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. Bioclim deliverable D8a: development of the rule-based down-scaling methodology for BIOCLIM Work-package 3

    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 (WP) have been identified to fulfill the project objectives. One of the tasks of BIOCLIM WP3 was to develop a rule-based approach for down-scaling from the MoBidiC model of intermediate complexity in order to provide consistent estimates of monthly temperature and precipitation for the specific regions of interest to BIOCLIM (Central Spain, Central England and Northeast France, together with Germany and the Czech Republic). A statistical down-scaling methodology has been developed by Philippe Marbaix of CEA/LSCE for use with the second climate model of intermediate complexity used in BIOCLIM - CLIMBER-GREMLINS. The rule-based methodology assigns climate states or classes to a point on the time continuum of a region according to a combination of simple threshold values which can be determined from the coarse scale climate model. Once climate states or classes have been defined, monthly temperature and precipitation climatologies are constructed using analogue stations identified from a data base of present-day climate observations. The most appropriate climate classification for BIOCLIM purposes is the Koeppen/Trewartha scheme. This scheme has the advantage of being empirical, but only requires monthly averages of temperature and precipitation as input variables. Section 2 of this deliverable (D8a) outline how each of the eight methodological steps have been undertaken for each of the three main BIOCLIM study regions (Central England, Northeast France and Central Spain) using Mo

  5. Bioclim Deliverable D8b: development of the physical/statistical down-scaling methodology and application to climate model Climber for BIOCLIM Work-package 3

    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. The main aim of this deliverable is to provide time series of climatic variables at the high resolution as needed by performance assessment (PA) of radioactive waste repositories, on the basis of coarse output from the CLIMBER-GREMLINS climate model. The climatological variables studied here are long-term (monthly) mean temperature and precipitation, as these are the main variables of interest for performance assessment. CLIMBER-GREMLINS is an earth-system model of intermediate complexity (EMIC), designed for long climate simulations (glacial cycles). Thus, this model has a coarse resolution (about 50 degrees in longitude) and other limitations which are sketched in this report. For the purpose of performance assessment, the climatological variables are required at scales pertinent for the knowledge of the conditions at the depository site. In this work, the final resolution is that of the best available global gridded present-day climatology, which is 1/6 degree in both longitude and latitude. To obtain climate-change information at this high resolution on the basis of the climate model outputs, a 2-step down-scaling method is designed. First, physical considerations are used to define variables which are expected to have links which climatological values; secondly a statistical model is used to find the links between these variables and the high-resolution climatology of temperature and precipitation. Thus the method is termed as 'physical/statistical': it involves physically based assumptions to compute predictors from model variables and then relies on statistics to find empirical links between these predictors and the climatology. The simple connection of coarse model results to regional values can not be done on a purely empirical way because the model does not provide enough information - it is both

  6. Bioclim Deliverable D6a: regional climatic characteristics for the European sites at specific times: the dynamical down-scaling

    International Nuclear Information System (INIS)

    many millennia. These results are then interpreted in terms of regional climatic changes using rule-based and statistical down-scaling approaches. This deliverable, D6a, focuses on the hierarchical strategy, and in particular the MAR simulations. According to the hierarchical strategy developed in the BIOCLIM project to predict future climate, six BIOCLIM experiments were run with the MAR model. In addition to these experiments a baseline experiment, presenting the present-day climate simulated by MAR, was also undertaken. In the first step of the hierarchical strategy the LLN 2-D NH climate model simulated the gross features of the climate of the next 1 Myr. Six snapshot experiments were selected from these results. In a second step a GCM and a biosphere model were used to simulate in more detail the climate of the selected time periods. These simulations were performed on a global scale. The third step of the procedure is to derive the regional features of the climate at the same time periods. Therefore the results of the GCM are used as boundary conditions to force the regional climate model (MAR) for the six selected periods and the baseline simulation. The control simulation (baseline) corresponds to the regional climate simulated under present-day conditions, both insolation forcing and atmospheric CO2 concentration. All the BIOCLIM simulations are compared to that baseline simulation. In addition, other comparisons will also be presented

  7. Bioclim Deliverable D3: global climatic features over the next million years and recommendation for specific situations to be considered

    International Nuclear Information System (INIS)

    The BIOCLIM project aims at assessing the possible long-term impacts of climate change on the safety of waste repositories in deep formations using climate simulations of the long-term climate in various European areas. One of the objectives of the project is to develop two strategies for representing sequential climatic changes to the geosphere-biosphere system for different sites over Europe, addressing the time scale of one million years. The results of this work will be interpreted in terms of global or regional changes of climate and of vegetation. The first strategy (hierarchical strategy) will use the full hierarchy of existing climate models (a climate model is a numerical simplified representation of the climate system behaviour and evolution). Simple models (LLN 2-D NH and threshold models; see the description here after) will simulate the overall long-term evolution of the global climate. Their results will then be used as inputs to more complex models (LMD climate models possibly coupled with vegetation models, either SECHIBA or ORCHIDE) and finally climate and vegetation cover will be determined for specific sites at specific times. A second strategy (integrated strategy) will consist in building an integrated climate model, which represents most of the physical mechanisms for studying long-term climatic variations. The results will then be interpreted on a regional scale. This deliverable is the first step of the hierarchical strategy. The purpose of this deliverable is to identify and justify some specific climatic situations amongst different long-term simulations that are of interest for assessing the safety of radioactive waste repository sites and that will be further studied with GCMs (General Circulation Model). The simple threshold (or multi-state) climate model is a modified version of the model from Paillard. It describes the time evolution of the ice volume and the CO2 concentration. It has two distinct regimes (interglacial and glacial

  8. 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

  9. 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

  10. IKS Deliverable - D1.1 Report: Design of the Semantic Benchmark Experiment

    OpenAIRE

    Kowatsch, Tobias; Maass, Wolfgang; Damjanovic, Violeta; Behrendt, Wernher; Gruber, Andreas; Nagel, Benjamin; Sauer, Stefan; Engels, Gregor

    2009-01-01

    Public Deliverable - The objective of this deliverable is to design a benchmark model for Content Management Systems (CMSs) in order to identify relevant requirements for the Interactive Knowledge Stack (IKS). The IKS will be a layered set of software components and specifications with the goal to improve the interaction with knowledge objects of CMSs by using Semantic Web technologies. In contrast to projects that benchmarked rather technical aspects of CMSs, we propose a model that evaluate...

  11. 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...

  12. 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

  13. 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....... Gordon Dalton (HMRC) and Hans C. Sorensen (SPOK). It included 3 main parts: a first introduction to microeconomics at project level, a second practical session on the use of economic model Retscreen and a final session introducing macro and socio-economic aspects....

  14. 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.

  15. Wavetrain 2 : Deliverable 29

    DEFF Research Database (Denmark)

    Crom, Izan Le; Pecher, Arthur; Parmeggiani, Stefano; Chozas, Julia Fernandez

    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...

  16. 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...

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

    Science.gov (United States)

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

    2012-01-01

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

  18. 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

  19. 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.

  20. 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.

  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

    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.

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

    OpenAIRE

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

    2011-01-01

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

  3. 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

  4. The afterlife of 'living deliverables': angels or zombies?

    OpenAIRE

    Wild, Fridolin; Ullmann, Thomas

    2010-01-01

    Within the STELLAR project, we provide the possibility to use living documents for the collaborative writing work on deliverables. Compared to 'normal' deliverables, 'living' deliverables come into existence much earlier than their delivery deadline and are expected to 'live on' after their official delivery to the European Commission. They are expected to foster collaboration. Within this contribution we investigate, how these deliverables have been used over the first 16 months of the proje...

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

    DEFF Research Database (Denmark)

    Hansen, Kurt Schaldemose

    The development of wind energy is hindered by measurement problems: in particular the fluctu-ating wind speed introduces large uncertainties. For example: to confirm a theoretical improve-ment of around 5% in production of a new design by field experiments is very hard to almost impossible. As long...... 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 performance measurements - Improvement of aerodynamic codes - Assessment of wind resources In general terms the uncertainty of the testing techniques and methods are typically much higher than the need. Since this problem covers many areas of wind energy, the work package is de-fined as a...

  6. Diseño de una vivienda bioclimática para la sierra andina peruana

    OpenAIRE

    Ballespí i Lladonosa, Arnau

    2010-01-01

    Este PFC está enmarcado dentro del proyecto “Apoyo técnico a la investigación peruana en energías renovables y en eficiencia energética”, el cuál se desarrolla gracias al apoyo del CCD (UPC). El objetivo principal es el de mejorar la habitabilidad de las viviendas de la zona alto andina peruana, obteniendo un diseño preliminar de una vivienda bioclimática que consiga mantener su temperatura interior dentro de unos rangos de confort utilizando únicamente como energía la radiació...

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

    OpenAIRE

    Claudia Fernanda Martinez; Érica Norma Correa Cantaloube

    2015-01-01

    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 parti...

  8. 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.

  9. 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, ...

  10. Modelling sequential Biosphere systems under Climate change for radioactive waste disposal. Project BIOCLIM

    International Nuclear Information System (INIS)

    The BIOCLIM project (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. It is coordinated by ANDRA, the French national radioactive waste management agency. The project brings together a number of European radioactive waste management organisations that have national responsibilities for the safe disposal of radioactive wastes, and several highly experienced climate research teams. Waste management organisations involved are: NIREX (UK), GRS (Germany), ENRESA (Spain), NRI (Czech Republic) and ANDRA (France). Climate research teams involved are: LSCE (CEA/CNRS, France), CIEMAT (Spain), UPMETSIMM (Spain), UCL/ASTR (Belgium) and CRU (UEA, UK). The Environmental Agency for England and Wales provides a regulatory perspective. The consulting company Enviros Consulting (UK) assists ANDRA by contributing to both the administrative and scientific aspects of the project. This paper describes the project and progress to date. (authors)

  11. 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

  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. 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

  14. 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

  15. 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.

  16. Record of principal work activities/deliverables

    International Nuclear Information System (INIS)

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

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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 to di...... 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...... 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...

  2. 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.

  3. 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...

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. Deliverable 1.2.1 Market Analysis and Business Plan

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth

    2009-01-01

    Deliverable 1.2.1 - Market Analysis and Business Plan The main objective of this deliverable is to provide a short overview of 4 communities involved in the pilots, envisaged type of solutions and architectures to be deployed (chapter 2) and market analysis at regional level (chapter 3) with...... related business cases. The Market analysis will provide an overview of market requirements, current status and opportunities for the pilot service that will be provided in the context of ISISEMD. This will be realised by performing detailed studies on various sources. Proposals for business modelling and...... business cases (chapter 4) will rely on the concept of value chains. Value chains typically consist of several providers, which together produce a complex product or service....

  9. COLOMBO Deliverable 5.3: Traffic Light Algorithm Evaluation System

    OpenAIRE

    Krajzewicz, Daniel; Blokpoel, Robbin; Niebel, Wolfgang; Lu, Ting; Hebenstreit, Cornelia; Reixis, Martin; Bieker, Laura

    2015-01-01

    Deliverable 5.3 describes the work performed in Task 5.3 on a “Traffic Light Algorithm Evaluation System”. This work includes two approaches. The first is the derivation of a single performance indicator that combines conventional traffic efficiency measures, measures describing how drivers perceive the traffic state as well as environmental measures. The work is accompanied by a summary on nowadays benchmarking of traffic lights. The developed performance indicator may be used for both, benc...

  10. 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.

  11. 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

  12. 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....

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  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. El lenguaje vernáculo de las ventanas tradicionales canarias: antecedentes, tipología y funcionamiento bioclimático

    OpenAIRE

    Gil Crespo, Ignacio Javier

    2014-01-01

    La ventana tradicional canaria es uno de los elementos más característicos de la arquitectura vernácula de las Islas Canarias. El artículo estudia sus tipos fundamentales (ventana de cuarterones, ventana de celosía y ventana de guillotina) desde la perspectiva histórica mencionando su origen y antecedentes, desde el punto de vista tipológico, analizando su estructura formal y constructiva, y, por último, desde el ángulo del funcionamiento bioclimático. Los antecedentes culturales que favor...

  5. 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

  6. 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.

  7. Cyclin D1 expression in prostate carcinoma

    International Nuclear Information System (INIS)

    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. 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

  9. 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...

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Braaten, F.D.

    1995-02-27

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

  12. 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...

  13. (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_...

  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

    International Nuclear Information System (INIS)

    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. (paper)

  18. 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.

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

    DEFF Research Database (Denmark)

    Tølle, Martin; Vesterager, Johan

    2002-01-01

    This document is a deliverable of Work package 2 of the IMS Globemen (GMN) project: D23 Guidelines for Inter-Enterprise Management (IEM). IMS Globemen is an inter-regional project aiming to develop methods, tools and architectures to support inter-enterprise operations in one-of-kind industries, in...... different lifecycle phases. This report focuses on management of the inter-enterprise delivery process. It is based on the identification of industrial requirements and the specification of the tools in GMN industrial case in EU. These have been reported in earlier deliverables D21 (Requirements) and D22...... (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...

  1. 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...

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

    DEFF Research Database (Denmark)

    Faiella, Mariano; Hennig, Tobias; Cutululis, Nicolaos Antonio; Van Hulle, Frans

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

  3. Evaluation of state of the art technologies, GLOBEMEN Deliverable D411

    DEFF Research Database (Denmark)

    van den Berg, Roel; Hannus, Matti; Pedersen, Jens Dahl;

    2000-01-01

    and constructs for background information. The frame for the remainder of the document is set in chapter 4, where ALIVE (Architecture for Layered Integration of Virtual Enterprises) is introduced. Each of the components in ALIVE is subsequently discussed in detail in the chapters 6 to 10. Chapter 5...... discusses reference architectures and methodologies, which should guide a user to fill in the various types of integration as indicated by ALIVE. The first type of integration, inter-enterprise coordination, is not described in this deliverable, but in the various WP1-3 deliverables. The topic of modelling...

  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. 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....

  6. D1.1 Stakeholders Needs Regarding EA

    DEFF Research Database (Denmark)

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

    2009-01-01

    university course about EA. This deliverable commences with a detailed description of the methodology followed for the identification of stakeholders needs regarding Enterprise Architecture (EA) training and education. It then presents the results of the methodology application in terms of EA related...

  7. 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. Fluctuations and predictability of wind and hydropower. Deliverable 2.1

    DEFF Research Database (Denmark)

    Giebel, Gregor; Holttinen, H.; Söder, L.; Petterteig, A.

    2004-01-01

    The report forms the deliverable D2.1 of the EU supported project Wind Power Integration in a Liberalised Electricity Market (WILMAR). The handling and generation of the necessary wind and hydro time series for the project’s power system planningsimulation model is described. The wind power and t...

  9. Stereocontrolled total synthesis of neuroprotectin D1 / protectin D1 and its aspirin-triggered stereoisomer

    OpenAIRE

    Petasis, Nicos A.; Yang, Rong; Winkler, Jeremy W.; Zhu, Min; Uddin, Jasim; Bazan, Nicolas G.; Serhan, Charles N.

    2012-01-01

    Neuroprotectin D1 / protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne prec...

  10. Short-term natural gas deliverability from the Western Canada Sedimentary Basin 2000-2002

    International Nuclear Information System (INIS)

    Factors which affect natural gas supply in the short term are discussed and a forecast for deliverability to the year 2002 is provided as part of the ongoing effort by the National Energy Board to provide analyses of the major energy commodities on either an individual or integrated commodity basis. The objective of these energy market assessment reports is to advance the understanding of the short-term supply situation by reviewing recent trends in the production characteristics of the Western Canada Sedimentary Basin and to update previous reports on short-term deliverability. This report focuses on a review of producing characteristics of natural gas wells from 1990 to 1999. These producing characteristics are then combined with forecasts of drilling activity in order to generate a forecast of natural gas deliverability from 2000 to 2002. Two key trends were identified during the review process. First, recently drilled wells were found to produce at lower rates than wells drilled more than five years ago; second, production from these wells were shown to decline more quickly than production from older wells. Based on these observations, it was concluded that future wells will be generally less productive than wells which were drilled a few years ago, therefore, more wells will have to be drilled to offset production declines from existing gas wells if deliverability is to be maintained or increased. The National Energy Board expects 8,100 wells to be drilled in 2000, followed by 8,700 natural gas wells in 2001 and 8,900 in 2002. A shift in drilling activity to more prolific areas located in the western and northern parts of the Western Canada Sedimentary Basin is also expected. Based on these estimates of expected drilling activity, total deliverability is projected to increase from 465 million cubic feet per day in 1999 to 495 million cubic feet in 2002. Specialized statistics and forecast data are provided in the appendices. 3 tabs., 11 figs., 6 appendices

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

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

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

    Directory of Open Access Journals (Sweden)

    J. Janse van Rensburg

    2010-07-01

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

  13. 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 ...

  14. 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....

  15. 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 ...

  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. A Reflection of the Development, Activities and Deliverables of the Construction IT Alliance (CITA) In Ireland

    OpenAIRE

    Thomas, Ken; Hore, Alan V

    2003-01-01

    This paper reflects on the development, activities and deliverables of the Construction IT Alliance in the Republic of Ireland. This alliance was formed in 2001 with the vision of harnessing the potential of information and communication technologies in the Irish construction sector. CITA is a prime example of academia-industry-government collaboration in Ireland. A key driver in the development of CITA is the need to increase the extent of IT knowledge within the Irish construction sector. M...

  18. 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...

  19. PRESTOPRIME: Deliverable D3.1: Design and specification of the audiovisual preservation toolkit

    OpenAIRE

    Phillips, Stephen

    2010-01-01

    This deliverable is a specification and design document for an audiovisual content preservation environment. It contains a review of current digital preservation support for AV files, a survey of File-Corruption Detection methods and technologies, a review of threats to data integrity from use of large-scale data management environments; SLA schemas and QoS parameters for using online storage services in audiovisual preservation, the design of a system for preservation using both migration an...

  20. Testing the FPS approach in d = 1

    Science.gov (United States)

    Bellucci, S.; Krivonos, S.; Sutulin, A.

    2015-04-01

    We apply the approach of S. Ferrara, M. Porrati and A. Sagnotti [1] to the one dimensional system described by the N = 2 , d = 1 supersymmetric action for two particles in which one of N = 1 supersymmetries is spontaneously broken. Using the nonlinear realization approach we reconsider the system in the basis where only one superfield has the Goldstone nature while the second superfield can be treated as the matter one, being invariant under transformations of the spontaneously broken N = 1 supersymmetry. We establish the transformations relating the two selected FPS-like cases with our more general one, and find the field redefinitions which relate these two cases. Thus we demonstrate, at least in one dimension, that the only difference between two FPS cases lies in the different choice of the actions, while the supermultiplets specified by the FPS-like constraints are really the same. Going further with the nonlinear realization approach, we construct the most general action for the system of two N = 1 superfields possessing one additional hidden spontaneously broken N = 1 supersymmetry. The constructed action contains two arbitrary functions and reduces to the FPS actions upon specification of these functions. Unfortunately, the exact form of these functions corresponding to FPS actions is not very informative and gives no explanation on why the FPS cases are selected.

  1. Testing the FPS approach in d=1

    CERN Document Server

    Bellucci, S; Sutulin, A

    2015-01-01

    We apply the approach of S. Ferrara, M. Porrati and A. Sagnotti \\cite{FPS} to the one dimensional system described by the $N=2, d=1$ supersymmetric action for two particles in which one of $N=1$ supersymmetries is spontaneously broken. Using the nonlinear realization approach we reconsider the system in the basis where only one superfield has the Goldstone nature while the second superfield can be treated as the matter one, being invariant under transformations of the spontaneously broken $N=1$ supersymmetry. We establish the transformations relating the two selected FPS-like cases with our more general one, and find the field redefinitions which relate these two cases. Thus we demonstrate, at least in one dimension, that the only difference between two FPS cases lies in the different choice of the actions, while the supermultiplets specified by the FPS-like constraints are really the same. Going further with the nonlinear realization approach, we construct the most general action for the system of two $N=1$ ...

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

    DEFF Research Database (Denmark)

    Lostanlen, Yves; Pedersen, Troels; Steinboeck, Gerhard; Stéphan, Julien; Wang, Wei

    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 outdoor-to-indoor...

  3. 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....

  4. D1-protein dynamics in photosystem II: the lingering enigma

    Science.gov (United States)

    The D1/D2 heterodimer core dominates the photosystem II reaction center. A characteristic feature of this heterodimer is the differentially rapid, light-dependent degradation of the D1 protein. The D1 protein is possibly the most researched photosynthetic polypeptide, with aspects of structure–funct...

  5. 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.; Schiødt, M; Hansen, A; Suhr-Jessen, P; Scheideler, M; Thastrup, O; Andersen, P H

    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...... receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Transferrin D1: identity in Australian aborigines and American Negroes.

    Science.gov (United States)

    Wang, A C; Sutton, H E; Scott, I D

    1967-05-19

    Human transferrin D(1) obtained from an Australian aborigine was found to have the same substitution of glycine for aspartic acid in peptide 1C previously shown in transferrin D(1) from an American Negro. This finding is relevant to formation of distinct Australoid and African populations. PMID:6023254

  17. 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

  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. 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

  20. 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

  1. Seventh annual survey of Canadian natural gas deliverability, production, reserves, and investment

    International Nuclear Information System (INIS)

    A survey was conducted to obtain information on the state of natural gas producers' price expectations and investment intentions in Canada. Forecasts for drilling, reserve additions, reserves, deliverability and production were estimated from survey responses. Survey projections were analyzed and compared with other forecasts. The study covers a five-year period starting with 1996 actuals, 1997 estimates, and forecasts for 1998 through 2000. The forecast is for substantial increases to Western Canada Sedimentary Basin (WCSB) pipeline capacity by the third quarter of 2000. Major projects include TransCanada's 1998 facilities expansion, the 1998 Foothills Pipe Lines-Northern Border pipeline expansion, TransCanada's 1999 facilities expansion, and the Alliance Pipeline project which is scheduled to be in service by the third quarter of 2000. Given the low market price for crude oil, industry participants are hoping that additional capacity will lead to improved prices and strong markets for natural gas. refs., tabs., figs

  2. 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...... for them. This will be done via integrating intelligent scalable ICT services which will be tested for a period of 12 months under realistic conditions. Offering the services could not be complete without evaluating quality of life improvement, user acceptance and user satisfaction with a representative...... group of the target user groups. This document is devoted to describing important aspects of services evaluation such as: who the test participants will be, inclusion and exclusion criterion, selection standards, how the test participants will be recruited, ethical considerations, etc. Test methodology...

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

    International Nuclear Information System (INIS)

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

  4. The pathophysiological functions mediated by D-1 dopamine receptors

    International Nuclear Information System (INIS)

    This chapter describes some behavioral responses which might be mediated by D1 and D2 DA receptors, and the authors discuss their clinical relevance. It was of considerable interest to determine whether a selective D1 DA antagonist, such as SCH 23390, will induce catalepsy and whether this behavior is mediated by D1, or by both D1 and D2 DA receptors. Rats were used in the experiments. The authors examined whether the addition of the S2 antagonist ketanserin affects the displacement of 3H-Spi by SCH 23390. Induction of self-mutilating biting (SMB) behavior in monkeys with unilateral ventromedial tegmental (VMT) lesions by DA agonists and its prevention by DA antagonists is examined. The authors also discuss the possible relationships between abnormal guanine nucleotide metabolism and dopaminergic neuronal function through the implications in LeschNyhan syndrome and in some mental disorders

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

    Science.gov (United States)

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

    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. PMID:25088042

  6. 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...

  7. Underground storage tank 291-D1U1: Closure plan

    Energy Technology Data Exchange (ETDEWEB)

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    The 291-D1U1 tank system was installed in 1983 on the north side of Building 291. It supplies diesel fuel to the Building 291 emergency generator and air compressor. The emergency generator and air compressor are located southwest and southeast, respectively, of the tank (see Appendix B, Figure 2). The tank system consists of a single-walled, 2,000- gallon, fiberglass tank and a fuel pump system, fill pipe, vent pipe, electrical conduit, and fuel supply and return piping. The area to be excavated is paved with asphalt and concrete. It is not known whether a concrete anchor pad is associated with this tank. Additionally, this closure plan assumes that the diesel tank is below the fill pad. The emergency generator and air compressor for Building 291 and its associated UST, 291-D1U1, are currently in use. The generator and air compressor will be supplied by a temporary above-ground fuel tank prior to the removal of 291-D1U1. An above-ground fuel tank will be installed as a permanent replacement for 291-D1U1. The system was registered with the State Water Resources Control Board on June 27, 1984, as 291-41D and has subsequently been renamed 291-D1U1. Figure 1 (see Appendix B) shows the location of the 291-D1U1 tank system in relation to the Lawrence Livermore National Laboratory (LLNL). Figure 2 (see Appendix B) shows the 291-D1U1 tank system in relation to Building 291. Figure 3 (see Appendix B) shows a plan view of the 291-D1U1 tank system.

  8. 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.

  9. 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)

  10. Evidence against dopamine D1/D2 receptor heteromers

    Science.gov (United States)

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

    2014-01-01

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

  11. Linoleic acid attenuates cardioprotection induced by resolvin D1.

    Science.gov (United States)

    Gilbert, Kim; Malick, Mandy; Madingou, Ness; Bourque-Riel, Valérie; Touchette, Charles; Rousseau, Guy

    2016-05-01

    We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1μg RvD1 alone or with one of three LA doses (1, 5 or 10μg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1. PMID:27133431

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    McGurk, R [NC Cancer Hospital, Chapel Hill, NC (United States); Smith, VA [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Price, M [NC Cancer Hospital, Chapel Hill, NC (United States); UNC School of Medicine, Chapel Hill, NC (United States)

    2014-06-15

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

  14. 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.

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

    DEFF Research Database (Denmark)

    Thuesen, Christian; Hvam, Lars

    2013-01-01

    literature combined with theories on mass-customization and platform development identifying the optimization of cost and value through the handling of complexity as the central process. This framework is developed in order to analyze a specific case on system deliverances – the prefabrication of...... installation shafts. Findings from the development and production of the installation shaft show that system deliveries represent a promising strategy for moving from red ocean competitive environment with the predominant cost+ business model, to a blue ocean situation in which the competition emerges in the...... constant pursue of value creation and cost reduction. On the basis of that system deliverances represent a promising strategy in the future development and application of off-site manufacturing practices. The application of system deliveries is however demanding as it represents a fundamental shift in the...

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. Evolution of dopamine receptor genes of the D1 class in vertebrates.

    Science.gov (United States)

    Yamamoto, Kei; Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michaël; Vernier, Philippe

    2013-04-01

    The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D1 dopamine receptor genes. First, we show that D1C and D1D receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D1X sequence is a teleost-specific paralog of the D1B sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D1-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D1E. Ancestral jawed vertebrates are thus likely to have possessed four classes of D1 receptor genes-D1A, D1B(X), D1C(D), and D1E-which arose from large-scale gene duplications. The D1C receptor gene would have been secondarily lost in the mammalian lineage, whereas the D1E receptor gene would have been lost independently in several lineages of modern vertebrates. The D1A receptors are well conserved throughout jawed vertebrates, whereas sauropsid D1C receptors have rapidly diverged, to the point that they were misidentified as D1D. The functional significance of the D1C receptor loss is not known. It is possible that the function may have been substituted with D1A or D1B receptors in mammals, following the disappearance of D1C receptors in these species. PMID:23197594

  1. 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......-link large scale parameters, such as rms delay spread, from outdoor to indoor scenarios and for different carrier frequencies. Furthermore indoor radio propagation in in-room scenarios is considered and first modeling approaches, potantially suitable for multi-link channels are presented. A sparse estimator...

  2. 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.

  3. 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... registered investment company and any series of the investment company. (2) Assets means net assets, plus...

  4. 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

  5. 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

  6. 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.

  7. Short-term Canadian natural gas deliverability 2006-2008 : an energy market assessment

    International Nuclear Information System (INIS)

    This report presented an assessment of the expected capability of Canadian gas production through to the year 2008. Strong natural gas prices have led to record drilling levels in Canada's natural gas industry. North American natural gas prices reached a peak near the end of 2005. The rise in prices during 2005 reflected high world crude oil prices, a tight balance between natural gas supply and demand, and disruptions to United States gas supply from 2 hurricanes. In response to rising prices, western Canada drilling activity achieved new highs in early 2006. Higher drilling rates also reflected rising costs for key inputs of steel, fuel, and labour. Gas prices have since softened due to a storage overhang resulting from a mild winter. The combination of rising costs and softening prices has impacted margins for Canadian gas producers. In response, some producers have reduced drilling expansion plans in coalbed methane (CBM) and shallow gas plays in the Western Canadian Sedimentary Basin (WCSB). Increases in deeper gas drilling have been maintained. Total gas drilling for 2006 is expected to rise by 3 per cent compared to 2005. The report projected a small increase in Canada's total annual gas production from 484 million m3/d in 2005 to 491 million m3/d in 2008. Annual average deliverability of conventional gas is expected to decline slightly over the projection period. The decrease is expected to be more than offset by growth in CBM production in western Canada, which is expected to increase from 8 million m3/d in 2005 to 27 million m3/d in 2008. 5 tabs., 5 figs

  8. Excitations and interactions in d = 1 string theory

    International Nuclear Information System (INIS)

    In this paper, the authors discuss the singlet sector of the d = 1 matrix model in terms of a Dirac fermion formalism. The leading order two- and three-point functions of the density fluctuations are obtained by this method. This allows the authors to construct the effective action to that order and hence provide the equation of motion. This equation is compared with the one obtained from the continuum approach. The authors also compare continuum results for correlation functions with the matrix model ones and discuss the nature of gravitational dressing for this regularization. Finally, the authors address the question of boundary conditions within the framework of the d = 1 unitary matrix model, considered as a regularized version of the Hermitian model, and study the implications of a generalized action with an additional parameter (analogous to the θ parameter) which give rise to quasi-periodic wave functions

  9. Fuzzball solutions and D1-D5 microstates

    CERN Document Server

    Skenderis, K; Skenderis, Kostas; Taylor, Marika

    2006-01-01

    We revisit the relation between fuzzball solutions and D1-D5 microstates. A consequence of the fact that the RR ground states (in the usual basis) are eigenstates of the R-charge is that only neutral operators can have non-vanishing expectation values on these states. We compute the holographic 1-point functions of the fuzzball solutions and find that charged chiral primaries have non-zero expectation values, except when the curve characterizing the solution is circular. The non-zero vevs reflect the fact that a generic curve breaks R-symmetry completely. This implies that fuzzball solutions (excepting circular ones) can only correspond to superpositions of RR states. We construct new solutions by appropriately superimposing fuzzball solutions that have vanishing vevs for all charged chiral primary operators and can therefore correspond to D1-D5 microstates.

  10. 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.

  11. 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.

  12. 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

  13. Ontogeny of dopamine D1 receptors in rat striatum

    International Nuclear Information System (INIS)

    In recent years direct analysis of dopamine D1 receptors has been made possible by the development of ligands with high affinity and specificity for these receptors. The authors examined the development of dopamine D1 receptors in postnatal rat striatum using standard membrane binding techniques. Rat pups 0 to 35 days of age were decapitated and striata dissected. Membranes were prepared by homogenization and centrifugation. The ligand used was 3H-piflutixol (1.5 nM). Dopamine D2 and serotonin S2 receptors were blocked by 50 nM spiperone. Blanks were generated by 1 μM cis-flupenthixol. Assays were carried out at 370C for 15 min and terminated by vacuum filtration (GF/B). Receptor number increased 9-fold from birth to 26 days of age, when adult levels were reached. Equilibrium was reached within 4 min. half-time of dissociation was approx. 1.5 min. Pharmacologically the receptors were identified as D1 type by the IC50's of numerous compounds: cis-flupenthixol (30nM), SCH 23390 (25 nM), fluphenazine (200 nM), chlorpromazine (300 nM), haloperidol (4 μM). Sulpiride, domperidone, atropine and naloxone had IC50's greater than 10 μM. Initial saturation studies indicate a Km of 0.6 nM with increasing Bmax with increasing age

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

    Science.gov (United States)

    Ashton, Gary

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

  15. Socio-economic characteristics of case study sites (regions and laus) and alternative scenarios for multifunctional land use activities on national and regional scales. DeliverableD1.3

    OpenAIRE

    Kopeva, D.; Brscic, K.; Dobruchowski, A.; Franic, R.; Garrod, G.; Hautdidier, B.; Konecna, M.; Laplana, R.; Ostermeyer, A.; Peneva, M.; Raley, M.; Sahrbacher, A

    2010-01-01

    The report gives an overview over the methodological approach used in the PRIMA project for the development of alternative scenarios. Scenarios focus on policy changes and possible results/outputs of EU policy implementation on regional and local (LAU) level. In a first step a social economic analysis is implemented in each case study and bears on 5 domains: general characteristics, demographic trends, economic system, transport and environment. In a second step, and after identification of...

  16. 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

  17. Evolution of Dopamine Receptor Genes of the D1 Class in Vertebrates

    OpenAIRE

    Yamamoto, Kei(Department of Physics, Niigata University, Niigata 950-2181, Japan); Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michaël; Vernier, Philippe

    2012-01-01

    The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D...

  18. Suggested Guidelines for Transparency and Participation in Nuclear Waste Management Programmes. Deliverable 22

    International Nuclear Information System (INIS)

    . Annex 2 gives references for the various sections of the guidelines to more background information in ARGONA deliverables and in the ARGONA Final Report. These guidelines concern nuclear waste management, however, this issue represents only one part of society's concerns in complex and controversial matters. The ARGONA participants believe that many of the following suggested guidelines should be of relevance in a much wider context than nuclear waste management only

  19. CO2-emission trading and green markets for renewable electricity. WILMAR - deliverable 4.1

    International Nuclear Information System (INIS)

    This report is Deliverable 4.1 of the EU project 'Wind Power Integration in Liberalised Electricity Markets' (WILMAR) and de-scribes the application of two policy instruments, Tradable Emissions 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 significant 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 CO2 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 advanced model for the TGC market seems to be

  20. 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.

  1. Evaluation, testing and application of participatory approaches in the Czech Republic. Guidelines on approaches to siting a deep repository. Deliverable D21

    International Nuclear Information System (INIS)

    Based on the review of experiences in SEA and EIA in the Czech Republic summarized in Deliverable No.3 and the testing of novel participatory and dialogue approaches summarized in Deliverables No.7, 11 and 12 in this report a model for the siting process specifically in the Czech Republic, that takes into account the need for transparency and interaction with the public, within the framework of legal requirements is outlined. Lessons learnt are summarised and a road map specified. The guidelines / recommendations in this report are proposed based on mapping the situation in the Czech Republic and experience gained in connection with the testing and application of novel participatory approaches and dialogue, but many of them are of general validity and can be applied in other countries outside the Czech Republic. This reports links directly to Work package 6, where general guidelines for participation and transparency, reflecting institutional and cultural differences, are given - Deliverable No.22

  2. 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...

  3. Canonical D = 1 supergravity framework for FLRW cosmology

    Science.gov (United States)

    Bogers, M. P.; van Holten, J. W.

    2015-05-01

    We construct an extension of standard flat FLRW cosmology with matter, possessing local D = 1, N=1 proper-time supersymmetry. The fundamental equation for the resulting mini-superspace models of quantum universes is a Dirac-like analogue of the Friedmann and Wheeler-DeWitt equations. We provide solutions of this equation for specific matter configurations based on the supersymmetric O(3) and O(2,1) σ-models. It turns out that in the compact model the volume rate of growth of the universe is quantized and non-vanishing due to the zero-point energy of the scalar fields. In the non-compact model the spectrum of the growth rates is continuous but subject to an uncertainty relation involving the scale and the growth factor.

  4. Canonical D = 1 supergravity framework for FLRW cosmology

    CERN Document Server

    Bogers, M P

    2015-01-01

    We construct an extension of standard flat FLRW cosmology with matter, possessing local D = 1, N = 1 proper-time supersymmetry. The fundamental equation for the resulting mini-superspace models of quantum universes is a Dirac-like analogue of the Friedmann and Wheeler-DeWitt equations. We provide solutions of this equation for specific matter configurations based on the supersymmetric O(3) and O(2, 1) sigma-models. It turns out that in the compact model the volume rate of growth of the universe is quantized and non-vanishing due to the zero-point energy of the scalar fields. In the non-compact model the spectrum of the growth rates is continuous but subject to an uncertainty relation involving the scale and the growth factor.

  5. Assessment of the 2D/1D implementation in MPACT

    International Nuclear Information System (INIS)

    The 2D/1D method is used in the MPACT code to obtain 3D solutions of the Boltzmann transport equation for practical reactor geometries. The OECD C5G7 transport benchmark problem is used first to assess the accuracy of the method with a fixed set of cross-sections. The VERA Core Physics Progression Problems are then used to compare the accuracy of the transport solver using a 56-group library based on ENDFB-VII.0. Single assembly PWR designs are simulated, and the eigenvalue and pin powers are compared to continuous-energy Monte Carlo results. A 3x3 assembly cluster with a control rod inserted into the center assembly is then compared to Monte Carlo to assess the ability of MPACT to predict a control rod worth curve. Finally, MPACT is used to simulate the initial critical states of a full 3D initial core of a PWR at zero power conditions. (author)

  6. 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 ...

  7. 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

  8. 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

  9. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function

    OpenAIRE

    Wang, Chenguang; Li, Zhiping; Lu, Yinan; Du, Runlei; Katiyar, Sanjay; Yang, Jianguo; Fu, Maofu; Leader, Jennifer E.; Quong, Andrew; Novikoff, Phyllis M.; Pestell, Richard G

    2006-01-01

    Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis...

  10. 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.

  11. 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...

  12. 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...

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

    Science.gov (United States)

    2010-04-01

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

  14. 3D/1D Analysis of ICRF Antennas

    Science.gov (United States)

    Maggiora, Riccardo; Lancellotti, Vito; Vecchi, Giuseppe

    2003-10-01

    An innovative tool has been realized for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model. The approach to the problem is based on an integral-equation formulation for the self-consistent evaluation of the current distribution on the conductors. The environment has been subdivided in two coupled region: the plasma region and the vacuum region. The two problems are linked by means of a magnetic current (electric field) distribution on the aperture between the two regions. In the vacuum region all the calculations are executed in the spatial domain while in the plasma region an extraction in the spectral domain of some integrals is employed that permits to significantly reduce the integration support and to obtain a high numerical efficiency leading to the practical possibility of using a large number of sub-domain (rectangular or triangular) basis functions on each solid conductor of the system. The plasma enters the formalism of the plasma region via a surface impedance matrix; for this reason any plasma model can be used; at present the FELICE code has been adopted, that affords density and temperature profiles, and FLR effects. The source term directly models the TEM mode of the coax feeding the antenna and the current in the coax is determined self-consistently, giving the input impedance/admittance of the antenna itself. Calculation of field distributions (both magnetic and electric), useful for sheath considerations, is included. This tool has been implemented in a suite, called TOPICA, that is modular and applicable to ICRF antenna structures of arbitrary shape. This new simulation tool can assist during the detailed design phase and for this reason can be considered a "Virtual Prototyping Laboratory" (VPL). The TOPICA suite has been tested against assessed codes and against measurements and data of mock-ups and existing antennas. The VPL is being used in

  15. TBC1D1 Regulates Insulin- and Contraction-Induced Glucose Transport in Mouse Skeletal Muscle

    OpenAIRE

    Toyoda, Taro; Yu, Haiyan; Fujii, Nobuharu; Hirshman, Michael F.; An, Ding Jeff; Goodyear, Laurie Joy; Taylor, Eric B.

    2010-01-01

    OBJECTIVE: TBC1D1 is a member of the TBC1 Rab-GTPase family of proteins and is highly expressed in skeletal muscle. Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known. Genetic linkage analyses show a TBC1D1 R125W missense variant confers risk for severe obesity in humans. The objective of this study was to determine whether TBC1D1 regulates glucose transport in skeletal muscle. RESEARCH DESIGN AND M...

  16. 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

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

    Science.gov (United States)

    Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2016-01-01

    Purpose Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. Materials and methods C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Results Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. Conclusion RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. PMID:27313451

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

    Science.gov (United States)

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

    2016-03-15

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

  19. 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...

  20. 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...

  1. 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.

  2. 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

  3. Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models

    International Nuclear Information System (INIS)

    Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer

  4. Cyclin D1 Governs Adhesion and Motility of MacrophagesV⃞

    OpenAIRE

    Neumeister, Peter; Pixley, Fiona J.; Xiong, Ying; Xie, Huafeng; Wu, Kongming; Ashton, Anthony; Cammer, Michael; Chan, Amanda; Symons, Marc; Stanley, E. Richard; Pestell, Richard G.

    2003-01-01

    The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein, thereby promoting cell-cycle progression. Cyclin D1 is overexpressed in hematopoetic and epithelial malignancies correlating with poor prognosis and metastasis in several cancer types. Because tumor-associated macrophages have been shown to enhance malignant progression and metastasis, and cyclin D1-deficient mice are resistant to oncogene-induced malignancie...

  5. 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. PMID:26477316

  6. 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.

  7. 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.

  8. Comparative effects of nodularin and microcystin-LR in zebrafish: 1. Uptake by organic anion transporting polypeptide Oatp1d1 (Slco1d1).

    Science.gov (United States)

    Faltermann, Susanne; Prétôt, René; Pernthaler, Jakob; Fent, Karl

    2016-02-01

    Microcystin-LR (MC-LR) and nodularin are hepatotoxins produced by several cyanobacterial species. Their toxicity is based on active cellular uptake and subsequent inhibition of protein phosphatases PP1/2A, leading to hyperphosphorylation and cell death. To date, uptake of MC-LR and nodularin in fish is poorly understood. Here, we investigated the role of the organic anion transporting polypeptide Oatp1d1 in zebrafish (drOatp1d1, Slco1d1) in cellular uptake in zebrafish. We stably transfected CHO and HEK293 cell lines expressing drOatp1d1. In both transfectants, uptake of MC-LR and nodularin was demonstrated by competitive inhibition of uptake with fluorescent substrate lucifer yellow. Direct uptake of MC-LR was demonstrated by immunostaining, and indirectly by the high cytotoxicity in stable transfectants. By means of a synthesized fluorescent labeled MC-LR derivative, direct uptake was further confirmed in HEK293 cells expressing drOatp1d1. Additionally, uptake and toxicity was investigated in the permanent zebrafish liver cell line ZFL. These cells had only a low relative abundance of drOatp1d1, drOatp2b1 and drOatp1f transcripts, which correlated with the lack of MC-LR induced cytotoxicity and transcriptional changes of genes indicative of endoplasmic reticulum stress, a known effect of this toxin. Our study demonstrates that drOatp1d1 functions as an uptake transporter for both MC-LR and nodularin in zebrafish. PMID:26769064

  9. Tank waste remediation system retrieval and disposal mission readiness-to-proceed guidance and requirements to deliverables crosswalk

    International Nuclear Information System (INIS)

    In September 1996, the US Department of Energy, Richland Operations Office (RL) initiated the first of a two-phase program to remediate waste storage in tanks at the Hanford Site in Washington State. Initiating the first phase, RL signed contracts with two private companies who agreed to receive and vitrify a portion of the tank waste in a demonstration and to return the vitrified product and by-products to the Project Management Hanford Contract (PHMC) team for disposition. The first phase of the overall remediation effort is a demonstration of treatment concepts, and the second phase includes treatment of the remaining tank wastes. The demonstration phase, Phase 1 of the project, is further subdivided into two parts, A and B. During Phase 1A, the vitrification contractors are to establish the technical, operational, regulatory, business, and financial elements required to provide treatment services on a fixed unit price basis. Phase 1A deliverables will be evaluated by RL to determine whether it is in the best interest of the government to have one or more vitrification contractors proceed with Phase 1B, in which 6% to 13% of the tank waste would be treated in the demonstration. In addition, before RL can authorize proceeding with Phase 1B, the PHMC team must demonstrate its readiness to retrieve and deliver the waste to the private contractor(s) and to receive and dispose of the products and by-products returned from the treatment. The PHMC team has organized their plans for providing these vitrification-support services into the Retrieval and Disposal Mission within the Tank Waste Remediation System (TWRS) Project. Three RL core teams were established to assist in evaluating the PHMC team's readiness specifically in regard to three task areas: Waste feed delivery; Infrastructure and by-products delivery; and Immobilized products. The core teams each developed a set of criteria and plans to be used in evaluating the PHMC team's readiness to proceed (RTP)

  10. 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...

  11. 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...

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390, was administe...

  14. 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

  15. 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

  16. Summary of breakout Sessions D1 and D2: D1 and D2, mechanical recovery: Containment recovery and standards; and storage, disposal and landfill options

    International Nuclear Information System (INIS)

    The discussions in breakout sessions D1 and D2 are summarized. The topics discussed include the need to improve existing equipment, the need to take advantage of the window of opportunity, the need to minimize research and development redundancy, and the need to keep communications going between researchers and users

  17. 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.

  18. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies.

    Science.gov (United States)

    Levey, A I; Hersch, S M; Rye, D B; Sunahara, R K; Niznik, H B; Kitt, C A; Price, D L; Maggio, R; Brann, M R; Ciliax, B J

    1993-10-01

    Five or more dopamine receptor genes are expressed in brain. However, the pharmacological similarities of the encoded D1-D5 receptors have hindered studies of the localization and functions of the subtypes. To better understand the roles of the individual receptors, antibodies were raised against recombinant D1 and D2 proteins and were shown to bind to the receptor subtypes specifically in Western blot and immunoprecipitation studies. Each antibody reacted selectively with the respective receptor protein expressed both in cells transfected with the cDNAs and in brain. By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra. Within each region, however, the precise distributions of each subtype were distinct and often complementary. D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the olfactory bulb, and in either substantia nigra pars compacta or reticulata. Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions. In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum. Presynaptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release. D1 was also present in axon terminals in the substantia nigra. These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain. PMID:8415621

  19. 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.

  20. 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

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

    Science.gov (United States)

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

    2016-04-01

    D1 protease is a C-terminal processing protease that has been predicted to be an ideal herbicidal target. Three novel series of benzothiazole derivatives were synthesized and evaluated for their herbicidal activities against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass). The preliminary bioassay indicated that most of the synthesized compounds possess promising D1 protease inhibitory activities and considerable herbicidal activities. Molecular docking was performed to position representative compounds into the active site of D1 protease to determine a probable binding model. PMID:26905829

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

    Directory of Open Access Journals (Sweden)

    Hasbi Ahmed

    2011-06-01

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

  3. D1 protein of Drosophila melanogaster. Purification and AT-DNA binding properties

    International Nuclear Information System (INIS)

    D1 protein of Drosophila melanogaster is a sequence-specific DNA-binding protein which recognizes AT-rich DNA sequences. AT-rich DNA sequences in eukaryotic organisms are distributed in two characteristic ways: flanking transcriptional units and in constitutive heterochromatin. D1 could play a role in regulation of gene expression and in geographical localization of DNA sequences within the nucleus. D1 has been partially purified by ion exchange chromatography. DNA-binding activity was investigated by nucleoprotein gel electrophoresis, using end-labeled restriction fragments varying in AT sequence content. D1 binds most tightly to the satellite sequence -AATAT-, with intermediate strength to the complex satellite (359-base pair repeat) and another AT-rich (68% AT) mixed sequence DNA, and least to the simple satellite sequence -AAGAG-

  4. [Dopamine slows phagocytosis of rods from bovine pigment epithelium in vitro trough D1 receptor].

    Science.gov (United States)

    Masri, H; Goureau, O; Hecquet, C; Simon, A; Nguyen-Legros, J

    1996-08-01

    Photoreceptor disc shedding and their phagocytosis by the retinal pigment epithelium undergo a daily rhythm entrained by an intrinsic oscillator involving melatonin and dopamine in non-mammals. Such a mechanism is not demonstrated in mammals, but the rhythm of photoreceptor renewal can be modulated by exogenous melatonin and dopamine. The present experiments were designed to show whether a direct action of DA occurs on pigment epithelial cells, and to identify the receptor mediating this action. Primary cultures of bovine retinal pigment epithelium were incubated with bovine rod outer segments in the presence of dopamine, D1 and D2 agonists, D1 antagonist and forskolin. Dopamine, D1 agonist and forskolin decreased phagocytosis, while D2 agonist was inactive. Thus dopamine slows pigment epithelium phagocytosis in vitro through a D1 receptor. Increased phagocytosis following blockade of the receptor by an antagonist suggests a more complex modulation of phagocytosis by dopamine. PMID:8949392

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

    International Nuclear Information System (INIS)

    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

  6. 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

  7. 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)

  8. 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.

  9. Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression.

    Science.gov (United States)

    Liu, Meng-Min; Albanese, Chris; Anderson, Carol M; Hilty, Kristin; Webb, Paul; Uht, Rosalie M; Price, Richard H; Pestell, Richard G; Kushner, Peter J

    2002-07-01

    Induction of cyclin D1 gene transcription by estrogen receptor alpha (ERalpha) plays an important role in estrogen-mediated proliferation. There is no classical estrogen response element in the cyclin D1 promoter, and induction by ERalpha has been mapped to an alternative response element, a cyclic AMP-response element at -57, with possible participation of an activating protein-1 site at -954. The action of ERbeta at the cyclin D1 promoter is unknown, although evidence suggests that ERbeta may inhibit the proliferative action of ERalpha. We examined the response of cyclin D1 promoter constructs by luciferase assay and the response of the endogenous protein by Western blot in HeLa cells transiently expressing ERalpha, ERalphaK206A (a derivative that is superactive at alternative response elements), or ERbeta. In each case, ER activation at the cyclin D1 promoter is mediated by both the cyclic AMP-response element and the activating protein-1 site, which play partly redundant roles. The activation by ERbeta occurs only with antiestrogens. Estrogens, which activate cyclin D1 gene expression with ERalpha, inhibit expression with ERbeta. Strikingly, the presence of ERbeta completely inhibits cyclin D1 gene activation by estrogen and ERalpha or even by estrogen and the superactive ERalphaK206A. The observation of the opposing action and dominance of ERbeta over ERalpha in activation of cyclin D1 gene expression has implications for the postulated role of ERbeta as a modulator of the proliferative effects of estrogen. PMID:11986316

  10. The corticosterone synthesis inhibitor metyrapone decreases dopamine D1 receptors in the rat brain

    International Nuclear Information System (INIS)

    Experiments were performed to examine the effect of metyrapone, an inhibitor of corticosterone synthesis, on the level of dopamine D1 receptors and their transcripts in the caudate-putamen, nucleus accumbens and olfactory tubercle of the rat brain. The binding to dopamine D1 receptors was measured by receptor autoradiography using the specific D1 receptor antagonist [3H]SCH 23390. The level of dopamine D1 receptor messenger RNA was determined by in situ hybridization histochemistry. The results obtained have shown that metyrapone (two injections of 150 and 50 mg/kg, i.p., given 20 and 3 h before killing, respectively) induced a decrease in the D1 receptor-specific binding in the studied areas of the rat brain. In the caudate-putamen, the decrease in [3H]SCH 23390 binding was stronger in the medial (31-39%) than in the lateral part (24-27%). Decreases similar to those in the caudate-putamen were observed in the nucleus accumbens (21%) and olfactory tubercle (32%). Furthermore, metyrapone decreased the level of dopamine D1 receptor messenger RNA in the caudate-putamen (17-28%), nucleus accumbens (20%) and olfactory tubercle (18%).In conclusion, our study indicates that glucocorticoids might be involved in the regulation of dopamine D1 receptor level in the rat brain, since metyrapone (which inhibits the synthesis of these hormones) decreases the messenger RNA encoding D1 receptor synthesis, as well as the specific binding to this receptor. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  11. 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.

  12. Exercise increases TBC1D1 phosphorylation in human skeletal muscle

    OpenAIRE

    Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders; Goodyear, Laurie J.

    2011-01-01

    Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulatin...

  13. *609850 TBC1 DOMAIN FAMILY, MEMBER 1; TBC1D1 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 609850 FIELD TI 609850 TBC1 DOMAIN FAMILY, MEMBER 1; TBC1D1 ;;KIAA1108 FIELD TX DESCRIP ... o obesity, see BMIQ7 (608410). ANIMAL MODEL In the lean ... Swiss Jim Lambert (SJL) strain of obesity-resistan ... .; Joost, H.-G.; Al-Hasani, H.: Tbc1d1 mutation in lean ... mouse strain confers lean ness and protects from di ...

  14. 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...

  15. 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.

  16. 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.

  17. NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program.

    Science.gov (United States)

    Pataskar, Abhijeet; Jung, Johannes; Smialowski, Pawel; Noack, Florian; Calegari, Federico; Straub, Tobias; Tiwari, Vijay K

    2016-01-01

    Cell fate specification relies on the action of critical transcription factors that become available at distinct stages of embryonic development. One such factor is NeuroD1, which is essential for eliciting the neuronal development program and possesses the ability to reprogram other cell types into neurons. Given this capacity, it is important to understand its targets and the mechanism underlying neuronal specification. Here, we show that NeuroD1 directly binds regulatory elements of neuronal genes that are developmentally silenced by epigenetic mechanisms. This targeting is sufficient to initiate events that confer transcriptional competence, including reprogramming of transcription factor landscape, conversion of heterochromatin to euchromatin, and increased chromatin accessibility, indicating potential pioneer factor ability of NeuroD1. The transcriptional induction of neuronal fate genes is maintained via epigenetic memory despite a transient NeuroD1 induction during neurogenesis. NeuroD1 also induces genes involved in the epithelial-to-mesenchymal transition, thereby promoting neuronal migration. Our study not only reveals the NeuroD1-dependent gene regulatory program driving neurogenesis but also increases our understanding of how cell fate specification during development involves a concerted action of transcription factors and epigenetic mechanisms. PMID:26516211

  18. 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

  19. 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.

  20. A novel IgE-binding epitope of cat major allergen, Fel d 1.

    Science.gov (United States)

    Tasaniyananda, Natt; Tungtrongchitr, Anchalee; Seesuay, Watee; Sakolvaree, Yuwaporn; Indrawattana, Nitaya; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-02-12

    Information on the antigenic repertoire, especially the IgE-binding epitopes of an allergen is important for understanding the allergen induced immune response and cross-reactivity, as well as for generating the hypoallergenic variants for specific component resolved immunotherapy/diagnosis (CRIT and CRD). Data on the IgE-binding epitopes of cat allergens are scarce. In this study, a novel IgE-binding epitope of the cat major allergen, Fel d 1, was identified. Mouse monoclonal antibody (MAb) specific to the Fel d 1 was produced. Computerized intermolecular docking was used for determining the residues of the Fel d 1 bound by the specific MAb. The presumptive surface exposed residues of the Fel d 1 intrigued by the MAb are located on the chain 1. They are: L34 and T37 (helix 1); T39 (between helices 1 and 2); P40, E42 and E45 (helix 2); R61, K64, N65 and D68 (helix 3); and E73 and K76 (helix 4). The MAb competed efficiently with the cat allergic patients' serum IgE for Fel d 1 binding in the competitive IgE binding assay, indicating allergenicity of the MAb epitope. The newly identified allergenic epitope of the Fel d 1 is useful in a design of the CRIT and CRD for cat allergy. PMID:26797272

  1. 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.

  2. Identification of D1-like dopamine receptors on human blood platelets

    International Nuclear Information System (INIS)

    Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study the authors report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D1 dopamine receptor antagonist (3H)SCH 23390. (3H)SCH 23390 appeared to label a single class of binding sites with a B/sub max/ of 18.6 +- 1.6 fmolmg protein and a K/sub D/ of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (3H)SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D1 receptors, e.g. those in striatum, the D1 receptor sites on platelets appeared no to be coupled to the adenylate cyclase system, hence the term D1-like. The D1 agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D1-like receptors

  3. Rapid anti-depressant and anxiolytic actions following dopamine D1-D2 receptor heteromer inactivation.

    Science.gov (United States)

    Shen, Maurice Y F; Perreault, Melissa L; Bambico, Francis R; Jones-Tabah, Jace; Cheung, Marco; Fan, Theresa; Nobrega, José N; George, Susan R

    2015-12-01

    A role for the mesolimbic dopaminergic system in the pathophysiology of depression has become increasingly evident. Specifically, brain-derived neurotrophic factor (BDNF) has been shown to be elevated in the nucleus accumbens of depressed patients and to positively contribute to depression-like behaviour in rodents. The dopamine D1-D2 receptor heteromer exhibits significant expression in NAc and has also been shown to enhance BDNF expression and signalling in this region. We therefore examined the effects of D1-D2 heteromer stimulation in rats by SKF 83959, or its inactivation by a selective heteromer-disrupting TAT-D1 peptide on depression- and anxiety-like behaviours in non-stressed animals and in animals exposed to chronic unpredictable stress. SKF 83959 treatment significantly enhanced the latency to immobility in the forced swim test, increased the latency to drink condensed milk and reduced total milk consumption in the novelty-induced hypophagia test, and additionally reduced the total time spent in the open arms in the elevated plus maze test. These pro-depressant and anxiogenic effects of SKF 83959 were consistently abolished or attenuated by TAT-D1 peptide pre-treatment, signifying the behaviours were mediated by the D1-D2 heteromer. More importantly, in animals exposed to chronic unpredictable stress (CUS), TAT-D1 peptide treatment alone induced significant and rapid anxiolytic and antidepressant-like effects in two tests for CUS-induced anhedonia-like reactivity and in the novelty-suppressed feeding test. Together these findings indicate a positive role for the D1-D2 heteromer in mediating depression- and anxiety-like behaviours and suggest its possible value as a novel therapeutic target. PMID:26431907

  4. 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.

  5. Detection of cyclin D1 in B cell lymphoproliferative disorders by flow cytometry

    Science.gov (United States)

    Jain, P; Giustolisi, G M; Atkinson, S; Elnenaei, M O; Morilla, R; Owusu-Ankomah, K; Rafiq-Mohammed, F; Matutes, E; Wotherspoon, A; Catovsky, D

    2002-01-01

    Aims: To describe and revise a flow cytometric assay for evaluating cyclin D1 overexpression in B cell lymphoproliferative disorders (B-LPDs). Methods: Cyclin D1 expression was evaluated in 11 healthy controls and 51 patients with B-LPD by flow cytometry using the 5D4 monoclonal antibody. In 25 cases, experiments were repeated up to four times with mononuclear cells (MNC) fixed in ethanol for 1–120 days to evaluate the consistency of cyclin D1 expression. Flow cytometry results were compared with fluorescence in situ hybridisation (FISH) for the t(11;14) translocation in 19 patients and with immunohistochemistry (IHC) using the DCS-6 monoclonal antibody in nine patients. Results: A mean fluorescence intensity ratio (MFIR) of 4.8 was defined as the cut off point for positivity based on cyclin D1 expression in healthy controls (mean + 3 SD). Ten patients overexpressed cyclin D1 by flow cytometry. These included five of eight patients with mantle cell lymphoma, four of 19 with chronic lymphocytic leukaemia, and one with follicular lymphoma. MFIR in the repeat experiments differed less than 25% in 20 of 25 patients and in no cases did it cross the cut off point. There was a good correlation between cyclin D1 expression by flow cytometry and FISH for t(11;14) in 15 of 19 patients and six of nine had concordant results with flow cytometry, FISH, and IHC. Conclusion: Cyclin D1 expression remains fairly stable once MNC are fixed in ethanol and the flow cytometric assay can be used for the routine screening of B-LPD. Further comparisons between flow cytometry, IHC, and FISH may be needed to ascertain the diagnostic value of the flow cytometric assay. PMID:12461064

  6. 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

  7. BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells

    International Nuclear Information System (INIS)

    The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERα signaling. However, many ERα-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERα signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERα-negative cells. We previously noticed that both ERα-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERα-negative cell lines even exceeded its over-expression level in ERα-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERα-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene

  8. 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

  9. Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1.

    Science.gov (United States)

    Hong, Juyeong; Lee, Ji Hoon; Chung, In Kwon

    2016-04-15

    Telomerase is a ribonucleoprotein enzyme that is required for the maintenance of telomere repeats. Although overexpression of telomerase in normal human somatic cells is sufficient to overcome replicative senescence, the ability of telomerase to promote tumorigenesis requires additional activities that are independent of its role in telomere extension. Here, we identify proliferation-associated nucleolar antigen 120 (NOL1, also known as NOP2) as a telomerase RNA component (TERC)-binding protein that is found in association with catalytically active telomerase. Although NOL1 is highly expressed in the majority of human tumor cells, the molecular mechanism by which NOL1 contributes to tumorigenesis remained unclear. We show that NOL1 binds to the T-cell factor (TCF)-binding element of the cyclin D1 promoter and activates its transcription. Interestingly, telomerase is also recruited to the cyclin D1 promoter in a TERC-dependent manner through the interaction with NOL1, further enhancing transcription of the cyclin D1 gene. Depletion of NOL1 suppresses cyclin D1 promoter activity, thereby leading to induction of growth arrest and altered cell cycle distributions. Collectively, our findings suggest that NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity. PMID:26906424

  10. 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.

  11. 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.

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

    CERN Document Server

    Hollands, Stefan

    2016-01-01

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

  13. Renal imaging with a new agent sup(99m)Tc-d1-DMS

    International Nuclear Information System (INIS)

    By using sup(99m)-Tc-d1 DMS labeled with 99 m-Tc using stannous chloride and prepared with freeze-dried d1-DMS containing a 3:1 molar ratio of DMS and Sn+2 the effect of stereochemical factor of DMS on kidney affinity, renal images, blood clearance, urinary excretion was studied in experimental animals and two normal volunteers and 75 patients. The comparation revealed a quite similar formation of complex II from d1-DMS to that from the meso-form, judge from its absorption spectra and absorption behavior into the gel. The stereochemical difference of DMS is not a critical factor for the formation of the sup(99m)-Tc-DMS complex with high affinity for the kidney, although it is believed that the renal accumulation of Tc-complex will depend greatly on chemical configuration of the complex. (APR)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-15

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

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

    International Nuclear Information System (INIS)

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

  16. 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

  17. A transgenic mouse model of neuroepithelial cell specific inducible overexpression of dopamine D1-receptor.

    Science.gov (United States)

    Fujimoto, K; Araki, K; McCarthy, D M; Sims, J R; Ren, J Q; Zhang, X; Bhide, P G

    2010-10-27

    Dopamine and its receptors appear in the brain during early embryonic period suggesting a role for dopamine in brain development. In fact, dopamine receptor imbalance resulting from impaired physiological balance between D1- and D2-receptor activities can perturb brain development and lead to persisting changes in brain structure and function. Dopamine receptor imbalance can be produced experimentally using pharmacological or genetic methods. Pharmacological methods tend to activate or antagonize the receptors in all cell types. In the traditional gene knockout models the receptor imbalance occurs during development and also at maturity. Therefore, assaying the effects of dopamine imbalance on specific cell types (e.g. precursor versus postmitotic cells) or at specific periods of brain development (e.g. pre- or postnatal periods) is not feasible in these models. We describe a novel transgenic mouse model based on the tetracycline dependent inducible gene expression system in which dopamine D1-receptor transgene expression is induced selectively in neuroepithelial cells of the embryonic brain at experimenter-chosen intervals of brain development. In this model, doxycycline-induced expression of the transgene causes significant overexpression of the D1-receptor and significant reductions in the incorporation of the S-phase marker bromodeoxyuridine into neuroepithelial cells of the basal and dorsal telencephalon indicating marked effects on telencephalic neurogenesis. The D1-receptor overexpression occurs at higher levels in the medial ganglionic eminence (MGE) than the lateral ganglionic eminence (LGE) or cerebral wall (CW). Moreover, although the transgene is induced selectively in the neuroepithelium, D1-receptor protein overexpression appears to persist in postmitotic cells. The mouse model can be modified for neuroepithelial cell-specific inducible expression of other transgenes or induction of the D1-receptor transgene in other cells in specific brain regions by

  18. 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.

  19. 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

  20. 26 CFR 1.410(d)-1 - Election by church to have participation, vesting, funding, etc. provisions apply.

    Science.gov (United States)

    2010-04-01

    ..., vesting, funding, etc. provisions apply. 1.410(d)-1 Section 1.410(d)-1 Internal Revenue INTERNAL REVENUE...-Sharing, Stock Bonus Plans, Etc. § 1.410(d)-1 Election by church to have participation, vesting, funding, etc. provisions apply. (a) In general. If a church or convention or association of churches...

  1. 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...

  2. 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

  3. Continuum Limits of ``Induced QCD": Lessons of the Gaussian Model at d=1 and Beyond

    OpenAIRE

    Kogan, I. I.; Morozov, A; Semenoff, G. W.; Weiss, N.

    1992-01-01

    We analyze the scalar field sector of the Kazakov--Migdal model of induced QCD. We present a detailed description of the simplest one dimensional {($d$$=$$1$)} model which supports the hypothesis of wide applicability of the mean--field approximation for the scalar fields and the existence of critical behaviour in the model when the scalar action is Gaussian. Despite the ocurrence of various non--trivial types of critical behaviour in the $d=1$ model as $N\\rightarrow\\infty$, only the conventi...

  4. Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses

    OpenAIRE

    Holl, Eda K.; O’Connor, Brian P.; Holl, T. Matt; Roney, Kelly E.; Zimmermann, Albert G.; Jha, Sushmita; Kelsoe, Garnett; Ting, Jenny P.-Y.

    2011-01-01

    Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone...

  5. 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

    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 <0.05) and 16 that are up-regulated...... (>twofold, p <0.05). According to quantitative RT-PCR, the most dramatically down-regulated gene is kinesin family member 5C ( approximately 100-fold) and the most dramatically up-regulated gene is glutamic acid decarboxylase 1 ( approximately fourfold). Other impacted transcripts encode proteins involved...

  6. 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).

  7. Towards implementation of transparency and participation in radioactive waste management programmes. ARGONA Final Summary Report. Deliverable 23b

    International Nuclear Information System (INIS)

    organization. In such a case, it may be better to clarify the different aims of the two processes . The suggested guidelines in ARGONA Deliverable No. 22 give more advice on how mediation by demonstration and mediation by dialogue can be used and combined. It is evident that participative processes and transparency arenas can improve the quality of societal decision making in specific situations. But, as we have seen any project or programme with this purpose has it limits. Then somehow, society should be able to continue the process in a wider context than the explicit decision situations where transparency arenas take place. This wider context, or philosophical orientation, which we call reflexivity has two meanings; reflexivity as 'contextualisation' or 'becoming aware of how knowledge is produced', and reflexivity' in the meaning of 'self-confrontation' to become aware of the potential of and limits to own knowledge and own role in a discourse setting. Based on the analysis made in ARGONA it is recommended that formally organised transparency arenas should become a universal norm that should inspire and steer the practical political organisation of governance. For any decision making process, to be legitimate it needs to have a certain degree of trust among those affected, those participating and citizens at large. If a stakeholder does not trust the organization of a particular deliberative or transparency setting he will not take part and immediately it will lose legitimacy. This project highlighted four elements in building trust: 1) a jointly agreed aim to gain insight into the complexity of radioactive waste management, 2) real justification meaning that there is a real chance for stakeholders to influence the process, 3) looking back for understating 'why things went the way they went', and 4) adaptability of a decision process to the social and physical reality including reversibility of decisions

  8. 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.

  9. 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

  10. D1+ Simulator: A cost and risk optimized approach to nuclear power plant simulator modernization

    International Nuclear Information System (INIS)

    D1-Simulator is operated by Kraftwerks-Simulator-Gesellschaft (KSG) and Gesellschaft f?r Simulatorschulung (GfS) at the Simulator Centre in Essen since 1977. The full-scope control room training simulator, used for Kernkraftwerk Biblis (KWB) is based on a PDP-11 hardware platform and is mainly programmed in ASSEMBLER language. The Simulator has reached a continuous high availability of operation throughout the years due to specialized hardware and software support from KSG maintenance team. Nevertheless, D1-Simulator largely reveals limitations with respect to computer capacity and spares and suffers progressively from the non-availability of hardware replacement materials. In order to ensure long term maintainability within the framework of the consensus on nuclear energy, a 2-years refurbishing program has been launched by KWB focusing on quality and budgetary aspects. The so-called D1+ Simulator project is based on the re-use of validated data from existing simulators. Allowing for flexible project management methods, the project outlines a cost and risk optimized approach to Nuclear Power Plant (NPP) Simulator modernization. D1+ Simulator is being built by KSG/GfS in close collaboration with KWB and the simulator vendor THALES by re-using a modern hardware and software development environment from D56-Simulator, used by Kernkraftwerk Obrigheim (KWO) before its decommissioning in 2005. The Simulator project, launched in 2004, is expected to be completed by end of 2006. (author)

  11. [11C]NNC 22-0215, a metabolically stable dopamine D1 radioligand for PET

    International Nuclear Information System (INIS)

    NNC 22-0215 has been found to be a metabolically stable dopamine D1 antagonist with high affinity and selectivity for D1 receptors in vitro. We prepared [11C]NNC 22-0215 with a specific radioactivity of about 50 GBq/μmol at time of administration. In PET experiments with [11C]NNC 22-0215 there was a rapid uptake of radioactivity in the cynomolgus monkey brain (1.8% of total radioactivity injected). Radioactivity accumulated most markedly in the striatum and the neocortex. The striatum to cerebellum ratio was about 4, with specific binding that remained at a plateau level from 50 min to 100 min after injection. Binding in the striatum and neocortex was markedly displaced by SCH 23390, whereas binding in the cerebellum was not reduced. Metabolite studies showed that about 80% of the radioactivity in the monkey plasma represented unchanged radioligand 30 min after injection. The rate of metabolism in monkey plasma in vivo was also determined for a series of structurally related 11C-labelled benzazepines, previously used as dopamine D1 receptor ligands for PET. Results indicate a significantly slower rate of metabolism for [11C]NNC 22-0215 than for any of the previously labelled benzazepines. Thus [11C]NNC 22-0215 has potential for imaging of selective binding to the dopamine D1 receptors in the human brain with high count rates at time of equilibrium

  12. 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.

  13. Integrability of a D1-brane on a group manifold with mixed three-form flux

    Science.gov (United States)

    KlusoÅ, Josef

    2016-02-01

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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. ( 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.

  19. 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"

  20. 2D/1D approximations to the 3D neutron transport equation. I: Theory

    International Nuclear Information System (INIS)

    A new class of '2D/1D' approximations is proposed for the 3D linear Boltzmann equation. These approximate equations preserve the exact transport physics in the radial directions x and y and diffusion physics in the axial direction z. Thus, the 2D/1D equations are more accurate approximations of the 3D Boltzmann equation than the conventional 3D diffusion equation. The 2D/1D equations can be systematically discretized, to yield accurate simulation methods for 3D reactor core problems. The resulting solutions will be more accurate than 3D diffusion solutions, and less expensive to generate than standard 3D transport solutions. In this paper, we (i) show that the simplest 2D/1D equation has certain desirable properties, (ii) systematically discretize this equation, and (iii) derive a stable iteration scheme for solving the discrete system of equations. In a companion paper [1], we give numerical results that confirm the theoretical predictions of accuracy and iterative stability. (authors)

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

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.30d-1 Filing of copies of reports to shareholders. A registered management investment company, other than a small business investment company... business investment company registered on Form N-5 that is required to file annual and quarterly...

  2. D1D5 systems and AdS/CFT correspondences with 16 supercharges

    CERN Document Server

    Gava, E; Morales, J F; Narain, Kumar S; Gava, Edi; Hammou, Amine B.; Morales, Jose F.; Narain, Kumar S.

    2002-01-01

    We study the spectra of BPS excitations of D1D5 bound states in a class of free orbifolds/orientifolds of type IIB theory and its dual descriptions in terms of chiral primaries of the corresponding $AdS_3$ supergravities.

  3. Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus.

    Science.gov (United States)

    Gangarossa, Giuseppe; Longueville, Sophie; De Bundel, Dimitri; Perroy, Julie; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-12-01

    The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor-expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ-Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network. PMID:22777829

  4. 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

  5. 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

  6. Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements

    Science.gov (United States)

    Liu, Shu; Bolger, Joshua K.; Kirkland, Lindsay O.; Premnath, Padmavathy N.; McInnes, Campbell

    2012-01-01

    An alternative strategy for inhibition of the cyclin dependent kinases in anti-tumor drug discovery is afforded through the substrate recruitment site on the cyclin positive regulatory subunit. Critical CDK substrates such as the Rb and E2F families must undergo cyclin groove binding before phosphorylation and hence inhibitors of this interaction also block substrate specific kinase activity. This approach offers the potential of generating highly selective and cell cycle specific CDK inhibitors and to reduce the inhibition of transcription mediated through CDK7 and 9, commonly observed with ATP competitive compounds. While highly potent peptide and small molecule inhibitors of CDK2/cyclin A, E substrate recruitment have been reported, little information has been generated on the determinants of inhibitor binding to the cyclin groove of the CDK4/cyclin D1 complex. CDK4/cyclin D is a validated anti-cancer drug target and continues to be widely pursued in the development of new therapeutics based on cell cycle blockade. We have therefore investigated the structural basis for peptide binding to its cyclin groove and have examined the features contributing to potency and selectivity of inhibitors. Peptidic inhibitors of CDK4/cyclin D of pRb phosphorylation have been synthesized, and their complexes with CDK4/cyclin D1 crystal structures have been generated. Based on available structural information, comparisons of the cyclin grooves of cyclin A2 and D1 are presented and provide insights into the determinants for peptide binding and the basis for differential binding and inhibition. In addition, a complex structure has been generated in order to model the interactions of the CDKI, p27KIP1, with cyclin D1. This information has been used shed light onto the endogenous inhibition of CDK4 and also to identify unique aspects of cyclin D1 and which can be exploited in the design of cyclin groove based CDK inhibitors. Peptidic and non-peptidic compounds have been synthesized

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    2015-06-01

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

  13. Integrated physics analysis of plasma operation control scenario of helical reactor FFHR-d1

    International Nuclear Information System (INIS)

    1-D analysis of the plasma operation control scenario of the LHD-type helical reactor FFHR-d1 was conducted. A stable variation of the fusion power can be realized by feedback control of the pellet fuelling and the simple staged variation of the external heating power with a small number of simple diagnostics (line-averaged electron density, edge electron density and fusion power). Detailed physics assessment on MHD equilibrium and neo-classical energy loss was conducted by the integrated transport analysis code TASK3D. Although some more measures to suppress Shafranov shift are preferable in high beta conditions, a baseline operation control scenario of FFHR-d1 (plasma start-up and steady-state sustainment) for both self-ignition and sub-ignition conditions was established. (author)

  14. 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.

  15. 2D/1D approximations to the 3D neutron transport equation. II: Numerical comparisons

    International Nuclear Information System (INIS)

    In a companion paper [1], (i) several new '2D/1D equations' are introduced as accurate approximations to the 3D Boltzmann transport equation, (ii) the simplest of these approximate equations is systematically discretized, and (iii) a theoretically stable iteration scheme is developed to solve the discrete equations. In this paper, numerical results are presented that confirm the theoretical predictions made in [1]. (authors)

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-15

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

  18. 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. ...

  19. 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.

  20. 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...

  1. 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....

  2. 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....

  3. 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

  4. 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

  5. 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.

  6. THE QUIET SOLAR ATMOSPHERE OBSERVED AND SIMULATED IN Na I D1

    International Nuclear Information System (INIS)

    The Na I D1 line in the solar spectrum is sometimes attributed to the solar chromosphere. We study its formation in quiet-Sun network and internetwork. We first present high-resolution profile-resolved images taken in this line with the imaging spectrometer Interferometric Bidimensional Spectrometer at the Dunn Solar Telescope and compare these to simultaneous chromospheric images taken in Ca II 8542 A and Hα. We then model Na I D1 formation by performing three-dimensional (3D) non-local thermodynamic equilibrium profile synthesis for a snapshot from a 3D radiation-magnetohydrodynamics simulation. We find that most Na I D1 brightness is not chromospheric but samples the magnetic concentrations that make up the quiet-Sun network in the photosphere, well below the height where they merge into chromospheric canopies, with aureoles from 3D resonance scattering. The line core is sensitive to magneto-acoustic shocks in and near magnetic concentrations, where shocks occur deeper than elsewhere, and may provide evidence of heating deep within magnetic concentrations.

  7. 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...

  8. 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

  9. 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.

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

    International Nuclear Information System (INIS)

    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

  11. 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.

  12. Regulation of c-fos expression by the dopamine D1–D2 receptor heteromer

    Science.gov (United States)

    Perreault, Melissa L.; Shen, Maurice Y.F.; George, Susan R.

    2015-01-01

    The dopamine D1 and D2 receptors form the D1–D2 receptor heteromer in a subset of neurons and couple to the Gq protein to regulated intracellular calcium signaling. In the present study the effect of D1–D2 heteromer activation and disruption on neuronal activation in rat brain was mapped. This was accomplished using the dopamine agonist SKF 83959 to activate the D1–D2 heteromer in combination with a TAT-D1 disrupting peptide we developed, and which has been shown to disrupt the D1/D2 receptor interaction and antagonize D1–D2 heteromer-induced cell signaling and behaviour. Acute SKF 83959 administration to rats induced significant c-fos expression in nucleus accumbens that was significantly inhibited by TAT-D1 pretreatment. No effects of SKF 83959 were seen in caudate putamen. D1–D2 heteromer disruption by TAT-D1 did not have any effects in any striatal subregions, but induced significant c-fos immunoreactivity in a number of cortical regions including the orbitofrontal cortex, prelimbic and infralimbic cortices and the piriform cortex. The induction of c-fos by TAT-D1 was also evident in the anterior olfactory nucleus, as well as the lateral habenula and thalamic nuclei. These findings show for the first time that the D1–D2 heteromer can differentially regulate c-fos expression in a region-dependent manner either through its activation or through tonic inhibition of neuronal activity. PMID:25446350

  13. 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...

  14. 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.

  15. Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors

    OpenAIRE

    Huang, Yan-You; Simpson, Eleanor; Kellendonk, Christoph; Kandel, Eric R.

    2004-01-01

    To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 r...

  16. 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...

  17. 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.

  18. Assessment and improvement of the 2D/1D method stability in DeCART

    International Nuclear Information System (INIS)

    As part of ongoing work with Consortium for Advanced Simulation of Light Water Reactors (CASL), the 2D/1D code, DeCART, has demonstrated some of the advantages of the 2D/1D method with respect to realistic, full-core analysis, particularly over explicit 3D transport methods, which generally have higher memory and computation requirements. The 2D/1D method performs 2D-radial transport sweeps coupled with ID-axial diffusion calculations to provide a full 3D simulation. DeCART employs the 2D method of characteristics for the radial sweeps and ID one-node nodal diffusion for the axial sweeps, coupling the two methods with transverse leakages to ensure a more consistent representation of the transport equation. It has been observed that refinement of the axial plane thickness leads to instabilities in the calculation scheme. This work assesses the sources of these instabilities and the approaches to improve them, especially with respect to negative scattering cross sections and the tightness of the 2D-radial/ID-axial coupling schemes. Fourier analyses show that the existing iteration scheme is not unconditionally stable, suggesting a tighter coupling scheme is required. For this reason 3D-CMFD has been implemented, among other developments, to ensure more stable calculation. A matrix of test cases has been used to assess the convergence, with the primary parameter being the axial plane thickness, which has been refined down to 1 cm. These cases demonstrate the issues observed and how the modification improve the stability. However, it is apparent that more work is necessary to ensure unconditional stability. (authors)

  19. Assessment and improvement of the 2D/1D method stability in DeCART

    Energy Technology Data Exchange (ETDEWEB)

    Stimpson, S.; Young, M.; Collins, B.; Kelley, B.; Downar, T. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, 2355 Bonisteel Boulevard, Ann Arbor, MI 48109-2104 (United States)

    2013-07-01

    As part of ongoing work with Consortium for Advanced Simulation of Light Water Reactors (CASL), the 2D/1D code, DeCART, has demonstrated some of the advantages of the 2D/1D method with respect to realistic, full-core analysis, particularly over explicit 3D transport methods, which generally have higher memory and computation requirements. The 2D/1D method performs 2D-radial transport sweeps coupled with ID-axial diffusion calculations to provide a full 3D simulation. DeCART employs the 2D method of characteristics for the radial sweeps and ID one-node nodal diffusion for the axial sweeps, coupling the two methods with transverse leakages to ensure a more consistent representation of the transport equation. It has been observed that refinement of the axial plane thickness leads to instabilities in the calculation scheme. This work assesses the sources of these instabilities and the approaches to improve them, especially with respect to negative scattering cross sections and the tightness of the 2D-radial/ID-axial coupling schemes. Fourier analyses show that the existing iteration scheme is not unconditionally stable, suggesting a tighter coupling scheme is required. For this reason 3D-CMFD has been implemented, among other developments, to ensure more stable calculation. A matrix of test cases has been used to assess the convergence, with the primary parameter being the axial plane thickness, which has been refined down to 1 cm. These cases demonstrate the issues observed and how the modification improve the stability. However, it is apparent that more work is necessary to ensure unconditional stability. (authors)

  20. The multivariate Meixner polynomials as matrix elements of SO(d, 1) representations on oscillator states

    Science.gov (United States)

    Genest, Vincent X.; Miki, Hiroshi; Vinet, Luc; Zhedanov, Alexei

    2014-01-01

    The multivariate Meixner polynomials are shown to arise as matrix elements of unitary representations of the SO(d, 1) group on oscillator states. These polynomials depend on d discrete variables and are orthogonal with respect to the negative multinomial distribution. The emphasis is put on the bivariate case for which the SO(2, 1) connection is used to derive the main properties of the polynomials: orthogonality relation, raising/lowering relations, generating function, recurrence relations and difference equations as well as explicit expressions in terms of standard (univariate) Krawtchouk and Meixner polynomials. It is explained how these results generalize directly to d variables.

  1. The multivariate Meixner polynomials as matrix elements of SO(d, 1) representations on oscillator states

    International Nuclear Information System (INIS)

    The multivariate Meixner polynomials are shown to arise as matrix elements of unitary representations of the SO(d, 1) group on oscillator states. These polynomials depend on d discrete variables and are orthogonal with respect to the negative multinomial distribution. The emphasis is put on the bivariate case for which the SO(2, 1) connection is used to derive the main properties of the polynomials: orthogonality relation, raising/lowering relations, generating function, recurrence relations and difference equations as well as explicit expressions in terms of standard (univariate) Krawtchouk and Meixner polynomials. It is explained how these results generalize directly to d variables. (paper)

  2. 2D 1/2 visual servoing stability analysis with respect to camera calibration errors

    OpenAIRE

    Malis, E.; Chaumette, François; Boudet, S.

    1998-01-01

    In this paper, the robustness of a new visual servoing scheme with respect to camera calibration errors is analyzed. This scheme, called 2D~1/2 visual servoing, is based on the estimation of the partial camera displacement from the current to the desired camera poses at each iteration of the control law. Visual features and data extracted from the partial displacement allow us to design a decoupled control law controlling the six camera d.o.f. The necessary and sufficient conditions for local...

  3. 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.; Foss, N.; Briza, P.; Oberhuber, C.; Radauer, C.; Alessandri, S.; Knulst, A.C.; Fernandez-Rivas, M.; Barkholt, Vibeke

    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...... commercially available, these preparations contain impurities, which affect exact in vitro diagnosis. The aim of the present study was to set up further purification protocols and to extend the characterization of the physicochemical and immunological properties of the final batches. The egg white allergens...

  4. High-precision Monte Carlo study of directed percolation in (d+1) dimensions.

    Science.gov (United States)

    Wang, Junfeng; Zhou, Zongzheng; Liu, Qingquan; Garoni, Timothy M; Deng, Youjin

    2013-10-01

    We present a Monte Carlo study of the bond- and site-directed (oriented) percolation models in (d+1) dimensions on simple-cubic and body-centered-cubic lattices, with 2 ≤ d ≤ 7. A dimensionless ratio is defined, and an analysis of its finite-size scaling produces improved estimates of percolation thresholds. We also report improved estimates for the standard critical exponents. In addition, we study the probability distributions of the number of wet sites and radius of gyration, for 1 ≤ d ≤ 7. PMID:24229111

  5. Shape-independent expansion for the 3S1 - 3D1 mixing parameter

    International Nuclear Information System (INIS)

    A low-energy shape-independent expansion is suggested for the function [tan(2εBB)/(2 k2)], where εBB is the Blatt-Biedenharn mixing parameter for the 3 S1-3 D1 channel. This expansion allows an evaluation of the mixing parameters εBB from a knowledge of the deuteron asymptotic D to S ratio, pion mass and other low-energy observables, such as the scattering lengths, deuteron binding etc., of the nucleon-nucleon system. It is demonstrated that the correct long range behavior of the tensor potential is essential for a realistic reproduction of εBB. (author)

  6. Lack of Self-Administration of Cocaine in Dopamine D1 Receptor Knock-Out Mice

    OpenAIRE

    Caine, S. Barak; Thomsen, Morgane; Gabriel, Kara I.; Berkowitz, Jill S.; Gold, Lisa H.; Koob, George F; Tonegawa, Susumu; Zhang, Jianhua; Xu, Ming

    2007-01-01

    Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, “knock-out” of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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...

  13. Experimental Conditions: SE37_S04_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S04_M1_D1 SE37 Medicago truncatula shoot metabolite analysis using stable isot...opes SE37_S04 13C-labeled Medicago truncatula Jemalong A17 shoot SE37_S04_M1 0.25mg Metabolites were extract...ed from 10.81mg of plant sample. [MassBase ID] MDLC1_43502 SE37_MS1 Metabolites extraction with 80% methanol... and analysis by LC-Orbitrap-MS SE37_DS2 Peak extraction for labeled data 6|ITMS 2 ...

  14. Second order effect of twist deformation in the D1D5 CFT

    CERN Document Server

    Carson, Zaq; Mathur, Samir D

    2015-01-01

    Thermalization in the D1D5 CFT should occur via interactions caused by the twist operator, which deforms the theory off its free orbifold point. Earlier studies investigating this deformation at first order did not show any definite evidence of thermalization. In this paper we study the deformation to second order, where we do expect to see the effects that should give thermalization. We compute the effect of two twist operators on an initial vacuum state, which generates a squeezed state analogous to the case for a single twist. We obtain expressions for the Bogoliubov coefficients in this 2-twist case.

  15. 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...

  16. 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.

  17. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

    International Nuclear Information System (INIS)

    Dopamine receptor types D1 and D2 can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D1-D2 interaction in homogenized tissue as revealed by ligand binding. D2 agonists lowered the binding of [3H]raclopride to D2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D1-selective antagonist SCH 23390 prevented the agonist-induced decrease in [3H]raclopride binding to D2 sites in the striatum but not in the anterior pituitary, which has no D1 receptors. Conversely, a dopamine-induced reduction in the binding of [3H]SCH 23390 to D1 receptors could be prevented by the D2-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D1-D2 interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D2 receptors in the high-affinity state. Thus, the D1-D2 link may be mediated by guanine nucleotide-binding protein components. The link may underlie D1-D2 interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata

  18. 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.

  19. 26 CFR 301.6511(d)-1 - Overpayment of income tax on account of bad debts, worthless securities, etc.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Overpayment of income tax on account of bad debts, worthless securities, etc. 301.6511(d)-1 Section 301.6511(d)-1 Internal Revenue INTERNAL REVENUE... bad debts, worthless securities, etc. (a)(1) If the claim for credit or refund relates to...

  20. 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

  1. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    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

  4. 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)

  5. Identification and characterization of major cat allergen Fel d 1 mimotopes on filamentous phage carriers.

    Science.gov (United States)

    Luzar, Jernej; Molek, Peter; Šilar, Mira; Korošec, Peter; Košnik, Mitja; Štrukelj, Borut; Lunder, Mojca

    2016-03-01

    Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. PMID:26908079

  6. 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.

  7. 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

  8. Dopamine D1 receptor expression is bipolar cell type-specific in the mouse retina.

    Science.gov (United States)

    Farshi, Pershang; Fyk-Kolodziej, Bozena; Krolewski, David M; Walker, Paul D; Ichinose, Tomomi

    2016-07-01

    In the retina, dopamine is a key molecule for daytime vision. Dopamine is released by retinal dopaminergic amacrine cells and transmits signaling either by conventional synaptic or by volume transmission. By means of volume transmission, dopamine modulates all layers of retinal neurons; however, it is not well understood how dopamine modulates visual signaling pathways in bipolar cells. Here we analyzed Drd1a-tdTomato BAC transgenic mice and found that the dopamine D1 receptor (D1R) is expressed in retinal bipolar cells in a type-dependent manner. Strong tdTomato fluorescence was detected in the inner nuclear layer and localized to type 1, 3b, and 4 OFF bipolar cells and type 5-2, XBC, 6, and 7 ON bipolar cells. In contrast, type 2, 3a, 5-1, 9, and rod bipolar cells did not express Drd1a-tdTomato. Other interneurons were also found to express tdTomato including horizontal cells and a subset (25%) of AII amacrine cells. Diverse visual processing pathways, such as color or motion-coded pathways, are thought to be initiated in retinal bipolar cells. Our results indicate that dopamine sculpts bipolar cell performance in a type-dependent manner to facilitate daytime vision. J. Comp. Neurol. 524:2059-2079, 2016. © 2015 Wiley Periodicals, Inc. PMID:26587737

  9. 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.

  10. 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; de Sousa, Rodrigo Cunha; da Silva, Marcos Vinícius; Correia, Dalmo; Rodrigues Junior, Virmondes; Levy, Bruce David; de Paula Rogério, Alexandre

    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. PMID:26927755

  11. Depotentiation in the dentate gyrus of freely moving rats is modulated by D1/D5 dopamine receptors.

    Science.gov (United States)

    Kulla, A; Manahan-Vaughan, D

    2000-06-01

    Hippocampal depotentiation comprises a reversal of tetanization- induced long-term potentiation (LTP) which occurs following low-frequency stimulation. In the CA1 region, it has been reported that agonist activation of D1/D5 dopamine receptors enhances LTP expression and inhibits depotentiation. The role of these receptors in synaptic plasticity in the dentate gyrus (DG) has not been characterized. This study therefore investigated the role of D1/D5 receptors in LTP and depotentiation in the DG of freely moving rats. Male Wistar rats underwent chronic implantation of a recording electrode in the DG granule cell layer, a bipolar stimulating electrode in the medial perforant path and a cannula in the ipsilateral cerebral ventricle (to enable drug administration). The D1/D5 agonist Chloro-PB dose-dependently inhibited depotentation in the DG. This effect was prevented by the D1/D5 antagonist SCH 23390. Neither D1/D5 agonist nor antagonist had an effect on LTP expression or basal synaptic transmission. These results highlight differences between D1/D5 receptor-involvement in LTP and depotentiation in the CA1 region and DG, and indicate that whereas D1/D5 receptor activation may not be a critical factor in LTP induction in the DG, a differential role for these receptors in the expression of depotentiation, in this hippocampal subfield, may exist. PMID:10859139

  12. 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.

  13. 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.

  14. 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).

  15. 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

  16. 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.

  17. 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...

  18. 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...

  19. Semaphorin 3E Initiates Antiangiogenic Signaling through Plexin D1 by Regulating Arf6 and R-Ras▿ †

    OpenAIRE

    Sakurai, Atsuko; Gavard, Julie; Annas-Linhares, Yuliya; Basile, John R.; Amornphimoltham, Panomwat; Palmby, Todd R.; Yagi, Hiroshi; Zhang, Fan; Randazzo, Paul A; Li, Xuri; Weigert, Roberto; Gutkind, J. Silvio

    2010-01-01

    Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here that Sema3E acts as a potent inhibitor of adult and tumor-induced angiogenesis. Activation of plexin D1 by Sema3E causes the rapid disassembly of integrin-m...

  20. 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

  1. Trapping Spin-$0$ particles on $p-$balls in $(D,1)$ dimensions

    CERN Document Server

    Casana, R; Simas, F C

    2015-01-01

    p-Balls are topological defects in $(D,1)$ dimensions constructed with $\\mathcal{M}\\ge 1$ scalar fields which depend radially on only $2 \\le p\\le D-2$ spatial dimensions. Such defects are characterized by an action that breaks translational invariance and are inspired on the physics of a brane with $D-p$ extra dimensions. Here we consider the issue of localization of bosonic states described by a scalar field $\\Phi$ sufficiently weak to not disturb sensibly the defect configuration. After describing the general formalism, we consider some specify examples with $\\mathcal{M}=1,2$ and $3$, looking for some region of parameters where bound and resonant bosonic states can be found. We investigate the way the influence of the defect structure, number of radial dimensions and coupling between the fields are related to the occurrence of bound and resonant states.

  2. Analysis of ocular torsion data from Space Labs D-1 and SL-1

    Science.gov (United States)

    Oman, C. M.

    1990-01-01

    A series of preflight, inflight, and postflight vestibular experiments were conducted on Spacelab missions SL-1 and D-1. Two portions of the investigation, the 'sled' and 'dome' functional objectives, involved recording the torsional motion of human subject's eyes. In the SL-1 sled and dome experiments, preflight and postflight ocular torsion was recorded on 35 mm film using a Nikon motor driven camera (2.6 frames/sec). The film was to be analyzed by measuring the motion of contact lens landmarks using a Hermes senior film scanner. However, an inflight failure of the dome experiment camera flash unit led the crew to utilize the Spacelab video camera as an alternative contingency method for imaging the eye in this FO. A suitable method for analysis of the video data was developed. Results of the analysis are presented.

  3. 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.

  4. 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.

  5. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    International Nuclear Information System (INIS)

    This chapter describes the displacement of 3H-23390 and 3H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3H-SCH 23390 and 3H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. Protein Kinase D1 Signaling in Angiogenic Gene Expression and VEGF-Mediated Angiogenesis.

    Science.gov (United States)

    Ren, Bin

    2016-01-01

    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. PMID:27200349

  12. 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...

  13. 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)

  14. 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

  15. 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

  16. 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, D*2 and D+s1 in ep collisions has been measured with the ZEUS detector at Hera. The data sample taken by the ZEUS detector in the years 2003-2007, corresponding to an integrated luminosity of 373 pb-1 has been used. The masses of the neutral, charged and strange states, the widths of the neutral states, the helicity parameters of D01 and D+s1 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameters of the D01 and D+s1 allows for some mixing of S- and D-waves in their decays to D*±π-+ and D*±K0 respectively. The measured value of the D01 helicity parameter is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D*02, D*±2 and D+s1 states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D1, D*2 and D+s1 were measured and are consistent with those obtained in e+e- annihilations. The Grid computing technology has a high importance for modern High Energy Physics. This technology has been successfully used in Zeus experiment for the MC simulations and data analysis. The dedicated infrastructure has been maintained by the author since 2010. In addition to continuous support, the author has upgraded and improved the performance of the Grid MC simulations and contributed to the Zeus data preservation project.

  17. 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.

  18. 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

  19. 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.

  20. 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 1435......1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression. RESULTS: In total, 30 patients...... patients expressed cyclin D2. Gene expression profiling indicated that 17 tumors were of the germinal center type, and 13 were of the activated B-cell type. Genetic aberrations of B-cell leukemia/lymphoma 2 (BCL2), BCL6, v-myc avian myelocytomatosis viral oncogene homolog (MYC), mouse double minute 2...

  1. The Enzymatic Activity of Type 1 Iodothyronine Deiodinase (D1) is Low in Liver Hemangioma: A Preliminary Study

    OpenAIRE

    Kornasiewicz, Oskar; Debski, Marcin; Stepnowska, Marta; Szałas, Anna; Bar-Andziak, Ewa; Krawczyk, Marek

    2010-01-01

    Type 1 iodothyronine deiodinase (D1) is a crucial enzyme which converts the prohormone thyroxine (T4) into active tri-iodothyronine (T3). There has been strong evidence that the metabolism of thyroid hormones is disturbed in some neoplastic tissues such as thyroid, renal, and breast cancer. However, there are few available data about D1 enzyme activity in benign tumors such as hemangioma, which is the most common primary liver tumor. Hence this study aimed to determine the enzymatic activity ...

  2. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine-mediated regulation of Tiam1

    OpenAIRE

    Chandra, Ramesh; Lenz, Jeffrey D.; Gancarz, Amy M.; Chaudhury, Dipesh; Schroeder, Gabrielle L.; Han, Ming-Hu; Cheer, Joseph F; Dietz, David M.; Lobo, Mary Kay

    2013-01-01

    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 T-lymphoma invasion and metastasis 1 (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 acc...

  3. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine- mediated regulation of Tiam1

    OpenAIRE

    Gancarz, Amy M.; Dipesh Chaudhury; Mary Kay Lobo

    2013-01-01

    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 s...

  4. 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...

  5. 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 ...

  6. 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.

  7. 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 ...

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► 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.

  15. Final repository for spent nuclear fuel. Underground design Simpevarp, Layout D1

    International Nuclear Information System (INIS)

    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 4,500. However, in

  16. 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

  17. 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

  18. 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.

  19. \\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.

  20. 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.

  1. 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...

  2. 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...

  3. 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)

  4. 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.

  5. Pairing gaps in Hartree-Fock Bogoliubov theory with the Gogny D1S interaction

    CERN Document Server

    Robledo, L M; Bertsch, G F

    2012-01-01

    As part of a program to study odd-A nuclei in the Hartree-Fock-Bogoliubov (HFB) theory, we have developed a new calculational tool to find the HFB minima of odd-A nuclei based on the gradient method and using interactions of Gogny's form. The HFB minimization includes both time-even and time-odd fields in the energy functional, avoiding the commonly used "filling approximation". Here we apply the method to calculate neutron pairing gaps in some representative isotope chains of spherical and deformed nuclei, namely the Z=8,50 and 82 spherical chains and the Z=62 and 92 deformed chains. We find that the gradient method is quite robust, permitting us to carry out systematic surveys involving many nuclei. We find that the time-odd field does not have large effect on the pairing gaps calculated with the Gogny D1S interaction. Typically, adding the T-odd field as a perturbation increases the pairing gap by ~100 keV, but the re-minimization brings the gap back down. This outcome is very similar to results reported f...

  6. 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.

  7. 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...

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

    Science.gov (United States)

    Chakrabarty, Bidisha; Turton, David; Virmani, Amitabh

    2015-11-01

    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-supersymmetric black hole microstate geometries with identified CFT duals presently known.

  9. Xylanase Production by Bacillus circulans D1 Using Maltose as Carbon Source

    Science.gov (United States)

    Bocchini, D. A.; Gomes, E.; da Silva, R.

    Bacillus circulans D1 is a good producer of extracellular thermostable xylanase. Xylanase production in different carbon sources was evaluated and the enzyme synthesis was induced by various carbon sources. It was found that d-maltose is the best inducer of the enzyme synthesis (7.05 U/mg dry biomass at 48 h), while d-glucose and d-arabinose lead to the production of basal levels of xylanase. The crude enzyme solution is free of cellulases, even when the microorganism was cultivated in a medium with d-cellobiose. When oat spelt xylan was supplemented with d-glucose, the repressive effect of this sugar on xylanase production was observed at 24 h, only when used at 5.0 g/L, leading to a reduction of 60% on the enzyme production. On the other hand, when the xylan medium was supplemented with d-xylose (3.0 or 5.0 g/L), this effect was more evident (80 and 90% of reduction on the enzyme production, respectively). Unlike that observed in the xylan medium, glucose repressed xylanase production in the maltose medium, leading to a reduction of 55% on the enzyme production at 24 h of cultivation. Xylose, at 1.0 g/L, induced xylanase production on the maltose medium. On this medium, the repressive effect of xylose, at 3.0 or 5.0 g/L, was less expressive when compared to its effect on the xylan medium.

  10. 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...

  11. 膀胱移行细胞癌细胞周期蛋白D1的表达及其意义%Expression and Significance of CyclinD1 in Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    漆贯华; 宋旭

    2001-01-01

    目的:检测细胞周期蛋白D1(cyclinD1)在膀胱移行细胞癌(TCC)中的表达,研究其与该肿瘤生物学行为的关系.方法:应用免疫组化SP法检测33例膀胱TCC和12例正常膀胱cyclinD1组织的表达.结果:cyclinD1阳性表达率膀胱TCC组为54.54%,对照组无表达(P=0.001);临床分期To~TJ为76.19%,T2~T4为16.67%;肿瘤分级G1为81.25%,G2为40.00%,G3为14.28%;随着肿瘤分期分级上升,阳性表达率逐渐升高(P=0.001,P=0.001);但与肿瘤的复发性差异无显著性(P=0.183).结论:cyclinD1在膀胱TCC形成的早期起重要的作用;在评估膀胱TCC的生物学行为方面有着重要的临床意义.

  12. 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.

  13. 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.

  14. Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

    International Nuclear Information System (INIS)

    The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

  15. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine- mediated regulation of Tiam1

    Directory of Open Access Journals (Sweden)

    Amy M Gancarz

    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.

  16. 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%.

  17. Intangible assets for intangible deliverables

    DEFF Research Database (Denmark)

    Elsmore, Matthew J.

    2008-01-01

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

  18. 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

  19. 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.

  20. 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)

  1. 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.

  2. 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

  3. 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.

  4. Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers

    Science.gov (United States)

    Conley, C. A.; Fowler, V. M.

    1999-01-01

    PURPOSE. To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy. METHODS. Recombinant 64kD human autoantigen D1 was generated in a bacterial expression system and used to immunize rabbits. Specific antibodies were affinity-purified and used for Western blots on normal and hyperthyroid rat and rabbit tissue, and immunofluorescence localization on cryosections of rat tissue. RESULTS. Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle. Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle. The level of this protein is not altered in extraocular muscles from hyperthyroid rabbits. CONCLUSIONS. The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism.

  5. 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.

  6. 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.

  7. Axial transport solvers for the 2D/1D scheme in MPACT

    International Nuclear Information System (INIS)

    The MPACT code being developed collaboratively at the University of Michigan (UM) and Oak Ridge National Laboratory (ORNL) provides users with a variety of deterministic methods for solving the 2D and 3D Boltzmann transport equation. One of these methods, the 2D/1D technique, decomposes 3D problems into a 1D axial stack of 2D radial planes. In this scheme, the 2D planes are typically solved using a method such as the Method of Characteristics (MOC) to preserve the geometric heterogeneity in the radial direction. These planes are incorporated into a 1D axial solver, which can use a variety of methods. This work demonstrates the use of the traditional nodal methods for solving the 1D axial problem (finite difference, NEM, SANM, SP3), but also introduces a discrete ordinates (Sn) solver which uses up to cubic Legendre expansion spatially and can also incorporate higher order angular distributions of the radial transverse leakage. Several test cases are presented to demonstrate the accuracy of the solvers for various axial sizes. The first three are the 3D-C5G7 extension benchmark cases. The fourth case is a single quarter assembly benchmark problem with explicit nozzle, plenum, and core plate modelling known as AMA Problem 3. The final case is a quarter core benchmark problem that is an extension of the quarter assembly problem known as AMA Problem 5. In general, the diffusion-based axial solvers perform very well, though higher-order solvers provide some benefit in more difficult problems, particularly rodded cases. (author)

  8. Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma

    International Nuclear Information System (INIS)

    Differentiation-inducing factors (DIFs) are morphogens which induce cell differentiation in Dictyostelium. We reported that DIF-1 and DIF-3 inhibit proliferation and induce differentiation in mammalian cells. In this study, we investigated the effect of DIF-1 on oral squamous cell carcinoma cell lines NA and SAS, well differentiated and poorly differentiated cell lines, respectively. Although DIF-1 did not induce the expression of cell differentiation makers in these cell lines, it inhibited the proliferation of NA and SAS in a dose-dependent manner by restricting the cell cycle in the G0/G1 phase. DIF-1 induced cyclin D1 degradation, but this effect was prevented by treatment with lithium chloride and SB216763, the inhibitors of glycogen synthase kinase-3β (GSK-3β). Depletion of endogenous GSK-3β by RNA interference also attenuated the effect of DIF-1 on cyclin D1 degradation. Therefore, we investigated the effect of DIF-1 on GSK-3β and found that DIF-1 dephosphorylated GSK-3β on Ser9 and induced the nuclear translocation of GSK-3β, suggesting that DIF-1 activated GSK-3β. Then, we examined the effect of DIF-1 on cyclin D1 mutants (Thr286Ala, Thr288Ala, and Thr286/288Ala). We revealed that Thr286Ala and Thr286/288Ala mutants were highly resistant to DIF-1-induced degradation compared with wild-type cyclin D1, indicating that the phosphorylation of Thr286 was critical for cyclin D1 degradation induced by DIF-1. These results suggest that DIF-1 induces degradation of cyclin D1 through the GSK-3β-mediated phosphorylation of Thr286

  9. The cyanobacterium Synechococcus resists UV-B by exchanging photosystem II reaction-center D1 proteins

    International Nuclear Information System (INIS)

    Current ambient UV-B levels can significantly depress productivity in aquatic habitats, largely because UV-B inhibits several steps of photosynthesis, including the photooxidation of water catalyzed by photosystem II. We show that upon UV-B exposure the cyanobacterium Synechococcus sp. PCC 7942 rapidly changes the expression of a family of three psbA genes encoding photosystem II D1 proteins. In wild-type cells the psbAI gene is expressed constitutively, but strong accumulations of psbAII and psbAIII transcripts are induced within 15 min of moderate UV-B exposure (0.4 W/m2). This transcriptional response causes an exchange of two distinct photosystem II D1 proteins. D1:1 is encoded by psbAI, but on UV-B exposure, it is largely replaced by the alternate D1:2 form, encoded by both psbAII and psbAIII. The total content of D1 and other photosystem II reaction center protein, D2, remained unchanged throughout the UV exposure, as did the content and composition of the phycobilisome. Wild-type cells suffered only slight transient inhibition of photosystem II function under UV-B exposure. In marked contrast, under the same UV-B treatment, a mutant strain expressing only psbAI suffered severe (40%) and sustained inhibition of photosystem II function. Another mutant strain with constitutive expression of psbAII and psbAIII was almost completely resistant to the UV-B treatment, showing no inhibition of photosystem II function and only a slight drop in electron transport. In Synechococcus the rapid exchange of alternate D1 forms, therefore, accounts for much of the cellular resistance to UV-B inhibition of photosystem II activity and photosynthetic electron transport. This molecular plasticity may be an important element in community-level responses to UV-B, where susceptibility to UV-B inhibition of photosynthesis changes diurnally

  10. 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.

  11. Cytochrome P450 1D1: A novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD

    DEFF Research Database (Denmark)

    Goldstone, J.V.; Jönsson, M.E.; Behrendt, Lars;

    2009-01-01

    Enzymes in the cytochrome P450 1 family oxidize many common environmental toxicants. We identified a new CYP1, termed CYP1D1, in zebrafish. Phylogenetically, CYP1D1 is paralogous to CYP1A and the two share 45% amino acid identity and similar gene structure. In adult zebrafish, CYP1D1 is most high...

  12. Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 minutes after a single bout of exercise

    DEFF Research Database (Denmark)

    Vendelbo, Mikkel; Møller, Andreas Buch; Treebak, Jonas T;

    2014-01-01

    Background: Phosphorylation of AS160 and TBC1D1 plays an important role for GLUT4 mobilization to the cell surface. The phosphorylation of AS160 and TBC1D1 in humans in response to acute exercise is not fully characterized. Objective: To study AS160 and TBC1D1 phosphorylation in human skeletal...

  13. Kazakov-Migdal induced gauge theory and the coupling of 2d quantum gravity to d=1 matter

    International Nuclear Information System (INIS)

    Recently Kazakov and Migdal proposed a new approach to the large N limit of SU(N) gauge theories which could hopefully describe the asymptotically free fixed point of QCD in 4 dimensions. In this contribution we review the exact solution of their model in the case of a d = 1 compactified lattice and its connection with the partition function of the vortex-free sector of the d=1 compactified bosonic string. Some new results on the addition of a linear term in the K-M model and on the SU(N) restriction of the general U(N) model are also presented. (orig.)

  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. 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

  16. 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...

  17. 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.

  18. Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy

    OpenAIRE

    Kinaciyan, T; Nagl, B.; Faustmann, S.; Kopp, S.; Wolkersdorfer, M.; Bohle, B

    2015-01-01

    It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients w...

  19. 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...

  20. 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

  1. Systematic validation of predicted microRNAs for cyclin D1

    Directory of Open Access Journals (Sweden)

    Feng Ming-Guang

    2009-06-01

    Full Text Available Abstract Background MicroRNAs are the endogenous small non-coding RNA molecules capable of silencing protein coding genes at the posttranscriptional level. Based on computer-aided predictions, a single microRNA could have over a hundred of targets. On the other hand, a single protein-coding gene could be targeted by many potential microRNAs. However, only a relatively small number of these predicted microRNA/mRNA interactions are experimentally validated, and no systematic validation has been carried out using a reporter system. Methods In this study, we used luciferease reporter assays to validate microRNAs that can silence cyclin D1 (CCND1 because CCND1 is a well known proto-oncogene implicated in a variety of types of cancers. We chose miRanda http://www.microRNA.org as a primary prediction method. We then cloned 51 of 58 predicted microRNA precursors into pCDH-CMV-MCS-EF1-copGFP and tested for their effect on the luciferase reporter carrying the 3'-untranslated region (UTR of CCND1 gene. Results Real-time PCR revealed the 45 of 51 cloned microRNA precursors expressed a relatively high level of the exogenous microRNAs which were used in our validation experiments. By an arbitrary cutoff of 35% reduction, we identified 7 microRNAs that were able to suppress Luc-CCND1-UTR activity. Among them, 4 of them were previously validated targets and the rest 3 microRNAs were validated to be positive in this study. Of interest, we found that miR-503 not only suppressed the luciferase activity, but also suppressed the endogenous CCND1 both at protein and mRNA levels. Furthermore, we showed that miR-503 was able to reduce S phase cell populations and caused cell growth inhibition, suggesting that miR-503 may be a putative tumor suppressor. Conclusion This study provides a more comprehensive picture of microRNA/CCND1 interactions and it further demonstrates the importance of experimental target validation.

  2. Efficient Self Consistent 3D/1D Analysis of ICRF Antennas

    Science.gov (United States)

    Maggiora, R.; Vecchi, G.; Lancellotti, V.; Kyrytsya, V.

    2003-12-01

    An innovative tool has been realized for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model. The approach to the problem is based on an integral-equation formulation for the self-consistent evaluation of the current distribution on the conductors. The environment has been subdivided in two coupled region: the plasma region and the vacuum region. The two problems are linked by means of a magnetic current (electric field) distribution on the aperture between the two regions. In the vacuum region all the calculations are executed in the spatial domain while in the plasma region an extraction in the spectral domain and an analytical evaluation of some integrals are employed that permit to significantly reduce the integration support and to obtain a high numerical efficiency leading to the practical possibility of using a large number of sub-domain basis functions on each solid conductor of the system. The plasma enters the formalism of the plasma region via a surface impedance matrix; for this reason any plasma model can be used; at present the FELICE code has been adopted, that affords density and temperature profiles, and FLR effects. The source term directly models the TEM mode of the coax feeding the antenna and the current in the coax is determined self-consistently, giving the input impedance/admittance of the antenna itself. Calculation of field distributions (both magnetic and electric), useful for sheath considerations, is included. This tool has been implemented in a suite, called TOPICA, that is modular and applicable to ICRF antenna structures of arbitrary shape. This new simulation tool can assist during the detailed design phase and for this reason can be considered a "Virtual Prototyping Laboratory" (VPL). The TOPICA suite has been tested against assessed codes and against measurements and data of mock-ups and existing antennas. The VPL is being used

  3. 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.

  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. Thermal bioclimate in Strasbourg - the 2003 heat wave

    Science.gov (United States)

    Matzarakis, Andreas; de Rocco, Manuela; Najjar, Georges

    2009-10-01

    This case study highlights the implications of the 2003 heat wave for the city of Strasbourg, France. The urban centers of France and other European countries were particularly affected by the heat wave. In some urban areas, the mortality rate was 60% above the expected value (Institute de Veille Sanitaire, 2003). The 2003 heat wave demonstrated once again that populations in urban centers are much more affected by extreme meteorological events than people living in rural areas. The aim of this analysis is to explore differences in thermal comfort conditions of (a) the city center of Strasbourg, and (b) its hinterland. The differences in thermal conditions existing between rural and urban areas are quantified by using a bio-climatological index termed physiologically equivalent temperature (PET). This index is based on the human energy balance and builds a relevant index for the quantification of the thermal environment of humans. We calculate the PET for the years 2003 and 2004 to highlight the temporal changes in the severity of climate extremes. The spatial scope of this study is improved compared to previous works in the field through the inclusion of PET calculations for five different sites on a central place in Strasbourg (Place Kléber). The calculations are characterized by different sky view factors and are compared to the reference site, which is located in a rural area. In the rural hinterland (Entzheim), the analysis of PET indicates a strong cold thermal stress during the winter months but no significant stress in summer. In 2003, summer temperatures were sensed as warmer compared to other years, but did not reach the extreme temperatures that may cause severe heat stress. For both the rural and the urban study sites PET was higher in the summer of 2003 than in 2004, which reflects the inferior thermal conditions in the urban area during the heat wave in 2003. For the entire study period, urban and rural day-time PET reached similar maximal values. Strong differences in PET, however, were observed between the rural and urban areas at night-time. The study of PET for several study sites on a central place in the city (Place Kléber) of Strasbourg for the years 2003 and 2004 showed that the sites with a higher sky view factor present higher values than sites with a lower sky view factor. The comparison of these PET values (Place Kléber) to the results for the rural area showed that during the day and the night the rural city of Entzheim has the lowest PET. During the day, the site at Place Kléber, which is located under a tree, has the lowest PET. The comparison of PET for the years 2003 and 2004 shows that PET in 2003 was about 5 to 7 K higher.

  8. Climate and bioclimate analysis of Ondo State, Nigeria

    Energy Technology Data Exchange (ETDEWEB)

    Omonijo, Akinyemi Gabriel [Freiburg Univ. (Germany). Meteorological Inst.; Rufus Giwa Polytechnic, Owo (Nigeria). Dept. of Agricultural Technology; Matzarakis, Andreas [Freiburg Univ. (Germany). Meteorological Inst.

    2011-10-15

    Most of the previous analyses of climate of Nigeria, particularly Ondo State have been for agricultural use. They have little or no application for biometeorological purposes. This paper examines and analyse the climate of Ondo State, Nigeria with respect to biometeorological parameters based on air temperature, relative humidity, wind speed, solar radiation and rainfall from 1998 to 2008. It assesses the previous methods of climatic analysis with respect to biometeorology. It then use complete heat budget model approach and RayMan model as analytical tool to calculate physiologically equivalent temperature (PET) in order to define thermo-physiological thresholds and classify biometeorological parameters in Ondo State. Detailed analysis of thermal comfort patterns indicate that there are marked spatial and seasonal variations in thermal comfort over the study area. The result shows three different grade of physiological stress over the two zones of Ondo State, that is the humid forest zone and derived savannah zone. The study recommends incorporation of atmospheric environmental parameters into health management systems of the country in order to achieve the Millennium Development Goals (MDG) in health sector. (orig.)

  9. 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...

  10. 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 $N(13,3)=N(31,97)=3$.

  11. D1 dopamine receptor-induced cyclic AMP-dependent protein kinase phosphorylation and potentiation of striatal glutamate receptors.

    Science.gov (United States)

    Price, C J; Kim, P; Raymond, L A

    1999-12-01

    Dopamine receptor activation regulates cyclic AMP levels and is critically involved in modulating neurotransmission in the striatum. Others have shown that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor-mediated current is potentiated by cyclic AMP-dependent protein kinase (PKA) activation. We made whole-cell patch clamp recordings from cultured striatal neurons and tested whether D1-type dopamine receptor activation affected AMPA receptor-mediated currents. After a 5-min exposure to the D1 agonist SKF 81297 (1 microM), kainate-evoked current amplitude was enhanced in approximately 75% of cells to 121+/-2.5% of that recorded prior to addition of drug. This response was inhibited by the D1 antagonist SCH 23390 and mimicked by activators of PKA. Moreover, by western blot analysis using an antibody specific for the phosphorylated PKA site Ser845 of GluR1, we observed a marked increase in phosphorylated GluR1 following a 10-min exposure of striatal neurons to 1 microM SKF 81297. Our data demonstrate that activation of D1-type dopamine receptors on striatal neurons promotes phosphorylation of AMPA receptors by PKA as well as potentiation of current amplitude. These results elucidate one mechanism by which dopamine can modulate neurotransmission in the striatum. PMID:10582604

  12. 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

  13. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

    Directory of Open Access Journals (Sweden)

    Zuzana Hořejší

    2014-04-01

    Full Text Available The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs, RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit.

  14. 26 CFR 1.924(d)-1 - Requirement that economic processes take place outside the United States.

    Science.gov (United States)

    2010-04-01

    ... unrelated to the FSC, may perform any activity required to satisfy this section, provided that the activity... requirements of section 924(d)(1)(A). For example, if a FSC sells a product to a foreign customer by first meeting with the customer in New York to discuss the product and then by mailing to it from outside...

  15. 26 CFR 404.6334(d)-1 - Minimum exemption from levy for wages, salary, or other income.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Minimum exemption from levy for wages, salary... ADMINISTRATION UNDER THE TAX REFORM ACT OF 1976 § 404.6334(d)-1 Minimum exemption from levy for wages, salary, or... period. Paragraph (c) of this section contains rules relating to the minimum amount of wages, salary,...

  16. Effects of dopamine D1 and D2 receptor agonists and antagonists on bombesin-induced behaviors.

    Science.gov (United States)

    Merali, Z; Piggins, H

    1990-12-01

    Central administration of bombesin elicits excessive grooming and locomotor activity in rats. This grooming activity is one characterised by vigorous scratching of the face, nape and body flanks. Pretreatment with the D1 receptor antagonist SCH 23390 inhibited the expression of bombesin-induced activity with grooming being more inhibited than locomotion. Blockade of D2 receptors with eticlopride significantly attenuated the behavioral responses to bombesin. When SCH 23390 and eticlopride were administered concurrently, it was apparent that D1 blockade had a greater effect on grooming and D2 blockade a larger effect on locomotion. Stimulation of D1 receptors by SKF 38393 elicited non-stereotyped locomotor activity and a form of grooming behavior characterised by vigorous washing of the face and ventral body surfaces. Co-administration of bombesin and SKF 38393 resulted in a form of grooming which resembled that elicited by SKF 38393 alone. The specific D2 agonist PPHT elicited a form of locomotion characterised by a downward oriented head posture and slow ambulatory activity around the cage perimeter. Co-administration of PPHT and bombesin resulted in a complete suppression of bombesin-induced behaviors and was largely indistinguishable from activity observed under PPHT alone conditions. These data implicate both D1 and D2 receptor based mechanisms in the modulation/mediation of the behavioral effects of bombesin. Part of the bombesin-induced behavioral effects may be explained by (indirect) activation of (a) dopamine system(s). PMID:2086245

  17. 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; Knudsen, Gitte M; Wilson, Alan A

    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...

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

    International Nuclear Information System (INIS)

    The most recent parametrization D1M of the Gogny energy density functional is used to describe fission in the isotopes 232-280Pu. 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 tSF, 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 tSF values is demonstrated with the help of calculations for 232-280Pu, 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 242-262Fm. 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.)

  19. 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

  20. Expression of cyclin D1, p21WAF1, p53 and Ki-67 in hepatocellular carcinoma: a pathological study

    Directory of Open Access Journals (Sweden)

    Yu-lan WANG

    2014-03-01

    Full Text Available Objective To explore the expression of cyclin D1, p21WAF1, p53 and Ki-67 protein in hepatocellular carcinoma (HCC and its relationship with prognosis of HCC patients. Methods Liver specimens were collected from 80 HCC patients who received hepatectomy in the General Hospital of PLA from Jan. 2000 to Jan. 2005, and the expressions of cyclin D1, p21WAF1, p53 and Ki-67 protein were determined by immunohistochemical staining (EliVision method to investigate the relationship between the protein expressions and the clinicopathologic characteristics of HCC, and their relationship with the survival rate of the patients was analyzed. Results The positive expression rates of cyclin D1, p21WAF1, p53 and Ki-67 in HCC were 38.8%, 40.5%, 65.4% and 80.0% respectively, and they were significantly higher than those in matched normal tissues (19.0%, 11.5%, 0.0% and 6.3% respectively, P<0.005. Correlation analysis showed that the expression of cyclin D1 was positively related to the nuclear grade (P=0.041, the expression of p21WAF1 and p53 were positively related to the tumor differentiation (P=0.032, P=0.031 and vascular invasion (P=0.036, P=0.011, the expression of Ki-67 was positively related to the tumor differentiation (P=0.004, nuclear grade (P=0.045 and vascular invasion (P=0.001. Survival analysis showed the prognosis was poor in patients with high expression of cyclin D1 or/and Ki-67. The expression of Ki-67 was significantly related to the expression of p53 (P=0.000 and p21WAF1 (P=0.047, but no significant relation was found among the expression of other proteins. Cox regression analysis showed that the tumor size (P=0.042, tumor number (P=0.004 and vascular invasion (P=0.000 were independent prognostic factors of HCC. Conclusions The cyclin D1, p21WAF1, p53 and Ki-67 protein may be involved in the biological process of HCC. The positive expression of cyclin D1 and Ki-67 may be used to evaluate the prognosis of patients with HCC. DOI: 10.11855/j

  1. 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

  2. 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...

  3. 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.

  4. D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum.

    Science.gov (United States)

    Avila-Luna, Alberto; Prieto-Leyva, Jacqueline; Gálvez-Rosas, Arturo; Alfaro-Rodriguez, Alfonso; Gonzalez-Pina, Rigoberto; Bueno-Nava, Antonio

    2015-07-01

    The striatum is known to possess high levels of D1-like and D2-like receptors (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition of D1Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D2Rs by endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and L-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-L-phenylalanine (L-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P DOPAC levels, L-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects. PMID:25981954

  5. 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

  6. Identification of domains and amino acids essential to the collagen galactosyltransferase activity of GLT25D1.

    Directory of Open Access Journals (Sweden)

    Claire Perrin-Tricaud

    Full Text Available Collagen is modified by hydroxylation and glycosylation of hydroxylysine residues. This glycosylation is initiated by the β1,O galactosyltransferases GLT25D1 and GLT25D2. The structurally similar protein cerebral endothelial cell adhesion molecule CEECAM1 was previously reported to be inactive when assayed for collagen glycosyltransferase activity. To address the cause of the absent galactosyltransferase activity, we have generated several chimeric constructs between the active human GLT25D1 and inactive human CEECAM1 proteins. The assay of these chimeric constructs pointed to a short central region and a large C-terminal region of CEECAM1 leading to the loss of collagen galactosyltransferase activity. Examination of the three DXD motifs of the active GLT25D1 by site-directed mutagenesis confirmed the importance of the first (amino acids 166-168 and second motif (amino acids 461-463 for enzymatic activity, whereas the third one was dispensable. Since the second DXD motif is incomplete in CEECAM1, we have restored the motif by introducing the substitution S461D. This change did not restore the activity of the C-terminal region, thereby showing that additional amino acids were required in this C-terminal region to confer enzymatic activity. Finally, we have introduced the substitution Q471R-V472M-N473Q-P474V in the CEECAM1-C-terminal construct, which is found in most animal GLT25D1 and GLT25D2 isoforms but not in CEECAM1. This substitution was shown to partially restore collagen galactosyltransferase activity, underlining its importance for catalytic activity in the C-terminal domain. Because multiple mutations in different regions of CEECAM1 contribute to the lack of galactosyltransferase activity, we deduced that CEECAM1 is functionally different from the related GLT25D1 protein.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism

    Science.gov (United States)

    Hasbi, Ahmed; Perreault, Melissa L.; Shen, Maurice Y. F.; Zhang, Lucia; To, Ryan; Fan, Theresa; Nguyen, Tuan; Ji, Xiaodong; O'Dowd, Brian F.; George, Susan R.

    2014-01-01

    Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues 404Glu and 405Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.—Hasbi, A., Perreault, M. L., Shen, M. Y. F., Zhang, L., To, R., Fan, T., Nguyen, T., Ji, X., O'Dowd, B. F., George, S. R. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism. PMID:25063849

  17. 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.

  18. PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease

    International Nuclear Information System (INIS)

    Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using 11C-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of 18F-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of 11C-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease

  19. 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.

  20. Rottlerin inhibits the nuclear factor kappaB/cyclin-D1 cascade in MCF-7 breast cancer cells

    Czech Academy of Sciences Publication Activity Database

    Torricelli, C.; Fortino, V.; Capurro, E.; Valacchi, G.; Pacini, A.; Muscettola, M.; Souček, Karel; Maioli, E.

    2008-01-01

    Roč. 82, 11-12 (2008), s. 638-643. ISSN 0024-3205 R&D Projects: GA ČR(CZ) GA310/07/0961; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Rottlerin * MCF-7 cells * cyclin-D1 Subject RIV: BO - Biophysics Impact factor: 2.583, year: 2008

  1. Specificity of Monosynaptic Sensory-Motor Connections Imposed by Repellent Sema3E-PlexinD1 Signaling

    OpenAIRE

    Kaori Fukuhara; Fumiyasu Imai; David R. Ladle; Kei-ichi Katayama; Jennifer R. Leslie; Silvia Arber; Thomas M. Jessell; Yutaka Yoshida

    2013-01-01

    In mammalian spinal cord, group Ia proprioceptive afferents form selective monosynaptic connections with a select group of motor pool targets. The extent to which sensory recognition of motor neurons contributes to the selectivity of sensory-motor connections remains unclear. We show here that proprioceptive sensory afferents that express PlexinD1 avoid forming monosynaptic connections with neurons in Sema3E+ motor pools yet are able to form direct connections with neurons in Sema3Eoff motor ...

  2. 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.)

  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; 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

  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. 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...

  6. 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...

  7. The effect of full agonist/antagonist of D1 receptor on cognitive function in dizocilpine-treated rats

    Czech Academy of Sciences Publication Activity Database

    Bubeníková-Valešová, V.; Svoboda, Jan; Stuchlík, Aleš; Valeš, Karel

    2008-01-01

    Roč. 11, Suppl.1 (2008), s. 263-263. ISSN 1461-1457. [CINP Congress /26./. 13.07.2008-17.07.2008, Munich] R&D Projects: GA MŠk(CZ) 1M0517; GA MZd(CZ) NR9178; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * D1 receptor * schizophrenia * cognitive function Subject RIV: FH - Neurology

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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

  13. 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.

  14. CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression

    International Nuclear Information System (INIS)

    Highlights: ► CARMA3 expression is elevated in colon cancers. ► CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. ► CARMA3 upregulates cyclinD1 through NF-κB 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-IκB levels and NF-κB activity and its overexpression increased p-IκB expression and NF-κB activity. NF-κB 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-κB mediated upregulation of cyclin D1.

  15. 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

  16. 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...

  17. 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

  18. Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

    International Nuclear Information System (INIS)

    Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

  19. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  20. Cyclin D1 expression during rat mammary tumor development and its potential role in the resistance of the Copenhagen rat

    International Nuclear Information System (INIS)

    Resistance to mammary tumorigenesis in Copenhagen rats is associated with loss of early preneoplastic lesions known as intraductal proliferations. The cause of this disappearance, however, is unknown. There were no differences in the numbers of lesions in mammary whole-mounts prepared from Copenhagen or Wistar-Furth rats at 20 or 30 days after N-methyl-N-nitrosourea treatment, but at 37 days there were significantly fewer lesions in Copenhagen glands. Furthermore, lesions in Copenhagen glands were exclusively intraductal proliferations, whereas in Wistar-Furth glands more advanced lesions were also present. Immunohistochemical staining showed frequent cyclin D1 overexpression in Wistar-Furth lesions at 37 days, but not in Copenhagen lesions. There were, however, no differences in p16INK4a protein expression, bromodeoxyuridine labeling and apoptotic indices, or mast cell infiltration between Copenhagen and Wistar-Furth lesions at any time. Overexpression of cyclin D1 in preneoplastic lesions may be important in the development of mammary tumors in susceptible rats, although this overexpression does not appear to cause significant changes in cell kinetics. Furthermore, the low levels of cyclin D1 expression in Copenhagen intraductal proliferations may play a role in the resistance of these rats to mammary tumorigenesis

  1. 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

  2. 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.

  3. Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy.

    Science.gov (United States)

    Kinaciyan, T; Nagl, B; Faustmann, S; Kopp, S; Wolkersdorfer, M; Bohle, B

    2016-02-01

    It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients with apple allergy. The dose of 1.6 μg induced oral allergy syndromes in 26.4%, 3.2 μg in 15.3%, 6.3 μg in 27.8%, 12.5 μg in 8.3%, 25 μg in 11.1%, and 50 μg in 4.2% of the patients. No severe reactions occurred. None of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 μg of rMal d 1 induced no reactions in three nonallergic individuals. Our approach allows straight forward, dose-defined sublingual challenge tests in a high number of birch pollen-allergic patients that inter alia can be applied to evaluate the therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy. PMID:26443126

  4. 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.

  5. Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome.

    Science.gov (United States)

    Ammann, Sandra; Schulz, Ansgar; Krägeloh-Mann, Ingeborg; Dieckmann, Nele M G; Niethammer, Klaus; Fuchs, Sebastian; Eckl, Katja Martina; Plank, Roswitha; Werner, Roland; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Bank, Julia; Strauss, Anne; von Bernuth, Horst; Zur Stadt, Udo; Grieve, Samantha; Griffiths, Gillian M; Lehmberg, Kai; Hennies, Hans Christian; Ehl, Stephan

    2016-02-25

    Genetic disorders affecting biogenesis and transport of lysosome-related organelles are heterogeneous diseases frequently associated with albinism. We studied a patient with albinism, neutropenia, immunodeficiency, neurodevelopmental delay, generalized seizures, and impaired hearing but with no mutation in genes so far associated with albinism and immunodeficiency. Whole exome sequencing identified a homozygous mutation in AP3D1 that leads to destabilization of the adaptor protein 3 (AP3) complex. AP3 complex formation and the degranulation defect in patient T cells were restored by retroviral reconstitution. A previously described hypopigmented mouse mutant with an Ap3d1 null mutation (mocha strain) shares the neurologic phenotype with our patient and shows a platelet storage pool deficiency characteristic of Hermansky-Pudlak syndrome (HPS) that was not studied in our patient because of a lack of bleeding. HPS2 caused by mutations in AP3B1A leads to a highly overlapping phenotype without the neurologic symptoms. The AP3 complex exists in a ubiquitous and a neuronal form. AP3D1 codes for the AP3δ subunit of the complex, which is essential for both forms. In contrast, the AP3β3A subunit, affected in HPS2 patients, is substituted by AP3β3B in the neuron-specific heterotetramer. AP3δ deficiency thus causes a severe neurologic disorder with immunodeficiency and albinism that we propose to classify as HPS10. PMID:26744459

  6. 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

  7. Mu dX, a derivative of Mu d1 (lac Apr) which makes stable lacZ fusions at high temperature.

    OpenAIRE

    Baker, T A; Howe, M M; Gross, C A

    1983-01-01

    We describe defective Mu phage Mu dX (Mu d1 Bx::Tn9 [lac Apr Cmr]) which is useful for insertion mutagenesis and for construction of lac operon fusions in vivo. Mu dX retains the insertion properties of Mu d1 but produces temperature-resistant lysogens and transposes at a reduced frequency. A method is described to convert existing Mu d1 insertions to Mu dX.

  8. 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.

  9. ADAM adaptation and mitigation strategies: supporting European climate policy. Deliverable D3 of work package M1 (code D-M1.3). ADAM 2-degree scenario for Europe - policies and impacts

    Energy Technology Data Exchange (ETDEWEB)

    Schade, Wolfgang; Jochem, Eberhard; Barker, Terry (and others)

    2009-07-31

    ADAM research identifies and appraises existing and new policy options that can contribute to different combinations of adaptation and mitigation strategies. These options address the demands a changing climate will place on protecting citizens and valuable ecosystems - i.e., adaptation - as well as addressing the necessity to restrain/control humankind's perturbation to global climate to a desirable level - i.e., mitigation. The work package Mitigation 1 (Ml) has the core objective to simulate mitigation options and their related costs for Europe until 2050 and 2100 respectively. The focus of this deliverable is on the period 2005 to 2050. The long-term period until 2100 is covered in the previous deliverable D2, applying the POLES model for this time horizon. The analysis constitutes basically a techno-economic analysis. Depending on the sector analyzed it is either directly combined with a policy analysis (e.g. in the transport sector, renewables sector) or the policy analysis is performed qualitatively as a subsequent and independent step after the techno-economic analysis is completed (e.g. in the residential and service sectors). The book includes the following chapters: scenarios and macroeconomic assumptions; methodological issues analyzing mitigation options; the integrated global energy model POLES and its projections for the reference and 2 deg C scenarios; forest and basic materials sector; residential sector in Europe; the service (tertiary) and the primary sectors in Europe; basic products and other manufacturing industry sectors; transport sectors in Europe; renewable sector in Europe; conversion sector in Europe; syntheses and sectoral analysis in Europe; macroeconomic impacts of climate policy in the EU; the effects of the financial crisis on baseline simulations with implications for climate policy modeling: an analysis using the global model E3MG 2008-2012; conclusions and policy recommendations.

  10. The dopamine D1-D2 receptor heteromer exerts tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization

    Science.gov (United States)

    Shen, Maurice Y.F.; Perreault, Melissa L.; Fan, Theresa; George, Susan R.

    2014-01-01

    A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioural model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5 day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5 day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants. PMID:25444866

  11. 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).

  12. 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.

  13. Activation of mRNA translation by phage protein and low temperature: the case of Lactococcus lactis abortive infection system AbiD1

    Directory of Open Access Journals (Sweden)

    Ehrlich S Dusko

    2009-01-01

    Full Text Available Abstract Background Abortive infection (Abi mechanisms comprise numerous strategies developed by bacteria to avoid being killed by bacteriophage (phage. Escherichia coli Abis are considered as mediators of programmed cell death, which is induced by infecting phage. Abis were also proposed to be stress response elements, but no environmental activation signals have yet been identified. Abis are widespread in Lactococcus lactis, but regulation of their expression remains an open question. We previously showed that development of AbiD1 abortive infection against phage bIL66 depends on orf1, which is expressed in mid-infection. However, molecular basis for this activation remains unclear. Results In non-infected AbiD1+ cells, specific abiD1 mRNA is unstable and present in low amounts. It does not increase during abortive infection of sensitive phage. Protein synthesis directed by the abiD1 translation initiation region is also inefficient. The presence of the phage orf1 gene, but not its mutant AbiD1R allele, strongly increases abiD1 translation efficiency. Interestingly, cell growth at low temperature also activates translation of abiD1 mRNA and consequently the AbiD1 phenotype, and occurs independently of phage infection. There is no synergism between the two abiD1 inducers. Purified Orf1 protein binds mRNAs containing a secondary structure motif, identified within the translation initiation regions of abiD1, the mid-infection phage bIL66 M-operon, and the L. lactis osmC gene. Conclusion Expression of the abiD1 gene and consequently AbiD1 phenotype is specifically translationally activated by the phage Orf1 protein. The loss of ability to activate translation of abiD1 mRNA determines the molecular basis for phage resistance to AbiD1. We show for the first time that temperature downshift also activates abortive infection by activation of abiD1 mRNA translation.

  14. Dopamine D1 receptor activity is involved in the increased anxiety levels observed in STZ-induced diabetes in rats.

    Science.gov (United States)

    Rebolledo-Solleiro, Daniela; Araiza, Luis Fernando Ontiveros; Broccoli, Laura; Hansson, Anita C; Rocha-Arrieta, Luisa Lilia; Aguilar-Roblero, Raúl; Crespo-Ramírez, Minerva; Fuxe, Kjell; Pérez de la Mora, Miguel

    2016-10-15

    Epidemiological surveys have indicated that anxiety disorders are more frequent in diabetic patients than in the general population. Similar results have been shown in animal studies using the streptozotocin (STZ)-induced diabetes model. The mechanisms underlying this relationship are not clearly understood, but it has been suggested that alterations in the dopaminergic neurotransmission, which plays an important role in the amygdaloid modulation of fear and anxiety, may be involved. The aim of this study was to ascertain whether or not the amygdaloid DA D1 receptors are involved in the increase of anxiety-like behavior observed in "diabetic" animals. Adult Wistar male rats were injected with STZ (50mg/kg, i.p.) in two consecutive days and subjected to the Shock-Probe Burying Test 10days after the beginning of treatment. STZ-treated rats showed a significant increase in immobility/freezing behavior whereas no effects were elicited in latency to bury, burying behavior itself and the number of shocks received during testing as compared with non-diabetic controls. These results suggest the triggering of a passive coping response in the STZ-treated rats. Interestingly, immobility/freezing behavior was reversed following the intra-amygdaloid dopamine D1 receptor blockade by the local microinfusion of SCH23390 (100ng/side). Autoradiographic experiments showed a selective increase of [(3)H]-SCH23390 binding in the ventral intercalated paracapsular islands of STZ-treated rats when compared to the non-treated control group. Our results suggest that a hyperdopaminergic state involving DA D1 receptors within the amygdala may have a role in the increase of anxiety observed in diabetic rats. PMID:27374159

  15. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    International Nuclear Information System (INIS)

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination

  16. Regulation of the ERK pathway in the dentate gyrus by in vivo dopamine D1 receptor stimulation requires glutamatergic transmission.

    Science.gov (United States)

    Gangarossa, Giuseppe; Valjent, Emmanuel

    2012-11-01

    Acute systemic administration of the dopamine D1/D5 receptors (D1Rs) agonist, SKF81297, activates the extracellular signal-regulated protein kinases (ERK) pathway selectively in the granule cells of the dentate gyrus. In this study, we examined the mechanisms involved in this regulation and investigated the molecular components that could promote ERK-dependent transcription and translation. SKF81297 induced phosphorylation of ERK and histone H3 required intact glutamatergic transmission. Blockade of glutamate release achieved by the mGluR2/3 agonist, LY354740 or the selective adenosine A1R agonist, CCPA as well as neurotoxic lesions of lateral entorhinal cortex reduced the ability of SKF81297 to induce ERK activation in the dentate gyrus. This activation required the combined stimulation of NR2B-containing NMDARs, mGluR1 and mGluR5. SKF81297 evoked phosphorylation of the ribosomal protein S6 (rpS6) selectively at the Ser235/236 site while the Ser240/244 site remains unchanged. The SKF81297 induced increased phosphorylation of rpS6 was dependent on PKC and ERK/p90RSK activation. Surprisingly, administration of D1Rs agonist suppressed mTORC1/p70S6K pathway suggesting an mTOR-independent regulation of rpS6 phosphorylation. Taken together, our results show that intact glutamatergic transmission plays a major role in the regulation of ERK-dependent phosphorylation of histone H3 and rpS6 observed in the mouse dentate gyrus after systemic administration of SKF81297. PMID:22796106

  17. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

    OpenAIRE

    Zuzana Hořejší; Lasse Stach; Thomas G. Flower; Dhira Joshi; Helen Flynn; J. Mark Skehel; Nicola J. O’Reilly; Roksana W. Ogrodowicz; Stephen J. Smerdon; Simon J. Boulton

    2014-01-01

    Summary 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 ...

  18. M5-brane as a Nambu-Poisson geometry of a multi-D1-brane theory

    International Nuclear Information System (INIS)

    We introduce a Nambu-Poisson bracket in the geometrical description of the D=11 M5-brane. This procedure allows us, under some assumptions, to eliminate the local degrees of freedom of the antisymmetric field in the M5-brane Hamiltonian and to express it as a D=11 p-brane theory invariant under symplectomorphisms. The explicit expression of the Hamiltonian is obtained. The existence of nontrivial physical configurations annihilating the energy density is shown. Finally, a regularization of the M5-brane in terms of a multi D1-brane theory invariant under the SU(N)xSU(N) group in the limit when N→∞ is constructed

  19. Strong decays of the charmed mesons $D_1^*(2680)$, $D^*_3(2760)$, $D_2^*(3000)$

    CERN Document Server

    Wang, Zhi-Gang

    2016-01-01

    In this article, we assign the higher charmed mesons $D^*_1(2680)$, $D_3^*(2760)$ and $D_2^*(3000)$ to be the 2S $1^-$, 1D $3^-$ and 1F $2^+$ states, respectively, and study the two-body strong decays to the ground state charmed mesons and light pseudoscalar mesons with the heavy meson effective theory. We obtain the ratios among the strong decays, which can be confronted to the experimental data in the future and shed light on the nature of those higher charmed mesons.

  20. Protein Kinase D1 Inhibits Cell Proliferation through Matrix Metalloproteinase (MMP) -2 and -9 Secretion in Prostate Cancer

    OpenAIRE

    Uddin Biswas, Md. Helal; Du, Cheng; Zhang, Chuanyou; Straubhaar, Juerg; LANGUINO, LUCIA R.; Balaji, K.C.

    2010-01-01

    We and others previously demonstrated that Protein Kinase D1 (PKD1) is down regulated in several cancers including prostate, interacts with E-cadherin, a major cell adhesion epithelial protein and causes increased cell aggregation and decreased motility of prostate cancer cells. In this study, we demonstrate that PKD1 complexes with β3-integrin resulting in activation of Mek-Erk pathway, which causes increased production of MMP-2 and -9, that is associated with shedding of soluble 80 kDa E-ca...