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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 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

  15. 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

  16. 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

  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

    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.

  12. 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.

  13. 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

  14. 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.

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  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. 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...

  8. 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

  9. 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

  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--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…

  20. 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…

  1. 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…

  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. 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.

  7. 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.

  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

    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

  16. 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.

  17. 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.

  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. 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.

  14. 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).

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. 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....

  2. 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....

  3. 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....

  4. 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....

  5. 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....

  6. 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…

  7. 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...

  8. 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.

  9. 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…

  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. 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.

  12. 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.

  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. 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.

  1. 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.

  2. 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.

  3. 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…

  4. 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,...

  5. 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...

  6. 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...

  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. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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...

  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. 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.

  8. 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.

  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. 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.

  13. 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

  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. 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.)

  7. 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.

  8. 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…

  9. 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…

  10. 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…

  11. 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.…

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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…

  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. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  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. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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).

  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. 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.

  18. 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.

  19. 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.

  20. 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?

  1. 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…

  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. 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.

  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. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  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. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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…

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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....

  16. 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....

  17. 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…

  18. 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…

  19. 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...

  20. 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…

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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