  5. Current status of the Faraday Filter-Based Spectrometer to Measure Sodium Nightglow D2/D1 Intensity Ratios

    Science.gov (United States)

    Harrell, S.; She, C.; Krueger, D. A.; Yuan, T.

    2009-12-01

    Slanger et al. (2005) first observed an annual variation in the sodium nightglow intensity ratio of D2 (589.158 nm) to D1 (589.756 nm) emissions. Their proposed modified Chapman mechanism invokes two competing chemical pathways, showing that the intensity ratio is related to the concentration ratio of atomic oxygen [O] to molecular oxygen [O2]. This paper will describe laboratory and field testing of the compact, Faraday filter-based spectrometer to measure the D2/D1 intensity ratio of the nightglow--particularly results of our study on the effects of sky background on ratio measurements. This method also permits determination of the fractional contributions of the two chemical pathways to test the validity of the modified Chapman mechanism. Since delineation of the two chemical pathways requires a spectral resolution of 0.0002 nm, this is not possible with any other existing instrument.

  6. Efficient all-optical production of large Li6 quantum gases using D1 gray-molasses cooling

    Science.gov (United States)

    Burchianti, A.; Valtolina, G.; Seman, J. A.; Pace, E.; De Pas, M.; Inguscio, M.; Zaccanti, M.; Roati, G.

    2014-10-01

    We use a gray molasses operating on the D1 atomic transition to produce degenerate quantum gases of Li6 with a large number of atoms. This sub-Doppler cooling phase allows us to lower the initial temperature of 109 atoms from 500 to 40 μK in 2 ms. We observe that D1 cooling remains effective into a high-intensity infrared dipole trap where two-state mixtures are evaporated to reach the degenerate regime. We produce molecular Bose-Einstein condensates of up to 5 × 105 molecules and weakly interacting degenerate Fermi gases of 7×105 atoms at T /TF<0.1 with a typical experimental duty cycle of 11 s.

  7. 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.

  8. 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)

  9. Analysis of an avtA::Mu d1(Ap lac) mutant: metabolic role of transaminase C.

    OpenAIRE

    Whalen, W A; Berg, C M

    1982-01-01

    Escherichia coli can synthesize alpha-ketoisovalerate, the precursor of valine, leucine, and pantothenate, by three routes: anabolically via dihydroxyacid dehydrase and catabolically via both the branched-chain amino acid transaminase (transaminase B) and the alanine-valine transaminase (transaminase C). An E. coli K-12 mutant devoid of transaminase C (avtA) was isolated by mutagenizing an isoleucine-requiring strain devoid of transaminase B (ilvE::Tn5) with Mu d1(Ap lac) and selecting for va...

  10. 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.

  11. 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.

  12. Microscopic description of fission in neutron-rich plutonium isotopes with the Gogny-D1M energy density functional

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Guzman, R. [Rice University, Department of Physics and Astronomy, Houston, Texas (United States); Rice University, Department of Chemistry, Houston, Texas (United States); Robledo, L.M. [Universidad Autonoma de Madrid, Departamento de Fisica Teorica, Madrid (Spain)

    2014-09-15

    The most recent parametrization D1M of the Gogny energy density functional is used to describe fission in the isotopes {sup 232-280}Pu. We resort to the methodology introduced in our previous studies (Phys. Rev. C 88, 054325 (2013) and Phys. Rev. C 89, 054310 (2014)) to compute the fission paths, collective masses and zero point quantum corrections within the Hartree-Fock-Bogoliubov framework. The systematics of the spontaneous fission half-lives t{sub SF}, masses and charges of the fragments in plutonium isotopes is analyzed and compared with available experimental data. We also pay attention to isomeric states, the deformation properties of the fragments as well as to the competition between the spontaneous fission and α-decay modes. The impact of pairing correlations on the predicted t{sub SF} values is demonstrated with the help of calculations for {sup 232-280}Pu, in which the pairing strengths of the Gogny-D1M energy density functional are modified by 5% and 10%, respectively. We further validate the use of the D1M parametrization through the discussion of the half-lives in {sup 242-262}Fm. Our calculations corroborate that, though the uncertainties in the absolute values of physical observables are large, the Gogny-D1M Hartree-Fock-Bogoliubov framework still reproduces the trends with mass and/or neutron numbers and therefore represents a reasonable starting point to describe fission in heavy nuclear systems from a microscopic point of view. (orig.)

  13. 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.

  14. 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.

  15. Lack of lysosomal fusion with phagosomes containing Ehrlichia risticii in P388D1 cells: abrogation of inhibition with oxytetracycline.

    OpenAIRE

    Wells, M Y; Rikihisa, Y

    1988-01-01

    Fusion of lysosomes with phagosomes containing Ehrlichia risticii, an obligate intracellular parasite, was evaluated in P388D1 murine macrophagelike cells. Lysosomes in cells ranging in infectivity from 30 to 70% were labeled cytochemically with acid phosphatase or via endocytosis of thorium dioxide or cationized ferritin to document phagosome-lysosome (P-L) fusion in untreated cells and cells treated with oxytetracycline. Regardless of the marker used, P-L fusion was generally not observed i...

  16. Role of HDL in cholesteryl ester metabolism of lipopolysaccharide-activated P388D1 macrophages[S

    OpenAIRE

    Uda, Sabrina; Spolitu, Stefano; Angius, Fabrizio; Collu, Maria; Accossu, Simonetta; Banni, Sebastiano; Murru, Elisabetta; Sanna, Francesca; Batetta, Barbara

    2013-01-01

    Infections share with atherosclerosis similar lipid alterations, with accumulation of cholesteryl esters (CEs) in activated macrophages and concomitant decrease of cholesterol-HDL (C-HDL). Yet the precise role of HDL during microbial infection has not been fully elucidated. Activation of P388D1 by lipopolysaccharide (LPS) triggered an increase of CEs and neutral lipid contents, along with a remarkable enhancement in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-HDL uptake...

  17. Immunohistochemical Expression of P53 and Cyclin D1 Proteins in Follicular Thyroid Tumors: Evaluation of Their Significance

    Directory of Open Access Journals (Sweden)

    Ahmed H. Abdel-Rahman El-Rashidy1- Samir Abdel Salam A. Ibraheim2

    2007-12-01

    Full Text Available The sequential mutational events which may underlie the tumorigenesis of thyroid neoplasia are gradually becoming apparent. To clarify the role of P53 and cyclin D1 in the oncogenesis and tumor progression of thyroid neoplasms, we examined the immunoreactivity of these proteins in one hundred and thirty (130 thyroid tumors originating from the follicular epithelium using immunohistochemistry. The tumors were divided into two groups group I: included thirty five (35 follicular adenomas and group II: included ninety five (95 follicular carcinomas; 65 of which were well differentiated (WDC while the remaining (30 were poorly differentiated (PDC. P53 positivity was more frequent in group II (20/95; 21.1% than in group I (6/35; 17.1% and in PDC (11/30; 26.6% than WDC (9/65; 13.8%. On the other hand, cyclin D1 positivity was frequent in WDC (21/65; 32.3% and rarely seen in adenoma group (2/35; 5.7%. Co ­positivity for P53 and cyclin D1 proteins was more observed in PDC (5/30; 16.7% than in WDC (3/65; 4.6%. The study suggested that cyclin DI may be involved in the thyroid oncogenesis and concluded that both proteins may be incriminated in the progression of follicular thyroid neoplasms. Moreover, we found that age at the time of diagnosis, the histologic differentiation, necrosis in primary tumor, extrathyroidal invasion and the presence of distant metastases are important prognostic and risk factors. In addition, our study revealed that the detection of P53, but not cyclin D1, in primary follicular carcinomas is a significant independent prognostic indicator which, together with the above mentioned important prognostic factors, may be of value in the theraputic planning of these tumors

  18. 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.

  19. Similarity of Recombinant Human Perlecan Domain 1 by Alternative Expression Systems Bioactive Heterogenous Recombinant Human Perlecan D1

    OpenAIRE

    Ellis April L; Pan Wensheng; Yang Guang; Jones Kim; Chuang Christine; Whitelock John M; DeCarlo Arthur A

    2010-01-01

    Abstract 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 SD...

  20. Evaluation of D1 and D2 Dopamine Receptor Segregation in the Developing Striatum Using BAC Transgenic Mice

    OpenAIRE

    Dominic Thibault; Fabien Loustalot; Fortin, Guillaume M.; Marie-Josée Bourque; Louis-Éric Trudeau

    2013-01-01

    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 proces...

  1. Loop Quantization of a Model for D=1+2 (Anti)de Sitter Gravity Coupled to Topological Matter

    OpenAIRE

    Constantinidis, Clisthenis P.; Oporto, Zui; Piguet, Olivier

    2014-01-01

    We present a complete quantization of Lorentzian D=1+2 gravity with cosmological constant, coupled to a set of topological matter fields. The approach of Loop Quantum Gravity is used thanks to a partial gauge fixing leaving a residual gauge invariance under a compact semi-simple gauge group, namely Spin(4) = SU(2) x SU(2). A pair of quantum observables is constructed, which are non-trivial despite of being null at the classical level.

  2. Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats.

    Science.gov (United States)

    Izquierdo, Alicia; Pozos, Hilda; Torre, Adrianna De La; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

    2016-07-15

    Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

  3. Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

    Science.gov (United States)

    Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

    2016-01-01

    Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

  4. 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.

  5. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function.

    Science.gov (United States)

    Kain, Vasundhara; Ingle, Kevin A; Colas, Romain A; Dalli, Jesmond; Prabhu, Sumanth D; Serhan, Charles N; Joshi, Medha; Halade, Ganesh V

    2015-07-01

    Unresolved inflammation is a major contributor to the development of heart failure following myocardial infarction (MI). Pro-resolving lipid mediators, such as resolvins (e.g. RvD1), are biosynthesized endogenously. The role of RvD1 in resolving post-MI inflammation has not been elucidated due to its unstable nature. Here, we have tested the role for two forms of RvD1, after incorporation into liposomes (Lipo-RvD1) and its free acid form (RvD1) in the left ventricle (LV) and splenic remodeling post-MI. 8 to 12-week old male, C57BL/6J-mice were subjected to coronary artery ligation and Lipo-RvD1 or RvD1 (3 μg/kg/day) was injected 3h post-MI for day (d)1 or until d5. No-MI mice and saline-injected MI mice served as controls. RvD1 injected groups showed improved fractional shortening post-MI; preserving transient changes in the splenic reservoir compared to MI-saline. RvD1-groups showed an early exit of neutrophils from LV and spleen at d5 post-MI with an increased expression of lipoxin A4 receptor (ALX; synonym formyl peptide receptor; FPR2) compared to the MI-saline group. The levels of pro-resolving mediators RvD1, RvD2, Maresin 1 (MaR1) and Lipoxin A4 (LXA4) were increased in spleens from RvD1 injected mice at d5 post-MI. RvD1 administration reduced macrophage density, ccr5 and cxcl5 levels at d5 post-MI compared to saline injected mice (both, p macrophage-mediated clearance of necrotic cells in RvD1-groups. RvD1 reduced the pro-fibrotic genes (colla1, coll2a1 and tnc (all; p < 0.05)) and decreased collagen deposition, thereby reducing post-MI fibrosis and thus stabilizing the extracellular matrix. In summary, RvD1 and Lipo-RvD1 promote the resolution of acute inflammation initiated by MI, thereby delaying the onset of heart failure. PMID:25870158

  6. 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).

  7. 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.

  8. Molecular and pharmacological characterization of two D(1)-like dopamine receptors in the Lyme disease vector, Ixodes scapularis.

    Science.gov (United States)

    Meyer, Jason M; Ejendal, Karin F K; Watts, Val J; Hill, Catherine A

    2011-08-01

    Advancements in tick neurobiology may impact the development of acaricides to control those species that transmit human and animal diseases. Here, we report the first cloning and pharmacological characterization of two neurotransmitter binding G protein-coupled receptors in the Lyme disease (blacklegged) tick, Ixodes scapularis. The genes IscaGPRdop1 and IscaGPRdop2 were identified in the I. scapularis genome assembly and predicted as orthologs of previously characterized D(1)-like dopamine receptors in the fruit fly Drosophila melanogaster and honeybee Apis mellifera. Heterologous expression in HEK 293 cells demonstrated that each receptor functioned as a D(1)-like dopamine receptor because significant increases in levels of intracellular cyclic adenosine monophosphate (cAMP) were detected following dopamine treatment. Importantly, the receptors were distinct in their pharmacological properties regarding concentration-dependent response to dopamine, constitutive activity, and response to other biogenic amines. Exposure to a variety of dopamine receptor agonists and antagonists further demonstrated a D(1)-like pharmacology of these dopamine receptors and highlighted their differential activities in vitro. PMID:21457782

  9. 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.

  10. 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.

  11. 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...

  12. Atomic Parity Violation, Muon Pair Production in e+e - Collisions and Detection of CDM WIMP-Physics Related to Neutral Vector Boson D1

    Science.gov (United States)

    Senju, H.

    1999-11-01

    In our preon model there exists a neutral vector boson D1 which is an isoscalar partner of W(Z) in the vector boson octet. It is shown that the exchange of a D1 of about 1 TeV mass naturally explains a positive excess of the weak charge of atomic cesium recently observed. Other processes occurring through the D1 exchange are discussed, including the detection of CDM WIMP.

  13. 无滤波器D类音频功率放大器TPA2005D1%Filter-Free Class-D Audio Power Amplifier

    Institute of Scientific and Technical Information of China (English)

    吴祖国

    2003-01-01

    TPA2005D1是Texas Instruments公司生产的一款新型无滤波器D类音频功率放大器.文章以TPA2005D1为例介绍了TPA200xDx系列器件的基本性能和特点,给出了TPA2005D1在便携设备上的应用电路.

  14. Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder.

    Science.gov (United States)

    Rosell, Daniel R; Zaluda, Lauren C; McClure, Margaret M; Perez-Rodriguez, M Mercedes; Strike, K Sloan; Barch, Deanna M; Harvey, Philip D; Girgis, Ragy R; Hazlett, Erin A; Mailman, Richard B; Abi-Dargham, Anissa; Lieberman, Jeffrey A; Siever, Larry J

    2015-01-01

    Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive

  15. Positive Integer Solution on the Generalized Ramanujan- Nagell Equation D1 x2 + D2 = pn%关于广义Ramanujan-Nagell方程的整数解

    Institute of Scientific and Technical Information of China (English)

    陈锡庚; 黄寿生

    2006-01-01

    D1,D2是互素的正整数,且设p是一个满足p D1D2的奇素数.该文证明:如果D1+D2=4p',这里r是一个正整数,则方程D1x2+D2=pn有正整数解(x,n)当且仅当3p'-D2=±2,则方程只有一个解(x,n)=| p'-D2|/2,3r).

  16. Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way in human colorectal cancer cells.

    Science.gov (United States)

    Kim, Mi Kyoung; Park, Gwang Hun; Eo, Hyun Ji; Song, Hun Min; Lee, Jin Wook; Kwon, Min Ji; Koo, Jin Suk; Jeong, Jin Boo

    2015-03-01

    Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer activity. However, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to elucidate the biological mechanism by which TAN I may induce the inhibition of cell growth in human colorectal cancer cells. The treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of cyclin D1 at threonine-286 was increased by TAN I and a point mutation of threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation. Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent downregulation by TAN I. From these results, we suggest that TAN I-mediated cyclin D1 downregulation may result from proteasomal degradation through its ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current study provides new mechanistic link between TAN I, cyclin D1 downregulation and cell growth in human colorectal cancer cells. PMID:25615593

  17. 小麦Wx-A1和Wx-D1位点的PCR分子标记%PCR-based Molecular Markers for Wx-A1 and Wx-D1 Genes of Wheat

    Institute of Scientific and Technical Information of China (English)

    刘迎春; 朱惠兰; 程顺和; 马正强

    2005-01-01

    为了获得筛选低直链淀粉含量的分子标记,根据已知小麦Waxy基因序列设计PCR引物,通过在基因水平和蛋白质水平进行分离群体验证,建立分别专一检测Wx-Al位点和Wx-D1位点的PCR标记MAG264和MAG269.在分离群体中,MAG264标记能清楚地区分Wx-A1位点的三种不同基因型,呈共显性遗传.MAG269标记引物在野生型中扩增片段为1 400bp,在突变型(Wx-D1bWx-D1b)中的扩增片段为800bp.但在分离群体中没有出现杂合体带型,从而使本应该表现为共显性的标记表现为显性遗传.MAG264和MAG269引物对DNA的扩增稳定性、重复性好.这些结果表明,本研究获得的Waxy基因分子标记可以用于小麦Waxy基因缺失类型的鉴定和糯质专用小麦的分子标记辅助选育.

  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. Expression of E2F -1 and cyclinD1 in colorectal adenocarcinoma and its significance%大肠癌E2F -1、CyclinD1的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    王蕾; 何妍; 李希芳; 刘岩; 时志民; 刘惠民

    2011-01-01

    Objective To study the expression of E2K - 1 and ryclinDl in human colorectal adenocarcinoma and its significance. Methods Terminal deoxynucleotidyl transferase - mediated nick end labeling TUNEL method and immunohistochemical SP method were used to detect 78 cases of colorectal adenocarcinoma, 20 cases of normal eoloreclal mucosa, 30 cases of colorectal polyps, and 30 cases of coloreotal adenoma cells in situ withered death ( Al) , and E2F - 1 and cyclinDl expression. Results The positive expression rate of E2F - 1 and cyclinDl in esophageal carcinoma was much higher than that in colorectal mucosa, colorectal polyps, and colorectal adenoma (P < 0. 05 ). The expression of E2F - 1 was closely correlated with the differentiation, TNM and lymph node metastasis (P <0. 05). Conclusions E2F - 1 and cyclinDl are closely related to the occurrence of colorectal adenocarcinoma. Both of them are important biological markers in colorectal adenocarcinoma occurrence and development.%目的 探讨E2F -1和cyclinD1在大肠腺癌组织中的表达及其意义 方法 采用脱氧核糖核酸末端转移酶介导的TUNEL法缺口末端标记和免疫组化SP法检测大肠腺癌78例、正常大肠黏膜20例、大肠息肉30例,以及大肠腺瘤细胞30例的原位凋亡(Al)及E2F-1和cyclin D1的表达情况.结果 E2F-1和cyclin D1在大肠腺癌中的阳性率显著高于正常大肠黏膜、大肠息肉以及大肠腺瘤(P<0.05).E2F-1表达与大肠腺癌的病理分化程度、淋巴结转移和临床分期具有相关性(P<0 05).从正常大肠黏膜、大肠息肉、大肠腺瘤到大肠腺癌细胞凋亡呈梯度降低.结论 E2F -1和cyclinD1的表达与大肠腺癌发生关系密切,是大肠腺癌发生、发展的重要生物学标记物

  20. Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

    Directory of Open Access Journals (Sweden)

    Sheeja Aravindan

    Full Text Available Pancreatic cancer (PC remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27. Total anti-oxidant capacity (TAC analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.