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Sample records for met office unified

  1. INFERNO, a simple approach for interactive fires and their emissions within the Met Office Unified Model

    NASA Astrophysics Data System (ADS)

    Mangeon, Stephane; Voulgarakis, Apostolos; Folberth, Gerd

    2015-04-01

    Forest fires remain a crucial element of the Earth system, affecting and affected by the biosphere and the atmosphere. In particular emissions of trace gases (CO2, CO, NOx...) from forest fires can affect radiative forcing as well as atmospheric composition, similarly aerosols such as Black Carbon (also a strong sunlight absorber) and Organic Carbon emitted by fires can participate in cloud droplet nucleation, contributing to the aerosol indirect effect. Global estimates of fire emissions have greatly improved over the last decade, mainly through the developments in satellite observations. However, such estimates remain constrained to the recent satellite observational period; to study fires under past and future climates one has to resort to models. We will present the INteractive Fire and Emission algoRithm for Natural envirOnments (INFERNO) scheme for the Met Office's Unified Model, which builds on previous work for the GISS climate model. We start from simulated fire counts using proxies for flammability (meteorology and vegetation), ignitions and fire suppression. We then extend this parameterisation to predict burnt area, burnt biomass and subsequent emissions. This climate-sensitive parameterisation utilises temperature, relative humidity, precipitation and vegetation modelling (biomass and leaf area index) to model flammability. Ignitions depend on population density and lightning strikes. Of all these variables, only population density needs to be prescribed, hence INFERNO can be run interactively within a coupled earth system model. Our approach is also distinct owing to its simplicity and is computationally inexpensive, a necessary characteristic as it is aimed to run interactively over climatological timescales. The performance of this scheme is assessed against the Global Fire Emissions Database (GFED); early analysis shows this new approach effectively captures the spatial and inter-annual variability of burnt area and fire emissions of CO2 and CO

  2. Efficient performance of the Met Office Unified Model v8.2 on Intel Xeon partially used nodes

    NASA Astrophysics Data System (ADS)

    Bermous, I.; Steinle, P.

    2015-03-01

    The atmospheric Unified Model (UM) developed at the UK Met Office is used for weather and climate prediction by forecast teams at a number of international meteorological centres and research institutes on a wide variety of hardware and software environments. Over its 25 year history the UM sources have been optimised for better application performance on a number of High Performance Computing (HPC) systems including NEC SX vector architecture systems and recently the IBM Power6/Power7 platforms. Understanding the influence of the compiler flags, Message Passing Interface (MPI) libraries and run configurations is crucial to achieving the shortest elapsed times for a UM application on any particular HPC system. These aspects are very important for applications that must run within operational time frames. Driving the current study is the HPC industry trend since 1980 for processor arithmetic performance to increase at a faster rate than memory bandwidth. This gap has been growing especially fast for multicore processors in the past 10 years and it can have significant implication for the performance and performance scaling of memory bandwidth intensive applications, such as the UM. Analysis of partially used nodes on Intel Xeon clusters is provided in this paper for short- and medium-range weather forecasting systems using global and limited-area configurations. It is shown that on the Intel Xeon-based clusters the fastest elapsed times and the most efficient system usage can be achieved using partially committed nodes.

  3. Efficient performance of the Met Office Unified Model v8.2 on Intel Xeon partially used nodes

    NASA Astrophysics Data System (ADS)

    Bermous, I.

    2014-11-01

    The atmospheric Unified Model (UM) developed at the UK Met Office is used for weather and climate prediction by forecast teams at a number of international meteorological centres and research institutes on a wide variety of hardware and software environments. Over its 25 year history the UM sources have been optimised for a better application performance on a number of HPC systems including NEC SX vector architecture systems and recently the IBM Power6/Power7 platforms. Understanding the influence of the compiler flags, MPI libraries and run configurations is crucial to achieving the shortest elapsed times for a UM application on any particular HPC system. These aspects are very important for applications that must run within operational time frames. Driving the current study is the HPC industry trend since 1980 for processor arithmetic performance to increase at a faster rate than memory bandwidth. This gap has been growing especially fast for multicore processors in the past 10 years and it can have significant implication for the performance and performance scaling of memory bandwidth intensive applications, such as the UM. Analysis of partially used nodes on Intel Xeon clusters is provided in this paper for short and medium range weather forecasting systems using global and limited-area configurations. It is shown that on the Intel Xeon based clusters the fastest elapsed times and the most efficient system usage can be achieved using partially committed nodes.

  4. Air quality modelling using the Met Office Unified Model (AQUM OS24-26): model description and initial evaluation

    NASA Astrophysics Data System (ADS)

    Savage, N. H.; Agnew, P.; Davis, L. S.; Ordóñez, C.; Thorpe, R.; Johnson, C. E.; O'Connor, F. M.; Dalvi, M.

    2013-03-01

    The on-line air quality model AQUM (Air Quality in the Unified Model) is a limited-area forecast configuration of the Met Office Unified Model which uses the UKCA (UK Chemistry and Aerosols) sub-model. AQUM has been developed with two aims: as an operational system to deliver regional air quality forecasts and as a modelling system to conduct air quality studies to inform policy decisions on emissions controls. This paper presents a description of the model and the methods used to evaluate the performance of the forecast system against the automated UK surface network of air quality monitors. Results are presented of evaluation studies conducted for a year-long period of operational forecast trials and several past cases of poor air quality episodes. The results demonstrate that AQUM tends to over-predict ozone (~8 μg m-3 mean bias for the year-long forecast), but has a good level of responsiveness to elevated ozone episode conditions - a characteristic which is essential for forecasting poor air quality episodes. AQUM is shown to have a negative bias for PM10, while for PM2.5 the negative bias is much smaller in magnitude. An analysis of speciated PM2.5 data during an episode of elevated particulate matter (PM) suggests that the PM bias occurs mainly in the coarse component. The sensitivity of model predictions to lateral boundary conditions (LBCs) has been assessed by using LBCs from two different global reanalyses and by comparing the standard, single-nested configuration with a configuration having an intermediate European nest. We conclude that, even with a much larger regional domain, the LBCs remain an important source of model error for relatively long-lived pollutants such as ozone. To place the model performance in context we compare AQUM ozone forecasts with those of another forecasting system, the MACC (Monitoring Atmospheric Composition and Climate) ensemble, for a 5-month period. An analysis of the variation of model skill with forecast lead time is

  5. Evaluating the Met Office Unified Model simulated land surface temperature (LST) using a multi-platform approach

    NASA Astrophysics Data System (ADS)

    Brooke, Jennifer; Harlow, Chawn; Best, Martin; Newman, Stuart; Scott, Russell; Edwards, John; Thelen, Jean-Claude; Pavelin, Ed; Weeks, Mark

    2015-04-01

    The Met Office Unified Model (UM) has a significant cold bias in land surface temperature (LST) in semi-arid regions at global resolution, and limited area 4.4 km and 2.2 km configurations. The daytime LST cold bias simulated by the JULES land surface scheme within the UM is present throughout the annual cycle in semi-arid regions of the globe in comparison to IASI retrievals. These errors are largest in late spring and early summer and have magnitudes of 5 to 15 K, dependent on model resolution. This work will show verification of model biases through ground-based, in-situ airborne and satellite observations during the Semi-Arid Land Surface Temperature and IASI Calibration Experiment (SALSTICE) in semi-arid south-eastern Arizona in May 2013. Airborne observations of LST from the FAAM research aircraft using the Airborne Research Interferometer Evaluation System (ARIES) were used to investigate the spatial distribution of the model errors and evaluate IASI retrievals. Airborne retrievals of surface temperature were found to broadly agree with IASI retrievals; uncertainties are attributed to the spatial variability in the ARIES measurements compared with the IASI footprints and due to differences within the retrieval, such as assumed emissivity. The UM errors in LST were found to vary with model resolution as well as topographic complexity, with the coarse resolution global model having larger errors than the limited area models. Regions with complex terrain had the highest LST errors while the errors over the less complex basins were lower, in the range of 4-5 K. Evaluation of the JULES land surface scheme has been performed for flux tower sites in the Walnut Gulch Experimental Watershed in south-eastern Arizona. An annual dataset of flux tower measurements confirms the LST biases seen with aircraft and satellite observations and indicates that night-time LST biases are of the order of those observed during the day. Comparisons of different model resolutions show

  6. Modelling Volcanic Aerosol-Cloud Interactions in Warm Cumulus Cloud Using the High Resolution Nested Suite of the UK Met Office Unified Model

    NASA Astrophysics Data System (ADS)

    Hodgson, A. K.; Field, P.; Carslaw, K. S.; Hill, A. A.; Shipway, B. J.; Grosvenor, D. P.; Marsham, J. H.

    2014-12-01

    The impacts that aerosols have on clouds and clouds have on aerosols remain the largest uncertainty in terms of the effect on radiative forcing. Regional and global models are unable to resolve these small scale interactions, while high resolution eddy-resolving models are unable to capture the larger scale dynamics of the atmosphere and can only be run over a limited size domain for a limited time. Here we present results using the high resolution (1km, 0.3km) nested version of the UK Met Office Unified Model (UM) which bridges the scale gap between models. A new microphysics scheme, Cloud and AeroSol Interactive Microphysics (CASIM) is coupled to a chemistry and aerosol scheme (GLOMAP-mode) which allows for fully interactive aerosol and cloud microphysics.Results showing the effect of volcanic aerosol from the slowly degassing Kilauea volcano, Hawaii on trade wind cumuli will be presented. The presence of a subtropical high pressure in the summer allows the study of aerosol-cloud interactions in a uniform unpolluted marine background environment without the complications of anthropogenic pollution. Satellite data has shown that cumulus clouds affected by the volcanic plume had smaller cloud droplets, reduced precipitation efficiency, increased cloud amount and higher cloud tops. Other researchers have hypothesised that that the observed changes in cloud properties cannot be explained by the orographic effect of the island or the sea surface temperature anomaly. We present results using CASIM in the UM at high resolution to systematically compare the relative effects of dynamical and aerosol-cloud interactions. Initial results show that the orography of the island does not have a significant impact on the cumulus cloud further downwind from the island but there is an effect in the immediate vicinity of the island. Initial results also indicate that 1km resolution is not high enough to resolve small cumulus cloud.

  7. Contrail Cirrus Parameterization in the UK Met Office Climate Model

    NASA Astrophysics Data System (ADS)

    Rap, A.; Forster, P.; Dobbie, S.

    2011-12-01

    Air travel and its associated emissions are growing faster than other sectors and they are predicted to contribute a significant warming of climate over the coming century. According to current best estimates, the largest single radiative forcing component associated with aviation is due to aviation-induced cloudiness (AIC), which includes contrail cirrus and changes in the natural cirrus caused by air traffic. However, there is still a high level of uncertainty associated with these, and limited estimates for the forcing of the total effect of aviation induced cloudiness exist. This study, as part of the Contrails Spreading into Cirrus (COSIC) project, aimed to build a physically based parameterization of contrails spreading into cirrus within the UK Met Office Unified Model (UM) and thus to give an independent estimate of the climate impact of AIC. In-situ observations of contrails properties and their spreading have been performed during a series of flights with the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft. These observations were used in the development of the parameterization, which simulates contrail formation and ageing interactively with the natural cirrus module within the UM. Based on this new parameterisation, estimates of global contrail cirrus coverage, optical depth, and radiative forcing are given, investigating also the contrail effect on the natural cirrus cloud and contrail saturation regional effects of future air traffic growth.

  8. Aerosol impacts in the Met Office global NWP model

    NASA Astrophysics Data System (ADS)

    Mulcahy, Jane P.; Brooks, Malcolm E.; Milton, Sean F.

    2010-05-01

    An accurate representation of the direct and indirect effect of aerosols is of growing concern for global numerical weather prediction (NWP). Increased scattering and absorption of incoming shortwave (SW) and outgoing longwave radiation (OLR) fields due to the presence of aerosol layers in the atmosphere modifies the atmospheric heating profile and can affect large-scale circulation patterns. The current representation of aerosols in the global NWP configuration of the Met Office Unified ModelTM (MetUM) is based on a simple aerosol climatology (Cusack et al., 1998). Profiles of water soluble dust, soot, oceanic and stratospheric sulphate aerosols are described separately for land and ocean surfaces and are distributed over the boundary layer, free troposphere and stratosphere (sulphates only). While this improved the reflected SW radiative bias at the top-of-atmosphere (TOA), there is evidence that the climatology is too absorbing leading to a temperature bias in the lower troposphere of approximately 0.5 K/day. Furthermore, the omission of the scattering and absorption properties of mineral dust and biomass burning aerosol particles in particular, is believed to be the principal cause of significant model biases (in the region of 50-56 W m-2) in both the model OLR at the TOA (Haywood et al., 2005) and the surface SW radiation fields (Milton et al., 2008). One of the objectives of the Global Aerosols (G-AER) component of the MACC (Monitoring Atmospheric Composition and Climate) project is to evaluate the impact of an improved aerosol representation on the performance of global NWP models. In a stepwise approach of increasing the aerosol complexity in the MetUM, the Cusack climatology is being replaced by the CLASSIC (Coupled Large-scale Aerosol Simulator for Studies in Climate) aerosol scheme, developed for the HadGEM (Hadley Centre Global Environmental Model) climate model. CLASSIC includes representations of external mixtures of sulphate, black carbon, organic

  9. Remote Sensing of Volcanic ASH at the Met Office

    NASA Astrophysics Data System (ADS)

    Marenco, F.; Kent, J.; Adam, M.; Buxmann, J.; Francis, P.; Haywood, J.

    2016-06-01

    The eruption of Eyjafjallajökull in 2010 has triggered the rapid development of volcanic ash remote sensing activities at the Met Office. Volcanic ash qualitative and quantitative mapping have been achieved using lidar on board the Facility for Airborne Atmospheric Measurements (FAAM) research aircraft, and using improved satellite retrieval algorithms. After the eruption, a new aircraft facility, the Met Office Civil Contingencies Aircraft (MOCCA), has been set up to enable a rapid response, and a network of ground-based remote sensing sites with lidars and sunphotometers is currently being developed. Thanks to these efforts, the United Kingdom (UK) will be much better equipped to deal with such a crisis, should it happen in the future.

  10. Operational Use of OGC Web Services at the Met Office

    NASA Astrophysics Data System (ADS)

    Wright, Bruce

    2010-05-01

    The Met Office has adopted the Service-Orientated Architecture paradigm to deliver services to a range of customers through Rich Internet Applications (RIAs). The approach uses standard Open Geospatial Consortium (OGC) web services to provide information to web-based applications through a range of generic data services. "Invent", the Met Office beta site, is used to showcase Met Office future plans for presenting web-based weather forecasts, product and information to the public. This currently hosts a freely accessible Weather Map Viewer, written in JavaScript, which accesses a Web Map Service (WMS), to deliver innovative web-based visualizations of weather and its potential impacts to the public. The intention is to engage the public in the development of new web-based services that more accurately meet their needs. As the service is intended for public use within the UK, it has been designed to support a user base of 5 million, the analysed level of UK web traffic reaching the Met Office's public weather information site. The required scalability has been realised through the use of multi-tier tile caching: - WMS requests are made for 256x256 tiles for fixed areas and zoom levels; - a Tile Cache, developed in house, efficiently serves tiles on demand, managing WMS request for the new tiles; - Edge Servers, externally hosted by Akamai, provide a highly scalable (UK-centric) service for pre-cached tiles, passing new requests to the Tile Cache; - the Invent Weather Map Viewer uses the Google Maps API to request tiles from Edge Servers. (We would expect to make use of the Web Map Tiling Service, when it becomes an OGC standard.) The Met Office delivers specialist commercial products to market sectors such as transport, utilities and defence, which exploit a Web Feature Service (WFS) for data relating forecasts and observations to specific geographic features, and a Web Coverage Service (WCS) for sub-selections of gridded data. These are locally rendered as maps or

  11. The new Met Office strategy for seasonal forecasts

    NASA Astrophysics Data System (ADS)

    Hewson, T. D.

    2012-04-01

    In October 2011 the Met Office began issuing a new-format UK seasonal forecast, called "The 3-month Outlook". Government interest in a UK-relevant product had been heightened by infrastructure issues arising during the severe cold of previous winters. At the same time there was evidence that the Met Office's "GLOSEA4" long range forecasting system exhibited some hindcast skill for the UK, that was comparable to its hindcast skill for the larger (and therefore less useful) 'northern Europe' region. Also, the NAO- and AO- signals prevailing in the previous two winters had been highlighted by the GLOSEA4 model well in advance. This presentation will initially give a brief overview of GLOSEA4, describing key features such as evolving sea-ice, a well-resolved stratosphere, and the perturbation strategy. Skill measures will be shown, along with forecasts for the last 3 winters. The new structure 3-month outlook will then be described and presented. Previously, our seasonal forecasts had been based on a tercile approach. The new format outlook aims to substantially improve upon this by illustrating graphically, and with text, the full range of possible outcomes, and by placing those outcomes in the context of climatology. In one key component the forecast pdfs (probability density functions) are displayed alongside climatological pdfs. To generate the forecast pdf we take the bias-corrected GLOSEA4 output (42 members), and then incorporate, via expert team, all other relevant information. Firstly model forecasts from other centres are examined. Then external 'forcing factors', such as solar, and the state of the land-ocean-ice system, are referenced, assessing how well the models represent their influence, and bringing in statistical relationships where appropriate. The expert team thereby decides upon any changes to the GLOSEA4 data, employing an interactive tool to shift, expand or contract the forecast pdfs accordingly. The full modification process will be illustrated

  12. The Met Office Global Coupled model 2.0 (GC2) configuration

    NASA Astrophysics Data System (ADS)

    Williams, K. D.; Harris, C. M.; Bodas-Salcedo, A.; Camp, J.; Comer, R. E.; Copsey, D.; Fereday, D.; Graham, T.; Hill, R.; Hinton, T.; Hyder, P.; Ineson, S.; Masato, G.; Milton, S. F.; Roberts, M. J.; Rowell, D. P.; Sanchez, C.; Shelly, A.; Sinha, B.; Walters, D. N.; West, A.; Woollings, T.; Xavier, P. K.

    2015-05-01

    The latest coupled configuration of the Met Office Unified Model (Global Coupled configuration 2, GC2) is presented. This paper documents the model components which make up the configuration (although the scientific description of these components is detailed elsewhere) and provides a description of the coupling between the components. The performance of GC2 in terms of its systematic errors is assessed using a variety of diagnostic techniques. The configuration is intended to be used by the Met Office and collaborating institutes across a range of timescales, with the seasonal forecast system (GloSea5) and climate projection system (HadGEM) being the initial users. In this paper GC2 is compared against the model currently used operationally in those two systems. Overall GC2 is shown to be an improvement on the configurations used currently, particularly in terms of modes of variability (e.g. mid-latitude and tropical cyclone intensities, the Madden-Julian Oscillation and El Nino Southern Oscillation). A number of outstanding errors are identified with the most significant being a considerable warm bias over the Southern Ocean and a dry precipitation bias in the Indian and West African summer monsoons. Research to address these is ongoing.

  13. The Met Office Global Coupled model 2.0 (GC2) configuration

    NASA Astrophysics Data System (ADS)

    Williams, K. D.; Harris, C. M.; Bodas-Salcedo, A.; Camp, J.; Comer, R. E.; Copsey, D.; Fereday, D.; Graham, T.; Hill, R.; Hinton, T.; Hyder, P.; Ineson, S.; Masato, G.; Milton, S. F.; Roberts, M. J.; Rowell, D. P.; Sanchez, C.; Shelly, A.; Sinha, B.; Walters, D. N.; West, A.; Woollings, T.; Xavier, P. K.

    2015-01-01

    The latest coupled configuration of the Met Office Unified Model (Global Coupled configuration 2, GC2) is presented. This paper documents the model components which make up the configuration (although the scientific description of these components is detailed elsewhere) and provides a description of the coupling between the components. The performance of GC2 in terms of its systematic errors is assessed using a variety of diagnostic techniques. The configuration is intended to be used by the Met Office and collaborating institutes across a range of timescales, with the seasonal forecast system (GloSea5) and climate projection system (HadGEM) being the initial users. In this paper GC2 is compared against the model currently used operationally in those two systems.

  14. Impacts of increasing the aerosol complexity in the Met Office global numerical weather prediction model

    NASA Astrophysics Data System (ADS)

    Mulcahy, J. P.; Walters, D. N.; Bellouin, N.; Milton, S. F.

    2014-05-01

    The inclusion of the direct and indirect radiative effects of aerosols in high-resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three-dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing long-wave radiation over West Africa due to a better representation of dust. However, uncertainties in dust optical properties propagate to its direct effect and the subsequent model response. Inclusion of the indirect aerosol effects improves surface radiation biases at the North Slope of Alaska ARM site due to lower cloud amounts in high-latitude clean-air regions. This leads to improved temperature and height forecasts in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short-range forecasts. However, the indirect aerosol effect leads to a strengthening of the low-level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. Regional impacts on the African Easterly Jet (AEJ) are also presented with the large dust loading in the aerosol climatology enhancing of the heat low over West Africa and weakening the AEJ. This study highlights the

  15. Impacts of increasing the aerosol complexity in the Met Office global NWP model

    NASA Astrophysics Data System (ADS)

    Mulcahy, J. P.; Walters, D. N.; Bellouin, N.; Milton, S. F.

    2013-11-01

    Inclusion of the direct and indirect radiative effects of aerosols in high resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing longwave radiation over West Africa due to a better representation of dust. However, uncertainties in dust optical properties propogate to its direct effect and the subsequent model response. Inclusion of the indirect aerosol effects improves surface radiation biases at the North Slope of Alaska ARM site due to lower cloud amounts in high latitude clean air regions. This leads to improved temperature and height forecasts in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short range forecasts. However, the indirect aerosol effect leads to a strengthening of the low level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. Regional impacts on the African Easterly Jet (AEJ) are also presented with the large dust loading in the aerosol climatology enhancing of the heat low over West Africa and weakening the AEJ. This study highlights the importance

  16. Impacts of increasing the aerosol complexity in the Met Office global NWP model

    NASA Astrophysics Data System (ADS)

    Mulcahy, Jane; Walters, David; Bellouin, Nicolas; Milton, Sean

    2014-05-01

    Inclusion of the direct and indirect radiative effects of aerosols in high resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing longwave radiation over West Africa due to a better representation of dust. Inclusion of the indirect aerosol effects has significant impacts on the SW radiation particularly at high latitudes due to lower cloud amounts in high latitude clean air regions. This leads to improved surface radiation biases at the North Slope of Alaska ARM site. Verification of temperature and height forecasts is also improved in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short range forecasts. However, the indirect aerosol effect leads to a strengthening of the low level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. This study highlights the importance of including a more realistic treatment of aerosol-cloud interactions in global NWP models and the potential for improved global environmental prediction systems through the incorporation of more complex

  17. The Met Office Coupled Atmosphere/Land/Ocean/Sea-Ice Data Assimilation System

    NASA Astrophysics Data System (ADS)

    Lea, Daniel; Mirouze, Isabelle; King, Robert; Martin, Matthew; Hines, Adrian

    2015-04-01

    The Met Office has developed a weakly-coupled data assimilation (DA) system using the global coupled model HadGEM3 (Hadley Centre Global Environment Model, version 3). At present the analysis from separate ocean and atmosphere DA systems are combined to produced coupled forecasts. The aim of coupled DA is to produce a more consistent analysis for coupled forecasts which may lead to less initialisation shock and improved forecast performance. The HadGEM3 coupled model combines the atmospheric model UM (Unified Model) at 60 km horizontal resolution on 85 vertical levels, the ocean model NEMO (Nucleus for European Modelling of the Ocean) at 25 km (at the equator) horizontal resolution on 75 vertical levels, and the sea-ice model CICE at the same resolution as NEMO. The atmosphere and the ocean/sea-ice fields are coupled every 1-hour using the OASIS coupler. The coupled model is corrected using two separate 6-hour window data assimilation systems: a 4D-Var for the atmosphere with associated soil moisture content nudging and snow analysis schemes on the one hand, and a 3D-Var FGAT for the ocean and sea-ice on the other hand. The background information in the DA systems comes from a previous 6-hour forecast of the coupled model. To isolate the impact of the coupled DA, 13-month experiments have been carried out, including 1) a full atmosphere/land/ocean/sea-ice coupled DA run, 2) an atmosphere-only run forced by OSTIA SSTs and sea-ice with atmosphere and land DA, and 3) an ocean-only run forced by atmospheric fields from run 2 with ocean and sea-ice DA. In addition, 5-day and 10-day forecast runs, have been produced from initial conditions generated by either run 1 or a combination of runs 2 and 3. The different results have been compared to each other and, whenever possible, to other references such as the Met Office atmosphere and ocean operational analyses or the OSTIA SST data. The performance of the coupled DA is similar to the existing separate ocean and atmosphere

  18. In Brief: U.K. Met Office forecast for Atlantic hurricane season

    NASA Astrophysics Data System (ADS)

    2007-07-01

    GloSea, the U.K. Meteorological Office's computer model of the global atmosphere-ocean system, has predicted a cooling trend in sea surface temperatures in the tropical North Atlantic that will result in a less active hurricane season. The Met Office has predicted that there is a 70% chance of a less active hurricane season in the North Atlantic this year, with only 7-13 named storms occurring within the remaining five months of the season (July through November). There have already been two named storms this year-Andrea and Barry. From 1990-2005, there were an average of 12.4 storms during July-November. The U.K. Met Office forecast contrasts with NOAA's, which was released in May and predicted a busier season than average, with 13-17 named storms.

  19. A seamless approach to understanding and predicting Arctic sea ice in Met Office modelling systems.

    PubMed

    Hewitt, Helene T; Ridley, Jeff K; Keen, Ann B; West, Alex E; Peterson, K Andrew; Rae, Jamie G L; Milton, Sean F; Bacon, Sheldon

    2015-07-13

    Recent CMIP5 models predict large losses of summer Arctic sea ice, with only mitigation scenarios showing sustainable summer ice. Sea ice is inherently part of the climate system, and heat fluxes affecting sea ice can be small residuals of much larger air-sea fluxes. We discuss analysis of energy budgets in the Met Office climate models which point to the importance of early summer processes (such as clouds and meltponds) in determining both the seasonal cycle and the trend in ice decline. We give examples from Met Office modelling systems to illustrate how the seamless use of models for forecasting on time scales from short range to decadal might help to unlock the drivers of high latitude biases in climate models. PMID:26032316

  20. Signal to Noise Ratio Estimations for a Volcanic ASH Detection Lidar. Case Study: The Met Office

    NASA Astrophysics Data System (ADS)

    Georgoussis, George; Adam, Mariana; Avdikos, George

    2016-06-01

    In this paper we calculate the Signal-to-Noise (SNR) ratio of a 3-channel commercial (Raymetics) volcanic ash detection system, (LR111-D300), already operating under Met Office organization. The methodology for the accurate estimation is presented for day and nighttime conditions. The results show that SNR values are higher than 10 for ranges up to 13 km for both nighttime and daytime conditions. This is a quite good result compared with other values presented in bibliography and proves that such system is able to detect volcanic ash over a range of 20 km.

  1. Latest decadal climate prediction research at the Met Office Hadley Centre

    NASA Astrophysics Data System (ADS)

    Dunstone, Nick; Smith, Doug; Scaife, Adam; Hermanson, Leon

    2014-05-01

    Here we present an overview of work, much of which is undertaken as contributions to the EU SPECS project, that explore mechanisms and hindcast skill using Met Office climate models and different versions of the DePreSys decadal prediction system. Here we focus on: - showing skilful predictions of the North Atlantic sub-polar gyre region in decadal hindcasts. Furthermore, we present evidence and physical mechanisms for a shift in the forecast sub-polar gyre, that would suggest a forthcoming local cooling and examine the associated likely regional climate impacts, - presenting results of experiments design to elucidate the possible impact of further anthropogenic reductions in Arctic sea-ice extent on atmospheric circulation on interannual to decadal timescales. A modest but significant negative NAO signal is seen in winter, - finally, we present details, and preliminary results, from the new high-resolution Met Office DePreSys system, which is a major step towards a seamless monthly to decadal prediction system.

  2. Research priorities in support of ocean monitoring and forecasting at the Met Office

    NASA Astrophysics Data System (ADS)

    Siddorn, J. R.; Good, S. A.; Harris, C. M.; Lewis, H. W.; Maksymczuk, J.; Martin, M. J.; Saulter, A.

    2016-02-01

    Ocean monitoring and forecasting services are increasingly being used by a diverse community of public and commercial organizations. The Met Office, as the body responsible for severe weather prediction, has for many years been involved in providing forecasts of aspects of the marine environment. This paper describes how these have evolved to include a range of wave, surge, and ocean reanalysis, analysis, and forecasts services. To support these services, and to ensure they evolve to meet the demands of users and are based on the best available science, a number of scientific challenges need to be addressed. The paper goes on to summarize the key challenges, and highlights some priorities for the ocean monitoring and forecasting research group at the Met Office. There is a need to both develop the underpinning science of the modelling and data assimilation systems and to maximize the benefits from observations and other inputs to the systems. Systematic evaluation underpins this science, and also needs to be the focus of research.

  3. Research priorities in support of ocean monitoring and forecasting at the Met Office

    NASA Astrophysics Data System (ADS)

    Siddorn, J. R.; Good, S. A.; Harris, C. M.; Lewis, H. W.; Maksymczuk, J.; Martin, M. J.; Saulter, A.

    2015-11-01

    Ocean monitoring and forecasting services are increasingly being used by a diverse community of public and commercial organisations. The Met Office, as the body responsible for severe weather prediction, has for many years been involved in providing forecasts of aspects of the marine environment. This paper describes how these have evolved to include a range of wave, surge and ocean reanalysis, analysis and forecasts services. To support these services, and to ensure they evolve to meet the demands of users and are based on the best available science, a number of scientific challenges need to be addressed. The paper goes on to summarise the key challenges, and highlights some priorities for the ocean monitoring and forecasting research group at the Met Office. There is a need to both develop the underpinning science of the modelling and data assimilation systems and to maximise the benefits from observations and other inputs to the systems. Systematic evaluation underpins this science, and also needs to be the focus of research.

  4. Impacts of Increased Vertical Resolution in the Met Office UK Model

    NASA Astrophysics Data System (ADS)

    Finnenkoetter, Anke; Van Weverberg, Kwinten; Morcrette, Cyril

    2016-04-01

    As computing resources increase, NWP models continue to move to finer grid resolutions in order to improve the representation of small scale atmospheric processes. While improvements resulting from increasing horizontal resolution are often obviously linked to the better orographic representation and finer scale land use data, the benefits seen from an increased vertical resolution can be more subtle and the underlying mechanisms complex to understand. Increasing the number of vertical levels from 70 to 120, we performed a number of case studies with the Met Office's 1.5km horizontal resolution UK model (UKV). Statistical analyses show a slight, but systematic decrease in low rain rates and high-level cloud amount. The most significant impact can be seen in the representation of widespread low-level cloud. While there is little change to cloud top heights, the cloud base lifts in runs with the new vertical level set. The resulting thinned cloud layers are more prone to break up, offering a better agreement with low cloud cover seen in satellite imagery. Ongoing work aims to fully understand the mechanisms leading to the changes in the vertical humidity distribution and the enhanced decoupling seen within the boundary layer.

  5. The Met Office's new operational analysis system for diurnally varying skin-SST

    NASA Astrophysics Data System (ADS)

    While, James; Mao, Chongyuan; Martin, Matthew; Good, Simon; Sykes, Peter

    2016-04-01

    Diurnal variations in skin Sea Surface Temperature (skin SST), which can be as large as several degrees, play an important role in determining the heat flux between the ocean and atmosphere. As such, since February 2015 the Met Office, as part of the Copernicus Marine Environment Monitoring Service (CMEMS), has been producing an operational analysis of the diurnal cycle of skin SST. This product consists of three components: an underlying 'foundation' SST (based on the OSTIA analysis), a warm layer where solar heating is important, and a cool skin where cooling due to long wave radiation dominates. A major development in this system is the use of a 4D-Var data assimilation technique with multiple outer-loops to improve estimates of the warm layer. Observations assimilated come from the SEVIRI, GOES-W, MTSAT2, and NOAA-AVHRR infra-red satellite instruments. Through their assimilation, the observations act to update the applied heat and wind flux such that the diurnal cycle in the warm layer is improved. In this presentation we describe the analysis system and how it produces a skin SST product. Particular attention is paid to the data assimilation aspects and on the observation processing. We also present results from a three month validation period showing that the system is well able to reproduce a drifter based climatology of the diurnal cycle in SST. A direct validation of our diurnal SST output against near surface Argo data is also given.

  6. Asian summer monsoon seasonal prediction skill in the Met Office GloSea5 model and its dependence on mean state biases

    NASA Astrophysics Data System (ADS)

    Bush, Stephanie; Turner, Andrew; Martin, Gill; Woolnough, Steve

    2015-04-01

    Predicting the circulation and precipitation features of the Asian monsoon on time scales of weeks to the season ahead remains a challenge for prediction centres. Current state-of-the-art models retain large biases, particularly dryness over India, which evolve rapidly from initialization and persist into centennial length climate integrations, illustrating the seamless nature of the monsoon problem. We present initial results from our Ministry of Earth Sciences Indian Monsoon Mission collaboration project to assess and improve weekly-to-seasonal forecasts in the Met Office Unified Model (MetUM) coupled initialized Global Seasonal Prediction System (GloSea5). Using a 14-year hindcast ensemble of integrations in which atmosphere, ocean and sea-ice components are initialized from May start dates, we assess the monsoon seasonal prediction skill and global mean state biases of GloSea5. Initial May and June biases include a lack of precipitation over the Indian peninsula, and a weakened monsoon flow, and these give way to a more robust pattern of excess precipitation in the western north Pacific, lack of precipitation over the Maritime Continent, excess westerlies across the Indian peninsula and Indochina, and cool SSTs in the eastern equatorial Indian Ocean and western north Pacific in July and August. Despite these mean state biases, the interannual correlation of predicted JJA all India rainfall from 1998 to 2009 with TRMM is fairly high at 0.68. Future work will focus on the prospects for further improving this skill with bias correction techniques.

  7. Evaluation of stratocumulus cloud prediction in the Met Office forecast model during VOCALS-REx

    NASA Astrophysics Data System (ADS)

    Abel, S. J.; Walters, D. N.; Allen, G.

    2010-11-01

    Observations in the subtropical southeast Pacific obtained during the VOCALS-REx field experiment are used to evaluate the representation of stratocumulus cloud in the Met Office forecast model and to identify key areas where model biases exist. Marked variations in the large scale structure of the cloud field were observed during the experiment on both day-to-day and on diurnal timescales. In the remote maritime region the model is shown to have a good representation of synoptically induced variability in both cloud cover and marine boundary layer depth. Satellite observations show a strong diurnal cycle in cloud fraction and liquid water path in the stratocumulus with enhanced clearances of the cloud deck along the Chilean and Peruvian coasts on certain days. The model accurately simulates the phase of the diurnal cycle but is unable to capture the coastal clearing of cloud. Observations along the 20° S latitude line show a gradual increase in the depth of the boundary layer away from the coast. This trend is well captured by the model (typical low bias of 200 m) although significant errors exist at the coast where the model marine boundary layer is too shallow and moist. Drizzle in the model responds to changes in liquid water path in a manner that is consistent with previous ship-borne observations in the region although the intensity of this drizzle is likely to be too high, particularly in the more polluted coastal region where higher cloud droplet number concentrations are typical. Another mode of variability in the cloud field that the model is unable to capture are regions of pockets of open cellular convection embedded in the overcast stratocumulus deck and an example of such a feature that was sampled during VOCALS-REx is shown.

  8. Evaluation of stratocumulus cloud prediction in the Met Office forecast model during VOCALS-REx

    NASA Astrophysics Data System (ADS)

    Abel, S. J.; Walters, D. N.; Allen, G.

    2010-07-01

    Observations in the subtropical south east Pacific obtained during the VOCALS-REx field experiment are used to evaluate the representation of stratocumulus cloud in the Met Office forecast model and to identify key areas where model biases exist. Marked variations in the large scale structure of the cloud field were observed during the experiment on both day to day and on diurnal timescales. In the remote maritime region the model is shown to have a good representation of synoptically induced variability in both cloud cover and marine boundary layer depth. Satellite observations show a strong diurnal cycle in cloud fraction and liquid water path in the stratocumulus with enhanced clearances of the cloud deck along the Chilean and Peruvian coasts on certain days. The model accurately simulates the phase of the diurnal cycle but is unable to capture the coastal clearing of cloud. Observations along the 20° S latitude line show a gradual increase in the depth of the boundary layer away from the coast. This trend is well captured by the model (typical low bias of 200 m) although significant errors exist at the coast where the model marine boundary layer is too shallow and moist. Drizzle in the model responds to changes in liquid water path in a manner that is consistent with previous ship-borne observations in the region although the intensity of this drizzle is likely to be too high, particularly in the more polluted coastal region where higher cloud droplet number concentrations are typical. Another mode of variability in the cloud field that the model is unable to capture are regions of pockets of open cellular convection embedded in the overcast stratocumulus deck and an example of such a feature that was sampled during VOCALS-REx is shown.

  9. Recent assimilation developments of FOAM the Met Office ocean forecast system

    NASA Astrophysics Data System (ADS)

    Lea, Daniel; Martin, Matthew; Waters, Jennifer; Mirouze, Isabelle; While, James; King, Robert

    2015-04-01

    FOAM is the Met Office's operational ocean forecasting system. This system comprises a range of models from a 1/4 degree resolution global to 1/12 degree resolution regional models and shelf seas models at 7 km resolution. The system is made up of the ocean model NEMO (Nucleus for European Modeling of the Ocean), the Los Alomos sea ice model CICE and the NEMOVAR assimilation run in 3D-VAR FGAT mode. Work is ongoing to transition to both a higher resolution global ocean model at 1/12 degrees and to run FOAM in coupled models. The FOAM system generally performs well. One area of concern however is the performance in the tropics where spurious oscillations and excessive vertical velocity gradients are found after assimilation. NEMOVAR includes a balance operator which in the extra-tropics uses geostrophic balance to produce velocity increments which balance the density increments applied. In the tropics, however, the main balance is between the pressure gradients produced by the density gradient and the applied wind stress. A scheme is presented which aims to maintain this balance when increments are applied. Another issue in FOAM is that there are sometimes persistent temperature and salinity errors which are not effectively corrected by the assimilation. The standard NEMOVAR has a single correlation length scale based on the local Rossby radius. This means that observations in the extra tropics have influence on the model only on short length-scales. In order to maximise the information extracted from the observations and to correct large scale model biases a multiple correlation length-scale scheme has been developed. This includes a larger length scale which spreads observation information further. Various refinements of the scheme are also explored including reducing the longer length scale component at the edge of the sea ice and in areas with high potential vorticity gradients. A related scheme which varies the correlation length scale in the shelf seas is also

  10. The Met Office NWP-based Nowcasting Demonstration Project for the summer 2012 floods and London Olympics 2012

    NASA Astrophysics Data System (ADS)

    Ballard, Susan P.; Li, Zhihong; Simonin, David; Tubbs, Robert; Kelly, Graeme; Caron, Jean-Francois

    2013-04-01

    The Met Office developed a high resolution (1.5km) NWP system covering southern England and Wales for nowcasting (NDP) for the London Olympics 2012 using the Unified Model and hourly cycling 4D-Var data assimilation. The system produces 6 hour forecasts every hour. This has been running near-real-time since March 2012 on the IBM Power 6 and moved to the new IBM Power 7 in September 2012. The system uses latent heat nudging of radar derived rain rates provided every 15mins, direct assimilation in VAR of an hourly 3D cloud cover analysis and high time frequency subhourly radar Doppler winds (6 per hour), wind profiler and MSG SEVIRI upper tropospheric water vapour channels every 15mins as well as hourly surface synoptic reports and AMDAR reports. Eumetsat Satellite winds (AMVs) are used but they are very coarse horizontally and temporally eg at T-30mins only. The domain includes 8 of the UK network radars of which 5 were providing Doppler radial winds by the time of the Olympics and 4 wind. Boundary condition updates were provided every 30mins from 1.5km resolution 6hourly forecasts from a 3hourly cycling 3-km 3D-VAR for the UK region, UKV model. The NDP uses a 4D-Var data assimilation system with 1/2 UM resolution (i.e. 3km), hourly assimilation windows with 10 minute LS states, and 100 second timestep. The PF model and its adjoint have dimensions of 180 x 144 x 70. Observations are extracted in the observation time window T-30 mins to T+30 mins. The 1.5km UM (360 x 288 x 70) uses 50 sec time-stepping on 6 nodes in 12 x16 decomposition. 4D-Var increments are added to UM at the initial forecast time T-30 mins (at first UM time step). A 45 minute data cutoff was used and forecasts were available within 1 hour of nominal analysis time ie taking 15mins for observation processing, data assimilation and forecast. Summer 2012 was an excellent time to assess the skill of the system for flash flood prediction due to the extreme weather over the UK during that period

  11. Development of the Global Sea Ice 6.0 CICE configuration for the Met Office Global Coupled model

    NASA Astrophysics Data System (ADS)

    Rae, J. G. L.; Hewitt, H. T.; Keen, A. B.; Ridley, J. K.; West, A. E.; Harris, C. M.; Hunke, E. C.; Walters, D. N.

    2015-07-01

    The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration and with observationally based data sets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST data set. In the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is required to rectify this in future configurations.

  12. Development of the global sea ice 6.0 CICE configuration for the Met Office global coupled model

    SciTech Connect

    Rae, J. G. L.; Hewitt, H. T.; Keen, A. B.; Ridley, J. K.; West, A. E.; Harris, C. M.; Hunke, E. C.; Walters, D. N.

    2015-07-24

    The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration and with observationally based data sets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST data set. As a result, in the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is required to rectify this in future configurations.

  13. Development of global sea ice 6.0 CICE configuration for the Met Office global coupled model

    SciTech Connect

    Rae, J. . G. L; Hewitt, H. T.; Keen, A. B.; Ridley, J. K.; West, A. E.; Harris, C. M.; Hunke, E. C.; Walters, D. N.

    2015-03-05

    The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration and with observationally-based datasets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST dataset. In the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is required to rectify this in future configurations.

  14. Development of the global sea ice 6.0 CICE configuration for the Met Office global coupled model

    DOE PAGESBeta

    Rae, J. G. L.; Hewitt, H. T.; Keen, A. B.; Ridley, J. K.; West, A. E.; Harris, C. M.; Hunke, E. C.; Walters, D. N.

    2015-07-24

    The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration and with observationally based data sets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST data set. As a result, in the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extentmore » and volume; further work is required to rectify this in future configurations.« less

  15. Development of global sea ice 6.0 CICE configuration for the Met Office global coupled model

    DOE PAGESBeta

    Rae, J. . G. L; Hewitt, H. T.; Keen, A. B.; Ridley, J. K.; West, A. E.; Harris, C. M.; Hunke, E. C.; Walters, D. N.

    2015-03-05

    The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration and with observationally-based datasets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST dataset. In the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is requiredmore » to rectify this in future configurations.« less

  16. Innovation in the role of the Office of the Ombudsman of the Unified Health System (SUS) - reflections and potential benefits.

    PubMed

    Fernandes, Fernando Manuel Bessa; Moreira, Marcelo Rasga; Ribeiro, José Mendes; Ouverney, Assis Mafort; Oliveira, Flávio José Fonseca de; Moro, Maria Francisca Abritta

    2016-08-01

    This article seeks to reflect on the potential of innovative practices in the design and work of the government bodies that comprise the National System of Offices of the Ombudsman of the Unified Health System. It is divided into two parts, seeking to answer the following question: How to think of and implement innovative practices - which include sustainability - when the people are voicing their urgent demands and these are being heard by the public authorities? These grievances are all the more urgent as they involve the area of Health and can they be promptly discussed, attended and resolved? In the first part, the article discusses the polysemic concept of innovation, focusing on its application in the three spheres of public administration, and highlights the importance of its close correlation with the different notions of information and knowledge in a society such as the one we live in. In the second, it develops a task-force of ideas for the office of the ombudsman and based on this, a draft operational concept of innovation in the role of the office of the ombudsman, considering the context of high speed change and transformations and the complexity inherent to contemporary life and the need for resource management and expertise development in information management. PMID:27557027

  17. Improved scheme for parametrization of convection in the Met Office's Numerical Atmospheric-dispersion Modelling Environment (NAME)

    NASA Astrophysics Data System (ADS)

    Meneguz, Elena; Thomson, David; Witham, Claire; Kusmierczyk-Michulec, Jolanta

    2015-04-01

    NAME is a Lagrangian atmospheric dispersion model used by the Met Office to predict the dispersion of both natural and man-made contaminants in the atmosphere, e.g. volcanic ash, radioactive particles and chemical species. Atmospheric convection is responsible for transport and mixing of air resulting in a large exchange of heat and energy above the boundary layer. Although convection can transport material through the whole troposphere, convective clouds have a small horizontal length scale (of the order of few kilometres). Therefore, for large-scale transport the horizontal scale on which the convection exists is below the global NWP resolution used as input to NAME and convection must be parametrized. Prior to the work presented here, the enhanced vertical mixing generated by non-resolved convection was reproduced by randomly redistributing Lagrangian particles between the cloud base and cloud top with probability equal to 1/25th of the NWP predicted convective cloud fraction. Such a scheme is essentially diffusive and it does not make optimal use of all the information provided by the driving meteorological model. To make up for these shortcomings and make the parametrization more physically based, the convection scheme has been recently revised. The resulting version, presented in this paper, is now based on the balance equation between upward, entrainment and detrainment fluxes. In particular, upward mass fluxes are calculated with empirical formulas derived from Cloud Resolving Models and using the NWP convective precipitation diagnostic as closure. The fluxes are used to estimate how many particles entrain, move upward and detrain. Lastly, the scheme is completed by applying a compensating subsidence flux. The performance of the updated convection scheme is benchmarked against available observational data of passive tracers. In particular, radioxenon is a noble gas that can undergo significant long range transport: this study makes use of observations of

  18. Improved predictions of global climate in the decade ahead using a new version of the Met Office Hadley Centre Decadal Prediction System

    NASA Astrophysics Data System (ADS)

    Knight, Jeff; Andrews, Martin; Smith, Doug; Arribas, Alberto; Dunstone, Nick; Maclachlan, Craig; Peterson, Drew; Scaife, Adam; Williams, Andrew

    2013-04-01

    The Met Office Hadley Centre Decadal Prediction System (DePreSys) produced the first initialised short-term climate prediction in 2007. It showed, for the first time, that climate prediction up to a decade ahead was improved by including an accurate representation of the initial state of the ocean and atmosphere. Decadal predictions have subsequently been produced by a wide range of climate modelling centres, and this activity is an important new feature of IPCC AR5. Here, results from a comprehensively revised version of the Decadal Prediction System (DePreSys version 2) will be presented. The key enhancement is the use of the Met Office's latest climate model HadGEM3 within the forecast system (as opposed to the HadCM3 model used in the original system). This has approximately doubled the horizonal resolution of HadCM3, and quadrupled the number of vertical levels, in both atmospheric and oceanic components. In addition, the atmospheric component has an improved dynamical core, fully revised parameterisations, and is coupled to a different ocean model (NEMO). The initialisation methodology is essentially the same as for DePreSys version 1. Taking a global overview, indices of local predictive skill show significant improvements for key surface variables across a range of timescales relative to the previous system. In particular, there appears to be more skill in predicting multiannual to decadal variability in the Pacific Ocean and regions with which it has teleconnections. A forecast for global climate over the next few years produced by DePreSys version 2 will also be presented.

  19. Climate Variability over India and Bangladesh from the Perturbed UK Met Office Hadley Model: Impacts on Flow and Nutrient Fluxes in the Ganges Delta System

    NASA Astrophysics Data System (ADS)

    Whitehead, P. G.; Caesar, J.; Crossman, J.; Barbour, E.; Ledesma, J.; Futter, M. N.

    2015-12-01

    A semi-distributed flow and water quality model (INCA- Integrated Catchments Model) has been set up for the whole of the Ganges- Brahmaputra- Meghna (GBM) River system in India and Bangladesh. These massive rivers transport large fluxes of water and nutrients into the Bay of Bengal via the GBM Delta system in Bangladesh. Future climate change will impact these fluxes with changing rainfall, temperature, evapotranspiration and soil moisture deficits being altered in the catchment systems. In this study the INCA model has been used to assess potential impacts of climate change using the UK Met Office Hadley Centre GCM model linked to a regionally coupled model of South East Asia, covering India and Bangladesh. The Hadley Centre model has been pururbed by varying the parameters in the model to generate 17 realisations of future climates. Some of these reflect expected change but others capture the more extreme potential behaviour of future climate conditions. The 17 realisations have been used to drive the INCA Flow and Nitrogen model inorder to generate downstream times series of hydrology and nitrate- nitrogen. The variability of the climates on these fluxes are investigated and and their likley impact on the Bay of Begal Delta considered. Results indicate a slight shift in the monsoon season with increased wet season flows and increased temperatures which alter nutrient fluxes. Societal Importance to Stakeholders The GBM Delta supports one of the most densely populated regions of people living in poverty, who rely on ecosystem services provided by the Delta for survival. These ecosystem services are dependent upon fluxes of water and nutrients. Freshwater for urban, agriculture, and aquaculture requirements are essential to livelihoods. Nutrient loads stimulate estuarine ecosystems, supporting fishing stocks, which contribute significantly the economy of Bangladesh. Thus the societal importance of upstream climate driven change change in Bangladesh are very

  20. Evolution of dynamic and thermodynamic fields during the Indian summer monsoon onset in the initialised atmosphere-ocean seasonal forecasting model of the UK Met Office

    NASA Astrophysics Data System (ADS)

    Menon, Arathy; Turner, Andrew; Martin, Gill

    2016-04-01

    The onset of the Indian summer monsoon has significant influence on the agricultural planning that affects food production and the gross domestic product of the country. Hence understanding and prediction of the monsoon onset is of paramount importance. Here we use hindcast simulations from the Met Office fully coupled atmosphere-ocean Global Seasonal Forecast System 5 (GloSea5) to study the monsoon onset over India. The GloSea5 hindcast simulations are produced for three different start dates in late April or early May prior to the monsoon season and the atmosphere and ocean components are both initialized. Rather than focus on skill metrics of the performance at simulating the onset timing, we use common objective indices of the onset circulation and wind shears in the meridional (Wang-Fan) and vertical (Webster-Yang) directions to determine the monsoon onset over India. We find that the dynamic indices obtained from GloSea5 ensemble mean are consistent with those from the ERA-Interim reanalysis dataset. GloSea5 is also very effective in capturing the spatial pattern of the monsoon rainfall progression following the onset. We next analyse the composite evolution of various dynamic and thermodynamic fields associated with these indices, focusing on recent findings suggesting the importance of dry air incursions above the surface from the northwest. We further extend our analysis by looking at the physical mechanisms leading to onset in the GloSea5 simulations, and examine case studies comparing late and early onset years in both the model hindcasts and reanalysis data.

  1. An assessment of Indian monsoon seasonal forecasts and mechanisms underlying monsoon interannual variability in the Met Office GloSea5-GC2 system

    NASA Astrophysics Data System (ADS)

    Johnson, Stephanie J.; Turner, Andrew; Woolnough, Steven; Martin, Gill; MacLachlan, Craig

    2016-06-01

    We assess Indian summer monsoon seasonal forecasts in GloSea5-GC2, the Met Office fully coupled subseasonal to seasonal ensemble forecasting system. Using several metrics, GloSea5-GC2 shows similar skill to other state-of-the-art seasonal forecast systems. The prediction skill of the large-scale South Asian monsoon circulation is higher than that of Indian monsoon rainfall. Using multiple linear regression analysis we evaluate relationships between Indian monsoon rainfall and five possible drivers of monsoon interannual variability. Over the time period studied (1992-2011), the El Niño-Southern Oscillation (ENSO) and the Indian Ocean dipole (IOD) are the most important of these drivers in both observations and GloSea5-GC2. Our analysis indicates that ENSO and its teleconnection with Indian rainfall are well represented in GloSea5-GC2. However, the relationship between the IOD and Indian rainfall anomalies is too weak in GloSea5-GC2, which may be limiting the prediction skill of the local monsoon circulation and Indian rainfall. We show that this weak relationship likely results from a coupled mean state bias that limits the impact of anomalous wind forcing on SST variability, resulting in erroneous IOD SST anomalies. Known difficulties in representing convective precipitation over India may also play a role. Since Indian rainfall responds weakly to the IOD, it responds more consistently to ENSO than in observations. Our assessment identifies specific coupled biases that are likely limiting GloSea5-GC2 Indian summer monsoon seasonal prediction skill, providing targets for model improvement.

  2. Validation of the surface energy balance over the Antarctic ice sheets in the U.K. Meteorological Office unified climate model

    SciTech Connect

    King, J.C.; Connolley, W.M.

    1997-06-01

    Surface radiation measurements and other climatological data were used to validate the representation of the surface energy balance over the East Antarctic Ice Sheet in the U.K. Meteorological Office Unified Climate Model. Model calculations of incident and reflected shortwave radiation are in good agreement with observations, but the downward component of longwave radiation at the surface appears to be underestimated by up to 20 W m-1 in the model. Over much of the interior of Antarctica this error appears to be compensated for by an overestimate in turbulent transport of heat to the surface, while over the steep coastal slopes the heat flux is in good agreement with observations but the surface temperature is too low. The excessive heat flux over the interior results largely from the use of an inappropriately large bulk transfer coefficient under very stable conditions, suggesting that the surface heat flux scheme in the model is not ideally formulated for the conditions that prevail in the Antarctic boundary layer.

  3. Unified cosmology

    SciTech Connect

    Cho, Y.M. Department of Physics, Seoul National University, Seoul )

    1990-04-15

    Recently a unified cosmology was proposed as a higher-dimensional generalization of the standard big-bang cosmology. In this paper we discuss its foundation, characteristics, and possible cosmological solutions in detail. In particular we discuss how the missing-mass problem, the horizon problem, and the flatness problem of the standard model can be resolved within the context of this unified cosmology.

  4. ASI/MET Mast

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Mars Pathfinder meteorology mast casts a shadow on the lander solar array, as seen in this superpan mosaic. Looking to the southeast during the morning, the windsocks are slightly tilted, indicating the presence of a light wind from the southwest. The MET mast measured the temperature, pressure, and wind speed at the Pathfinder landing site. During the mission, the instrument returned 8.5 million individual measurements from the surface of Mars.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  5. ASI/MET mast

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Atmospheric Structure Instrument/Meteorology Package (ASI/MET) mast is visible against a backdrop of rocky Martian terrain in this image, taken by the Imager for Mars Pathfinder (IMP). The windsocks are slightly tilted, showing some wind activity. Distortions in the background are due to parallax.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  6. Unifying Physics

    NASA Astrophysics Data System (ADS)

    Goradia, Shantilal

    2013-04-01

    Century old GR fails to unify quantum physics, nuclear force or distinguish between the mass of living bodies from inert mass. Probabilistic gravity [1] explains strong coupling (nuclear force). The natural log of the age of the universe, 10E60 in Planck times, equaling 137 (1/Alpha) extends physics to deeper science, if we stand on the shoulders of giants like Feynman and Gamow. Implications of [1] are that it is not the earth, but M and S numbers of the particles of the earth are remotely interacting with corresponding numbers of the particles of the moon and the sun respectively, neglecting other heavenly bodies in this short draft. This new physics is likely to enable creative scientific minds to throw light on a theoretical basis for an otherwise arbitrary cosmological constant, uniformity of microwave background, further vindication of Boltzmann, quantum informatics, Einstein’s later publicized views and more, eliminating the need to spend money for implicitly nonexistent quantum gravity and graviton.[4pt] [1] Journal of Physical Science and Applications 2 (7) (2012) 265-268.

  7. Meteorological effects of the solar eclipse of 20 March 2015: analysis of UK Met Office automatic weather station data and comparison with automatic weather station data from the Faroes and Iceland.

    PubMed

    Hanna, Edward; Penman, John; Jónsson, Trausti; Bigg, Grant R; Björnsson, Halldór; Sjúrðarson, Sølvi; Hansen, Mads A; Cappelen, John; Bryant, Robert G

    2016-09-28

    Here, we analyse high-frequency (1 min) surface air temperature, mean sea-level pressure (MSLP), wind speed and direction and cloud-cover data acquired during the solar eclipse of 20 March 2015 from 76 UK Met Office weather stations, and compare the results with those from 30 weather stations in the Faroe Islands and 148 stations in Iceland. There was a statistically significant mean UK temperature drop of 0.83±0.63°C, which occurred over 39 min on average, and the minimum temperature lagged the peak of the eclipse by about 10 min. For a subset of 14 (16) relatively clear (cloudy) stations, the mean temperature drop was 0.91±0.78 (0.31±0.40)°C but the mean temperature drops for relatively calm and windy stations were almost identical. Mean wind speed dropped significantly by 9% on average during the first half of the eclipse. There was no discernible effect of the eclipse on the wind-direction or MSLP time series, and therefore we can discount any localized eclipse cyclone effect over Britain during this event. Similar changes in air temperature and wind speed are observed for Iceland, where conditions were generally clearer, but here too there was no evidence of an eclipse cyclone; in the Faroes, there was a much more muted meteorological signature.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID:27550769

  8. MET ONE 831

    EPA Science Inventory

    The Met One 831 sensor measures particulate matter (PM) by counting and sizing individual particles using scattered laser light. The unit then converts the count data to mass measurements in micrograms per cubic meter (µg/m3). The Met One 831 counts particles in four different PM...

  9. ASI/MET - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Atmospheric Structure Instrument/Meteorology Package (ASI/MET) is the mast and windsocks at the center of this color image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. The instrument appears in two different sections due to image parallax. The ASI/MET is an engineering subsytem that acquired atmospheric data during Pathfinder's descent, and will continue to get more data through the entire landed mission. The windsocks are seen pointing almost completely up, representing little wind movement at the three locations of the windsocks. A rock at left holds a shadow of the ASI/MET, indicating the sun's position is at the rear right. Portions of a lander petal and deflated airbag are visible, in addition to several rocks of varying sizes in the distance.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  10. Evaluation of the UK Met Office's HadGEM3-RA and HadRM3P regional climate models within South America-CORDEX simulations: ENSO related interannual precipitation variability

    NASA Astrophysics Data System (ADS)

    Bozkurt, D.; Rojas, M.

    2014-12-01

    This study aims to investigate and compare the ability of the UK Met Office's HadGEM3-RA and HadRM3P regional climate models (RCMs) to simulate mean and interannual variability of precipitation over South America with a special focus on Chile. The HadGEM3-RA is a regional version of the newly developed HadGEM3 global model and the HadRM3P is based on the earlier HadCM3 global model. The RCMs simulations were carried out at 0.44o x 0.44o degree resolution over South America-CORDEX domain for the period 1989-2008. The initial and boundary conditions were provided by ERA-Interim Reanalysis data available at 6-h intervals with a resolution of 1.5o x 1.5o in the horizontal and 37 pressure levels. We compare the results against a number of observational datasets, including gridded dataset of CRU, UDEL, TRMM and GPCP. Moreover, available station data is derived from Direccion General de Aguas (DGA) mainly for Central Chile, which is the heartland of Chile with the highest population and important economic activities. The analysis is mainly focused on evaluating the abilities of the RCMs in simulating spatial pattern and ENSO related precipitation variability in different subregions of South America-CORDEX domain. In general, both RCMs have a good skill in reproducing spatial pattern and annual cycle of observed precipitation in climatically different subregions. However, both RCMs tend to underestimate precipitation in the Amazon Basin, which is more pronounced in the HadRM3P simulations. On the contrary, the RCMs tend to overestimate the precipitation over the Andes and southern Chile. The overestimation could be related to the physical core of the RCMs, but the discrepancies could also arise due to insufficient station network, especially in the mountainous areas, potentially yielding smaller precipitation quantities in the observed data than the true ones. In terms of interannual variability, the models capture ENSO related wet and dry interannual precipitation

  11. 34 CFR 648.70 - What conditions must be met by a fellow?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What conditions must be met by a fellow? 648.70 Section 648.70 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF... Must Be Met by a Fellow After an Award? § 648.70 What conditions must be met by a fellow? To...

  12. 34 CFR 648.70 - What conditions must be met by a fellow?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What conditions must be met by a fellow? 648.70 Section 648.70 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF... Must Be Met by a Fellow After an Award? § 648.70 What conditions must be met by a fellow? To...

  13. 34 CFR 648.70 - What conditions must be met by a fellow?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What conditions must be met by a fellow? 648.70 Section 648.70 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF... Must Be Met by a Fellow After an Award? § 648.70 What conditions must be met by a fellow? To...

  14. 34 CFR 648.70 - What conditions must be met by a fellow?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What conditions must be met by a fellow? 648.70 Section 648.70 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF... Must Be Met by a Fellow After an Award? § 648.70 What conditions must be met by a fellow? To...

  15. 34 CFR 648.70 - What conditions must be met by a fellow?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What conditions must be met by a fellow? 648.70 Section 648.70 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF... Must Be Met by a Fellow After an Award? § 648.70 What conditions must be met by a fellow? To...

  16. 76 FR 401 - MetLife Insurance Company of Connecticut, et al.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ..., Branch Chief, Office of Insurance Products, Division of Investment Management, at (202) 551-6795... COMMISSION MetLife Insurance Company of Connecticut, et al. December 28, 2010. AGENCY: Securities and...: MetLife Insurance Company of Connecticut (``MetLife of CT''), MetLife of CT Separate Account...

  17. ASI/MET

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Atmospheric Structure Instrument/Meteorology Package (ASI/MET) is the mast and windsocks at the center of this color image, taken by the Imager for Mars Pathfinder (IMP) on Sol 4. The instrument appears in two different sections due to image parallax. The ASI/MET is an engineering subsytem that acquired atmospheric data during Pathfinder's descent, and will continue to get more data through the entire landed mission. The windsocks are seen pointing almost completely up, representing little wind movement at the three locations of the windsocks. A rock at left holds a shadow of the ASI/MET, indicating the sun's position is at the rear right. Portions of a lander petal and deflated airbag are visible, in addition to several rocks of varying sizes in the distance.

    Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. JPL is an operating division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  18. Perspectives of Key Central Office Staff and School Principals Regarding Resource Allocation Policies and Procedures. A Report Prepared for Los Angeles Unified School District. SSFR Research Report #02 (LAUSD)

    ERIC Educational Resources Information Center

    Chambers, Jay G.; Jubb, Steve; Manship, Karen; Rosas, Rigo; Brown, James R.

    2010-01-01

    This report summarizes the perspectives and attitudes of a selected set of district and school site administrators whom the authors interviewed in Los Angeles Unified School District (LAUSD) during the fall and winter of the 2009-2010 school year. The authors carried out interviews with selected district administrators and a series of focus groups…

  19. Perspectives of Key Central Office Staff and School Principals Regarding Resource Allocation Policies and Procedures. A Report Prepared for Twin Rivers Unified School District. SSFR Research Report #02 (TRUSD)

    ERIC Educational Resources Information Center

    Chambers, Jay G.; Brown, James R.; Tolleson, Ray; Manship, Karen; Knudson, Joel

    2010-01-01

    This report summarizes the perspectives and attitudes of a selected set of district and school site administrators whom the authors interviewed in Twin Rivers Unified School District (TRUSD) during the fall of 2009. The authors carried out interviews and focus groups with these individuals to gain an understanding of how the current budgeting…

  20. Perspectives of Key Central Office Staff and School Principals Regarding Resource Allocation Policies and Procedures--Technical Appendix. A Report Prepared for Twin Rivers Unified School District. SSFR Research Report #02 (TRUSD)

    ERIC Educational Resources Information Center

    Chambers, Jay G.; Brown, James R.; Tolleson, Ray; Manship, Karen; Knudson, Joel

    2010-01-01

    Strategic School Funding for Results (SSFR) interviews in Twin Rivers Unified School District (TRUSD) took place in October 2009. Three key district officials were interviewed, and five principals (representing elementary, middle, and high schools) participated in a focus group. District officials were chosen for interviews because of their key…

  1. Perspectives of Central Office Staff, Principals, Teachers, and School Site Councils on Resource Allocation and "Budgeting for Student Achievement" Implementation in 2010-11. A Report Prepared for the Los Angeles Unified School District

    ERIC Educational Resources Information Center

    Haxton, Clarisse L.; Chambers, Jay G.; Manship, Karen; Cruz, Lisa; O'Neil, Caitlin

    2012-01-01

    As part of the evaluation of the Strategic School Funding for Results (SSFR) project (called Budgeting for Student Success, or BSA, in Los Angeles Unified School District), the American Institutes for Research (AIR) conducted surveys of principals, teachers, and members of School Site Councils (SSCs) to gather information on their attitudes and…

  2. Soar and the case for unified theories of cognition.

    PubMed

    Cooper, R; Shallice, T

    1995-05-01

    Despite the potential importance to cognitive psychology of unified theories no attempt has been made to assess concretely the methodological problems that such theorising produces. This paper addresses this issue of unified theorising, and in particular the arguments for unified theories put forward by Newell (1990). Close examination of these arguments reveals that Newell's approach does not adequately counter the difficulties which beset the grand theories of the 1930s, nor the problems of irrelevant specification which arise in modern computational psychological work. These difficulties do not prevent the development of unified theories, but they do pose serious problems, problems which it is argued can only be met by rigorous empirical testing together with extreme methodological sensitivity. The methodological concerns lead us to examine Soar, perhaps the most well-developed unified theory, from methodological, computational, and empirical perspectives. Our conclusions are that, whilst Soar represents an impressive body of research, its methodological foundations are insecure, it is ill specified as a computational/psychological theory, and under empirical testing it does not stand up to close scrutiny as a unified theory. The Soar research programme as it currently stands thus fails to meet the necessary methodological demands imposed by unified theorising. PMID:7789089

  3. MET inhibition in lung cancer

    PubMed Central

    Giaj Levra, Matteo; Novello, Silvia

    2013-01-01

    Targeted agents have completely changed cancer treatment strategy, leading it from a “one size fits all” approach to a customized therapy. In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming “druggable” only in this last period of time. Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell-cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization. Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis. Met amplification is also described to be linked to EGFR acquired resistance. Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment. This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation. PMID:25806202

  4. Outdoor Unified Studies.

    ERIC Educational Resources Information Center

    Liston, Louise

    Escalante (Utah) High School's outdoor unified studies field trip is a learning experience to be remembered. The four-day camping experience begins with pre-trip plans, pretests, and lecture/introductions to the Anasazi culture and to geologic formations to be visited. Horses (and equipment-carrying trucks) take the students into the desert to set…

  5. MET deregulation in breast cancer

    PubMed Central

    Landi, Lorenza

    2015-01-01

    Background Mesenchymal-epithelial transition (MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life. Deregulation of HGF/MET signaling pathway is frequently observed in many cancer types, conferring invasive growth and tendency to progression. MET deregulation is due to gene amplification or increased copy number, gene mutation, receptor over-expression or ligand autocrine loops activation. These events lead to migration, invasion, proliferation, metastatic spread and neo-angiogenesis of cancer cells, suggesting that anti-HGF/MET agents may represent a potential antitumor strategy. In breast cancer (BC), preclinical and clinical data demonstrated the role of HGF/MET signalling pathway in carcinogenesis, disease progression and resistance features. Methods For this review article, all published data on HGF/MET in BC were collected and analyzed. Results Several evidences underline that, in early BC, MET over-expression has an independent negative prognostic significance, regardless of method used for evaluation and BC subtypes. Available data suggest that MET is a relevant target particularly in basal-like (BL) and in triple negative BC. Moreover, preclinical and retrospective data support the critical role of MET deregulation in the development of resistance to target-agents, such as anti-HER2 strategies. Conclusions MET is a promising new target in BC. Several anti-MET agents are under investigation and ongoing clinical trials will clarify its relevance in BC treatment. PMID:26366398

  6. Evaluation of high-resolution MetUM and AMPS forecasts of near-surface meteorological variables over Larsen C ice shelf and northern Antarctic Peninsula

    NASA Astrophysics Data System (ADS)

    Orr, Andrew; Kirchgaessner, Amelie; King, John; Weeks, Mark; Gadian, Alan; Kuipers Munneke, Peter; van den Broeke, Michiel; Steffen, Konrad

    2016-04-01

    High-resolution weather forecasts are an important tool for understanding the detailed patterns of surface melt on the Larsen C ice shelf (LCIS), Antarctic Peninsula. We investigate the skill of UK Met Office Unified Model (MetUM) and Antarctic Mesoscale Prediction System (AMPS) forecasts with horizontal grid spacing of 4-5 km for a 1 month period during January-February 2011 by comparing near-surface model output to automatic weather station measurements at 5 sites on the LCIS and 3 on the northern Antarctic Peninsula. Forecasts for the range 12-24 h showed a fairly homogeneous performance over the LCIS. The 2 m temperature simulated by AMPS has a correlation with observations of 0.5-0.6 and a systematic cold bias of around -1 degrees centigrade. By comparison, the MetUM had a higher correlation and was less negatively biased. The simulated surface pressure has a correlation of 0.99 and small biases in both models. AMPS yielded better results than the MetUM for 10 m wind speed, being able to capture particularly well synoptically-driven high wind speeds which the MetUM systematically underestimated. Both models struggle to simulate the 10 m wind direction when the wind conditions are highly variable. The simulation of specific humidity by both models was poor. Both models showed a general reduction in performance over the northern Antarctic Peninsula compared to the LCIS. Extending the analysis to consider the 12-36 h forecast range demonstrated a relatively weak dependence of model skill to the length of the forecast. The study focuses particularly on the representation of foehn wind events, which are an important contributor to surface melt over the LCIS, by examining additional ~1 km scale forecasts using the MetUM.

  7. The Unified Astronomy Thesaurus

    NASA Astrophysics Data System (ADS)

    Erdmann, Christopher; Frey, Katie

    2015-08-01

    The Unified Astronomy Thesaurus (UAT) is an open, interoperable and community-supported thesaurus which unifies the existing divergent and isolated Astronomy & Astrophysics vocabularies into a single high-quality, freely-available open thesaurus formalizing astronomical concepts and their inter-relationships. The UAT builds upon both the International Astronomical Union Thesaurus and the International Virtual Observatory Alliance Thesaurus with major contributions from the astronomy portions of the thesauri developed by the Institute of Physics Publishing, the American Institute of Physics, and SPIE, donated to the American Astronomical Society (AAS). In this talk, I will describe the effort behind the creation of the UAT, its continued development through the leadership of the AAS, and discuss some of its current and potential applications.

  8. Unified powered flight guidance

    NASA Technical Reports Server (NTRS)

    Brand, T. J.; Brown, D. W.; Higgins, J. P.

    1973-01-01

    A complete revision of the orbiter powered flight guidance scheme is presented. A unified approach to powered flight guidance was taken to accommodate all phases of exo-atmospheric orbiter powered flight, from ascent through deorbit. The guidance scheme was changed from the previous modified version of the Lambert Aim Point Maneuver Mode used in Apollo to one that employs linear tangent guidance concepts. This document replaces the previous ascent phase equation document.

  9. Unifying Theories of Confidentiality

    NASA Astrophysics Data System (ADS)

    Banks, Michael J.; Jacob, Jeremy L.

    This paper presents a framework for reasoning about the security of confidential data within software systems. A novelty is that we use Hoare and He's Unifying Theories of Programming (UTP) to do so and derive advantage from this choice. We identify how information flow between users can be modelled in the UTP and devise conditions for verifying that system designs may not leak secret information to untrusted users. We also investigate how these conditions can be combined with existing notions of refinement to produce refinement relations suitable for deriving secure implementations of systems.

  10. MET — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: The proto-oncogene MET product is the hepatocyte growth factor receptor and encodes tyrosine-kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor. Various mutations in the MET gene are associated with papillary renal carcinoma. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008

  11. LCLS Heavy Met Outgassing Tests

    SciTech Connect

    Kishiyama, K. I.

    2010-12-01

    A Heavy Met that is 95% tungsten, 3% nickel and 2% iron and sintered to 100% density and is Ultra High Vacuum (UHV) compatible is proposed for use as the X-ray slit in the Front End Enclosure and the Fixed Mask for the Linac Coherent Light Source (LCLS). The Heavy Met was tested in the LLNL Vacuum Sciences and Engineering Lab (VSEL) to determine its outgassing rate and its overall compatibility with the vacuum requirements for LCLS.

  12. Unified Bohm criterion

    SciTech Connect

    Kos, L.; Tskhakaya, D. D.; Jelić, N.

    2015-09-15

    Recent decades have seen research into the conditions necessary for the formation of the monotonic potential shape in the sheath, appearing at the plasma boundaries like walls, in fluid, and kinetic approximations separately. Although either of these approaches yields a formulation commonly known as the much-acclaimed Bohm criterion (BC), the respective results involve essentially different physical quantities that describe the ion gas behavior. In the fluid approach, such a quantity is clearly identified as the ion directional velocity. In the kinetic approach, the ion behavior is formulated via a quantity (the squared inverse velocity averaged by the ion distribution function) without any clear physical significance, which is, moreover, impractical. In the present paper, we try to explain this difference by deriving a condition called here the Unified Bohm Criterion, which combines an advanced fluid model with an upgraded explicit kinetic formula in a new form of the BC. By introducing a generalized polytropic coefficient function, the unified BC can be interpreted in a form that holds, irrespective of whether the ions are described kinetically or in the fluid approximation.

  13. 78 FR 18235 - Unified Rule for Loss on Subsidiary Stock

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 Unified Rule for Loss on Subsidiary Stock CFR Correction 0 In Title..., the preferred stock is treated as entitled to a distribution no later than the time the...

  14. 78 FR 18235 - Unified Rule for Loss on Subsidiary Stock

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 Unified Rule for Loss on Subsidiary Stock CFR Correction 0 In Title 26 of the Code of Federal Regulations, Part 1 (Sec. Sec. 1.1401 to 1.1550), revised as of April...

  15. Unified Parallel Software

    SciTech Connect

    McKay, Mike

    2003-12-01

    UPS (Unified Paralled Software is a collection of software tools libraries, scripts, executables) that assist in parallel programming. This consists of: o libups.a C/Fortran callable routines for message passing (utilities written on top of MPI) and file IO (utilities written on top of HDF). o libuserd-HDF.so EnSight user-defined reader for visualizing data files written with UPS File IO. o ups_libuserd_query, ups_libuserd_prep.pl, ups_libuserd_script.pl Executables/scripts to get information from data files and to simplify the use of EnSight on those data files. o ups_io_rm/ups_io_cp Manipulate data files written with UPS File IO These tools are portable to a wide variety of Unix platforms.

  16. Unified nonclassicality criteria

    NASA Astrophysics Data System (ADS)

    Ryl, S.; Sperling, J.; Agudelo, E.; Mraz, M.; Köhnke, S.; Hage, B.; Vogel, W.

    2015-07-01

    In this work we generalize the Bochner criterion addressing the characteristic function, i.e., the Fourier transform, of the Glauber-Sudarshan phase-space function. For this purpose we extend the Bochner theorem by including derivatives of the characteristic function. The resulting necessary and sufficient nonclassicality criteria unify previously known moment-based criteria with those based on the characteristic function. For applications of the generalized nonclassicality probes, we provide direct sampling formulas for balanced homodyne detection. A squeezed vacuum state is experimentally realized and characterized with our method. This complete framework—theoretical unification, sampling approach, and experimental implementation—presents an efficient toolbox to characterize quantum states of light for applications in quantum technology.

  17. Unified Parallel Software

    Energy Science and Technology Software Center (ESTSC)

    2003-12-01

    UPS (Unified Paralled Software is a collection of software tools libraries, scripts, executables) that assist in parallel programming. This consists of: o libups.a C/Fortran callable routines for message passing (utilities written on top of MPI) and file IO (utilities written on top of HDF). o libuserd-HDF.so EnSight user-defined reader for visualizing data files written with UPS File IO. o ups_libuserd_query, ups_libuserd_prep.pl, ups_libuserd_script.pl Executables/scripts to get information from data files and to simplify the use ofmore » EnSight on those data files. o ups_io_rm/ups_io_cp Manipulate data files written with UPS File IO These tools are portable to a wide variety of Unix platforms.« less

  18. 20 CFR 10.205 - What conditions must be met to receive COP?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true What conditions must be met to receive COP? 10.205 Section 10.205 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR..., AS AMENDED Continuation of Pay Eligibility for Cop § 10.205 What conditions must be met to...

  19. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 4 2013-07-01 2013-07-01 false What requirements must be met by a State partnership? 692.101 Section 692.101 Education Regulations of the Offices of the Department of Education (Continued...? § 692.101 What requirements must be met by a State partnership? (a) State. A State that is receiving...

  20. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 4 2014-07-01 2014-07-01 false What requirements must be met by a State partnership? 692.101 Section 692.101 Education Regulations of the Offices of the Department of Education (Continued...? § 692.101 What requirements must be met by a State partnership? (a) State. A State that is receiving...

  1. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 4 2012-07-01 2012-07-01 false What requirements must be met by a State partnership? 692.101 Section 692.101 Education Regulations of the Offices of the Department of Education (Continued...? § 692.101 What requirements must be met by a State partnership? (a) State. A State that is receiving...

  2. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What requirements must be met by a State partnership? 692.101 Section 692.101 Education Regulations of the Offices of the Department of Education (Continued... What requirements must be met by a State partnership? (a) State. A State that is receiving an...

  3. 34 CFR 692.101 - What requirements must be met by a State partnership?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 4 2011-07-01 2011-07-01 false What requirements must be met by a State partnership? 692.101 Section 692.101 Education Regulations of the Offices of the Department of Education (Continued...? § 692.101 What requirements must be met by a State partnership? (a) State. A State that is receiving...

  4. 20 CFR 10.205 - What conditions must be met to receive COP?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What conditions must be met to receive COP? 10.205 Section 10.205 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF...' COMPENSATION ACT, AS AMENDED Continuation of Pay Eligibility for Cop § 10.205 What conditions must be met...

  5. 34 CFR 692.21 - What requirements must be met by a State program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 4 2011-07-01 2011-07-01 false What requirements must be met by a State program? 692.21 Section 692.21 Education Regulations of the Offices of the Department of Education (Continued... Participate in the Leap Program? § 692.21 What requirements must be met by a State program? To receive...

  6. 34 CFR 692.21 - What requirements must be met by a State program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 4 2012-07-01 2012-07-01 false What requirements must be met by a State program? 692.21 Section 692.21 Education Regulations of the Offices of the Department of Education (Continued... Participate in the Leap Program? § 692.21 What requirements must be met by a State program? To receive...

  7. 34 CFR 692.21 - What requirements must be met by a State program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 4 2013-07-01 2013-07-01 false What requirements must be met by a State program? 692.21 Section 692.21 Education Regulations of the Offices of the Department of Education (Continued... Participate in the Leap Program? § 692.21 What requirements must be met by a State program? To receive...

  8. 20 CFR 10.205 - What conditions must be met to receive COP?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true What conditions must be met to receive COP? 10.205 Section 10.205 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR..., AS AMENDED Continuation of Pay Eligibility for Cop § 10.205 What conditions must be met to...

  9. 34 CFR 692.21 - What requirements must be met by a State program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 4 2014-07-01 2014-07-01 false What requirements must be met by a State program? 692.21 Section 692.21 Education Regulations of the Offices of the Department of Education (Continued... Participate in the Leap Program? § 692.21 What requirements must be met by a State program? To receive...

  10. 20 CFR 10.205 - What conditions must be met to receive COP?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false What conditions must be met to receive COP? 10.205 Section 10.205 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF...' COMPENSATION ACT, AS AMENDED Continuation of Pay Eligibility for Cop § 10.205 What conditions must be met...

  11. 20 CFR 10.205 - What conditions must be met to receive COP?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false What conditions must be met to receive COP? 10.205 Section 10.205 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF...' COMPENSATION ACT, AS AMENDED Continuation of Pay Eligibility for Cop § 10.205 What conditions must be met...

  12. ASI/MET shadow & airbags

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A shadow of the Atmospheric Structure Instrument/Meteorology Package (ASI/MET) has been cast on a rock at right in this image, taken by the Imager for Mars Pathfinder (IMP) on Sol 4. The instrument appears in two different sections due to image parallax. The ASI/MET is an engineering subsytem that acquired atmospheric data during Pathfinder's descent, and will continue to get more data through the entire landed mission. Portions of a lander petal and deflated airbag are visible, in addition to several rocks of varying sizes in the distance.

    Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. JPL is an operating division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  13. 41 CFR 109-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... furniture and office machines. 109-25.104 Section 109-25.104 Public Contracts and Property Management... furniture and office machines. DOE offices and designated contractors shall make the determination as to whether requirements can be met through the utilization of DOE owned furniture and office machines....

  14. 41 CFR 109-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... furniture and office machines. 109-25.104 Section 109-25.104 Public Contracts and Property Management... furniture and office machines. DOE offices and designated contractors shall make the determination as to whether requirements can be met through the utilization of DOE owned furniture and office machines....

  15. 41 CFR 109-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... furniture and office machines. 109-25.104 Section 109-25.104 Public Contracts and Property Management... furniture and office machines. DOE offices and designated contractors shall make the determination as to whether requirements can be met through the utilization of DOE owned furniture and office machines....

  16. 41 CFR 109-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... furniture and office machines. 109-25.104 Section 109-25.104 Public Contracts and Property Management... furniture and office machines. DOE offices and designated contractors shall make the determination as to whether requirements can be met through the utilization of DOE owned furniture and office machines....

  17. 41 CFR 109-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... furniture and office machines. 109-25.104 Section 109-25.104 Public Contracts and Property Management... furniture and office machines. DOE offices and designated contractors shall make the determination as to whether requirements can be met through the utilization of DOE owned furniture and office machines....

  18. Ionospheric Profiling using GPS/MET Data

    NASA Technical Reports Server (NTRS)

    Hajj, George; Romans, Larry

    1996-01-01

    A report on ionospheric profiling using GPS and MET data is presented. A description of the GPS occultation technique, some examples of GPS/MET data products, the data processing system and a preliminary validation of ionospheric profiles is discussed.

  19. Department of Education Revives Civil Rights Office

    ERIC Educational Resources Information Center

    Finkel, Ed

    2010-01-01

    This article reports on the mission of the Office for Civil Rights in the U.S. Department of Education to ensure equal access to education through compliance reviews. The Office hopes to use these reviews to provide technical assistance to help districts improve their performance. In late March, the Los Angeles Unified School District became the…

  20. 34 CFR 472.32 - What other requirements must be met under this program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What other requirements must be met under this program? 472.32 Section 472.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY...

  1. 34 CFR 472.32 - What other requirements must be met under this program?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What other requirements must be met under this program? 472.32 Section 472.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY...

  2. 34 CFR 472.32 - What other requirements must be met under this program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What other requirements must be met under this program? 472.32 Section 472.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY...

  3. 34 CFR 472.32 - What other requirements must be met under this program?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What other requirements must be met under this program? 472.32 Section 472.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY...

  4. 34 CFR 472.32 - What other requirements must be met under this program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What other requirements must be met under this program? 472.32 Section 472.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY...

  5. Designers' unified cost model

    NASA Technical Reports Server (NTRS)

    Freeman, W.; Ilcewicz, L.; Swanson, G.; Gutowski, T.

    1992-01-01

    The Structures Technology Program Office (STPO) at NASA LaRC has initiated development of a conceptual and preliminary designers' cost prediction model. The model will provide a technically sound method for evaluating the relative cost of different composite structural designs, fabrication processes, and assembly methods that can be compared to equivalent metallic parts or assemblies. The feasibility of developing cost prediction software in a modular form for interfacing with state-of-the-art preliminary design tools and computer aided design programs is being evaluated. The goal of this task is to establish theoretical cost functions that relate geometric design features to summed material cost and labor content in terms of process mechanics and physics. The output of the designers' present analytical tools will be input for the designers' cost prediction model to provide the designer with a database and deterministic cost methodology that allows one to trade and synthesize designs with both cost and weight as objective functions for optimization. This paper presents the team members, approach, goals, plans, and progress to date for development of COSTADE (Cost Optimization Software for Transport Aircraft Design Evaluation).

  6. Reactions of Met-Cars

    SciTech Connect

    Castleman, A.W. Jr.; Guo, B.C.

    1993-12-31

    A new class of metal-carbon complexes, termed metallo-carbohedrenes (Met-Cars), have been discovered to form in a plasma reactor in which early transition metals are vaporized into a stream carrying small hydrocarbon molecules. The initial discovery involved the species Ti{sub 8}c{sub 12}{sup +}, while subsequent studies revealed the stability of the anon and, most importantly, the neutral species. Subsequent investigations show that similar molecules, predicted to have a pentagonal dodecahedral structure, can also be formed with vanadium, hafnium, and zirconium. In the case of the latter, more recent investigations have displaced an interesting growth pattern. In particular, pentagonal dodecahedrons with dangling carbon atoms can undergo further growth, adding at least a second and third cage. The latest results on the properties and reactivities of these new cage-like molecular clusters will be discussed.

  7. Toward a Unified Communication Theory.

    ERIC Educational Resources Information Center

    McMillan, Saundra

    After discussing the nature of theory itself, the author explains her concept of the Unified Communication Theory, which rests on the assumption that there exists in all living structures a potential communication factor which is delimited by species and ontogeny. An organism develops "symbol fixation" at the level where its perceptual abilities…

  8. UNIFYING SCALER FOR BIOASSAY TESTS

    EPA Science Inventory

    An extensive set of interlaboratory root bioassay data was unified using centroids of individual tests as scalers. It is shown that the dose response obeys a first order differential equation with the constant of the equation related to the sensitivity of the dose response relati...

  9. Weyl's Abandonment of Unified Field Theory

    NASA Astrophysics Data System (ADS)

    Sieroka, Norman

    2015-01-01

    In 1918, Hermann Weyl proposed a generalisation of Riemannian geometry, in order to unify general relativity and electrodynamics. This paper investigates the physical, mathematical and philosophical reasons for his subsequent abandonment of any such attempt towards a unified field theory.

  10. Unified theory of effective interaction

    NASA Astrophysics Data System (ADS)

    Takayanagi, Kazuo

    2016-09-01

    We present a unified description of effective interaction theories in both algebraic and graphic representations. In our previous work, we have presented the Rayleigh-Schrödinger and Bloch perturbation theories in a unified fashion by introducing the main frame expansion of the effective interaction. In this work, we start also from the main frame expansion, and present various nonperturbative theories in a coherent manner, which include generalizations of the Brandow, Brillouin-Wigner, and Bloch-Horowitz theories on the formal side, and the extended Krenciglowa-Kuo and the extended Lee-Suzuki methods on the practical side. We thus establish a coherent and comprehensive description of both perturbative and nonperturbative theories on the basis of the main frame expansion.

  11. Recurrence theorems: A unified account

    SciTech Connect

    Wallace, David

    2015-02-15

    I discuss classical and quantum recurrence theorems in a unified manner, treating both as generalisations of the fact that a system with a finite state space only has so many places to go. Along the way, I prove versions of the recurrence theorem applicable to dynamics on linear and metric spaces and make some comments about applications of the classical recurrence theorem in the foundations of statistical mechanics.

  12. SU(9) grand unified theory

    SciTech Connect

    Fujimoto, Y.; Sodano, P.

    1981-04-01

    Frampton's SU(9) model is considered in detail as a grand unified theory with SU(4) horizontal symmetry. We find a correlation among neutrino, horizontal-gauge-boson, and new-fermion masses. With neutrino mass around 10 eV, the horizontal gauge boson is estimated to be as heavy as 6 x 10/sup 10/ GeV. The theory also contains new charged-current processes, which are B+L conserving and ..delta..L=2.

  13. How best to unify crowding?

    PubMed

    Pachai, Matthew V; Doerig, Adrien C; Herzog, Michael H

    2016-05-01

    In crowding, the perception of an object deteriorates in the presence of nearby elements. Obviously, crowding is a ubiquitous phenomenon, as elements are rarely seen in isolation. One of the main characteristics of crowding is that the elements themselves are not rendered invisible, but their features are averaged[1] or substituted[2] with those of neighboring elements. Recently, Harrison and Bex [3] presented "A Unifying Model of Orientation Crowding in Peripheral Vision", which elegantly explains these two characteristics of crowding with one unifying mechanism. They tested their model using a new crowding paradigm and demonstrated an excellent match between human and model results. A key prediction of their model is that a higher number of flankers leads to stronger crowding, simply because more non-target features contribute to the model's output and thus deteriorate performance. However, several recent studies have shown that increasing the number of flankers can actually improve performance [4-9]. Using the same experimental design as Harrison and Bex [3], we report here that adding more flankers can also improve performance in their paradigm, whereas their model predicts the opposite result. We propose that a truly unified model of crowding must include a grouping stage. PMID:27166689

  14. 78 FR 44108 - MET West Trading LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission MET West Trading LLC; Supplemental Notice That Initial Market- Based Rate... notice in the above-referenced proceeding, of MET West Trading LLC's application for market-based...

  15. 78 FR 44108 - MET New York Trading LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission MET New York Trading LLC; Supplemental Notice That Initial Market-Based Rate... notice in the above-referenced proceeding, of MET New York Trading LLC's application for...

  16. 77 FR 74658 - MET Southwest Trading LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission MET Southwest Trading LLC; Supplemental Notice That Initial Market-Based... above-referenced proceeding, of MET Southwest Trading LLC's application for market-based rate...

  17. Clinical significance of MET in gastric cancer

    PubMed Central

    Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC. PMID:26600931

  18. c-Met expression and MET amplification in malignant pleural mesothelioma.

    PubMed

    Bois, Melanie C; Mansfield, Aaron S; Sukov, William R; Jenkins, Sarah M; Moser, Justin C; Sattler, Christopher A; Smith, Carin Y; Molina, Julian R; Peikert, Tobias; Roden, Anja C

    2016-08-01

    c-Met is a receptor tyrosine kinase shown to be overexpressed in malignant pleural mesothelioma (MPM). Whereas MET mutations have been identified in 3%-16% of MPMs, MET amplification has recently been reported in a single epithelioid MPM. We studied c-Met expression and MET amplification in a large MPM cohort and correlated results with morphologic and clinical features. We report the first case of MET amplification in sarcomatoid MPM. MPMs from surgical pathology files (1989-2014) were reviewed. c-Met immunohistochemistry was performed. Staining intensity and distribution were multiplied (H-score). Staining localization (cytoplasmic and/or membranous) was noted. Fluorescence in situ hybridization was performed using probes for MET and centromere 7. One hundred forty-nine patients (median age, 68.0years; interquartile range, 61-75) had epithelioid (n=97), biphasic (n=18), or sarcomatoid (n=34) MPM. Median follow-up was 10.1months (range, 0.1-222.5). One hundred thirty patients died of disease; 2 were alive with disease. c-Met was expressed in 147 MPMs. c-Met staining intensity, distribution, and H-score differed among the histologic subtypes (P=.015; P=.0001, and P=.0005, respectively), but none were predictive of survival. Epithelioid subtype had greater c-Met expression. MET amplification was identified in 1 sarcomatoid MPM and MET duplication in 1 epithelioid MPM; both had poor outcomes. Chromosome 7 aneusomy was observed in 54 of 144 (37.5%) MPMs and associated with decreased overall survival in sarcomatoid MPMs (hazard ratio=2.81; 95% confidence interval, 1.21-6.51; P=.01). In conclusion, c-Met is expressed in MPM, with significant differences in expression among histologic subtypes. MET amplification is a rare event in MPM, making it an unlikely common pathogenesis for c-Met expression. PMID:27402216

  19. Assessing the sensitivity to horizontal resolution of Unified Model simulations of Hurricane Katrina

    NASA Astrophysics Data System (ADS)

    O'Hara, J. P.; Webster, S.

    2012-12-01

    In August 2005 Hurricane Katrina made landfall close to New Orleans with devastating consequences. It was one of the strongest storms to impact the coast of the United States and was also one of the most costly. At peak intensity, its central pressure was 902 hPa and 10 m wind speeds were 175 mph. The extreme nature of this weather system therefore makes it an ideal case study to assess the ability of the Met Office Unified Model to simulate and potentially forecast such phenomena. In this study we assess the ability of the Met Office Unified Model (UM) to simulate Hurricane Katrina at a range of horizontal resolutions. Thus a set of limited area model simulations have been performed at resolutions of 1.5 km, 4 km and 24 km. By careful implementation of the lateral boundary conditions it has been possible to (one way) nest all these simulations inside the 25 km operational global forecast model version of the UM. The configuration of the 1.5 km and 4 km models is based on the 1.5 km and 4 km models used operationally over the UK and hence convection is treated explicitly, whilst the 24 km LAM is configured in the same way as the operational global forecast model and hence convection is parametrized. The simulations are all performed on a 2400 km x 1600 km domain and are all initialised around four days prior to landfall, when the observed central pressure was close to 990 hPa. The initial data for the simulations are ERA-interim analyses with the 25 km global forecast generating hourly LBCs via a series of 24 hour long forecasts initialised from successive 12z analyses. Overall, these simulations have been configured in order to make as clean an assessment as possible of the impact of horizontal resolution on the simulation of Hurricane Katrina. In this presentation we first describe and illustrate results summarising the impact of model resolution on the simulated hurricane. Consistent with the systematic tropical cyclone behaviour of the global forecast model

  20. A unifying concept for astrobiology

    NASA Astrophysics Data System (ADS)

    Chaisson, E. J.

    2003-04-01

    Evolution, broadly construed, has become a powerful unifying concept in much of science - not only in the biological evolution of plants and animals, but also in the physical evolution of stars and planets, and the cultural evolution of society and its many varied products. This paper (1) explores the bulk structure and functioning of open, non-equilibrium, thermodynamic systems relevant to the interdisciplinary field of astrobiology, (2) places the astrobiological landscape into an even larger, cosmological context, (3) defines life, complexity and evolution writ large, (4) claims that life depends ultimately on the expansion of the Universe and the flow of energy derived therefrom and (5) proposes a quantitative metric to characterize the rise of complexity throughout all of natural history. That metric is neither information nor negentropy, for these inveterate yet qualitative terms cannot be quantified, nor even defined, to everyone's satisfaction in today's scientific community. Rather, the newly proposed metric is normalized energy flow, a revision of a long-cherished term - energy - that is physically intuitive, well defined and readily measurable. All ordered systems = from rocky planets and shining stars, to buzzing bees and redwood trees - can be best judged empirically and uniformly by gauging the amount of energy acquired, stored and expressed by those systems. Appeals to anthropism are unnecessary to appreciate the impressive hierarchy of the cosmic evolutionary narrative, including a technological civilization that now embraces an energetics agenda designed to better understand, and perhaps to unify, all the natural sciences.

  1. Unifying Memory and Database Transactions

    NASA Astrophysics Data System (ADS)

    Dias, Ricardo J.; Lourenço, João M.

    Software Transactional Memory is a concurrency control technique gaining increasing popularity, as it provides high-level concurrency control constructs and eases the development of highly multi-threaded applications. But this easiness comes at the expense of restricting the operations that can be executed within a memory transaction, and operations such as terminal and file I/O are either not allowed or incur in serious performance penalties. Database I/O is another example of operations that usually are not allowed within a memory transaction. This paper proposes to combine memory and database transactions in a single unified model, benefiting from the ACID properties of the database transactions and from the speed of main memory data processing. The new unified model covers, without differentiating, both memory and database operations. Thus, the users are allowed to freely intertwine memory and database accesses within the same transaction, knowing that the memory and database contents will always remain consistent and that the transaction will atomically abort or commit the operations in both memory and database. This approach allows to increase the granularity of the in-memory atomic actions and hence, simplifies the reasoning about them.

  2. Examination of Grants Awarded to the Berkeley Unified School District and to Bilingual Children's Television, Inc.

    ERIC Educational Resources Information Center

    Comptroller General of the U.S., Washington, DC.

    At the request of Congresswoman Edith Green, the Comptroller General of the United States reviewed grant procedures covering two awards made by the Office of Education (OE). The first award, made to the Berkeley Unified School District, was funded under Title VII of the Elementary and Secondary Education Act of 1965, as amended, which provides…

  3. 76 FR 33181 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... Air Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve a revision to the San Joaquin Valley Unified Air Pollution Control...'' subject to review by the Office of Management and Budget under Executive Order 12866 (58 FR 51735,...

  4. 77 FR 745 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-06

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) Correction In rule document 2011-33660 appearing on...

  5. 77 FR 7536 - Revisions to the California State Implementation Plan, Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... is finalizing approval of revisions to the San Joaquin Valley Unified Air Pollution Control District.... Proposed Action On October 6, 2011 (76 FR 62002), EPA proposed to approve the following rules into the... Office of Management and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does...

  6. Mars MetNet Mission Payload Overview

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

  7. Mars MetNet Precursor Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

    2013-09-01

    We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  8. Mars MetNet Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.; Palin, M.; Nikkanen, T.

    2015-10-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semihard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  9. MMPM - Mars MetNet Precursor Mission

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

    2008-09-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

  10. MetNet - Martian Network Mission

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.

    2009-04-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The actual practical mission development work started in January 2009 with participation from various countries and space agencies. The scientific rationale and goals as well as key mission solutions will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. This development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development.

  11. Mars MetNet Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, Ari-Matti; Aleksashkin, Sergei; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2015-04-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Scientific Payload The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: 1. MetBaro Pressure device 2. MetHumi Humidity device 3. MetTemp Temperature sensors Optical devices: 1. PanCam Panoramic 2. MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer 3. DS Dust sensor The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the

  12. 76 FR 19893 - Unified Command Plan 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... HOUSE, Washington, April 6, 2011 [FR Doc. 2011-8644 Filed 4-7-11; 11:15 am] Billing code 5000-04-P ...#0;#0; ] Memorandum of April 6, 2011 Unified Command Plan 2011 Memorandum for the Secretary of... the revised Unified Command Plan. Consistent with title 10, United States Code, section 161(b)(2)...

  13. 34 CFR 461.46 - What requirements for program reviews and evaluations must be met by a State?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-administered Workplace Literacy Program (See 34 CFR part 462) and the State-administered English Literacy Program (See 34 CFR part 463). (Approved by the Office of Management and Budget under control number 1830... must be met by a State? 461.46 Section 461.46 Education Regulations of the Offices of the Department...

  14. 34 CFR 461.46 - What requirements for program reviews and evaluations must be met by a State?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-administered Workplace Literacy Program (See 34 CFR part 462) and the State-administered English Literacy Program (See 34 CFR part 463). (Approved by the Office of Management and Budget under control number 1830... must be met by a State? 461.46 Section 461.46 Education Regulations of the Offices of the Department...

  15. 34 CFR 461.46 - What requirements for program reviews and evaluations must be met by a State?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-administered Workplace Literacy Program (See 34 CFR part 462) and the State-administered English Literacy Program (See 34 CFR part 463). (Approved by the Office of Management and Budget under control number 1830... must be met by a State? 461.46 Section 461.46 Education Regulations of the Offices of the Department...

  16. Unifying physical concepts of reality

    SciTech Connect

    Gilbert, T.L.

    1983-08-01

    Physics may be characterized as the science of matter and energy. It anchors the two ends of the frontiers of science: the frontier of the very small and the frontier of the very large. All of the phenomena that we observe and study at the frontiers of science - all external experiences - are manifestations of matter and energy. One may, therefore, use physics to exemplify both the diversity and unity of science. This theme will be developed in two separate examples: first by sketching, very briefly, the historical origins of frontiers of the very small and very large and the converging unity of these two frontiers; and then by describing certain unifying concepts that play a central role in physics and provide a framework for relating developments in different sciences.

  17. Unified scaling law for earthquakes

    PubMed Central

    Christensen, Kim; Danon, Leon; Scanlon, Tim; Bak, Per

    2002-01-01

    We propose and verify a unified scaling law that provides a framework for viewing the probability of the occurrence of earthquakes in a given region and for a given cutoff magnitude. The law shows that earthquakes occur in hierarchical correlated clusters, which overlap with other spatially separated correlated clusters for large enough time periods and areas. For a small enough region and time-scale, only a single correlated group can be sampled. The law links together the Gutenberg–Richter Law, the Omori Law of aftershocks, and the fractal dimensions of the faults. The Omori Law is shown to be the short time limit of general hierarchical phenomenon containing the statistics of both “main shocks” and “aftershocks,” indicating that they are created by the same mechanism. PMID:11875203

  18. Cosmology and unified gauge theory

    NASA Astrophysics Data System (ADS)

    Oraifeartaigh, L.

    1981-09-01

    Theoretical points in common between cosmology and unified gauge theory (UGT) are reviewed, with attention given to areas of one which have proven useful for the other. The underlying principles for both theoretical frameworks are described, noting the differences in scale, i.e., 10 to the 25th cm in cosmology and 10 to the -15th cm for UGT. Cosmology has produced bounds on the number of existing neutrino species, and also on the mass of neutrinos, two factors of interest in particle physics. Electrons, protons, and neutrinos, having been spawned from the same massive leptons, each composed of three quarks, have been predicted to be present in equal numbers in the Universe by UGT, in line with necessities of cosmology. The Grand UGT also suggests specific time scales for proton decay, thus accounting for the observed baryon assymmetry.

  19. Toward a Unified AGN Structure

    NASA Technical Reports Server (NTRS)

    Kazanas, Demosthenes; Fukumura, Keigo; Shrader, Chris; Behar, Ehud; Contopoulosa, Ioannis

    2012-01-01

    We present a unified model for the structure and appearance of accretion powered sources across their entire luminosity range from galactic X-ray binaries (XRB) to luminous quasars, with emphasis on AG N and their phenomenology. Central to this model is the notion of MHD winds launched by the accretion disks that power these objects. These winds provide the matter that manifests as blueshifted absorption features in the UV and X-ray spectra of a large fraction of these sources; furthermore, their density distribution in the poloidal plane determines their "appearance" (i.e. the column and velocity structure of these absorption features and the obscuration of the continuum source) as a function of the observer inclination angle (a feature to which INTEGRAL has made significant contributions). This work focuses on just the broadest characteristics of these objects; nonetheless, it provides scaling laws that allow one to reproduce within this model the properties of objects extending in luminosity from luminous quasars to XRBs. Our general conclusion is that the AGN phenomenology can be accounted for in terms of three parameters: The wind maSS flux in units of the Eddington value, m(dot), the observers' inclination angle Theta and the logarithmic slope between the 0/UV and X-ray fluxes alpha(sub ox); however because of a correlation between alpha(sub ox) and UV luminosity the number of significant parameters is two. The AGN correlations implied by this model appear to extend to and consistent with the XRB phenomenology, suggesting the presence of a truly unified underlying structure for accretion powered sources.

  20. Mars MetNet Mission Payload Overview

    NASA Astrophysics Data System (ADS)

    Haukka, H.; Harri, A.-M.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-04-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The main idea behind the MetNet landing vehicles is to use a state-of-the-art inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized and more mass and volume resources are spared for the science payload. The vehicle decelerates its entry speed using the inflatable structure and final landing sequence includes a cone headed body penetrating the Martian soil. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - Pressure device (MetBaro): mass 100g, measurement range 0..1015 hPa. - Humidity device (MetHumi): mass 15g, measurement range 0..100%RH. - Temperature sensors (MetTemp): mass 2g each, measurement range -110C..+30C. Optical devices: - Panoramic camera (PanCam): mass 100g, FOV 4 lenses mounted at 90 deg - Solar irradiance sensor (MetSIS) with optical wireless system (OWLS) for data transfer: mass 115g (MetSIS) and 7g (OWLS module), wavelength range 190..1100nm. MetSIS equipped with 28 optical detectors, two temperature sensors and two solar incidence angle detectors. - Dust sensor (DS): mass 42g, resolution: 10 particles / cm3. Composition and structure device: - Magnetometer (MOURA): mass 80g, measurement range: ±30uT. MetNet Mission payload instruments are specially designed to operate in very low power conditions. MNL flexible solar panels provides a total of

  1. A Unified Approach to Modeling Multidisciplinary Interactions

    NASA Technical Reports Server (NTRS)

    Samareh, Jamshid A.; Bhatia, Kumar G.

    2000-01-01

    There are a number of existing methods to transfer information among various disciplines. For a multidisciplinary application with n disciplines, the traditional methods may be required to model (n(exp 2) - n) interactions. This paper presents a unified three-dimensional approach that reduces the number of interactions from (n(exp 2) - n) to 2n by using a computer-aided design model. The proposed modeling approach unifies the interactions among various disciplines. The approach is independent of specific discipline implementation, and a number of existing methods can be reformulated in the context of the proposed unified approach. This paper provides an overview of the proposed unified approach and reformulations for two existing methods. The unified approach is specially tailored for application environments where the geometry is created and managed through a computer-aided design system. Results are presented for a blended-wing body and a high-speed civil transport.

  2. Regulation of the MET oncogene: molecular mechanisms.

    PubMed

    Zhang, Jack; Babic, Andy

    2016-04-01

    TheMEToncogene is a predictive biomarker and an attractive therapeutic target for various cancers. Its expression is regulated at multiple layers via various mechanisms. It is subject to epigenetic modifications, i.e. DNA methylation and histone acetylation. Hypomethylation and acetylation of theMETgene have been associated with its high expression in some cancers. Multiple transcription factors including Sp1 and Ets-1 govern its transcription. After its transcription,METmRNA is spliced into multiple species in the nucleus before being transported to the cytoplasm where its translation is modulated by at least 30 microRNAs and translation initiation factors, e.g. eIF4E and eIF4B.METmRNA produces a single chain pro-Met protein of 170kDa which is cleaved into α and β chains. These two chains are bound together through disulfide bonds to form a heterodimer which undergoes either N-linked or O-linked glycosylation in the Golgi apparatus before it is properly localized in the membrane. Upon interactions with its ligand, i.e. hepatocyte growth factor (HGF), the activity of Met kinase is boosted through various phosphorylation mechanisms and the Met signal is relayed to downstream pathways. The phosphorylated Met is then internalized for subsequent degradation or recycle via proteasome, lysosome or endosome pathways. Moreover, the Met expression is subject to autoregulation and activation by other EGFRs and G-protein coupled receptors. Since deregulation of theMETgene leads to cancer and other pathological conditions, a better understanding of theMETregulation is critical for Met-targeted therapeutics. PMID:26905592

  3. Prototype of the Modular Equipment Transporter (MET)

    NASA Technical Reports Server (NTRS)

    1970-01-01

    A prototype of the Modular Equipment Transporter (MET), nicknamed the 'Rickshaw' after its shape and method of propulsion. This equipment was used by the Apollo 14 astronauts during their geological and lunar surface simulation training in the Pinacate volcanic area of northwestern Sonora, Mexico. The Apollo 14 crew will be the first one to use the MET. It will be a portable workbench with a place for the lunar handtools and their carrier, three cameras, two sample container bags, a Special Environmental Sample Container, spare film magazines, and a Lunar Surface Penetrometer.

  4. Introduction to Grand Unified Theories

    NASA Astrophysics Data System (ADS)

    Masiero, Antonio

    The following sections are included: * THE STANDARD MODEL: A CRITICAL APPRAISAL * The "Low Energy" Limit of Renormalizable Gauge Theories * The Standard Model: its purity * The Standard Model: its impurity * Vices and Virtues of the Standard Model * INTRODUCTION TO GRAND UNIFIED THEORIES * When "Strong" and "Weak" Merge Together * The "Big Desert" Picture of the World * A Persistent Cloud: the hierarchy problem * PHENOMENOLOGICAL CONSEQUENCES OF GUTs * What is New in GUTs * General Features of the B and L Violating Processes * A FIRST GLIMPSE AT THE SU(5) MODEL * Why SU(5)? * The Higgs Sector and the Hierarchy Nightmare * LOW ENERGY PHENOMENOLOGICAL CONSEQUENCES OF SU(5) * The Successful sin2θW Prediction of SU(5) * Fermion Masses in SU(5) * Mixing Angles and Phases * Proton Lifetime: A Death Blow to the SU(5) Model? * B-L and Neutrino Masses in SU(5) * SU(5): A Final Score * NEW PHYSICS NOT FAR FROM THE FERMI SCALE? * L-Right Symmetry: A Fundamental Symmetry? * Massive Majorana Neutrinos * Neutron -Antineutron Oscillations * Lepton Number as a Fourth Colour * THE SO(10) MODEL * Few Generalities on the Orthogonal Groups * The SO(10) Gauge Interactions * Patterns of Symmetry Breaking in the SO(10) Model * The Fermion Mass Spectrum * The Question of the Neutrino Mass * PHENOMENOLOGY OF THE INTERMEDIATE MASS SCALES * Renormalization Group Equations in the Presence of IMS * MI and MX in IMS models * Higgs Contributions to the β-Functions * Phenomenological Consequences of IMS * A GENERAL OUTLOOK ON GUTs * General Constraints on GUTs * Major Unsolved Questions in GUTs * Bibliography * References

  5. Beyond Dirac - a Unified Algebra

    NASA Astrophysics Data System (ADS)

    Lundberg, Wayne R.

    2001-10-01

    A introductory insight will be shared regarding a 'separation of variables' approach to understanding the relationship between QCD and the origins of cosmological and particle mass. The discussion will then build upon work presented at DFP 2000, focussing on the formal basis for using 3x3x3 matrix algebra as it underlies and extends Dirac notation. A set of restrictions are established which break the multiple symmetries of the 3x3x3 matrix algebra, yielding Standard Model QCD objects and interactions. It will be shown that the 3x3x3 matrix representation unifies the algebra of strong and weak (and by extension, electromagnetic) interactions. A direct correspondence to string theoretic objects is established by considering the string to be partitioned in thirds. Rubik's cube is used as a graphical means of handling algebraic manipulation of 3x3x3 algebra. Further, its potential utility for advancing pedagogical methods through active engagement is discussed. A simulated classroom exercize will be conducted.

  6. Unifying Quantum Physics with Biology

    NASA Astrophysics Data System (ADS)

    Goradia, Shantilal

    2014-09-01

    We find that the natural logarithm of the age of the universe in quantum mechanical units is close to 137. Since science is not religion, it is our moral duty to recognize the importance of this finding on the following ground. The experimentally obtained number 137 is a mystical number in science, as if written by the hand of God. It is found in cosmology; unlike other theories, it works in biology too. A formula by Boltzmann also works in both: biology and physics, as if it is in the heart of God. His formula simply leads to finding the logarithm of microstates. One of the two conflicting theories of physics (1) Einstein's theory of General Relativity and (2) Quantum Physics, the first applies only in cosmology, but the second applies in biology too. Since we have to convert the age of the universe, 13 billion years, into 1,300,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000 Planck times to get close to 137, quantum physics clearly shows the characteristics of unifying with biology. The proof of its validity also lies in its ability to extend information system observed in biology.

  7. Airbag and ASI/MET instrument in 360-degree panorama

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This view from the lander was imaged by the Imager for Mars Pathfinder (IMP) as part of a 360-degree color panorama, taken over sols 8, 9 and 10. A deflated airbag is at the bottom of the image. At the extreme right, the Atmospheric Structure Instrument and Meteorology package (ASI/MET)mast, with its three windsocks, is visible.are at the bottom right of the image.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  8. Unified universal quantum cloning machine and fidelities

    SciTech Connect

    Wang Yinan; Shi Handuo; Xiong Zhaoxi; Jing Li; Mu Liangzhu; Ren Xijun; Fan Heng

    2011-09-15

    We present a unified universal quantum cloning machine, which combines several different existing universal cloning machines together, including the asymmetric case. In this unified framework, the identical pure states are projected equally into each copy initially constituted by input and one half of the maximally entangled states. We show explicitly that the output states of those universal cloning machines are the same. One importance of this unified cloning machine is that the cloning procession is always the symmetric projection, which reduces dramatically the difficulties for implementation. Also, it is found that this unified cloning machine can be directly modified to the general asymmetric case. Besides the global fidelity and the single-copy fidelity, we also present all possible arbitrary-copy fidelities.

  9. Timeline as Unifying Concept for Spacecraft Operations

    NASA Technical Reports Server (NTRS)

    Reinholtz, Kirk

    2012-01-01

    The notion of Timeline has been used informally in spacecraft operations software for some time, but it has not heretofore been formalized and unified either syntactically or semantically. We have formalized and unified the Timeline so that the commonality can be exploited to reduce the cost of developing and using spacecraft operations software. The Timeline can then be used as the common data structure for storage and communications between spacecraft planning and operations software elements.

  10. Unified approach for incompressible flows

    NASA Technical Reports Server (NTRS)

    Chang, Tyne-Hsien

    1995-01-01

    A unified approach for solving incompressible flows has been investigated in this study. The numerical CTVD (Centered Total Variation Diminishing) scheme used in this study was successfully developed by Sanders and Li for compressible flows, especially for the high speed. The CTVD scheme possesses better mathematical properties to damp out the spurious oscillations while providing high-order accuracy for high speed flows. It leads us to believe that the CTVD scheme can equally well apply to solve incompressible flows. Because of the mathematical difference between the governing equations for incompressible and compressible flows, the scheme can not directly apply to the incompressible flows. However, if one can modify the continuity equation for incompressible flows by introducing pseudo-compressibility, the governing equations for incompressible flows would have the same mathematical characters as compressible flows. The application of the algorithm to incompressible flows thus becomes feasible. In this study, the governing equations for incompressible flows comprise continuity equation and momentum equations. The continuity equation is modified by adding a time-derivative of the pressure term containing the artificial compressibility. The modified continuity equation together with the unsteady momentum equations forms a hyperbolic-parabolic type of time-dependent system of equations. Thus, the CTVD schemes can be implemented. In addition, the physical and numerical boundary conditions are properly implemented by the characteristic boundary conditions. Accordingly, a CFD code has been developed for this research and is currently under testing. Flow past a circular cylinder was chosen for numerical experiments to determine the accuracy and efficiency of the code. The code has shown some promising results.

  11. Unified approach for incompressible flows

    NASA Technical Reports Server (NTRS)

    Chang, Tyne-Hsien

    1993-01-01

    An unified approach for solving both compressible and incompressible flows was investigated in this study. The difference in CFD code development between incompressible and compressible flows is due to the mathematical characteristics. However, if one can modify the continuity equation for incompressible flows by introducing pseudocompressibility, the governing equations for incompressible flows would have the same mathematical characters as compressible flows. The application of a compressible flow code to solve incompressible flows becomes feasible. Among numerical algorithms developed for compressible flows, the Centered Total Variation Diminishing (CTVD) schemes possess better mathematical properties to damp out the spurious oscillations while providing high-order accuracy for high speed flows. It leads us to believe that CTVD schemes can equally well solve incompressible flows. In this study, the governing equations for incompressible flows include the continuity equation and momentum equations. The continuity equation is modified by adding a time-derivative of the pressure term containing the artificial compressibility. The modified continuity equation together with the unsteady momentum equations forms a hyperbolic-parabolic type of time-dependent system of equations. The continuity equation is modified by adding a time-derivative of the pressure term containing the artificial compressibility. The modified continuity equation together with the unsteady momentum equations forms a hyperbolic-parabolic type of time-dependent system of equations. Thus, the CTVD schemes can be implemented. In addition, the boundary conditions including physical and numerical boundary conditions must be properly specified to obtain accurate solution. The CFD code for this research is currently in progress. Flow past a circular cylinder will be used for numerical experiments to determine the accuracy and efficiency of the code before applying this code to more specific applications.

  12. Rebound Effects Caused by Withdrawal of MET Kinase Inhibitor Are Quenched by a MET Therapeutic Antibody.

    PubMed

    Pupo, Emanuela; Ducano, Nadia; Lupo, Barbara; Vigna, Elisa; Avanzato, Daniele; Perera, Timothy; Trusolino, Livio; Lanzetti, Letizia; Comoglio, Paolo M

    2016-09-01

    MET oncogene amplification is emerging as a major mechanism of acquired resistance to EGFR-directed therapy in lung and colorectal cancers. Furthermore, MET amplification predicts responsiveness to MET inhibitors currently in clinical trials. Among the anti-MET drugs available, ATP-competitive small-molecule kinase inhibitors abrogate receptor autophosphorylation and downstream activation of ERK1/2 and AKT, resulting in cell-cycle arrest. However, this antiproliferative effect allows persistence of a pool of cancer cells that are quiescent but alive. Once the inhibition is removed, rebound activation of MET-driven cell proliferative pathways and tumor growth may occur, an adverse event observed frequently in clinical settings after drug discontinuation. Here we show that inhibitor withdrawal prompts receptor phosphorylation to levels higher than those displayed at steady-state and generates a rebound effect pushing quiescent cancer cells back into the cell cycle, both in vitro and in experimental tumor models in vivo Mechanistically, we found that inhibitor treatment blocks MET endocytosis, causing a local increase in the number of receptors at the plasma membrane. Upon inhibitor washout, the receptor is readily rephosphorylated. The initial phosphorylation is not only increased but also prolonged in duration due to downmodulation of a phosphatase-mediated MET-negative feedback loop, which accompanies receptor internalization. Notably, treatment with a MET therapeutic antibody that induces proteolytic cleavage of the receptor at the cell surface substantially prevents this rebound effect, providing a rationale to combine or alternate these mechanistically different types of MET-targeted therapy. Cancer Res; 76(17); 5019-29. ©2016 AACR. PMID:27364553

  13. An Innovative Course Featuring Action Research Integrated with Unifying Science Themes

    NASA Astrophysics Data System (ADS)

    Otto, Charlotte A.; Luera, Gail R.; Everett, Susan A.

    2009-12-01

    In this article, we describe an innovative capstone course for preservice K-8 teachers integrating action research and a unifying theme in science (AAAS in Science for all Americans. Oxford University Press, New York, 1989; NRC in National science education standards. National Academy Press, Washington, DC, 1996). The goals of the capstone course are to increase student knowledge of the unifying theme, improve written communication skills, and introduce students to educational research. We provide evidence that each of these goals is met. Student growth in theme knowledge is demonstrated through concept maps, questionnaires, and previously reported assessments. Improved writing ability is demonstrated using the spelling and grammar checking feature of Microsoft Word. The analysis of action research reports demonstrates that students are able to connect their action research project results to previous research.

  14. Could the organ shortage ever be met?

    PubMed

    Levitt, Mairi

    2015-01-01

    The organ shortage is commonly presented as having a clear solution, increase the number of organs donated and the problem will be solved. In the light of the Northern Ireland Assembly's consultation on moving to an opt-out organ donor register this article focuses on the social factors and complexities which impact strongly on both the supply of, and demand for, transplantable organs. Judging by the experience of other countries presumed consent systems may or may not increase donations but have not met demand. Donation rates have risen considerably in all parts of the UK recently but there is also an increasing demand for organs. Looking at international donation rates and attitudes, future demand for organs and education on donation, the question is whether the organ shortage could ever be met. The increase in longevity, in rates of diabetes and obesity and in alcohol related liver disease all contribute both to increased demand for transplants, and re-transplants, and a reduction in the number of usable organs. It is unlikely that demand could ever be met, since, if supply was unlimited, the focus would move to financial resources and competing demands on the health care budget in a publicly funded health system. These factors point to the need to focus on ways of reducing, or at least stabilizing, demand where lifestyle factors contribute to the underlying disease. PMID:26201829

  15. Smart Polymeric Nanocarriers of Met-enkephalin.

    PubMed

    Szweda, Roza; Trzebicka, Barbara; Dworak, Andrzej; Otulakowski, Lukasz; Kosowski, Dominik; Hertlein, Justyna; Haladjova, Emi; Rangelov, Stanislav; Szweda, Dawid

    2016-08-01

    This study describes a novel approach to polymeric nanocarriers of the therapeutic peptide met-enkephalin based on the aggregation of thermoresponsive polymers. Thermoresponsive bioconjugate poly((di(ethylene glycol) monomethyl ether methacrylate)-ran-(oligo(ethylene glycol) monomethyl ether methacrylate) is synthesized by AGET ATRP using modified met-enkephalin as a macroinitiator. The abrupt heating of bioconjugate water solution leads to the self-assembly of bioconjugate chains and the formation of mesoglobules of controlled sizes. Mesoglobules formed by bioconjugates are stabilized by coating with cross-linked two-layer shell via nucleated radical polymerization of N-isopropylacrylamide using a degradable cross-linker. The targeting peptide RGD, containing the fluorescence marker carboxyfluorescein, is linked to a nanocarrier during the formation of the outer shell layer. In the presence of glutathione, the whole shell is completely degradable and the met-enkephalin conjugate is released. It is anticipated that precisely engineered nanoparticles protecting their cargo will emerge as the next-generation platform for cancer therapy and many other biomedical applications. PMID:27409457

  16. Truncated RAF kinases drive resistance to MET inhibition in MET-addicted cancer cells

    PubMed Central

    Petti, Consalvo; Picco, Gabriele; Martelli, Maria Luisa; Trisolini, Elena; Bucci, Enrico; Perera, Timothy; Isella, Claudio; Medico, Enzo

    2015-01-01

    Constitutively active receptor tyrosine kinases (RTKs) are known oncogenic drivers and provide valuable therapeutic targets in many cancer types. However, clinical efficacy of RTK inhibitors is limited by intrinsic and acquired resistance. To identify genes conferring resistance to inhibition of the MET RTK, we conducted a forward genetics screen in the GTL-16 gastric cancer cell line, carrying MET amplification and exquisitely sensitive to MET inhibition. Cells were transduced with three different retroviral cDNA expression libraries and selected for growth in the presence of the MET inhibitor PHA-665752. Selected cells displayed robust and reproducible enrichment of library-derived cDNAs encoding truncated forms of RAF1 and BRAF proteins, whose silencing reversed the resistant phenotype. Transduction of naïve GTL-16 cells with truncated, but not full length, RAF1 and BRAF conferred in vitro and in vivo resistance to MET inhibitors, which could be reversed by MEK inhibition. Induction of resistance by truncated RAFs was confirmed in other MET-addicted cell lines, and further extended to EGFR-addicted cells. These data show that truncated RAF1 and BRAF proteins, recently described as products of genomic rearrangements in gastric cancer and other malignancies, have the ability to render neoplastic cells resistant to RTK-targeted therapy. PMID:25473895

  17. Toward a Unifying Hypothesis of Metabolic Syndrome

    PubMed Central

    Bremer, Andrew A.; Mietus-Snyder, Michele

    2012-01-01

    Despite a lack of consistent diagnostic criteria, the metabolic syndrome (MetS) is increasingly evident in children and adolescents, portending a tsunami of chronic disease and mortality as this generation ages. The diagnostic criteria for MetS apply absolute cutoffs to continuous variables and fail to take into account aging, pubertal changes, and race/ethnicity. We attempt to define MetS mechanistically to determine its specific etiologies and to identify targets for therapy. Whereas the majority of studies document a relationship of visceral fat to insulin resistance, ectopic liver fat correlates better with dysfunctional insulin dynamics from which the rest of MetS derives. In contrast to the systemic metabolism of glucose, the liver is the primary metabolic clearinghouse for 4 specific foodstuffs that have been associated with the development of MetS: trans-fats, branched-chain amino acids, ethanol, and fructose. These 4 substrates (1) are not insulin regulated and (2) deliver metabolic intermediates to hepatic mitochondria without an appropriate “pop-off” mechanism for excess substrate, enhancing lipogenesis and ectopic adipose storage. Excessive fatty acid derivatives interfere with hepatic insulin signal transduction. Reactive oxygen species accumulate, which cannot be quenched by adjacent peroxisomes; these reactive oxygen species reach the endoplasmic reticulum, leading to a compensatory process termed the “unfolded protein response,” driving further insulin resistance and eventually insulin deficiency. No obvious drug target exists in this pathway; thus, the only rational therapeutic approaches remain (1) altering hepatic substrate availability (dietary modification), (2) reducing hepatic substrate flux (high fiber), or (3) increasing mitochondrial efficiency (exercise). PMID:22351884

  18. Unified theory in the worldline approach

    NASA Astrophysics Data System (ADS)

    Edwards, James P.

    2015-11-01

    We explore unified field theories based on the gauge groups SU (5) and SO (10) using the worldline approach for chiral fermions with a Wilson loop coupling to a background gauge field. Representing path ordering and chiral projection operators with functional integrals has previously reproduced the sum over the chiralities and representations of standard model particles in a compact way. This paper shows that for SU (5) the 5 bar and 10 representations - into which the Georgi-Glashow model places the left-handed fermionic content of the standard model - appear naturally and with the familiar chirality. We carry out the same analysis for flipped SU (5) and uncover a link to SO (10) unified theory. We pursue this by exploring the SO (10) theory in the same framework, the less established unified theory based on SU (6) and briefly consider the Pati-Salam model using SU (4) × SU (2) × SU (2).

  19. A Unified Fault-Tolerance Protocol

    NASA Technical Reports Server (NTRS)

    Miner, Paul; Gedser, Alfons; Pike, Lee; Maddalon, Jeffrey

    2004-01-01

    Davies and Wakerly show that Byzantine fault tolerance can be achieved by a cascade of broadcasts and middle value select functions. We present an extension of the Davies and Wakerly protocol, the unified protocol, and its proof of correctness. We prove that it satisfies validity and agreement properties for communication of exact values. We then introduce bounded communication error into the model. Inexact communication is inherent for clock synchronization protocols. We prove that validity and agreement properties hold for inexact communication, and that exact communication is a special case. As a running example, we illustrate the unified protocol using the SPIDER family of fault-tolerant architectures. In particular we demonstrate that the SPIDER interactive consistency, distributed diagnosis, and clock synchronization protocols are instances of the unified protocol.

  20. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer

    PubMed Central

    Sun, Wenze; Song, Liping; Ai, Ting; Zhang, Yingbing; Gao, Ying; Cui, Jie

    2013-01-01

    The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer (NSCLC) tissues and patient clinicopathologic characteristics and survival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymerase chain reaction (Q-PCR). Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation (P = 0.009). Increased MET gene copy number was significantly associated with lymph node metastasis (P = 0.004) and advanced tumor stage (P = 0.048), while the expression of cyclin D1 was not associated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number (P = 0.002). Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number (P = 0.002 and P = 0.017, respectively). MET-positivity and increased MET gene copy number were significantly associated with poor overall survival (P = 0.003 and P < 0.001, respectively) in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC (P = 0.003 and P = 0.001, respectively). The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcinogenesis and the development of NSCLC, and may represent a target for therapy. PMID:23720678

  1. Selecting Finite Unified Theories with Current Data

    SciTech Connect

    Heinemeyer, S.; Mondragon, M.; Zoupanos, G.

    2008-11-23

    Finite Unified Theories (FUTs) are N = 1 supersymmetric Grand Unified Theories that can be made all-loop finite, leading to a severe reduction of the free parameters. We review the investigation of FUTs based on SU(5) in the context of low-energy phenomenology observables. Using the restrictions from the top and bottom quark masses, it is possible to discriminate between different models. Including further low-energy constraints such as B physics observables, the bound on the lightest Higgs boson mass and the cold dark matter density, we derive the predictions for the supersymmetric particle spectrum and the prospects for discoveries at the LHC.

  2. Technical writing practically unified through industry

    NASA Technical Reports Server (NTRS)

    Houston, L. S.

    1981-01-01

    General background details in the development of a university level technical writing program, based upon the writing tasks of the student's occupations, are summarized. Objectives and methods for unifying the courses of study with the needs of industry are discussed. Four academic course divisions, Industries Technologies, in which preparation and training are offered are: Animal, Horticulture, Agriculture, and Agricultural Business. Occupational competence is cited as the main goal for these programs in which technical writing is to be practically unified through industry. Course descriptions are also provided.

  3. ARM mobile facility surface meteorology (MET) handbook.

    SciTech Connect

    Ritsche, M. T.; Environmental Science Division

    2006-04-01

    The Atmospheric Radiation Measurement (ARM) Mobile Facility Surface Meteorology station (MET) uses mainly conventional in situ sensors to obtain 1-min statistics of surface wind speed, wind direction, air temperature, relative humidity (RH), barometric pressure, and rainrate. Additional sensors may be added to or removed from the base set of sensors depending upon the deployment location, climate regime, or programmatic needs. In addition, sensor types may change depending upon the climate regime of the deployment. These changes/additions are noted in Section 3.

  4. MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR tyrosine kinase inhibitors

    PubMed Central

    Kubo, Takafumi; Yamamoto, Hiromasa; Lockwood, William W.; Valencia, Ilse; Soh, Junichi; Peyton, Michael; Jida, Masaru; Otani, Hiroki; Fujii, Tetsuya; Ouchida, Mamoru; Takigawa, Nagio; Kiura, Katsuyuki; Shimizu, Kenji; Date, Hiroshi; Minna, John D.; Varella-Garcia, Marileila; Lam, Wan L.; Gazdar, Adi F.; Toyooka, Shinichi

    2009-01-01

    We analyzed MET protein and copy number in NSCLC with or without EGFR mutations untreated with EGFR tyrosine kinase inhibitors (TKIs). MET copy number was examined in 28 NSCLC and 4 human bronchial epithelial cell lines (HBEC) and 100 primary tumors using quantitative real-time PCR. Positive results were confirmed by array comparative genomic hybridization and fluorescence in-situ hybridization. Total and phospho-MET protein expression was determined in 24 NSCLC and 2 HBEC cell lines using Western blot. EGFR mutations were examined for exon 19 deletions, T790M, and L858R. Knockdown of EGFR with siRNA was performed to examine the relation between EGFR and MET activation. High-level MET amplification was observed in 3 of 28 NSCLC cell lines and in 2 of 100 primary lung tumors that had not been treated with EGFR-TKIs. MET protein was highly expressed and phosphorylated in all the 3 cell lines with high MET amplification. In contrast, 6 NSCLC cell lines showed phospho-MET among 21 NSCLC cell lines without MET amplification (p = 0.042). Furthermore, those 6 cell lines harboring phospho-MET expression without MET amplification were all EGFR mutant (p = 0.0039). siRNA-mediated knockdown of EGFR abolished phospho-MET expression in examined 3 EGFR mutant cell lines of which MET gene copy number was not amplified. By contrast, phospho-MET expression in 2 cell lines with amplified MET gene was not down-regulated by knockdown of EGFR. Our results indicated that MET amplification was present in untreated NSCLC and EGFR mutation or MET amplification activated MET protein in NSCLC. PMID:19117057

  5. Mars MetNet Precursor Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, Ari-Matti; Aleksashkin, Sergey; Guerrero, Héctor; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2013-04-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL), using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. For the precursor mission (MMPM) intended to verify the landing concept and key technology during a real Mars mission all qualification activities are completed and the payload and system flight model components are being manufactured. The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the descent phase starting shortly after separation from the spacecraft. Details of the current MMPM system and payload configuration and their performance parameters will be shown.

  6. 76 FR 66505 - Unified Registration System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-26

    ... in the Federal Register on January 17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo... Federal Register on May 12, 2006 (71 FR 27777). The Board's duties include issuing rules and regulations... structure for the Unified Carrier Registration Agreement in the Federal Register (72 FR 48585). The...

  7. A Unified Stability Property in Spin Glasses

    NASA Astrophysics Data System (ADS)

    Panchenko, Dmitry

    2012-08-01

    Gibbs' measures in the Sherrington-Kirkpatrick type models satisfy two asymptotic stability properties, the Aizenman-Contucci stochastic stability and the Ghirlanda-Guerra identities, which play a fundamental role in our current understanding of these models. In this paper we show that one can combine these two properties very naturally into one unified stability property.

  8. Unified chromatography: Fundamentals, instrumentation and applications.

    PubMed

    Silva, Meire R; Andrade, Felipe N; Fumes, Bruno H; Lanças, Fernando M

    2015-09-01

    The concept of unified chromatography has been in existence for 50 years after the work of Giddings proposing that all modes of chromatography (gas chromatography, liquid chromatography, supercritical fluid chromatography and so on) may be treated together under a single unified theory. His idea was partially fulfilled 23 years later by Ishii, Takeuchi and colleagues, who demonstrated for the first time the possibility to analyze a complex sample containing substances with a wide range of boiling points and polarities in the same instrument and column, just by varying the mobile phase pressure and temperature to change from one chromatographic mode to another. This approach has been demonstrated through application to the separation of complex mixtures in several areas including crude oil, edible oils and polymers. Still, unified chromatography has not yet been fully developed. In the present work, we will review the fundamentals, instrumentation and several applications of the technique. Also discussed are the drawbacks that still hinder development, as well as the recent developments and trends in instrumentation and columns that suggest the most feasible ways forward to the full development of unified chromatography. PMID:26105757

  9. Vertically Integrated Nanowire-Based Unified Memory.

    PubMed

    Lee, Byung-Hyun; Ahn, Dae-Chul; Kang, Min-Ho; Jeon, Seung-Bae; Choi, Yang-Kyu

    2016-09-14

    A vertically integrated nanowire-based device for multifunctional unified memory that combine dynamic random access memory (DRAM) and flash memory in a single transistor is demonstrated for the first time. The device utilizes a gate-all-around (GAA) structure that completely surrounds the nanowire; the structure is built on a bulk silicon wafer. A vertically integrated unified memory (VIUM) device composed of five-story channels was fabricated via the one-route all-dry etching process (ORADEP) with reliable reproducibility, stiction-free stability, and high uniformity. In each DRAM and flash memory operation, the five-story VIUM showed a remarkably enhanced sensing current drivability compared with one-story unified memory (UM) characteristics. In addition to each independent memory mode, the switching endurance of the VIUM was evaluated in the unified mode, which alternatively activates two memory modes, resulting in an even higher sensing memory window than that of the UM. In addition to our previous work on a logic transistor joining high performance with good scalability, this work describes a novel memory hierarchy design with high functionality for system-on-chip (SoC) architectures, demonstrating the practicality and versatility of the vertically integrated nanowire configuration for use in various applications. PMID:27579769

  10. Molecular selection in a unified evolutionary sequence

    NASA Technical Reports Server (NTRS)

    Fox, S. W.

    1986-01-01

    With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

  11. Toward a Unified Theory of Reading

    ERIC Educational Resources Information Center

    Sadoski, Mark; Paivio, Allan

    2007-01-01

    Despite nearly 40 years of scientific theorizing about reading, the field remains fragmented with little progress toward unification. In this article, we (a) emphasize the privileged position of unified theories in all science, (b) compare the growth of theory in cognitive science and reading, (c) identify the phenomenal domain of a unified…

  12. Unified perspective on proteins: A physics approach

    NASA Astrophysics Data System (ADS)

    Banavar, Jayanth R.; Hoang, Trinh X.; Maritan, Amos; Seno, Flavio; Trovato, Antonio

    2004-10-01

    We study a physical system which, while devoid of the complexity one usually associates with proteins, nevertheless displays a remarkable array of proteinlike properties. The constructive hypothesis that this striking resemblance is not accidental not only leads to a unified framework for understanding protein folding, amyloid formation, and protein interactions but also has implications for natural selection.

  13. Unified Technical Concepts. Math for Technicians.

    ERIC Educational Resources Information Center

    Center for Occupational Research and Development, Inc., Waco, TX.

    Unified Technical Concepts (UTC) is a modular system for teaching applied physics in two-year postsecondary technician programs. This UTC classroom textbook, consisting of 10 chapters, deals with mathematical concepts as they apply to the study of physics. Addressed in the individual chapters of the text are the following topics: angles and…

  14. Unified Technical Concepts. Application Modules Volume II.

    ERIC Educational Resources Information Center

    Center for Occupational Research and Development, Inc., Waco, TX.

    Unified Technical Concepts (UTC) is a modular system for teaching applied physics in two-year postsecondary technician programs. This UTC laboratory textbook, the second of two volumes, consists of 45 learning modules dealing with basic concepts of physics. Addressed in the individual chapters of the guide are the following topics: force…

  15. Unified Technical Concepts. Physics for Technicians.

    ERIC Educational Resources Information Center

    Center for Occupational Research and Development, Inc., Waco, TX.

    Unified Technical Concepts (UTC) is a modular system for teaching applied physics in two-year postsecondary programs. This UTC classroom textbook, consisting of 14 chapters, deals with physics for technicians. Addressed in the individual chapters of the guide are the following topics: force, work, rate, momentum, resistance, power, potential and…

  16. A Unified Introduction to Ordinary Differential Equations

    ERIC Educational Resources Information Center

    Lutzer, Carl V.

    2006-01-01

    This article describes how a presentation from the point of view of differential operators can be used to (partially) unify the myriad techniques in an introductory course in ordinary differential equations by providing students with a powerful, flexible paradigm that extends into (or from) linear algebra. (Contains 1 footnote.)

  17. A Unifying Curriculum for Museum-Schools

    ERIC Educational Resources Information Center

    Povis, Kaleen E.

    2011-01-01

    There are over two dozen schools in the United States with the word "museum" in their names. However, the philosophy and pedagogy that tie these schools together is unclear. A consistent definition, criteria for classification, and a unifying curriculum to guide museum- schools is lacking. Yet, museum-schools continue to open across the country.…

  18. Unifying Quantitative Methodology in Social Research.

    ERIC Educational Resources Information Center

    Willson, Victor L.

    A case is made for representing quantitative methods in use in the social sciences within a unified framework based on structural equation methodology (SEM). Most of the methods now in use are shown in their SEM representation. It is suggested that the visual and verbal representations of SEM are of most use, while specific estimation and…

  19. A Grand Unified Theory of Interdisciplinarity

    ERIC Educational Resources Information Center

    Davis, Lennard J.

    2007-01-01

    Aside from the appeal to administrators as a tool to reduce costs by combining less robust departments with heftier relations, interdisciplinarity is a powerful idea because it implies that different branches of knowledge can benefit from talking to one another: a grand, unified theory of knowledge in which each discipline contributes building…

  20. Gastrointestinal malignancies harbor actionable MET exon 14 deletions

    PubMed Central

    Hong, Mineui; Kim, Sun Young; Jang, Jiryeon; Ahn, Soomin; Kang, So Young; Lee, Sujin; Kim, Seung Tae; Kim, Bogyou; Choi, Jaehyun; Kim, Kyung-Ah; Lee, Jiyun; Park, Charny; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Keunchil; Park, Young Suk; Kim, Kyoung-Mee

    2015-01-01

    Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies. PMID:26375439

  1. 19 CFR 10.133 - Conditions required to be met.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Conditions required to be met. 10.133 Section 10... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification of any article is controlled by its actual use in the United States, three conditions must be met...

  2. 19 CFR 10.133 - Conditions required to be met.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Conditions required to be met. 10.133 Section 10... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification of any article is controlled by its actual use in the United States, three conditions must be met...

  3. 19 CFR 10.133 - Conditions required to be met.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Conditions required to be met. 10.133 Section 10... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification of any article is controlled by its actual use in the United States, three conditions must be met...

  4. 19 CFR 10.133 - Conditions required to be met.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Conditions required to be met. 10.133 Section 10... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification of any article is controlled by its actual use in the United States, three conditions must be met...

  5. 19 CFR 10.133 - Conditions required to be met.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Conditions required to be met. 10.133 Section 10... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification of any article is controlled by its actual use in the United States, three conditions must be met...

  6. 34 CFR 461.46 - What requirements for program reviews and evaluations must be met by a State?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Program (See 34 CFR part 463). (Approved by the Office of Management and Budget under control number 1830... 34 Education 3 2010-07-01 2010-07-01 false What requirements for program reviews and evaluations... requirements for program reviews and evaluations must be met by a State? (a) An SEA shall provide for...

  7. 34 CFR 461.46 - What requirements for program reviews and evaluations must be met by a State?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Program (See 34 CFR part 463). (Approved by the Office of Management and Budget under control number 1830... 34 Education 3 2011-07-01 2011-07-01 false What requirements for program reviews and evaluations... requirements for program reviews and evaluations must be met by a State? (a) An SEA shall provide for...

  8. National Symposium for Business and Office Education Curriculum Guidelines.

    ERIC Educational Resources Information Center

    Kingston, Carmela C.; Thomas, Ellis R.

    Symposium participants met to develop guidelines for developing curriculum for the area of business and office education, K through adult. The session reports are presented in outline form according to topic definition, problem areas, and recommendations. Topics discussed include: organizational patterns in the business and office education…

  9. Tidal analysis of Met rocket wind data

    NASA Technical Reports Server (NTRS)

    Bedinger, J. F.; Constantinides, E.

    1976-01-01

    A method of analyzing Met Rocket wind data is described. Modern tidal theory and specialized analytical techniques were used to resolve specific tidal modes and prevailing components in observed wind data. A representation of the wind which is continuous in both space and time was formulated. Such a representation allows direct comparison with theory, allows the derivation of other quantities such as temperature and pressure which in turn may be compared with observed values, and allows the formation of a wind model which extends over a broader range of space and time. Significant diurnal tidal modes with wavelengths of 10 and 7 km were present in the data and were resolved by the analytical technique.

  10. Depleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic Advantage over Inhibiting HGF/MET Signaling.

    PubMed

    Hultberg, Anna; Morello, Virginia; Huyghe, Leander; De Jonge, Natalie; Blanchetot, Christophe; Hanssens, Valérie; De Boeck, Gitte; Silence, Karen; Festjens, Els; Heukers, Raimond; Roux, Benjamin; Lamballe, Fabienne; Ginestier, Christophe; Charafe-Jauffret, Emmanuelle; Maina, Flavio; Brouckaert, Peter; Saunders, Michael; Thibault, Alain; Dreier, Torsten; de Haard, Hans; Michieli, Paolo

    2015-08-15

    Hepatocyte growth factor (HGF) and its receptor MET represent validated targets for cancer therapy. However, HGF/MET inhibitors being explored as cancer therapeutics exhibit cytostatic activity rather than cytotoxic activity, which would be more desired. In this study, we engineered an antagonistic anti-MET antibody that, in addition to blocking HGF/MET signaling, also kills MET-overexpressing cancer cells by antibody-dependent cellular cytotoxicity (ADCC). As a control reagent, we engineered the same antibody in an ADCC-inactive form that is similarly capable of blocking HGF/MET activity, but in the absence of any effector function. In comparing these two antibodies in multiple mouse models of cancer, including HGF-dependent and -independent tumor xenografts, we determined that the ADCC-enhanced antibody was more efficacious than the ADCC-inactive antibody. In orthotopic mammary carcinoma models, ADCC enhancement was crucial to deplete circulating tumor cells and to suppress metastases. Prompted by these results, we optimized the ADCC-enhanced molecule for clinical development, generating an antibody (ARGX-111) with improved pharmacologic properties. ARGX-111 competed with HGF for MET binding, inhibiting ligand-dependent MET activity, downregulated cell surface expression of MET, curbing HGF-independent MET activity, and engaged natural killer cells to kill MET-expressing cancer cells, displaying MET-specific cytotoxic activity. ADCC assays confirmed the cytotoxic effects of ARGX-111 in multiple human cancer cell lines and patient-derived primary tumor specimens, including MET-expressing cancer stem-like cells. Together, our results show how ADCC provides a therapeutic advantage over conventional HGF/MET signaling blockade and generates proof-of-concept for ARGX-111 clinical testing in MET-positive oncologic malignancies. PMID:26141862

  11. Accelerometer Output and MET Values of Common Physical Activities

    PubMed Central

    Kozey, Sarah L.; Lyden, Kate; Howe, Cheryl A.; Staudenmayer, John W.; Freedson, Patty S.

    2010-01-01

    Purpose This paper 1) provides the calibration procedures and methods for metabolic and activity monitor data collection, 2) compares measured MET values to the MET values from the Compendium of Physical Activities, and 3) examines the relationship between accelerometer output and METs for a range of physical activities Methods Participants (n=277) completed 11 activities for seven minutes each from a menu of 23 physical activities. Oxygen consumption (VO2) was measured using a portable metabolic system and an accelerometer was worn. MET values were defined as follows; measuredMETs (VO2/measured RMR) and standardMETs (VO2/3.5ml·kg·min−1). For the total sample and by sub-group (age [young <40y], sex and BMI [normal-weight <25 kg·m2]), measuredMETs and standardMETs were compared to the Compendium, using 95% confidence intervals to determine statistical significance (α=0.05). Average count·min−1 for each activity and the linear association between count·min−1 and METs are presented. Results Compendium METs were different than measured METs for 17/21 activities (81%). The number of activities different than the Compendium were similar between sub-groups or when standard METs were used. The average counts for the activities ranged from 11 counts·min−1(dishes) to 7490 counts·min−1 (2.23m·s−1, 3%) The r2 between counts and METs was 0.65. Conclusions This study provides valuable information about data collection, metabolic responses, and accelerometer output for common physical activities in a diverse participant sample. The Compendium should be updated with additional empirical data and linear regression models are inappropriate for accurately predicting METs from accelerometer output. PMID:20142781

  12. Unified Viscoplastic Behavior of Metal Matrix Composites

    NASA Technical Reports Server (NTRS)

    Arnold, S. M.; Robinson, D. N.; Bartolotta, P. A.

    1992-01-01

    The need for unified constitutive models was recognized more than a decade ago in the results of phenomenological tests on monolithic metals that exhibited strong creep-plasticity interaction. Recently, metallic alloys have been combined to form high-temperature ductile/ductile composite materials, raising the natural question of whether these metallic composites exhibit the same phenomenological features as their monolithic constituents. This question is addressed in the context of a limited, yet definite (to illustrate creep/plasticity interaction) set of experimental data on the model metal matrix composite (MMC) system W/Kanthal. Furthermore, it is demonstrated that a unified viscoplastic representation, extended for unidirectional composites and correlated to W/Kanthal, can accurately predict the observed longitudinal composite creep/plasticity interaction response and strain rate dependency. Finally, the predicted influence of fiber orientation on the creep response of W/Kanthal is illustrated.

  13. A unified approach to computational drug discovery.

    PubMed

    Tseng, Chih-Yuan; Tuszynski, Jack

    2015-11-01

    It has been reported that a slowdown in the development of new medical therapies is affecting clinical outcomes. The FDA has thus initiated the Critical Path Initiative project investigating better approaches. We review the current strategies in drug discovery and focus on the advantages of the maximum entropy method being introduced in this area. The maximum entropy principle is derived from statistical thermodynamics and has been demonstrated to be an inductive inference tool. We propose a unified method to drug discovery that hinges on robust information processing using entropic inductive inference. Increasingly, applications of maximum entropy in drug discovery employ this unified approach and demonstrate the usefulness of the concept in the area of pharmaceutical sciences. PMID:26189935

  14. Accuracy of the Unified Sheath Model

    NASA Astrophysics Data System (ADS)

    Riley, Merle E.

    1997-10-01

    The Unified Sheath Model ( M. E. Riley, Sandia Labs Tech Reports SAND95-0775 UC-401 (May, 1995) and SAND96-1948 UC-401 (August, 1996)) is designed to bridge the intermediate region of ion response between the high frequency Lieberman model and the low frequency Metze, Ernie, and Oskam model. In order to make a quantitative check of the effective ion response time (inverse ion plasma radian frequency at the presheath boundary), I have compared the semi-analytic Unified Model predictions to time- and space-dependent numerical solutions of the ion fluid equations in an rf-biased plasma sheath. In so doing, one is testing the most crucial of the physical approximations made in the model. The comparisons are good and lend confidence to use of the sheath model in the simulation of rf-biased plasmas in processing applications.

  15. A survey of unified constitutive theories

    NASA Technical Reports Server (NTRS)

    Chan, K. S.; Lindholm, U. S.; Bodner, S. R.; Walker, K. P.

    1985-01-01

    The state of the art of time temperature dependent elastic viscoplastic constitutive theories which are based on the unified approach werre assessed. This class of constitutive theories is characterized by the use of kinetic equations and internal variables with appropriate evolutionary equations for treating all aspects of inelastic deformation including plasticity, creep, and stress relaxation. More than 10 such unified theories which are shown to satisfy the uniqueness and stability criteria imposed by Drucker's postulate and Ponter's inequalities are identified. The theories are compared for the types of flow law, kinetic equation, evolutionary equation of the internal variables, and treatment of temperature dependence. The similarities and differences of these theories are outlined in terms of mathematical formulations and illustrated by comparisons of theoretical calculations with experimental results which include monotonic stress-strain curves, cyclic hysteresis loops, creep and stress relaxation rates, and thermomechanical loops. Numerical methods used for integrating these stiff time temperature dependent constitutive equations are reviewed.

  16. Embodiment as a unifying perspective for psychology.

    PubMed

    Glenberg, Arthur M

    2010-07-01

    A basic claim of the embodiment framework is that all psychological processes are influenced by body morphology, sensory systems, motor systems, and emotions. As such, the framework holds the promise of providing a unifying perspective for psychological research. This article begins with a sketch of several arguments, from evolution to philosophy, as to why the embodiment framework is a good bet. These arguments are followed by a review of approaches to embodiment, including those from cognitive linguistics, perceptual symbol theory, and action-based theories. Finally, examples are provided for how a unifying perspective might work for cognition (including language and memory), cognitive and social development, social psychology, neuroscience, clinical psychology, and psychology applied to education. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID:26271505

  17. Shuttle unified navigation filter, revision 1

    NASA Technical Reports Server (NTRS)

    Muller, E. S., Jr.

    1973-01-01

    Equations designed to meet the navigation requirements of the separate shuttle mission phases are presented in a series of reports entitled, Space Shuttle GN and C Equation Document. The development of these equations is based on performance studies carried out for each particular mission phase. Although navigation equations have been documented separately for each mission phase, a single unified navigation filter design is embodied in these separate designs. The purpose of this document is to present the shuttle navigation equations in a form in which they would most likely be coded-as the single unified navigation filter used in each mission phase. This document will then serve as a single general reference for the navigation equations replacing each of the individual mission phase navigation documents (which may still be used as a description of a particular navigation phase).

  18. Unified models of inflation and quintessence

    NASA Astrophysics Data System (ADS)

    Gonzalez, Andro; Matos, Tonatiuh; Quiros, Israel

    2005-04-01

    We apply an extended version of the method developed by Chimento and Jakubi [Int. J. Mod. Phys. D 5, 71 (1996), IMPDEO, 0218-2718, 10.1142/S0218271896000084], to derive exact cosmological (flat) Friedmann-Robertson-Walker solutions in RS2 brane models with a perfect fluid of ordinary matter plus a scalar field fluid trapped on the brane. We found new exact solutions, which could serve to unify inflation and quintessence in a common theoretical framework.

  19. Unified treatment of lifting atmospheric entry

    NASA Technical Reports Server (NTRS)

    Nachtsheim, P. R.; Lehman, L. L.

    1980-01-01

    This paper presents a unified treatment of the effect of lift on peak acceleration during atmospheric entry. Earlier studies were restricted to different regimes because of approximations invoked to solve the same transcendental equation. This paper shows the connection between the earlier studies by employing a general expression for the peak acceleration and obtains solutions to the transcendental equation without invoking the earlier approximations. Results are presented and compared with earlier studies where appropriate.

  20. Unified viscoplastic constitutive equations and their applications

    NASA Technical Reports Server (NTRS)

    Lindholm, U. S.

    1987-01-01

    Unified constitutive equations for time- and temperature-dependent metallic plastic deformation have been applied in FEM simulations of forming processes; increasingly powerful computational tools and physical models are being used to numerically model complex engineering problems. Once confidence has been gained through adequate verification, these numerical models will increasingly replace experimental models. Attention is presently given to the contributions made by physical metallurgy, continuum mechanics, and computational mechanics.

  1. Unifying theory for terrestrial research infrastructures

    NASA Astrophysics Data System (ADS)

    Mirtl, Michael

    2016-04-01

    The presentation will elaborate on basic steps needed for building a common theoretical base between Research Infrastructures focusing on terrestrial ecosystems. This theoretical base is needed for developing a better cooperation and integrating in the near future. An overview of different theories will be given and ways to a unifying approach explored. In the second step more practical implications of a theory-guided integration will be developed alongside the following guiding questions: • How do the existing and planned European environmental RIs map on a possible unifying theory on terrestrial ecosystems (covered structures and functions, scale; overlaps and gaps) • Can a unifying theory improve the consistent definition of RÍs scientific scope and focal science questions? • How could a division of tasks between RIs be organized in order to minimize parallel efforts? • Where concretely do existing and planned European environmental RIs need to interact to respond to overarching questions (top down component)? • What practical fora and mechanisms (across RIs) would be needed to bridge the gap between PI driven (bottom up) efforts and the centralistic RI design and operations?

  2. 3D RoboMET Characterization

    SciTech Connect

    Madison, Jonathan D.; Susan, Donald F.; Kilgo, Alice C.

    2015-10-01

    The goal of this project is to generate 3D microstructural data by destructive and non-destructive means and provide accompanying characterization and quantitative analysis of such data. This work is a continuing part of a larger effort to relate material performance variability to microstructural variability. That larger effort is called “Predicting Performance Margins” or PPM. In conjunction with that overarching initiative, the RoboMET.3D™ is a specific asset of Center 1800 and is an automated serialsectioning system for destructive analysis of microstructure, which is called upon to provide direct customer support to 1800 and non-1800 customers. To that end, data collection, 3d reconstruction and analysis of typical and atypical microstructures have been pursued for the purposes of qualitative and quantitative characterization with a goal toward linking microstructural defects and/or microstructural features with mechanical response. Material systems examined in FY15 include precipitation hardened 17-4 steel, laser-welds of 304L stainless steel, thermal spray coatings of 304L and geological samples of sandstone.

  3. A unified analysis and design procedure for a standardized control module for dc-dc switching regulators

    NASA Technical Reports Server (NTRS)

    Lee, F. C.; Yu, Y.; Mahmoud, M. F.

    1980-01-01

    Three basic switching regulators: buck, boost, and buck/boost, employing a multi-loop control module (SCM) were characterized by a common small signal block diagram. Employing the unified model, regulator performances such as stability, audiosusceptibility, output impedance and step load transient are analyzed and key performance indexes are expressed in simple analytical forms. More importantly, the performance characteristics of all three regulators are shown to enjoy common properties due to the unique SCM control scheme which nullifies the positive zero and provides adaptive compensation to the moving poles of the boost and buck/boost converters. This allows a simple unified design procedure to be devised for selecting the key SCM control parameters for an arbitrarily given power stage configuration and parameter values, such that all regulator performance specifications can be met and optimized concurrently in a single design attempt.

  4. MET Inhibition in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Xie, Zuoquan; Lee, Young H.; Boeke, Marta; Jilaveanu, Lucia B.; Liu, Zongzhi; Bottaro, Donald P.; Kluger, Harriet M.; Shuch, Brian

    2016-01-01

    Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID:27390595

  5. Office myomectomy.

    PubMed

    DI Spiezio Sardo, Attilio; Ceci, Oronzo; Zizolfi, Brunella; Nappi, Carmine; Bettocchi, Stefano

    2016-06-01

    Small myomas have a high potential to grow and either to become symptomatic or to cause complications in women of reproductive age. Furthermore, although the risk of malignancy is rare, even the most experienced operator cannot replace the histological analysis to exclude malignancy or premalignant lesions. Such small symptomatic and asymptomatic totally or partially intracavitary myomas may be treated effectively and safety in office setting. The aim of this paper is to describe the currently available hysteroscopic techniques to treat myomas <1.5 cm also with a minimal intramural component without anaesthesia or analgesia in ambulatory setting reducing patient's discomfort. PMID:26928418

  6. Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia.

    PubMed

    Gray, Mary J; Kannu, Peter; Sharma, Swarkar; Neyt, Christine; Zhang, Dongping; Paria, Nandina; Daniel, Philip B; Whetstone, Heather; Sprenger, Hans-Georg; Hammerschmidt, Philipp; Weng, Angela; Dupuis, Lucie; Jobling, Rebekah; Mendoza-Londono, Roberto; Dray, Michael; Su, Peiqiang; Wilson, Megan J; Kapur, Raj P; McCarthy, Edward F; Alman, Benjamin A; Howard, Andrew; Somers, Gino R; Marshall, Christian R; Manners, Simon; Flanagan, Adrienne M; Rathjen, Karl E; Karol, Lori A; Crawford, Haemish; Markie, David M; Rios, Jonathan J; Wise, Carol A; Robertson, Stephen P

    2015-12-01

    The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (MET(Δ14)) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the MET(Δ14) mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone. PMID:26637977

  7. Mars MetNet Mission Pressure and Humidity Devices

    NASA Astrophysics Data System (ADS)

    Haukka, H.; Harri, A.-M.; Schmidt, W.; Genzer, M.; Polkko, J.; Kemppinen, O.; Leinonen, J.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). MetBaro and MetHumi are part of the scientific payload of the MNL. Main scientific goal of both devices is to measure the meteorological phenomena (pressure and humidity) of the Martian atmosphere and complement the previous Mars mission atmospheric measurements (Viking and Phoenix) for better understanding of the Martian atmospheric conditions.

  8. Unified Field Mechanics: A Brief Introduction

    NASA Astrophysics Data System (ADS)

    Amoroso, Richard L.

    Recently we hear more and more physicists saying, `spacetime is doomed', `spacetime is a mirage', the `end of spacetime', `spacetime is not fundamental but emergent' etc. "Henceforth space by itself and time by itself are doomed to fade into the mere shadows, and only a union of the two will preserve an independent reality." - 1908 Hermann Minkowski. We have come full circle from the time of Minkowski's 1908 statement to the brink of an imminent new age of discovery. The basis of our understanding of the natural world has evolved in modern times from Newtonian Mechanics to the 2nd regime of Quantum Mechanics; and now to the threshold of a 3rd regime - Unified Field Mechanics (UFM). The Planck scale stochastic quantum realm can no longer be considered the `basement' or fundamental level of reality. As hard as quantum reality was to imagine so is the fact that the quantum domain is a manifold of finite radius; and that the `sacrosanct - indelible' Quantum Uncertainty Principle can now be surmounted. For decades main stream physicists have been stymied by efforts to reconcile General Relativity with Quantum Mechanics. The stumbling block lies with the two theories conflicting views of space and time: For quantum theory, space and time offer a fixed backcloth against which particles move. In Einstein's relativities, space and time are not only inextricably linked, but the resultant spacetime is warped by the matter within it. In our nascent UFM paradigm for arcane reasons the quantum manifold is not the regime of integration with gravity; it is instead integrated with the domain of the unified field where the forces of nature are deemed to unify. We give a simplistic survey of the fundamental premises of UFM and summarize experimental protocols to falsify the model at this stage of the paradigm's development.

  9. Proposal for a unified CCN nomenclature.

    PubMed

    Brigstock, D R; Goldschmeding, R; Katsube, K-i; Lam, S C-T; Lau, L F; Lyons, K; Naus, C; Perbal, B; Riser, B; Takigawa, M; Yeger, H

    2003-04-01

    A proposal is put forth to unify the nomenclature of the CCN family of secreted, cysteine rich regulatory proteins. In the order of their description in the literature, CCN1 (CYR61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3) constitute a family of matricellular proteins that regulate cell adhesion, migration, proliferation, survival, and differentiation, at least in part through integrin mediated mechanisms. This proposal is endorsed by the International CCN Society and will serve to eliminate confusion from the multiple names that have been given to these molecules. PMID:12665631

  10. Unified formalism for nonautonomous mechanical systems

    NASA Astrophysics Data System (ADS)

    Barbero-Liñán, María; Echeverría-Enríquez, Arturo; Diego, David Martín de; Muñoz-Lecanda, Miguel C.; Román-Roy, Narciso

    2008-06-01

    We present a unified geometric framework for describing both the Lagrangian and Hamiltonian formalisms of regular and nonregular time-dependent mechanical systems, which is based on the approach of Skinner and Rusk ["Generalized Hamiltonian dynamics I. Formulation on T*Q⊗TQ," J. Math. Phys. 24, 2589 (1983)]. The dynamical equations of motion and their compatibility and consistency are carefully studied, making clear that all the characteristics of the Lagrangian and the Hamiltonian formalisms are recovered in this formulation. As an example, a semidiscretization of the nonlinear wave equation is studied, proving the applicability of the proposed formalism.

  11. A Unifying Probabilistic View of Associative Learning

    PubMed Central

    Gershman, Samuel J.

    2015-01-01

    Two important ideas about associative learning have emerged in recent decades: (1) Animals are Bayesian learners, tracking their uncertainty about associations; and (2) animals acquire long-term reward predictions through reinforcement learning. Both of these ideas are normative, in the sense that they are derived from rational design principles. They are also descriptive, capturing a wide range of empirical phenomena that troubled earlier theories. This article describes a unifying framework encompassing Bayesian and reinforcement learning theories of associative learning. Each perspective captures a different aspect of associative learning, and their synthesis offers insight into phenomena that neither perspective can explain on its own. PMID:26535896

  12. Management of the Unified Astronomy Thesaurus

    NASA Astrophysics Data System (ADS)

    Frey, K.; Erdmann, C.; Accomazzi, A.; Rubin, L.; Biemesderfer, C.; Gray, N.; Soles, J.

    2015-04-01

    The Unified Astronomy Thesaurus (UAT) is an open, interoperable, and community-supported thesaurus of astronomical and astrophysical concepts and their relationships. Management of the UAT is based on a community-supported approach. This will ensure that the thesaurus stays current by allowing users to suggest an addition or revision. These suggestions will then be subjected to a thorough expert review process before being accepted for addition to the UAT or rejected. Many leading astronomical institutions, professional associations, journal publishers, learned societies, and data repositories support the UAT as a standard astronomical terminology.

  13. General unifying features of controlled quantum phenomena

    SciTech Connect

    Pechen, Alexander; Brif, Constantin; Wu, Rebing; Chakrabarti, Raj; Rabitz, Herschel

    2010-09-15

    Many proposals have been put forth for controlling quantum phenomena, including open-loop, adaptive feedback, and real-time feedback control. Each of these approaches has been viewed as operationally, and even physically, distinct from the others. This work shows that all such scenarios inherently share the same fundamental control features residing in the topology of the landscape relating the target physical observable to the applied controls. This unified foundation may provide a basis for development of hybrid control schemes that would combine the advantages of the existing approaches to achieve the best overall performance.

  14. Berkeley Unified Parallel C (UPC) Compiler

    Energy Science and Technology Software Center (ESTSC)

    2003-04-06

    This program is a portable, open-source, compiler for the UPC language, which is based on the Open64 framework, and has extensive support for optimizations. This compiler operated by translating UPC into ANS/ISO C for compilation by a native compiler and linking with a UPC Runtime Library. This design eases portability to both shared and distributed memory parallel architectures. For proper operation the "Berkeley Unified Parallel C (UPC) Runtime Library" and its dependencies are required. Compatiblemore » replacements which implement "The Berkeley UPC Runtime Specification" are possible.« less

  15. A Unifying Probabilistic View of Associative Learning.

    PubMed

    Gershman, Samuel J

    2015-11-01

    Two important ideas about associative learning have emerged in recent decades: (1) Animals are Bayesian learners, tracking their uncertainty about associations; and (2) animals acquire long-term reward predictions through reinforcement learning. Both of these ideas are normative, in the sense that they are derived from rational design principles. They are also descriptive, capturing a wide range of empirical phenomena that troubled earlier theories. This article describes a unifying framework encompassing Bayesian and reinforcement learning theories of associative learning. Each perspective captures a different aspect of associative learning, and their synthesis offers insight into phenomena that neither perspective can explain on its own. PMID:26535896

  16. SO(10) unified theories and cosmology

    NASA Astrophysics Data System (ADS)

    Buccella, F.; Mangano, G.; Pisanti, O.; Rosa, L.

    1998-06-01

    We review the status of a class of gauge unified models based on SO(10) group. After a pedagogical introduction to SO(10) gauge theories, we discuss the main phenomenological implications of these models. The upper limit on proton lifetime are obtained and the prediction for neutrino masses are compared with the astrophysical and cosmological constraints coming from solar neutrino data and dark matter problem. Possible scenarios for the production of the baryon asymmetry of the universe required by primordial nucleosynthesis are also discussed.

  17. Structure of the fMet-tRNAfMet-binding domain of B.stearothermophilus initiation factor IF2

    PubMed Central

    Meunier, Sylvie; Spurio, Roberto; Czisch, Michael; Wechselberger, Rainer; Guenneugues, Marc; Gualerzi, Claudio O.; Boelens, Rolf

    2000-01-01

    The three-dimensional structure of the fMet-tRNAfMet -binding domain of translation initiation factor IF2 from Bacillus stearothermophilus has been determined by heteronuclear NMR spectroscopy. Its structure consists of six antiparallel β-strands, connected via loops, and forms a closed β-barrel similar to domain II of elongation factors EF-Tu and EF-G, despite low sequence homology. Two structures of the ternary complexes of the EF-Tu⋅aminoacyl-tRNA⋅ GDP analogue have been reported and were used to propose and discuss the possible fMet-tRNAfMet-binding site of IF2. PMID:10775275

  18. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping

    PubMed Central

    Paik, Paul K.; Drilon, Alexander; Fan, Pang-Dian; Yu, Helena; Rekhtman, Natasha; Ginsberg, Michelle S.; Borsu, Laetitia; Schultz, Nikolaus; Berger, Michael F.; Rudin, Charles M.; Ladanyi, Marc

    2015-01-01

    Mutations in the MET exon 14 RNA splice acceptor and donor sites, which lead to exon skipping, deletion of the juxtamembrane domain containing the Cbl E3-ubiquitin ligase binding site, and decreased turnover of the resultant aberrant MET protein, were previously reported to be oncogenic in preclinical models. We now report responses to the MET inhibitors crizotinib and cabozantinib in four patients with stage IV lung adenocarcinomas harboring mutations leading to MET exon 14 skipping, highlighting a new therapeutic strategy for the 4% of lung adenocarcinoma patients whose tumors harbor this previously underappreciated genetic alteration. PMID:25971939

  19. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    PubMed Central

    Shuch, Brian; Falbo, Ryan; Parisi, Fabio; Adeniran, Adebowale; Kluger, Yuval; Kluger, Harriet M.; Jilaveanu, Lucia B.

    2015-01-01

    Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P = 0.1). MET expression weakly correlated between primary and matched metastatic sites (R = 0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P = 0.39). Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents. PMID:26448928

  20. Improving our understanding of tropical convection using multi-day kilometre-scale Unified Model simulations of the Indian Monsoon

    NASA Astrophysics Data System (ADS)

    Stratton, R. A.; Webster, S.

    2012-12-01

    At the UK Met Office the Unified Model is used operationally for both global and limited area numerical weather prediction. The current global model has a horizontal resolution of 25 km whilst the finest resolution limited area model (LAM) for the United Kingdom region has a grid length of 1.5 km. In the former, atmospheric convection is parametrized whilst in the latter it is represented explicitly. In this study we use the 1.5 km model to simulate explicitly the convection over the Indian Monsoon region. The 1.5 km model is significantly modified from the version used operationally over the UK and so, amongst other things, the vertical resolution above 10 km is greatly improved so that the termination of deep convection is better resolved. The 1.5 km model has been run over a domain of 4500 km x 4500 km for selected periods of up to a week for the 2011 monsoon season. Careful implementation of the lateral boundary conditions has enabled the 1.5 km model to be nested directly inside the 25km global NWP model. The global model is run for six hours between successive operational analyses so that the lateral boundary conditions provided to the 1.5 km model are as close to reality as possible. Since it is no longer necessary to use intermediate resolution LAMs to nest the 1.5 km model inside the global model, additional independent LAM simulations at 4 km, 24 km and 120 km resolutions have been performed. The initial and lateral boundary conditions for these LAM simulations are identical to those for the 1.5 km model and so this set of four LAM simulations permits a direct assessment of the impact of model resolution on the simulation of the Indian Monsoon. The 4km model is configured identically to the 1.5 km whilst the 24 km and 120 km LAMs both parametrize convection and are configured in the same way as the current global NWP and global climate models respectively. Thus, if we can use the 1.5 km model as a high resolution truth, we can assess the performance of

  1. Operating plan for the Office of International Health Programs

    SciTech Connect

    1996-01-01

    In this report unified ideas are presented about what the Office of International Health Programs does, what the individual contributions are, and how the organization connects to the Department of Energy. The planning efforts have focused on the office`s three areas of responsibility: Europe, Japan, and the Marshall Islands. Common to each technical program area are issues related to the following: health of populations exposed to radiation incidents and the associated medical aspects of exposure; dose reconstruction; training; and public involvement. Each of the program areas, its customers, and primary customer interests are described.

  2. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration

    PubMed Central

    Piater, Birgit; Doerner, Achim; Guenther, Ralf; Kolmar, Harald; Hock, Bjoern

    2015-01-01

    The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF). Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2’-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX). CLN64 and a previously described single-stranded DNA (ssDNA) aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding. PMID:26658271

  3. Success, but Slowly, as Met School Redefines Learning

    ERIC Educational Resources Information Center

    Pearson, George

    2012-01-01

    Seven Oaks Met School, the only high school in Canada that is part of the U.S.-based Big Picture Learning network of innovative schools, graduated its first class this spring. Internships with businesses and institutions in the community are a core element of the Met School experience. Students report on their internship experience, as well as on…

  4. Targeting the HGF/MET signalling pathway in cancer therapy

    PubMed Central

    Cecchi, Fabiola; Rabe, Daniel C.; Bottaro, Donald P.

    2012-01-01

    Introduction Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis and tumor progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Area covered The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programs. The authors review Met structure and function, the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development, as well as the latest clinical trial results. Expert opinion Clinical trials with HGF/Met pathway antagonists show that as a class these agents are well tolerated. Although widespread efficacy was not seen in several completed phase 2 studies, promising results have been reported in lung, gastric, prostate and papillary renal cancer patients treated with these agents. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment are optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control. PMID:22530990

  5. Astronaut Alan Shepard using MET during geological training in Mexico

    NASA Technical Reports Server (NTRS)

    1970-01-01

    Astronaut Alan B. Shepard Jr., commander of the Apollo 14 lunar landing mission, takes a piece of equipment from the Modular Equipment Transporter (MET) during geological and lunar surface simulation training training in the Pinacate volcanic area of northwestern Sonora, Mexico. The MET has been nicknamed 'Rickshaw' after its shape and method of propulsion.

  6. Solving CASMI 2013 with MetFrag, MetFusion and MOLGEN-MS/MS

    PubMed Central

    Schymanski, Emma L.; Gerlich, Michael; Ruttkies, Christoph; Neumann, Steffen

    2014-01-01

    The second Critical Assessment of Small Molecule Identification (CASMI) contest took place in 2013. A joint team from the Swiss Federal Institute of Aquatic Science and Technology (Eawag) and Leibniz Institute of Plant Biochemistry (IPB) participated in CASMI 2013 with an automatic workflow-style entry. MOLGEN-MS/MS was used for Category 1, molecular formula calculation, restricted by the information given for each challenge. MetFrag and MetFusion were used for Category 2, structure identification, retrieving candidates from the compound databases KEGG, PubChem and ChemSpider and joining these lists pre-submission. The results from Category 1 were used to guide whether formula or exact mass searches were performed for Category 2. The Category 2 results were impressive considering the database size and automated regime used, although these could not compete with the manual approach of the contest winner. The Category 1 results were affected by large m/z and ppm values in the challenge data, where strategies beyond pure enumeration from other participants were more successful. However, the combination used for the CASMI 2013 entries was extremely useful for developing decision-making criteria for automatic, high throughput general unknown (non-target) identification and for future contests. PMID:26819879

  7. The unified model, a fully-compressible, non-hydrostatic, deep atmosphere global circulation model, applied to hot Jupiters. ENDGame for a HD 209458b test case

    NASA Astrophysics Data System (ADS)

    Mayne, Nathan J.; Baraffe, Isabelle; Acreman, David M.; Smith, Chris; Browning, Matthew K.; Skålid Amundsen, David; Wood, Nigel; Thuburn, John; Jackson, David R.

    2014-01-01

    We are adapting the global circulation model (GCM) of the UK Met Office, the so-called unified model (UM), for the study of hot Jupiters. In this work we demonstrate the successful adaptation of the most sophisticated dynamical core, the component of the GCM which solves the equations of motion for the atmosphere, available within the UM, ENDGame (Even Newer Dynamics for General atmospheric modelling of the environment). Within the same numerical scheme ENDGame supports solution to the dynamical equations under varying degrees of simplification. We present results from a simple, shallow (in atmospheric domain) hot Jupiter model (SHJ), and a more realistic (with a deeper atmosphere) HD 209458b test case. For both test cases we find that the large-scale, time-averaged (over the 1200 days prescribed test period), dynamical state of the atmosphere is relatively insensitive to the level of simplification of the dynamical equations. However, problems exist when attempting to reproduce the results for these test cases derived from other models. For the SHJ case the lower (and upper) boundary intersects the dominant dynamical features of the atmosphere meaning the results are heavily dependent on the boundary conditions. For the HD 209458b test case, when using the more complete dynamical models, the atmosphere is still clearly evolving after 1200 days, and in a transient state. Solving the complete (deep atmosphere and non-hydrostatic) dynamical equations allows exchange between the vertical and horizontal momentum of the atmosphere, via Coriolis and metric terms. Subsequently, interaction between the upper atmosphere and the deeper more slowly evolving (radiatively inactive) atmosphere significantly alters the results, and acts over timescales longer than 1200 days. Figures 1, 4-8, 10 and 11 are available in electronic form at http://www.aanda.org

  8. Artificial human Met agonists based on macrocycle scaffolds

    PubMed Central

    Ito, Kenichiro; Sakai, Katsuya; Suzuki, Yoshinori; Ozawa, Naoya; Hatta, Tomohisa; Natsume, Tohru; Matsumoto, Kunio; Suga, Hiroaki

    2015-01-01

    Hepatocyte growth factor (HGF) receptor, also known as Met, is a member of the receptor tyrosine kinase family. The Met–HGF interaction regulates various signalling pathways involving downstream kinases, such as Akt and Erk. Met activation is implicated in wound healing of tissues via multiple biological responses triggered by the above-mentioned signalling cascade. Here we report the development of artificial Met-activating dimeric macrocycles. We identify Met-binding monomeric macrocyclic peptides by means of the RaPID (random non-standard peptide integrated discovery) system, and dimerize the respective monomers through rational design. These dimeric macrocycles specifically and strongly activate Met signalling pathways through receptor dimerization and induce various HGF-like cellular responses, such as branching morphogenesis, in human cells. This work suggests our approach for generating dimeric macrocycles as non-protein ligands for cell surface receptors can be useful for developing potential therapeutics with a broad range of potential applications. PMID:25758345

  9. Toward a unifying framework for evolutionary processes

    PubMed Central

    Paixão, Tiago; Badkobeh, Golnaz; Barton, Nick; Çörüş, Doğan; Dang, Duc-Cuong; Friedrich, Tobias; Lehre, Per Kristian; Sudholt, Dirk; Sutton, Andrew M.; Trubenová, Barbora

    2015-01-01

    The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. PMID:26215686

  10. Simplification of the unified gas kinetic scheme.

    PubMed

    Chen, Songze; Guo, Zhaoli; Xu, Kun

    2016-08-01

    The unified gas kinetic scheme (UGKS) is an asymptotic preserving (AP) scheme for kinetic equations. It is superior for transition flow simulation and has been validated in the past years. However, compared to the well-known discrete ordinate method (DOM), which is a classical numerical method solving the kinetic equations, the UGKS needs more computational resources. In this study, we propose a simplification of the unified gas kinetic scheme. It allows almost identical numerical cost as the DOM, but predicts numerical results as accurate as the UGKS. In the simplified scheme, the numerical flux for the velocity distribution function and the numerical flux for the macroscopic conservative quantities are evaluated separately. The equilibrium part of the UGKS flux is calculated by analytical solution instead of the numerical quadrature in velocity space. The simplification is equivalent to a flux hybridization of the gas kinetic scheme for the Navier-Stokes (NS) equations and the conventional discrete ordinate method. Several simplification strategies are tested, through which we can identify the key ingredient of the Navier-Stokes asymptotic preserving property. Numerical tests show that, as long as the collision effect is built into the macroscopic numerical flux, the numerical scheme is Navier-Stokes asymptotic preserving, regardless the accuracy of the microscopic numerical flux for the velocity distribution function. PMID:27627418

  11. Unified slip boundary condition for fluid flows.

    PubMed

    Thalakkottor, Joseph John; Mohseni, Kamran

    2016-08-01

    Determining the correct matching boundary condition is fundamental to our understanding of several everyday problems. Despite over a century of scientific work, existing velocity boundary conditions are unable to consistently explain and capture the complete physics associated with certain common but complex problems, such as moving contact lines and corner flows. The widely used Maxwell and Navier slip boundary conditions make an implicit assumption that velocity varies only in the wall normal direction. This makes their boundary condition inapplicable in the vicinity of contact lines and corner points, where velocity gradient exists both in the wall normal and wall tangential directions. In this paper, by identifying this implicit assumption we are able to extend Maxwell's slip model. Here, we present a generalized velocity boundary condition that shows that slip velocity is a function of not only the shear rate but also the linear strain rate. In addition, we present a universal relation for slip length, which shows that, for a general flow, slip length is a function of the principal strain rate. The universal relation for slip length along with the generalized velocity boundary condition provides a unified slip boundary condition to model a wide range of steady Newtonian fluid flows. We validate the unified slip boundary for simple Newtonian liquids by using molecular dynamics simulations and studying both the moving contact line and corner flow problems. PMID:27627398

  12. Unifying Geometrical Representations of Gauge Theory

    NASA Astrophysics Data System (ADS)

    Alsid, Scott; Serna, Mario

    2015-01-01

    We unify three approaches within the vast body of gauge-theory research that have independently developed distinct representations of a geometrical surface-like structure underlying the vector-potential. The three approaches that we unify are: those who use the compactified dimensions of Kaluza-Klein theory, those who use Grassmannian models (also called gauge theory embedding or models) to represent gauge fields, and those who use a hidden spatial metric to replace the gauge fields. In this paper we identify a correspondence between the geometrical representations of the three schools. Each school was mostly independently developed, does not compete with other schools, and attempts to isolate the gauge-invariant geometrical surface-like structures that are responsible for the resulting physics. By providing a mapping between geometrical representations, we hope physicists can now isolate representation-dependent physics from gauge-invariant physical results and share results between each school. We provide visual examples of the geometrical relationships between each school for electric and magnetic fields. We highlight a first new result: in all three representations a static electric field (electric field from a fixed ring of charge or a sphere of charge) has a hidden gauge-invariant time dependent surface that is underlying the vector potential.

  13. Multicategory Large-Margin Unified Machines

    PubMed Central

    Zhang, Chong; Liu, Yufeng

    2013-01-01

    Hard and soft classifiers are two important groups of techniques for classification problems. Logistic regression and Support Vector Machines are typical examples of soft and hard classifiers respectively. The essential difference between these two groups is whether one needs to estimate the class conditional probability for the classification task or not. In particular, soft classifiers predict the label based on the obtained class conditional probabilities, while hard classifiers bypass the estimation of probabilities and focus on the decision boundary. In practice, for the goal of accurate classification, it is unclear which one to use in a given situation. To tackle this problem, the Large-margin Unified Machine (LUM) was recently proposed as a unified family to embrace both groups. The LUM family enables one to study the behavior change from soft to hard binary classifiers. For multicategory cases, however, the concept of soft and hard classification becomes less clear. In that case, class probability estimation becomes more involved as it requires estimation of a probability vector. In this paper, we propose a new Multicategory LUM (MLUM) framework to investigate the behavior of soft versus hard classification under multicategory settings. Our theoretical and numerical results help to shed some light on the nature of multicategory classification and its transition behavior from soft to hard classifiers. The numerical results suggest that the proposed tuned MLUM yields very competitive performance. PMID:24415909

  14. A unifying description of dark energy

    NASA Astrophysics Data System (ADS)

    Gleyzes, Jérôme; Langlois, David; Vernizzi, Filippo

    2014-01-01

    We review and extend a novel approach that we recently introduced, to describe general dark energy or scalar-tensor models. Our approach relies on an Arnowitt-Deser-Misner (ADM) formulation based on the hypersurfaces where the underlying scalar field is uniform. The advantage of this approach is that it can describe in the same language and in a minimal way a vast number of existing models, such as quintessence, F(R) theories, scalar tensor theories, their Horndeski extensions and beyond. It also naturally includes Horava-Lifshitz theories. As summarized in this review, our approach provides a unified treatment of the linear cosmological perturbations about a Friedmann-Lemaître-Robertson-Walker (FLRW) universe, obtained by a systematic expansion of our general action up to quadratic order. This shows that the behavior of these linear perturbations is generically characterized by five time-dependent functions. We derive the full equations of motion in the Newtonian gauge. In the Horndeski case, we obtain the equation of state for dark energy perturbations in terms of these functions. Our unifying description thus provides the simplest and most systematic way to confront theoretical models with current and future cosmological observations.

  15. Annual report, Office of the Inspector General

    SciTech Connect

    Mansfield, J.K.

    1980-03-01

    Activities during the period January 1, 1979 through December 31, 1979 are reported. First, an overview of the progress and problems encountered by this office during the last calendar year is given. Next, certain matters of concern relating to the independence of the office and the ability to work effectively are discussed. Then progress being made and problems being met in forward planning are reviewed. The existing office organizational and staffing patterns are described in the subsequent section. Then weaknesses of the existing DOE overall audit system are discussed. Work done by the IG audit, inspection, and investigative staffs during 1979 is reviewed. Summaries of significant IG findings and recommendations, and of departmental responses thereto, are included. Finally, follow-through activities and certain developments during 1979 that were of importance to the office are described. (RWR)

  16. Work Stress and Metabolic Syndrome in Police Officers. A Prospective Study

    PubMed Central

    Garbarino, Sergio; Magnavita, Nicola

    2015-01-01

    Objective The aim of this longitudinal study was to evaluate the association between occupational stress and metabolic syndrome (MetS) in a rapid response police unit. Method Work-related stress was continuously monitored during the 5-year period with both the Demand-Control-Support (DCS) and the Effort-Reward Imbalance (ERI) models. Blood pressure, body mass index (BMI), waist circumference, triglycerides, HDL-cholesterol, and fasting blood glucose were measured at baseline in January 2009, and in January 2014. 234 out of 290 police officers (81%) completed the follow-up. Results The majority of police officers had high stress levels. At follow-up, police officers in the highest quartile of stress had significantly higher mean levels of triglycerides, and lower levels of HDL-cholesterol than their colleagues in the lowest quartile. Police officers with high stress had an increased adjusted risk of developing MetS (aOR = 2.68; CI95% = 1.08–6.70), and hypertriglyceridemia (aOR = 7.86; CI95 = 1.29–48.04). Demand and Effort were significant predictors of MetS. Conclusion Our study supports the hypothesis that work-related stress induces MetS, particularly through its effects on blood lipids. Future longitudinal studies with continuous monitoring of stress levels will definitively confirm this hypothesis. PMID:26641879

  17. Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia

    PubMed Central

    Gray, Mary J.; Kannu, Peter; Sharma, Swarkar; Neyt, Christine; Zhang, Dongping; Paria, Nandina; Daniel, Philip B.; Whetstone, Heather; Sprenger, Hans-Georg; Hammerschmidt, Philipp; Weng, Angela; Dupuis, Lucie; Jobling, Rebekah; Mendoza-Londono, Roberto; Dray, Michael; Su, Peiqiang; Wilson, Megan J.; Kapur, Raj P.; McCarthy, Edward F.; Alman, Benjamin A.; Howard, Andrew; Somers, Gino R.; Marshall, Christian R.; Manners, Simon; Flanagan, Adrienne M.; Rathjen, Karl E.; Karol, Lori A.; Crawford, Haemish; Markie, David M.; Rios, Jonathan J.; Wise, Carol A.; Robertson, Stephen P.

    2015-01-01

    The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (METΔ14) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the METΔ14 mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone. PMID:26637977

  18. FOXC2 promotes colorectal cancer metastasis by directly targeting MET.

    PubMed

    Cui, Y-M; Jiao, H-L; Ye, Y-P; Chen, C-M; Wang, J-X; Tang, N; Li, T-T; Lin, J; Qi, L; Wu, P; Wang, S-Y; He, M-R; Liang, L; Bian, X-W; Liao, W-T; Ding, Y-Q

    2015-08-13

    Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC. PMID:25381815

  19. Targeting the oncogenic Met receptor by antibodies and gene therapy.

    PubMed

    Vigna, E; Comoglio, P M

    2015-04-01

    The receptor for hepatocyte growth factor (HGF), a tyrosine kinase encoded by the Met oncogene, has a crucial role in cancer growth, invasion and metastasis. It is a validated therapeutic target for 'personalized' treatment of a number of malignancies. Therapeutic tools prompting selective, robust and highly effective Met inhibition potentially represent a major step in the battle against cancer. Antibodies targeting either Met or its ligand HGF, although challenging, demonstrate to be endowed with promising features. Here we briefly review and discuss the state of the art in the field. PMID:24882574

  20. MetNet Precursor - Network Mission to Mars

    NASA Astrophysics Data System (ADS)

    Harri, Arri-Matti

    2010-05-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The first MetNet vehicle, MetNet Precursor, slated for launch in 2011. The MetNet development work started already in 2001. The actual practical Precursor Mission development work started in January 2009 with participation from various space research institutes and agencies. The scientific rationale and goals as well as key mission solutions will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Time-resolved in situ Martian meteorological measurements acquired by the Viking, Mars Pathfinder and Phoenix landers and remote sensing observations by the Mariner 9, Viking, Mars Global Surveyor, Mars Odyssey and the Mars Express orbiters have provided the basis for our current understanding of the behavior of weather and climate on Mars. However, the available amount of data is still scarce and a wealth of additional in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes to address microscale and mesoscale atmospheric phenomena. Detailed characterization of the Martian atmospheric circulation patterns and climatological cycles requires simultaneous in situ atmospheric observations. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe

  1. Unified Science Approach K-12, Proficiency Levels 7-12.

    ERIC Educational Resources Information Center

    Oickle, Eileen M., Ed.

    Presented is the second part of the K-12 unified science materials used in the public schools of Anne Arundel County, Maryland. Detailed descriptions are made of the roles of students and teachers, purposes of the bibliography, major concepts in unified science, processes of inquiry, a scheme and model for scientific literacy, and program…

  2. 24 CFR 578.41 - Unified Funding Agency costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Unified Funding Agency costs. 578.41 Section 578.41 Housing and Urban Development Regulations Relating to Housing and Urban Development... § 578.41 Unified Funding Agency costs. (a) In general. UFAs may use up to 3 percent of their FPRN, or...

  3. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 12 2014-04-01 2014-04-01 false Unified loss rule. 1.1502-36 Section 1.1502-36 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis, Stock Ownership, and Earnings and Profits Rules § 1.1502-36 Unified loss rule. (a) In general—(1) Scope....

  4. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 12 2013-04-01 2013-04-01 false Unified loss rule. 1.1502-36 Section 1.1502-36 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis, Stock Ownership, and Earnings and Profits Rules § 1.1502-36 Unified loss rule. (a) In general—(1) Scope....

  5. Unified Science Approach K-12, Proficiency Levels 1-6.

    ERIC Educational Resources Information Center

    Oickle, Eileen M., Ed.

    Presented are first-revision materials of the K-12 unified science program implemented in the public schools of Anne Arundel County, Maryland. Detailed descriptions are given of the roles of students and teachers, purposes of bibliography, major concepts in unified science, processes of inquiry, scheme and model for scientific literacy, and…

  6. Educating All Students Together: How School Leaders Create Unified Systems.

    ERIC Educational Resources Information Center

    Burrello, Leonard C.; Lashley, Carl; Beatty, Edith E.

    This book established a plan for creating a truly integrated educational system, one that unifies the separate and parallel systems of special and general education. Chapter 1, "Students at the Margins," explores the dual tragedy of discouraged and disinterested students and presents eight essential questions guiding a unified system of…

  7. UniPOPS: Unified data reduction suite

    NASA Astrophysics Data System (ADS)

    Maddalena, Ronald J.; Garwood, Robert W.; Salter, Christopher J.; Stobie, Elizabeth B.; Cram, Thomas R.; Morgan, Lorrie; Vance, Bob; Hudson, Jerome

    2015-03-01

    UniPOPS, a suite of programs and utilities developed at the National Radio Astronomy Observatory (NRAO), reduced data from the observatory's single-dish telescopes: the Tucson 12-m, the Green Bank 140-ft, and archived data from the Green Bank 300-ft. The primary reduction programs, 'line' (for spectral-line reduction) and 'condar' (for continuum reduction), used the People-Oriented Parsing Service (POPS) as the command line interpreter. UniPOPS unified previous analysis packages and provided new capabilities; development of UniPOPS continued within the NRAO until 2004 when the 12-m was turned over to the Arizona Radio Observatory (ARO). The submitted code is version 3.5 from 2004, the last supported by the NRAO.

  8. Unified theory of nonlinear electrodynamics and gravity

    SciTech Connect

    Torres-Gomez, Alexander; Krasnov, Kirill; Scarinci, Carlos

    2011-01-15

    We describe a class of unified theories of electromagnetism and gravity. The Lagrangian is of the BF type, with a potential for the B field, the gauge group is U(2) (complexified). Given a choice of the potential function the theory is a deformation of (complex) general relativity and electromagnetism, and describes just two propagating polarizations of the graviton and two of the photon. When gravity is switched off the theory becomes the usual nonlinear electrodynamics with a general structure function. The Einstein-Maxwell theory can be recovered by sending some of the parameters of the defining potential to zero, but for any generic choice of the potential the theory is indistinguishable from Einstein-Maxwell at low energies. A real theory is obtained by imposing suitable reality conditions. We also study the spherically-symmetric solution and show how the usual Reissner-Nordstrom solution is recovered.

  9. Unified statistical approach to cortical thickness analysis.

    PubMed

    Chung, Moo K; Robbins, Steve; Evans, Alan C

    2005-01-01

    This paper presents a unified image processing and analysis framework for cortical thickness in characterizing a clinical population. The emphasis is placed on the development of data smoothing and analysis framework. The human brain cortex is a highly convoluted surface. Due to the convoluted non-Euclidean surface geometry, data smoothing and analysis on the cortex are inherently difficult. When measurements lie on a curved surface, it is natural to assign kernel smoothing weights based on the geodesic distance along the surface rather than the Euclidean distance. We present a new data smoothing framework that address this problem implicitly without actually computing the geodesic distance and present its statistical properties. Afterwards, the statistical inference is based on the random field theory based multiple comparison correction. As an illustration, we have applied the method in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children. PMID:17354731

  10. On the History of Unified Field Theories

    NASA Astrophysics Data System (ADS)

    Goenner, Hubert F. M.

    2004-02-01

    This article is intended to give a review of the history of the classical aspects of unified field theories in the 20th century. It includes brief technical descriptions of the theories suggested, short biographical notes concerning the scientists involved, and an extensive bibliography. The present first installment covers the time span between 1914 and 1933, i.e., when Einstein was living and working in Berlin - with occasional digressions into other periods. Thus, the main theme is the unification of the electromagnetic and gravitational fields augmented by short-lived attempts to include the matter field described by Schrödinger's or Dirac's equations. While my focus lies on the conceptual development of the field, by also paying attention to the interaction of various schools of mathematicians with the research done by physicists, some prosopocraphical remarks are included.

  11. Neutrino dark energy in grand unified theories

    NASA Astrophysics Data System (ADS)

    Bhatt, Jitesh R.; Gu, Pei-Hong; Sarkar, Utpal; Singh, Santosh K.

    2009-10-01

    We studied a left-right symmetric model that can accommodate the neutrino dark energy (νDE) proposal. The type-III seesaw mechanism is implemented to give masses to the neutrinos. After explaining the model, we study the consistency of the model by minimizing the scalar potential and obtaining the conditions for the required vacuum expectation values of the different scalar fields. This model is then embedded in an SO(10) grand unified theory and the allowed symmetry breaking scales are determined by the condition of the gauge coupling unification. Although SU(2)R breaking is required to be high, its Abelian subgroup U(1)R is broken in the TeV range, which can then give the required neutrino masses and predicts new gauge bosons that could be detected at LHC. The neutrino masses are studied in detail in this model, which shows that at least 3 singlet fermions are required.

  12. Unified Ultrasonic/Eddy-Current Data Acquisition

    NASA Technical Reports Server (NTRS)

    Chern, E. James; Butler, David W.

    1993-01-01

    Imaging station for detecting cracks and flaws in solid materials developed combining both ultrasonic C-scan and eddy-current imaging. Incorporation of both techniques into one system eliminates duplication of computers and of mechanical scanners; unifies acquisition, processing, and storage of data; reduces setup time for repetitious ultrasonic and eddy-current scans; and increases efficiency of system. Same mechanical scanner used to maneuver either ultrasonic or eddy-current probe over specimen and acquire point-by-point data. For ultrasonic scanning, probe linked to ultrasonic pulser/receiver circuit card, while, for eddy-current imaging, probe linked to impedance-analyzer circuit card. Both ultrasonic and eddy-current imaging subsystems share same desktop-computer controller, containing dedicated plug-in circuit boards for each.

  13. Unified Data Resource for CryoEM

    PubMed Central

    Lawson, Catherine L.

    2010-01-01

    3D cryo-electron microscopy reconstruction methods are uniquely able to reveal structures of many important macromolecules and macromolecular complexes. EMDataBank.org, a joint effort of the Protein Data Bank in Europe (PDBe), the Research Collaboratory for Structural Bioinformatics (RCSB), and the National Center for Macromolecular Imaging (NCMI), is a “one-stop shop” resource for global deposition and retrieval of cryoEM map, model and associated metadata. The resource unifies public access to the two major EM Structural Data archives: EM Data Bank (EMDB) and Protein Data Bank (PDB), and facilitates use of EM structural data of macromolecules and macromolecular complexes by the wider scientific community. PMID:20888470

  14. A unified approach to the Darwin approximation

    SciTech Connect

    Krause, Todd B.; Apte, A.; Morrison, P. J.

    2007-10-15

    There are two basic approaches to the Darwin approximation. The first involves solving the Maxwell equations in Coulomb gauge and then approximating the vector potential to remove retardation effects. The second approach approximates the Coulomb gauge equations themselves, then solves these exactly for the vector potential. There is no a priori reason that these should result in the same approximation. Here, the equivalence of these two approaches is investigated and a unified framework is provided in which to view the Darwin approximation. Darwin's original treatment is variational in nature, but subsequent applications of his ideas in the context of Vlasov's theory are not. We present here action principles for the Darwin approximation in the Vlasov context, and this serves as a consistency check on the use of the approximation in this setting.

  15. Unified detection and tracking in retinal microsurgery.

    PubMed

    Sznitman, Raphael; Basu, Anasuya; Richa, Rogerio; Handa, Jim; Gehlbach, Peter; Taylor, Russell H; Jedynak, Bruno; Hager, Gregory D

    2011-01-01

    Traditionally, tool tracking involves two subtasks: (i) detecting the tool in the initial image in which it appears, and (ii) predicting and refining the configuration of the detected tool in subsequent images. With retinal microsurgery in mind, we propose a unified tool detection and tracking framework, removing the need for two separate systems. The basis of our approach is to treat both detection and tracking as a sequential entropy minimization problem, where the goal is to determine the parameters describing a surgical tool in each frame. The resulting framework is capable of both detecting and tracking in situations where the tool enters and leaves the field of view regularly. We demonstrate the benefits of this method in the context of retinal tool tracking. Through extensive experimentation on a phantom eye, we show that this method provides efficient and robust tool tracking and detection. PMID:22003593

  16. Neutrino dark energy in grand unified theories

    SciTech Connect

    Bhatt, Jitesh R.; Sarkar, Utpal; Singh, Santosh K.; Gu, P.-H.

    2009-10-01

    We studied a left-right symmetric model that can accommodate the neutrino dark energy ({nu}DE) proposal. The type-III seesaw mechanism is implemented to give masses to the neutrinos. After explaining the model, we study the consistency of the model by minimizing the scalar potential and obtaining the conditions for the required vacuum expectation values of the different scalar fields. This model is then embedded in an SO(10) grand unified theory and the allowed symmetry breaking scales are determined by the condition of the gauge coupling unification. Although SU(2){sub R} breaking is required to be high, its Abelian subgroup U(1){sub R} is broken in the TeV range, which can then give the required neutrino masses and predicts new gauge bosons that could be detected at LHC. The neutrino masses are studied in detail in this model, which shows that at least 3 singlet fermions are required.

  17. A unified theory of coronal heating

    NASA Technical Reports Server (NTRS)

    Ionson, J. A.

    1985-01-01

    Solar coronal heating mechanisms are analyzed within the framework of a unified theory of heating processes. The theory is based on the standing wave equation of Ionson (1982) for the global current driven by emfs from the convection Beta less than 1. The equation has the same form as a driven LRC equation in which the equivalent inductance is scaled with the coronal loop length. The theory is used to classify various heating mechanisms inside the coronal loops. It is shown that the total global current can be obtained from an integration of the local currents, the degree of coherency between local currents being the dominant factor governing the global current amplitude. Active region loops appear to be heated by electrodynamic coupling to p-mode oscillations in the convection Beta less than 1.

  18. Hilltop supernatural inflation and SUSY unified models

    SciTech Connect

    Kohri, Kazunori; Lim, C.S.; Lin, Chia-Min; Mimura, Yukihiro E-mail: lim@lab.twcu.ac.jp E-mail: mimura@hep1.phys.ntu.edu.tw

    2014-01-01

    In this paper, we consider high scale (100TeV) supersymmetry (SUSY) breaking and realize the idea of hilltop supernatural inflation in concrete particle physics models based on flipped-SU(5)and Pati-Salam models in the framework of supersymmetric grand unified theories (SUSY GUTs). The inflaton can be a flat direction including right-handed sneutrino and the waterfall field is a GUT Higgs. The spectral index is n{sub s} = 0.96 which fits very well with recent data by PLANCK satellite. There is no both thermal and non-thermal gravitino problems. Non-thermal leptogenesis can be resulted from the decay of right-handed sneutrino which plays (part of) the role of inflaton.

  19. Hilltop supernatural inflation and SUSY unified models

    NASA Astrophysics Data System (ADS)

    Kohri, Kazunori; Lim, C. S.; Lin, Chia-Min; Mimura, Yukihiro

    2014-01-01

    In this paper, we consider high scale (100TeV) supersymmetry (SUSY) breaking and realize the idea of hilltop supernatural inflation in concrete particle physics models based on flipped-SU(5)and Pati-Salam models in the framework of supersymmetric grand unified theories (SUSY GUTs). The inflaton can be a flat direction including right-handed sneutrino and the waterfall field is a GUT Higgs. The spectral index is ns = 0.96 which fits very well with recent data by PLANCK satellite. There is no both thermal and non-thermal gravitino problems. Non-thermal leptogenesis can be resulted from the decay of right-handed sneutrino which plays (part of) the role of inflaton.

  20. Oxidation of Met(144) and Met(145) in Calmodulin Blocks Calmodulin Dependent Activation of the Plasma Membrane Ca-ATPase.

    SciTech Connect

    Bartlett, Ryan K.; Urbauer, Ramona J.; Anbanandam, A; Smallwood, Heather S.; Urbauer, Jeffrey L.; Squier, Thomas C.

    2003-04-15

    Methionine oxidation in calmodulin (CaM) isolated from senescent brain results in an inability to fully activate the plasma membrane (PM) Ca-ATPase which may contribute to observed increases in cytosolic calcium levels under conditions of oxidative stress and biological aging. To identify the functional importance of the oxidation of Met-144 and Met-145 near the carboxyl-terminus of CaM, we have used site-directed mutagenesis to substitute leucines for methionines at other positions in CaM, permitting the site-specific oxidation of Met-144 and Met-145. Prior to the oxidation, the CaM-dependent activation of the PM-CA-ATPase by these CaM mutants is similar to that of wild-type CaM. Likewise, oxidation of individual methionines has a minimal effect on the CaM concentration necessary for half-maximal activation of the PM-Ca-ATPase. These results are consistent with previous suggestions that no single methionine within CaM is essential for activation of the PM-CA-ATPase. Oxidation of either Met-144 or Met-145 or all nine methionines in CaM results in an equivalent inhibition of the PM-Ca-ATPase, resulting in a 50-60% reduction in the level of enzyme activation. Oxidation of Met-144 is largely responsible for the decreased extent of enzyme activation, suggesting that this site is critical in modulating the sensitivity of CaM to oxidant-induced loss-of-function. These results are discussed in terms of a possible functional role for Met-144 and Met-145 in CaM as redox sensors that function to modulate calcium homeostasis and energy metabolism in response to conditions of oxidative stress.

  1. Regular Expression-Based Learning for METs Value Extraction.

    PubMed

    Redd, Douglas; Kuang, Jinqiu; Mohanty, April; Bray, Bruce E; Zeng-Treitler, Qing

    2016-01-01

    Functional status as measured by exercise capacity is an important clinical variable in the care of patients with cardiovascular diseases. Exercise capacity is commonly reported in terms of Metabolic Equivalents (METs). In the medical records, METs can often be found in a variety of clinical notes. To extract METs values, we adapted a machine-learning algorithm called REDEx to automatically generate regular expressions. Trained and tested on a set of 2701 manually annotated text snippets (i.e. short pieces of text), the regular expressions were able to achieve good accuracy and F-measure of 0.89 and 0.86. This extraction tool will allow us to process the notes of millions of cardiovascular patients and extract METs value for use by researchers and clinicians. PMID:27570673

  2. Regular Expression-Based Learning for METs Value Extraction

    PubMed Central

    Redd, Douglas; Kuang, Jinqiu; Mohanty, April; Bray, Bruce E.; Zeng-Treitler, Qing

    2016-01-01

    Functional status as measured by exercise capacity is an important clinical variable in the care of patients with cardiovascular diseases. Exercise capacity is commonly reported in terms of Metabolic Equivalents (METs). In the medical records, METs can often be found in a variety of clinical notes. To extract METs values, we adapted a machine-learning algorithm called REDEx to automatically generate regular expressions. Trained and tested on a set of 2701 manually annotated text snippets (i.e. short pieces of text), the regular expressions were able to achieve good accuracy and F-measure of 0.89 and 0.86. This extraction tool will allow us to process the notes of millions of cardiovascular patients and extract METs value for use by researchers and clinicians. PMID:27570673

  3. ASI/MET Within Color-Enhanced Panorama

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This is a sub-section of the 'geometrically improved, color enhanced' version of the 360-degree panorama heretofore known as the 'Gallery Pan', the first contiguous, uniform panorama taken by the Imager for Mars Pathfinder (IMP) over the course of Sols 8, 9, and 10. Different regions were imaged at different times over the three Martian days to acquire consistent lighting and shadow conditions for all areas of the panorama.

    The IMP is a stereo imaging system that, in its fully deployed configuration, stands 1.8 meters above the Martian surface, and has a resolution of two millimeters at a range of two meters. In this geometrically improved version of the panorama, distortion due to a 2.5 degree tilt in the IMP camera mast has been removed, effectively flattening the horizon.

    The IMP has color capability provided by 24 selectable filters -- twelve filters per 'eye'. Its red, green, and blue filters were used to take this image. The color was digitally balanced according to the color transmittance capability of a high-resolution TV at the Jet Propulsion Laboratory (JPL), and is dependent on that device. In this color enhanced version of the panorama, detail in surface features are brought out via changes to saturation and intensity, holding the original hue constant. A threshold was applied to avoid changes to the sky.

    At the bottom of the image, two of the Lander petals are visible. At the extreme right of the image, the Atmospheric Structure Instrument and Meteorology package (ASI/MET) mast, with its three windsocks, is visible.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract

  4. MMPM - Mission implementation of Mars MetNet Precursor

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.

    2009-04-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The key technical aspects and solutions of the mission will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. This development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development.

  5. Decreased Expression of Met During Differentiation in Rat Lung

    PubMed Central

    Kato, T.; Oka, K.; Nakamura, T.; Ito, A.

    2016-01-01

    Organ-specific stem cells play key roles in maintaining the epithelial cell layers of lung. Bronchioalveolar stem cells (BASCs) are distal lung epithelial stem cells of adult mice. Alveolar type 2 (AT2) cells have important functions and serve as progenitor cells of alveolar type 1 (AT1) cells to repair the epithelium when they are injured. Hepatocyte growth factor (HGF) elicits mitogenic, morphogenic, and anti-apoptotic effects on lung epithelial cells through tyrosine phosphorylation of Met receptor, and thus is recognized as a pulmotrophic factor. To understand which cells HGF targets in lung, we identified the cells expressing Met by immunofluorescence assay. Met was strongly expressed in BASCs, which expressed an AT2 cell marker, pro-SP-C, and a club cell marker, CCSP. In alveoli, we found higher expression of Met in primary AT2 than in AT1 cells, which was confirmed using primary AT2 cells. We further examined the mitogenic activity of HGF in AT2-cell-derived alveolar-like cysts (ALCs) in 3D culture. Multicellular ALCs expressed Met, and HGF enhanced the ALC production. Taking these findings together, BASCs could also be an important target for HGF, and HGF-Met signaling could function more potent on cells that have greater multipotency in adult lung. PMID:26972715

  6. The role of the HGF/Met axis in mesothelioma.

    PubMed

    Thayaparan, Thivyan; Spicer, James F; Maher, John

    2016-04-15

    Malignant mesothelioma is an asbestos-related cancer that occurs most commonly in the pleural space and is incurable. Increasing evidence suggests that aberrant receptor tyrosine kinase (RTK)-directed signalling plays a key role in the pathogenesis of this cancer. In the majority of mesotheliomas, up-regulated expression or signalling by Met, the receptor for hepatocyte growth factor (HGF) can be demonstrated. Following binding of ligand, Met relays signals that promote cell survival, proliferation, movement, invasiveness, branching morphogenesis and angiogenesis. Here we describe the HGF/Met axis and review the mechanisms that lead to the aberrant activation of this signalling system in mesothelioma. We also describe the cross-talk that occurs between HGF/Met and a number of other receptors, ligands and co-receptor systems. The prevalent occurrence of HGF/Met dysregulation in patients with mesothelioma sets the scene for the investigation of pharmaceutical inhibitors of this axis. In light of the inter-relationship between HGF/Met and other ligand receptor, combinatorial targeting strategies may provide opportunities for therapeutic advancement in this challenging tumour. PMID:27068941

  7. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    NASA Astrophysics Data System (ADS)

    Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Ponomarenko, Andrey; Apestigue, Victor; Genzer, Maria; Vazquez, Luis; Uspensky, Mikhail; Haukka, Harri

    2016-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: • MetBaro Pressure device • MetHumi Humidity device • MetTemp Temperature sensors Optical devices: • PanCam Panoramic • MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer • DS Dust sensor Composition and Structure Devices: • Tri-axial magnetometer MOURA • Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special

  8. Structure of the fMet-tRNA(fMet)-binding domain of B. stearothermophilus initiation factor IF2.

    PubMed

    Meunier, S; Spurio, R; Czisch, M; Wechselberger, R; Guenneugues, M; Gualerzi, C O; Boelens, R

    2000-04-17

    The three-dimensional structure of the fMet-tRNA(fMet) -binding domain of translation initiation factor IF2 from Bacillus stearothermophilus has been determined by heteronuclear NMR spectroscopy. Its structure consists of six antiparallel beta-strands, connected via loops, and forms a closed beta-barrel similar to domain II of elongation factors EF-Tu and EF-G, despite low sequence homology. Two structures of the ternary complexes of the EF-Tu small middle dotaminoacyl-tRNA small middle dot GDP analogue have been reported and were used to propose and discuss the possible fMet-tRNA(fMet)-binding site of IF2. PMID:10775275

  9. [Aerobic fitness in police officers].

    PubMed

    Capodaglio, E M; Imbriani, M; Criffò, A; Tronconi, E

    1996-01-01

    According to act n. 626, individual assessment of fitness and absence of contraindications for carrying on a job is fundamental. We considered a group of 44 Urban Police officers (36 males, 8 females), age 39.7 +/- 9.1, whose principal job requirement is a good energetic and motor availability, for a fitness evaluation through a submaximal treadmill test, with subsequent steps of 6 minutes. During the test, physiological variables (VO2, VE, QR through a metabograph, Hr trough an Ec-monitor and Pa through a manual sphygmomanometer) and subjective evaluations of fatigue and dyspnea were monitored. Studying the individual variables trend it was possible to identify the critical metabolic level that was easily tolerated by each individual. This level, an average of 6.8 MET corresponding to a heavy activity, is an endurance predictor and can be utilized in subsequent controls. PMID:9312450

  10. Towards a unification of unified theories of biodiversity.

    PubMed

    McGill, Brian J

    2010-05-01

    A unified theory in science is a theory that shows a common underlying set of rules that regulate processes previously thought to be distinct. Unified theories have been important in physics including the unification of electricity and magnetism and the unification of the electromagnetic with the weak nuclear force. Surprisingly, ecology, specifically the subfields of biodiversity and macroecology, also possess not one but at least six unified theories. This is problematic as only one unified theory is desirable. Superficially, the six unified theories seem very different. However, I show that all six theories use the same three rules or assertions to describe a stochastic geometry of biodiversity. The three rules are: (1) intraspecifically individuals are clumped together; (2) interspecifically global or regional abundance varies according to a hollow curve distribution; and (3) interspecifically individuals are placed without regard to individuals of other species. These three rules appear sufficient to explain local species abundance distributions, species-area relationships, decay of similarity of distance and possibly other patterns of biodiversity. This provides a unification of the unified theories. I explore implications of this unified theory for future research. PMID:20337695

  11. Hyperresonance Unifying Theory and the resulting Law

    NASA Astrophysics Data System (ADS)

    Omerbashich, Mensur

    2012-07-01

    Hyperresonance Unifying Theory (HUT) is herein conceived based on theoretical and experimental geophysics, as that absolute extension of both Multiverse and String Theories, in which all universes (the Hyperverse) - of non-prescribed energies and scales - mutually orbit as well as oscillate in tune. The motivation for this is to explain oddities of "attraction at a distance" and physical unit(s) attached to the Newtonian gravitational constant G. In order to make sure HUT holds absolutely, we operate over non-temporal, unitless and quantities with derived units only. A HUT's harmonic geophysical localization (here for the Earth-Moon system; the Georesonator) is indeed achieved for mechanist and quantum scales, in form of the Moon's Equation of Levitation (of Anti-gravity). HUT holds true for our Solar system the same as its localized equation holds down to the precision of terrestrial G-experiments, regardless of the scale: to 10^-11 and 10^-39 for mechanist and quantum scales, respectively. Due to its absolute accuracy (within NIST experimental limits), the derived equation is regarded a law. HUT can indeed be demonstrated for our entire Solar system in various albeit empirical ways. In summary, HUT shows: (i) how classical gravity can be expressed in terms of scale and the speed of light; (ii) the tuning-forks principle is universal; (iii) the body's fundamental oscillation note is not a random number as previously believed; (iv) earthquakes of about M6 and stronger arise mainly due to Earth's alignments longer than three days to two celestial objects in our Solar system, whereas M7+ earthquakes occur mostly during two simultaneous such alignments; etc. HUT indicates: (v) quantum physics is objectocentric, i.e. trivial in absolute terms so it cannot be generalized beyond classical mass-bodies; (vi) geophysics is largely due to the magnification of mass resonance; etc. HUT can be extended to multiverse (10^17) and string scales (10^-67) too, providing a constraint

  12. Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma

    PubMed Central

    2014-01-01

    Background To investigate on the expressions and the clinical significances of hepatocyte growth factor receptor (c-MET), phosphorylated c-MET (p-MET) and e2f-1 transcription factor in primary lesion of gastric adenocarcinoma (GC). Method Tissue samples from the primary lesion of GC in patients who accepted D2/D3 radical gastrectomy with R0/R1 resection were stained by immunohistochemistry of c-MET, p-MET, e2f-1 and Ki-67. The univariate and the multivariate analyses involving in clinicopathological parameters and prognostic factors were evaluated. Results The positivity rates for c-MET (66.12%, 80 cases/121 cases), p-MET (59.50%, 72 cases/121 cases), e2f-1 (38.84%, 47 cases/121 cases) and Ki-67 (72.73%, 88 cases/121 cases) in primary lesion of GC was significantly higher than that in non-cancerous tissue at 5 cm places far from the margin of primary lesion (P < 0.05, respectively). The deeper tumor invasion, the severer lymph node metastasis, the later stage of TNM and the higher expression of Ki-67 was respectively an independent risk factor for the higher expression of c-MET or p-MET, but the younger age and the shorter survival time was an independent risk factor for the higher expression of e2f-1 respectively. Survival analysis showed that the worse prognosis could be observed in the patients with the combination of both c-MET-positive and e2f-1-negative (P = 0.038) or both p-MET-positive and e2f-1-negative (P = 0.042). Cox analysis demonstrated that the severer lymphatic node metastasis and the higher positivity rate of c-MET, p-MET or e2f-1 were an independent prognosis factor respectively. The higher expression of e2f-1 was identified in patients with Stage I-II, which correlated with a shorter survival time. Survival analysis also revealed that the prognosis of patients with positive expression of e2f-1 at Stage I-II was significantly worse than that in patients with negative expression of e2f-1 (χ2 = 13.437, P = 0.001). However, in

  13. Unifying Temporal and Structural Credit Assignment Problems

    NASA Technical Reports Server (NTRS)

    Agogino, Adrian K.; Tumer, Kagan

    2004-01-01

    Single-agent reinforcement learners in time-extended domains and multi-agent systems share a common dilemma known as the credit assignment problem. Multi-agent systems have the structural credit assignment problem of determining the contributions of a particular agent to a common task. Instead, time-extended single-agent systems have the temporal credit assignment problem of determining the contribution of a particular action to the quality of the full sequence of actions. Traditionally these two problems are considered different and are handled in separate ways. In this article we show how these two forms of the credit assignment problem are equivalent. In this unified frame-work, a single-agent Markov decision process can be broken down into a single-time-step multi-agent process. Furthermore we show that Monte-Carlo estimation or Q-learning (depending on whether the values of resulting actions in the episode are known at the time of learning) are equivalent to different agent utility functions in a multi-agent system. This equivalence shows how an often neglected issue in multi-agent systems is equivalent to a well-known deficiency in multi-time-step learning and lays the basis for solving time-extended multi-agent problems, where both credit assignment problems are present.

  14. Randomized central limit theorems: A unified theory

    NASA Astrophysics Data System (ADS)

    Eliazar, Iddo; Klafter, Joseph

    2010-08-01

    The central limit theorems (CLTs) characterize the macroscopic statistical behavior of large ensembles of independent and identically distributed random variables. The CLTs assert that the universal probability laws governing ensembles’ aggregate statistics are either Gaussian or Lévy, and that the universal probability laws governing ensembles’ extreme statistics are Fréchet, Weibull, or Gumbel. The scaling schemes underlying the CLTs are deterministic—scaling all ensemble components by a common deterministic scale. However, there are “random environment” settings in which the underlying scaling schemes are stochastic—scaling the ensemble components by different random scales. Examples of such settings include Holtsmark’s law for gravitational fields and the Stretched Exponential law for relaxation times. In this paper we establish a unified theory of randomized central limit theorems (RCLTs)—in which the deterministic CLT scaling schemes are replaced with stochastic scaling schemes—and present “randomized counterparts” to the classic CLTs. The RCLT scaling schemes are shown to be governed by Poisson processes with power-law statistics, and the RCLTs are shown to universally yield the Lévy, Fréchet, and Weibull probability laws.

  15. Unified creep-plasticity model for halite

    SciTech Connect

    Krieg, R. D.

    1980-11-01

    There are two national energy programs which are considering caverns in geological salt (NaCl) as a storage repository. One is the disposal of nuclear wastes and the other is the storage of oil. Both short-time and long-time structural deformations and stresses must be predictable for these applications. At 300K, the nominal initial temperature for both applications, the salt is at 0.28 of the melting temperature and exhibits a significant time dependent behavior. A constitutive model has been developed which describes the behavior observed in an extensive set of triaxial creep tests. Analysis of these tests showed that a single deformation mechanism seems to be operative over the stress and temperature range of interest so that the secondary creep data can be represented by a power of the stress over the entire test range. This simple behavior allowed a new unified creep-plasticity model to be applied with some confidence. The resulting model recognizes no inherent difference between plastic and creep strains yet models the total inelastic strain reasonably well including primary and secondary creep and reverse loadings. A multiaxial formulation is applied with a back stress. A Bauschinger effect is exhibited as a consequence and is present regardless of the time scale over which the loading is applied. The model would be interpreted as kinematic hardening in the sense of classical plasticity. Comparisons are made between test data and model behavior.

  16. A Unified Picture of S* in Carotenoids.

    PubMed

    Balevičius, Vytautas; Abramavicius, Darius; Polívka, Tomáš; Galestian Pour, Arpa; Hauer, Jürgen

    2016-09-01

    In π-conjugated chain molecules such as carotenoids, coupling between electronic and vibrational degrees of freedom is of central importance. It governs both dynamic and static properties, such as the time scales of excited state relaxation as well as absorption spectra. In this work, we treat vibronic dynamics in carotenoids on four electronic states (|S0⟩, |S1⟩, |S2⟩, and |Sn⟩) in a physically rigorous framework. This model explains all features previously associated with the intensely debated S* state. Besides successfully fitting transient absorption data of a zeaxanthin homologue, this model also accounts for previous results from global target analysis and chain length-dependent studies. Additionally, we are able to incorporate findings from pump-deplete-probe experiments, which were incompatible to any pre-existing model. Thus, we present the first comprehensive and unified interpretation of S*-related features, explaining them by vibronic transitions on either S1, S0, or both, depending on the chain length of the investigated carotenoid. PMID:27509302

  17. The Unified Radio and Plasma wave investigation

    NASA Technical Reports Server (NTRS)

    Stone, R. G.; Bougeret, J. L.; Caldwell, J.; Canu, P.; De Conchy, Y.; Cornilleau-Wehrlin, N.; Desch, M. D.; Fainberg, J.; Goetz, K.; Goldstein, M. L.

    1992-01-01

    The scientific objectives of the Ulysses Unified Radio and Plasma wave (URAP) experiment are twofold: (1) the determination of the direction, angular size, and polarization of radio sources for remote sensing of the heliosphere and the Jovian magnetosphere and (2) the detailed study of local wave phenomena, which determine the transport coefficients of the ambient plasma. A brief discussion of the scientific goals of the experiment is followed by a comprehensive description of the instrument. The URAP sensors consist of a 72.5 m electric field antenna in the spin plane, a 7.5-m electric field monopole along the spin axis of a pair of orthogonal search coil magnetic antennas. The various receivers, designed to encompass specific needs of the investigation, cover the frequency range from dc to 1 MHz. A relaxation sounder provides very accurate electron density measurements. Radio and plasma wave observations are shown to demonstrate the capabilities and limitations of the URAP instruments: radio observations include solar bursts, auroral kilometric radiation, and Jovian bursts; plasma waves include Langmuir waves, ion acousticlike noise, and whistlers.

  18. UPM: unified policy-based network management

    NASA Astrophysics Data System (ADS)

    Law, Eddie; Saxena, Achint

    2001-07-01

    Besides providing network management to the Internet, it has become essential to offer different Quality of Service (QoS) to users. Policy-based management provides control on network routers to achieve this goal. The Internet Engineering Task Force (IETF) has proposed a two-tier architecture whose implementation is based on the Common Open Policy Service (COPS) protocol and Lightweight Directory Access Protocol (LDAP). However, there are several limitations to this design such as scalability and cross-vendor hardware compatibility. To address these issues, we present a functionally enhanced multi-tier policy management architecture design in this paper. Several extensions are introduced thereby adding flexibility and scalability. In particular, an intermediate entity between the policy server and policy rule database called the Policy Enforcement Agent (PEA) is introduced. By keeping internal data in a common format, using a standard protocol, and by interpreting and translating request and decision messages from multi-vendor hardware, this agent allows a dynamic Unified Information Model throughout the architecture. We have tailor-made this unique information system to save policy rules in the directory server and allow executions of policy rules with dynamic addition of new equipment during run-time.

  19. A Testable Unified Theory That Works

    NASA Astrophysics Data System (ADS)

    Chakeres, Donald; Vento, Richard

    2015-03-01

    The harmonic neutron hypothesis is a unified theory of a dimensionally consistent harmonic point set space defining physical phenomena. It is based on equality-pair transformations (EPTs), of the n0; e; α0; and the Rydberg constant, R, and 3 finite integer sets: (Vf) , defined below; the first 12 natural numbers to derive the first generation of particles and bosons; and a finite set of primes for higher generations. All of the derivations/ predictions are made using the natural units and the 3 number sets. The purpose is to demonstrate that it is possible to derive, sets of integers, which inter-relate and predict many of the physical constants from Planck time to the Higgs boson starting with just these 4 sets within a harmonic system. All the physical constants are evaluated as frequency equivalent ratios. The fundamental EPT is based on the transformation of electromagnetic energy into matter via the set (Vf) , scaled from neutron pair production. Elements vf in (Vf) are based on the ratio of the annihilation frequency equivalent of the neutron and 1 Hz, 2.271859078 x 1023 Hz.

  20. Unified force law for granular impact cratering

    NASA Astrophysics Data System (ADS)

    Katsuragi, Hiroaki; Durian, Douglas J.

    2007-06-01

    Experiments on the low-speed impact of solid objects into granular media have been used both to mimic geophysical events and to probe the unusual nature of the granular state of matter. Observations have been interpreted in terms of conflicting stopping forces: product of powers of projectile depth and speed; linear in speed; constant, proportional to the initial impact speed; and proportional to depth. This is reminiscent of high-speed ballistics impact in the nineteenth and twentieth centuries, when a plethora of empirical rules were proposed. To make progress, we developed a means to measure projectile dynamics with 100nm and 20μs precision. For a 1-inch-diameter steel sphere dropped from a wide range of heights into non-cohesive glass beads, we reproduce previous observations either as reasonable approximations or as limiting behaviours. Furthermore, we demonstrate that the interaction between the projectile and the medium can be decomposed into the sum of velocity-dependent inertial drag plus depth-dependent friction. Thus, we achieve a unified description of low-speed impact phenomena and show that the complex response of granular materials to impact, although fundamentally different from that of liquids and solids, can be simply understood.

  1. New unifying procedure for PC index calculations.

    NASA Astrophysics Data System (ADS)

    Stauning, P.

    2012-04-01

    The Polar Cap (PC) index is a controversial topic within the IAGA scientific community. Since 1997 discussions of the validity of the index to be endorsed as an official IAGA index have ensued. Currently, there are now the three separate PC index versions constructed from the different procedures used at the three institutes: the Arctic and Antarctic Research Institute (AARI), the Danish Meteorological Institute (DMI), and the Danish National Space Institute (DTU Space). It is demonstrated in this presentation, that two consistent unifying procedures can be built from the best elements of the three different versions. One procedure uses a set of coefficients aimed at the calculation of final PC index values to be accepted by IAGA. The other procedure uses coefficients aimed at on-line real-time production of preliminary PC index values for Space Weather monitoring applications. For each of the two cases the same procedure is used for the northern (PCN) and the southern (PCS) polar cap indices, and the derived PCN and PCS coefficients are similar.

  2. Unify the electromagnetic force and gravitation

    NASA Astrophysics Data System (ADS)

    Sheng Ming, Zheng

    2013-04-01

    In the process of mankind investigate natural rule: people know four kinds of force: electromagnetic force, gravitation, weak force, and strong force. Meanwhile people use these four kinds force to explain all phenomena in the Nature. Obviously people do not know their mechanism of origin until now. On the other hand, these four kinds force is the difference showing form of one force, is not it? For solve these questions and find their mechanism of origin, I do some experiments and discover that the moving photons produce gravitation. This discovery shows the origin of gravitation. Meanwhile I also do experiments show that light is a particle, but is not a wave-particle duality. My experiments show that the elementary particles moving produce gravitation and electromagnetic force, this effect also produce wave effect. That is to say my experiment and calculate not only reveal the origin of gravitation, but also reveal the origin of electric charge and magnetic force. Base on this I first unify the electromagnetic force and gravitation. The more detail see below website: https://www.lap-publishing.com/catalog/details/store/gb/book/978-3-8473-2658-8/mechanism-of-interaction-in-moving-matter.

  3. Unify the electromagnetic force and gravitation

    NASA Astrophysics Data System (ADS)

    Ming, Zheng Sheng

    2013-04-01

    In the process of mankind investigate natural rule: people know four kinds of force: electromagnetic force, gravitation, weak force, and strong force. Meanwhile people use these four kinds force to explain all phenomena in the Nature. Obviously people do not know their mechanism of origin until now. On the other hand, these four kinds force is the difference showing form of one force, is not it? For solve these questions and find their mechanism of origin, I do some experiments and discover that the moving photons produce gravitation. This discovery shows the origin of gravitation. Meanwhile I also do experiments show that light is a particle, but is not a wave-particle duality. My experiments show that the elementary particles moving produce gravitation and electromagnetic force, this effect also produce wave effect. That is to say my experiment and calculate not only reveal the origin of gravitation, but also reveal the origin of electric charge and magnetic force. Base on this I first unify the electromagnetic force and gravitation. The more detail see below website: https://www.lap-publishing.com/catalog/details/store/gb/book/978-3-8473-2658-8/mechanism-of-interaction-in-moving-matter

  4. A Unified Picture of S* in Carotenoids

    PubMed Central

    2016-01-01

    In π-conjugated chain molecules such as carotenoids, coupling between electronic and vibrational degrees of freedom is of central importance. It governs both dynamic and static properties, such as the time scales of excited state relaxation as well as absorption spectra. In this work, we treat vibronic dynamics in carotenoids on four electronic states (|S0⟩, |S1⟩, |S2⟩, and |Sn⟩) in a physically rigorous framework. This model explains all features previously associated with the intensely debated S* state. Besides successfully fitting transient absorption data of a zeaxanthin homologue, this model also accounts for previous results from global target analysis and chain length-dependent studies. Additionally, we are able to incorporate findings from pump-deplete-probe experiments, which were incompatible to any pre-existing model. Thus, we present the first comprehensive and unified interpretation of S*-related features, explaining them by vibronic transitions on either S1, S0, or both, depending on the chain length of the investigated carotenoid. PMID:27509302

  5. Observational constraints to a unified cosmological model

    NASA Astrophysics Data System (ADS)

    Cuzinatto, Rodrigo R.; de Morais, Eduardo M.; Medeiros, Leo G.

    2016-01-01

    We propose a phenomenological unified model (UM) for dark matter and dark energy based on an equation of state parameter w that scales with the arctan of the redshift. The free parameters of the model are three constants: Ωb0, α and β. Parameter α dictates the transition rate between the matter dominated era and the accelerated expansion period. The ratio β/α gives the redshift of the equivalence between both regimes. Cosmological parameters are fixed by observational data from primordial nucleosynthesis (PN), supernovae of the type Ia (SNIa), gamma-ray bursts (GRBs) and baryon acoustic oscillations (BAOs). The calibration of the 138 GRB events is performed using the 580 SNIa of the Union2.1 data set and a new set of 79 high-redshift GRB is obtained. The various sets of data are used in different combinations to constraint the parameters through statistical analysis. The UM is compared to the ΛCDM model and their differences are emphasized.

  6. Statistical mechanics unifies different ecological patterns.

    PubMed

    Dewar, Roderick C; Porté, Annabel

    2008-04-01

    Recently there has been growing interest in the use of maximum relative entropy (MaxREnt) as a tool for statistical inference in ecology. In contrast, here we propose MaxREnt as a tool for applying statistical mechanics to ecology. We use MaxREnt to explain and predict species abundance patterns in ecological communities in terms of the most probable behaviour under given environmental constraints, in the same way that statistical mechanics explains and predicts the behaviour of thermodynamic systems. We show that MaxREnt unifies a number of different ecological patterns: (i) at relatively local scales a unimodal biodiversity-productivity relationship is predicted in good agreement with published data on grassland communities, (ii) the predicted relative frequency of rare vs. abundant species is very similar to the empirical lognormal distribution, (iii) both neutral and non-neutral species abundance patterns are explained, (iv) on larger scales a monotonic biodiversity-productivity relationship is predicted in agreement with the species-energy law, (v) energetic equivalence and power law self-thinning behaviour are predicted in resource-rich communities. We identify mathematical similarities between these ecological patterns and the behaviour of thermodynamic systems, and conclude that the explanation of ecological patterns is not unique to ecology but rather reflects the generic statistical behaviour of complex systems with many degrees of freedom under very general types of environmental constraints. PMID:18237750

  7. Unified framework of topological phases with symmetry

    NASA Astrophysics Data System (ADS)

    Gu, Yuxiang; Hung, Ling-Yan; Wan, Yidun

    2014-12-01

    In topological phases in 2 +1 dimensions, anyons fall into representations of quantum group symmetries. As proposed in our work [Hung and Wan, Int. J. Mod. Phys. B 28, 1450172 (2014), 10.1142/S0217979214501720], the physics of a symmetry enriched phase can be extracted by the mathematics of (hidden) quantum group symmetry breaking of a "parent phase." This offers a unified framework and classification of the symmetry enriched (topological) phases, including symmetry protected trivial phases as well. In this paper, we extend our investigation to the case where the "parent" phases are non-Abelian topological phases. We show explicitly how one can obtain the topological data and symmetry transformations of the symmetry enriched phases from that of the "parent" non-Abelian phase. Two examples are computed: (1) the Ising×Ising¯ phase breaks into the Z2 toric code with Z2 global symmetry; (2) the SU (2) 8 phase breaks into the chiral Fibonacci × Fibonacci phase with a Z2 symmetry, a first non-Abelian example of symmetry enriched topological phase beyond the gauge-theory construction.

  8. Constraints on dissipative unified dark matter

    SciTech Connect

    Velten, Hermano; Schwarz, Dominik J. E-mail: dschwarz@physik.uni-bielefeld.de

    2011-09-01

    Modern cosmology suggests that the Universe contains two dark components — dark matter and dark energy — both unkown in laboratory physics and both lacking direct evidence. Alternatively, a unified dark sector, described by a single fluid, has been proposed. Dissipation is a common phenomenon in nature and it thus seems natural to consider models dominated by a viscous dark fluid. We focus on the study of bulk viscosity, as isotropy and homogeneity at large scales implies the suppression of shear viscosity, heat flow and diffusion. The generic ansatz ξ∝ρ{sup ν} for the coefficient of bulk viscosity (ρ denotes the mass/energy density), which for ν = −1/2 mimics the ΛCDM background evolution, offers excellent fits to supernova and H(z) data. We show that viscous dark fluids suffer from large contributions to the integrated Sachs-Wolfe effect (generalising a previous study by Li and Barrow) and a suppression of structure growth at small-scales (as seen from a generalized Meszaros equation). Based on recent observations, we conclude that viscous dark fluid models (with ξ∝ρ{sup ν} and neglecting baryons) are strongly challenged.

  9. Berkeley Unified Parallel C (UPC) Runtime Library

    Energy Science and Technology Software Center (ESTSC)

    2003-03-31

    This software comprises a portable, open source implementation of a runtime library to support applications written in the Unified Parallel C (UPC) language. This library implements the UPC-specific functionality, including shared memory allocation and locks. The network-dependent functionality is implemented as a thin wrapper around a separate library implementing the GASNet (Global-Address Space Networking) specification. For true shared memory machines. GASNet is bypassed in favor of direct memory operations and local synchronization mechanisms. The Berkeleymore » UPC Runtime Library is currently the only implementation of the "Berkeley UPC Runtime Specification", and thus the only runtme library usable with the Berkeley UPC Compiler. Also, it is the only UPC runtime known to the author to provide two shared pointer representations: one for arbitrary blocksizes and one to optimize for the common cases of phaseless and blocksize=1. For distributed memory environments a library implementing the GASNet (Global-Address Space Networking) specification is required for communication. While no specialized hardware is required, a high-speed interconnet supported by the GASNet implementation is suggested for preformance. If no supported high-speed interconnect is available. GASNet can run over MPI. An external library is reqired for certain local memory allocation operations. A well defined interface allows for multiple implementations of this library, but at present the "umalloc" library from LBNL is the only compatible implementation.« less

  10. A unifying review of linear gaussian models.

    PubMed

    Roweis, S; Ghahramani, Z

    1999-02-15

    Factor analysis, principal component analysis, mixtures of gaussian clusters, vector quantization, Kalman filter models, and hidden Markov models can all be unified as variations of unsupervised learning under a single basic generative model. This is achieved by collecting together disparate observations and derivations made by many previous authors and introducing a new way of linking discrete and continuous state models using a simple nonlinearity. Through the use of other nonlinearities, we show how independent component analysis is also a variation of the same basic generative model. We show that factor analysis and mixtures of gaussians can be implemented in autoencoder neural networks and learned using squared error plus the same regularization term. We introduce a new model for static data, known as sensible principal component analysis, as well as a novel concept of spatially adaptive observation noise. We also review some of the literature involving global and local mixtures of the basic models and provide pseudocode for inference and learning for all the basic models. PMID:9950734

  11. MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells.

    PubMed

    Presutti, Dario; Santini, Simonetta; Cardinali, Beatrice; Papoff, Giuliana; Lalli, Cristiana; Samperna, Simone; Fustaino, Valentina; Giannini, Giuseppe; Ruberti, Giovina

    2015-01-01

    Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30-40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation

  12. MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

    PubMed Central

    Presutti, Dario; Santini, Simonetta; Cardinali, Beatrice; Papoff, Giuliana; Lalli, Cristiana; Samperna, Simone; Fustaino, Valentina; Giannini, Giuseppe; Ruberti, Giovina

    2015-01-01

    Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30–40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation

  13. c-Met as a Target for Personalized Therapy

    PubMed Central

    Garajová, Ingrid; Giovannetti, Elisa; Biasco, Guido; Peters, Godefridus J.

    2015-01-01

    MET and its ligand HGF are involved in many biological processes, both physiological and pathological, making this signaling pathway an attractive therapeutic target in oncology. Downstream signaling effects are transmitted via mitogen-activated protein kinase (MAPK), PI3K (phosphoinositide 3-kinase protein kinase B)/AKT, signal transducer and activator of transcription proteins (STAT), and nuclear factor-κB. The final output of the terminal effector components of these pathways is activation of cytoplasmic and nuclear processes leading to increases in cell proliferation, survival, mobilization and invasive capacity. In addition to its role as an oncogenic driver, increasing evidence implicates MET as a common mechanism of resistance to targeted therapies including EGFR and VEGFR inhibitors. In the present review, we summarize the current knowledge on the role of the HGF-MET signaling pathway in cancer and its therapeutic targeting (HGF activation inhibitors, HGF inhibitors, MET antagonists and selective/nonselective MET kinase inhibitors). Recent advances in understanding the role of this pathway in the resistance to current anticancer strategies used in lung, kidney and pancreatic cancer are discussed. PMID:26628860

  14. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG... determining whether established specifications are met? You must determine whether the specifications you establish under § 111.70 are met....

  15. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG... determining whether established specifications are met? You must determine whether the specifications you establish under § 111.70 are met....

  16. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG... determining whether established specifications are met? You must determine whether the specifications you establish under § 111.70 are met....

  17. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG... determining whether established specifications are met? You must determine whether the specifications you establish under § 111.70 are met....

  18. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG... determining whether established specifications are met? You must determine whether the specifications you establish under § 111.70 are met....

  19. Suppression of superheavy magnetic monopoles in grand unified theories

    SciTech Connect

    Pi, S.Y.

    1980-08-01

    The superheavy magnetic monopoles predicted by grand unified theories would not be produced in significant numbers if electromagnetic gauge invariance is spontaneously broken when the temperature T is greater than T/sub c/ >approx. 1 TeV.

  20. A Unified Mathematical Definition of Classical Information Retrieval.

    ERIC Educational Resources Information Center

    Dominich, Sandor

    2000-01-01

    Presents a unified mathematical definition for the classical models of information retrieval and identifies a mathematical structure behind relevance feedback. Highlights include vector information retrieval; probabilistic information retrieval; and similarity information retrieval. (Contains 118 references.) (Author/LRW)

  1. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  2. BacMet: antibacterial biocide and metal resistance genes database

    PubMed Central

    Pal, Chandan; Bengtsson-Palme, Johan; Rensing, Christopher; Kristiansson, Erik; Larsson, D. G. Joakim

    2014-01-01

    Antibiotic resistance has become a major human health concern due to widespread use, misuse and overuse of antibiotics. In addition to antibiotics, antibacterial biocides and metals can contribute to the development and maintenance of antibiotic resistance in bacterial communities through co-selection. Information on metal and biocide resistance genes, including their sequences and molecular functions, is, however, scattered. Here, we introduce BacMet (http://bacmet.biomedicine.gu.se)—a manually curated database of antibacterial biocide- and metal-resistance genes based on an in-depth review of the scientific literature. The BacMet database contains 470 experimentally verified resistance genes. In addition, the database also contains 25 477 potential resistance genes collected from public sequence repositories. All resistance genes in the BacMet database have been organized according to their molecular function and induced resistance phenotype. PMID:24304895

  3. A unified optical theorem for scalar and vectorial wave fields.

    PubMed

    Wapenaar, Kees; Douma, Huub

    2012-05-01

    The generalized optical theorem is an integral relation for the angle-dependent scattering amplitude of an inhomogeneous scattering object embedded in a homogeneous background. It has been derived separately for several scalar and vectorial wave phenomena. Here a unified optical theorem is derived that encompasses the separate versions for scalar and vectorial waves. Moreover, this unified theorem also holds for scattering by anisotropic elastic and piezoelectric scatterers as well as bianisotropic (non-reciprocal) EM scatterers. PMID:22559339

  4. Unified Model Deformation and Flow Transition Measurements

    NASA Technical Reports Server (NTRS)

    Burner, Alpheus W.; Liu, Tianshu; Garg, Sanjay; Bell, James H.; Morgan, Daniel G.

    1999-01-01

    The number of optical techniques that may potentially be used during a given wind tunnel test is continually growing. These include parameter sensitive paints that are sensitive to temperature or pressure, several different types of off-body and on-body flow visualization techniques, optical angle-of-attack (AoA), optical measurement of model deformation, optical techniques for determining density or velocity, and spectroscopic techniques for determining various flow field parameters. Often in the past the various optical techniques were developed independently of each other, with little or no consideration for other techniques that might also be used during a given test. Recently two optical techniques have been increasingly requested for production measurements in NASA wind tunnels. These are the video photogrammetric (or videogrammetric) technique for measuring model deformation known as the video model deformation (VMD) technique, and the parameter sensitive paints for making global pressure and temperature measurements. Considerations for, and initial attempts at, simultaneous measurements with the pressure sensitive paint (PSP) and the videogrammetric techniques have been implemented. Temperature sensitive paint (TSP) has been found to be useful for boundary-layer transition detection since turbulent boundary layers convect heat at higher rates than laminar boundary layers of comparable thickness. Transition is marked by a characteristic surface temperature change wherever there is a difference between model and flow temperatures. Recently, additional capabilities have been implemented in the target-tracking videogrammetric measurement system. These capabilities have permitted practical simultaneous measurements using parameter sensitive paint and video model deformation measurements that led to the first successful unified test with TSP for transition detection in a large production wind tunnel.

  5. Convergent Margin Structure and a Unifying Concept

    NASA Astrophysics Data System (ADS)

    von Huene, R.; Ranero, C. R.; Scholl, D. W.

    2008-12-01

    Marine observations of the past decade resolve 3 domains of different mechanics in space that probably respond differently from each other during an earthquake cycle. Accretion is common along thickly (>1 km) sedimented trenches and slowly (<50km/myr) converging margins. Erosion is common where convergence is greater which also reduces trench sediment thickness by rapid subduction. However erosion and accretion can be coeval, for instance, subducted seamounts erode the upper plate as adjacent sediment accretes. Trench sediment abundance appears to be a master control of tectonic erosion or accretion. Subducting plate relief and bending, fluid systems, input plate temperature, and material differences seem less important. From recent observations a unifying framework concept to aid interpretations of both accreting and eroding margins is proposed. Over a long term (Ma) the subduction channel accepts a finite amount of material. The excess amount will accrete and a shortage of trench sediment enhances erosion (Cloos and Shreve, 1988). If conditions remain consistent over ~1 Ma periods, the margin configuration becomes typically accretionary or erosional. In each margin segment the short term inter plate friction and material strength changes during the earthquake cycle as proposed by Wang and Hu, 2006. Mechanics probably changes locally during the cycle as well. K. Wang, Y. Hu, Accretionary prisms in subduction earthquake cycles: the theory of dynamic Coulomb wedge, J. Geophys. Res. 111 (2006) B06410, doi:10.1029/2005JB004094. Cloos, M., and R.L. Shreve, (1988), Subduction channel model of prism accretion, melange formation, sediment subduction, and subduction erosion at convergent plate margins: 2. Implications and discussion, Pageoph, v. 129, n. ¾ 501-545

  6. A unified approach to sparse signal processing

    NASA Astrophysics Data System (ADS)

    Marvasti, Farokh; Amini, Arash; Haddadi, Farzan; Soltanolkotabi, Mahdi; Khalaj, Babak Hossein; Aldroubi, Akram; Sanei, Saeid; Chambers, Janathon

    2012-12-01

    A unified view of the area of sparse signal processing is presented in tutorial form by bringing together various fields in which the property of sparsity has been successfully exploited. For each of these fields, various algorithms and techniques, which have been developed to leverage sparsity, are described succinctly. The common potential benefits of significant reduction in sampling rate and processing manipulations through sparse signal processing are revealed. The key application domains of sparse signal processing are sampling, coding, spectral estimation, array processing, component analysis, and multipath channel estimation. In terms of the sampling process and reconstruction algorithms, linkages are made with random sampling, compressed sensing, and rate of innovation. The redundancy introduced by channel coding in finite and real Galois fields is then related to over-sampling with similar reconstruction algorithms. The error locator polynomial (ELP) and iterative methods are shown to work quite effectively for both sampling and coding applications. The methods of Prony, Pisarenko, and MUltiple SIgnal Classification (MUSIC) are next shown to be targeted at analyzing signals with sparse frequency domain representations. Specifically, the relations of the approach of Prony to an annihilating filter in rate of innovation and ELP in coding are emphasized; the Pisarenko and MUSIC methods are further improvements of the Prony method under noisy environments. The iterative methods developed for sampling and coding applications are shown to be powerful tools in spectral estimation. Such narrowband spectral estimation is then related to multi-source location and direction of arrival estimation in array processing. Sparsity in unobservable source signals is also shown to facilitate source separation in sparse component analysis; the algorithms developed in this area such as linear programming and matching pursuit are also widely used in compressed sensing. Finally

  7. Unified Model of Multiple Wind Turbines

    NASA Astrophysics Data System (ADS)

    Mutule, A.; Kochukov, O.

    2014-08-01

    An approach is proposed to the modelling of wind farms in the electric power system long-term planning. It allows a specialist to perform calculations based on scanty information and offers a set of ready-to-use data for easy, fast, and precise modelling. The authors exemplify the calculations of wind speed probability density and power curves and give an idea for relevant corrections. They also show how to pass from a single wind turbine model to the unified model of multiple wind turbines which would meet the requirements of long-term planning tasks. The paper presents the data on wind farms that are operating in UK and Oceania Rakstā ir apskatīta vēja elektrostaciju modelēšana ilgtermiņa attīstības plānošanas uzdevumos. Modelēšana tika veikta, izmantojot ierobežotu datu apjomu, kuri bija piejami lietotājam. Gatavie dati deva iespēju veikt ātru un precīzu modelēšanu. Raksts piedāva metodi kā pāriet no viena vēja ģeneratora modeli uz vēja elektrostaciju (vairāki vēja ģeneratori) modeli, kas atbilst ilgtermiņa attīstības plānošanas prasībām. Rakstā atspoguļoti dati no Okeānijas un Lielbritānijas eksistējošām vēja elektrostacijām

  8. Project Outreach: Organizations Unified to Reach Youth.

    PubMed Central

    Dunnington, B C; Hayes, M L

    1989-01-01

    Youths of today are forced to deal with the external pressures of alcohol and drug abuse on all levels-from the older youngsters across the street pressuring them to be "cool," to the "cute dog" enticing them with the glamour of being the original "party animal." Through today's mass communications, young people are exposed to negative, self-destructive attitudes. It is important, therefore, to expose them to a more positive influence and try to reach them through parental guidance, personal contact, and peer pressure. To achieve this, the University of Missouri's Kansas City Chapter of the American Pharmaceutical Association's Academy of Students of Pharmacy, in conjunction with the Metropolitan Kansas City Area Task Force on Alcohol and Other Drug Abuse, proposed the development of an annual drug abuse prevention program that specifically targets fifth graders in the greater Kansas City metropolitan area. A primary goal of Project Outreach (Organizations Unified to Reach Youth) is to unite drug abuse prevention programs in the greater Kansas City metropolitan area in their outreach efforts to give positive support to Kansas City's youth against alcohol and other drugs. Phase I of Project Outreach consisted of a series of programs for the parents in the community. Phase II entailed college students who spoke to fifth graders in their classrooms. These students also participated in poster and poem contents centered around drug abuse prevention. In Phase III, which featured an outstanding, motivated speaker, the sample group of 600 fifth graders in the area participated in a major event to give positive peer pressure to say no to drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2493666

  9. Evolutionary mechanism unifies the hallmarks of cancer.

    PubMed

    Horne, Steven D; Pollick, Sarah A; Heng, Henry H Q

    2015-05-01

    The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene-level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced the hallmarks of cancer, as such synthesis has supported the notions that common cancer genes are responsible for the majority of cancers and the complexity of cancer can be dissected into simplified molecular principles. The gene/pathway classification based on individual hallmarks provides explanation for the large number of diverse gene mutations, which is in contrast to the original estimation that only a handful of gene mutations would be discovered. Further, these hallmarks have been highly influential as they also provide the rationale and research direction for continued gene-based cancer research. While the molecular knowledge of these hallmarks is drastically increasing, the clinical implication remains limited, as cancer dynamics cannot be summarized by a few isolated/fixed molecular principles. Furthermore, the highly heterogeneous genetic signature of cancers, including massive stochastic genome alterations, challenges the utility of continuously studying each individual gene mutation under the framework of these hallmarks. It is therefore necessary to re-evaluate the concept of cancer hallmarks through the lens of cancer evolution. In this analysis, the evolutionary basis for the hallmarks of cancer will be discussed and the evolutionary mechanism of cancer suggested by the genome theory will be employed to unify the diverse molecular mechanisms of cancer. PMID:24957955

  10. A unified data embedding and scrambling method.

    PubMed

    Rad, Reza Moradi; Wong, Koksheik; Guo, Jing-Ming

    2014-04-01

    Conventionally, data embedding techniques aim at maintaining high-output image quality so that the difference between the original and the embedded images is imperceptible to the naked eye. Recently, as a new trend, some researchers exploited reversible data embedding techniques to deliberately degrade image quality to a desirable level of distortion. In this paper, a unified data embedding-scrambling technique called UES is proposed to achieve two objectives simultaneously, namely, high payload and adaptive scalable quality degradation. First, a pixel intensity value prediction method called checkerboard-based prediction is proposed to accurately predict 75% of the pixels in the image based on the information obtained from 25% of the image. Then, the locations of the predicted pixels are vacated to embed information while degrading the image quality. Given a desirable quality (quantified in SSIM) for the output image, UES guides the embedding-scrambling algorithm to handle the exact number of pixels, i.e., the perceptual quality of the embedded-scrambled image can be controlled. In addition, the prediction errors are stored at a predetermined precision using the structure side information to perfectly reconstruct or approximate the original image. In particular, given a desirable SSIM value, the precision of the stored prediction errors can be adjusted to control the perceptual quality of the reconstructed image. Experimental results confirmed that UES is able to perfectly reconstruct or approximate the original image with SSIM value > 0.99 after completely degrading its perceptual quality while embedding at 7.001 bpp on average. PMID:24565789

  11. Remembering the early days of the Met Lab

    SciTech Connect

    Katz, J.J.

    1990-01-01

    The Met Lab was set up by the war-time Manhattan District, US Corp of Engineers to (i) find a system using normal uranium in which a chain reaction would occur; (ii) to show that if such a chain reaction did occur, it would be possible to separate plutonium chemically from the uranium matrix and the fission products formed in the chain reactions; and (iii) to prepare plans for the large-scale production of plutonium. Chemistry Section C-1 of the Met Lab was assigned the responsibility for developing separation methods for plutonium production on the industrial scale. This report describes some aspects of daily life in Section C-1.

  12. MET-targeted therapy for gastric cancer: the importance of a biomarker-based strategy.

    PubMed

    Kawakami, Hisato; Okamoto, Isamu

    2016-07-01

    The MET protooncogene encodes the receptor tyrosine kinase c-MET (MET). Aberrant activation of MET signaling occurs in a subset of advanced malignancies, including gastric cancer, and promotes tumor cell growth, survival, migration, and invasion as well as tumor angiogenesis, suggesting its potential importance as a therapeutic target. MET can be activated by two distinct pathways that are dependent on or independent of its ligand, hepatocyte growth factor (HGF), with the latter pathway having been attributed mostly to MET amplification in gastric cancer. Preclinical evidence has suggested that interruption of the HGF-MET axis either with antibodies to HGF or with MET tyrosine kinase inhibitors (TKIs) has antitumor effects in gastric cancer cells. Overexpression of MET occurs frequently in gastric cancer and has been proposed as a potential predictive biomarker for anti-MET therapy. However, several factors can trigger such MET upregulation in a manner independent of HGF, suggesting that gastric tumors with MET overexpression are not necessarily MET driven. On the other hand, gastric cancer cells with MET amplification are dependent on MET signaling for their survival and are thus vulnerable to MET TKI treatment. Given the low prevalence of MET amplification in gastric cancer (approximately 8 %), testing for this genetic change would substantially narrow the target population but it might constitute a better biomarker than MET overexpression for MET TKI therapy. We compare aberrant MET signaling dependent on the HGF-MET axis or on MET amplification as well as address clinical issues and challenges associated with the identification of appropriate biomarkers for MET-driven tumors. PMID:26690587

  13. Cetuximab-induced MET activation acts as a novel resistance mechanism in colon cancer cells.

    PubMed

    Song, Na; Liu, Shizhou; Zhang, Jingdong; Liu, Jing; Xu, Ling; Liu, Yunpeng; Qu, Xiujuan

    2014-01-01

    Aberrant MET expression and hepatocyte growth factor (HGF) signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR) inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer. PMID:24714091

  14. NARSTO EPA SS ST LOUIS AIR CHEM PM MET DATA

    Atmospheric Science Data Center

    2014-05-07

    NARSTO EPA SS ST LOUIS AIR CHEM PM MET DATA Project Title:  NARSTO ... Amount Surface Pressure Solar Radiation Surface Air Temperature Particulates Trace Metals Order Data:  ... Data Guide Documents:  St Louis Air Chem Guide St Louis Final Report  (PDF) St Louis QA ...

  15. NARSTO EPA SS NEW YORK AIR CHEM PM MET DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO EPA SS NEW YORK AIR CHEM PM MET DATA Project Title:  NARSTO ... Thermooptical Transmission Location:  New York Spatial Resolution:  Point Measurements ...   Order Data Guide Documents:  New York Air Chem Guide CPM Summary Report  (PDF) ...

  16. The MET Project: The Wrong 45 Million Dollar Question

    ERIC Educational Resources Information Center

    Gabriel, Rachael; Allington, Richard

    2012-01-01

    In 2009, the Bill and Melinda Gates Foundation funded the investigation of a $45 million question: How can we identify and develop effective teaching? Now that the findings from their Measures of Effective Teaching (MET) project have been released, it's clear they asked a simpler question, namely, What other measures match up well with value-added…

  17. Seven Oaks Met School Builds Curriculum around Each Student

    ERIC Educational Resources Information Center

    Pearson, George

    2009-01-01

    This article features Seven Oaks School Division Met School in Winnipeg, a high school that limits class size to 15, tailors its curriculum to the needs and interests of its individual students, places students in community-based internships two days a week, and keeps the teacher--called an advisor--with the same group of students from Grade 9…

  18. Radical AdoMet enzymes in complex metal cluster biosynthesis.

    PubMed

    Duffus, Benjamin R; Hamilton, Trinity L; Shepard, Eric M; Boyd, Eric S; Peters, John W; Broderick, Joan B

    2012-11-01

    Radical S-adenosylmethionine (AdoMet) enzymes comprise a large superfamily of proteins that engage in a diverse series of biochemical transformations through generation of the highly reactive 5'-deoxyadenosyl radical intermediate. Recent advances into the biosynthesis of unique iron-sulfur (FeS)-containing cofactors such as the H-cluster in [FeFe]-hydrogenase, the FeMo-co in nitrogenase, as well as the iron-guanylylpyridinol (FeGP) cofactor in [Fe]-hydrogenase have implicated new roles for radical AdoMet enzymes in the biosynthesis of complex inorganic cofactors. Radical AdoMet enzymes in conjunction with scaffold proteins engage in modifying ubiquitous FeS precursors into unique clusters, through novel amino acid decomposition and sulfur insertion reactions. The ability of radical AdoMet enzymes to modify common metal centers to unusual metal cofactors may provide important clues into the stepwise evolution of these and other complex bioinorganic catalysts. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology. PMID:22269887

  19. The Marshall Engineering Thermosphere (MET) Model. Volume 1; Technical Description

    NASA Technical Reports Server (NTRS)

    Smith, R. E.

    1998-01-01

    Volume 1 presents a technical description of the Marshall Engineering Thermosphere (MET) model atmosphere and a summary of its historical development. Various programs developed to augment the original capability of the model are discussed in detail. The report also describes each of the individual subroutines developed to enhance the model. Computer codes for these subroutines are contained in four appendices.

  20. San Diego Met High School: Personalization as a Foundation

    ERIC Educational Resources Information Center

    Principal Leadership, 2010

    2010-01-01

    The mission of San Diego Met High School is to prepare students for college and the workforce through active learning, academic rigor, and community involvement in a small school setting. Because personalization is a key component of the school culture, advisories of 20-25 students work with the same teachers for all four years. Advisers, parents,…

  1. NARSTO PAC2001 CESSNA VOC PM OZONE MET DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO PAC2001 CESSNA VOC PM OZONE MET DATA Project Title:  NARSTO Discipline:  ... Temperature Probe Humidity Probe Wind Sensor UV Ozone Detector Optical Counter GC Location:  Lower Fraser ... Air Temperature Humidity Upper Level Winds Ozone Aerosol Particle Properties Volatile Organic Compounds ...

  2. NARSTO PAC2001 CONVAIR PM OZONE MET DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO PAC2001 CONVAIR PM OZONE MET DATA Project Title:  NARSTO Discipline:  ... Temperature Probe Humidity Probe Wind Sensor UV Ozone Detector Optical Counter Location:  Lower Fraser ... Air Temperature Humidity Upper Level Winds Ozone Aerosol Particle Properties Order Data:  ASDC Order ...

  3. Altered white matter architecture in BDNF met carriers.

    PubMed

    Ziegler, Erik; Foret, Ariane; Mascetti, Laura; Muto, Vincenzo; Le Bourdiec-Shaffii, Anahita; Stender, Johan; Balteau, Evelyne; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Phillips, Christophe

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture. PMID:23935975

  4. Lessons Learned: The MetLife Foundation Awards

    ERIC Educational Resources Information Center

    Kazis, Richard; Haynes, Leslie; Liebowitz, Martin

    2002-01-01

    This past year, Jobs for the Future studied strategies that community colleges are using to improve the quality and effectiveness of their services to low-income youth and adults. Much of this research was conducted for the MetLife Foundation Community College Excellence Awards Initiative. Across the country, in urban, rural, and suburban…

  5. Project Outreach: Organizations Unified to Reach Youth.

    PubMed

    Dunnington, B C; Hayes, M L

    1989-01-01

    Youths of today are forced to deal with the external pressures of alcohol and drug abuse on all levels-from the older youngsters across the street pressuring them to be "cool," to the "cute dog" enticing them with the glamour of being the original "party animal." Through today's mass communications, young people are exposed to negative, self-destructive attitudes. It is important, therefore, to expose them to a more positive influence and try to reach them through parental guidance, personal contact, and peer pressure. To achieve this, the University of Missouri's Kansas City Chapter of the American Pharmaceutical Association's Academy of Students of Pharmacy, in conjunction with the Metropolitan Kansas City Area Task Force on Alcohol and Other Drug Abuse, proposed the development of an annual drug abuse prevention program that specifically targets fifth graders in the greater Kansas City metropolitan area. A primary goal of Project Outreach (Organizations Unified to Reach Youth) is to unite drug abuse prevention programs in the greater Kansas City metropolitan area in their outreach efforts to give positive support to Kansas City's youth against alcohol and other drugs. Phase I of Project Outreach consisted of a series of programs for the parents in the community. Phase II entailed college students who spoke to fifth graders in their classrooms. These students also participated in poster and poem contents centered around drug abuse prevention. In Phase III, which featured an outstanding, motivated speaker, the sample group of 600 fifth graders in the area participated in a major event to give positive peer pressure to say no to drugs. Pertinent entertainment also was provided, and the governor of Missouri, John Ashcroft, attended the rally. In the future, each fifth grader will receive a free T-shirt as a tangible reminder of the main event. In Phase IV, to reinforce concepts presented in previous programming, the college students returned to the fifth grade

  6. Evaporative partitioning in a unified land model

    NASA Astrophysics Data System (ADS)

    Livneh, B.; Lettenmaier, D. P.; Restrepo, P. J.

    2009-12-01

    Accurate partitioning of precipitation into evapotranspiration and runoff, and more generally estimation of the surface water balance, is crucial both for hydrologic forecasting and numerical weather and climate prediction. One important aspect of this issue is the partitioning of evapotranspiration into soil evaporation, canopy evaporation, and plant transpiration, which in turn has implications for other terms in the surface water balance. In the first part of the study, we tested several well known land surface models in multi-year simulations over the continental U.S. Among the models, which included the Variable Infiltration Capacity (VIC) model, the Community Land Model (CLM), the Noah Land Surface Model (Noah LSM), and the NASA Catchment model, there were substantial variations in the partitioning. These results motivated a more detailed evaluation, using data for two catchments that were a part of the second phase of the Distributed Model Intercomparison Project (DMIP-2), the East Fork Carson River Basin and the Illinois River Basin. In this portion of the study, we evaluated a unified land model (ULM) which is a merger of the NWS Sacramento Soil Moisture Accounting model (SAC-SMA), which is used operationally for flood and seasonal streamflow prediction, and the Noah LSM, which is the land scheme used in NOAA’s suite of weather and climate prediction models. Our overall objective is to leverage the operational strengths of each model, specifically to improve streamflow prediction and soil moisture states within the Noah LSM framework, and to add a vegetation component to the SAC-SMA model. Partitioning of evapotranspiration into its three components is a key part of the ULM performance, and controls our ability to use calibrated SAC-SMA parameters within the ULM framework. In our evaluations at the DMIP-2 sites, we examined sensitivities of soil moisture and evaporative components in ULM to changes in vegetation cover, root zone depth, canopy

  7. In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models.

    PubMed

    Hughes, Paul E; Rex, Karen; Caenepeel, Sean; Yang, Yajing; Zhang, Yihong; Broome, Martin A; Kha, Hue T; Burgess, Teresa L; Amore, Benny; Kaplan-Lefko, Paula J; Moriguchi, Jodi; Werner, Jonathan; Damore, Michael A; Baker, Daniel; Choquette, Deborah M; Harmange, Jean-Christophe; Radinsky, Robert; Kendall, Richard; Dussault, Isabelle; Coxon, Angela

    2016-07-01

    The MET receptor tyrosine kinase is involved in cell growth, survival, and invasion. Clinical studies with small molecule MET inhibitors have shown the role of biomarkers in identifying patients most likely to benefit from MET-targeted therapy. AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor. Herein, we describe AMG 337 preclinical activity and mechanism of action in MET-dependent tumor models. These studies suggest MET is the only therapeutic target for AMG 337. In an unbiased tumor cell line proliferation screen (260 cell lines), a closely related analogue of AMG 337, Compound 5, exhibited activity in 2 of 260 cell lines; both were MET-amplified. Additional studies examining the effects of AMG 337 on the proliferation of a limited panel of cell lines with varying MET copy numbers revealed that high-level focal MET amplification (>12 copies) was required to confer MET oncogene addiction and AMG 337 sensitivity. One MET-amplified cell line, H1573 (>12 copies), was AMG 337 insensitive, possibly because of a downstream G12A KRAS mutation. Mechanism-of-action studies in sensitive MET-amplified cell lines demonstrated that AMG 337 inhibited MET and adaptor protein Gab-1 phosphorylation, subsequently blocking the downstream PI3K and MAPK pathways. AMG 337 exhibited potency in pharmacodynamic assays evaluating MET signaling in tumor xenograft models; >90% inhibition of Gab-1 phosphorylation was observed at 0.75 mg/kg. These findings describe the preclinical activity and mechanism of action of AMG 337 in MET-dependent tumor models and indicate its potential as a novel therapeutic for the treatment of MET-dependent tumors. Mol Cancer Ther; 15(7); 1568-79. ©2016 AACR. PMID:27196782

  8. Interactive Office user's manual

    NASA Technical Reports Server (NTRS)

    Montgomery, Edward E.; Lowers, Benjamin; Nabors, Terri L.

    1990-01-01

    Given here is a user's manual for Interactive Office (IO), an executive office tool for organization and planning, written specifically for Macintosh. IO is a paperless management tool to automate a related group of individuals into one productive system.

  9. Office of Child Care

    MedlinePlus

    ... 2014 OCC has a variety of resources and tools related to the law. Visit our Reauthorization site to find webinars, program instructions, and other guidance and information. > What is the Office of Child Care (OCC)? The Office of Child ...

  10. LMAL Accounting Office 1936

    NASA Technical Reports Server (NTRS)

    1936-01-01

    Accounting Office: The Langley Memorial Aeronautical Laboratory's accounting office, 1936, with photographs of the Wright brothers on the wall. Although the Lab was named after Samuel P. Langley, most of the NACA staff held the Wrights as their heroes.

  11. Nothing From Everything- A Unified Theory

    NASA Astrophysics Data System (ADS)

    Mehra, Vijay Kumar

    2016-07-01

    Nothing From Everything-A Unified Theory is a philosophical insight into principles of nature through principle of complementary spontaneity and principle of vertical continuity. This work is intended to explain various cosmological phenomena in light of behaviour of particles in range of their respective and relative speed of light. This theory explains creation of Universe from nothing or zero spacetime through scalar energy field collapsing into Higgs field resulting into giving mass to various particles. The energy particles taking origin from nothing while moving away from zero space-time would create space-time of their own order because energy/matter needs space to exist. The particles while moving away from zero space-time would end up in breaking symmetry of matter/energy at their mass infinity (highest possible mass of any particle, which is function of speed of spin). This break in symmetry would lead to curving of particles upon themselves and hence would lead to creation of antiparticles going back in time towards zero spacetime. Therefore the Universe could have been created by alternate layers of particles and antiparticles and also alternate layers of matter and antimatter with decelerating speed of light, which would lead to creation a closed and flat Universe. With increase in mass of Universe (creation of more and more Universe's matter from nothing), the gravitational force of Universe is bound to increase and hence with quantum by quantum increase in gravity, it would apply brakes on relative speed of photon/light out of its reference frame or designated space and hence speed of photon would decrease. If closed and flat Universe was created with decelerating speed of light, then such Universe is bound to contract back with accelerating speed of light which would have inverse impact on gravitational constant across various spacetime zones of Universe. And hence mass bodies would drift away spontaneously purely on basis and proportional to

  12. A unified theory for laminated plates

    NASA Astrophysics Data System (ADS)

    Guiamatsia Tafeuvoukeng, Irene

    A literature survey on plate and beam theories show how the advent of the finite element method and the variational method circa 1940 have been a great stimulant for the research in this field. The initial thin plate formulation has been incrementally expanded to treat the isotropic thick plate, the anisotropic single layer, and then laminated plates. It appears however that current formulations still fall into one of two categories: (1) The formulation is tailored for a specific laminate and/or loading case; (2) or the formulation is too complicated to be of practical relevance. In this work a new unifying approach to laminated plate formulation is presented. All laminated plates, including sandwich panels, subjected to any surface load and with any boundary conditions are treated within a single model. In addition, the fundamental behavior of the plate as a two-dimensional structural element is explained. The novel idea is the introduction of fundamental state solutions, which are analytical far field stress and strain solutions of the laminated plate subjected to a set of hierarchical primary loads, the fundamental loads. These loads are carefully selected to form a basis of the load space, and corresponding solutions are superposed to obtain extremely accurate predictions of the three dimensional solution. six,y,z =aklx,y sikl z where i = 1,..., 6; 1=1,...,l max is a substate of the kth fundamental state k=1,2,3,... Typically, a fundamental state solution is expressed as a through-thickness function (z), while the amplitudes of each fundamental load are found from two dimensional finite element solution as a function of in-plane coordinates (x,y). Three major contributions are produced in this work: (1) A complete calibration of the plate as a two-dimensional structure is performed with pure bending and constant shear fundamental states. (2) There are four independent ways to apply a constant shear resultant on a plate, as opposed to one for a beam. This makes

  13. A Unifying Theory for Lunar Water

    NASA Astrophysics Data System (ADS)

    Sharp, Z. D.; McCubbin, F. M.; Shearer, C. M.

    2011-12-01

    A number of provocative and apparently contradictory studies have been published in the last several years regarding the water content of the Moon. Several authors claim initial water contents equal to that of the Earth, others argue for a dry Moon and still others fall midway between the extremes. Whether or not the Moon was always an anhydrous planet is critical for understand volatile retention of planets. In this communication, we provide a unifying volatile history for the Moon that reconciles all recent studies. Glass beads and melt inclusions from lunar fire fountain samples have high H abundance, suggesting water contents approaching those of the Earth's mantle. The anion compositions of lunar apatites indicate a moderate hydroxyl melt component during late crystallization. However, the extremely elevated Cl isotope compositions of lunar samples indicate degassing from an anhydrous melt, and thermodynamic calculations of evolved metallic iron-bearing KREEP basalts constrain the water content of the lunar interior to <10ppm. Elevated D/H ratio of apatite (~600%) is interpreted as a cometary water source. The oxygen fugacity (f(O2) of the lunar mantle may be as much as ~5 orders of magnitude lower than that of Earth. On Earth, H2O is the dominant phase in the H-O system for the upper mantle, whereas on the Moon, H2 will predominate. The different speciation has important implications. 1) the diffusion rate of H2 in basalt is >100 times higher than for water. A shallow-level magma can degas H2 far more rapidly than H2O, explaining the immeasurably low H content in most lunar basalts. In an unbuffered system, loss of H2 would increase the H2O/H2 ratio, but as long as Fe metal is present, the f(O2) and H2O/H2 ratio will be buffered, allowing for continued loss of H2. 2) Only samples that were rapidly quenched (glass beads) or preserved as melt inclusions could retain any measurable H. 3) H2 degassing and loss to space would significantly increase the D/H ratio

  14. Directory of Federal offices.

    PubMed

    1993-01-01

    This year the Directory of Federal Offices has been updated to include additional publication/catalog resources, most available free of charge. Also, included are some additional offices dedicated to AIDS, infection control and medical device problems. The directory lists major departments and offices, followed by their specific areas of expertise. It should help get you going in the right direction. PMID:10130631

  15. Office Computers: Ergonomic Considerations.

    ERIC Educational Resources Information Center

    Ganus, Susannah

    1984-01-01

    Each new report of the office automation market indicates technology is overrunning the office. The impacts of this technology are described and some ways to manage and physically "soften" the change to a computer-based office environment are suggested. (Author/MLW)

  16. A novel unified coding analytical method for Internet of Things

    NASA Astrophysics Data System (ADS)

    Sun, Hong; Zhang, JianHong

    2013-08-01

    This paper presents a novel unified coding analytical method for Internet of Things, which abstracts out the `displacement goods' and `physical objects', and expounds the relationship thereof. It details the item coding principles, establishes a one-to-one relationship between three-dimensional spatial coordinates of points and global manufacturers, can infinitely expand, solves the problem of unified coding in production phase and circulation phase with a novel unified coding method, and further explains how to update the item information corresponding to the coding in stages of sale and use, so as to meet the requirement that the Internet of Things can carry out real-time monitoring and intelligentized management to each item.

  17. Unified constitutive models for high-temperature structural applications

    NASA Technical Reports Server (NTRS)

    Lindholm, U. S.; Chan, K. S.; Bodner, S. R.; Weber, R. M.; Walker, K. P.

    1988-01-01

    Unified constitutive models are characterized by the use of a single inelastic strain rate term for treating all aspects of inelastic deformation, including plasticity, creep, and stress relaxation under monotonic or cyclic loading. The structure of this class of constitutive theory pertinent for high temperature structural applications is first outlined and discussed. The effectiveness of the unified approach for representing high temperature deformation of Ni-base alloys is then evaluated by extensive comparison of experimental data and predictions of the Bodner-Partom and the Walker models. The use of the unified approach for hot section structural component analyses is demonstrated by applying the Walker model in finite element analyses of a benchmark notch problem and a turbine blade problem.

  18. An Adaptive Unified Differential Evolution Algorithm for Global Optimization

    SciTech Connect

    Qiang, Ji; Mitchell, Chad

    2014-11-03

    In this paper, we propose a new adaptive unified differential evolution algorithm for single-objective global optimization. Instead of the multiple mutation strate- gies proposed in conventional differential evolution algorithms, this algorithm employs a single equation unifying multiple strategies into one expression. It has the virtue of mathematical simplicity and also provides users the flexibility for broader exploration of the space of mutation operators. By making all control parameters in the proposed algorithm self-adaptively evolve during the process of optimization, it frees the application users from the burden of choosing appro- priate control parameters and also improves the performance of the algorithm. In numerical tests using thirteen basic unimodal and multimodal functions, the proposed adaptive unified algorithm shows promising performance in compari- son to several conventional differential evolution algorithms.

  19. Testing ATLAS Z+MET excess with LHC Run 2

    NASA Astrophysics Data System (ADS)

    Lu, Xiaochuan; Shirai, Satoshi; Terada, Takahiro

    2016-05-01

    The ATLAS collaboration reported a 3σ excess in the search of events containing on- Z dilepton, jets, and large missing momentum (MET) in the 8 TeV LHC run. Motivated by this excess, many models of new physics have been proposed. Recently, the ATLAS and CMS collaborations reported new results for similar Z+MET channels in the 13 TeV run. In this paper, we comprehensively discuss the consistency between the proposed models and the LHC results of Run 1 and Run 2. We find that in models with heavy gluino production, there is generically some tension between the 8 TeV and 13 TeV results. On the other hand, models with light squark production provide relatively better fitting to both results.

  20. Preliminary Results from the Mars Pathfinder ASI/MET Experiment

    NASA Technical Reports Server (NTRS)

    Haberle, R. M.; Schofield, J. T.; Crisp, D.; Barnes, J. R.; Magalhaes, J. A.; Murphy, J. R.; Seiff, A.; Wilson, G.; Larsen, S.; Young, Richard E. (Technical Monitor)

    1997-01-01

    Mars Pathfinder successfully landed in the Ares Vallis flood plain (19.3 N, 33.6 W) on July 4, 1997. The spacecraft carried a suite of instruments to record the structure of the atmosphere during the entry, descent, and landing as well as for monitoring meteorological phenomenon while on the surface. Collectively, these instruments are known as the ASI/MET experiment (Atmospheric Structure Investigation/Meteorology). In this paper we present preliminary results from the ASI/MET experiment. As of this writing, the spacecraft is healthy and continues to take daily meteorological measurements. We expect this will continue for almost one more earth year. Additional information is contained in the original extended abstract.

  1. The MET receptor tyrosine kinase in invasion and metastasis.

    PubMed

    Benvenuti, Silvia; Comoglio, Paolo M

    2007-11-01

    Various cytokines and soluble growth factors upon interaction with their membrane receptors are responsible for inducing cellular proliferation, differentiation, movement, and protection from anoikis (a planned suicide activated by normal cells in absence of attachment to neighboring cells or extracellular matrix (EMC)). Among those soluble factors a major position is exerted by hepatocyte growth factor (HGF) together with its receptor MET and macrophage-stimulating protein (MSP) in cooperation with its receptor RON. PMID:17607709

  2. Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS

    PubMed Central

    Vincent, M.D.; Kuruvilla, M.S.; Leighl, N.B.; Kamel–Reid, S.

    2012-01-01

    New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-small-cell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers. The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest. Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents. These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies. PMID:22787409

  3. Astronaut Alan Shepard walks toward MET during first EVA

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut Alan B. Shepard Jr., foreground, Apollo 14 commander, walks toward the Modularized Equipment Transporter (MET), out of view at right, during the first Apollo 14 extravehicular activity (EVA-1). An EVA checklist is attached to Shepard's left wrist. Astronaut Edgar D. Mitchell, lunar module pilot, is in the background working at a subpackage of the Apollo Lunar Surface Experiments Package (ALSEP). The cylindrical keg-like object directly under Mitchell's extended left hand is the Passive Seismic Experiment (PSE).

  4. Unified formalism for higher order non-autonomous dynamical systems

    NASA Astrophysics Data System (ADS)

    Prieto-Martínez, Pedro Daniel; Román-Roy, Narciso

    2012-03-01

    This work is devoted to giving a geometric framework for describing higher order non-autonomous mechanical systems. The starting point is to extend the Lagrangian-Hamiltonian unified formalism of Skinner and Rusk for these kinds of systems, generalizing previous developments for higher order autonomous mechanical systems and first-order non-autonomous mechanical systems. Then, we use this unified formulation to derive the standard Lagrangian and Hamiltonian formalisms, including the Legendre-Ostrogradsky map and the Euler-Lagrange and the Hamilton equations, both for regular and singular systems. As applications of our model, two examples of regular and singular physical systems are studied.

  5. HGF/Met and FOXM1 Form a Positive Feedback Loop and Render Pancreatic Cancer Cells Resistance to Met Inhibition and Aggressive Phenotypes

    PubMed Central

    Cui, Jiujie; Xia, Tian; Xie, Dacheng; Gao, Yong; Jia, Zhiliang; Wei, Daoyan; Wang, Liang; Huang, Suyun; Quan, Ming; Xie, Keping

    2015-01-01

    Purpose Hepatocyte growth factor (HGF)/Met signaling plays critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. Experimental Design The mechanistic role of cross-talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Results Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including RAS/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT, and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross-talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Conclusions Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA. PMID:26876216

  6. Absolute Quantitation of Met Using Mass Spectrometry for Clinical Application: Assay Precision, Stability, and Correlation with MET Gene Amplification in FFPE Tumor Tissue

    PubMed Central

    Catenacci, Daniel V. T.; Liao, Wei-Li; Thyparambil, Sheeno; Henderson, Les; Xu, Peng; Zhao, Lei; Rambo, Brittany; Hart, John; Xiao, Shu-Yuan; Bengali, Kathleen; Uzzell, Jamar; Darfler, Marlene; Krizman, David B.; Cecchi, Fabiola; Bottaro, Donald P.; Karrison, Theodore; Veenstra, Timothy D.; Hembrough, Todd; Burrows, Jon

    2014-01-01

    Background Overexpression of Met tyrosine kinase receptor is associated with poor prognosis. Overexpression, and particularly MET amplification, are predictive of response to Met-specific therapy in preclinical models. Immunohistochemistry (IHC) of formalin-fixed paraffin-embedded (FFPE) tissues is currently used to select for ‘high Met’ expressing tumors for Met inhibitor trials. IHC suffers from antibody non-specificity, lack of quantitative resolution, and, when quantifying multiple proteins, inefficient use of scarce tissue. Methods After describing the development of the Liquid-Tissue-Selected Reaction Monitoring-mass spectrometry (LT-SRM-MS) Met assay, we evaluated the expression level of Met in 130 FFPE gastroesophageal cancer (GEC) tissues. We assessed the correlation of SRM Met expression to IHC and mean MET gene copy number (GCN)/nucleus or MET/CEP7 ratio by fluorescence in situ hybridization (FISH). Results Proteomic mapping of recombinant Met identified 418TEFTTALQR426 as the optimal SRM peptide. Limits of detection (LOD) and quantitation (LOQ) for this peptide were 150 and 200 amol/µg tumor protein, respectively. The assay demonstrated excellent precision and temporal stability of measurements in serial sections analyzed one year apart. Expression levels of 130 GEC tissues ranged (<150 amol/µg to 4669.5 amol/µg. High correlation was observed between SRM Met expression and both MET GCN and MET/CEP7 ratio as determined by FISH (n = 30; R2 = 0.898). IHC did not correlate well with SRM (n = 44; R2 = 0.537) nor FISH GCN (n = 31; R2 = 0.509). A Met SRM level of ≥1500 amol/µg was 100% sensitive (95% CI 0.69–1) and 100% specific (95% CI 0.92–1) for MET amplification. Conclusions The Met SRM assay measured the absolute Met levels in clinical tissues with high precision. Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET

  7. An Evaluation of Global Address Space Languages: Co-Array Fortran and Unified Parallel C

    SciTech Connect

    Coarfa, Cristian; Dotsenko, Yuri; Mellor-Crummey, John M.; Cantonnet, Franois; El-Ghazawi, Tarek; Mohanti, Ashrujit; Yao, Yiyi; Chavarría-Miranda, Daniel

    2005-06-10

    Co-array Fortran (CAF) and Unified Parallel C (UPC) are two emerging languages for single-program, multiple-data global address space programming. These languages boost programmer productivity by providing shared variables for communication instead of message passing. However, the performance of these emerging languages still has room for improvement. In this paper, we study the performance of variants of the NAS MG, CG, SP, and BT benchmarks on several modern cluster architectures to identify challenges that must be met to deliver top performance. We compare CAF and UPC variants of these programs with the original Fortran+MPI code. Today, CAF and UPC programs deliver scalable performance on clusters only when written to use bulk communication. However, our experiments uncovered some significant performance bottlenecks limiting UPC performance on all platforms. We account for the root causes of these performance anomalies and show that they can be remedied with additional compiler improvements, in particular we show that many of these obstacles can be resolved with adequate optimizations by the backend C compilers.

  8. Heating and flooding: A unified approach for rapid generation of free energy surfaces

    NASA Astrophysics Data System (ADS)

    Chen, Ming; Cuendet, Michel A.; Tuckerman, Mark E.

    2012-07-01

    We propose a general framework for the efficient sampling of conformational equilibria in complex systems and the generation of associated free energy hypersurfaces in terms of a set of collective variables. The method is a strategic synthesis of the adiabatic free energy dynamics approach, previously introduced by us and others, and existing schemes using Gaussian-based adaptive bias potentials to disfavor previously visited regions. In addition, we suggest sampling the thermodynamic force instead of the probability density to reconstruct the free energy hypersurface. All these elements are combined into a robust extended phase-space formalism that can be easily incorporated into existing molecular dynamics packages. The unified scheme is shown to outperform both metadynamics and adiabatic free energy dynamics in generating two-dimensional free energy surfaces for several example cases including the alanine dipeptide in the gas and aqueous phases and the met-enkephalin oligopeptide. In addition, the method can efficiently generate higher dimensional free energy landscapes, which we demonstrate by calculating a four-dimensional surface in the Ramachandran angles of the gas-phase alanine tripeptide.

  9. 6. Interior, rear offices: operations assistant office looking north toward ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Interior, rear offices: operations assistant office looking north toward security operations officer's office. - Ellsworth Air Force Base, Rushmore Air Force Station, Security Central Control Building, Quesada Drive, Blackhawk, Meade County, SD

  10. Integration Defended: Berkeley Unified's Strategy to Maintain School Diversity

    ERIC Educational Resources Information Center

    Chavez, Lisa; Frankenberg, Erica

    2009-01-01

    In June 2007, the Supreme Court limited the tools that school districts could use to voluntarily integrate schools. In the aftermath of the decision, educators around the country have sought models of successful plans that would also be legal. One such model may be Berkeley Unified School District's (BUSD) plan. Earlier this year, the California…

  11. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) INCOME TAXES (CONTINUED) Basis, Stock Ownership, and Earnings and Profits Rules § 1.1502-36 Unified loss... shares of S stock. If the transferred share is a loss share after any basis redetermination under paragraph (b) of this section, paragraph (c) of this section applies and may reduce M's basis in...

  12. Unified (Russian) State Exam in English: Reading Comprehension Tasks

    ERIC Educational Resources Information Center

    Solnyshkina, Marina I.; Harkova, Elena V.; Kiselnikov, Aleksander S.

    2014-01-01

    The article summarizes the study of Reading Comprehension Tasks utilized in preparation for Unified (Russian) State Exam. The corpus of reading tasks was analyzed with the use of the classification algorithm developed by Weir and Urquhart (1998), and aimed at determining the level of engagement (local or global) and type of engagement (literal or…

  13. Unified Science: Solving Problems in Science, Technology, and Society.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Curriculum Development.

    The unified science approach to instruction is one in which the concepts and processes of science are presented to emphasize the fundamental unity of scientific thought rather than the distinctions among the various scientific disciplines. The general thrust of this program is to provide students with motivating, meaningful units that will…

  14. When Unified Teacher Pay Scales Meet Differential Alternative Returns

    ERIC Educational Resources Information Center

    Walsh, Patrick

    2014-01-01

    This paper quantifies the extent to which unified teacher pay scales and differential alternatives produce opportunity costs that are asymmetric in math and verbal skills. Data from the Baccalaureate and Beyond 1997 and 2003 follow-ups are used to estimate a fully parametric, selection-corrected wage equation for nonteachers, which is then used to…

  15. Columbus Unified High School: Every Adult Advocates, Every Student Graduates

    ERIC Educational Resources Information Center

    Principal Leadership, 2011

    2011-01-01

    This article features Columbus Unified High School, a school that takes pride in knowing that each student will graduate prepared for his or her future. Although poverty (45%) and unemployment (25%) are widespread in this rural Kansas community, the community members are fierce in their loyalty to the school. Last year, 97.8% of the four-year…

  16. 24 CFR 578.11 - Unified Funding Agency.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... collaborative applicant has financial management systems that meet the standards set forth in 24 CFR 84.21 (for nonprofit organizations) and 24 CFR 85.20 (for States); (3) The collaborative applicant demonstrates the... as the Unified Funding Agency (UFA) for a Continuum, a collaborative applicant must be selected...

  17. A Unified Approach for Patterning via Frontal Photopolymerization.

    PubMed

    Vitale, Alessandra; Hennessy, Matthew G; Matar, Omar K; Cabral, João T

    2015-10-28

    A unified patterning strategy via frontal photopolymerization (FPP) that is robust to a wide range of radical photopolymerizing systems, including thiol-ene and acrylic monomers is reported. The factors governing the spatiotemporal solidification process, including front position, profile shape, and thermal effects, are investigated and modeled theoretically, resulting in the predictive FPP patterning of polymer networks with prescribed dimensions. PMID:26333100

  18. Unified model of primordial black holes and dark matter formation

    NASA Astrophysics Data System (ADS)

    Grobov, A. V.; Dmitriev, A. E.; Dokuchaev, V. I.; Rubin, S. G.

    2016-02-01

    We propose a unified model of primordial black holes and soliton dark matter formation. Dynamic of spherically symmetric clumps of scalar field is considered in Newtonian approximation. The formation of hidden mass of the Universe is discussed. Numerical solution of the system of interacting scalar and gravitational fields is used to obtain the mass of a clumps.

  19. A unifying theory for the functional architecture of endothermic thermoregulation

    PubMed Central

    Flouris, Andreas D

    2014-01-01

    Developing a unifying theory for the functional architecture of endothermic thermoregulation has been proven to be a challenging endeavor. Three papers published in this issue of Temperature take a closer look at this problem and add interesting views to our knowledge about the way that endothermic thermoregulation works.

  20. The Vector Space as a Unifying Concept in School Mathematics.

    ERIC Educational Resources Information Center

    Riggle, Timothy Andrew

    The purpose of this study was to show how the concept of vector space can serve as a unifying thread for mathematics programs--elementary school to pre-calculus college level mathematics. Indicated are a number of opportunities to demonstrate how emphasis upon the vector space structure can enhance the organization of the mathematics curriculum.…

  1. Schr"odinger's Unified Field Theory: Physics by Public Relations

    NASA Astrophysics Data System (ADS)

    Halpern, Paul

    2009-05-01

    We will explore the circumstances surrounding Erwin Schr"odinger's announcement in January 1947 that he had developed a comprehensive unified field theory of gravitation and electromagnetism. We will speculate on Schr"odinger's motivations for the mode and tone of his statements, consider the reaction of the international press within the context of the postwar era, and examine Einstein's response.

  2. Are There Unifying Trends in the Psychologies of 1990?

    ERIC Educational Resources Information Center

    Anastasi, Anne

    The complexity and rapid expansion of the entire field of psychology make it appropriate to speak of "psychologies" when acknowledging the need for specialization of training and expertise. Nevertheless, unifying trends (UTs) exist in psychology, even though there can be no single set of theoretical principles to account for all empirical…

  3. Exemplary Teaching and Programs in Santa Clara Unified School District.

    ERIC Educational Resources Information Center

    Carter, Norman

    Gathered together are descriptions of exemplary teaching programs, systems, techniques, innovations, teaching items, or methods that have been collected from teachers and administrators in the Santa Clara Unified School District. Listed under schools, each description offers different learning conventions that have proved successful or useful.…

  4. Effects of Positive Unified Behavior Support on Instruction

    ERIC Educational Resources Information Center

    Scott, John S.; White, Richard; Algozzine, Bob; Algozzine, Kate

    2009-01-01

    "Positive Unified Behavior Support" (PUBS) is a school-wide intervention designed to establish uniform attitudes, expectations, correction procedures, and roles among faculty, staff, and administration. PUBS is grounded in the general principles of positive behavior support and represents a straightforward, practical implementation model. When…

  5. Calculus of Functions and Their Inverses: A Unified Approach

    ERIC Educational Resources Information Center

    Krishnan, Srilal N.

    2006-01-01

    In this pedagogical article, I explore a unified approach in obtaining the derivatives of functions and their inverses by adopting a guided self-discovery approach. I begin by finding the derivative of the exponential functions and the derivative of their inverses, the logarithmic functions. I extend this approach to generate formulae for the…

  6. Unified hazardous waste and hazardous materials management regulatory program

    SciTech Connect

    Neese, K.J. )

    1994-04-01

    The administration and regulation of hazardous wastes and materials in the state of California has for many years been overseen by a number of regulatory agencies that have jurisdiction to undertake or compel cleanup. The jurisdiction and authority of each of these agencies differ, as do their philosophical underpinnings, in terms of protection of human health and the environment versus protection of groundwater resources. In 1993, Senate Bill 1082 was enacted to require the Secretary for Environmental Protection, by January 1, 1996, to adopt implementing regulations and implement a unified hazardous materials management regulatory program to consolidate the administration of specific statutory requirements for the regulation of hazardous wastes and minerals. All aspects of the unified program related to the adoption and interpretation of statewide standards and requirements will be the responsibility under existing law. For example, for underground storage tanks, that agency shall be the state Water Resources Control Board. The Department of Toxic Substances Control shall have the sole responsibility for the determination of whether a waste is hazardous or nonhazardous. Those aspects of the unified program related to the application of statewide standards to particular facilities, including the grant of authorizations, the issuance of permits, the review of reports and plans, and the enforcement of those standards and requirements against particular facilities, will be the responsibility of the certified unified program agency.

  7. The Unified Core: A "Major" Learning Community Model in Action

    ERIC Educational Resources Information Center

    Powell, Gwynn M.; Johnson, Corey W.; James, J. Joy; Dunlap, Rudy

    2011-01-01

    The Unified Core is an innovative approach to higher education that blends content through linked courses within a major to create a community of learners. This article offers the theoretical background for the approach, describes the implementation, and offers suggestions to educators who would like to design their own version of this innovative…

  8. Four Courses within a Discipline: UGA Unified Core

    ERIC Educational Resources Information Center

    Powell, Gwynn M.; Johnson, Corey W.; James, Joy; Dunlap, Rudy

    2013-01-01

    This article introduces the reader to the Unified Core Curriculum model developed and implemented at the University of Georgia (UGA). Four courses are taught as one course to the juniors coming into the Recreation and Leisure Studies major. An overview of the blended course and sample assignments are provided, as well as a discussion of challenges…

  9. Alameda Unified School District, 2009-2011. Alameda Case Study

    ERIC Educational Resources Information Center

    Pivot Learning Partners, 2011

    2011-01-01

    When the five-member Board of the Alameda Unified School District selected Kirsten Vital as the new superintendent in 2009, they chose someone from outside their tight-knit community. Board Trustee Margie Sherratt thought Vital was chosen to "get us moving," to be a change agent on closing the achievement gap. Vital, in her initial conversations…

  10. In Search of a Unified Model of Language Contact

    ERIC Educational Resources Information Center

    Winford, Donald

    2013-01-01

    Much previous research has pointed to the need for a unified framework for language contact phenomena -- one that would include social factors and motivations, structural factors and linguistic constraints, and psycholinguistic factors involved in processes of language processing and production. While Contact Linguistics has devoted a great deal…

  11. Unified Technical Concepts. Supplementary Modules S1-S8.

    ERIC Educational Resources Information Center

    Technical Education Research Center, Waco, TX.

    Prepared for use with thirteen modules (CE 025 468-480) in the Unified Technical Concepts postsecondary physics instructional package, this set of eight support modules is designed to strengthen mathematical and laboratory skills in areas such as units, graphing, logarithms, dimensional analysis, and basic trigonometry. Module titles include…

  12. Unified Model for Academic Competence, Social Adjustment, and Psychopathology.

    ERIC Educational Resources Information Center

    Schaefer, Earl S.; And Others

    A unified conceptual model is needed to integrate the extensive research on (1) social competence and adaptive behavior, (2) converging conceptualizations of social adjustment and psychopathology, and (3) emerging concepts and measures of academic competence. To develop such a model, a study was conducted in which teacher ratings were collected on…

  13. Unified symmetry: In the small and in the large

    SciTech Connect

    Kursunoglu, B.N.; Mintz, S.; Perlmutter, A.

    1995-12-31

    The agenda for the Coral Gables conferences is the unification of cosmology and elementary particle physics. This 22nd conference was divided into the following sections: Unified General Relativity and Quantum Theory; The Very Early Universe; Progress in New and Old ideas; Aspects of Particle Physics; and Further Inspirations from the Electroweak Theory, Supersymmetry, Supergravity.

  14. Alternative Test Criteria in Covariance Structure Analysis: A Unified Approach.

    ERIC Educational Resources Information Center

    Satorra, Albert

    1989-01-01

    Within covariance structural analysis, a unified approach to asymptotic theory of alternative test criteria for testing parametric restrictions is provided. More general statistics for addressing the case where the discrepancy function is not asymptotically optimal, and issues concerning power analysis and the asymptotic theory of testing-related…

  15. A Unified Approach for Solving Nonlinear Regular Perturbation Problems

    ERIC Educational Resources Information Center

    Khuri, S. A.

    2008-01-01

    This article describes a simple alternative unified method of solving nonlinear regular perturbation problems. The procedure is based upon the manipulation of Taylor's approximation for the expansion of the nonlinear term in the perturbed equation. An essential feature of this technique is the relative simplicity used and the associated unified…

  16. Project CERES. Ceres Unified School District, Ceres, California.

    ERIC Educational Resources Information Center

    Baker, Octave V.; Lish, Virginia

    This description of career education activities in the Ceres (California) Unified School District was prepared as part of a study conducted to identify evaluated, exemplary career education activities which represent the best of the current career education programs and practices referred to in Public Law 93-380. (See CE 018 212 for the final…

  17. Unified treatment of bound-state and scattering problems

    SciTech Connect

    Adhikari, S.K.; Tomio, L.

    1988-01-01

    The iteration-subtraction method for the unified treatment of bound-state and scattering problems is compared and contrasted with a similar method for the two-body bound-state problem via nonsingular scattering equations developed recently. We also compare another recent method for solving bound-state problems with the iteration-subtraction method.

  18. Teachers' Perceptions of Technology Integration in a Unified School District

    ERIC Educational Resources Information Center

    Bloodman, Suzette L.

    2014-01-01

    A unified school district (USD) continues to invest millions of dollars into its technology integration initiatives with minimal academic gains. Since teachers are essential to effective technology integration, the purpose of this phenomenological study was to analyze the perceptions of 13 teachers within the USD relative to how they could more…

  19. Access to Biomedical Information: The Unified Medical Language System.

    ERIC Educational Resources Information Center

    Squires, Steven J.

    1993-01-01

    Describes the development of a Unified Medical Language System (UMLS) by the National Library of Medicine that will retrieve and integrate information from a variety of information resources. Highlights include the metathesaurus; the UMLS semantic network; semantic locality; information sources map; evaluation of the metathesaurus; future…

  20. Unified Budget Recommendations for Fiscal Year 1987-88.

    ERIC Educational Resources Information Center

    Alabama State Commission on Higher Education, Montgomery.

    Recommendations for appropriations to each public college and university in Alabama are presented by the Alabama Commission on Higher Education (ACHE) in its 1987-1988 unified budget report. For each institution and type of expenditure (e.g., academic, research, public service, and capital outlay), data are provided for: 1985-1986 appropriations,…

  1. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

    SciTech Connect

    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-11-15

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  2. 76 FR 41745 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... Air Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule... Valley Unified Air Pollution Control District portion of the California State Implementation Plan (SIP... Valley Unified Air Pollution Control District (SJVUAPCD) Rule 4682, Polystyrene, Polyethylene,...

  3. MET17 and Hydrogen Sulfide Formation in Saccharomyces cerevisiae

    PubMed Central

    Spiropoulos, Apostolos; Bisson, Linda F.

    2000-01-01

    Commercial isolates of Saccharomyces cerevisiae differ in the production of hydrogen sulfide (H2S) during fermentation, which has been attributed to variation in the ability to incorporate reduced sulfur into organic compounds. We transformed two commercial strains (UCD522 and UCD713) with a plasmid overexpressing the MET17 gene, which encodes the bifunctional O-acetylserine/O-acetylhomoserine sulfhydrylase (OAS/OAH SHLase), to test the hypothesis that the level of activity of this enzyme limits reduced sulfur incorporation, leading to H2S release. Overexpression of MET17 resulted in a 10- to 70-fold increase in OAS/OAH SHLase activity in UCD522 but had no impact on the level of H2S produced. In contrast, OAS/OAH SHLase activity was not as highly expressed in transformants of UCD713 (0.5- to 10-fold) but resulted in greatly reduced H2S formation. Overexpression of OAS/OAH SHLase activity was greater in UCD713 when grown under low-nitrogen conditions, but the impact on reduction of H2S was greater under high-nitrogen conditions. Thus, there was not a good correlation between the level of enzyme activity and H2S production. We measured cellular levels of cysteine to determine the impact of overexpression of OAS/OAH SHLase activity on sulfur incorporation. While Met17p activity was not correlated with increased cysteine production, conditions that led to elevated cytoplasmic levels of cysteine also reduced H2S formation. Our data do not support the simple hypothesis that variation in OAS/OAH SHLase activity is correlated with H2S production and release. PMID:11010893

  4. Office of Inspector General audit report on small disadvantaged business program at the Chicago Operations Office

    SciTech Connect

    1999-01-01

    The Office of Inspector General performed audits of the Small Disadvantaged Business Program at five management and operating contractors in FY 1994. The audits disclosed that none of the contractors fully met the intent of the Act and implementing regulations. The contractors awarded some subcontracts to firms of questionable program eligibility. Also, two of the contractors concentrated awards among a limited number of small disadvantaged businesses, and used procurement practices that precluded opportunities for many small disadvantaged businesses to participate. The objective of this audit was to determine whether Chicago was providing the maximum practicable opportunity for small disadvantaged businesses to participate in contract awards.

  5. 76 FR 13272 - Branch Offices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... Office of Thrift Supervision Branch Offices AGENCY: Office of Thrift Supervision (OTS), Treasury. ACTION... 1995, 44 U.S.C. 3507. The Office of Thrift Supervision within the Department of the Treasury will... approval number, to Information Collection Comments, Chief Counsel's Office, Office of Thrift...

  6. The BDNF Val66Met Polymorphism Modulates the Generalization of Cued Fear Responses to a Novel Context

    PubMed Central

    Mühlberger, Andreas; Andreatta, Marta; Ewald, Heike; Glotzbach-Schoon, Evelyn; Tröger, Christian; Baumann, Christian; Reif, Andreas; Deckert, Jürgen; Pauli, Paul

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) has a crucial role in activity-dependent synaptic plasticity and learning and memory. The human functional single-nucleotide BDNF rs6265 (Val66Met) polymorphism has been found to be associated with alteration in neural BDNF release and function correlating with altered emotional behavior. Here, we investigated for the first time the hypothesis that this polymorphism in humans modulates the context dependency of conditioned fear responses. Applying a new paradigm examining generalization of cued fear across contexts, 70 participants stratified for BDNF Val66Met polymorphism were guided through two virtual offices (context) in which briefly illuminated blue and yellow lights served as cues. In the fear context, one light (conditioned stimulus, CS+) but not the other light (CS−) was associated with an electric shock (unconditioned stimulus, US). In the safety context, both lights were presented too, but no US was delivered. During the test phase, lights were presented again both in learning contexts and in a novel generalization context without any US. All participants showed clear fear conditioning to the CS+ in the fear context as indicated by potentiation of startle responses and reports of fear. No fear reactions were found for the CS+ in the safety context. Importantly, generalization of fear responses indicated by the potentiation of startle response to the CS+ compared with the CS− in the novel context was evident only in the Met-carrying group. These are the first results to provide evidence in humans that BDNF modulates the generalization of fear responses. Such context-dependent generalization processes might predispose Met carriers for affective and anxiety disorders. PMID:24247044

  7. Project UNIFY. National Dropout Prevention Center/Network Newsletter. Volume 22, Number 1

    ERIC Educational Resources Information Center

    Duckenfield, Marty, Ed.

    2011-01-01

    The "National Dropout Prevention Newsletter" is published quarterly by the National Dropout Prevention Center/Network. This issue contains the following articles: (1) Special Olympics Project UNIFY (Andrea Cahn); (2) The Impact of Project UNIFY; (3) Project UNIFY Brings Youth Together to Learn and Graduate (William H. Hughes); (4) Physical…

  8. 78 FR 1919 - Sunshine Act Meetings; Unified Carrier Registration Plan Board of Directors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... Unified Carrier Registration Plan Board of Directors Meeting. TIME AND DATE: The meeting will be held on.... MATTERS TO BE CONSIDERED: The Unified Carrier Registration Plan Board of Directors (the Board) will... Gutierrez, Chair, Unified Carrier Registration Board of Directors at (505) 827-4565. Issued on: December...

  9. 76 FR 16471 - Sunshine Act Meetings; Unified Carrier Registration Plan Board of Directors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... Federal Motor Carrier Safety Administration Sunshine Act Meetings; Unified Carrier Registration Plan Board.... STATUS: Open to the public. MATTERS TO BE CONSIDERED: The Unified Carrier Registration Plan Board of Directors (the Board) will continue its work in developing and implementing the Unified Carrier...

  10. 75 FR 58467 - Sunshine Act Meetings; Unified Carrier Registration Plan Board of Directors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... Federal Motor Carrier Safety Administration Sunshine Act Meetings; Unified Carrier Registration Plan Board... telephone. STATUS: Open to the public. MATTERS TO BE CONSIDERED: The Unified Carrier Registration Plan Board of Directors (the Board) will continue its work in developing and implementing the Unified...

  11. 75 FR 51161 - Sunshine Act Meetings; Unified Carrier Registration Plan Board of Directors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ... Federal Motor Carrier Safety Administration Sunshine Act Meetings; Unified Carrier Registration Plan Board... telephone. STATUS: Open to the public. MATTERS TO BE CONSIDERED: The Unified Carrier Registration Plan Board of Directors (the Board) will continue its work in developing and implementing the Unified...

  12. 76 FR 69793 - Sunshine Act Meetings; Unified Carrier Registration Plan Board of Directors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... Federal Motor Carrier Safety Administration Sunshine Act Meetings; Unified Carrier Registration Plan Board.... STATUS: Open to the public. MATTERS TO BE CONSIDERED: The Unified Carrier Registration Plan Board of Directors (the Board) will continue its work in developing and implementing the Unified Carrier...

  13. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption

    PubMed Central

    2014-01-01

    Forward A composite unifying theory on causes of obesity related-MetS has been formulated and published in an accompanying article (1). In the current article, the historical and recent past, present and future corollaries of this theory are discussed. By presenting this composite theory and corollaries, it is hoped that human evolution and physiology will be viewed and studied from a new vantage point. The politics of management of ecological farming and nutrition will change, a profound reconfiguration of scientific theory generation and advancement in a ‘high-tech’ world can be made, and pathways for solutions recognised. Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome’s underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to

  14. Materials Evaluation Test Series (METS) 04, 05, and 06

    SciTech Connect

    Zalk, D; Ingram, C; Simmons, L; Arganbright, R; Lyle, J; Wong, K

    2006-03-23

    The purpose of this work is to examine the environmental, safety, health and operational aspects of detonating a confined explosive test apparatus that has been designed to maximize the dynamics of impact on beryllium metal components for Contained Firing Facility (CFF) applications. A combination of experimental collection and evaluation methods were designed and implemented to provide an evaluation of immediately postdetonation by-products reflecting a potential worst-case scenario beryllium aerosolization explosive event. The collective Material Evaluation Test Series (METS) 04 - 06 provided explosive devices designed to scale for the dedicated METS firing tank that would provide a post-detonation internal environment comparable to the CFF. The experimental results provided appropriate information to develop operational parameters to be considered for conducting full-scale beryllium-containing experimental tests with similar designs within CFF and B801A. These operational procedures include the inclusion of chelating agents in pre-shot CFF cardboard containers with a minimum of 600 gallons content, an extended time period post-test before purging the CFF chamber, and an adaptation of approaches toward applications of the scrubber and HEPA systems during the post-shot sequence for an integrated environmental, safety, and health approach. In addition, re-entry and film retrieval procedures will be adapted, in line with abatement techniques for cleaning the chamber, that will be required for work inside a CFF that will contain an elevated concentration of spherical and highly aerosolizable beryllium particulate.

  15. MicroRNA and MET in lung cancer

    PubMed Central

    2015-01-01

    MicroRNAs (miRNAs) are a class of small non-protein coding RNAs that modulate important cellular functions via their post-transcriptional regulation of messenger RNAs (mRNAs). Recent evidences from multiple tumor types and model systems implicate miRNA dysregulation as a common mechanism of tumorigenesis, cancer progression and resistance to therapy. Several miRNAs are dysregulated in cancers and a single miRNA can have multiple targets involved in different oncogenic pathways. MET, the tyrosine kinase receptor for hepatocyte growth factor (HGF), has a central role in lung cancer development and in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors; it has been predicted and shown to be the target gene of multiple miRNAs, which play a crucial role in controlling its activity in a stimulatory or inhibitory sense. In this review we will focus on the most important and recent studies about the role of miRNAs in the control of MET expression, reporting also the progress made using miRNAs for therapy of lung cancer. PMID:25992367

  16. Computational study of Met-Car analogue heterofullerenes

    NASA Astrophysics Data System (ADS)

    Domingos, H. S.

    2006-06-01

    Structural, chemical and electronic properties of a number of Met-Car analogue heterofullerenes were investigated using a combination of ab initio and semi-empirical quantum mechanical calculations.Met-Car clusters of known structure and chemistry were studied together with some new hypothetical configurations. In particular, the stability of clusters of the form Y8C12 (Y = Al, S, Si, Ti, As, Bi, Sb, P, N, B, Sn, Sc, Cr, V), XY7C12 (X, Y = B, N, Si) and Y8Z12 (Y, Z = N, B, Si) were investigated based on computed binding energies, Mulliken charges, bond orders and ionization potentials. The results indicate that some novel clusters are due for observation. Clusters of this type are known to form the building blocks of new polymerized solids and may exhibit some novel dielectric, magnetic and superconducting properties. Isomers of D3d symmetry, which are possible global energy minima for Cr, V and Sc carbide clusters, were also identified.

  17. MetOp/HIRS pre-launch characterization data reanalysis

    NASA Astrophysics Data System (ADS)

    Chang, Tiejun; Cao, Changyong

    2011-09-01

    Instrument self-emission and nonlinear response play important roles in satellite thermal infrared radiometers, and can affect the accuracy of Earth scene radiance retrieval if uncorrected. This paper presents a simplified self-emission model for infrared radiometers and analyzes the interrelationships between the instrument selfemission, detector nonlinearity, and calibration intercept and slope variations using MetOp-A/HIRS prelaunch characterization data. HIRS is a traditional cross-track line scanning radiometer in the infrared and visible spectrum, including 12 long wave infrared channels (669-1529cm-1), 7 short wave infrared channels (2188- 2657cm-1), and 1 visible channel, with beamsplitters and a rotating filter wheel assembly consisting of 20 spectral filters separates individual channels. The warm filters and other in-path components generate selfemission which becomes the majority of the total radiance falling on the detector. The pre-launch TV data allow us to evaluate the self-emission using the simplified model. It was found that the self-emission contributions at the detectors are in the range of 95% to 97%. The self-emission fluctuates with the instrument temperature and causes the variation in instrument response, including the variations of intercept and the instrument gain. The quantification of these variations provides guideline for on-orbit calibration algorithm improvement. The selfemission model is improved and its impact on MetOp-A/HIRS on-orbit calibration and Earth scene retrieval are also assessed.

  18. Biology of MET: a double life between normal tissue repair and tumor progression

    PubMed Central

    2015-01-01

    MNNG HOS transforming gene (MET) is a class IV receptor tyrosine kinase, expressed on the surface of epithelial cells. The interaction with the hepatocyte grow factor (HGF) induces MET dimerization and the activation of multiple intracellular pathways leading to cell proliferation, anti-apoptosis, morphogenic differentiation, motility, invasion, and angiogenesis. Knock out mice have demonstrated that MET is necessary for normal embryogenesis including the formation of striate muscles, liver and trophoblastic structures. The overexpression of MET and HGF are common in solid tumors and contribute to determine their growth. Indeed, MET has been cloned as a transforming gene from a chemically induced human osteosarcoma cell line and therefore is considered a proto-oncogene. Germline MET mutations are characteristic of hereditary papillary kidney cancers and MET amplification is observed in tumors including lung and gastric adenocarcinomas. The inhibition of MET signaling is the target for specific drugs that are raising exciting expectation for medical treatment of cancer. PMID:25992381

  19. GOME-2 total ozone columns from MetOp-A/MetOp-B and assimilation in the MACC system

    NASA Astrophysics Data System (ADS)

    Hao, N.; Koukouli, M. E.; Inness, A.; Valks, P.; Loyola, D. G.; Zimmer, W.; Balis, D. S.; Zyrichidou, I.; Van Roozendael, M.; Lerot, C.; Spurr, R. J. D.

    2014-03-01

    The two Global Ozone Monitoring Instrument (GOME-2) sensors operated in tandem are flying onboard EUMETSAT's MetOp-A and MetOp-B satellites, launched in October 2006 and September 2012 respectively. This paper presents the operational GOME-2/MetOp-A (GOME-2A) and GOME-2/MetOp-B (GOME-2B) total ozone products provided by the EUMETSAT Satellite Application Facility on Ozone and Atmospheric Chemistry Monitoring (O3M-SAF). These products are generated using the latest version of the GOME Data Processor (GDP version 4.7). The enhancements in GDP 4.7, including the application of Brion-Daumont-Malicet ozone absorption cross-sections, are presented here. On a global scale, GOME-2B has the same high accuracy as the corresponding GOME-2A products. There is an excellent agreement between the ozone total columns from the two sensors, with GOME-2B values slightly lower with a mean difference of only 0.55 ± 0.29%. First global validation results for 6 months of GOME-2B total ozone using ground-based measurements show that on average the GOME-2B total ozone data obtained with GDP 4.7 slightly overestimate Dobson observations by about 2.0 ± 1.0% and Brewer observations by about 1.0 ± 0.8%. It is concluded that the total ozone columns (TOCs) provided by GOME-2A and GOME-2B are consistent and may be used simultaneously without introducing trends or other systematic effects. GOME-2A total ozone data have been used operationally in the Copernicus atmospheric service project MACC-II (Monitoring Atmospheric Composition and Climate - Interim Implementation) near-real-time (NRT) system since October 2013. The magnitude of the bias correction needed for assimilating GOME-2A ozone is reduced (to about -6 DU in the global mean) when the GOME-2 ozone retrieval algorithm changed to GDP 4.7.

  20. GOME-2 total ozone columns from MetOp-A/MetOp-B and assimilation in the MACC system

    NASA Astrophysics Data System (ADS)

    Hao, N.; Koukouli, M. E.; Inness, A.; Valks, P.; Loyola, D. G.; Zimmer, W.; Balis, D. S.; Zyrichidou, I.; Van Roozendael, M.; Lerot, C.; Spurr, R. J. D.

    2014-09-01

    The two Global Ozone Monitoring Instrument (GOME-2) sensors operated in tandem are flying onboard EUMETSAT's (European Organisation for the Exploitation of Meteorological Satellites) MetOp-A and MetOp-B satellites, launched in October 2006 and September 2012 respectively. This paper presents the operational GOME-2/MetOp-A (GOME-2A) and GOME-2/MetOp-B (GOME-2B) total ozone products provided by the EUMETSAT Satellite Application Facility on Ozone and Atmospheric Chemistry Monitoring (O3M-SAF). These products are generated using the latest version of the GOME Data Processor (GDP version 4.7). The enhancements in GDP 4.7, including the application of Brion-Daumont-Malicet ozone absorption cross sections, are presented here. On a global scale, GOME-2B has the same high accuracy as the corresponding GOME-2A products. There is an excellent agreement between the ozone total columns from the two sensors, with GOME-2B values slightly lower with a mean difference of only 0.55±0.29%. First global validation results for 6 months of GOME-2B total ozone using ground-based measurements show that on average the GOME-2B total ozone data obtained with GDP 4.7 are slightly higher than, both, Dobson observations by about 2.0±1.0% and Brewer observations by about 1.0±0.8%. It is concluded that the total ozone columns (TOCs) provided by GOME-2A and GOME-2B are consistent and may be used simultaneously without introducing systematic effects, which has been illustrated for the Antarctic ozone hole on 18 October 2013. GOME-2A total ozone data have been used operationally in the Copernicus atmospheric service project MACC-II (Monitoring Atmospheric Composition and Climate - Interim Implementation) near-real-time (NRT) system since October 2013. The magnitude of the bias correction needed for assimilating GOME-2A ozone is reduced (to about -6 DU in the global mean) when the GOME-2 ozone retrieval algorithm changed to GDP 4.7.

  1. Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

    2016-03-01

    Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. PMID:26923413

  2. An Examination of Tri-Level Collaboration around Student Achievement Using the Gap Analysis Approach: Central Office Leadership Factors

    ERIC Educational Resources Information Center

    Llamas, Sonia Rodarte

    2013-01-01

    Using the Gap Analysis problem-solving framework (Clark & Estes, 2008), this study examined collaboration around student achievement at the central office leadership level in the Pasadena Unified School District (PUSD). This study is one of three concurrent studies focused on collaboration around student achievement in the PUSD that include…

  3. Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors

    SciTech Connect

    Williams, David K; Chen, Xiao-Tao; Tarby, Christine; Kaltenbach, Robert; Cai, Zhen-Wei; Tokarski, John S; An, Yongmi; Sack, John S; Wautlet, Barri; Gullo-Brown, Johnni; Henley, Benjamin J; Jeyaseelan, Robert; Kellar, Kristen; Manne, Veeraswamy; Trainor, George L; Lombardo, Louis J; Fargnoli, Joseph; Borzilleri, Robert M

    2010-09-03

    Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.

  4. The Educator's "Action" Office.

    ERIC Educational Resources Information Center

    Martin, Dikran J.

    Design criteria, standards, and human factors related to designing and planning flexible and efficient work environments for college faculty members are overviewed with six model (example) office plans included. The physical and psychological design needs in such an office facility are given, with task performance data on student faculty…

  5. Office Education Handbook.

    ERIC Educational Resources Information Center

    Powell, Theressa

    This handbook is designed to serve as a reference for office education instructors. Addressed in the individual sections of the guide are the following topics: design and delivery of office education, teacher qualifications and certification requirements, cooperative programs, preemployment laboratory programs, advisory committees, public…

  6. Chief Academic Officers.

    ERIC Educational Resources Information Center

    Mathews, Jay

    2001-01-01

    The emergence of a number 2 post (chief academic officer) focused on instructional leadership brings a new dynamic to the central office-particularly those headed by nontraditional superintendents. Used in universities, the CAO title lends cache. Women can get stuck in CAO positions; a few districts are eliminating them. (MLH)

  7. The Chief Diversity Officer

    ERIC Educational Resources Information Center

    Williams, Damon; Wade-Golden, Katrina

    2007-01-01

    Numerous institutions are moving toward the chief diversity officer model of leading and managing diversity in higher education. These officers carry formal administrative titles and ranks that range from vice president for institutional diversity to associate vice chancellor for diversity and climate and dean of diversity and academic engagement.…

  8. Planning for Office Automation.

    ERIC Educational Resources Information Center

    Sherron, Gene T.

    1982-01-01

    The steps taken toward office automation by the University of Maryland are described. Office automation is defined and some types of word processing systems are described. Policies developed in the writing of a campus plan are listed, followed by a section on procedures adopted to implement the plan. (Author/MLW)

  9. The Automated Office.

    ERIC Educational Resources Information Center

    Naclerio, Nick

    1979-01-01

    Clerical personnel may be able to climb career ladders as a result of office automation and expanded job opportunities in the word processing area. Suggests opportunities in an automated office system and lists books and periodicals on word processing for counselors and teachers. (MF)

  10. Office Procedures Curriculum Guidelines.

    ERIC Educational Resources Information Center

    Washington Office of the State Superintendent of Public Instruction, Olympia. Div. of Vocational-Technical and Adult Education Services.

    This guideline is intended as a resource for instructors who are teaching an office procedures course. This course offers closure for all students completing a scope and sequence in the business education program--accounting, secretarial, office services, and related areas. The stated purpose of the course is to prepare a secondary learner for…

  11. The MetLife Survey of the American Teacher: Collaborating for Student Success

    ERIC Educational Resources Information Center

    MetLife, Inc., 2010

    2010-01-01

    "The MetLife Survey of the American Teacher: Collaborating for Student Success (2009)" was conducted by Harris Interactive and is twenty-sixth in a series sponsored by MetLife since 1984 to give voice to those closest to the classroom. This "MetLife Survey" examines the views of teachers, principals and students about respective roles and…

  12. 29 CFR 779.227 - Conditions which must be met for exception.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Conditions which must be met for exception. 779.227 Section... met for exception. This exception, in accordance with its specific terms, will apply to exclude an establishment from enterprise coverage only if the following conditions are met: (a) The establishment must be...

  13. 29 CFR 779.510 - Conditions that must be met for section 13(b)(11) exemption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Conditions that must be met for section 13(b)(11) exemption... met for section 13(b)(11) exemption. In order that an employee be exempt from the overtime provisions... under section 7(a) of the Act. If all the preceding conditions are not met the exemption is inapplicable....

  14. 29 CFR 779.227 - Conditions which must be met for exception.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Conditions which must be met for exception. 779.227 Section... met for exception. This exception, in accordance with its specific terms, will apply to exclude an establishment from enterprise coverage only if the following conditions are met: (a) The establishment must be...

  15. 29 CFR 779.510 - Conditions that must be met for section 13(b)(11) exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Conditions that must be met for section 13(b)(11) exemption... met for section 13(b)(11) exemption. In order that an employee be exempt from the overtime provisions... under section 7(a) of the Act. If all the preceding conditions are not met the exemption is inapplicable....

  16. 43 CFR 1810.2 - Communications by mail; when mailing requirements are met.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... requirements are met. 1810.2 Section 1810.2 Public Lands: Interior Regulations Relating to Public Lands... GENERAL GUIDANCE General Rules § 1810.2 Communications by mail; when mailing requirements are met. (a... requirement for mailing is met when the communication, addressed to the addressee at his last address...

  17. 29 CFR 779.227 - Conditions which must be met for exception.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Conditions which must be met for exception. 779.227 Section... met for exception. This exception, in accordance with its specific terms, will apply to exclude an establishment from enterprise coverage only if the following conditions are met: (a) The establishment must be...

  18. 34 CFR 650.34 - What conditions must be met by fellows?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What conditions must be met by fellows? 650.34 Section... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION JACOB K. JAVITS FELLOWSHIP PROGRAM What Conditions Must be Met By Fellows? § 650.34 What conditions must be met by fellows? In order to continue to receive...

  19. 43 CFR 1810.2 - Communications by mail; when mailing requirements are met.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... requirements are met. 1810.2 Section 1810.2 Public Lands: Interior Regulations Relating to Public Lands... GENERAL GUIDANCE General Rules § 1810.2 Communications by mail; when mailing requirements are met. (a... requirement for mailing is met when the communication, addressed to the addressee at his last address...

  20. 34 CFR 272.40 - What conditions must be met by a recipient of a grant?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... with appropriate SEAs funded under 34 CFR part 271. As part of this coordination, the recipient shall... 34 Education 1 2012-07-01 2012-07-01 false What conditions must be met by a recipient of a grant... Conditions Must Be Met by a Recipient of a Grant? § 272.40 What conditions must be met by a recipient of...

  1. 29 CFR 779.510 - Conditions that must be met for section 13(b)(11) exemption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Conditions that must be met for section 13(b)(11) exemption... met for section 13(b)(11) exemption. In order that an employee be exempt from the overtime provisions... under section 7(a) of the Act. If all the preceding conditions are not met the exemption is inapplicable....

  2. 29 CFR 779.510 - Conditions that must be met for section 13(b)(11) exemption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Conditions that must be met for section 13(b)(11) exemption... met for section 13(b)(11) exemption. In order that an employee be exempt from the overtime provisions... under section 7(a) of the Act. If all the preceding conditions are not met the exemption is inapplicable....

  3. 43 CFR 1810.2 - Communications by mail; when mailing requirements are met.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements are met. 1810.2 Section 1810.2 Public Lands: Interior Regulations Relating to Public Lands... GENERAL GUIDANCE General Rules § 1810.2 Communications by mail; when mailing requirements are met. (a... requirement for mailing is met when the communication, addressed to the addressee at his last address...

  4. 34 CFR 650.34 - What conditions must be met by fellows?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What conditions must be met by fellows? 650.34 Section... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION JACOB K. JAVITS FELLOWSHIP PROGRAM What Conditions Must be Met By Fellows? § 650.34 What conditions must be met by fellows? In order to continue to receive...

  5. 34 CFR 650.34 - What conditions must be met by fellows?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What conditions must be met by fellows? 650.34 Section... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION JACOB K. JAVITS FELLOWSHIP PROGRAM What Conditions Must be Met By Fellows? § 650.34 What conditions must be met by fellows? In order to continue to receive...

  6. 34 CFR 272.40 - What conditions must be met by a recipient of a grant?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... with appropriate SEAs funded under 34 CFR part 271. As part of this coordination, the recipient shall... 34 Education 1 2011-07-01 2011-07-01 false What conditions must be met by a recipient of a grant... Conditions Must Be Met by a Recipient of a Grant? § 272.40 What conditions must be met by a recipient of...

  7. 34 CFR 650.34 - What conditions must be met by fellows?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What conditions must be met by fellows? 650.34 Section... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION JACOB K. JAVITS FELLOWSHIP PROGRAM What Conditions Must be Met By Fellows? § 650.34 What conditions must be met by fellows? In order to continue to receive...

  8. 34 CFR 650.34 - What conditions must be met by fellows?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What conditions must be met by fellows? 650.34 Section... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION JACOB K. JAVITS FELLOWSHIP PROGRAM What Conditions Must be Met By Fellows? § 650.34 What conditions must be met by fellows? In order to continue to receive...

  9. 34 CFR 272.40 - What conditions must be met by a recipient of a grant?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... with appropriate SEAs funded under 34 CFR part 271. As part of this coordination, the recipient shall... 34 Education 1 2013-07-01 2013-07-01 false What conditions must be met by a recipient of a grant... Conditions Must Be Met by a Recipient of a Grant? § 272.40 What conditions must be met by a recipient of...

  10. 29 CFR 779.227 - Conditions which must be met for exception.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Conditions which must be met for exception. 779.227 Section... met for exception. This exception, in accordance with its specific terms, will apply to exclude an establishment from enterprise coverage only if the following conditions are met: (a) The establishment must be...

  11. 34 CFR 272.40 - What conditions must be met by a recipient of a grant?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... with appropriate SEAs funded under 34 CFR part 271. As part of this coordination, the recipient shall... 34 Education 1 2014-07-01 2014-07-01 false What conditions must be met by a recipient of a grant... Conditions Must Be Met by a Recipient of a Grant? § 272.40 What conditions must be met by a recipient of...

  12. 29 CFR 779.510 - Conditions that must be met for section 13(b)(11) exemption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Conditions that must be met for section 13(b)(11) exemption... met for section 13(b)(11) exemption. In order that an employee be exempt from the overtime provisions... under section 7(a) of the Act. If all the preceding conditions are not met the exemption is inapplicable....

  13. 29 CFR 779.227 - Conditions which must be met for exception.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Conditions which must be met for exception. 779.227 Section... met for exception. This exception, in accordance with its specific terms, will apply to exclude an establishment from enterprise coverage only if the following conditions are met: (a) The establishment must be...

  14. 43 CFR 1810.2 - Communications by mail; when mailing requirements are met.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... requirements are met. 1810.2 Section 1810.2 Public Lands: Interior Regulations Relating to Public Lands... GENERAL GUIDANCE General Rules § 1810.2 Communications by mail; when mailing requirements are met. (a... requirement for mailing is met when the communication, addressed to the addressee at his last address...

  15. 34 CFR 272.40 - What conditions must be met by a recipient of a grant?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... with appropriate SEAs funded under 34 CFR part 271. As part of this coordination, the recipient shall... 34 Education 1 2010-07-01 2010-07-01 false What conditions must be met by a recipient of a grant... Conditions Must Be Met by a Recipient of a Grant? § 272.40 What conditions must be met by a recipient of...

  16. Effects of Wearing Compression Stockings on the Physical Performance of T2DM Men with MetS.

    PubMed

    Brinkmann, C; Hermann, R; Rühl, E; Kerzel, H; Reinhardt, L; Grau, M; Latsch, J; Kohl-Bareis, M; Bloch, W; Brixius, K

    2016-05-01

    Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are associated with macro- and microcirculatory complications that reduce physical performance. Wearing compression garments to potentially optimize hemodynamics has been discussed. This study investigates the effects of wearing compression stockings on physical performance-related variables in type 2 diabetic men with metabolic syndrome (n=9, 57±12 years, BMI: 36±4 kg/m(2)). Participants served as their own controls in a randomized 3*3 crossover study wearing below-knee stockings with either compression (24 or 30 mmHg ankle pressure) or no compression. Venous pooling and lower limb oxygenation profiles were determined with near-infrared spectroscopy and arterial oxygen saturation was determined using a pulse oxymeter. Measurements were performed in the supine lying position, during standing, following 10 tiptoe exercises and after submaximal intensity cycling. In addition, lactate and erythrocyte deformability were analyzed in capillary blood pre- and post-exercise. Erythrocyte deformability was analyzed using a laser-assisted optical rotational red cell analyzer. No significant differences in any variables when wearing different compression or regular stockings were evident at any point of measurement. This study did not reveal any beneficial effects of wearing compression stockings at rest and during acute bouts of moderately intense exercise in this particular patient group. PMID:26859644

  17. A novel antagonist anti-cMet antibody with antitumor activities targeting both ligand-dependent and ligand-independent c-Met receptors.

    PubMed

    Gonzalez, Alexandra; Broussas, Matthieu; Beau-Larvor, Charlotte; Haeuw, Jean-François; Boute, Nicolas; Robert, Alain; Champion, Thierry; Beck, Alain; Bailly, Christian; Corvaïa, Nathalie; Goetsch, Liliane

    2016-10-15

    c-Met is a prototypic member of a sub-family of RTKs. Inappropriate c-Met activation plays a crucial role in tumor formation, proliferation and metastasis. Using a key c-Met dimerization assay, a set of 12 murine whole IgG1 monoclonal antibodies was selected and a lead candidate, m224G11, was humanized by CDR-grafting and engineered to generate a divalent full antagonist humanized IgG1 antibody, hz224G11. Neither m224G11 nor hz224G11 bind to the murine c-Met receptor. Their antitumor activity was investigated in vitro in a set of experiments consistent with the reported pleiotropic effects mediated by c-Met and, in vivo, using several human tumor xenograft models. Both m224G11 and hz224G11 exhibited nanomolar affinities for the receptor and inhibited HGF binding, c-Met phosphorylation, and receptor dimerization in a similar fashion, resulting in a profound inhibition of all c-Met functions in vitro. These effects were presumably responsible for the inhibition of c-Met's major functions including cell proliferation, migration, invasion scattering, morphogenesis and angiogenesis. In addition to these in vitro properties, hz224G11 dramatically inhibits the growth of autocrine, partially autophosphorylated and c-Met amplified cell lines in vivo. Pharmacological studies performed on Hs746T gastric cancer xenografts demonstrate that hz224G11 strongly downregulates c-Met expression and phosphorylation. It also decreases the tumor mitotic index (Ki67) and induces apoptosis. Taken together, the in vitro and in vivo data suggest that hz224G11 is a promising candidate for the treatment of tumors. This antibody, now known as ABT-700 and currently in Phase I clinical trials, may provide a novel therapeutic approach to c-Met-expressing cancers. PMID:27144973

  18. Unified Planetary Coordinates System: A Searchable Database of Geodetic Information

    NASA Technical Reports Server (NTRS)

    Becker, K. J.a; Gaddis, L. R.; Soderblom, L. A.; Kirk, R. L.; Archinal, B. A.; Johnson, J. R.; Anderson, J. A.; Bowman-Cisneros, E.; LaVoie, S.; McAuley, M.

    2005-01-01

    Over the past 40 years, an enormous quantity of orbital remote sensing data has been collected for Mars from many missions and instruments. Unfortunately these datasets currently exist in a wide range of disparate coordinate systems, making it extremely difficult for the scientific community to easily correlate, combine, and compare data from different Mars missions and instruments. As part of our work for the PDS Imaging Node and on behalf of the USGS Astrogeology Team, we are working to solve this problem and to provide the NASA scientific research community with easy access to Mars orbital data in a unified, consistent coordinate system along with a wide variety of other key geometric variables. The Unified Planetary Coordinates (UPC) system is comprised of two main elements: (1) a database containing Mars orbital remote sensing data computed using a uniform coordinate system, and (2) a process by which continual maintainance and updates to the contents of the database are performed.

  19. Planetary and Solar Data Labeled with IVOA Unified Content Descriptors

    NASA Astrophysics Data System (ADS)

    Louys, Mireille; Cecconi, Baptiste; Derriere, Sébastien; Erard, S.; André, N.; Preite-Martinez, A.; Ochsenbein, F.; Jacquey, C.; Génot, V.; Henry, F.; Bonnin, X.; Le Sidaner, P.; Chauvin, C.; Fuller, N.; Braga, V. F.; Aboudarham, J.

    2015-09-01

    Astronomical data collections are widely using tabular formats to expose their data to the community and especially in the Virtual Observatory. In order to label the content of physical quantities stored in table columns, The Unified Content Descriptors (UCDs) [Preite Martinez et al. (2011)] labels have been standardized and attached as semantic tags to a wide range of measurements and metadata. This unifies the content description across multiple data collections and archive centers. The Planetary and Solar science communities proposed, together with the IVOA Semantics Working group, to extend this bank of semantic labels for the distribution of their own collections and to adopt compatible standards such as VOTable, TAP, etc. This work shows the new UCD set proposed and how it is made available in the Virtual Observatory framework. A reference vocabulary is set up, UCD assigning tools and tests are presented.

  20. Unified Formulation of the Aeroelasticity of Swept Lifting Surfaces

    NASA Technical Reports Server (NTRS)

    Silva, Walter; Marzocca, Piergiovanni; Librescu, Liviu

    2001-01-01

    An unified approach for dealing with stability and aeroelastic response to time-dependent pressure pulses of swept wings in an incompressible flow is developed. To this end the indicial function concept in time and frequency domains, enabling one to derive the proper unsteady aerodynamic loads is used. Results regarding stability in the frequency and time domains, and subcritical aeroelastic response to arbitrary time-dependent external excitation obtained via the direct use of the unsteady aerodynamic derivatives for 3-D wings are supplied. Closed form expressions for unsteady aerodynamic derivatives using this unified approach have been derived and used to illustrate their application to flutter and aeroelastic response to blast and sonic-boom signatures. In this context, an original representation of the aeroelastic response in the phase space was presented and pertinent conclusions on the implications of some basic parameters have been outlined.

  1. Unified Picture for Magnetic Correlations in Iron-Based Superconductors

    SciTech Connect

    Yin, W.G.; Lee, E.-C.; Ku, W.

    2010-09-02

    The varying metallic antiferromagnetic correlations observed in iron-based superconductors are unified in a model consisting of both itinerant electrons and localized spins. The decisive factor is found to be the sensitive competition between the superexchange antiferromagnetism and the orbital-degenerate double-exchange ferromagnetism. Our results reveal the crucial role of Hund's rule coupling for the strongly correlated nature of the system and suggest that the iron-based superconductors are closer kin to manganites than cuprates in terms of their diverse magnetism and incoherent normal-state electron transport. This unified picture would be instrumental for exploring other exotic properties and the mechanism of superconductivity in this new class of superconductors.

  2. Toward a Unified Theory of Visual Area V4

    PubMed Central

    Roe, Anna W.; Chelazzi, Leonardo; Connor, Charles E.; Conway, Bevil R.; Fujita, Ichiro; Gallant, Jack L.; Lu, Haidong; Vanduffel, Wim

    2016-01-01

    Visual area V4 is a midtier cortical area in the ventral visual pathway. It is crucial for visual object recognition and has been a focus of many studies on visual attention. However, there is no unifying view of V4’s role in visual processing. Neither is there an understanding of how its role in feature processing interfaces with its role in visual attention. This review captures our current knowledge of V4, largely derived from electrophysiological and imaging studies in the macaque monkey. Based on recent discovery of functionally specific domains in V4, we propose that the unifying function of V4 circuitry is to enable selective extraction of specific functional domain-based networks, whether it be by bottom-up specification of object features or by top-down attentionally driven selection. PMID:22500626

  3. Development of Unified Lab Test Result Master for Multiple Facilities.

    PubMed

    Kume, Naoto; Suzuki, Kenji; Kobayashi, Shinji; Araki, Kenji; Yoshihara, Hiroyuki

    2015-01-01

    A clinical study requires massive amounts of of lab test data, especially for rare diseases. Before creating a protocol, the hypothesis if the protocol will work with enough amount of patients' dataset has to be proved. However, a single facility, such as a university hospital, often faces a lack of number of patients for specific target diseases. Even if collecting datasets from several facilities, there is no active master table that can merge lab test results between the facility datasets. Therefore, the authors develop a unified lab test result master. Because test master standards such as JLAC10 and LOINC are provided from a viewpoint of academic classification of laboratory medicine, the classification does not fit clinical classification, which doctors understand with a mind-set of establishing a clinical study protocol. The authors establish a method to unify masters using an active lab test result master from two university hospitals. PMID:26262349

  4. Sandia/Stanford Unified Creep Plasticity Damage Model for ANSYS

    Energy Science and Technology Software Center (ESTSC)

    2006-09-03

    A unified creep plasticity (UCP) model was developed, based upon the time-dependent and time-independent deformation properties of the 95.5Sn-3.9Ag-0.6Cu (wt.%) soldier that were measured at Sandia. Then, a damage parameter, D, was added to the equation to develop the unified creep plasticity damage (UCPD) model. The parameter, D, was parameterized, using data obtained at Sandia from isothermal fatigue experiments on a double-lap shear test. The softwae was validated against a BGA solder joint exposed tomore » thermal cycling. The UCPD model was put into the ANSYS finite element as a subroutine. So, the softwae is the subroutine for ANSYS 8.1.« less

  5. Skinner-Rusk unified formalism for higher-order systems

    NASA Astrophysics Data System (ADS)

    Prieto-Martínez, Pedro Daniel; Román-Roy, Narciso

    2012-07-01

    The Lagrangian-Hamiltonian unified formalism of R. Skinner and R. Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, first-order and higher-order field theories, and higher-order autonomous systems. In this work we present a generalization of this formalism for higher-order non-autonomous mechanical systems.

  6. Gauge Coupling Unification in F-Theory Grand Unified Theories

    SciTech Connect

    Blumenhagen, Ralph

    2009-02-20

    We investigate gauge coupling unification for F-theory type IIB orientifold constructions of SU(5) grand unified theories (GUT) with gauge symmetry breaking via nontrivial hypercharge flux. This flux has the nontrivial effect that it splits the values of the three minimal supersymmetric standard model gauge couplings at the string scale, thus potentially spoiling the celebrated one-loop gauge coupling unification. It is shown how F-theory can evade this problem in a natural way.

  7. Gauge coupling unification in F-theory grand unified theories.

    PubMed

    Blumenhagen, Ralph

    2009-02-20

    We investigate gauge coupling unification for F-theory type IIB orientifold constructions of SU(5) grand unified theories (GUT) with gauge symmetry breaking via nontrivial hypercharge flux. This flux has the nontrivial effect that it splits the values of the three minimal supersymmetric standard model gauge couplings at the string scale, thus potentially spoiling the celebrated one-loop gauge coupling unification. It is shown how F-theory can evade this problem in a natural way. PMID:19257658

  8. A unified approach to infinite-dimensional integration

    NASA Astrophysics Data System (ADS)

    Albeverio, S.; Mazzucchi, S.

    2016-04-01

    An approach to infinite-dimensional integration which unifies the case of oscillatory integrals and the case of probabilistic type integrals is presented. It provides a truly infinite-dimensional construction of integrals as linear functionals, as much as possible independent of the underlying topological and measure theoretical structure. Various applications are given, including, next to Feynman path integrals, Schrödinger and diffusion equations, as well as higher order hyperbolic and parabolic equations.

  9. Cytotoxic activity of Tivantinib (ARQ 197) is not due solely to MET inhibition

    PubMed Central

    Katayama, Ryohei; Aoyama, Aki; Yamori, Takao; Qi, Jie; Oh-hara, Tomoko; Song, Youngchul; Engelman, Jeffrey A.; Fujita, Naoya

    2013-01-01

    The receptor tyrosine kinase c-MET is the high-affinity receptor for the hepatocyte growth factor (HGF). The HGF/c-MET axis is often dysregulated in tumors. c-MET activation can be caused by MET gene amplification, activating mutations, and auto- or paracrine mechanisms. Thus, c-MET inhibitors are under development as anti-cancer drugs. Tivantinib (ARQ 197) was reported as a small molecule c-MET inhibitor and early clinical studies suggest anti-tumor activity. To assess if the anti-tumor activity of tivantinib was due to inhibition of c-MET, we compared the activity of tivantinib to other c-MET inhibitors in both c-MET addicted and non-addicted cancer cells. As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET addicted cancers, but not the growth of cancers that are not addicted to c-MET. In contrast, tivantinib inhibited cell viability with similar potency in both c-MET addicted and non-addicted cells. These results suggest that tivantinib exhibits its antitumor activity in a manner independent of c-MET status. Tivantinib treatment induced a G2/M cell cycle arrest in EBC1 cells similarly to vincristine treatment, whereas PHA-665752 or crizotinib treatment markedly induced G0/G1 cell cycle arrest. To identify the additional molecular target of tivantinib, we performed COMPARE analysis, an in silico screening of a database of drug sensitivities across 39 cancer cell lines (JFCR39), and identified microtubule as a target of tivantinib. Tivantinib treated cells demonstrated typical microtubule disruption similar to vincristine and inhibited microtubule assembly in vitro. These results suggest that tivantinib inhibits microtubule polymerization in addition to inhibiting c-MET. PMID:23598276

  10. Metallography at the Met Lab -- The first fifty years

    SciTech Connect

    Lee, R.H.

    1995-12-31

    The Met Lab at the University of Chicago was established to build the world`s first nuclear reactor. The object was to see if a pile (CP-1) could be built to create a sustained chain reaction, i.e., controlled nuclear fission. New materials of the very best quality were needed and people of many skills worked together to achieve the goal as quickly as possible. This is the story of a select group of people who were scientific and engineering pioneers in this new field. Research continued at new sites on more advanced reactors and cooling systems. Many problems were encountered in the fabrication of reactor components, and metallography was a crucial method of analyzing the reactions and quality of consolidation. 1996 will be the 50th anniversary of the beginning of the National Laboratories, so it is appropriate to commemorate and recall some pioneering achievements.

  11. Operational Numerical Weather Prediction at the Met Office and potential ways forward for operational space weather prediction systems

    NASA Astrophysics Data System (ADS)

    Jackson, David

    NICT (National Institute of Information and Communications Technology) has been in charge of space weather forecast service in Japan for more than 20 years. The main target region of the space weather is the geo-space in the vicinity of the Earth where human activities are dominant. In the geo-space, serious damages of satellites, international space stations and astronauts take place caused by energetic particles or electromagnetic disturbances: the origin of the causes is dynamically changing of solar activities. Positioning systems via GPS satellites are also im-portant recently. Since the most significant effect of positioning error comes from disturbances of the ionosphere, it is crucial to estimate time-dependent modulation of the electron density profiles in the ionosphere. NICT is one of the 13 members of the ISES (International Space Environment Service), which is an international assembly of space weather forecast centers under the UNESCO. With help of geo-space environment data exchanging among the member nations, NICT operates daily space weather forecast service every day to provide informa-tion on forecasts of solar flare, geomagnetic disturbances, solar proton event, and radio-wave propagation conditions in the ionosphere. The space weather forecast at NICT is conducted based on the three methodologies: observations, simulations and informatics (OSI model). For real-time or quasi real-time reporting of space weather, we conduct our original observations: Hiraiso solar observatory to monitor the solar activity (solar flare, coronal mass ejection, and so on), domestic ionosonde network, magnetometer HF radar observations in far-east Siberia, and south-east Asia low-latitude ionosonde network (SEALION). Real-time observation data to monitor solar and solar-wind activities are obtained through antennae at NICT from ACE and STEREO satellites. We have a middle-class super-computer (NEC SX-8R) to maintain real-time computer simulations for solar and solar-wind, magnetosphere and ionosphere. The three simulations are directly or indirectly connected each other based on real-time observa-tion data to reproduce a virtual geo-space region on the super-computer. Informatics is a new methodology to make precise forecast of space weather. Based on new information and communication technologies (ICT), it provides more information in both quality and quantity. At NICT, we have been developing a cloud-computing system named "space weather cloud" based on a high-speed network system (JGN2+). Huge-scale distributed storage (1PB), clus-ter computers, visualization systems and other resources are expected to derive new findings and services of space weather forecasting. The final goal of NICT space weather service is to predict near-future space weather conditions and disturbances which will be causes of satellite malfunctions, tele-communication problems, and error of GPS navigations. In the present talk, we introduce our recent activities on the space weather services and discuss how we are going to develop the services from the view points of space science and practical uses.

  12. MetNH3: Metrology for ammonia in ambient air

    NASA Astrophysics Data System (ADS)

    Braban, Christine; Twigg, Marsailidh; Tang, Sim; Leuenberger, Daiana; Ferracci, Valerio; Martin, Nick; Pascale, Celine; Hieta, Tuomas; Pogany, Andrea; Persijn, Stefan; van Wijk, Janneke; Gerwig, Holger; Wirtze, Klaus; Tiebe, Carlo; Balslev-Harder, David; Niederhausen, Bernhardt

    2015-04-01

    Measuring ammonia in ambient air is a sensitive and priority issue due to its harmful effects on human health and ecosystems. The European Directive 2001/81/EC on 'National Emission Ceilings for Certain Atmospheric Pollutants (NEC)' regulates ammonia emissions in the member states. However, there is a lack of regulation to ensure reliable ammonia measurements namely in applicable analytical technology, maximum allowed uncertainty, quality assurance and quality control (QC/QA) procedures as well as in the infrastructure to attain metrological traceability. Validated ammonia measurement data of high quality from air monitoring networks are vitally important for identifying changes due to implementations of environment policies, for understanding where the uncertainties in current emission inventories are derived from and for providing independent verification of atmospheric model predictions. The new EURAMET project MetNH3 aims to develop improved reference gas mixtures by static and dynamic gravimetric generation methods, develop and characterise laser based optical spectrometric standards and establish the transfer from high-accuracy standards to field applicable methods. MetNH3started in June 2014 and in this presentation the first results from the metrological characterisation of a commercially available cavity ring-down spectrometer (CRDS) will be discussed. Also first tests and results from a new design, Controlled Atmosphere Test Facility (CATFAC), which is to be characterised and used to validate the performance of diffusive samplers, denuders and on-line instruments, will be reported. CAFTEC can be used to control test parameters such as ammonia concentration, relative humidity and wind speed. Outline plans for international laboratory and field intercomparisons in 2016 will be presented.

  13. CLUBB as a unified cloud parameterization: Opportunities and challenges

    NASA Astrophysics Data System (ADS)

    Guo, H.; Golaz, J.-C.; Donner, L. J.; Wyman, B.; Zhao, M.; Ginoux, P.

    2015-06-01

    CLUBB (Cloud Layers Unified by Binormals) is a higher-order closure (HOC) method with an assumed joint probability density function (PDF) for the subgrid variations in vertical velocity, temperature, and moisture. CLUBB has been implemented in the atmospheric component (AM3) of the Geophysical Fluid Dynamics Laboratory general circulation model AM3-CLUBB and successfully unifies the treatment of shallow convection, resolved clouds, and planetary boundary layer (PBL). In this study, we further explore the possibility for CLUBB to unify the deep convection in a new configuration referred as AM3-CLUBB+. AM3-CLUBB+ simulations with prescribed sea surface temperature are discussed. Cloud, radiation, and precipitation fields compare favorably with observations and reanalyses. AM3-CLUBB+ successfully captures the transition from stratocumulus to deep convection and the modulated response of liquid water path to aerosols. Simulations of tropical variability and the Madden-Julian oscillation (MJO) are also improved. Deficiencies include excessive tropical water vapor and insufficient ice clouds in the midlatitudes.

  14. SB 1082 -- Unified hazardous materials/waste program: Local implementation

    SciTech Connect

    Jones, W.

    1995-12-31

    California Senate Bill 1082 was signed into law in the fall of 1993 because business and industry believed there were too many hazardous materials inspectors asking the same questions, looking at the same items and requiring similar information on several variations of the same form. Industry was not happy with the large diversity of programs, each with its own inspectors, permits and fees, essentially doing what industry believed was the same inspection. SB 1082 will allow local city and county agencies to apply to the California Environmental Protection Agency to become a Certified Unified Program Agency (CUPA) or work with a CUPA as a Participating Agency (PA) to manage specific program elements. The CUPA will unify six regulatory programs including hazardous waste/tiered permitting, aboveground storage tanks, underground storage tanks, business and area plans/inventory or disclosure, acutely hazardous materials/risk management prevention and Uniform Fire Code programs related to hazardous materials inventory/plan requirements. The bill requires the CUPA to (1) implement a permit consolidation program; (2) implement a single fee system with a state surcharge; (3) consolidate, coordinate and make consistent any local or regional requirements or guidance documents; and (4) implement a single unified inspection and enforcement program.

  15. Unified Field Theory and Force Formulas of Interactions

    NASA Astrophysics Data System (ADS)

    Ma, Tian; Wang, Shouhong

    2013-04-01

    The main objective of this talk is to drive a unified field model coupling four interactions, based on the principle of interaction dynamics (PID) and the principle of representation invariance (PID). Intuitively, PID takes the variation of the action functional under energy-momentum conservation constraint. PRI requires that physical laws be independent of representations of the gauge groups. One important outcome of this unified field model is a natural duality between the interacting fields (g, A, W^a, S^k), corresponding to graviton, photon, intermediate vector bosons W^± and Z and gluons, and the adjoint bosonic fields (φ,, ^aw, ^ks). This duality predicts two Higgs particles of similar mass with one due to weak interaction and the other due to strong interaction. PID and PRI can be applied directly to individual interactions, leading to 1) modified Einstein equations, giving rise to a unified theory for dark matter and dark energy, 2) three levels of strong interaction potentials for quark, nucleon/hadron, and atom respectively, and 3) a weak interaction potential. These potential/force formulas offer a clear mechanism for both quark confinement and asymptotic freedom.

  16. Phenomenology of nonuniversal gaugino masses in supersymmetric grand unified theories

    SciTech Connect

    Huitu, Katri; Laamanen, Jari; Pandita, Pran N.; Roy, Sourov

    2005-09-01

    Grand unified theories can lead to nonuniversal boundary conditions for the gaugino masses at the unification scale. We consider the implications of such nonuniversal boundary conditions for the composition of the lightest neutralino as well as for the upper bound on its mass in the simplest supersymmetric grand unified theory based on the SU(5) gauge group. We derive sum rules for neutralino and chargino masses in different representations of SU(5) which lead to different nonuniversal boundary conditions for the gaugino masses at the unification scale. We also consider the phenomenological implications of the nonuniversal gaugino masses arising from a grand unified theory in the context of large hadron collider. In particular we investigate the detection of heavy neutral Higgs bosons H{sup 0}, A{sup 0}from H{sup 0}, A{sup 0}{yields}{chi}-tilde{sub 2}{sup 0}{chi}-tilde{sub 2}{sup 0}{yields}4l and study the possibilities of detecting the neutral Higgs bosons in cascade decays, including the decays {chi}-tilde{sub 2}{sup 0}{yields}h{sup 0}(H{sup 0},A{sup 0}){chi}-tilde{sub 1}{sup 0}{yields}bb{chi}-tilde{sub 1}{sup 0}.

  17. Creation and Maintenance of a Unified Astronomy Thesaurus

    NASA Astrophysics Data System (ADS)

    Gray, Norman; Erdmann, C.; Accomazzi, A.; Soles, J.; McCann, G.; Cassar, M.; Biemesderfer, C.

    2013-01-01

    We describe a collaborative effort to update and unify the various vocabularies currently in use in Astronomy into a single thesaurus that can be further developed and updated through broad community participation. The Unified Astronomy Thesaurus (UAT) will be an open, interoperable and community-supported thesaurus which unifies the existing divergent and isolated Astronomy & Astrophysics thesauri into a single high-quality, freely-available open thesaurus formalizing astronomical concepts and their inter-relationships. The UAT builds upon the existing IAU Thesaurus with major contributions from the Astronomy portions of the thesauri developed by the Institute of Physics Publishing and the American Institute of Physics. While the AAS has assumed formal ownership of the UAT, the work will be available under a Creative Commons License, ensuring its widest use while protecting the intellectual property of the contributors. We envision that development and maintenance will be stewarded by a broad group of parties having a direct stake in it. This includes professional associations (IVOA, IAU), learned societies (AAS, RAS), publishers (IOP, AIP), librarians and other curators working for major astronomy institutes and data archives. While the impetus behind the creation of a single thesaurus has been the wish to support semantic enrichment of the literature, we expect that use of the UAT (along with other vocabularies and ontologies currently being developed) will be much broader and will have a greater impact on discovery of both literatue and data products.

  18. Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.

    PubMed

    Meikle, Peter J; Wong, Gerard; Tan, Ricardo; Giral, Philippe; Robillard, Paul; Orsoni, Alexina; Hounslow, Neil; Magliano, Dianna J; Shaw, Jonathan E; Curran, Joanne E; Blangero, John; Kingwell, Bronwyn A; Chapman, M John

    2015-12-01

    The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (-41%), remnant cholesterol (-55%), and LDL-cholesterol (-39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D. PMID:26486974

  19. PEA3 transcription factors are downstream effectors of Met signaling involved in migration and invasiveness of Met-addicted tumor cells.

    PubMed

    Kherrouche, Zoulika; Monte, Didier; Werkmeister, Elisabeth; Stoven, Luc; De Launoit, Yvan; Cortot, Alexis B; Tulasne, David; Chotteau-Lelievre, Anne

    2015-11-01

    Various solid tumors including lung or gastric carcinomas display aberrant activation of the Met receptor which correlates with aggressive phenotypes and poor prognosis. Although downstream signaling of Met is well described, its integration at the transcriptional level is poorly understood. We demonstrate here that in cancer cells harboring met gene amplification, inhibition of Met activity with tyrosine kinase inhibitors or specific siRNA drastically decreased expression of ETV1, ETV4 and ETV5, three transcription factors constituting the PEA3 subgroup of the ETS family, while expression of the other members of the family were less or not affected. Similar link between Met activity and PEA3 factors expression was found in lung cancer cells displaying resistance to EGFR targeted therapy involving met gene amplification. Using silencing experiments, we demonstrate that the PEA3 factors are required for efficient migration and invasion mediated by Met, while other biological responses such as proliferation or unanchored growth remain unaffected. PEA3 overexpression or silencing revealed that they participated in the regulation of the MMP2 target gene involved in extracellular matrix remodeling. Our results demonstrated that PEA3-subgroup transcription factors are key players of the Met signaling integration involved in regulation of migration and invasiveness. PMID:26238631

  20. NASA's Meteoroid Environment Office

    NASA Technical Reports Server (NTRS)

    Suggs, Robert M.; Cooke, William; McNamara, Heather

    2004-01-01

    The Meteoroid Environment Office (MEO) has recently been formed within the Engineering Directorate at NASA's Marshall Space Flight Center. With agency-wide responsibility for defining the meteoroid environments for spacecraft engineering operations purposes, the MEO will distribute a state-of-the-art sporadic meteoroid model as well as meteor shower forecasts for spacecraft operators. To improve these models and forecasts, the MEO will manage an observation and research program. Office responsibilities, products, and plans will be discussed in this paper. The MEO is sponsored by the Office of Safety and Mission Assurance at NASA Headquarters.

  1. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors

    PubMed Central

    Smyth, Elizabeth C; Sclafani, Francesco; Cunningham, David

    2014-01-01

    The MET/hepatocyte growth-factor (HGF) signaling pathway plays a key role in the processes of embryogenesis, wound healing, and organ regeneration. Aberrant activation of MET/HGF occurs through multiple mechanisms including gene amplification, mutation, protein overexpression, and abnormal gene splicing interrupting autocrine and paracrine regulatory feedback mechanisms. In many cancers including non-small-cell lung cancer, colorectal, gastric, renal, and hepatocellular cancer, dysregulation of MET may lead to a more aggressive cancer phenotype and may be a negative prognostic indicator. Successful therapeutic targeting of the MET/HGF pathway has been achieved using monoclonal antibodies against the MET receptor and its ligand HGF in addition to MET-specific and multitargeted small-molecule tyrosine-kinase inhibitors with several drugs in late-phase clinical trials including onartuzumab, rilotumumab, tivantinib, and cabozantinib. MET frequently interacts with other key oncogenic tyrosine kinases including epidermal growth-factor receptor (EGFR) and HER-3 and these interactions may be responsible for resistance to anti-EGFR therapies. Similarly, resistance to MET inhibition may be mediated through EGFR activation, or alternatively by increasing levels of MET amplification or acquisition of novel “gatekeeper” mutations. In order to optimize development of effective inhibitors of the MET/HGF pathway clinical trials must be enriched for patients with demonstrable MET-pathway dysregulation for which robustly standardized and validated assays are required. PMID:24959087

  2. PAX3 and ETS1 synergistically activate MET expression in melanoma cells

    PubMed Central

    Kubic, Jennifer D.; Little, Elizabeth C.; Lui, Jason W.; Iizuka, Takumi; Lang, Deborah

    2014-01-01

    Melanoma is a highly aggressive disease that is difficult to treat due to rapid tumor growth, apoptotic resistance, and high metastatic potential. The MET tyrosine kinase receptor promotes many of these cellular processes, and while MET is often overexpressed in melanoma, the mechanism driving this overexpression is unknown. Since the MET gene is rarely mutated or amplified in melanoma, MET overexpression may be driven by to increased activation through promoter elements. In this report, we find that transcription factors PAX3 and ETS1 directly interact to synergistically activate MET expression. Inhibition of PAX3 and ETS1 expression in melanoma cells leads to a significant reduction of MET receptor levels. The 300 bp 5′ proximal MET promoter contains a PAX3 response element and two ETS1 consensus motifs. While ETS1 can moderately activate both of these sites without cofactors, robust MET promoter activation of the first site is PAX-dependent and requires the presence of PAX3, while the second site is PAX-independent. The induction of MET by ETS1 via this second site is enhanced by HGF-dependent ETS1 activation, thereby MET indirectly promotes its own expression. We further find that expression of a dominant negative ETS1 reduces the ability of melanoma cells to grow both in culture and in vivo. Thus, we discover a pathway where ETS1 advances melanoma through the expression of MET via PAX-dependent and independent mechanisms. PMID:25531327

  3. OFFICE OF WATER RESOURCE CENTER

    EPA Science Inventory

    Resource Purpose:The Resource Center provides support to the management of the Immediate Office, Office of Groundwater and Drinking Water, Office of Science and Technology, Office of Wastewater Management, and Office of Wetlands, Oceans, and Watersheds. Support includes: ...

  4. Prognostic and predictive value of MET deregulation in non-small cell lung cancer

    PubMed Central

    Toschi, Luca; Gianoncelli, Letizia; Baretti, Marina; Santoro, Armando

    2015-01-01

    Recent progress in cancer biology has led to the discovery of increasing number of oncogene alterations that have dramatically changed the paradigm of lung cancer treatment. MET is a tyrosine kinase receptor for the hepatocyte growth factor (HGF) that is deregulated in several malignancies, including non-small cell lung cancer (NSCLC). Abnormal MET-HGF signaling pathway activation can occur via different mechanisms, including HGF and/or MET overexpression, MET gene amplification, mutations or rearrangements. MET protein overexpression and increased MET gene number have been identified as poor prognostic factors in several series of surgically resected NSCLC making this receptor an attractive target for cancer treatment. Several clinical trials have recently evaluated the activity of a variety of anti-MET strategies in NSCLC patients with or without molecular selection with a variable degree of success, underscoring the need of establishing the best predictive biomarker for the identification of responding patients. PMID:25992382

  5. 14. Second floor office (coast guard) in area office building ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Second floor office (coast guard) in area office building looking southwest - Duluth Ship Canal, Marine Museum-Area Office, North end of Minnesota Point at Canal Park, Duluth, St. Louis County, MN

  6. Office of the Chief Financial Officer Annual Report 2009

    SciTech Connect

    Fernandez, Jeffrey

    2009-12-15

    Presented is the 2009 Chief Financial Officer's Annual Report. The data included in this report has been compiled from the Budget Office, the Controller, Procurement and Property Management and the Sponsored Projects Office.

  7. 19. GROUND STORY, POST OFFICE LOBBY DETAIL OF POST OFFICE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. GROUND STORY, POST OFFICE LOBBY DETAIL OF POST OFFICE BOXES ALONG WEST WALL OF LEXINGTON AVENUE ARM - Grand Central Post Office Annex, Forty-fifth Street & Lexington Avenue, Southwest corner, New York County, NY

  8. Antitumor activity of SNX-2112, a synthetic heat shock protein-90 inhibitor, in MET-amplified tumor cells with or without resistance to selective MET inhibition

    PubMed Central

    Bachleitner-Hofmann, Thomas; Sun, Mark Y.; Chen, Chin-Tung; Liska, David; Zeng, Zhaoshi; Viale, Agnes; Olshen, Adam B.; Mittlboeck, Martina; Christensen, James G.; Rosen, Neal; Solit, David B.; Weiser, Martin R.

    2012-01-01

    Purpose Heat shock protein-90 (HSP-90), a molecular chaperone required by numerous oncogenic kinases (e.g. HER-2, EGFR, Raf-1, v-Src, AKT) for conformational stability, has attracted wide interest as a novel target for cancer therapy. HSP-90 inhibition induces degradation of HSP-90 client proteins, leading to a combinatorial inhibition of multiple oncogenic signaling pathways with consecutive growth arrest and apoptosis. MET, a tyrosine kinase which is constitutively active in tumor cells with MET oncogene amplification, has recently been identified as another HSP-90 client. Experimental Design Aim of our study was to assess the efficacy of SNX-2112, a synthetic HSP-90 inhibitor, in 3 different MET-amplified tumor cell lines (GTL-16, MKN-45 and EBC-1) as well as PR-GTL-16 cells, a GTL-16 subline selected for resistance to the highly selective MET kinase inhibitor PHA-665752. Results In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR and AKT as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest. SNX-5542, an orally bioavailable prodrug of SNX-2112, displayed significant antitumor efficacy in vivo in nude mice bearing MET-amplified tumor xenografts. Importantly, HSP-90 inhibition maintained its antitumor efficacy in PR-GTL-16 cells both in vitro and in vivo, suggesting that HSP-90 inhibition could be a particularly valuable strategy in MET-amplified tumors which have acquired resistance to MET kinase inhibition. Conclusions Our study provides evidence for the efficacy of HSP-90 inhibition in MET-amplified cancer cells, particularly when MET kinase inhibitor resistance has emerged. PMID:21208906

  9. Total column water vapour measurements from GOME-2 MetOp-A and MetOp-B

    NASA Astrophysics Data System (ADS)

    Grossi, M.; Valks, P.; Loyola, D.; Aberle, B.; Slijkhuis, S.; Wagner, T.; Beirle, S.; Lang, R.

    2015-03-01

    Knowledge of the total column water vapour (TCWV) global distribution is fundamental for climate analysis and weather monitoring. In this work, we present the retrieval algorithm used to derive the operational TCWV from the GOME-2 sensors aboard EUMETSAT's MetOp-A and MetOp-B satellites and perform an extensive inter-comparison in order to evaluate their consistency and temporal stability. For the analysis, the GOME-2 data sets are generated by DLR in the framework of the EUMETSAT O3M-SAF project using the GOME Data Processor (GDP) version 4.7. The retrieval algorithm is based on a classical Differential Optical Absorption Spectroscopy (DOAS) method and combines a H2O and O2 retrieval for the computation of the trace gas vertical column density. We introduce a further enhancement in the quality of the H2O total column by optimizing the cloud screening and developing an empirical correction in order to eliminate the instrument scan angle dependencies. The overall consistency between measurements from the newer GOME-2 instrument on board of the MetOp-B platform and the GOME-2/MetOp-A data is evaluated in the overlap period (December 2012-June 2014). Furthermore, we compare GOME-2 results with independent TCWV data from the ECMWF ERA-Interim reanalysis, with SSMIS satellite measurements during the full period January 2007-June 2014 and against the combined SSM/I + MERIS satellite data set developed in the framework of the ESA DUE GlobVapour project (January 2007-December 2008). Global mean biases as small as ±0.035 g cm-2 are found between GOME-2A and all other data sets. The combined SSM/I-MERIS sample and the ECMWF ERA-Interim data set are typically drier than the GOME-2 retrievals, while on average GOME-2 data overestimate the SSMIS measurements by only 0.006 g cm-2. However, the size of these biases is seasonally dependent. Monthly average differences can be as large as 0.1 g cm-2, based on the analysis against SSMIS measurements, which include only data over

  10. Planning for Office Automation.

    ERIC Educational Resources Information Center

    Mick, Colin K.

    1983-01-01

    Outlines a practical approach to planning for office automation termed the "Focused Process Approach" (the "what" phase, "how" phase, "doing" phase) which is a synthesis of the problem-solving and participatory planning approaches. Thirteen references are provided. (EJS)

  11. MetPetDB: New Directions for Metamorphic Studies

    NASA Astrophysics Data System (ADS)

    Spear, F. S.; Adali, S.; Szymanski, B. K.; Hallett, B. K.; Waters, A. J.; Linder, Z. J.; Fyffe, M. E.; Goldfarb, D.; Barlett, K.

    2008-12-01

    It is estimated that less than 1% of the data collected on metamorphic rocks is published, and MetPetDB (database for metamorphic geochemistry) is being developed and populated to preserve these data and to foster new and innovative directions for scientific research and education. The data model is based on a sample of metamorphic rock and includes information about location, rock type, mineral assemblage, fabric, plus images of all types and mineral composition data. Mineral analyses are linked to locations on appropriate images so the spatial integrity of the data is preserved. Tools will be available for mineral recalculation, plotting, and thermobarometric applications. Derivative data such as peak P-T conditions, metamorphic P-T path, and cooling rate will also be stored. The database will be searchable based on any number of data fields, permitting rapid location of samples that can be used to test hypotheses and discover new relationships. For example: A student is designing a thesis project and MetPetDB will be a first resource to determine the types of rocks present in a region, the work that has been done on them, and links to the published findings. The Fe/Mg zoning in migmatitic garnets has been used to infer cooling rates. What is the range of cooling rates recorded by migmatitic garnets, and is there a correlation between peak metamorphic temperature and cooling rate? Is it possible that melting triggers rapid thrusting that causes the rapid cooling? A search on: rock type = migmatite plus Fe and Mg X-ray maps of garnet would reveal all samples that could be used in this study. A new geobarometer based on a specific mineral assemblage is proposed that permits pressures to be estimated to within 50 MPa. A search of the database for all samples with this assemblage plus analyses of the necessary minerals would provide a set of samples to which this new barometer can be applied. Recalculating pressures and temperatures for an entire region using new

  12. Author's reply to discussion of a unified approach to drillstem failure prevention

    SciTech Connect

    Hill, T.H.

    1993-06-01

    This paper was written to defend the author's previous paper entitled A Unified Approach to Drillstem Failure Prevention', presented in the December 1992, SPE Drilling Engineering. The original paper was written from the point of view that rental companies will often use lower quality drill stem in order to keep it in service for longer periods while an operator would probably refuse the same piece of pipe to help ensure that drillstem failure is minimized. A rebuttal was submitted as a result which stated that rental company equipment met the standards specified in the contracts and if there was problems with the drill pipes, then a stricter specification should be applied. In defense of this author's original paper, this response made several clarifications. The author describes the inspection process by which a drillstem is measured to be acceptable or unacceptable. The standards developed by the American Petroleum Institute (API) allow for a significant variation on the acceptability of drillstem based on the standpoint of the inspector. Obvious cracked, damaged, or corroded pipes would fail while non-abraded, non-pitted, or non-damaged pipes would pass. The big problems lie in the larger number or pipes which fall somewhere in-between these extremes, where arbitrary limits have to be established because measuring equipment cannot detect the flaws. The author states that an inspector hired by the rental company would lean toward passing the pipes while an inspector for the operator might fail the same pipe. He goes on to recommend modifications in the API damage classification system.

  13. The Tenth Summative Report of the Office of Computer-Based Instruction.

    ERIC Educational Resources Information Center

    Hofstetter, Fred T.

    The University of Delaware's work with computer-based instruction since 1974 is summarized with attention to the history and development of the Office of Computer-Based Instruction, university applications, outside user applications, and research and evaluation. PLATO was the system that met the university's criteria, which included support for…

  14. The Ninth Summative Report of the Office of Computer-Based Instruction.

    ERIC Educational Resources Information Center

    Hofstetter, Fred T.

    The University of Delaware's work with computer-based instruction since 1974 is summarized, with attention to the history and development of the Office of Computer-Based Instruction, university applications, outside user applications, and research and evaluation. PLATO was the system that met the university's criteria, which included: supporting…

  15. The Eleventh Summative Report of the Office of Computer-Based Instruction.

    ERIC Educational Resources Information Center

    Hofstetter, Fred T.

    The University of Delaware's work with computer-based instruction since 1974 is summarized with attention to the history and development of the Office of Computer-Based Instruction, university applications, outside user applications, and research and evaluation. PLATO was the system that met the university's criteria, which included support for…

  16. M-COPA, a Golgi Disruptor, Inhibits Cell Surface Expression of MET Protein and Exhibits Antitumor Activity against MET-Addicted Gastric Cancers.

    PubMed

    Ohashi, Yoshimi; Okamura, Mutsumi; Hirosawa, Asaka; Tamaki, Naomi; Akatsuka, Akinobu; Wu, Kuo-Ming; Choi, Hyeong-Wook; Yoshimatsu, Kentaro; Shiina, Isamu; Yamori, Takao; Dan, Shingo

    2016-07-01

    The Golgi apparatus is responsible for transporting, processing, and sorting numerous proteins in the cell, including cell surface-expressed receptor tyrosine kinases (RTK). The small-molecule compound M-COPA [2-methylcoprophilinamide (AMF-26)] disrupts the Golgi apparatus by inhibiting the activation of Arf1, resulting in suppression of tumor growth. Here, we report an evaluation of M-COPA activity against RTK-addicted cancers, focusing specifically on human gastric cancer (GC) cells with or without MET amplification. As expected, the MET-addicted cell line MKN45 exhibited a better response to M-COPA than cell lines without MET amplification. Upon M-COPA treatment, cell surface expression of MET was downregulated with a concurrent accumulation of its precursor form. M-COPA also reduced levels of the phosphorylated form of MET along with the downstream signaling molecules Akt and S6. Similar results were obtained in additional GC cell lines with amplification of MET or the FGF receptor FGFR2 MKN45 murine xenograft experiments demonstrated the antitumor activity of M-COPA in vivo Taken together, our results offer an initial preclinical proof of concept for the use of M-COPA as a candidate treatment option for MET-addicted GC, with broader implications for targeting the Golgi apparatus as a novel cancer therapeutic approach. Cancer Res; 76(13); 3895-903. ©2016 AACR. PMID:27197184

  17. Overexpression of FGFR2 contributes to inherent resistance to MET inhibitors in MET-amplified patient-derived gastric cancer xenografts

    PubMed Central

    LIU, KAI; SONG, XILIN; ZHU, MEIRONG; MA, HENG

    2015-01-01

    Gastric cancer is one of the most malignant diseases and one of the leading causes of cancer-associated mortality worldwide. Although advances have been made in surgical techniques, perioperative management and the combined use of surgery with chemotherapy and/or radiotherapy, patients with advanced stage gastric cancer continue to face poor outcomes. Furthermore, it was reported that MET gene amplification and overexpression predicted the sensitivity to MET inhibitors in gastric cancer. However, the identification of drug-resistant tumors has encouraged the pre-emptive elucidation of the possible mechanisms of clinical resistance. The current study assessed a number of patient-derived gastric cancer models with MET amplification and overexpression, including CNGAS028. The tumor tissues were subjected to microarray analysis (using single nucleotide polymorphism 6.0 and human genome U133 arrays) followed by western blotting. The results demonstrated that CNGAS028 xenograft tumors did not respond to treatment with a selective MET inhibitor. Additional analysis indicated that FGFR2 overexpression contributed to the resistance to MET inhibitors. Furthermore, treatment with a combination of fibroblast growth factor receptor 2 and MET inhibitors inhibited the growth of CNGAS028 xenograft tumors in vivo. In conclusion, the current results aid in understanding the mechanism of inherent resistance to selective MET inhibitors as well as provide important information for patient selection and clinical treatment strategies. PMID:26622787

  18. Off Target Effects of c-MET Inhibitors on Thyroid Cancer Cells

    PubMed Central

    Zhou, Yan; Zhao, Conghui; Gery, Sigal; Braunstein, Glenn D.; Okamoto, Ryoko; Alvarez, Rocio; Miles, Steven A.; Doan, Ngan B.; Said, Jonathan W.; Gu, Jiang; Koeffler, H. Phillip

    2013-01-01

    Aberrantly activated c-MET signaling occurs in several cancers, promoting the development of c-MET inhibitors. In this study, we found that eight of 8 thyroid cancer cell lines (including six anaplastic thyroid cell lines) have prominent expression of c-MET protein. Fifty percent of the thyroid cancer cell lines (four of 8) were growth-inhibited by two small molecule c-MET inhibitors (Tivantinib and Crizotinib), associated with apoptosis and G2/M cell cycle arrest. However, Crizotinib did not inhibit 50% proliferation of thyroid cancer cells (SW1736 and TL3) at a concentration at which the drug completely inhibited ligand-stimulated c-MET phosphorylation. On the other hand, Tivantinib was less potent than Crizotinib at inhibiting c-MET phosphorylation, but was more potent than Crizotinib at decreasing cell growth. Suppressing c-MET protein expression and phosphorylation using siRNA targeting c-MET did not induce cell cycle arrest and apoptosis. Taken together, Tivantinib and Crizotinib have off target(s) activity, contributing to their anti-tumor activity. In vivo study showed that Crizotinib markedly inhibited the growth of thyroid cancer cells (SW1736) in immunodeficient mice. In summary, c-MET inhibitors (Tivantinib and Crizotinib) suppress the growth of aggressive thyroid cancer cells, and this potential therapeutic benefit results from their non-MET-targeting effects. PMID:24170771

  19. Live cell imaging shows hepatocyte growth factor-induced Met dimerization.

    PubMed

    Koschut, David; Richert, Ludovic; Pace, Giuseppina; Niemann, Hartmut H; Mély, Yves; Orian-Rousseau, Véronique

    2016-07-01

    The canonical model of receptor tyrosine kinase (RTK) activation assumes that ligand-induced dimerization of inactive receptor monomers is a prerequisite for autophosphorylation. For several RTK families, recent results of fluorescence microscopy provided evidence for preformed receptor dimers that may or may not require ligand binding for kinase activity. Here we report, for the first time, the application of advanced quantitative fluorescence microscopy techniques to study changes in the oligomerization state of the RTK Met in response to stimulation by its endogenous ligand hepatocyte growth factor (HGF). We used inducible C-terminal fusions between Met and enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) in combination with fluorescence resonance energy transfer (FRET)-based fluorescence-lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS). A small fraction of HGF-independent Met dimers appeared to be present in cells even at low receptor density. At high receptor density, both the fraction of Met dimers and the level of Met autophosphorylation increased in the absence of HGF. Stimulation with HGF at low receptor density significantly increased the fraction of Met dimers on live cells. We found no indications of Met oligomers larger than dimers. Our findings thus confirm a model of Met activation through HGF-induced dimerization and at the same time they support previous reports of Met dimers in unstimulated cells. The tools established in this work will be useful to further characterize the mechanism of Met activation and to define the contribution of co-receptors. PMID:27094128

  20. Mechanistic Support for Combined MET and AR Blockade in Castration-Resistant Prostate Cancer12

    PubMed Central

    Qiao, Yuanyuan; Feng, Felix Y.; Wang, Yugang; Cao, Xuhong; Han, Sumin; Wilder-Romans, Kari; Navone, Nora M.; Logothetis, Christopher; Taichman, Russell S.; Keller, Evan T.; Palapattu, Ganesh S.; Alva, Ajjai S.; Smith, David C.; Tomlins, Scott A.; Chinnaiyan, Arul M.; Morgan, Todd M.

    2016-01-01

    A recent phase III trial of the MET kinase inhibitor cabozantinib in men with castration-resistant prostate cancer (CRPC) failed to meet its primary survival end point; however, most men with CRPC have intact androgen receptor (AR) signaling. As previous work supports negative regulation of MET by AR signaling, we hypothesized that intact AR signaling may have limited the efficacy of cabozantinib in some of these patients. To assess the role of AR signaling on MET inhibition, we first performed an in silico analysis of human CRPC tissue samples stratified by AR signaling status (+ or −), which identified MET expression as markedly increased in AR− samples. In vitro, AR signaling inhibition in AR+ CRPC models increased MET expression and resulted in susceptibility to ligand (HGF) activation. Likewise, MET inhibition was only effective in blocking cancer phenotypes in cells with MET overexpression. Using multiple AR+ CRPC in vitro and in vivo models, we showed that combined cabozantinib and enzalutamide (AR antagonist) treatment was more efficacious than either inhibitor alone. These data provide a compelling rationale to combine AR and MET inhibition in CRPC and may explain the negative results of the phase III cabozantinib study in CRPC. Similarly, the expression of MET in AR− disease, whether due to AR inhibition or loss of AR signaling, suggests potential utility for MET inhibition in select patients with AR therapy resistance and in AR− prostate cancer. PMID:26806347

  1. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  2. Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer

    PubMed Central

    Kaye, Deborah R.; Pinto, Peter A.; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C.; Gupta, Gopal; Choyke, Peter L.

    2016-01-01

    Objective To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. Patients and Methods 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9–10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. Results PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Conclusion Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa. PMID:27300295

  3. Cellular and molecular mechanisms of HGF/Met in the cardiovascular system.

    PubMed

    Gallo, Simona; Sala, Valentina; Gatti, Stefano; Crepaldi, Tiziana

    2015-12-01

    Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the

  4. Increasing sulphite formation in Saccharomyces cerevisiae by overexpression of MET14 and SSU1.

    PubMed

    Donalies, Ute E B; Stahl, Ulf

    2002-04-01

    Saccharomyces cerevisiae produces sulphite as an intermediate product during the assimilatory reduction of sulphate to sulphide. Three genes, MET3, MET14 and MET16, are essential for this reduction. We investigated the level of transcription of these genes in strains of S. cerevisiae with high, medium and low sulphite formation. The level of MET14- and MET16-mRNA varied with sulphite production, whereas the level of MET3-mRNA was very weak in almost all strains. We also analysed the effect of overexpression of MET14 and MET16 on sulphite formation. Two strains with low sulphite production were transformed with high-copy plasmids containing either or both MET14 and MET16. The overexpression of these two genes leads to a two- to three-fold sulphite formation. In addition, inactivation of MET10, encoding a subunit of the sulphite reductase, also leads to a distinct increase in sulphite formation; however, the cells became methionine auxotroph. The overexpression of SSU1, a gene encoding a putative sulphite pump, yields a slight increase in sulphite accumulation, whereas overexpression of SSU1, together with MET14, increases sulphite formation up to 10-fold. Furthermore, sulphite formation strongly depends on growth conditions, e.g. yeast transformants growing in wort produce much higher amounts of sulphite when compared to growth in minimal media. The addition of glucose can also increase the sulphite formation in strains overexpressing MET14 and/or SSU1 under oxygen-limiting conditions, while the addition of glucose has no significant effect under aerobic conditions. PMID:11921096

  5. MET is required for the recruitment of anti-tumoural neutrophils

    PubMed Central

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A.A. Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-01-01

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours1-4, which rely on the constitutive engagement of this pathway for their growth and survival1,5. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells although its precise role in this compartment is not well characterized6-11. Here, we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand HGF. Met deletion in neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both primary tumour and metastatic site. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived TNF-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and iNOS production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. Following systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect rising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential “Achilles’ heel” of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  6. Effects of met-enkephalin on the mechanical activity and distribution of met-enkephalin-like immunoreactivity in the cat small intestine.

    PubMed

    Radomirov, R; Venkova, K; Davidoff, M; Pencheva, N

    1990-01-01

    Naloxone-dependent effects of Met-enkephalin (10(-8) M) on the spontaneous and electrically induced mechanical activities were studied in longitudinal and circular preparations isolated from the cat duodenum, jejunum and ileum. Met-Enkephalin changed the spontaneous activity of all preparations tested with the exception of the circular preparations from the ileum. Met-Enkephalin-induced responses of the longitudinal preparations from the ileum were abolished by treatment with tetrodotoxin (10(-7) M), while the responses of both longitudinal and circular preparations from the duodenum and jejunum were only partially depressed, being resistant to tetrodotoxin components. The latter were most pronounced in the duodenum. The neurogenic electrically induced (0.5 msec, 5 Hz, 150 pulses) responses of all the preparations consisted mainly of contractile components which were significantly and naloxone-dependently reduced by Met-enkephalin (10(-8) M). The contractile components of the responses, which were reduced by Met-enkephalin, were entirely abolished by atropine (3 x 10(-6) M). Both Met-enkephalin and atropine inhibitory effects on the neurogenic responses were more pronounced in the ileum. Met-Enkephalin was found in nerve fibers of the myenteric plexus distributed mainly among the circular muscle. Single immunoreactive nerve fibers were observed in the longitudinal muscle layer of the duodenum but not in the jejunum and ileum. The distribution of Met-enkephalin-like immunoreactivity along the small intestine did not show significant differences among the three intestinal regions tested. The results obtained suggest that Met-enkephalin can modulate the mechanical activity of the cat small intestine, inhibiting cholinergic transmission and/or activating smooth muscle opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2199944

  7. Unified dark matter: constraints from galaxies and clusters

    NASA Astrophysics Data System (ADS)

    El-Zant, Amr A.

    2015-11-01

    Unified dark matter models are appealing in that they describe the dark sector in terms of a single component. They however face problems when attempting to account for structure formation: in the linear regime, density fluctuations can become Jeans stable and oscillate rather than collapse, though it is possible that this difficulty may be circumvented by invoking non-linear clustering. Here we examine the behaviour in the fully non-linear regime, of collapsed objects that should mimic standard dark matter haloes. It is shown that the pressure gradient associated with the unified dark matter fluid should be significant in the outer parts of galaxies and clusters, and its effects observable. In this case, no flat or falling rotation curve is possible for any (barotropic) equation of state with associated sound speed decreasing with density (a necessary condition if the fluid is to behave as pressureless matter at high density). The associated density profile is therefore also incompatible with that inferred in the outer part of clusters. For the prototypical case of the generalized Chaplygin gas, it is shown that this limits the values of the equation of state index α that are compatible with observations to α ≲ 0.0001 or α ≳ 2. This is in line from what is deduced from linear analysis. More generally, from the expected properties of dark matter haloes, constraints on the sound speed are derived. For the particular case of the generalized Chaplygin gas, this further constrains the index to α ≲ 10- 9 or α ≳ 6.7. For a unified dark matter fluid to mimic dark halo properties, therefore, it needs to have an equation of state such that the pressure gradients are either minimal or which decrease fast enough so as to be negligible at densities characteristic of the outer parts of haloes.

  8. MBAT: A scalable informatics system for unifying digital atlasing workflows

    PubMed Central

    2010-01-01

    Background Digital atlases provide a common semantic and spatial coordinate system that can be leveraged to compare, contrast, and correlate data from disparate sources. As the quality and amount of biological data continues to advance and grow, searching, referencing, and comparing this data with a researcher's own data is essential. However, the integration process is cumbersome and time-consuming due to misaligned data, implicitly defined associations, and incompatible data sources. This work addressing these challenges by providing a unified and adaptable environment to accelerate the workflow to gather, align, and analyze the data. Results The MouseBIRN Atlasing Toolkit (MBAT) project was developed as a cross-platform, free open-source application that unifies and accelerates the digital atlas workflow. A tiered, plug-in architecture was designed for the neuroinformatics and genomics goals of the project to provide a modular and extensible design. MBAT provides the ability to use a single query to search and retrieve data from multiple data sources, align image data using the user's preferred registration method, composite data from multiple sources in a common space, and link relevant informatics information to the current view of the data or atlas. The workspaces leverage tool plug-ins to extend and allow future extensions of the basic workspace functionality. A wide variety of tool plug-ins were developed that integrate pre-existing as well as newly created technology into each workspace. Novel atlasing features were also developed, such as supporting multiple label sets, dynamic selection and grouping of labels, and synchronized, context-driven display of ontological data. Conclusions MBAT empowers researchers to discover correlations among disparate data by providing a unified environment for bringing together distributed reference resources, a user's image data, and biological atlases into the same spatial or semantic context. Through its extensible

  9. A unified large/small-scale dynamo in helical turbulence

    NASA Astrophysics Data System (ADS)

    Bhat, Pallavi; Subramanian, Kandaswamy; Brandenburg, Axel

    2016-09-01

    We use high resolution direct numerical simulations (DNS) to show that helical turbulence can generate significant large-scale fields even in the presence of strong small-scale dynamo action. During the kinematic stage, the unified large/small-scale dynamo grows fields with a shape-invariant eigenfunction, with most power peaked at small scales or large k, as in Subramanian & Brandenburg. Nevertheless, the large-scale field can be clearly detected as an excess power at small k in the negatively polarized component of the energy spectrum for a forcing with positively polarized waves. Its strength overline{B}, relative to the total rms field Brms, decreases with increasing magnetic Reynolds number, ReM. However, as the Lorentz force becomes important, the field generated by the unified dynamo orders itself by saturating on successively larger scales. The magnetic integral scale for the positively polarized waves, characterizing the small-scale field, increases significantly from the kinematic stage to saturation. This implies that the small-scale field becomes as coherent as possible for a given forcing scale, which averts the ReM-dependent quenching of overline{B}/B_rms. These results are obtained for 10243 DNS with magnetic Prandtl numbers of PrM = 0.1 and 10. For PrM = 0.1, overline{B}/B_rms grows from about 0.04 to about 0.4 at saturation, aided in the final stages by helicity dissipation. For PrM = 10, overline{B}/B_rms grows from much less than 0.01 to values of the order the 0.2. Our results confirm that there is a unified large/small-scale dynamo in helical turbulence.

  10. Simulation of Aerosols and Chemistry with a Unified Global Model

    NASA Technical Reports Server (NTRS)

    Chin, Mian

    2004-01-01

    This project is to continue the development of the global simulation capabilities of tropospheric and stratospheric chemistry and aerosols in a unified global model. This is a part of our overall investigation of aerosol-chemistry-climate interaction. In the past year, we have enabled the tropospheric chemistry simulations based on the GEOS-CHEM model, and added stratospheric chemical reactions into the GEOS-CHEM such that a globally unified troposphere-stratosphere chemistry and transport can be simulated consistently without any simplifications. The tropospheric chemical mechanism in the GEOS-CHEM includes 80 species and 150 reactions. 24 tracers are transported, including O3, NOx, total nitrogen (NOy), H2O2, CO, and several types of hydrocarbon. The chemical solver used in the GEOS-CHEM model is a highly accurate sparse-matrix vectorized Gear solver (SMVGEAR). The stratospheric chemical mechanism includes an additional approximately 100 reactions and photolysis processes. Because of the large number of total chemical reactions and photolysis processes and very different photochemical regimes involved in the unified simulation, the model demands significant computer resources that are currently not practical. Therefore, several improvements will be taken, such as massive parallelization, code optimization, or selecting a faster solver. We have also continued aerosol simulation (including sulfate, dust, black carbon, organic carbon, and sea-salt) in the global model to cover most of year 2002. These results have been made available to many groups worldwide and accessible from the website http://code916.gsfc.nasa.gov/People/Chin/aot.html.

  11. HGF-independent Potentiation of EGFR Action by c-Met

    PubMed Central

    Dulak, Austin M.; Gubish, Christopher T.; Stabile, Laura P.; Henry, Cassandra; Siegfried, Jill M.

    2011-01-01

    The c-Met receptor is a potential therapeutic target for non-small cell lung cancer (NSCLC). Signaling interactions between c-Met and the mutant Epidermal Growth Factor Receptor (EGFR) have been studied extensively, but signaling intermediates and biological consequences of lateral signaling to c-Met in EGFR wild-type tumors is minimally understood. Our observations indicate that delayed c-Met activation in NSCLC cell lines is initiated by wild-type EGFR, the receptor most often found in NSCLC tumors. EGFR ligands induce accumulation of activated c-Met which begins at 8 h continues for 48 h. This effect is accompanied by an increase in c-Met expression and phosphorylation of critical c-Met tyrosine residues without activation of MAPK or Akt. Gene transcription is required for delayed c-Met activation; however, phosphorylation of c-Met by EGFR occurs without production of HGF or another secreted factor, supporting a ligand-independent mechanism. Lateral signaling is blocked by two selective c-Met tyrosine kinase inhibitors (TKIs), PF2341066 and SU11274, or with gefitinib, an EGFR TKI, suggesting kinase activity of both receptors is required for this effect. Prolonged c-Src phosphorylation is observed, and c-Src pathway is essential for EGFR to c-Met communication. Pre-treatment with pan-SFK inhibitors, PP2 and dasatinib, abolishes delayed c-Met phosphorylation. A c-Src dominant-negative construct reduces EGF-induced c-Met phosphorylation compared to control, further, confirming a c-Src requirement. Inhibition of c-Met with PF2341066 and siRNA decreases EGF-induced phenotypes of invasion by ~86% and motility by ~81%, suggesting that a novel form of c-Met activation is utilized by EGFR to maximize these biological effects. Combined targeting of c-Met and EGFR leads to increased xenograft anti-tumor activity, demonstrating that inhibition of downstream and lateral signaling from the EGFR-c-Src-c-Met axis might be effective in treatment of NSCLC. PMID:21423210

  12. 20 CFR 422.5 - District offices and branch offices.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false District offices and branch offices. 422.5 Section 422.5 Employees' Benefits SOCIAL SECURITY ADMINISTRATION ORGANIZATION AND PROCEDURES Organization and Functions of the Social Security Administration § 422.5 District offices and branch offices. There are over 700 social security...

  13. Fluctuation-response relation unifies dynamical behaviors in neural fields

    NASA Astrophysics Data System (ADS)

    Fung, C. C. Alan; Wong, K. Y. Michael; Mao, Hongzi; Wu, Si

    2015-08-01

    Anticipation is a strategy used by neural fields to compensate for transmission and processing delays during the tracking of dynamical information and can be achieved by slow, localized, inhibitory feedback mechanisms such as short-term synaptic depression, spike-frequency adaptation, or inhibitory feedback from other layers. Based on the translational symmetry of the mobile network states, we derive generic fluctuation-response relations, providing unified predictions that link their tracking behaviors in the presence of external stimuli to the intrinsic dynamics of the neural fields in their absence.

  14. A Unified Approach to Intra-Domain Security

    SciTech Connect

    Shue, Craig A; Kalafut, Andrew J.; Gupta, Prof. Minaxi

    2009-01-01

    While a variety of mechanisms have been developed for securing individual intra-domain protocols, none address the issue in a holistic manner. We develop a unified framework to secure prominent networking protocols within a single domain. We begin with a secure version of the DHCP protocol, which has the additional feature of providing each host with a certificate. We then leverage these certificates to secure ARP, prevent spoofing within the domain, and secure SSH and VPN connections between the domain and hosts which have previously interacted with it locally. In doing so, we also develop an incrementally deployable public key infrastructure which can later be leveraged to support inter-domain authentication.

  15. Skinner Rusk unified formalism for optimal control systems and applications

    NASA Astrophysics Data System (ADS)

    Barbero-Liñán, María; Echeverría-Enríquez, Arturo; Martín de Diego, David; Muñoz-Lecanda, Miguel C.; Román-Roy, Narciso

    2007-10-01

    A geometric approach to time-dependent optimal control problems is proposed. This formulation is based on the Skinner and Rusk formalism for Lagrangian and Hamiltonian systems. The corresponding unified formalism developed for optimal control systems allows us to formulate geometrically the necessary conditions given by a weak form of Pontryagin's maximum principle, provided that the differentiability with respect to controls is assumed and the space of controls is open. Furthermore, our method is also valid for implicit optimal control systems and, in particular, for the so-called descriptor systems (optimal control problems including both differential and algebraic equations).

  16. A unified cell biological perspective on axon–myelin injury

    PubMed Central

    2014-01-01

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon–myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders. PMID:25092654

  17. A Unified Topological Layer for Finite Element Space Discretization

    NASA Astrophysics Data System (ADS)

    Stimpfl, Franz; Weinbub, Josef; Heinzl, René; Schwaha, Philipp; Selberherr, Siegfried

    2010-09-01

    A unified topological layer for mesh generation has been created to benefit from current development, to reuse existing, well tested and reliable methods, such as the Delaunay or the Advancing Front mesh generation approach, and to combine them to be able to interchange these methods, without taking a detour using file formats. In addition, by modularizing existing meshing kernels, this approach allows to not only have one meshing interface for arbitrary dimensions, but also to have the possibility at hand to independently combine different meshing strategies.

  18. Unified inference for sparse and dense longitudinal models.

    PubMed

    Kim, Seonjin; Zhao, Zhibiao

    2013-03-01

    In longitudinal data analysis, statistical inference for sparse data and dense data could be substantially different. For kernel smoothing estimate of the mean function, the convergence rates and limiting variance functions are different under the two scenarios. The latter phenomenon poses challenges for statistical inference as a subjective choice between the sparse and dense cases may lead to wrong conclusions. We develop self-normalization based methods that can adapt to the sparse and dense cases in a unified framework. Simulations show that the proposed methods outperform some existing methods. PMID:24966413

  19. A unified approach to asphaltene precipitation: Laboratory measurement and modeling

    SciTech Connect

    MacMillan, D.J.; Tackett, J.E. Jr.; Jessee, M.A.; Monger-McClure, T.G.

    1995-11-01

    A unified approach to evaluating asphaltene precipitation based on laboratory measurement and modeling is presented. This approach used an organic deposition cell for measuring asphaltene drop out onset conditions. Asphaltene precipitation was detected by changes in optical fluorescence, electrical conductance, and visual observation. A series of experiments measured the effects of changing pressure, temperature and composition on asphaltene precipitation. A fully-compositional V-L-S mathematical model completed the analysis by matching the experimental results. The model was then used to forecast asphaltene precipitation under a variety of production scenarios including response to gas-lift operations, and to evaluate the possible location of a tar-mat.

  20. Towards a Unifying Framework for Pattern Transformation in Swarm Systems

    NASA Astrophysics Data System (ADS)

    Varghese, Blesson; McKee, Gerard

    2009-03-01

    This paper identifies the major challenges in the area of pattern formation. The work is also motivated by the need for development of a single framework to surmount these challenges. A framework based on the control of macroscopic parameters is proposed. The issue of transformation of patterns is specifically considered. A definition for transformation and four special cases, namely elementary and geometrical transformations by repositioning all or some robots in the pattern are provided. Two feasible tools for pattern transformation namely, a macroscopic parameter method and a mathematical tool—Moebius transformation also known as the linear fractional transformation are introduced. The realization of the unifying framework considering planning and communication is reported.