Sample records for met office unified

  1. Using Machine Learning as a fast emulator of physical processes within the Met Office's Unified Model

    NASA Astrophysics Data System (ADS)

    Prudden, R.; Arribas, A.; Tomlinson, J.; Robinson, N.

    2017-12-01

    The Unified Model is a numerical model of the atmosphere used at the UK Met Office (and numerous partner organisations including Korean Meteorological Agency, Australian Bureau of Meteorology and US Air Force) for both weather and climate applications.Especifically, dynamical models such as the Unified Model are now a central part of weather forecasting. Starting from basic physical laws, these models make it possible to predict events such as storms before they have even begun to form. The Unified Model can be simply described as having two components: one component solves the navier-stokes equations (usually referred to as the "dynamics"); the other solves relevant sub-grid physical processes (usually referred to as the "physics"). Running weather forecasts requires substantial computing resources - for example, the UK Met Office operates the largest operational High Performance Computer in Europe - and the cost of a typical simulation is spent roughly 50% in the "dynamics" and 50% in the "physics". Therefore there is a high incentive to reduce cost of weather forecasts and Machine Learning is a possible option because, once a machine learning model has been trained, it is often much faster to run than a full simulation. This is the motivation for a technique called model emulation, the idea being to build a fast statistical model which closely approximates a far more expensive simulation. In this paper we discuss the use of Machine Learning as an emulator to replace the "physics" component of the Unified Model. Various approaches and options will be presented and the implications for further model development, operational running of forecasting systems, development of data assimilation schemes, and development of ensemble prediction techniques will be discussed.

  2. The East Asian Atmospheric Water Cycle and Monsoon Circulation in the Met Office Unified Model

    NASA Astrophysics Data System (ADS)

    Rodríguez, José M.; Milton, Sean F.; Marzin, Charline

    2017-10-01

    In this study the low-level monsoon circulation and observed sources of moisture responsible for the maintenance and seasonal evolution of the East Asian monsoon are examined, studying the detailed water budget components. These observational estimates are contrasted with the Met Office Unified Model (MetUM) climate simulation performance in capturing the circulation and water cycle at a variety of model horizontal resolutions and in fully coupled ocean-atmosphere simulations. We study the role of large-scale circulation in determining the hydrological cycle by analyzing key systematic errors in the model simulations. MetUM climate simulations exhibit robust circulation errors, including a weakening of the summer west Pacific Subtropical High, which leads to an underestimation of the southwesterly monsoon flow over the region. Precipitation and implied diabatic heating biases in the South Asian monsoon and Maritime Continent region are shown, via nudging sensitivity experiments, to have an impact on the East Asian monsoon circulation. By inference, the improvement of these tropical biases with increased model horizontal resolution is hypothesized to be a factor in improvements seen over East Asia with increased resolution. Results from the annual cycle of the hydrological budget components in five domains show a good agreement between MetUM simulations and ERA-Interim reanalysis in northern and Tibetan domains. In simulations, the contribution from moisture convergence is larger than in reanalysis, and they display less precipitation recycling over land. The errors are closely linked to monsoon circulation biases.

  3. The evaluation and development of the Met Office Unified Model using surface and space borne radar.

    NASA Astrophysics Data System (ADS)

    Petch, J.

    2012-12-01

    The Met Office Unified Model is used for the prediction of weather and climate on time scales of hours through to centuries. Therefore, the parametrizations in that model need to work on weather and climate timescale, and with grid-lengths from hundres of meters through to several hundred kilometres. Focusing on the development of the cloud and radiation schemes I will discuss how we are using ground-based remote-sensing observations from Chilbolton (England) and a combination of Cloudsat and Calipso data to evaluate and improve the performance of the model. I will show how the prediction of the clouds has improved since the AR5 version of the model and how we have developed an improved cloud generator to rebresent the sub-grid variability of clouds for radiative transfer.

  4. Exploring the climate of Proxima B with the Met Office Unified Model

    NASA Astrophysics Data System (ADS)

    Boutle, Ian A.; Mayne, Nathan J.; Drummond, Benjamin; Manners, James; Goyal, Jayesh; Hugo Lambert, F.; Acreman, David M.; Earnshaw, Paul D.

    2017-05-01

    We present results of simulations of the climate of the newly discovered planet Proxima Centauri B, performed using the Met Office Unified Model (UM). We examine the responses of both an "Earth-like" atmosphere and simplified nitrogen and trace carbon dioxide atmosphere to the radiation likely received by Proxima Centauri B. Additionally, we explore the effects of orbital eccentricity on the planetary conditions using a range of eccentricities guided by the observational constraints. Overall, our results are in agreement with previous studies in suggesting Proxima Centauri B may well have surface temperatures conducive to the presence of liquid water. Moreover, we have expanded the parameter regime over which the planet may support liquid water to higher values of eccentricity (≳0.1) and lower incident fluxes (881.7 W m-2) than previous work. This increased parameter space arises because of the low sensitivity of the planet to changes in stellar flux, a consequence of the stellar spectrum and orbital configuration. However, we also find interesting differences from previous simulations, such as cooler mean surface temperatures for the tidally-locked case. Finally, we have produced high-resolution planetary emission and reflectance spectra, and highlight signatures of gases vital to the evolution of complex life on Earth (oxygen, ozone and carbon dioxide).

  5. The Met Office Unified Model Global Atmosphere 6.0/6.1 and JULES Global Land 6.0/6.1 configurations

    NASA Astrophysics Data System (ADS)

    Walters, David; Boutle, Ian; Brooks, Malcolm; Melvin, Thomas; Stratton, Rachel; Vosper, Simon; Wells, Helen; Williams, Keith; Wood, Nigel; Allen, Thomas; Bushell, Andrew; Copsey, Dan; Earnshaw, Paul; Edwards, John; Gross, Markus; Hardiman, Steven; Harris, Chris; Heming, Julian; Klingaman, Nicholas; Levine, Richard; Manners, James; Martin, Gill; Milton, Sean; Mittermaier, Marion; Morcrette, Cyril; Riddick, Thomas; Roberts, Malcolm; Sanchez, Claudio; Selwood, Paul; Stirling, Alison; Smith, Chris; Suri, Dan; Tennant, Warren; Vidale, Pier Luigi; Wilkinson, Jonathan; Willett, Martin; Woolnough, Steve; Xavier, Prince

    2017-04-01

    We describe Global Atmosphere 6.0 and Global Land 6.0 (GA6.0/GL6.0): the latest science configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) land surface model developed for use across all timescales. Global Atmosphere 6.0 includes the ENDGame (Even Newer Dynamics for General atmospheric modelling of the environment) dynamical core, which significantly increases mid-latitude variability improving a known model bias. Alongside developments of the model's physical parametrisations, ENDGame also increases variability in the tropics, which leads to an improved representation of tropical cyclones and other tropical phenomena. Further developments of the atmospheric and land surface parametrisations improve other aspects of model performance, including the forecasting of surface weather phenomena. We also describe GA6.1/GL6.1, which includes a small number of long-standing differences from our main trunk configurations that we continue to require for operational global weather prediction. Since July 2014, GA6.1/GL6.1 has been used by the Met Office for operational global numerical weather prediction, whilst GA6.0/GL6.0 was implemented in its remaining global prediction systems over the following year.

  6. The Effect of an Increased Convective Entrainment Rate on Indian Monsoon Biases in the Met Office Unified Model

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    Global circulation models (GCMs) are a key tool for understanding and predicting monsoon rainfall, now and under future climate change. However, many GCMs show significant, systematic biases in their simulation of monsoon rainfall and dynamics that spin up over very short time scales and persist in the climate mean state. We describe several of these biases as simulated in the Met Office Unified Model and show they are sensitive to changes in the convective parameterization's entrainment rate. To improve our understanding of the biases and inform efforts to improve convective parameterizations, we explore the reasons for this sensitivity. We show the results of experiments where we increase the entrainment rate in regions of especially large bias: the western equatorial Indian Ocean, western north Pacific and India itself. We use the results to determine whether improvements in biases are due to the local increase in entrainment or are the remote response of the entrainment increase elsewhere in the GCM. We find that feedbacks usually strengthen the local response, but the local response leads to a different mean state change in different regions. We also show results from experiments which demonstrate the spin-up of the local response, which we use to further understand the response in complex regions such as the Western North Pacific. Our work demonstrates that local application of parameterization changes is a powerful tool for understanding their global impact.

  7. Exoplanet modelling with the Met Office Unified Model

    NASA Astrophysics Data System (ADS)

    Boutle, Ian; Lines, Stefan; Mayne, Nathan; Lee, Graham; Helling, Christiane; Drummond, Ben; Manners, James; Goyal, Jayesh; Lambert, Hugo; Acreman, David; Earnshaw, Paul; Amundsen, David; Baraffe, Isabelle

    2017-04-01

    This talk will present an overview of work being done to adapt the Unified Model, one of the most sophisticated weather and climate models of this planet, into a flexible planet simulator for use in the study of any exoplanet. We will focus on two current projects: Clouds in hot Jupiter atmospheres - recent HST observations have revealed a continuum in atmospheric composition from cloudy to clear skies. The presence of clouds is inferred from a grey opacity in the near-IR that mutes key absorption features in the transmission spectra. Unlike the L-T Brown Dwarf sequence, this transition does not correlate well with equilibrium temperature, suggesting that a cloud formation scheme more comprehensive than simply considering the condensation temperature needed for homogenous cloud growth, is required. In our work, we conduct 3D simulations of cloud nucleation, growth, advection, evaporation and gravitational settling in the atmospheres of HD209458b and HD189733 using the kinetic and mixed-grain cloud formation code DIHRT, coupled to the Unified Model. We explore cloud composition, vertical structure and particle sizes, as well as highlighting the importance of the strong atmospheric dynamics seen in tidally locked hot Jupiters on the evolution and distribution of the cloud. Climate of Proxima B - we present results of simulations of the climate of the newly discovered planet Proxima Centauri B, examining the responses of both an `Earth-like' atmosphere and simplified nitrogen and trace carbon dioxide atmosphere to the radiation likely received. Overall, our results are in agreement with previous studies in suggesting Proxima Centauri B may well have surface temperatures conducive to the presence of liquid water. Moreover, we have expanded the parameter regime over which the planet may support liquid water to higher values of eccentricity and lower incident fluxes, guided by observational constraints. This increased parameter space arises because of the low sensitivity

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

    NASA Astrophysics Data System (ADS)

    Lea, Daniel; Mirouze, Isabelle; Martin, Matthew; Hines, Adrian; Guiavarch, Catherine; Shelly, Ann

    2014-05-01

    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). This model combines the atmospheric model UM (Unified Model) at 60 km horizontal resolution on 85 vertical levels, the ocean model NEMO (Nucleus for European Modeling 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 show the impact of coupled DA, one-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 forecast runs, started twice a day, 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 data. These all show the coupled DA system functioning well. Evidence of imbalances and initialisation shocks has also been looked for.

  9. 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

  10. A new Infrared Atmospheric Sounding Interferometer channel selection and assessment of its impact on Met Office NWP forecasts

    NASA Astrophysics Data System (ADS)

    Noh, Young-Chan; Sohn, Byung-Ju; Kim, Yoonjae; Joo, Sangwon; Bell, William; Saunders, Roger

    2017-11-01

    A new set of Infrared Atmospheric Sounding Interferometer (IASI) channels was re-selected from 314 EUMETSAT channels. In selecting channels, we calculated the impact of the individually added channel on the improvement in the analysis outputs from a one-dimensional variational analysis (1D-Var) for the Unified Model (UM) data assimilation system at the Met Office, using the channel score index (CSI) as a figure of merit. Then, 200 channels were selected in order by counting each individual channel's CSI contribution. Compared with the operationally used 183 channels for the UM at the Met Office, the new set shares 149 channels, while the other 51 channels are new. Also examined is the selection from the entropy reduction method with the same 1D-Var approach. Results suggest that channel selection can be made in a more objective fashion using the proposed CSI method. This is because the most important channels can be selected across the whole IASI observation spectrum. In the experimental trial runs using the UM global assimilation system, the new channels had an overall neutral impact in terms of improvement in forecasts, as compared with results from the operational channels. However, upper-tropospheric moist biases shown in the control run with operational channels were significantly reduced in the experimental trial with the newly selected channels. The reduction of moist biases was mainly due to the additional water vapor channels, which are sensitive to the upper-tropospheric water vapor.

  11. Incorporation of UK Met Office's radiation scheme into CPTEC's global model

    NASA Astrophysics Data System (ADS)

    Chagas, Júlio C. S.; Barbosa, Henrique M. J.

    2009-03-01

    Current parameterization of radiation in the CPTEC's (Center for Weather Forecast and Climate Studies, Cachoeira Paulista, SP, Brazil) operational AGCM has its origins in the work of Harshvardhan et al. (1987) and uses the formulation of Ramaswamy and Freidenreich (1992) for the short-wave absorption by water vapor. The UK Met Office's radiation code (Edwards and Slingo, 1996) was incorporated into CPTEC's global model, initially for short-wave only, and some impacts of that were shown by Chagas and Barbosa (2006). Current paper presents some impacts of the complete incorporation (both short-wave and long-wave) of UK Met Office's scheme. Selected results from off-line comparisons with line-by-line benchmark calculations are shown. Impacts on the AGCM's climate are assessed by comparing output of climate runs of current and modified AGCM with products from GEWEX/SRB (Surface Radiation Budget) project.

  12. Sandscape - engaging people in Met Office science through sand sculpture

    NASA Astrophysics Data System (ADS)

    Liggins, Felicity; Dowell, Ellen; Wardley, Jamie; Jamieson, Claire

    2017-04-01

    In 2015, the Met Office's award-winning outreach programme, designed to inspire the next generation of scientists and engineers, delivered one of its most ambitious and creative activities to date. It explored how scientists and artists can come together to create an engaging experience for young people and families. This activity was called Sandscape. Sandscape is an interactive sand sculpture workshop exploring how weather and climate affect our health. Budding sand sculptors are shown how to fashion elaborate structures from sand and water - creating a landscape with bridges, skyscrapers, forests and factories. As they work, participants are encouraged by the scientists delivering the activity to reflect on what makes a healthy city, considering how the natural and built environments influence air quality and circulation and how this impacts our health. Topics discussed include urban heat islands, air pollution and dispersion modelling, pollen forecasting and predicting the wind-borne spread of animal diseases. Each hour long workshop culminates in a dramatic demonstration that uses dry ice to represent clean air circulating from mountains, along rivers and into cities. Here we present an overview of Sandscape, identify the strengths and challenges of such a collaborative, innovative and playful approach to public engagement and share the results of our evaluation. Sandscape was originally supported by the Met Office and the Wellcome Trust, and produced by Einstein's Garden in collaboration with the Met Office, scientists from the University of Exeter and sand sculptors from Sand in Your Eye. It was first presented in Einstein's Garden at Green Man festival 2015, an independent music and arts festival held annually in Wales, and has since been invited to run at the 2015 Bournemouth Arts By the Sea Festival and Teignmouth's TRAIL Sculpture Festival in the summer of 2016.

  13. Verification of space weather forecasts at the UK Met Office

    NASA Astrophysics Data System (ADS)

    Bingham, S.; Sharpe, M.; Jackson, D.; Murray, S.

    2017-12-01

    The UK Met Office Space Weather Operations Centre (MOSWOC) has produced space weather guidance twice a day since its official opening in 2014. Guidance includes 4-day probabilistic forecasts of X-ray flares, geomagnetic storms, high-energy electron events and high-energy proton events. Evaluation of such forecasts is important to forecasters, stakeholders, model developers and users to understand the performance of these forecasts and also strengths and weaknesses to enable further development. Met Office terrestrial near real-time verification systems have been adapted to provide verification of X-ray flare and geomagnetic storm forecasts. Verification is updated daily to produce Relative Operating Characteristic (ROC) curves and Reliability diagrams, and rolling Ranked Probability Skill Scores (RPSSs) thus providing understanding of forecast performance and skill. Results suggest that the MOSWOC issued X-ray flare forecasts are usually not statistically significantly better than a benchmark climatological forecast (where the climatology is based on observations from the previous few months). By contrast, the issued geomagnetic storm activity forecast typically performs better against this climatological benchmark.

  14. The Met Office Global Coupled Model 3.0 and 3.1 (GC3.0 and GC3.1) Configurations

    NASA Astrophysics Data System (ADS)

    Williams, K. D.; Copsey, D.; Blockley, E. W.; Bodas-Salcedo, A.; Calvert, D.; Comer, R.; Davis, P.; Graham, T.; Hewitt, H. T.; Hill, R.; Hyder, P.; Ineson, S.; Johns, T. C.; Keen, A. B.; Lee, R. W.; Megann, A.; Milton, S. F.; Rae, J. G. L.; Roberts, M. J.; Scaife, A. A.; Schiemann, R.; Storkey, D.; Thorpe, L.; Watterson, I. G.; Walters, D. N.; West, A.; Wood, R. A.; Woollings, T.; Xavier, P. K.

    2018-02-01

    The Global Coupled 3 (GC3) configuration of the Met Office Unified Model is presented. Among other applications, GC3 is the basis of the United Kingdom's submission to the Coupled Model Intercomparison Project 6 (CMIP6). This paper documents the model components that make up the configuration (although the scientific descriptions of these components are in companion papers) and details the coupling between them. The performance of GC3 is assessed in terms of mean biases and variability in long climate simulations using present-day forcing. The suitability of the configuration for predictability on shorter time scales (weather and seasonal forecasting) is also briefly discussed. The performance of GC3 is compared against GC2, the previous Met Office coupled model configuration, and against an older configuration (HadGEM2-AO) which was the submission to CMIP5. In many respects, the performance of GC3 is comparable with GC2, however, there is a notable improvement in the Southern Ocean warm sea surface temperature bias which has been reduced by 75%, and there are improvements in cloud amount and some aspects of tropical variability. Relative to HadGEM2-AO, many aspects of the present-day climate are improved in GC3 including tropospheric and stratospheric temperature structure, most aspects of tropical and extratropical variability and top-of-atmosphere and surface fluxes. A number of outstanding errors are identified including a residual asymmetric sea surface temperature bias (cool northern hemisphere, warm Southern Ocean), an overly strong global hydrological cycle and insufficient European blocking.

  15. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. LFRic: Building a new Unified Model

    NASA Astrophysics Data System (ADS)

    Melvin, Thomas; Mullerworth, Steve; Ford, Rupert; Maynard, Chris; Hobson, Mike

    2017-04-01

    The LFRic project, named for Lewis Fry Richardson, aims to develop a replacement for the Met Office Unified Model in order to meet the challenges which will be presented by the next generation of exascale supercomputers. This project, a collaboration between the Met Office, STFC Daresbury and the University of Manchester, builds on the earlier GungHo project to redesign the dynamical core, in partnership with NERC. The new atmospheric model aims to retain the performance of the current ENDGame dynamical core and associated subgrid physics, while also enabling a far greater scalability and flexibility to accommodate future supercomputer architectures. Design of the model revolves around a principle of a 'separation of concerns', whereby the natural science aspects of the code can be developed without worrying about the underlying architecture, while machine dependent optimisations can be carried out at a high level. These principles are put into practice through the development of an autogenerated Parallel Systems software layer (known as the PSy layer) using a domain-specific compiler called PSyclone. The prototype model includes a re-write of the dynamical core using a mixed finite element method, in which different function spaces are used to represent the various fields. It is able to run in parallel with MPI and OpenMP and has been tested on over 200,000 cores. In this talk an overview of the both the natural science and computational science implementations of the model will be presented.

  2. Flare forecasting at the Met Office Space Weather Operations Centre

    NASA Astrophysics Data System (ADS)

    Murray, S. A.; Bingham, S.; Sharpe, M.; Jackson, D. R.

    2017-04-01

    The Met Office Space Weather Operations Centre produces 24/7/365 space weather guidance, alerts, and forecasts to a wide range of government and commercial end-users across the United Kingdom. Solar flare forecasts are one of its products, which are issued multiple times a day in two forms: forecasts for each active region on the solar disk over the next 24 h and full-disk forecasts for the next 4 days. Here the forecasting process is described in detail, as well as first verification of archived forecasts using methods commonly used in operational weather prediction. Real-time verification available for operational flare forecasting use is also described. The influence of human forecasters is highlighted, with human-edited forecasts outperforming original model results and forecasting skill decreasing over longer forecast lead times.

  3. Teaching weather and climate science in primary schools - a pilot project from the UK Met Office

    NASA Astrophysics Data System (ADS)

    Orrell, Richard; Liggins, Felicity; Challenger, Lesley; Lethem, Dom; Campbell, Katy

    2017-04-01

    Wow Schools is a pilot project from the Met Office with an aim to inspire and educate the next generation of scientists and, uniquely, use the data collected by schools to improve weather forecasts and warnings across the UK. Wow Schools was launched in late 2015 with a competition open to primary schools across the UK. 74 schools entered the draw, all hoping to be picked as one of the ten lucky schools taking part in the pilot scheme. Each winning school received a fully automatic weather station (AWS), enabling them to transmit real-time local weather observations to the Met Office's Weather Observation Website (WOW - wow.metoffice.gov.uk), an award winning web portal for uploading and sharing a range of environmental observations. They were also given a package of materials designed to get students out of the classroom to observe the weather, get hands-on with the science underpinning weather forecasting, and analyse the data they are collecting. The curriculum-relevant materials were designed with the age group 7 to 11 in mind, but could be extended to support other age groups. Each school was offered a visit by a Wow Schools Ambassador (a Met Office employee) to bring the students' learning to life, and access to a dedicated forecast for its location generated by our new supercomputer. These forecasts are improved by the school's onsite AWS reinforcing the link between observations and forecast production. The Wow Schools pilot ran throughout 2016. Here, we present the initial findings of the project, examining the potential benefits and challenges of working with schools across the UK to: enrich students' understanding of the science of weather forecasting; to source an ongoing supply of weather observations and discover how these might be used in the forecasting process; and explore what materials and business model(s) would be most useful and affordable if a wider roll-out of the initiative was undertaken.

  4. From big data analysis in the cloud to robotic pot drumming: tales from the Met Office Informatics Lab

    NASA Astrophysics Data System (ADS)

    Robinson, Niall; Tomlinson, Jacob; Prudden, Rachel; Hilson, Alex; Arribas, Alberto

    2017-04-01

    The Met Office Informatics Lab is a small multidisciplinary team which sits between science, technology and design. Our mission is simply "to make Met Office data useful" - a deliberately broad objective. Our prototypes often trial cutting edge technologies, and so far have included projects such as virtual reality data visualisation in the web browser, bots and natural language interfaces, and artificially intelligent weather warnings. In this talk we focus on our latest project, Jade, a big data analysis platform in the cloud. It is a powerful, flexible and simple to use implementation which makes extensive use of technologies such as Jupyter, Dask, containerisation, Infrastructure as Code, and auto-scaling. Crucially, Jade is flexible enough to be used for a diverse set of applications: it can present weather forecast information to meteorologists and allow climate scientists to analyse big data sets, but it is also effective for analysing non-geospatial data. As well as making data useful, the Informatics Lab also trials new working practises. In this presentation, we will talk about our experience of making a group like the Lab successful.

  5. Evaluation of Unified Model Microphysics in High-resolution NWP Simulations Using Polarimetric Radar Observations

    NASA Astrophysics Data System (ADS)

    Johnson, Marcus; Jung, Youngsun; Dawson, Daniel; Supinie, Timothy; Xue, Ming; Park, Jongsook; Lee, Yong-Hee

    2018-07-01

    The UK Met Office Unified Model (UM) is employed by many weather forecasting agencies around the globe. This model is designed to run across spatial and time scales and known to produce skillful predictions for large-scale weather systems. However, the model has only recently begun running operationally at horizontal grid spacings of ˜1.5 km [e.g., at the UK Met Office and the Korea Meteorological Administration (KMA)]. As its microphysics scheme was originally designed and tuned for large-scale precipitation systems, we investigate the performance of UM microphysics to determine potential inherent biases or weaknesses. Two rainfall cases from the KMA forecasting system are considered in this study: a Changma (quasi-stationary) front, and Typhoon Sanba (2012). The UM output is compared to polarimetric radar observations in terms of simulated polarimetric radar variables. Results show that the UM generally underpredicts median reflectivity in stratiform rain, producing high reflectivity cores and precipitation gaps between them. This is partially due to the diagnostic rain intercept parameter formulation used in the one-moment microphysics scheme. Model drop size is generally both underand overpredicted compared to observations. UM frozen hydrometeors favor generic ice (crystals and snow) rather than graupel, which is reasonable for Changma and typhoon cases. The model performed best with the typhoon case in terms of simulated precipitation coverage.

  6. Introducing the Met Office 2.2-km Europe-wide convection-permitting regional climate simulations

    NASA Astrophysics Data System (ADS)

    Kendon, Elizabeth J.; Chan, Steven C.; Berthou, Segolene; Fosser, Giorgia; Roberts, Malcolm J.; Fowler, Hayley J.

    2017-04-01

    The Met Office is currently conducting Europe-wide 2.2-km convection-permitting model (CPM) simulations driven by ERA-Interim reanalysis and present/future-climate GCM simulations. Here, we present the preliminary results of these new European simulations examining daily and sub-daily precipitation outputs in comparison with observations across Europe, 12-km European and 1.5-km UK climate model simulations. As the simulations are not yet complete, we focus on diagnostics that are relatively robust with a limited amount of data; for instance, the diurnal cycle and the probability distribution of daily and sub-daily precipitation intensities. We will also present specific case studies that showcase the benefits of using continental-scale CPM simulations over previously-available small-domain CPM simulations.

  7. The Met Office HadGEM3-ES chemistry-climate model: evaluation of stratospheric dynamics and its impact on ozone

    NASA Astrophysics Data System (ADS)

    Hardiman, Steven C.; Butchart, Neal; O'Connor, Fiona M.; Rumbold, Steven T.

    2017-03-01

    Free-running and nudged versions of a Met Office chemistry-climate model are evaluated and used to investigate the impact of dynamics versus transport and chemistry within the model on the simulated evolution of stratospheric ozone. Metrics of the dynamical processes relevant for simulating stratospheric ozone are calculated, and the free-running model is found to outperform the previous model version in 10 of the 14 metrics. In particular, large biases in stratospheric transport and tropical tropopause temperature, which existed in the previous model version, are substantially reduced, making the current model more suitable for the simulation of stratospheric ozone. The spatial structure of the ozone hole, the area of polar stratospheric clouds, and the increased ozone concentrations in the Northern Hemisphere winter stratosphere following sudden stratospheric warmings, were all found to be sensitive to the accuracy of the dynamics and were better simulated in the nudged model than in the free-running model. Whilst nudging can, in general, provide a useful tool for removing the influence of dynamical biases from the evolution of chemical fields, this study shows that issues can remain in the climatology of nudged models. Significant biases in stratospheric vertical velocities, age of air, water vapour, and total column ozone still exist in the Met Office nudged model. Further, these can lead to biases in the downward flux of ozone into the troposphere.

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

    DOE PAGES

    Rae, J. . G. L; Hewitt, H. T.; Keen, A. B.; ...

    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

  9. 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. ...

  10. 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.

  11. Alternative Fuels Data Center: Workplace Charging Success: MetLife

    Science.gov Websites

    people to use PEVs. " MetLife's Senior Vice President, Global Corporate Services, Joseph Sprouls vehicle (PEV) charging stations at 14 of its U.S. corporate offices as a partner in the Department of benefits of using alternative energy sources. MetLife's Senior Vice President, Global Corporate Services

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

    DOE PAGES

    Rae, J. G. L.; Hewitt, H. T.; Keen, A. B.; ...

    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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rae, J. G. L.; Hewitt, H. T.; Keen, A. B.

    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. Estimating the Contrail Impact on Climate Using the UK Met Office Model

    NASA Astrophysics Data System (ADS)

    Rap, A.; Forster, P. M.

    2008-12-01

    With air travel predicted to increase over the coming century, the emissions associated with air traffic are expected to have a significant warming effect on climate. According to current best estimates, an important contribution comes from contrails. However, as reported by the IPCC fourth assessment report, these current best estimates still have a high uncertainty. The development and validation of contrail parameterizations in global climate models is therefore very important. This current study develops a contrail parameterization within the UK Met Office Climate Model. Using this new parameterization, we estimate that for the 2002 traffic, the global mean annual contrail coverage is approximately 0.11%, a value which in good agreement with several other estimates. The corresponding contrail radiative forcing (RF) is calculated to be approximately 4 and 6 mWm-2 in all-sky and clear-sky conditions, respectively. These values lie within the lower end of the RF range reported by the latest IPCC assessment. The relatively high cloud masking effect on contrails observed by our parameterization compared with other studies is investigated, and a possible cause for this difference is suggested. The effect of the diurnal variations of air traffic on both contrail coverage and contrail RF is also investigated. The new parameterization is also employed in thirty-year slab-ocean model runs in order to give one of the first insights into contrail effects on daily temperature range and the climate impact of contrails.

  15. Verification of Space Weather Forecasts Issued by the Met Office Space Weather Operations Centre

    NASA Astrophysics Data System (ADS)

    Sharpe, M. A.; Murray, S. A.

    2017-10-01

    The Met Office Space Weather Operations Centre was founded in 2014 and part of its remit is a daily Space Weather Technical Forecast to help the UK build resilience to space weather impacts; guidance includes 4 day geomagnetic storm forecasts (GMSF) and X-ray flare forecasts (XRFF). It is crucial for forecasters, users, modelers, and stakeholders to understand the strengths and weaknesses of these forecasts; therefore, it is important to verify against the most reliable truth data source available. The present study contains verification results for XRFFs using Geo-Orbiting Earth Satellite 15 satellite data and GMSF using planetary K-index (Kp) values from the GFZ Helmholtz Centre. To assess the value of the verification results, it is helpful to compare them against a reference forecast and the frequency of occurrence during a rolling prediction period is used for this purpose. An analysis of the rolling 12 month performance over a 19 month period suggests that both the XRFF and GMSF struggle to provide a better prediction than the reference. However, a relative operating characteristic and reliability analysis of the full 19 month period reveals that although the GMSF and XRFF possess discriminatory skill, events tend to be overforecast.

  16. Chief Information Officer > About DoD CIO > Organization > DCIO R&A

    Science.gov Websites

    provide strategy, leadership, and guidance to create a unified information management and technology Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department

  17. 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…

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

    PubMed Central

    Garbarino, Sergio; Magnavita, Nicola

    2015-01-01

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

  19. Wartime Roles and Capabilities for the Unified Logistic Staffs

    DTIC Science & Technology

    1989-02-01

    standard Army ammunition system SAPO Subarea Petroleum Office SCP service control point (fuels) SHAPE Supreme Headquarters, Allied Powers Europe SIDATH... SAPOs ). Communication exists between the operations and logistic staffs within the unified, component, Service, and JS levels. But between...daily. The JPOs/ SAPOs receive the short-term requirements and consoli- date them for resupply by submitting slates (how much, when, and where needed

  20. Sacramento City Unified School District Chapter 1/State Compensatory Education Handbook Series.

    ERIC Educational Resources Information Center

    Sacramento City Unified School District, CA.

    Four handbooks developed by the Consolidated Programs Department of the Sacramento City Unified School District (California) provide a means by which the multitude of federal, state, and district rules and regulations pertaining to compensatory education can be understood. The "Consolidated Programs Office Management Procedures" handbook…

  1. 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

  2. 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 PROGRAM...

  3. Occupation and metabolic syndrome: is there correlation? A cross sectional study in different work activity occupations of German firefighters and office workers.

    PubMed

    Strauß, Markus; Foshag, Peter; Przybylek, Bianca; Horlitz, Marc; Lucia, Alejandro; Sanchis-Gomar, Fabian; Leischik, Roman

    2016-01-01

    The treatment and prevention of the metabolic syndrome (MetS) is currently one of the major challenges in medicine. The impact of working conditions on metabolic risk has not been adequately studied. Our objective was to compare the prevalence of MetS and metabolic risk in two extremely different occupational groups: firefighters and office workers. A total of 143 male subjects (97 firefighters and 46 office workers) from Germany participated in the study. Anthropometric characteristics, metabolic risk parameters as well as laboratory parameters were collected. MetS was diagnosed according to criteria of the International Diabetes Federation. Sedentary occupation showed a significant tendency towards obesity. Abdominal waist circumference was significantly greater in office workers than in firefighters [5.08 CI (1.44-8.71), p = 0.007]. Concerning metabolic risk factors, abnormal HDL, triglycerides, BMI, blood pressure and waist circumference values were more frequently found in office workers than in firefighters. The MetS was detected in almost 33 % of office workers as compared with only 14 % in firefighters (p = 0.015). Regarding MetS in an international comparison, the prevalence of MetS in German office workers was high and in firefighters it was extremely low. Sedentary occupation as an office worker is associated with a high risk of MetS. Both groups need to be made aware of the metabolic risks, and health promoting concepts such as corporate sports activities or education in healthy nutrition need to be implemented to counteract the development of the MetS and cardiovascular risk factors.

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

    PubMed

    McGill, Anne-Thea

    2014-01-01

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

  5. Met UM Upper-tropospheric summer jet teleconnections: A model assessment

    NASA Astrophysics Data System (ADS)

    Joao Carvalho, Maria; Rodriguez, Jose; Milton, Sean

    2017-04-01

    The upper tropospheric jet stream has been documented to act as a waveguide (Hoskins and Ambrizzi, 1993) and supporting quasi-stationary Rossby waves (Schubert et al. 2011). These have been associated with remote effects in surface level weather such as rainfall anomalies in the East Asian Summer Monsoon as well as extreme temperature events. The goal of this work was to analyse the intraseasonal to interannual upper level boreal summer jet variability and its coupling with low level atmospheric dynamics within the Met Office Unified Model using climate runs. Using the Wallace and Gutzler (1981) proposed approach to find teleconnection patterns on the 200 hPa level wind, lead-lag correlation and Empirical Orthogonal Function analysis on the upper-level jet and relating the results with surface weather variables as well as dynamical variables, it was found that the model presents too strong jet variability, particularly in the tropical region and. In addition, the model presents high teleconnectivity hotspots with higher importance in areas such as the Mediterranean and Caspian Sea which are important source areas for Rossby Waves. Further to this, the model was found to produce an area of teleconnectivity between the tropical Atlantic and western Africa which is not observed in the reanalysis but coexists with long lasting precipitation biases. As comparison for the model results, ERA-Interim circulation and wind data and the TRMM precipitation dataset were used. In order to assess the relative importance of relevant model parameters in the biases and process errors, work is currently underway using perturbed model parameter ensembles.

  6. Short-Range Prediction of Monsoon Precipitation by NCMRWF Regional Unified Model with Explicit Convection

    NASA Astrophysics Data System (ADS)

    Mamgain, Ashu; Rajagopal, E. N.; Mitra, A. K.; Webster, S.

    2018-03-01

    There are increasing efforts towards the prediction of high-impact weather systems and understanding of related dynamical and physical processes. High-resolution numerical model simulations can be used directly to model the impact at fine-scale details. Improvement in forecast accuracy can help in disaster management planning and execution. National Centre for Medium Range Weather Forecasting (NCMRWF) has implemented high-resolution regional unified modeling system with explicit convection embedded within coarser resolution global model with parameterized convection. The models configurations are based on UK Met Office unified seamless modeling system. Recent land use/land cover data (2012-2013) obtained from Indian Space Research Organisation (ISRO) are also used in model simulations. Results based on short-range forecast of both the global and regional models over India for a month indicate that convection-permitting simulations by the high-resolution regional model is able to reduce the dry bias over southern parts of West Coast and monsoon trough zone with more intense rainfall mainly towards northern parts of monsoon trough zone. Regional model with explicit convection has significantly improved the phase of the diurnal cycle of rainfall as compared to the global model. Results from two monsoon depression cases during study period show substantial improvement in details of rainfall pattern. Many categories in rainfall defined for operational forecast purposes by Indian forecasters are also well represented in case of convection-permitting high-resolution simulations. For the statistics of number of days within a range of rain categories between `No-Rain' and `Heavy Rain', the regional model is outperforming the global model in all the ranges. In the very heavy and extremely heavy categories, the regional simulations show overestimation of rainfall days. Global model with parameterized convection have tendency to overestimate the light rainfall days and

  7. Data Quality Assessment of FY-3C MWRI Microwave Imager from CMA, ECMWF and the Met Office

    NASA Astrophysics Data System (ADS)

    Lu, Q.; WU, S.; Dou, F.; Sun, F.; Lawrence, H.; Geer, A.; English, S.; Newman, S.; Bell, W.; Bormann, N.; Carminati, F.

    2017-12-01

    MWRI is a conical-scanning microwave imager following on from the heritage of similar instruments such as SSMI/S and AMSR-2, with ten channels at frequencies between 10.65 GHz and 89 GHz. MWRI is flown on the China Meteorological Administration's (CMA's) Feng-Yun-3 (FY-3) satellite series, including on FY-3C and the upcoming FY-3D, scheduled for launch in September 2017. Here we present an evaluation of the data from MWRI on the FY-3C satellite launched in 2013. At CMA, the MWRI instrumental parameters and statistics between observation and simulation from RTTOV and CRTM radiative transfer modeling were monitored to characterise instrumental uncertainty from calibration and assess the data quality. The data were also assessed using model-equivalent brightness temperatures from the ECMWF and Met Office short-range forecasts. The forecasts were first transformed into brightness temperature space using the RTTOV radiative transfer code. By analysing observed minus model background ("O-B") brightness temperature departures we were able to investigate the instrument and geophysical state dependence of biases. We show examples of how biases can impact the data quality, related to ascending/descending node differences and radio frequency interference. We discuss the prospects of assimilation of MWRI data at NWP centres.

  8. [Acoustic conditions in open plan offices - Pilot test results].

    PubMed

    Mikulski, Witold

    The main source of noise in open plan office are conversations. Office work standards in such premises are attained by applying specific acoustic adaptation. This article presents the results of pilot tests and acoustic evaluation of open space rooms. Acoustic properties of 6 open plan office rooms were the subject of the tests. Evaluation parameters, measurement methods and criterial values were adopted according to the following standards: PN-EN ISO 3382- 3:2012, PN-EN ISO 3382-2:2010, PN-B-02151-4:2015-06 and PN-B-02151-3:2015-10. The reverberation time was 0.33- 0.55 s (maximum permissible value in offices - 0.6 s; the criterion was met), sound absorption coefficient in relation to 1 m2 of the room's plan was 0.77-1.58 m2 (minimum permissible value - 1.1 m2; 2 out of 6 rooms met the criterion), distraction distance was 8.5-14 m (maximum permissible value - 5 m; none of the rooms met the criterion), A-weighted sound pressure level of speech at a distance of 4 m was 43.8-54.7 dB (maximum permissible value - 48 dB; 2 out of 6 rooms met the criterion), spatial decay rate of the speech was 1.8-6.3 dB (minimum permissible value - 7 dB; none of the rooms met the criterion). Standard acoustic treatment, containing sound absorbing suspended ceiling, sound absorbing materials on the walls, carpet flooring and sound absorbing workplace barriers, is not sufficient. These rooms require specific advanced acoustic solutions. Med Pr 2016;67(5):653-662. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  9. Document Storage and Retrieval in the Electronic Office.

    ERIC Educational Resources Information Center

    Ashford, John

    1985-01-01

    Proposals are made for practical approaches to the design of electronic office systems to provide for the effective storage and retrieval of the documents that they generate. Problems of records management and requirements to be met by the designer of an electronic office system are highlighted. Nineteen references are cited. (EJS)

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

    PubMed Central

    2014-01-01

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

  11. 77 FR 7663 - Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ...The Regulatory Flexibility Act requires that agencies publish semiannual regulatory agendas in the Federal Register describing regulatory actions they are developing that may have a significant economic impact on a substantial number of small entities (5 U.S.C. 602). Executive Order 12866 ``Regulatory Planning and Review,'' signed September 30, 1993 (58 FR 51735), and Office of Management and Budget memoranda implementing section 4 of that Order establish minimum standards for agencies' agendas, including specific types of information for each entry. The Unified Agenda of Federal Regulatory and Deregulatory Actions (Unified Agenda) helps agencies fulfill these requirements. All Federal regulatory agencies have chosen to publish their regulatory agendas as part of the Unified Agenda. Editions of the Unified Agenda prior to fall 2007 were printed in their entirety in the Federal Register. Beginning with the fall 2007 edition, the Internet is the basic means for conveying regulatory agenda information to the maximum extent legally permissible. The complete Unified Agenda for fall 2011, which contains the regulatory agendas for 59 Federal agencies, is available to the public at http:// reginfo.gov. The fall 2011 Unified Agenda publication appearing in the Federal Register consists of agency regulatory flexibility agendas, in accordance with the publication requirements of the Regulatory Flexibility Act. Agency regulatory flexibility agendas contain only those Agenda entries for rules that are likely to have a significant economic impact on a substantial number of small entities and entries that have been selected for periodic review under section 610 of the Regulatory Flexibility Act.

  12. The seasonal predictability of blocking frequency in two seasonal prediction systems (CMCC, Met-Office) and the associated representation of low-frequency variability.

    NASA Astrophysics Data System (ADS)

    Athanasiadis, Panos; Gualdi, Silvio; Scaife, Adam A.; Bellucci, Alessio; Hermanson, Leon; MacLachlan, Craig; Arribas, Alberto; Materia, Stefano; Borelli, Andrea

    2014-05-01

    Low-frequency variability is a fundamental component of the atmospheric circulation. Extratropical teleconnections, the occurrence of blocking and the slow modulation of the jet streams and storm tracks are all different aspects of low-frequency variability. Part of the latter is attributed to the chaotic nature of the atmosphere and is inherently unpredictable. On the other hand, primarily as a response to boundary forcings, tropospheric low-frequency variability includes components that are potentially predictable. Seasonal forecasting faces the difficult task of predicting these components. Particularly referring to the extratropics, the current generation of seasonal forecasting systems seem to be approaching this target by realistically initializing most components of the climate system, using higher resolution and utilizing large ensemble sizes. Two seasonal prediction systems (Met-Office GloSea and CMCC-SPS-v1.5) are analyzed in terms of their representation of different aspects of extratropical low-frequency variability. The current operational Met-Office system achieves unprecedented high scores in predicting the winter-mean phase of the North Atlantic Oscillation (NAO, corr. 0.74 at 500 hPa) and the Pacific-N. American pattern (PNA, corr. 0.82). The CMCC system, considering its small ensemble size and course resolution, also achieves good scores (0.42 for NAO, 0.51 for PNA). Despite these positive features, both models suffer from biases in low-frequency variance, particularly in the N. Atlantic. Consequently, it is found that their intrinsic variability patterns (sectoral EOFs) differ significantly from the observed, and the known teleconnections are underrepresented. Regarding the representation of N. hemisphere blocking, after bias correction both systems exhibit a realistic climatology of blocking frequency. In this assessment, instantaneous blocking and large-scale persistent blocking events are identified using daily geopotential height fields at

  13. Determining unmet, adequately met, and overly met needs for health care and services for persons living with HIV/AIDS in Mississippi.

    PubMed

    Krause, Denise D; May, Warren L; Butler, Kenneth R

    2013-08-01

    A statewide needs assessment of persons living with HIV/AIDS (PLWHA) was conducted to determine what is known about access to care, utilization of services, and perceived barriers to receiving care and services. Our objective was to determine which needs were being met or unmet among PLWHA in Mississippi to provide a better understanding of how effectively to allocate funding to provide for the needs of that group. In this cross-sectional study, a true random sample of PLWHA in Mississippi was interviewed in 2005-2006. Questions were asked to identify opinions about respondents' experiences with 23 health care services and 30 public or private assistance services. The kappa statistic was used to measure agreement between level of services needed and level of services provided. Services with the lowest kappa scores revealed which services were being either mostly unmet, or even overly met. Greatest service needs were HIV viral load test, Pap smear, CD4/T-cell count test, and medication for HIV/AIDS, which were reasonably well met. The most significantly unmet needs were dental care and dental exams, eye care and eye exams, help paying for housing, subsidized housing assistance, mental health therapy or counseling, access to emotional support groups, and job placement or employment. Overly met services included medical care at a physician's office or clinic and free condoms. This study identified needs perceived to be significantly unmet by PLWHA, as well as areas that were perceived to be adequately or overly met. This information may be used to target areas with the greatest impact for improvement and provide insight into how to effectively allocate health care resources and public/private assistance.

  14. Shall Organized Medicine be Unified, or Separate?

    PubMed Central

    1971-01-01

    At present, physicians in California who choose to join organized medicine do so through their county medical societies, and membership in the California Medical Association and the American Medical Association is then automatic. At the March meeting of the CMA House of Delegates, question was raised whether membership in CMA, and the AMA, or both should remain automatic. The House requested an ad hoc committee to cause a “poll and its attendant statements to be developed by May 21 for copy distribution to component medical societies and printing in the CMA membership news media—with mailing of the official questionnaires to the society members on September 1, 1971.” Members will be asked to express their opinions by ballot in September. The Speaker of the House appointed an ad hoc committee of the House to conduct this informed opinion poll of the membership. The committee has met to set ground rules, prepare accurate pro and con statements and write the poll questions—in accord with the directions of the House action. The Informed Membership Opinion Poll Committee, with the advice of Decision Making Information, Inc., an independent consultant, prepared statements regarding unified and separate membership in CMA and AMA from comments which were solicited from every county medical society. A statement by legal counsel for the California Medical Association on the structural relationship of AMA, CMA and component societies, and the statements on unified or separate membership prepared by the committee appear on the following two pages. PMID:18730549

  15. Sleep habits, mental health, and the metabolic syndrome in law enforcement officers.

    PubMed

    Yoo, Hyelim; Franke, Warren D

    2013-01-01

    To assess the association of sleep characteristics and mental health with the metabolic syndrome (MetS) in law enforcement officers (LEOs). Sleep duration (≤6, >6-<8, ≥8 hours/night), sleep quality ("good," "poor"), mental health (stress, burnout, depression), and MetS components were compared in 106 LEOs. The prevalence of MetS was 33%. After covariate adjustment including the mental health measures, long sleep duration was associated with MetS (odds ratio = 4.89, 95% confidence interval = 1.32 to 18.13), whereas sleep quality was not. LEOs with short sleep duration or poor sleep quality reported more stress, burnout, and depression symptoms. In LEOs, sleep duration is more strongly associated with the occurrence of MetS than sleep quality, independent of mental health. Nevertheless, short sleep duration and poor sleep quality may affect mental health in LEOs.

  16. Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody.

    PubMed

    Lee, J M; Kim, B; Lee, S B; Jeong, Y; Oh, Y M; Song, Y-J; Jung, S; Choi, J; Lee, S; Cheong, K H; Kim, D U; Park, H W; Han, Y K; Kim, G W; Choi, H; Song, P H; Kim, K A

    2014-01-02

    The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.

  17. Prescreening Military Officer Candidates for High Level Security Clearances

    DTIC Science & Technology

    1989-06-01

    the Navy’s policy on drug and alcohol abuse . 17 Applicants are restricted from acceptance into a nuclear officer program , or fields in support of the...Z1:36uCd met:iacone. vercodan, and others. DRUG ABUSE : The illegal, wrongful. or improper use of marijuana, any narcotic substance . hallucinogens, or...a. (OFFICERS PRE-COMMISSIONING PROGRAMS ) ( understand the U. S. Navy’s intolerance of substance

  18. 24 CFR 578.11 - Unified Funding Agency.

    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. 578.11... of Care § 578.11 Unified Funding Agency. (a) Becoming a Unified Funding Agency. To become designated as the Unified Funding Agency (UFA) for a Continuum, a collaborative applicant must be selected by...

  19. 3 CFR - Unified Command Plan 2011

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 3 The President 1 2012-01-01 2012-01-01 false Unified Command Plan 2011 Presidential Documents Other Presidential Documents Memorandum of April 6, 2011 Unified Command Plan 2011 Memorandum for the... implementation of the revised Unified Command Plan. Consistent with title 10, United States Code, section 161(b...

  20. Annual Technical Report to the Office of Naval Research.

    DTIC Science & Technology

    1981-11-01

    7 A A1 208 MICHIGAN TECHNOLOGICAL UNI V HOUGHTON DEP T OF MFTALLU--ETC IG 11/6 ANNUAL TECHNICAL REPORT TO THE OFFICE OF NAVAL RESEARCH(U) NOV 81 D...A KOSS N00014-76-C-0037 UNCLASSIFIED NLmhEIIIIIIEIIII ElllllEllEllEE ANNUAL TECHNICAL REPORT TO THE OFFICE OF NAVAL RESEARCH CONTRACT No, N00014-76-C... the Office of Naval Research through Contract No. N00014-76-C-0037, NR 031-756. 22 References 1. K. Okazaki, M. Kagawa, and H. Conrad, Acta. Met. 27

  1. Connecting spatial and temporal scales of tropical precipitation in observations and the MetUM-GA6

    NASA Astrophysics Data System (ADS)

    Martin, Gill M.; Klingaman, Nicholas P.; Moise, Aurel F.

    2017-01-01

    This study analyses tropical rainfall variability (on a range of temporal and spatial scales) in a set of parallel Met Office Unified Model (MetUM) simulations at a range of horizontal resolutions, which are compared with two satellite-derived rainfall datasets. We focus on the shorter scales, i.e. from the native grid and time step of the model through sub-daily to seasonal, since previous studies have paid relatively little attention to sub-daily rainfall variability and how this feeds through to longer scales. We find that the behaviour of the deep convection parametrization in this model on the native grid and time step is largely independent of the grid-box size and time step length over which it operates. There is also little difference in the rainfall variability on larger/longer spatial/temporal scales. Tropical convection in the model on the native grid/time step is spatially and temporally intermittent, producing very large rainfall amounts interspersed with grid boxes/time steps of little or no rain. In contrast, switching off the deep convection parametrization, albeit at an unrealistic resolution for resolving tropical convection, results in very persistent (for limited periods), but very sporadic, rainfall. In both cases, spatial and temporal averaging smoothes out this intermittency. On the ˜ 100 km scale, for oceanic regions, the spectra of 3-hourly and daily mean rainfall in the configurations with parametrized convection agree fairly well with those from satellite-derived rainfall estimates, while at ˜ 10-day timescales the averages are overestimated, indicating a lack of intra-seasonal variability. Over tropical land the results are more varied, but the model often underestimates the daily mean rainfall (partly as a result of a poor diurnal cycle) but still lacks variability on intra-seasonal timescales. Ultimately, such work will shed light on how uncertainties in modelling small-/short-scale processes relate to uncertainty in climate change

  2. Acquired MET D1228V mutation and resistance to MET inhibition in lung cancer

    PubMed Central

    Bahcall, Magda; Sim, Taebo; Paweletz, Cloud P.; Patel, Jyoti D.; Alden, Ryan S.; Kuang, Yanan; Sacher, Adrian G.; Kim, Nam Doo; Lydon, Christine A.; Awad, Mark M.; Jaklitsch, Michael T.; Sholl, Lynette M.; Jänne, Pasi A.; Oxnard, Geoffrey R.

    2016-01-01

    Amplified and/or mutated MET can act as both a primary oncogenic driver and as a promoter of tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). However, the landscape of MET-specific targeting agents remains underdeveloped and understanding of mechanisms of resistance to MET TKIs is limited. Here we present a case of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET, who after progression on erlotinib, responded dramatically to combined MET and EGFR inhibition with savolitinib and osimertinib. When resistance developed to this combination, a new MET kinase domain mutation, D1228V, was detected. Our in vitro findings demonstrate that MET D1228V induces resistance to type I MET TKIs through impaired drug binding while sensitivity to type II MET TKIs is maintained. Based on these findings, the patient was treated with erlotinib combined with cabozantinib, a type II MET inhibitor, and exhibited a response. PMID:27694386

  3. 75 FR 1007 - MetLife, Inc. and MetLife Capital Trust V; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-29101; 812-13549] MetLife, Inc. and MetLife... ``Act'') for an exemption from all provisions of the Act. Summary of Application: MetLife Capital Trust V (the ``Trust'') and MetLife, Inc. (``MetLife'') request an order that would permit the Trust to...

  4. Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.

    PubMed

    Oddo, Daniele; Siravegna, Giulia; Gloghini, Annunziata; Vernieri, Claudio; Mussolin, Benedetta; Morano, Federica; Crisafulli, Giovanni; Berenato, Rosa; Corti, Giorgio; Volpi, Chiara Costanza; Buscarino, Michela; Niger, Monica; Dunne, Philip D; Rospo, Giuseppe; Valtorta, Emanuele; Bartolini, Alice; Fucà, Giovanni; Lamba, Simona; Martinetti, Antonia; Di Bartolomeo, Maria; de Braud, Filippo; Bardelli, Alberto; Pietrantonio, Filippo; Di Nicolantonio, Federica

    2017-07-25

    Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF V600E and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown. We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation analyses in two bioptic specimens obtained at progression were used to confirm the plasma data. We identified in plasma MET gene hyper-amplification as a potential mechanism underlying therapy resistance. Increased MET gene copy and transcript levels were detected in liver and lymph node metastatic biopsies. Finally, transduction of MET in BRAF mutant colorectal cancer cells conferred refractoriness to BRAF and MET inhibition. We identified in a rectal cancer patient MET gene hyper-amplification as mechanism of resistance to dual BRAF and MET inhibition.

  5. Clouds over the summertime Sahara: an evaluation of Met Office retrievals from Meteosat Second Generation using airborne remote sensing

    NASA Astrophysics Data System (ADS)

    Kealy, John C.; Marenco, Franco; Marsham, John H.; Garcia-Carreras, Luis; Francis, Pete N.; Cooke, Michael C.; Hocking, James

    2017-05-01

    Novel methods of cloud detection are applied to airborne remote sensing observations from the unique Fennec aircraft dataset, to evaluate the Met Office-derived products on cloud properties over the Sahara based on the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) on-board the Meteosat Second Generation (MSG) satellite. Two cloud mask configurations are considered, as well as the retrievals of cloud-top height (CTH), and these products are compared to airborne cloud remote sensing products acquired during the Fennec campaign in June 2011 and June 2012. Most detected clouds (67 % of the total) have a horizontal extent that is smaller than a SEVIRI pixel (3 km × 3 km). We show that, when partially cloud-contaminated pixels are included, a match between the SEVIRI and aircraft datasets is found in 80 ± 8 % of the pixels. Moreover, under clear skies the datasets are shown to agree for more than 90 % of the pixels. The mean cloud field, derived from the satellite cloud mask acquired during the Fennec flights, shows that areas of high surface albedo and orography are preferred sites for Saharan cloud cover, consistent with published theories. Cloud-top height retrievals however show large discrepancies over the region, which are ascribed to limiting factors such as the cloud horizontal extent, the derived effective cloud amount, and the absorption by mineral dust. The results of the CTH analysis presented here may also have further-reaching implications for the techniques employed by other satellite applications facilities across the world.

  6. 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.

  7. Interannual rainfall variability over China in the MetUM GA6 and GC2 configurations

    NASA Astrophysics Data System (ADS)

    Stephan, Claudia Christine; Klingaman, Nicholas P.; Vidale, Pier Luigi; Turner, Andrew G.; Demory, Marie-Estelle; Guo, Liang

    2018-05-01

    Six climate simulations of the Met Office Unified Model Global Atmosphere 6.0 and Global Coupled 2.0 configurations are evaluated against observations and reanalysis data for their ability to simulate the mean state and year-to-year variability of precipitation over China. To analyse the sensitivity to air-sea coupling and horizontal resolution, atmosphere-only and coupled integrations at atmospheric horizontal resolutions of N96, N216 and N512 (corresponding to ˜ 200, 90 and 40 km in the zonal direction at the equator, respectively) are analysed. The mean and interannual variance of seasonal precipitation are too high in all simulations over China but improve with finer resolution and coupling. Empirical orthogonal teleconnection (EOT) analysis is applied to simulated and observed precipitation to identify spatial patterns of temporally coherent interannual variability in seasonal precipitation. To connect these patterns to large-scale atmospheric and coupled air-sea processes, atmospheric and oceanic fields are regressed onto the corresponding seasonal mean time series. All simulations reproduce the observed leading pattern of interannual rainfall variability in winter, spring and autumn; the leading pattern in summer is present in all but one simulation. However, only in two simulations are the four leading patterns associated with the observed physical mechanisms. Coupled simulations capture more observed patterns of variability and associate more of them with the correct physical mechanism, compared to atmosphere-only simulations at the same resolution. However, finer resolution does not improve the fidelity of these patterns or their associated mechanisms. This shows that evaluating climate models by only geographical distribution of mean precipitation and its interannual variance is insufficient. The EOT analysis adds knowledge about coherent variability and associated mechanisms.

  8. Boreal summer sub-seasonal variability of the South Asian monsoon in the Met Office GloSea5 initialized coupled model

    NASA Astrophysics Data System (ADS)

    Jayakumar, A.; Turner, A. G.; Johnson, S. J.; Rajagopal, E. N.; Mohandas, Saji; Mitra, A. K.

    2017-09-01

    Boreal summer sub-seasonal variability in the Asian monsoon, otherwise known as the monsoon intra-seasonal oscillation (MISO), is one of the dominant modes of intraseasonal variability in the tropics, with large impacts on total monsoon rainfall and India's agricultural production. However, our understanding of the mechanisms involved in MISO is incomplete and its simulation in various numerical models is often flawed. In this study, we focus on the objective evaluation of the fidelity of MISO simulation in the Met Office Global Seasonal forecast system version 5 (GloSea5), an initialized coupled model. We analyze a series of nine-member hindcasts from GloSea5 over 1996-2009 during the peak monsoon period (July-August) over the South-Asian monsoon domain focusing on aspects of the time-mean background state and air-sea interaction processes pertinent to MISO. Dominant modes during this period are evident in power spectrum analysis, but propagation and evolution characteristics of the MISO are not realistic. We find that simulated air-sea interactions in the central Indian Ocean are not supportive of MISO initiation in that region, likely a result of the low surface wind variance there. As a consequence, the expected near-quadrature phase relationship between SST and convection is not represented properly over the central equatorial Indian Ocean, and northward propagation from the equator is poorly simulated. This may reinforce the equatorial rainfall mean state bias in GloSea5.

  9. 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.

  10. 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...

  11. Lipid ratio as a suitable tool to identify individuals with MetS risk: A case- control study.

    PubMed

    Abbasian, Maryam; Delvarianzadeh, Mehri; Ebrahimi, Hossein; Khosravi, Farideh

    2017-11-01

    This study aimed to compare the serum lipids ratio in staff with and without metabolic syndrome (MetS) who were working in Shahroud University of Medical Sciences. This case-control study was conducted in 2015 on 499 personnel aged 30-60 years old. ATP III criteria were used to diagnose patients with MetS. The data were analyzed by using logistic regression and ROC curve. Mean lipid ratio was higher in individuals having the MetS in both sexes compared with those without. In addition, the mean levels of lipid ratios significantly increased with increasing number of MetS components in both sexes. Also it could be concluded that TG/HDL-C ratio is the best marker for the diagnosis of MetS in men and women. Moreover, the cut-off point for the TG/HDL-C was 2.86 in women and 4.03 in men. It was found that for any unit of increases in the TG/HDL-C, the risk of developing the MetS will increase by 2.12 times. TG/HDL-C ratio is found to be the best clinical marker for the diagnosis of MetS compare with other lipid ratios, therefore it is recommended to be used as a feasible tool to identify individuals with MetS risk. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. 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

  13. A description and evaluation of an air quality model nested within global and regional composition-climate models using MetUM

    NASA Astrophysics Data System (ADS)

    Neal, Lucy S.; Dalvi, Mohit; Folberth, Gerd; McInnes, Rachel N.; Agnew, Paul; O'Connor, Fiona M.; Savage, Nicholas H.; Tilbee, Marie

    2017-11-01

    There is a clear need for the development of modelling frameworks for both climate change and air quality to help inform policies for addressing these issues simultaneously. This paper presents an initial attempt to develop a single modelling framework, by introducing a greater degree of consistency in the meteorological modelling framework by using a two-step, one-way nested configuration of models, from a global composition-climate model (GCCM) (140 km resolution) to a regional composition-climate model covering Europe (RCCM) (50 km resolution) and finally to a high (12 km) resolution model over the UK (AQUM). The latter model is used to produce routine air quality forecasts for the UK. All three models are based on the Met Office's Unified Model (MetUM). In order to better understand the impact of resolution on the downscaling of projections of future climate and air quality, we have used this nest of models to simulate a 5-year period using present-day emissions and under present-day climate conditions. We also consider the impact of running the higher-resolution model with higher spatial resolution emissions, rather than simply regridding emissions from the RCCM. We present an evaluation of the models compared to in situ air quality observations over the UK, plus a comparison against an independent 1 km resolution gridded dataset, derived from a combination of modelling and observations, effectively producing an analysis of annual mean surface pollutant concentrations. We show that using a high-resolution model over the UK has some benefits in improving air quality modelling, but that the use of higher spatial resolution emissions is important to capture local variations in concentrations, particularly for primary pollutants such as nitrogen dioxide and sulfur dioxide. For secondary pollutants such as ozone and the secondary component of PM10, the benefits of a higher-resolution nested model are more limited and reasons for this are discussed. This study

  14. Geoengineering by stratospheric SO2 injection: results from the Met Office HadGEM2 climate model and comparison with the Goddard Institute for Space Studies ModelE

    NASA Astrophysics Data System (ADS)

    Jones, A.; Haywood, J.; Boucher, O.; Kravitz, B.; Robock, A.

    2010-03-01

    We examine the response of the Met Office Hadley Centre's HadGEM2-AO climate model to simulated geoengineering by continuous injection of SO2 into the lower stratosphere, and compare the results with those from the Goddard Institute for Space Studies ModelE. The HadGEM2 simulations suggest that the SO2 injection rate considered here (5 Tg[SO2] yr-1) could defer the amount of global warming predicted under the Intergovernmental Panel on Climate Change's A1B scenario by approximately 30-35 years, although both models indicate rapid warming if geoengineering is not sustained. We find a broadly similar geographic distribution of the response to geoengineering in both models in terms of near-surface air temperature and mean June-August precipitation. The simulations also suggest that significant changes in regional climate would be experienced even if geoengineering was successful in maintaining global-mean temperature near current values.

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

    ERIC Educational Resources Information Center

    Llamas, Sonia Rodarte

    2013-01-01

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

  16. Study of MET protein levels and MET gene copy number in 72 sinonasal intestinal-type adenocarcinomas.

    PubMed

    Projetti, Fabrice; Mesturoux, Laura; Coulibaly, Béma; Durand, Karine; Chaunavel, Alain; Léobon, Sophie; Gadeaud, Emilie; Caire, François; Bessède, Jean-Pierre; Labrousse, François

    2015-11-01

    Sinonasal intestinal-type adenocarcinomas (ITACs) have a poor prognosis, and are defined on the basis of their morphological similarities to colorectal adenocarcinomas. MET signaling pathway is involved in oncogenesis in various cancers. Nothing is currently known about the role of MET in ITACs. In a series of 72 ITACs, we investigated MET protein levels by immunohistochemistry (IHC) and gene copy number by in situ hybridization. These findings were analyzed as a function of clinical data, histological typing, and patient outcome. MET protein was overproduced in 64% of cases and chromosome 7 polysomy was observed in 52% of cases. No tumor displayed MET amplification. The presence of mucinous or solid histological components, T3/T4 tumors, and incomplete resection were associated with a poor outcome. MET is overproduced in about two third of ITACs, suggesting a role for the MET signaling pathway in the oncogenesis of these tumors. © 2014 Wiley Periodicals, Inc.

  17. Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities

    PubMed Central

    Peng, Xia; Shen, Yanyan; Chen, Fang; Ji, Yinchun; Liu, Weiren; Shi, Yinghong; Duan, Wenhu; Ding, Jian; Ai, Jing; Geng, Meiyu

    2016-01-01

    The aberrant c-Met activation has been implicated in a variety of human cancers for its critical role in tumor growth, metastasis and tumor angiogenesis. Thus, c-Met axis presents as an attractive therapeutic target. Notably, most of these c-Met inhibitors currently being evaluated in clinical trials lack selectivity and target multiple kinases, often accounting for the undesirable toxicities. Here we described Simm530 as a potent and selective c-Met inhibitor. Simm530 demonstrated >2,000 fold selectivity for c-Met compared with other 282 kinases, making it one of the most selective c-Met inhibitors described to date. This inhibitor significantly blocked c-Met signaling pathways regardless of mechanistic complexity implicated in c-Met activation. As a result, Simm530 led to substantial inhibition of c-Met-promoted cell proliferation, migration, invasion, ECM degradation, cell scattering and invasive growth. In addition, Simm530 inhibited primary human umbilical vascular endothelial cell (HUVEC) proliferation, decreased intratumoral CD31 expression and plasma pro-angiogenic factor interleukin-8 secretion, suggesting its significant anti-angiogenic properties. Simm530 resulted in dose-dependent inhibition of c-Met phosphorylation and tumor growth in c-Met-driven lung and gastric cancer xenografts. And, the inhibitor is well tolerated even at doses that achieve complete tumor regression. Together, Simm530 is a potent and highly selective c-Met kinase inhibitor that may have promising therapeutic potential in c-Met-driven cancer treatment. PMID:27191264

  18. 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.

  19. Measurement of functional capacity requirements of police officers to aid in development of an occupation-specific cardiac rehabilitation training program.

    PubMed

    Adams, Jenny; Schneider, Jonna; Hubbard, Matthew; McCullough-Shock, Tiffany; Cheng, Dunlei; Simms, Kay; Hartman, Julie; Hinton, Paul; Strauss, Danielle

    2010-01-01

    This study was designed to measure the functional capacity of healthy subjects during strenuous simulated police tasks, with the goal of developing occupation-specific training for cardiac rehabilitation of police officers. A calibrated metabolic instrument and an oxygen consumption data collection mask were used to measure the oxygen consumption and heart rates of 30 Dallas Police Academy officers and cadets as they completed an 8-event obstacle course that simulated chasing, subduing, and handcuffing a suspect. Standard target heart rates (85% of age-predicted maximum heart rate, or 0.85 x [220 - age]) and metabolic equivalents (METs) were calculated; a matched-sample t test based on differences between target and achieved heart rate and MET level was used for statistical analysis. Peak heart rates during the obstacle course simulation were significantly higher than the standard target heart rates (those at which treadmill stress tests in physicians' offices are typically stopped) (t(29) = 12.81, P < 0.001) and significantly higher than the suggested maximum of 150 beats/min during cardiac rehabilitation training (t(29) = 17.84, P < 0.001). Peak MET levels during the obstacle course simulation were also significantly higher than the goal level (8 METs) that patients typically achieve in a cardiac rehabilitation program (t(29) = 14.73, P < 0.001). We conclude that police work requires a functional capacity greater than that typically attained in traditional cardiac rehabilitation programs. Rehabilitation professionals should consider performing maximal stress tests and increasing the intensity of cardiac rehabilitation workouts to effectively train police officers who have had a cardiac event.

  20. 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.

  1. A unified universe

    NASA Astrophysics Data System (ADS)

    Codello, Alessandro; Jain, Rajeev Kumar

    2018-05-01

    We present a unified evolution of the universe from very early times until the present epoch by including both the leading local correction R^2 and the leading non-local term R1/\\square ^2R to the classical gravitational action. We find that the inflationary phase driven by R^2 term gracefully exits in a transitory regime characterized by coherent oscillations of the Hubble parameter. The universe then naturally enters into a radiation dominated epoch followed by a matter dominated era. At sufficiently late times after radiation-matter equality, the non-local term starts to dominate inducing an accelerated expansion of the universe at the present epoch. We further exhibit the fact that both the leading local and non-local terms can be obtained within the covariant effective field theory of gravity. This scenario thus provides a unified picture of inflation and dark energy in a single framework by means of a purely gravitational action without the usual need of a scalar field.

  2. 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

  3. VIDEO: Dr. Henry Rodriguez - Proteogenomics in Cancer Medicine | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research (OCCPR) at NCI, speaks with ecancer television at WIN 2017 about the translation of the proteins expressed in a patient's tumor into a map for druggable targets. By combining genomic and proteomic information (proteogenomics), leading scientists are gaining new insights into ways to detect and treat cancer due to a more complete and unified understanding of complex biological processes.

  4. Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab.

    PubMed

    Mai, Elaine; Zheng, Zhong; Chen, Youjun; Peng, Jing; Severin, Christophe; Filvaroff, Ellen; Romero, Mally; Mallet, William; Kaur, Surinder; Gelzleichter, Thomas; Nijem, Ihsan; Merchant, Mark; Young, Judy C

    2014-02-01

    Onartuzumab, a humanized, monovalent monoclonal anti-MET antibody, antagonizes MET signaling by inhibiting binding of its ligand, hepatocyte growth factor (HGF). We investigated the effects of onartuzumab on cell-associated and circulating (shed) MET (sMET) and circulating HGF in vitro and nonclinically to determine their utility as pharmacodynamic biomarkers for onartuzumab. Effects of onartuzumab on cell-associated MET were assessed by flow cytometry and immunofluorescence. sMET and HGF were measured in cell supernatants and in serum or plasma from multiple species (mouse, cynomolgus monkey, and human) using plate-based immunoassays. Unlike bivalent anti-MET antibodies, onartuzumab stably associates with MET on the surface of cells without inducing MET internalization or shedding. Onartuzumab delayed the clearance of human xenograft tumor-produced sMET from the circulation of mice, and endogenous sMET in cynomolgus monkeys. In mice harboring MET-expressing xenograft tumors, in the absence of onartuzumab, levels of human sMET correlated with tumor size, and may be predictive of MET-expressing tumor burden. Because binding of sMET to onartuzumab in circulation resulted in increasing sMET serum concentrations due to reduced clearance, this likely renders sMET unsuitable as a pharmacodynamic biomarker for onartuzumab. There was no observed effect of onartuzumab on circulating HGF levels in xenograft tumor-bearing mice or endogenous HGF in cynomolgus monkeys. Although sMET and HGF may serve as predictive biomarkers for MET therapeutics, these data do not support their use as pharmacodynamic biomarkers for onartuzumab.

  5. 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.

  6. Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

    PubMed

    Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

    2018-06-01

    Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018

  7. [c-MET Oncogene in Renal Cell Carcinomas].

    PubMed

    Erlmeier, F; Weichert, W; Autenrieth, M; Ivanyi, P; Hartmann, A; Steffens, S

    2016-12-01

    c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine. Especially for RCC, the dual inhibition of VEGF and c-MET tyrosine kinase in cases of metastatic, treatment-resistant tumours is gaining clinical relevance. The role of c-Met has not been fully elucidated for all subtypes of renal cell carcinomas. The relevance of c-Met for the remaining subtypes of renal tumours has yet to be clarified. © Georg Thieme Verlag KG Stuttgart · New York.

  8. GUDM: Automatic Generation of Unified Datasets for Learning and Reasoning in Healthcare.

    PubMed

    Ali, Rahman; Siddiqi, Muhammad Hameed; Idris, Muhammad; Ali, Taqdir; Hussain, Shujaat; Huh, Eui-Nam; Kang, Byeong Ho; Lee, Sungyoung

    2015-07-02

    A wide array of biomedical data are generated and made available to healthcare experts. However, due to the diverse nature of data, it is difficult to predict outcomes from it. It is therefore necessary to combine these diverse data sources into a single unified dataset. This paper proposes a global unified data model (GUDM) to provide a global unified data structure for all data sources and generate a unified dataset by a "data modeler" tool. The proposed tool implements user-centric priority based approach which can easily resolve the problems of unified data modeling and overlapping attributes across multiple datasets. The tool is illustrated using sample diabetes mellitus data. The diverse data sources to generate the unified dataset for diabetes mellitus include clinical trial information, a social media interaction dataset and physical activity data collected using different sensors. To realize the significance of the unified dataset, we adopted a well-known rough set theory based rules creation process to create rules from the unified dataset. The evaluation of the tool on six different sets of locally created diverse datasets shows that the tool, on average, reduces 94.1% time efforts of the experts and knowledge engineer while creating unified datasets.

  9. GUDM: Automatic Generation of Unified Datasets for Learning and Reasoning in Healthcare

    PubMed Central

    Ali, Rahman; Siddiqi, Muhammad Hameed; Idris, Muhammad; Ali, Taqdir; Hussain, Shujaat; Huh, Eui-Nam; Kang, Byeong Ho; Lee, Sungyoung

    2015-01-01

    A wide array of biomedical data are generated and made available to healthcare experts. However, due to the diverse nature of data, it is difficult to predict outcomes from it. It is therefore necessary to combine these diverse data sources into a single unified dataset. This paper proposes a global unified data model (GUDM) to provide a global unified data structure for all data sources and generate a unified dataset by a “data modeler” tool. The proposed tool implements user-centric priority based approach which can easily resolve the problems of unified data modeling and overlapping attributes across multiple datasets. The tool is illustrated using sample diabetes mellitus data. The diverse data sources to generate the unified dataset for diabetes mellitus include clinical trial information, a social media interaction dataset and physical activity data collected using different sensors. To realize the significance of the unified dataset, we adopted a well-known rough set theory based rules creation process to create rules from the unified dataset. The evaluation of the tool on six different sets of locally created diverse datasets shows that the tool, on average, reduces 94.1% time efforts of the experts and knowledge engineer while creating unified datasets. PMID:26147731

  10. A comparison of metabolic syndrome (MetS) risk factors in Filipino women and Filipino American women: a pilot study.

    PubMed

    Ancheta, Irma B; Battie, Cynthia A; Tuason, Teresa; Ancheta, Christine V

    2012-01-01

    Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in women of Filipino ethnicity. The objective of our work was to determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in women as a function of country of residency and to determine if, CVD prevention strategies need to differ for these groups of Filipino women. Data were collected in community-based health screenings for this cross-sectional study. PARTICIPANTS were recruited at places of worship in southeast United States (n=60) and Central Visayas, Philippines (n=56). Prevalence of MetS and its component factors as defined by the International Diabetes Federation criteria. The prevalence of MetS in Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs 55%, P=.08) although the prevalence of elevated waist circumference was greater for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk-associated high-density lipoprotein (HDL) levels was higher than the FAW group (84% vs 42%, P<.001). Other MetS component factors (blood pressure, glucose and triglycerides) did not significantly differ between groups. Similar high rates of MetS were observed in Filipino women regardless of the country of residency although the FAW tended to have higher rates of central obesity while the FW tended to have higher rates of risk-associated HDL levels. Further research should examine the cause of these differences in order to develop better cardiovascular screening and intervention strategies.

  11. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

    PubMed

    Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

  12. An Assessment of the Computer Science Activities of the Office of Naval Research

    DTIC Science & Technology

    1986-01-01

    A Panel of the Naval Studies Board of the National Research Council met for two days in October 1985 to assess the computer science programs of the ... Office of Naval (ONR). These programs are supported by the Contract Research Program (CRP) as well as the Naval Research Laboratory (NRL), the Naval

  13. 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 a...

  14. 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?

  15. Unified constitutive models for high-temperature structural applications

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  16. MET exon 14 skipping mutation in triple-negative pulmonary adenocarcinomas and pleomorphic carcinomas: An analysis of intratumoral MET status heterogeneity and clinicopathological characteristics.

    PubMed

    Kwon, Dohee; Koh, Jaemoon; Kim, Sehui; Go, Heounjeong; Kim, Young A; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Jeon, Yoon Kyung; Chung, Doo Hyun

    2017-04-01

    MET mutations leading to exon 14 skipping rarely occur in non-small cell lung cancer (NSCLC). Recently, small molecule inhibitors targeting MET mutations showed clinical benefit. However, the clinicopathological characteristics of NSCLC harboring MET mutations, and the correlation among mutations, protein expression, and gene copy number of MET in NSCLC remain unclear. Therefore, we address these issues. MET exon 14 skipping mutations were evaluated using real-time quantitative reverse-transcription-PCR (qRT-PCR) in 102 triple-negative (i.e., EGFR mutation (-)/ALK translocation (-)/KRAS mutation (-)) pulmonary adenocarcinomas, and 45 pleomorphic carcinomas. MET mutation and gene copy were also examined in microdissected tissues obtained from tumor areas with heterogeneous MET immunohistochemical expression. MET mutations were detected in 8.8% (9/102) of triple-negative adenocarcinomas and 20% (9/45) of pleomorphic carcinomas of the lung. Patients with MET-mutated adenocarcinomas was significantly older than those without MET mutations (P=0.015). The male to female and ever-to never-smoker ratios were 3:6 and 2:7, respectively, among patients with MET-mutated adenocarcinomas. All (9/9) of the MET-mutated adenocarcinomas showed acinar predominant histology with associated lepidic patterns. In contrast, the male to female and ever- to never-smoker ratios were 8:1 and 7:1, respectively, among patients with MET-mutated pleomorphic carcinomas. The carcinoma component of MET-mutated pleomorphic carcinomas was mostly adenocarcinoma of acinar pattern (8/9). MET mutation was detected by qRT-PCR in all samples with heterogeneous MET expression microdissected from five cases with MET-mutated adenocarcinoma, while MET gene amplification was detected in tumor areas expressing high MET protein levels among MET-mutated adenocarcinomas. MET-mutated NSCLC is characterized by older age in patients with adenocarcinoma and by an acinar histology and variable MET expression in patients

  17. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 12 2012-04-01 2012-04-01 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. This...

  18. 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. This...

  19. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 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. This...

  20. 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. This...

  1. Unified theory of effective interaction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takayanagi, Kazuo, E-mail: k-takaya@sophia.ac.jp

    2016-09-15

    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 perturbativemore » and nonperturbative theories on the basis of the main frame expansion.« less

  2. Unified Bohm criterion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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)more » 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.« less

  3. 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

    2017-03-01

    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.

  4. 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.

  5. Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors.

    PubMed

    Peacock, Jacqueline D; Pridgeon, Matthew G; Tovar, Elizabeth A; Essenburg, Curt J; Bowman, Megan J; Madaj, Zachary B; Koeman, Julie; Boguslawski, Elissa A; Grit, Jamie; Dodd, Rebecca D; Khachaturov, Vadim; Cardona, Diana M; Chen, Mark; Kirsch, David G; Maina, Flavio; Dono, Rosanna; Winn, Mary E; Graveel, Carrie R; Steensma, Matthew R

    2018-05-02

    Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly resistant sarcomas that occur in up to 13% of individuals with Neurofibromatosis Type 1 (NF1). Genomic analysis of longitudinally collected tumor samples in a case of MPNST disease progression revealed early hemizygous microdeletions in NF1 and TP53, with progressive amplifications of MET, HGF, and EGFR. To examine the role of MET in MPNST progression, we developed mice with enhanced MET expression and Nf1 ablation (Nf1fl/KO;lox-stop-loxMETtg/+;Plp-creERTtg/+; referred to as NF1 MET). NF1-MET mice express a robust MPNST phenotype in the absence of additional mutations. A comparison of NF1-MET MPNSTs with MPNSTs derived from Nf1KO/+;p53R172H;Plp-creERTtg/+ (NF1-P53) and Nf1KO/+;Plp-creERTtg/+ (NF1) mice revealed unique Met, Ras, and PI3K signaling patterns. NF1-MET MPNSTs were uniformly sensitive to the highly selective MET inhibitor, capmatinib, whereas a heterogeneous response to MET inhibition was observed in NF1-P53 and NF1 MPNSTs. Combination therapy of capmatinib and the MEK inhibitor trametinib resulted in reduced response variability, enhanced suppression of tumor growth, and suppressed RAS/ERK and PI3K/AKT signaling. These results highlight the influence of concurrent genomic alterations on RAS effector signaling and therapy response to tyrosine kinase inhibitors. Moreover, these findings expand our current understanding of the role of MET signaling in MPNST progression and identify a potential therapeutic niche for NF1-related MPNSTs. Copyright ©2018, American Association for Cancer Research.

  6. Benchmarking and Evaluating Unified Memory for OpenMP GPU Offloading

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mishra, Alok; Li, Lingda; Kong, Martin

    Here, the latest OpenMP standard offers automatic device offloading capabilities which facilitate GPU programming. Despite this, there remain many challenges. One of these is the unified memory feature introduced in recent GPUs. GPUs in current and future HPC systems have enhanced support for unified memory space. In such systems, CPU and GPU can access each other's memory transparently, that is, the data movement is managed automatically by the underlying system software and hardware. Memory over subscription is also possible in these systems. However, there is a significant lack of knowledge about how this mechanism will perform, and how programmers shouldmore » use it. We have modified several benchmarks codes, in the Rodinia benchmark suite, to study the behavior of OpenMP accelerator extensions and have used them to explore the impact of unified memory in an OpenMP context. We moreover modified the open source LLVM compiler to allow OpenMP programs to exploit unified memory. The results of our evaluation reveal that, while the performance of unified memory is comparable with that of normal GPU offloading for benchmarks with little data reuse, it suffers from significant overhead when GPU memory is over subcribed for benchmarks with large amount of data reuse. Based on these results, we provide several guidelines for programmers to achieve better performance with unified memory.« less

  7. Entanglement distribution in multi-particle systems in terms of unified entropy.

    PubMed

    Luo, Yu; Zhang, Fu-Gang; Li, Yongming

    2017-04-25

    We investigate the entanglement distribution in multi-particle systems in terms of unified (q, s)-entropy. We find that for any tripartite mixed state, the unified (q, s)-entropy entanglement of assistance follows a polygamy relation. This polygamy relation also holds in multi-particle systems. Furthermore, a generalized monogamy relation is provided for unified (q, s)-entropy entanglement in the multi-qubit system.

  8. Unified Phase Diagram for Iron-Based Superconductors.

    PubMed

    Gu, Yanhong; Liu, Zhaoyu; Xie, Tao; Zhang, Wenliang; Gong, Dongliang; Hu, Ding; Ma, Xiaoyan; Li, Chunhong; Zhao, Lingxiao; Lin, Lifang; Xu, Zhuang; Tan, Guotai; Chen, Genfu; Meng, Zi Yang; Yang, Yi-Feng; Luo, Huiqian; Li, Shiliang

    2017-10-13

    High-temperature superconductivity is closely adjacent to a long-range antiferromagnet, which is called a parent compound. In cuprates, all parent compounds are alike and carrier doping leads to superconductivity, so a unified phase diagram can be drawn. However, the properties of parent compounds for iron-based superconductors show significant diversity and both carrier and isovalent dopings can cause superconductivity, which casts doubt on the idea that there exists a unified phase diagram for them. Here we show that the ordered moments in a variety of iron pnictides are inversely proportional to the effective Curie constants of their nematic susceptibility. This unexpected scaling behavior suggests that the magnetic ground states of iron pnictides can be achieved by tuning the strength of nematic fluctuations. Therefore, a unified phase diagram can be established where superconductivity emerges from a hypothetical parent compound with a large ordered moment but weak nematic fluctuations, which suggests that iron-based superconductors are strongly correlated electron systems.

  9. Grand unified brane world scenario

    NASA Astrophysics Data System (ADS)

    Arai, Masato; Blaschke, Filip; Eto, Minoru; Sakai, Norisuke

    2017-12-01

    We present a field theoretical model unifying grand unified theory (GUT) and brane world scenario. As a concrete example, we consider S U (5 ) GUT in 4 +1 dimensions where our 3 +1 dimensional spacetime spontaneously arises on five domain walls. A field-dependent gauge kinetic term is used to localize massless non-Abelian gauge fields on the domain walls and to assure the charge universality of matter fields. We find the domain walls with the symmetry breaking S U (5 )→S U (3 )×S U (2 )×U (1 ) as a global minimum and all the undesirable moduli are stabilized with the mass scale of MGUT. Profiles of massless standard model particles are determined as a consequence of wall dynamics. The proton decay can be exponentially suppressed.

  10. Analysis and Recommendations on the Company-Grade Officer Shortfall in the Reserve Components of the U.S. Army

    DTIC Science & Technology

    2011-01-01

    available from www.rand.org as a public service of the RAND Corporation. CHILDREN AND FAMILIES EDUCATION AND THE ARTS ENERGY AND ENVIRONMENT HEALTH AND...conducted within the RAND National Defense Research Institute, a federally funded research and development center sponsored by OSD, the Joint Staff, the... develop - ment center sponsored by the Office of the Secretary of Defense, the Joint Staff, the Unified Combatant Commands, the Navy, the Marine Corps

  11. 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

  12. 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…

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

    ERIC Educational Resources Information Center

    Duckenfield, Marty, Ed.

    2011-01-01

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

  14. Unifying distribution functions: some lesser known distributions.

    PubMed

    Moya-Cessa, J R; Moya-Cessa, H; Berriel-Valdos, L R; Aguilar-Loreto, O; Barberis-Blostein, P

    2008-08-01

    We show that there is a way to unify distribution functions that describe simultaneously a classical signal in space and (spatial) frequency and position and momentum for a quantum system. Probably the most well known of them is the Wigner distribution function. We show how to unify functions of the Cohen class, Rihaczek's complex energy function, and Husimi and Glauber-Sudarshan distribution functions. We do this by showing how they may be obtained from ordered forms of creation and annihilation operators and by obtaining them in terms of expectation values in different eigenbases.

  15. 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…

  16. Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

    PubMed

    Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

    2008-01-01

    Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

  17. Adaptive feedback synchronization of a unified chaotic system

    NASA Astrophysics Data System (ADS)

    Lu, Junan; Wu, Xiaoqun; Han, Xiuping; Lü, Jinhu

    2004-08-01

    This Letter further improves and extends the work of Wang et al. [Phys. Lett. A 312 (2003) 34]. In detailed, the linear feedback synchronization and adaptive feedback synchronization with only one controller for a unified chaotic system are discussed here. It is noticed that this unified system contains the noted Lorenz and Chen systems. Two chaotic synchronization theorems are attained. Also, numerical simulations are given to show the effectiveness of these methods.

  18. Secondary tracheoesophageal puncture in-office using Seldinger technique.

    PubMed

    Britt, Christopher J; Lippert, Dylan; Kammer, Rachael; Ford, Charles N; Dailey, Seth H; McCulloch, Timothy; Hartig, Gregory

    2014-05-01

    Evaluate the safety and efficacy of in-office secondary tracheoesophageal puncture (TEP) technique using transnasal esophagoscopy (TNE) and the Seldinger technique in conjunction with a cricothyroidotomy kit for placement. Case series with chart review. Academic medical center. A retrospective chart review was performed on 83 subjects who underwent in-office secondary TEP. Variables that were examined included disease site, staging, histologic diagnosis, extent of resection and reconstruction, chemoradiation, functional voice status (as assessed by speech pathologist in most recent note), and complications directly related to the procedure. Eighty-three individuals from our institution met our criteria for in-office secondary TEP from 2005 to August 2012. Of these, 97.6% (81/83) had no complications of TEP. The overall complication rate was 2.4% (2/83). Complications included bleeding from puncture site and closure of puncture site after dislodgement of prosthesis at the time of puncture. Fluent conversational speech was achieved in 69.9% of all patients (58/83), and an additional 19.3% (16/83) achieved functional/intelligible speech; of those, 3.6% (3/83) were unable to achieve fluent conversational speech due to anatomic defects from previous surgery. An in-office TEP can be safely performed using the Seldinger technique with direct visualization using TNE, despite the extent of resection or reconstruction, with functional speech outcomes comparable to other studies available in the literature.

  19. MET amplification as a potential therapeutic target in gastric cancer

    PubMed Central

    Kawakami, Hisato; Okamoto, Isamu; Arao, Tokuzo; Okamoto, Wataru; Matsumoto, Kazuko; Taniguchi, Hirokazu; Kuwata, Kiyoko; Yamaguchi, Haruka; Nishio, Kazuto; Nakagawa, Kazuhiko; Yamada, Yasuhide

    2013-01-01

    Our aim was to investigate both the prevalence of MET amplification in gastric cancer as well as the potential of this genetic alteration to serve as a therapeutic target in gastric cancer. MET amplification was assessed by initial screening with a PCR-based copy number assay followed by confirmatory FISH analysis in formalin-fixed, paraffin-embedded specimens of gastric cancer obtained at surgery. The effects of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with or without MET amplification were also examined. The median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3. We performed FISH analysis for the 15 cases with the highest MET copy numbers. MET amplification was confirmed in the four assessable cases with a MET copy number of at least 4, whereas MET amplification was not detected in those with a gene copy number of <4. The prevalence of MET amplification was thus 1.5% (4 out of 266 cases). Inhibition of MET by MET-TKIs resulted in the induction of apoptosis accompanied by attenuation of downstream MET signaling in gastric cancer cell lines with MET amplification but not in those without this genetic change. MET amplification identifies a small but clinically important subgroup of gastric cancer patients who are likely to respond to MET-TKIs. Furthermore, screening with a PCR-based copy number assay is an efficient way to reduce the number of patients requiring confirmation of MET amplification by FISH analysis. PMID:23327903

  20. MET expression and amplification in patients with localized gastric cancer

    PubMed Central

    Janjigian, Yelena Y.; Tang, Laura H.; Coit, Daniel G.; Kelsen, David P.; Francone, Todd D.; Weiser, Martin R.; Jhanwar, Suresh C.; Shah, Manish A.

    2013-01-01

    Background MET, the receptor for hepatocyte growth factor has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer. Methods Tumor specimens from patients enrolled on a preoperative chemotherapy study (NCI 5700) were examined for presence of MET gene amplification by fluorescence in situ hybridization (FISH), MET mRNA expression by quantitative polymerase chain reaction, MET overexpression by immunohistochemistry (IHC), and for evidence of MET pathway activation by p-MET IHC. Results Although high-level of MET protein and mRNA were commonly encountered (in 63% and 50% of resected tumor specimens, respectively), none of these tumors had MET gene amplification by FISH, and only 6.6% had evidence of MET tyrosine kinase activity by p-MET IHC. Conclusions In this cohort of patients with localized gastric cancer, the presence of high MET protein and RNA expression does not correlate with MET gene amplification or pathway activation as evidenced by the absence of amplification by FISH and negative p-MET IHC analysis. Impact This paper demonstrates a lack of MET amplification and pathway activation in a cohort of 38 patients with localized gastric cancer, suggesting that MET-driven gastric cancers are relatively rare in Western patients. PMID:21393565

  1. UPWP Unified Planning Work Program

    DOT National Transportation Integrated Search

    1995-05-01

    The Unified Plannrng Work Program (UPWP) iS the planning document that guides the MPO staff in fulfilling its planning responstbilities for the upcoming year. Comprised of tasks that can be changed as the planning needs change. It is intended to serv...

  2. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy

    PubMed Central

    Musiani, Daniele; Konda, John David; Pavan, Simona; Torchiaro, Erica; Sassi, Francesco; Noghero, Alessio; Erriquez, Jessica; Perera, Timothy; Olivero, Martina; Di Renzo, Maria Flavia

    2014-01-01

    The tyrosine kinase encoded by the MET oncogene is activated by gene mutation or amplification in tumors, which in most instances maintain addiction, i.e., dependency, to MET activation. This makes MET an attractive candidate for targeted therapies. Here we show that, in 3/3 MET-addicted human gastric cancer cell lines, MET kinase inhibition resulted in a 3- to 4-fold increased expression of the antiapoptotic small heat-shock protein of 27 kDa (HSP27, HSPB1). HSP27 increase depended on the inhibition of the MEK/ERK pathway and on heat-shock factor 1 (HSF1) and hypoxia-inducible factor-1α (HIF-1α) regulation. Importantly, HSP27-silenced MET-addicted cells underwent 2- and 3-fold more apoptosis following MET inhibition in vitro and in vivo, respectively. Likewise, in human cancer cells susceptible to epidermal growth factor receptor (EGFR) inhibition, EGFR inhibitors induced HSP27 expression and were strengthened by HSP27 suppression. In control cell lines that were not affected by drugs targeting MET or EGFR, these drugs did not induce HSP27 increase. Therefore, in cancer therapies targeting the MET pathway, the induction of HSP27 might limit the efficacy of anti-MET agents. As HSP27 increase also impairs the effectiveness of EGFR inhibitors and is known to protect cells from chemotherapeutics, the induction of HSP27 by targeted agents might strongly affect the success of combination treatments.—Musiani, D., Konda, J. D., Pavan, S., Torchiaro, E., Sassi, F., Noghero, A., Erriquez, J., Perera, T., Olivero, M., Di Renzo, M. F. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy. PMID:24903273

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  4. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy.

    PubMed

    Musiani, Daniele; Konda, John David; Pavan, Simona; Torchiaro, Erica; Sassi, Francesco; Noghero, Alessio; Erriquez, Jessica; Perera, Timothy; Olivero, Martina; Di Renzo, Maria Flavia

    2014-09-01

    The tyrosine kinase encoded by the MET oncogene is activated by gene mutation or amplification in tumors, which in most instances maintain addiction, i.e., dependency, to MET activation. This makes MET an attractive candidate for targeted therapies. Here we show that, in 3/3 MET-addicted human gastric cancer cell lines, MET kinase inhibition resulted in a 3- to 4-fold increased expression of the antiapoptotic small heat-shock protein of 27 kDa (HSP27, HSPB1). HSP27 increase depended on the inhibition of the MEK/ERK pathway and on heat-shock factor 1 (HSF1) and hypoxia-inducible factor-1α (HIF-1α) regulation. Importantly, HSP27-silenced MET-addicted cells underwent 2- and 3-fold more apoptosis following MET inhibition in vitro and in vivo, respectively. Likewise, in human cancer cells susceptible to epidermal growth factor receptor (EGFR) inhibition, EGFR inhibitors induced HSP27 expression and were strengthened by HSP27 suppression. In control cell lines that were not affected by drugs targeting MET or EGFR, these drugs did not induce HSP27 increase. Therefore, in cancer therapies targeting the MET pathway, the induction of HSP27 might limit the efficacy of anti-MET agents. As HSP27 increase also impairs the effectiveness of EGFR inhibitors and is known to protect cells from chemotherapeutics, the induction of HSP27 by targeted agents might strongly affect the success of combination treatments. © FASEB.

  5. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    PubMed

    Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

    2018-04-08

    MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

  6. Making our offices universally accessible: guidelines for physicians

    PubMed Central

    Jones, K E; Tamari, I E

    1997-01-01

    OBJECTIVE: To develop recommendations for office-based physicians who wish to make their offices accessible to all patients. OPTIONS: Include taking steps to make offices more accessible, or not; offices may be accessible to varying degrees. OUTCOMES: Outcomes of accessibility involve patient-care, economic, ethical and legal issues. Stakeholders in these outcomes include patients, physicians, government and society. EVIDENCE: Data were obtained from a series of searches of MEDLINE, CINAHL and Healthstar (previously Health) databases for articles on disability and family medicine, primary (health) care and family practice, and on access and offices, and health services accessibility, and from a telephone survey of 50 stakeholders. VALUES: A high value was placed on services to persons with disabilities and on stakeholder input. Universal accessibility was valued as an overall goal; improved accessibility was also highly valued. BENEFITS, HARMS AND COSTS: Benefits to patients include improved access to care as guaranteed by the Canada Health Act and in keeping with provincial Human Rights Codes. Benefits to physicians include contact with a broader patient population and freedom from fear of litigation. Costs of improved accessibility vary depending on individual circumstances and on whether an office is being built or renovated; some improvement costs are minimal. RECOMMENDATIONS: All physicians should take measures to improve practice accessibility. Improved access should be considered in each of the following areas: transportation and entrance to the facility, entrance to the office, waiting rooms, rest rooms, examination rooms, general building features and other features. VALIDATION: No similar guidelines exist. To assess the content validity of these guidelines, the authors had a draft document reviewed by 18 stakeholders. All specific recommendations met the minimum criterion of adherence to current legislation, including national and provincial building

  7. PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells.

    PubMed

    Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

    2009-11-25

    c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-gamma agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors

  8. Alternative Fuels Data Center: Mesa Unified School District Reaps Economic

    Science.gov Websites

    and Environmental Benefits with Propane Buses Mesa Unified School District Reaps Economic and School District Reaps Economic and Environmental Benefits with Propane Buses on Facebook Tweet about Alternative Fuels Data Center: Mesa Unified School District Reaps Economic and Environmental Benefits with

  9. Unified Early Childhood Personnel Preparation Programs: Perceptions from the Field.

    ERIC Educational Resources Information Center

    LaMontagne, M. J.; Johnson, Lawrence J.; Kilgo, Jennifer L.; Stayton, Vicki; Carr, Victoria; Bauer, Anne M.; Carpenter, Jenny

    2002-01-01

    This study examined perceptions of unified early childhood personnel preparation programs by 28 faculty members in such programs and by graduates (n=42) of unified, dual, or separate exceptional child education or exceptional child special education programs. Faculty stressed the importance of commitment and collaborative problem solving. The…

  10. Dissection of combinatorial control by the Met4 transcriptional complex.

    PubMed

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  11. Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation.

    PubMed

    Yamaoka, Toshimitsu; Ohmori, Tohru; Ohba, Motoi; Arata, Satoru; Kishino, Yasunari; Murata, Yasunori; Kusumoto, Sojiro; Ishida, Hiroo; Shirai, Takao; Hirose, Takashi; Ohnishi, Tsukasa; Sasaki, Yasutsuna

    2016-12-01

    Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring 15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing concentrations of the Met-TKI PHA665752 and 1 μmol/L gefitinib for 1 year; three resistant clones were established via Met amplification. The three dual-resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and DR6, respectively) exhibited different mechanisms for evading both EGFR and Met inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2 and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified by association with HSP90, which protected Met from degradation and induced SET and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the first report describing the acquisition of dual resistance mechanisms in NSCLC harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous EGFR-TKI treatment. These results might inform the development of more effective therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040-54. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. a Unified Matrix Polynomial Approach to Modal Identification

    NASA Astrophysics Data System (ADS)

    Allemang, R. J.; Brown, D. L.

    1998-04-01

    One important current focus of modal identification is a reformulation of modal parameter estimation algorithms into a single, consistent mathematical formulation with a corresponding set of definitions and unifying concepts. Particularly, a matrix polynomial approach is used to unify the presentation with respect to current algorithms such as the least-squares complex exponential (LSCE), the polyreference time domain (PTD), Ibrahim time domain (ITD), eigensystem realization algorithm (ERA), rational fraction polynomial (RFP), polyreference frequency domain (PFD) and the complex mode indication function (CMIF) methods. Using this unified matrix polynomial approach (UMPA) allows a discussion of the similarities and differences of the commonly used methods. the use of least squares (LS), total least squares (TLS), double least squares (DLS) and singular value decomposition (SVD) methods is discussed in order to take advantage of redundant measurement data. Eigenvalue and SVD transformation methods are utilized to reduce the effective size of the resulting eigenvalue-eigenvector problem as well.

  13. 13 CFR 127.503 - When is a contracting officer authorized to restrict competition under this part?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... reasonable expectation based on market research that: (1) Two or more EDWOSBs will submit offers for the... requirements. If market research indicates that the criteria in paragraph (a) are not met for restricting...; and (2) The contracting officer has a reasonable expectation based on market research that— (i) Two or...

  14. 13 CFR 127.503 - When is a contracting officer authorized to restrict competition under this part?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... has a reasonable expectation based on market research that: (1) Two or more EDWOSBs will submit offers...) WOSB requirements. If market research indicates that the criteria in paragraph (a) are not met for...; and (2) The contracting officer has a reasonable expectation based on market research that— (i) Two or...

  15. Beyond the Unified Model

    NASA Astrophysics Data System (ADS)

    Frauendorf, S.

    2018-04-01

    The key elements of the Unified Model are reviewed. The microscopic derivation of the Bohr Hamiltonian by means of adiabatic time-dependent mean field theory is presented. By checking against experimental data the limitations of the Unified Model are delineated. The description of the strong coupling between the rotational and intrinsic degrees of freedom in framework of the rotating mean field is presented from a conceptual point of view. The classification of rotational bands as configurations of rotating quasiparticles is introduced. The occurrence of uniform rotation about an axis that differs from the principle axes of the nuclear density distribution is discussed. The physics behind this tilted-axis rotation, unknown in molecular physics, is explained on a basic level. The new symmetries of the rotating mean field that arise from the various orientations of the angular momentum vector with respect to the triaxial nuclear density distribution and their manifestation by the level sequence of rotational bands are discussed. Resulting phenomena, as transverse wobbling, rotational chirality, magnetic rotation and band termination are discussed. Using the concept of spontaneous symmetry breaking the microscopic underpinning of the rotational degrees is refined.

  16. NOAA Civil Rights Office - EEO Office

    Science.gov Websites

    Oceanic and Atmospheric Administration Office of the Chief Administration Officer Civil Rights Office (CRO Diversity and Inclusion Management Advisory Council (DIMAC) Diversity and Inclusion Toolkit The NOAA Civil Rights Office Welcome to the NOAA Civil Rights Office The NOAA Civil Rights Office provides overall

  17. Unified Research on Network-Based Hard/Soft Information Fusion

    DTIC Science & Technology

    2016-02-02

    types). There are a number of search tree run parameters which must be set depending on the experimental setting. A pilot study was run to identify...Unlimited Final Report: Unified Research on Network-Based Hard/Soft Information Fusion The views, opinions and/or findings contained in this report...Final Report: Unified Research on Network-Based Hard/Soft Information Fusion Report Title The University at Buffalo (UB) Center for Multisource

  18. 78 FR 18235 - Unified Rule for Loss on Subsidiary Stock

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... 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...) Example 6 (ii)(D)(3), reinstate the following sentence: Sec. 1.1502-36 Unified loss rule. * * * * * (d...

  19. Detection of MET amplification in gastroesophageal tumor specimens using IQFISH

    PubMed Central

    Nielsen, Karsten Bork; Mollerup, Jens; Jepsen, Anna; Go, Ning

    2017-01-01

    Background The gene mesenchymal epithelial transition factor (MET) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. Methods Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET/CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET amplification was defined as a MET/CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated. Results The prevalence of MET amplification was found to be 6.9%. The FISH assay demonstrated a high inter-observer reproducibility. The inter-observer results showed a 100% overall agreement with respect to the MET status (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 10.2–13.4). For the signal distribution, the inter-observer agreement was reported to be 98.7%. We also report an association of MET amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of MET amplification was markedly higher in tumors specimens with a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. Furthermore, specimens with a heterogeneous signal distribution had a statically significantly higher median MET/CEN-7 ratio (2.35 versus 1.04; P<0.0001). Conclusions The novel FISH assay showed a high inter-observer reproducibility both with respect to amplification status and signal distribution. Based on the finding in the study it is suggested that MET amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern. PMID:29285491

  20. Detection of MET amplification in gastroesophageal tumor specimens using IQFISH.

    PubMed

    Jørgensen, Jan Trøst; Nielsen, Karsten Bork; Mollerup, Jens; Jepsen, Anna; Go, Ning

    2017-12-01

    The gene mesenchymal epithelial transition factor ( MET ) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET /CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET amplification was defined as a MET /CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated. The prevalence of MET amplification was found to be 6.9%. The FISH assay demonstrated a high inter-observer reproducibility. The inter-observer results showed a 100% overall agreement with respect to the MET status (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 10.2-13.4). For the signal distribution, the inter-observer agreement was reported to be 98.7%. We also report an association of MET amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of MET amplification was markedly higher in tumors specimens with a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. Furthermore, specimens with a heterogeneous signal distribution had a statically significantly higher median MET /CEN-7 ratio (2.35 versus 1.04; P<0.0001). The novel FISH assay showed a high inter-observer reproducibility both with respect to amplification status and signal distribution. Based on the finding in the study it is suggested that MET amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern.

  1. MMPM - Mission implementation of Mars MetNet Precursor

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.

    2009-04-01

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

  2. Automating the business office.

    PubMed

    Wright, M A

    1996-10-01

    To measure the success of automating the business office with electronic billing and document management systems, the hospital's original goals were reviewed: Had the number of FTEs been maintained or reduced: Yes--claims volume is up 58% over 6 years with a 22% reduction in FTEs (see Exhibit 3). Was the cost of maintaining the paper filing system reduced? Yes--and the cost saving from the hospital's document imaging system will allow a 4.4 year payback. Is better customer service being provided? Yes--online access to patient demographic and financial information has improved response time. Having met all its goals, North Kansas City Hospital considers the installation of both systems to have been complete success. The facility expects to continue expansion of the document management system into accounts payable, payroll, home health, and other document-intensive areas to achieve further cost savings in the future.

  3. Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer.

    PubMed

    Kaye, Deborah R; Pinto, Peter A; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C; Gupta, Gopal; Choyke, Peter L; Bottaro, Donald P

    2016-01-01

    To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9-10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

  4. Unified method to integrate and blend several, potentially related, sources of information for genetic evaluation.

    PubMed

    Vandenplas, Jérémie; Colinet, Frederic G; Gengler, Nicolas

    2014-09-30

    A condition to predict unbiased estimated breeding values by best linear unbiased prediction is to use simultaneously all available data. However, this condition is not often fully met. For example, in dairy cattle, internal (i.e. local) populations lead to evaluations based only on internal records while widely used foreign sires have been selected using internally unavailable external records. In such cases, internal genetic evaluations may be less accurate and biased. Because external records are unavailable, methods were developed to combine external information that summarizes these records, i.e. external estimated breeding values and associated reliabilities, with internal records to improve accuracy of internal genetic evaluations. Two issues of these methods concern double-counting of contributions due to relationships and due to records. These issues could be worse if external information came from several evaluations, at least partially based on the same records, and combined into a single internal evaluation. Based on a Bayesian approach, the aim of this research was to develop a unified method to integrate and blend simultaneously several sources of information into an internal genetic evaluation by avoiding double-counting of contributions due to relationships and due to records. This research resulted in equations that integrate and blend simultaneously several sources of information and avoid double-counting of contributions due to relationships and due to records. The performance of the developed equations was evaluated using simulated and real datasets. The results showed that the developed equations integrated and blended several sources of information well into a genetic evaluation. The developed equations also avoided double-counting of contributions due to relationships and due to records. Furthermore, because all available external sources of information were correctly propagated, relatives of external animals benefited from the integrated

  5. Toward a Unified Science Curriculum.

    ERIC Educational Resources Information Center

    Showalter, Victor M.

    The two major models of science curriculum change, textbook revision and national curriculum projects, are derived from, and reinforce, the present curriculum structure. This is undesirable in a time of increasing fluidity and change, because adaptation to new situations is difficult. Unified science, based on the premise that science is a unity,…

  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. 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).

  8. Constitutively active c-Met kinase in PC-3 cells is autocrine-independent and can be blocked by the Met kinase inhibitor BMS-777607

    PubMed Central

    2012-01-01

    Background The c-Met receptor tyrosine kinase is aberrantly activated in many solid tumors. In a prior study we showed that prostate cancer PC-3 cells exhibit constitutively activated c-Met without exogenous hepatocyte growth factor (HGF); however whether this characteristic is due to an endogenous HGF/c-Met autocrine loop remains controversial. In the current study we examined the response of PC-3 cells to an anti-HGF neutralizing antibody or a small molecule Met kinase inhibitor (BMS-777607). Methods Cell scattering was tested by monitoring cell morphology after HGF stimulation. Cell migration was examined by both “wound-healing” and transwell assasy and invasion was detected by Matrigel-coated transwell assay. Proliferation, survival and anoikis were determined by MTT, colony formation and trypan blue exclusion assay, respectively. Gene and protein expression were assessed by real-time PCR and Western blot, respectively. Results Although HGF mRNA could be detected in PC-3 cells, the molecular weight of secreted “HGF” protein was inconsistent with the functional recombinant HGF. Furthermore, conditioned medium from PC-3 cell cultures was ineffective at triggering either motogenic behavior or c-Met signaling in DU145, another prostate cancer cell line expressing c-Met but lacking basal c-Met activation. PC-3 cells also were not responsive to the anti-HGF neutralizing antibody in experiments assessing proliferation, migration, or c-Met signaling. BMS-777607 treatment with micromolar doses nonetheless led to significant inhibition of multiple PC-3 cell functions including proliferation, clonogenicity, migration and invasion. At the molecular level, BMS-777607 suppressed autophosphorylated c-Met and downstream c-Src and Akt pathways. Conclusions These results suggest that the constitutive c-Met activation in PC-3 is independent of autocrine stimulation. Because PC-3 cells were responsive to BMS-777607 but not the anti-HGF antibody, the findings also indicate

  9. Unified Approximations: A New Approach for Monoprotic Weak Acid-Base Equilibria

    ERIC Educational Resources Information Center

    Pardue, Harry; Odeh, Ihab N.; Tesfai, Teweldemedhin M.

    2004-01-01

    The unified approximations reduce the conceptual complexity by combining solutions for a relatively large number of different situations into just two similar sets of processes. Processes used to solve problems by either the unified or classical approximations require similar degrees of understanding of the underlying chemical processes.

  10. 29 CFR 779.218 - Methods to accomplish “unified operation.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., join together to perform some or all of their activities as a unified business or business system. They may accomplish such unification through agreements, franchises, grants, leases, or other arrangements... others so that they constitute a single business or unified business system. Whether in any particular...

  11. MET: roles in epithelial-mesenchymal transition and cancer stemness

    PubMed Central

    Jeon, Hye-Min

    2017-01-01

    In a number of cancers, deregulated MET pathway leads to aberrantly activated proliferative and invasive signaling programs that promote malignant transformation, cell motility and migration, angiogenesis, survival in hypoxia, and invasion. A better understanding of oncogenic MET signaling will help us to discover effective therapeutic approaches and to identify which tumors are likely to respond to MET-targeted cancer therapy. In this review, we will summarize the roles of MET signaling in cancer, with particular focus on epithelial-mesenchymal transition (EMT) and cancer stemness. Then, we will provide update on MET targeting agents and discuss the challenges that should be overcome for the development of an effective therapy. PMID:28164090

  12. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

    PubMed

    Angevin, Eric; Spitaleri, Gianluca; Rodon, Jordi; Dotti, Katia; Isambert, Nicolas; Salvagni, Stefania; Moreno, Victor; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hollebecque, Antoine; Azaro, Analia; Hervieu, Alice; Rihawi, Karim; De Marinis, Filippo

    2017-12-01

    Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation. This was a phase I dose-escalation (3 + 3 design [50-740 mg/m 2 ]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort. In total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m 2 was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m 2 , five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number. The MTD of once-weekly SAR125844 was 570 mg/m 2 ; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC. NCT01391533. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. User's manual for UCAP: Unified Counter-Rotation Aero-Acoustics Program

    NASA Technical Reports Server (NTRS)

    Culver, E. M.; Mccolgan, C. J.

    1993-01-01

    This is the user's manual for the Unified Counter-rotation Aeroacoustics Program (UCAP), the counter-rotation derivative of the UAAP (Unified Aero-Acoustic Program). The purpose of this program is to predict steady and unsteady air loading on the blades and the noise produced by a counter-rotation Prop-Fan. The aerodynamic method is based on linear potential theory with corrections for nonlinearity associated with axial flux induction, vortex lift on the blades, and rotor-to-rotor interference. The theory for acoustics and the theory for individual blade loading and wakes are derived in Unified Aeroacoustics Analysis for High Speed Turboprop Aerodynamics and Noise, Volume 1 (NASA CR-4329). This user's manual also includes a brief explanation of the theory used for the modelling of counter-rotation.

  14. User's manual for UCAP: Unified Counter-Rotation Aero-Acoustics Program

    NASA Astrophysics Data System (ADS)

    Culver, E. M.; McColgan, C. J.

    1993-04-01

    This is the user's manual for the Unified Counter-rotation Aeroacoustics Program (UCAP), the counter-rotation derivative of the UAAP (Unified Aero-Acoustic Program). The purpose of this program is to predict steady and unsteady air loading on the blades and the noise produced by a counter-rotation Prop-Fan. The aerodynamic method is based on linear potential theory with corrections for nonlinearity associated with axial flux induction, vortex lift on the blades, and rotor-to-rotor interference. The theory for acoustics and the theory for individual blade loading and wakes are derived in Unified Aeroacoustics Analysis for High Speed Turboprop Aerodynamics and Noise, Volume 1 (NASA CR-4329). This user's manual also includes a brief explanation of the theory used for the modelling of counter-rotation.

  15. Effective implementation of novel MET pharmacodynamic assays in translational studies.

    PubMed

    Srivastava, Apurva K; Navas, Tony; Herrick, William G; Hollingshead, Melinda G; Bottaro, Donald P; Doroshow, James H; Parchment, Ralph E

    2017-01-01

    MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy. However, a wide range in type and frequency of these mutations suggest there is a need to carefully link these mutations to MET dysregulation, at least in proof-of-concept studies. In this review, we elaborate how we can utilize recently developed and validated pharmacodynamic biomarkers of MET not only to show target engagement, but more importantly to quantitatively measure MET dysregulation in tumor tissues. The MET assay endpoints provide evidence of both canonical and non-canonical MET signaling, can be used as "effect markers" to define biologically effective doses (BEDs) for molecularly targeted drugs, confirm mechanism-of-action in testing combination of drugs, and establish whether a diagnostic test is reporting MET dysregulation. We have established standard operating procedures for tumor biopsy collections to control pre-analytical variables that have produced valid results in proof-of-concept studies. The reagents and procedures are made available to the research community for potential implementation on multiple platforms such as ELISA, quantitative immunofluorescence assay (qIFA), and immuno-MRM assays.

  16. 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.

  17. Unified Engineering Software System

    NASA Technical Reports Server (NTRS)

    Purves, L. R.; Gordon, S.; Peltzman, A.; Dube, M.

    1989-01-01

    Collection of computer programs performs diverse functions in prototype engineering. NEXUS, NASA Engineering Extendible Unified Software system, is research set of computer programs designed to support full sequence of activities encountered in NASA engineering projects. Sequence spans preliminary design, design analysis, detailed design, manufacturing, assembly, and testing. Primarily addresses process of prototype engineering, task of getting single or small number of copies of product to work. Written in FORTRAN 77 and PROLOG.

  18. Introduction to The Regulatory Plan and the Unified Agenda of Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Unified Agenda 79451 Published? III. How Are The Regulatory Plan and the Unified Agenda 79451 Organized? IV. What Information Appears for Each Entry? 79452 V. Abbreviations 79454 VI. How Can Users Get... Department of Defense 79504 Department of Education 79509 Department of Energy 79512 Department of Health and...

  19. Phase noise suppression for coherent optical block transmission systems: a unified framework.

    PubMed

    Yang, Chuanchuan; Yang, Feng; Wang, Ziyu

    2011-08-29

    A unified framework for phase noise suppression is proposed in this paper, which could be applied in any coherent optical block transmission systems, including coherent optical orthogonal frequency-division multiplexing (CO-OFDM), coherent optical single-carrier frequency-domain equalization block transmission (CO-SCFDE), etc. Based on adaptive modeling of phase noise, unified observation equations for different coherent optical block transmission systems are constructed, which lead to unified phase noise estimation and suppression. Numerical results demonstrate that the proposal is powerful in mitigating laser phase noise.

  20. Analytic dyon solution in SU/N/ grand unified theories

    NASA Astrophysics Data System (ADS)

    Lyi, W. S.; Park, Y. J.; Koh, I. G.; Kim, Y. D.

    1982-10-01

    Analytic solutions which are regular everywhere, including at the origin, are found for certain cases of SU(N) grand unified theories. Attention is restricted to order-1/g behavior of the SU(N) grand unified theory, and aspects of the solutions of the Higgs field of the SU(N) near the origin are considered. Comments regarding the mass, the Pontryagin-like index of the dyon, and magnetic charge are made with respect to the recent report of a monopole discovery.

  1. 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. Copyright © 2015. Published by Elsevier Ltd.

  2. Evolution of Indian land surface biases in the seasonal hindcasts from the Met Office Global Seasonal Forecasting System GloSea5

    NASA Astrophysics Data System (ADS)

    Chevuturi, Amulya; Turner, Andrew G.; Woolnoug, Steve J.; Martin, Gill

    2017-04-01

    In this study we investigate the development of biases over the Indian region in summer hindcasts of the UK Met Office coupled initialised global seasonal forecasting system, GloSea5-GC2. Previous work has demonstrated the rapid evolution of strong monsoon circulation biases over India from seasonal forecasts initialised in early May, together with coupled strong easterly wind biases on the equator. These mean state biases lead to strong precipitation errors during the monsoon over the subcontinent. We analyse a set of three springtime start dates for the 20-year hindcast period (1992-2011) and fifteen total ensemble members for each year. We use comparisons with variety of observations to assess the evolution of the mean state biases over the Indian land surface. All biases within the model develop rapidly, particularly surface heat and radiation flux biases. Strong biases are present within the model climatology from pre-monsoon (May) in the surface heat fluxes over India (higher sensible / lower latent heat fluxes) when compared to observed estimates. The early evolution of such biases prior to onset rains suggests possible problems with the land surface scheme or soil moisture errors. Further analysis of soil moisture over the Indian land surface shows a dry bias present from the beginning of the hindcasts during the pre-monsoon. This lasts until the after the monsoon develops (July) after which there is a wet bias over the region. Soil moisture used for initialization of the model also shows a dry bias when compared against the observed estimates, which may lead to the same in the model. The early dry bias in the model may reduce local moisture availability through surface evaporation and thus may possibly limit precipitation recycling. On this premise, we identify and test the sensitivity of the monsoon in the model against higher soil moisture forcing. We run sensitivity experiments initiated using gridpoint-wise annual soil moisture maxima over the Indian

  3. Microenvironment-derived HGF overcomes genetically determined sensitivity to anti-MET drugs.

    PubMed

    Pennacchietti, Selma; Cazzanti, Manuela; Bertotti, Andrea; Rideout, William M; Han, May; Gyuris, Jeno; Perera, Timothy; Comoglio, Paolo M; Trusolino, Livio; Michieli, Paolo

    2014-11-15

    Cell-based drug screenings indicate that tumors displaying c-MET gene amplification are "addicted" to MET signaling and therefore are very sensitive to MET-targeted agents. However, these screenings were conducted in the absence of the MET ligand, hepatocyte growth factor (HGF), which is abundant in the tumor microenvironment. Sensitivity of six MET-addicted human tumor cells to three MET kinase inhibitors (JNJ-38877605, PHA-665752, crizotinib) and one antagonistic anti-MET antibody (DN30 Fab) was analyzed in the absence or presence of HGF, in a stroma-tumor coculture system, and by combining anti-MET drugs with an HGF neutralizing antibody (ficlatuzumab) in human HGF knock-in mice bearing c-MET-amplified tumors. In all models examined, HGF promoted resistance to MET-targeted agents, affecting both their potency and efficacy. HGF-induced resistance was due to restoration of physiologic GAB1-mediated PI3K activation that compensated for loss of aberrant HER3-dependent PI3K signaling. Ficlatuzumab restored sensitivity to MET-targeted agents in coculture systems and overcame resistance to JNJ-38877605, crizotinib, and DN30 Fab in human HGF knock-in mice. These data suggest that c-MET-amplified tumor cells-which normally exhibit ligand-independent, constitutive MET activation-become dependent on HGF for survival upon pharmacologic MET inhibition. Because HGF is frequently overexpressed in human cancer, this mechanism may represent a major cause of resistance to anti-MET therapies. The ability of ficlatuzumab to overcome HGF-mediated resistance generates proof of principle that vertical inhibition of both a tyrosine kinase receptor and its ligand can be therapeutically beneficial and opens new perspectives for the treatment of MET-dependent tumors. ©2014 American Association for Cancer Research.

  4. Job demands, resources and mental health in UK prison officers.

    PubMed

    Kinman, G; Clements, A J; Hart, J

    2017-08-01

    Research findings indicate that working as a prison officer can be highly stressful, but the aspects of work that predict their mental health status are largely unknown. To examine, using elements of the demands-resources model, the extent to which work pressure and several potential resources (i.e. control, support from managers and co-workers, role clarity, effective working relationships and positive change management) predict mental health in a sample of UK prison officers. The Health and Safety Executive Management Standards Indicator Tool was used to measure job demands and resources. Mental health was assessed by the General Health Questionnaire-28. The effects of demands and resources on mental health were examined via linear regression analysis with GHQ score as the outcome. The study sample comprised 1267 prison officers (86% male). Seventy-four per cent met 'caseness' criteria for mental health problems. Job demands, poor interpersonal relationships, role ambiguity and, to a lesser extent, low job control and poor management of change were key predictors of mental health status. The findings of this study can help occupational health practitioners and psychologists develop structured interventions to improve well-being among prison officers. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  5. 76 FR 19893 - Unified Command Plan 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... Plan 2011 Memorandum for the Secretary of Defense Pursuant to my authority as Commander in Chief, I hereby approve and direct the implementation of the revised Unified Command Plan. Consistent with title...

  6. The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma1

    PubMed Central

    Herrera, Luis J; El-Hefnawy, Talal; Queiroz de Oliveira, Pierre E; Raja, Siva; Finkelstein, Sydney; Gooding, William; Luketich, James D; Godfrey, Tony E; Hughes, Steven J

    2005-01-01

    Abstract The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted. PMID:15720819

  7. Development and application of unified algorithms for problems in computational science

    NASA Technical Reports Server (NTRS)

    Shankar, Vijaya; Chakravarthy, Sukumar

    1987-01-01

    A framework is presented for developing computationally unified numerical algorithms for solving nonlinear equations that arise in modeling various problems in mathematical physics. The concept of computational unification is an attempt to encompass efficient solution procedures for computing various nonlinear phenomena that may occur in a given problem. For example, in Computational Fluid Dynamics (CFD), a unified algorithm will be one that allows for solutions to subsonic (elliptic), transonic (mixed elliptic-hyperbolic), and supersonic (hyperbolic) flows for both steady and unsteady problems. The objectives are: development of superior unified algorithms emphasizing accuracy and efficiency aspects; development of codes based on selected algorithms leading to validation; application of mature codes to realistic problems; and extension/application of CFD-based algorithms to problems in other areas of mathematical physics. The ultimate objective is to achieve integration of multidisciplinary technologies to enhance synergism in the design process through computational simulation. Specific unified algorithms for a hierarchy of gas dynamics equations and their applications to two other areas: electromagnetic scattering, and laser-materials interaction accounting for melting.

  8. A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

    PubMed

    Sustar, A; Nikolac Perkovic, M; Nedic Erjavec, G; Svob Strac, D; Pivac, N

    2016-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more

  9. An under-met and over-met expectations model of employee reactions to merit raises.

    PubMed

    Schaubroeck, John; Shaw, Jason D; Duffy, Michelle K; Mitra, Atul

    2008-03-01

    The authors developed a model of how raise expectations influence the relationship between merit pay raises and employee reactions and tested it using a sample of hospital employees. Pay-for-performance (PFP) perceptions were consistently related to personal reactions (e.g., pay raise happiness, pay-level satisfaction, and turnover intentions). Merit pay raises were strongly related to reactions only among employees with high raise expectations and high PFP perceptions. The interactive effects of under-met/over-met expectations and PFP perceptions were mediated by the extent to which participants saw the raise as generous and they were happy with the raises they received. The authors discuss the implications of these findings for expectation-fulfillment theories, merit pay research, and the administration of incentives. Copyright 2008 APA

  10. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    NASA Astrophysics Data System (ADS)

    Hari, Ari-Matti; Haukka, Harri; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2017-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 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. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - MetBaro Pressure device - MetHumi Humidity device - MetTemp Temperature sensors Optical devices: - PanCam Panoramic - MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer - DS Dust sensor Composition and Structure Devices: Tri-axial magnetometer MOURA Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special 3-axis

  11. The Unified Levelling Network of Sarawak and its Adjustment

    NASA Astrophysics Data System (ADS)

    Som, Z. A. M.; Yazid, A. M.; Ming, T. K.; Yazid, N. M.

    2016-09-01

    The height reference network of Sarawak has seen major improvement in over the past two decades. The most significant improvement was the establishment of extended precise leveling network of which is now able to connect all three major datum points at Pulau Lakei, Original and Bintulu. Datum by following the major accessible routes across Sarawak. This means the leveling network in Sarawak has now been inter-connected and unified. By having such a unified network leads to the possibility of having a common single least squares adjustment been performed for the first time. The least squares adjustment of this unified levelling network was attempted in order to compute the height of all Bench Marks established in the entire levelling network. The adjustment was done by using MoreFix levelling adjustment package developed at FGHT UTM. The computational procedure adopted is linear parametric adjustment by minimum constraint. Since Sarawak has three separate datums therefore three separate adjustments were implemented by utilizing datum at Pulau Lakei, Original Miri and Bintulu Datum respectively. Results of the MoreFix unified adjustment agreed very well with adjustment repeated using Starnet. Further the results were compared with solution given by Jupem and they are in good agreement as well. The difference in height analysed were within 10mm for the case of minimum constraint at Pulau Lakei datum and with much better agreement in the case of Original Miri Datum.

  12. ATP3 Unified Field Study Data

    DOE Data Explorer

    Wolfrum, Ed (ORCID:0000000273618931); Knoshug, Eric (ORCID:000000025709914X); Laurens, Lieve (ORCID:0000000349303267); Harmon, Valerie; Dempster, Thomas (ORCID:000000029550488X); McGowan, John (ORCID:0000000266920518); Rosov, Theresa; Cardello, David; Arrowsmith, Sarah; Kempkes, Sarah; Bautista, Maria; Lundquist, Tryg; Crowe, Brandon; Murawsky, Garrett; Nicolai, Eric; Rowe, Egan; Knurek, Emily; Javar, Reyna; Saracco Alvarez, Marcela; Schlosser, Steve; Riddle, Mary; Withstandley, Chris; Chen, Yongsheng; Van Ginkel, Steven; Igou, Thomas; Xu, Chunyan; Hu, Zixuan

    2017-10-20

    ATP3 Unified Field Study Data The Algae Testbed Public-Private Partnership (ATP3) was established with the goal of investigating open pond algae cultivation across different geographic, climatic, seasonal, and operational conditions while setting the benchmark for quality data collection, analysis, and dissemination. Identical algae cultivation systems and data analysis methodologies were established at testbed sites across the continental United States and Hawaii. Within this framework, the Unified Field Studies (UFS) were designed to characterize the cultivation of different algal strains during all 4 seasons across this testbed network. The dataset presented here is the complete, curated, climatic, cultivation, harvest, and biomass composition data for each season at each site. These data enable others to do in-depth cultivation, harvest, techno-economic, life cycle, resource, and predictive growth modeling analysis, as well as develop crop protection strategies for the nascent algae industry. NREL Sub award Number: DE-AC36-08-GO28308

  13. Unified theory of motion of inner planets

    NASA Astrophysics Data System (ADS)

    Kotelnikov, V.; Kislik, M.

    1983-01-01

    A highly accurate, unified theory of motion for the Solar System's inner planets Mercury, Venus, the Earth, Mars was developed. It has practical importance and is used to solve various problems of interplanetary cosmonautics.

  14. Global Precipitation Measurement (GPM) Mission

    NASA Image and Video Library

    2014-02-26

    Chief officers from Mitsubishi Heavy Industries, Ltd., the Japan Aerospace Exploration Agency (JAXA) and NASA met on Wednesday, Feb. 26, 2014 in the Range Control Center (RCC) of the Tanegashima Space Center, Japan, to review the readiness of the Global Precipitation Measurement (GPM) Core Observatory for launch. The spacecraft is scheduled to launch aboard an H-IIA rocket early on the morning of Feb. 28 Japan time. Once launched, the GPM spacecraft will collect information that unifies data from an international network of existing and future satellites to map global rainfall and snowfall every three hours. Photo Credit: (NASA/Bill Ingalls)

  15. 29 CFR 779.219 - Unified operation may be achieved without common control or common ownership.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Unified operation may be achieved without common control or... Act May Apply; Enterprise Coverage Unified Operation Or Common Control § 779.219 Unified operation may be achieved without common control or common ownership. The performance of related activities through...

  16. [Arabian food pyramid: unified framework for nutritional health messages].

    PubMed

    Shokr, Adel M

    2008-01-01

    There are several ways to present nutritional health messages, particularly pyramidic indices, but they have many deficiencies such as lack of agreement on a unified or clear methodology for food grouping and ignoring nutritional group inter-relation and integration. This causes confusion for health educators and target individuals. This paper presents an Arabian food pyramid that aims to unify the bases of nutritional health messages, bringing together the function, contents, source and nutritional group servings and indicating the inter-relation and integration of nutritional groups. This provides comprehensive, integrated, simple and flexible health messages.

  17. Radiation chemical studies of Gly-Met-Gly in aqueous solution

    DOE PAGES

    Barata-Vallejo, Sebastian; Ferreri, Carla; Zhang, Tao; ...

    2016-10-25

    Important biological consequences are related to the reaction of HO radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest peptide where Met is not a terminal residue. The reactions of HO with Gly-Met-Gly and its N-acetyl derivative were studied by pulse radiolysis technique. The transient absorption spectra were resolved into contributions from specific components of radical intermediates. Moreover, a detailed product analysis is provided for the first time for Met-containing peptides in radiolytic studies tomore » support the mechanistic proposal. By parallel radiolytical and electrochemical reactions and consequent product identification, the formation of sulfoxide attributed to the direct HO radical attack on the sulfide functionality of the Met residue could be excluded, with the in situ generated hydrogen peroxide responsible for this oxidation. LC–MS and high resolution MS/MS were powerful analytical tools to envisage the structures of five products, thus allowing to complete the mechanistic picture of the overall Met-containing peptide reactivity.« less

  18. Toward a Unified Componential Theory of Human Reasoning. Technical Report No. 4.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.

    The unified theory described in this paper characterizes human reasoning as an information processing system with a hierarchical sequence of components and subtheories that account for performance on successively narrower tasks. Both deductive and inductive theories are subsumed in the unified componential theory, including transitive chain theory…

  19. Cincinnati's Bold New Venture: A Unified K-12 Reading/Communication Arts Program.

    ERIC Educational Resources Information Center

    Green, Reginald Leon

    1989-01-01

    Describes a unified reading/communication arts program in the Cincinnati Public School System which uses new basal texts, support materials, and a customized instructional system for each grade level, integrating listening, speaking, reading, writing, and thinking skills into a unified language approach. Discusses intervention strategies,…

  20. RAAAF's office landscape The End of Sitting: Energy expenditure and temporary comfort when working in non-sitting postures.

    PubMed

    Caljouw, Simone R; de Vries, Rutger; Withagen, Rob

    2017-01-01

    An earlier study suggested that the activity-inviting office landscape called "The End of Sitting", designed by Rietveld Architecture Art Affordances (RAAAF), should be considered as an alternative working environment to prevent sedentary behavior. The End of Sitting lacks chairs and tables but consists instead of a myriad of sloped surfaces at different heights that afford workers to stand, lean or recline at different locations. In this study, we assessed the impact of four of its workspaces on physical intensity, temporary comfort and productivity of office work and compared the outcomes with sitting and standing behind a desk. Twenty-four participants worked for 10 minutes in each of the six test conditions. Energy expenditure, measured by indirect calorimetry, and heart rate were recorded. Questionnaires were used to assess the perceived comfort. The number of words found in the word search test was counted as a measure of productivity. The majority of The End of Sitting workspaces led to a significant increase in energy expenditure compared with sitting behind a desk (ps < .05). Average MET values ranged from 1.40 to 1.58 which is a modest rise in energy expenditure compared to sitting (1.32 METs) and not significantly different from standing (1.47 METs). The scores on the general comfort scale indicated that some workspaces were less comfortable than sitting (ps < .05), but the vast majority of participants reported that at least one of The End of Sitting workspaces was equally or more comfortable than sitting. No differences in productivity between the test conditions were found. Further long-term studies are required to assess the behavioral adaptations, productivity and the level of comfort when using The End of Sitting as a permanent office.

  1. 76 FR 41745 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approval and limited disapproval of revisions to the San Joaquin Valley Unified Air Pollution Control... Valley Unified Air Pollution Control District (SJVUAPCD) Rule 4682, Polystyrene, Polyethylene, and...

  2. 76 FR 68103 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District Rule 4692...

  3. 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…

  4. 14 CFR 1221.108 - Establishment of the NASA Unified Visual Communications System.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Establishment of the NASA Unified Visual... ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA Program Identifiers, NASA Flags, and the Agency's Unified Visual...

  5. 14 CFR 1221.108 - Establishment of the NASA Unified Visual Communications System.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Establishment of the NASA Unified Visual... ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA Program Identifiers, NASA Flags, and the Agency's Unified Visual...

  6. Unified space--time trigonometry and its applications to relativistic kinematics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jaccarini, A.

    1973-06-15

    A geometrical approach to relativistic kinematics is presented. Owing to a unified space-time trigonometry, the spherical trigonometry formalism may be used to describe and study the kinematics of any collision process. Lorentz transformations may thus lie treated as purely geometrical problems. A different way to define a unified trigonometry is also proposed, which is based on the spinor representation of the Lorentz group. This leads to a different and more general formalism than the former one. (auth)

  7. Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice.

    PubMed

    Li, Wen-Jing; Yu, Hui; Yang, Jian-Min; Gao, Jing; Jiang, Hong; Feng, Min; Zhao, Yu-Xia; Chen, Zhe-Yu

    2010-08-06

    Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Can (should) theories of crowding be unified?

    PubMed Central

    Agaoglu, Mehmet N.; Chung, Susana T. L.

    2016-01-01

    Objects in clutter are difficult to recognize, a phenomenon known as crowding. There is little consensus on the underlying mechanisms of crowding, and a large number of models have been proposed. There have also been attempts at unifying the explanations of crowding under a single model, such as the weighted feature model of Harrison and Bex (2015) and the texture synthesis model of Rosenholtz and colleagues (Balas, Nakano, & Rosenholtz, 2009; Keshvari & Rosenholtz, 2016). The goal of this work was to test various models of crowding and to assess whether a unifying account can be developed. Adopting Harrison and Bex's (2015) experimental paradigm, we asked observers to report the orientation of two concentric C-stimuli. Contrary to the predictions of their model, observers' recognition accuracy was worse for the inner C-stimulus. In addition, we demonstrated that the stimulus paradigm used by Harrison and Bex has a crucial confounding factor, eccentricity, which limits its usage to a very narrow range of stimulus parameters. Nevertheless, reporting the orientations of both C-stimuli in this paradigm proved very useful in pitting different crowding models against each other. Specifically, we tested deterministic and probabilistic versions of averaging, substitution, and attentional resolution models as well as the texture synthesis model. None of the models alone was able to explain the entire set of data. Based on these findings, we discuss whether the explanations of crowding can (should) be unified. PMID:27936273

  9. 20 CFR 422.5 - District offices and branch offices.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... office is the manager. The principal officer in each branch office is the officer-in-charge. Each... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false District offices and branch offices. 422.5... and Functions of the Social Security Administration § 422.5 District offices and branch offices. There...

  10. 20 CFR 422.5 - District offices and branch offices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... office is the manager. The principal officer in each branch office is the officer-in-charge. Each... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false District offices and branch offices. 422.5... and Functions of the Social Security Administration § 422.5 District offices and branch offices. There...

  11. Preproghrelin Leu72Met polymorphism in obese Korean children.

    PubMed

    Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

    2005-11-01

    Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

  12. 76 FR 76046 - Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District AGENCY... Valley Unified Air Pollution Control District (SJVUAPCD or District) portion of the California State...), we finalized a limited approval and limited disapproval of San Joaquin Valley Unified Air Pollution...

  13. Patient safety issues in office-based surgery and anaesthesia in Switzerland: a qualitative study.

    PubMed

    McLennan, Stuart; Schwappach, David; Harder, Yves; Staender, Sven; Elger, Bernice

    2017-08-01

    To identify the spectrum of patient safety issues in office-based surgery and anaesthesia in Switzerland. Purposive sample of 23 experts in surgery and anaesthesia and quality and regulation in Switzerland. Data were collected via individual qualitative interviews using a researcher-developed semi-structured interview guide between March 2016 and September 2016. Interviews were transcribed and analysed using conventional content analysis. Issues were categorised under the headings "structure", "process", and "outcome". Experts identified two key overarching patient safety and regulatory issues in relation to office-based surgery and anaesthesia in Switzerland. First, experts repeatedly raised the current lack of data and transparency of the setting. It is unknown how many surgeons are operating in offices, how many and what types of operations are being done, and what the outcomes are. Secondly, experts also noted the limited oversight and regulation of the setting. While some standards exists, most experts felt that more minimal safety standards are needed regarding the requirements that must be met to do office-based surgery and what can and cannot be done in the office-based setting are needed, but they advocated a self-regulatory approach. There is a lack of empirical data regarding the quantity and quality office-based surgery and anaesthesia in Switzerland. Further research is needed to address these research gaps and inform health policy in relation to patient safety in office-based surgery and anaesthesia in Switzerland. Copyright © 2017. Published by Elsevier GmbH.

  14. 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.

  15. Cellular and molecular mechanisms of HGF/Met in the cardiovascular system.

    PubMed

    Gallo, Simona; Sala, Valentina; Gatti, Stefano; Crepaldi, Tiziana

    2015-12-01

    Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the

  16. 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…

  17. 75 FR 28509 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... Joaquin Valley Unified Air Pollution Control District, No. 08-17309 (9th Circuit)). In that case, NAHB...

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  19. Recurrence theorems: A unified account

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wallace, David, E-mail: david.wallace@balliol.ox.ac.uk

    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.

  20. Medical emergencies in a dental office: inhalation and ingestion of orthodontic objects.

    PubMed

    Bilder, Leon; Hazan-Molina, Hagai; Aizenbud, Dror

    2011-01-01

    The authors reviewed the literature regarding inhalation and ingestion of orthodontic appliances and suggest ways to manage and prevent these events. The authors conducted literature searches of free text and Medical Subject Headings terms by using PubMed and Embase databases and selected appropriate studies. They analyzed retrieved articles according to several parameters: inhalation or ingestion event, number of cases, patient's sex and age, type of orthodontic appliance, in-office event or out-of-office event, and medical treatment. The authors found a total of 2,279 articles in their preliminary search. Eighteen reports of 24 cases from this search met all of the search criteria (that is, clinical studies, case reports or reviews limited to English, Hebrew or Arabic on any form of aspiration or inhalation of orthodontic appliances). Most cases (67 percent) involved ingested objects, and of those cases, the majority (57 percent) occurred in female patients. Most cases (85 percent) occurred outside the orthodontist's office. Seventeen patients (71 percent) had been treated with a fixed orthodontic appliance. In 60 percent of cases, the maxilla was involved. With one exception, no severe complications were reported (only seven patients were examined in a hospital emergency department), and patients were discharged uneventfully from the orthodontic office or emergency department. Orthodontists and team members should participate in medical emergency management courses that emphasize the use of guidelines in cases of inhalation or ingestion of orthodontic objects. Each orthodontist's office should develop written emergency protocols for out-of-office events and present them to patients and their parents at the start of treatment.

  1. Triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index as a reference criterion of risk for metabolic syndrome (MetS) and low insulin sensitivity in apparently healthy subjects.

    PubMed

    Baez-Duarte, Blanca Guadalupe; Zamora-Gínez, Irma; González-Duarte, Ramiro; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pérez-Fuentes, Ricardo; Celis, The Multidisciplinary Research Group Of Diabetes

    To evaluate if the TG/HDL-C index can be considered as a reference criterion of MetS and low insulin sensitivity in apparently healthy subjects. The subjects were Mexican mestizos who resided in Puebla City, Mexico, who were anthropometrically, biochemically, and clinically characterized. The TG/HDL-C index was calculated by dividing triglyceride (TG) levels by HDL-C levels. MetS was diagnosed by the Third Report from the Adult Treatment Panel-National Cholesterol Education Program (ATP-III NCEP) criteria, while insulin sensitivity was evaluated by the Quantitative Insulin sensitivity Check Index (QUICKI). The study included 813 subjects, with an average age of 38.6 ± 12.1 years, of which 564 were women and 249 men. An association was found between high TG/HDL-C index and low insulin sensitivity (Odds ratio [OR]: 4.09; p < 0.01) and with MetS (OR: 15.29; p < 0.01). A correlation was found between the TG/HDL-C index and QUICKI (rho: -0.4989; p < 0.01) and with MetS (rho: 0.6581; p < 0.01). The results indicate that the TG/HDL-C index is associated with low insulin sensitivity and MetS in apparently healthy subjects, suggesting this index as a reference criterion of risk for low insulin sensitivity and MetS.

  2. Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

    PubMed Central

    Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

    2016-01-01

    It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

  3. Unified Science Approach K-12, Proficiency Levels 13-21 and Semester Courses.

    ERIC Educational Resources Information Center

    Oickle, Eileen M., Ed.

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

  4. 76 FR 401 - MetLife Insurance Company of Connecticut, et al.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-29544; File No. 812-13816] MetLife Insurance... Section 17(b) of the Act from Section 17(a) of the Act. Applicants: MetLife Insurance Company of Connecticut (``MetLife of CT''), MetLife of CT Separate Account Eleven for Variable Annuities (``Separate...

  5. 75 FR 16205 - MetLife Insurance Company of Connecticut, et al.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-29190; File No. 812-13700] MetLife Insurance... Section 17(b) of the Act from Section 17(a) of the Act. Applicants: MetLife Insurance Company of Connecticut (``MetLife of CT''), MetLife of CT Separate Account Eleven for Variable Annuities (``Separate...

  6. 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.

  7. 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.…

  8. Unified Database Development Program. Final Report.

    ERIC Educational Resources Information Center

    Thomas, Everett L., Jr.; Deem, Robert N.

    The objective of the unified database (UDB) program was to develop an automated information system that would be useful in the design, development, testing, and support of new Air Force aircraft weapon systems. Primary emphasis was on the development of: (1) a historical logistics data repository system to provide convenient and timely access to…

  9. RAAAF’s office landscape The End of Sitting: Energy expenditure and temporary comfort when working in non-sitting postures

    PubMed Central

    de Vries, Rutger; Withagen, Rob

    2017-01-01

    Abstract An earlier study suggested that the activity-inviting office landscape called “The End of Sitting”, designed by Rietveld Architecture Art Affordances (RAAAF), should be considered as an alternative working environment to prevent sedentary behavior. The End of Sitting lacks chairs and tables but consists instead of a myriad of sloped surfaces at different heights that afford workers to stand, lean or recline at different locations. In this study, we assessed the impact of four of its workspaces on physical intensity, temporary comfort and productivity of office work and compared the outcomes with sitting and standing behind a desk. Twenty-four participants worked for 10 minutes in each of the six test conditions. Energy expenditure, measured by indirect calorimetry, and heart rate were recorded. Questionnaires were used to assess the perceived comfort. The number of words found in the word search test was counted as a measure of productivity. The majority of The End of Sitting workspaces led to a significant increase in energy expenditure compared with sitting behind a desk (ps < .05). Average MET values ranged from 1.40 to 1.58 which is a modest rise in energy expenditure compared to sitting (1.32 METs) and not significantly different from standing (1.47 METs). The scores on the general comfort scale indicated that some workspaces were less comfortable than sitting (ps < .05), but the vast majority of participants reported that at least one of The End of Sitting workspaces was equally or more comfortable than sitting. No differences in productivity between the test conditions were found. Further long-term studies are required to assess the behavioral adaptations, productivity and the level of comfort when using The End of Sitting as a permanent office. PMID:29125854

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

    PubMed

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

    2016-03-01

    Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Unified-theory-of-reinforcement neural networks do not simulate the blocking effect.

    PubMed

    Calvin, Nicholas T; J McDowell, J

    2015-11-01

    For the last 20 years the unified theory of reinforcement (Donahoe et al., 1993) has been used to develop computer simulations to evaluate its plausibility as an account for behavior. The unified theory of reinforcement states that operant and respondent learning occurs via the same neural mechanisms. As part of a larger project to evaluate the operant behavior predicted by the theory, this project was the first replication of neural network models based on the unified theory of reinforcement. In the process of replicating these neural network models it became apparent that a previously published finding, namely, that the networks simulate the blocking phenomenon (Donahoe et al., 1993), was a misinterpretation of the data. We show that the apparent blocking produced by these networks is an artifact of the inability of these networks to generate the same conditioned response to multiple stimuli. The piecemeal approach to evaluate the unified theory of reinforcement via simulation is critiqued and alternatives are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Early application of Met-RANTES ameliorates chronic allograft nephropathy.

    PubMed

    Song, Erwei; Zou, Hequn; Yao, Yousheng; Proudfoot, Amanda; Antus, Balazs; Liu, Shanying; Jens, Lutz; Heemann, Uwe

    2002-02-01

    Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.

  13. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  14. New Constraints on the Unified Model of Seyfert Galaxies

    NASA Astrophysics Data System (ADS)

    Maiolino, R.; Ruiz, M.; Rieke, G. H.; Keller, L. D.

    1995-06-01

    We present new 10 microns (N-band) photometry for 70 Seyfert galaxies, 43 of them previously unobserved. These observations, together with those collected from the literature, complete the 10 microns photometry for the CfA Sy galaxies and cover 80% of the Sy found in the RSA and 70% of the Sy in the IRAS 12 microns sample. From this data set, we find that Sy not showing any evidence for broad lines are systematically weaker in 10 microns nuclear emission than Sy nuclei having broad lines. This result may indicate the existence of a group of very low-luminosity Sy2 galaxies that do not have Sy1 counterparts in equal numbers, contrary to the strict unified theory. Alternately, the result can be reconciled with unified theories if a specific type of geometry is assumed for the circumnuclear obscuring material. By comparing the 10 microns ground-based observations with the IRAS 12 microns fluxes, we also study the properties of the extended mid-IR emission, i.e., the star forming activity of the host galaxy of the Sy nucleus. We find Sy2 to lie preferentially in galaxies experiencing enhanced star-forming activity, while Sy1 lie in normal or quiescent galaxies. This result appears to be inconsistent with the strict unified model, since the host galaxy properties should be independent of the orientation of a circumnuclear torus and therefore should be independent of nuclear type. Our finding could be explained by adding to the unified model a link between star-forming activity and the amount of obscuring material collected in the circumnuclear region.

  15. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    NASA Astrophysics Data System (ADS)

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

    2017-09-01

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

  16. The reliability of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing metabolic syndrome (MetS) among Gaza Strip Palestinians.

    PubMed

    Sirdah, Mahmoud M; Abu Ghali, Asmaa S; Al Laham, Nahed A

    2012-01-01

    Metabolic syndrome (MetS) which is a multifaceted syndrome, has been demonstrated as a common precursor for developing cardiovascular diseases and/or type 2 diabetes mellitus. Different diagnostic definitions for MetS have been proposed and recommended. We set up to evaluate the reliabilities of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing MetS among Gaza Strip Palestinians. This cross sectional study involved a randomly selected two hundred and thirty apparently healthy adults from the Gaza Strip. Anthropometric measurements, blood pressure, fasting plasma glucose, lipid profile, and questionnaire interviews were performed. The overall prevalence of MetS in our Gaza Strip cohort was 23.0% and 39.5% according to NCEP/ATP III and IDF definitions respectively (p<0.001). No significant differences were seen in the number of MetS components in individuals having MetS by either definition (mean 3.42 ± 0.63 vs 3.52 ± 0.69 respectively, p=0.865). Both IDF and NCEP/ATP III showed an increased prevalence of MetS with age, and body mass index (BMI), however they revealed different prevalence trends with sex. Except for BMI, there were no significant differences in the general and metabolic related characteristics between subjects with MetS of IDF and NCEP/ATP III definitions. Independently of the definition used, MetS is highly prevalent in Gaza Strip population, with a steady increase in MetS prevalence through age and BMI. The IDF definition tends to give higher values for MetS prevalence, and therefore could be more appropriate for diagnosing MetS in Gaza Strip cohort. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  17. Sandia/Stanford Unified Creep Plasticity Damage Model for ANSYS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pierce, David M.; Vianco, Paul T.; Fossum, Arlo F.

    2006-09-03

    A unified creep plasticity (UCP) model was developed, based upon the time-dependent and time-independent deformation properties of the 95.5Sn-3.9Ag-0.6Cu (wt.%) soldier that were measured at Sandia. Then, a damage parameter, D, was added to the equation to develop the unified creep plasticity damage (UCPD) model. The parameter, D, was parameterized, using data obtained at Sandia from isothermal fatigue experiments on a double-lap shear test. The softwae was validated against a BGA solder joint exposed to thermal cycling. The UCPD model was put into the ANSYS finite element as a subroutine. So, the softwae is the subroutine for ANSYS 8.1.

  18. 20 CFR 422.5 - District offices and branch offices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false District offices and branch offices. 422.5... and Functions of the Social Security Administration § 422.5 District offices and branch offices. There are over 700 social security district offices and branch offices located in the principal cities and...

  19. Incubation, Insight, and Creative Problem Solving: A Unified Theory and a Connectionist Model

    ERIC Educational Resources Information Center

    Helie, Sebastien; Sun, Ron

    2010-01-01

    This article proposes a unified framework for understanding creative problem solving, namely, the explicit-implicit interaction theory. This new theory of creative problem solving constitutes an attempt at providing a more unified explanation of relevant phenomena (in part by reinterpreting/integrating various fragmentary existing theories of…

  20. Inhibition of c-Met as a Therapeutic Strategy for Esophageal Adenocarcinoma

    PubMed Central

    Watson, Gregory A; Zhang, Xinglu; Stang, Michael T; Levy, Ryan M; Queiroz de Oliveira, Pierre E; Gooding, William E; Christensen, James G; Hughes, Steven J

    2006-01-01

    Abstract The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established oncogenic properties. We have previously shown that c-Met is usually overexpressed in esophageal adenocarcinoma (EA), yet the implications of c-Met inhibition in EA remain unknown. Three c-Met-overexpressing EA cell lines (Seg-1, Bic-1, and Flo-1) were used to examine the effects of a c-Met-specific small molecule inhibitor (PHA665752) on cell viability, apoptosis, motility, invasion, and downstream signaling pathways. PHA665752 demonstrated dose-dependent inhibition of constitutive and/or HGF-induced phosphorylation of c-Met, which correlated with reduced cell viability and inhibition of extracellular regulated kinase 1/2 phosphorylation in all three EA cell lines. In contrast, PHA665752 induced apoptosis and reduced motility and invasion in only one EA cell line, Flo-1. Interestingly, Flo-1 was the only cell line in which phosphatidylinositol 3-kinase (PI3K)/Akt was induced following HGF stimulation. The PI3K inhibitor LY294002 produced effects equivalent to those of PHA665752 in these cells. We conclude that inhibition of c-Met may be a useful therapeutic strategy for EA. Factors other than receptor overexpression, such as c-Met-dependent PI3K/Akt signaling, may be predictive of an individual tumor's response to c-Met inhibition. PMID:17132227

  1. 14 CFR § 1221.108 - Establishment of the NASA Unified Visual Communications System.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Establishment of the NASA Unified Visual... ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA Program Identifiers, NASA Flags, and the Agency's Unified Visual...

  2. Contiguous triple spinal dysraphism associated with Chiari malformation Type II and hydrocephalus: an embryological conundrum between the unified theory of Pang and the unified theory of McLone.

    PubMed

    Dhandapani, Sivashanmugam; Srinivasan, Anirudh

    2016-01-01

    Triple spinal dysraphism is extremely rare. There are published reports of multiple discrete neural tube defects with intervening normal segments that are explained by the multisite closure theory of primary neurulation, having an association with Chiari malformation Type II consistent with the unified theory of McLone. The authors report on a 1-year-old child with contiguous myelomeningocele and lipomyelomeningocele centered on Type I split cord malformation with Chiari malformation Type II and hydrocephalus. This composite anomaly is probably due to select abnormalities of the neurenteric canal during gastrulation, with a contiguous cascading impact on both dysjunction of the neural tube and closure of the neuropore, resulting in a small posterior fossa, probably bringing the unified theory of McLone closer to the unified theory of Pang.

  3. Quantitation of Met tyrosine phosphorylation using MRM-MS.

    PubMed

    Meng, Zhaojing; Srivastava, Apurva K; Zhou, Ming; Veenstra, Timothy

    2013-01-01

    Phosphorylation has long been accepted as a key cellular regulator of cell signaling pathways. The recent development of multiple-reaction monitoring mass spectrometry (MRM-MS) provides a useful tool for measuring the absolute quantity of phosphorylation occupancy at pivotal sites within signaling proteins, even when the phosphorylation sites are in close proximity. Here, we described a targeted quantitation approach to measure the absolute phosphorylation occupancy at Y1234 and Y1235 of Met. The approach is utilized to obtain absolute occupancy of the two phosphorylation sites in the full-length recombinant Met. It is further applied to quantitate the phosphorylation state of these two sites in SNU-5 cells treated with a Met inhibitor.

  4. Biases of the MET Temperature and Relative Humidity Sensor (HMP45) Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kyrouac, Jenni; Theisen, Adam

    The U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility Data Quality (DQ) Office was alerted to a potential bias in the surface meteorological instrumentation (MET) temperature when compared with a nearby Mesonet station. This led to an investigation into this problem that was expanded to include many of the other extended facilities (EF) and both the temperature and relative humidity (RH) variables. For this study, the Mesonet was used as the standard reference due to results that showed an increased accuracy in high-humidity environments along with the fact that the Mesonet had previous documented a problemmore » with the HMP45C sensors. Some differences between the sites were taken into account during the analysis: 1. ARM MET sensors were upgraded from an HMP35 to an HMP45 throughout 2007 2. Mesonet switched to aspirated shields in 2009 – To mitigate the differences between aspirated and non-aspirated measurements, data were only analyzed when the wind speed was higher than 3 m/s. This reduced the uncertainty for the non-aspirated measurements from 1.51 ºC to 0.4 ºC. 3. ARM MET is mounted 0.5m higher than the Mesonet station (2.0m versus 1.5m) – This is assumed to have a negligible effect on the differences. 4. Sites were not co-located – For some locations, the distances between sites were as much as 45 km. As part of the investigation into the differences, the Mesonet had reported that the HMP45 sensors had a low-temperature bias in high-humidity environments. This was verified at two different sites where the ARM measurements were compared with the Mesonet measurements. The Mesonet provided redundant temperature measurements from two different sensors at each site. These measurements compared fairly well, while the ARM sensor showed a bias overnight when the humidities were higher. After reviewing the yearly average differences in the data and analyzing the RH data during fog events when we assume it

  5. 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…

  6. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and

  7. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    NASA Astrophysics Data System (ADS)

    Haukka, Harri; Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2016-10-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL).The scientific payload of the Mars MetNet Precursor 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.Full Qualification Model (QM) of the MetNet landing unit with the Precursor Mission payload is currently under functional tests. In the near future the QM unit will be exposed to environmental tests with qualification levels including vibrations, thermal balance, thermal cycling and mechanical impact shock. One complete flight unit of the entry, descent and landing systems (EDLS) has been manufactured and tested with acceptance levels. Another flight-like EDLS has been exposed to most of the qualification tests, and hence it may be used for flight after refurbishments. Accordingly two flight-capable EDLS systems exist. The eventual goal is to create a network of atmospheric observational posts around the Martian surface. The next step in the MetNet Precursor Mission is the demonstration of the technical robustness and scientific capabilities of the MetNet type of landing vehicle. Definition of the Precursor Mission and discussions on launch opportunities are currently under way. The baseline program development funding exists for the next five years. Flight unit manufacture of the payload bay takes about 18 months, and it will be commenced after the Precursor Mission has been defined.

  8. 37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN... Trademark Office as a Designated Office or Elected Office. (a) The United States Patent and Trademark Office...

  9. 37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN... Trademark Office as a Designated Office or Elected Office. (a) The United States Patent and Trademark Office...

  10. 37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN... Trademark Office as a Designated Office or Elected Office. (a) The United States Patent and Trademark Office...

  11. 37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN... Trademark Office as a Designated Office or Elected Office. (a) The United States Patent and Trademark Office...

  12. Unified planning work program federal fiscal year 2008

    DOT National Transportation Integrated Search

    2008-01-01

    This Unified Planning Work Program (UPWP) contains information about surface-transportation planning projects that will be conducted in the Boston metropolitan region during the period of October 1, 2007, through September 30, 2008 (federal fiscal ye...

  13. Sequential EMT-MET induces neuronal conversion through Sox2

    PubMed Central

    He, Songwei; Chen, Jinlong; Zhang, Yixin; Zhang, Mengdan; Yang, Xiao; Li, Yuan; Sun, Hao; Lin, Lilong; Fan, Ke; Liang, Lining; Feng, Chengqian; Wang, Fuhui; Zhang, Xiao; Guo, Yiping; Pei, Duanqing; Zheng, Hui

    2017-01-01

    Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial–mesenchymal transition (EMT) to late mesenchymal–epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ+ cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression. PMID:28580167

  14. MetReS, an Efficient Database for Genomic Applications.

    PubMed

    Vilaplana, Jordi; Alves, Rui; Solsona, Francesc; Mateo, Jordi; Teixidó, Ivan; Pifarré, Marc

    2018-02-01

    MetReS (Metabolic Reconstruction Server) is a genomic database that is shared between two software applications that address important biological problems. Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular networks based on automated text-mining analysis of published scientific literature. Homol-MetReS allows functional (re)annotation of proteomes, to properly identify both the individual proteins involved in the processes of interest and their function. The main goal of this work was to identify the areas where the performance of the MetReS database performance could be improved and to test whether this improvement would scale to larger datasets and more complex types of analysis. The study was started with a relational database, MySQL, which is the current database server used by the applications. We also tested the performance of an alternative data-handling framework, Apache Hadoop. Hadoop is currently used for large-scale data processing. We found that this data handling framework is likely to greatly improve the efficiency of the MetReS applications as the dataset and the processing needs increase by several orders of magnitude, as expected to happen in the near future.

  15. Toward a Unified Theory of Human Reasoning.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.

    1986-01-01

    The goal of this unified theory of human reasoning is to specify what constitutes reasoning and to characterize the psychological distinction between inductive and deductive reasoning. The theory views reasoning as the controlled and mediated application of three processes (encoding, comparison and selective combination) to inferential rules. (JAZ)

  16. A Unified Introduction to Ordinary Differential Equations

    ERIC Educational Resources Information Center

    Lutzer, Carl V.

    2006-01-01

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

  17. Electricity, Relativity and Magnetism: A Unified Text

    NASA Astrophysics Data System (ADS)

    Craik, Derek J.

    2003-09-01

    Electricity, Relativity and Magnetism: A Unified Text presents the first complete and systematic derivation of the principles of magnetism and electromagnetism from Coulomb s law and the theory of special relativity alone. Most books on magnetism introduce the subject in terms of experimental observations, as if magnetism were distinct from, albeit associated with, electricity. The topic of relativity is often mentioned, but almost as an afterthought, rather than as a crucial element of the argument. In this new book from Dr Derek Craik, the important links between electricity and magnetism, via special relativity, are emphasized, leading the reader to a more meaningful and profound understanding of the subject. Electricity, Relativity and Magnetism: A Unified Text gives a simple and brief review of Einstein s special theory of relativity, emphasizing force transformations. An outline of electrostatics, Coulomb s law and its consequences, is also given and is shown to lead to the basis of magnetostatics. Time-dependent electromagnetic effects are introduced naturally via the transformation equations for fields and for potentials, and Maxwell s equations are systematically derived. Magnetic dipoles and magnetization are shown to arise on transforming electric dipoles and polarizations. The author next discusses the application of the theory to practical magnetic calculations, and finally goes on to introduce the quantum theory of magnetism. The concept of spin is introduced, leading to spin statics and magnetic ordering, and spin dynamics and resonances. An account of crystal field theory is included. All whose work and research involves the understanding of magnetic phenomena will find Electricity, Relativity and Magnetism: A Unified Text an invaluable resource which will enhance and deepen their understanding of the subject.

  18. Investigation of unifying transcutaneous transformer for transmission of energy and information.

    PubMed

    Tamura, Nozomi; Yamamoto, Takahiko; Aoki, Hirooki; Koshiji, Kohji; Homma, Akihiko; Tatsumi, Eisuke; Taenaka, Yoshiyuki

    2009-01-01

    When patients are fitted with a totally implantable artificial heart (TAH), they need to be implanted with two additional devices: one for the transmission of energy and one for information. However, this is a cumbersome process that affects the quality of life of the recipient. Therefore, we investigated the use of electromagnetic coupling for the transmission of energy and information and the possibility of unifying two transcutaneous transformers for the simultaneous transmission of energy and information. While unifying the transformers, it is important to suppress the electromagnetic coupling between energy and information transmission. Therefore, we ensured that the electromagnetic fields generated from the transformer windings for the transmissions of information and energy intersected perpendicularly. If the fields are perpendicular, the electromagnetic coupling between the energy and information transmissions will be suppressed significantly. The characteristics of the simultaneous transmission of information and energy using the unified transcutaneous transformer, developed experimentally, were evaluated by changing the number of windings used for the transmission of information. The electromagnetic coupling between the energy and information transmissions was suppressed by determining the direction of the magnetic field. Moreover, the optimum number of transformer windings required for the simultaneous transmission of energy and information was determined. We concluded that the externally coupled transcutaneous transformer unified for the simultaneous transmission of energy and information performed with good transmission characteristics.

  19. Cell membrane organization is important for inner hair cell MET-channel gating

    NASA Astrophysics Data System (ADS)

    Effertz, Thomas; Scharr, Alexandra L.; Ricci, Anthony J.

    2018-05-01

    Specialized sensory cells, hair cells, translate mechanical stimuli into electro/chemical responses. This process, termed mechano-electrical transduction (MET), is localized to the hair cell's sensory organelle, the hair bundle. The mature hair bundle comprises three rows of actin filled stereocilia, arranged in a staircase pattern. Deflections towards the tallest row of stereocilia activate MET channels, residing at the top of stereocilia. While other MET channels can be activated or modulated by changes to their lipid environment, this remains unknown for the mammalian auditory MET channel. We show here that the effect of lipid and cholesterol depletion from the cell membrane affect the MET current as well. We used γ-cyclodextrin to extract lipids form the membrane, reversibly reducing the peak MET current, current adaptation, and decreasing the channels resting open probability. The recovery after γ-cyclodextrin treatment was slower than the initial peak current reduction, suggesting that a specific lipid organization is required for normal MET channel function, which requires time reestablish. Extraction of cholesterol, using Mβ-cyclodextrin, irreversibly reduces the peak MET current and reversibly increases the channel resting open probability, suggesting that cholesterol restricts MET channel opening. This restriction could be useful to increase the channel's signal to noise ratio. Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly restrict gating associated conformational changes of the MET channel.

  20. A Unified Mathematical Definition of Classical Information Retrieval.

    ERIC Educational Resources Information Center

    Dominich, Sandor

    2000-01-01

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

  1. Police officers' views of their encounters with people with personality disorder.

    PubMed

    Martin, T; Thomas, S

    2015-03-01

    In Australia, people experiencing personality disorder have featured little in policing studies and policy or mental health policy and legislation, and in the absence of specific guidance their behaviours represent an ongoing challenge for police. This paper presents police officers' accounts from a qualitative research project that explored police encounters with people experiencing mental illness. The officers singled out people with personality disorder and expressed frustration, anger, powerlessness and resignation with their referrals of this group to health services. Officers reported that emergency departments were reluctant to assess people with personality disorder and when they did assess them stated that the person did not meet criteria for admission to mental health services, or if admitted, they were quickly discharged. People with personality disorder were reported to take up considerable police resources. When police were told by mental health professionals that there was nothing they could do about people experiencing personality disorder, then the question from police was what was to be done with them. While pockets of collaborative practice exist between police and mental health services, much change is required to demonstrate that the needs of the person with personality disorder are being met. © 2013 John Wiley & Sons Ltd.

  2. Have Clinical Trials Properly Assessed c-Met Inhibitors?

    PubMed

    Hughes, Veronica S; Siemann, Dietmar W

    2018-02-01

    The c-Met/HGF pathway is implicated in cancer progression and dissemination. Many inhibitors have been developed to target this pathway. Unfortunately, most trials have failed to demonstrate efficacy. However, clinical trials have not adequately tested the concept of c-Met pathway inhibition due to the lack of appropriate patient selection criteria. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Vision for the Future of Counseling: The 20/20 "Principles for Unifying and Strengthening the Profession"

    ERIC Educational Resources Information Center

    Kaplan, David M.; Gladding, Samuel T.

    2011-01-01

    This article describes the development of the historic "Principles for Unifying and Strengthening the Profession." An outcome of the "20/20: A Vision for the Future of Counseling" initiative, this document delineates a core set of principles that unifies and advances the counseling profession. "Principles for Unifying and Strengthening the…

  4. SB 1082 -- Unified hazardous materials/waste program: Local implementation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jones, W.

    California Senate Bill 1082 was signed into law in the fall of 1993 because business and industry believed there were too many hazardous materials inspectors asking the same questions, looking at the same items and requiring similar information on several variations of the same form. Industry was not happy with the large diversity of programs, each with its own inspectors, permits and fees, essentially doing what industry believed was the same inspection. SB 1082 will allow local city and county agencies to apply to the California Environmental Protection Agency to become a Certified Unified Program Agency (CUPA) or work withmore » a CUPA as a Participating Agency (PA) to manage specific program elements. The CUPA will unify six regulatory programs including hazardous waste/tiered permitting, aboveground storage tanks, underground storage tanks, business and area plans/inventory or disclosure, acutely hazardous materials/risk management prevention and Uniform Fire Code programs related to hazardous materials inventory/plan requirements. The bill requires the CUPA to (1) implement a permit consolidation program; (2) implement a single fee system with a state surcharge; (3) consolidate, coordinate and make consistent any local or regional requirements or guidance documents; and (4) implement a single unified inspection and enforcement program.« less

  5. Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

    PubMed

    Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

    2014-06-14

    A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

  6. The oleocanthal-based homovanillyl sinapate as a novel c-Met inhibitor

    PubMed Central

    Mohyeldin, Mohamed M.; Akl, Mohamed R.; Ebrahim, Hassan Y.; Dragoi, Ana Maria; Dykes, Samantha; Cardelli, James A.; El Sayed, Khalid A.

    2016-01-01

    The hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-Met) signaling axis has gained considerable attention as an attractive molecular target for therapeutic blockade of cancer. Inspired by the chemical structure of S (−)-oleocanthal, a natural secoiridoid from extra-virgin olive oil with documented anticancer activity against c-Met-dependent malignancies, the research presented herein reports on the discovery of the novel olive-derived homovanillyl sinapate (HVS) as a promising c-Met inhibitor. HVS was distinguished for its remarkable potency against wild-type c-Met and its oncogenic variant in cell-free assays and confirmed by in silico docking studies. Furthermore, HVS substantially impaired the c-Met-mediated growth across a broad spectrum of breast cancer cells, while similar treatment doses had no effect on the non-tumorigenic mammary epithelial cell growth. In addition, HVS caused a dose-dependent inhibition of HGF-induced, but not epidermal growth factor (EGF)-induced, cell scattering in addition to HGF-mediated migration, invasion, and 3-dimensional (3D) proliferation of tumor cell spheroids. HVS treatment effects were mediated via inhibition of ligand-mediated c-Met activation and its downstream mitogenic signaling and blocking molecular mediators involved in cellular motility across different cellular contexts. An interesting feature of HVS is its good selectivity for c-Met and Abelson murine leukemia viral oncogene homolog 1 (ABL1) when profiled against a panel of kinases. Docking studies revealed interactions likely to impart high dual affinity for both ABL1 and c-Met kinases. HVS markedly reduced tumor growth, showed excellent pharmacodynamics, and suppressed cell proliferation and microvessel density in an orthotopic model of triple negative breast cancer. Collectively, the present findings suggested that the oleocanthal-based HVS is a promising c-Met inhibitor lead entity with excellent therapeutic potential to control

  7. 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…

  8. 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

  9. Unified theory of the nucleus. [Monograph

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wildermuth, K.; Tang, Y.C.

    1977-01-01

    The purpose of this monograph is to describe a microscopic nuclear theory which can be used to consider all low-energy nuclear phenomena from a unified viewpoint. In this theory, the Pauli principle is completely taken into account and translationally invariant wave functions are always employed. It can be utilized to study reactions initiated not only by nucleons but also by arbitrary composite particles.

  10. 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…

  11. Design and implementation of a unified certification management system based on seismic business

    NASA Astrophysics Data System (ADS)

    Tang, Hongliang

    2018-04-01

    Many business software for seismic systems are based on web pages, users can simply open a browser and enter their IP address. However, how to achieve unified management and security management of many IP addresses, this paper introduces the design concept based on seismic business and builds a unified authentication management system using ASP technology.

  12. An Estimation Procedure for the Structural Parameters of the Unified Cognitive/IRT Model.

    ERIC Educational Resources Information Center

    Jiang, Hai; And Others

    L. V. DiBello, W. F. Stout, and L. A. Roussos (1993) have developed a new item response model, the Unified Model, which brings together the discrete, deterministic aspects of cognition favored by cognitive scientists, and the continuous, stochastic aspects of test response behavior that underlie item response theory (IRT). The Unified Model blends…

  13. MetAMOS: a modular and open source metagenomic assembly and analysis pipeline

    PubMed Central

    2013-01-01

    We describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS. PMID:23320958

  14. Activated HGF-c-Met Axis in Head and Neck Cancer

    PubMed Central

    Arnold, Levi; Enders, Jonathan; Thomas, Sufi Mary

    2017-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K) alpha serine/threonine-protein kinase (Akt), mitogen activate protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes. PMID:29231907

  15. 76 FR 39991 - Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... Deregulatory Actions. SUMMARY: The Regulatory Flexibility Act requires that agencies publish semiannual... agencies have chosen to publish their regulatory agendas as part of the Unified Agenda. Editions of the... Published? III. How Is the Unified Agenda Organized? IV. What Information Appears for Each Entry? V...

  16. 49 CFR 1.48 - Office of the Chief Information Officer.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Office of the Chief Information Officer. 1.48... POWERS AND DUTIES Office of the Secretary Ost Officials § 1.48 Office of the Chief Information Officer. The Chief Information Officer (CIO) is the principal information technology (IT), cyber security...

  17. 49 CFR 1.48 - Office of the Chief Information Officer.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Office of the Chief Information Officer. 1.48... POWERS AND DUTIES Office of the Secretary Ost Officials § 1.48 Office of the Chief Information Officer. The Chief Information Officer (CIO) is the principal information technology (IT), cyber security...

  18. 49 CFR 1.48 - Office of the Chief Information Officer.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Office of the Chief Information Officer. 1.48... POWERS AND DUTIES Office of the Secretary Ost Officials § 1.48 Office of the Chief Information Officer. The Chief Information Officer (CIO) is the principal information technology (IT), cyber security...

  19. MET Receptor Tyrosine Kinase as an Autism Genetic Risk Factor

    PubMed Central

    Peng, Yun; Huentelman, Matthew; Smith, Christopher; Qiu, Shenfeng

    2014-01-01

    In this chapter, we will briefly discuss recent literature on the role of MET receptor tyrosine kinase (RTK) in brain development and how perturbation of MET signaling may alter normal neurodevelopmental outcomes. Recent human genetic studies have established MET as a risk factor for autism, and the molecular and cellular underpinnings of this genetic risk are only beginning to emerge from obscurity. Unlike many autism risk genes that encode synaptic proteins, the spatial and temporal expression pattern of MET RTK indicates this signaling system is ideally situated to regulate neuronal growth, functional maturation, and establishment of functional brain circuits, particularly in those brain structures involved in higher levels of cognition, social skills, and executive functions. PMID:24290385

  20. 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.

  1. Unified Technical Concepts. Application Modules Volume I.

    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 first of two volumes, consists of 56 learning modules dealing with basic concepts of physics. Addressed in the individual chapters of the guide are the following topics: force, work,…

  2. Concept of Draft International Standard for a Unified Approach to Space Program Quality Assurance

    NASA Astrophysics Data System (ADS)

    Stryzhak, Y.; Vasilina, V.; Kurbatov, V.

    2002-01-01

    For want of the unified approach to guaranteed space project and product quality assurance, implementation of many international space programs has become a challenge. Globalization of aerospace industry and participation of various international ventures with diverse quality assurance requirements in big international space programs requires for urgent generation of unified international standards related to this field. To ensure successful fulfillment of space missions, aerospace companies should design and process reliable and safe products with properties complying or bettering User's (or Customer's) requirements. Quality of the products designed or processed by subcontractors (or other suppliers) should also be in compliance with the main user (customer)'s requirements. Implementation of this involved set of unified requirements will be made possible by creating and approving a system (series) of international standards under a generic title Space Product Quality Assurance based on a system consensus principle. Conceptual features of the baseline standard in this system (series) should comprise: - Procedures for ISO 9000, CEN and ECSS requirements adaptation and introduction into space product creation, design, manufacture, testing and operation; - Procedures for quality assurance at initial (design) phases of space programs, with a decision on the end product made based on the principle of independence; - Procedures to arrange incoming inspection of products delivered by subcontractors (including testing, audit of supplier's procedures, review of supplier's documentation), and space product certification; - Procedures to identify materials and primary products applied; - Procedures for quality system audit at the component part, primary product and materials supplier facilities; - Unified procedures to form a list of basic performances to be under configuration management; - Unified procedures to form a list of critical space product components, and unified

  3. 75 FR 2549 - Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a Meeting of the NIH Blue Ribbon... Coordinator, Office of Biotechnology Activities, Office of Science Policy, Office of the Director, National...

  4. Defense.gov Special Report: Unified Combatant Commands

    Science.gov Websites

    in support of U.S. strategic objectives. Their mission is to maintain command and control of U.S coverage and more information. Unified Combatant Command strategic map U.S. Northern Command NORTHCOM U.S U.S. Strategic Command STRATCOM . Main Menu Home Today in DOD About DOD Leaders Biographies

  5. 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

  6. MET receptor tyrosine kinase as an autism genetic risk factor.

    PubMed

    Peng, Yun; Huentelman, Matthew; Smith, Christopher; Qiu, Shenfeng

    2013-01-01

    In this chapter, we will briefly discuss recent literature on the role of MET receptor tyrosine kinase (RTK) in brain development and how perturbation of MET signaling may alter normal neurodevelopmental outcomes. Recent human genetic studies have established MET as a risk factor for autism, and the molecular and cellular underpinnings of this genetic risk are only beginning to emerge from obscurity. Unlike many autism risk genes that encode synaptic proteins, the spatial and temporal expression pattern of MET RTK indicates this signaling system is ideally situated to regulate neuronal growth, functional maturation, and establishment of functional brain circuits, particularly in those brain structures involved in higher levels of cognition, social skills, and executive functions. © 2013 Elsevier Inc. All rights reserved.

  7. Loss of embryonic MET signaling alters profiles of hippocampal interneurons.

    PubMed

    Martins, Gabriela J; Plachez, Céline; Powell, Elizabeth M

    2007-01-01

    Hippocampal interneurons arise in the ventral forebrain and migrate dorsally in response to cues, including hepatocyte growth factor/scatter factor which signals via its receptor MET. Examination of the hippocampus in adult mice in which MET had been inactivated in the embryonic proliferative zones showed an increase in parvalbumin-expressing cells in the dentate gyrus, but a loss of these cells in the CA3 region. An overall loss of calretinin-expressing cells was seen throughout the hippocampus. A similar CA3 deficit of parvalbumin and calretinin cells was observed when MET was eliminated only in postmitotic cells. These data suggest that MET is required for the proper hippocampal development, and embryonic perturbations lead to long-term anatomical defects with possible learning and memory dysfunction.

  8. Toward a unifying framework for evolutionary processes.

    PubMed

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

    2015-10-21

    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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. 75 FR 37727 - Disapproval of California State Implementation Plan Revisions, Monterey Bay Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... California State Implementation Plan Revisions, Monterey Bay Unified Air Pollution Control District AGENCY... to the Monterey Bay Unified Air Pollution Control District (MBUAPCD) portion of the California State... Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental relations...

  10. Lagrangian-Hamiltonian unified formalism for autonomous higher order dynamical systems

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    The Lagrangian-Hamiltonian unified formalism of Skinner and Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, as well as for first-order and higher order field theories. However, a complete generalization to higher order mechanical systems is yet to be described. In this work, after reviewing the natural geometrical setting and the Lagrangian and Hamiltonian formalisms for higher order autonomous mechanical systems, we develop a complete generalization of the Lagrangian-Hamiltonian unified formalism for these kinds of systems, and we use it to analyze some physical models from this new point of view.

  11. Nonlinear adaptive inverse control via the unified model neural network

    NASA Astrophysics Data System (ADS)

    Jeng, Jin-Tsong; Lee, Tsu-Tian

    1999-03-01

    In this paper, we propose a new nonlinear adaptive inverse control via a unified model neural network. In order to overcome nonsystematic design and long training time in nonlinear adaptive inverse control, we propose the approximate transformable technique to obtain a Chebyshev Polynomials Based Unified Model (CPBUM) neural network for the feedforward/recurrent neural networks. It turns out that the proposed method can use less training time to get an inverse model. Finally, we apply this proposed method to control magnetic bearing system. The experimental results show that the proposed nonlinear adaptive inverse control architecture provides a greater flexibility and better performance in controlling magnetic bearing systems.

  12. Office spirometry in primary care pediatrics: a pilot study.

    PubMed

    Zanconato, Stefania; Meneghelli, Giorgio; Braga, Raffaele; Zacchello, Franco; Baraldi, Eugenio

    2005-12-01

    The aim of this study was to investigate the validity of office spirometry in primary care pediatric practices. Ten primary care pediatricians undertook a spirometry training program that was led by 2 pediatric pulmonologists from the Pediatric Department of the University of Padova. After the pediatricians' training, children with asthma or persistent cough underwent a spirometric test in the pediatrician's office and at a pulmonary function (PF) laboratory, in the same day in random order. Both spirometric tests were performed with a portable turbine flow sensor spirometer. We assessed the quality of the spirometric tests and compared a range of PF parameters obtained in the pediatricians' offices and in the PF laboratory according to the Bland and Altman method. A total of 109 children (mean age: 10.4 years; range: 6-15) were included in the study. Eighty-five (78%) of the spirometric tests that were performed in the pediatricians' offices met all of the acceptability and reproducibility criteria. The 24 unacceptable test results were attributable largely to a slow start and failure to satisfy end-of-test criteria. Only the 85 acceptable spirometric tests were considered for analysis. The agreement between the spirometric tests that were performed in the pediatrician's office and in the PF laboratory was good for the key parameters (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow between 25% and 75%). The repeatability coefficient was 0.26 L for forced expiratory volume in 1 second (83 of 85 values fall within this range), 0.30 L for forced vital capacity (81 values fall within this range), and 0.58 L/s for forced expiratory flow between 25% and 75% (82 values fall within this range). In 79% of cases, the primary care pediatricians interpreted the spirometric tests correctly. It seems justifiable to perform spirometry in pediatric primary care, but an integrated approach involving both the primary care pediatrician and

  13. 75 FR 13468 - Disapproval of California State Implementation Plan Revisions, Monterey Bay Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... California State Implementation Plan Revisions, Monterey Bay Unified Air Pollution Control District AGENCY... to the Monterey Bay Unified Air Pollution Control District (MBAPCD) portion of the California State... CFR Part 52 Environmental protection, Air pollution control, Intergovernmental relations, Nitrogen...

  14. Unifying hydrotropy under Gibbs phase rule.

    PubMed

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2017-09-13

    The task of elucidating the mechanism of solubility enhancement using hydrotropes has been hampered by the wide variety of phase behaviour that hydrotropes can exhibit, encompassing near-ideal aqueous solution, self-association, micelle formation, and micro-emulsions. Instead of taking a field guide or encyclopedic approach to classify hydrotropes into different molecular classes, we take a rational approach aiming at constructing a unified theory of hydrotropy based upon the first principles of statistical thermodynamics. Achieving this aim can be facilitated by the two key concepts: (1) the Gibbs phase rule as the basis of classifying the hydrotropes in terms of the degrees of freedom and the number of variables to modulate the solvation free energy; (2) the Kirkwood-Buff integrals to quantify the interactions between the species and their relative contributions to the process of solubilization. We demonstrate that the application of the two key concepts can in principle be used to distinguish the different molecular scenarios at work under apparently similar solubility curves observed from experiments. In addition, a generalization of our previous approach to solutes beyond dilution reveals the unified mechanism of hydrotropy, driven by a strong solute-hydrotrope interaction which overcomes the apparent per-hydrotrope inefficiency due to hydrotrope self-clustering.

  15. 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.

  16. Met Nuclear Localization and Signaling in Breast Cancer

    DTIC Science & Technology

    2006-05-01

    and in germinal regions of many tissues using 4 unique antibodies . Cell fractionation reveals a 60kDa band recognized by C-terminal Met antibodies ...cascades such as Gab1 , Grb2 and PI3K, leading to proliferation, scattering, increased motility, invasion and branching morphogenesis (reviewed in (2...Identification of Met antibodies for use on tissue microarray of normal and cancerous cells, Months 12-24 Task 2. Definition of the domain

  17. The three constituencies of the state: why the state has lost unifying energy.

    PubMed

    King, Desmond; Le Galès, Patrick

    2017-11-01

    We address resurgent populism by examining structural processes of state transformation in the UK, the US and France. Scholars stress the 'unifying energy of the state', a set of institutions and policies capable of limiting inequalities and defending legal regimes. One characteristic of modern Western statehood were packages of policies designed to integrate social groups and territories in part by ensuring common standards of provision and social citizenship across the nation state. This echoes James Scott's critical analysis of the modernist project of the state (1998). This 'unifying energy' had different origins including nationalist movements, combatting external influence or powers, war, and preparing citizens for the rigours of industrialization. Overcoming class differences and territorial differences (including cultural, social and economic differences) was a major source of mobilization to feed this 'unifying energy of the state' in France, Italy or Spain for instance. Political and cultural identities are related in significant part to respective nation states. We argue that this 'unifying energy' was an essential component of statehood in Europe and in the US. It is now largely lost. We explain why and the significance of its displacement. © London School of Economics and Political Science 2017.

  18. Targeting MET and EGFR crosstalk signaling in triple-negative breast cancers

    PubMed Central

    Essenburg, Curt J.; Turner, Lisa; Madaj, Zachary; Winn, Mary E.; Melnik, Marianne K.; Korkaya, Hasan; Maroun, Christiane R.; Christensen, James G.; Steensma, Matthew R.; Boerner, Julie L.; Graveel, Carrie R.

    2016-01-01

    There is a vital need for improved therapeutic strategies that are effective in both primary and metastatic triple-negative breast cancer (TNBC). Current treatment options for TNBC patients are restricted to chemotherapy; however tyrosine kinases are promising druggable targets due to their high expression in multiple TNBC subtypes. Since coexpression of receptor tyrosine kinases (RTKs) can promote signaling crosstalk and cell survival in the presence of kinase inhibitors, it is likely that multiple RTKs will need to be inhibited to enhance therapeutic benefit and prevent resistance. The MET and EGFR receptors are actionable targets due to their high expression in TNBC; however crosstalk between MET and EGFR has been implicated in therapeutic resistance to single agent use of MET or EGFR inhibitors in several cancer types. Therefore it is likely that dual inhibition of MET and EGFR is required to prevent crosstalk signaling and acquired resistance. In this study, we evaluated the heterogeneity of MET and EGFR expression and activation in primary and metastatic TNBC tumorgrafts and determined the efficacy of MET (MGCD265 or crizotinib) and/or EGFR (erlotinib) inhibition against TNBC progression. Here we demonstrate that combined MET and EGFR inhibition with either MGCD265 and erlotinib treatment or crizotinib and erlotinib treatment were highly effective at abrogating tumor growth and significantly decreased the variability in treatment response compared to monotherapy. These results advance our understanding of the RTK signaling architecture in TNBC and demonstrate that combined MET and EGFR inhibition may be a promising therapeutic strategy for TNBC patients. PMID:27655711

  19. 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.

  20. Effects of Positive Unified Behavior Support on Instruction

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  1. 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 10.133 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification...

  2. 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 10.133 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF... Duty Dependent Upon Actual Use § 10.133 Conditions required to be met. When the tariff classification...

  3. Official Japanese Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale: validation against the original English version.

    PubMed

    Kashihara, Kenichi; Kondo, Tomoyoshi; Mizuno, Yoshikuni; Kikuchi, Seiji; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Mochizuki, Hideki; Mori, Hideo; Murata, Miho; Nomoto, Masahiro; Takahashi, Ryosuke; Takeda, Atsushi; Tsuboi, Yoshio; Ugawa, Yoshikazu; Yamanmoto, Mitsutoshi; Yokochi, Fusako; Yoshii, Fumihito; Stebbins, Glenn T; Tilley, Barbara C; Luo, Sheng; Wang, Lu; LaPelle, Nancy R; Goetz, Christopher G

    2014-09-01

    The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results. In this trial, the MDS-UPDRS was translated into Japanese, underwent cognitive pre-testing, and the translation was modified after taking the results into account. The final translation was approved as Official Working Draft of the MDS-UPDRS Japanese version and tested in 365 native-Japanese-speaking patients with PD. Confirmatory analyses were used to determine whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Official Working Draft of the Japanese translation. As a secondary analysis, we used exploratory factor analyses to examine the underlying factor structure without the constraint of a pre-specified factor organization. Confirmatory factor analysis revealed that Comparative Fit Index for all Parts of the MDS-UPDRS exceeded the minimal standard of 0.90 relative to the English version and therefore Japanese translation met the pre-specified criterion to be designated called an OFFICIAL MDS TRANSLATION. Secondary analyses revealed some differences between the English-language MDS-UPDRS and the Japanese translation, however, these differences were considered to be within an acceptable range. The Japanese version of the MDS-UPDRS met the criterion as an Official MDS Translation and is now available for use (www.movementdisorders.org).

  4. Program Development and Effectiveness of Workplace Health Promotion Program for Preventing Metabolic Syndrome among Office Workers

    PubMed Central

    Ryu, Hosihn; Jung, Jiyeon; Cho, Jeonghyun; Chin, Dal Lae

    2017-01-01

    This paper aims to develop and analyze the effects of a socio-ecological model-based intervention program for preventing metabolic syndrome (MetS) among office workers. The intervention program was developed using regular health examinations, a “health behavior and need” assessment survey among workers, and a focus group study. According to the type of intervention, subjects took part in three groups: health education via an intranet-based web magazine (Group 1), self-monitoring with the U-health system (Group 2), and the target population who received intensive intervention (Group 3). The intervention programs of Group 1 and Group 2, which relied on voluntary participation, did not show significant effects. In Group 3, which relied on targeted and proactive programs, showed a decrease in waist circumference and in fasting glucose (p < 0.001). The MetS score in both males (−0.61 ± 3.35 versus −2.32 ± 2.55, p = 0.001) and females (−3.99 ± 2.05 versus −5.50 ± 2.19, p = 0.028) also showed a statistically significant decrease. In light of the effectiveness of the intensive intervention strategy for metabolic syndrome prevention among workers used in this study, companies should establish targeted and proactive health care programs rather than providing a healthcare system that is dependent on an individual’s voluntary participation. PMID:28777320

  5. Program Development and Effectiveness of Workplace Health Promotion Program for Preventing Metabolic Syndrome among Office Workers.

    PubMed

    Ryu, Hosihn; Jung, Jiyeon; Cho, Jeonghyun; Chin, Dal Lae

    2017-08-04

    This paper aims to develop and analyze the effects of a socio-ecological model-based intervention program for preventing metabolic syndrome (MetS) among office workers. The intervention program was developed using regular health examinations, a "health behavior and need" assessment survey among workers, and a focus group study. According to the type of intervention, subjects took part in three groups: health education via an intranet-based web magazine (Group 1), self-monitoring with the U-health system (Group 2), and the target population who received intensive intervention (Group 3). The intervention programs of Group 1 and Group 2, which relied on voluntary participation, did not show significant effects. In Group 3, which relied on targeted and proactive programs, showed a decrease in waist circumference and in fasting glucose ( p < 0.001). The MetS score in both males (-0.61 ± 3.35 versus -2.32 ± 2.55, p = 0.001) and females (-3.99 ± 2.05 versus -5.50 ± 2.19, p = 0.028) also showed a statistically significant decrease. In light of the effectiveness of the intensive intervention strategy for metabolic syndrome prevention among workers used in this study, companies should establish targeted and proactive health care programs rather than providing a healthcare system that is dependent on an individual's voluntary participation.

  6. c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

    PubMed

    Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2018-03-02

    Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. 76 FR 67369 - Revisions to the California State Implementation Plan, Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... the California State Implementation Plan, Joaquin Valley Unified Air Pollution Control District and Imperial County Air Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is finalizing approval of revisions to the San Joaquin Valley Unified Air Pollution...

  8. Epigenetic Upregulation of HGF and c-Met Drives Metastasis in Hepatocellular Carcinoma

    PubMed Central

    Ogunwobi, Olorunseun O.; Puszyk, William; Dong, Hui-Jia; Liu, Chen

    2013-01-01

    Hepatocyte growth factor (HGF) and its receptor, c-Met, are important regulators of growth and differentiation of healthy hepatocytes. However, upregulation of HGF and c-Met have been associated with tumor progression and metastasis in hepatocellular carcinoma (HCC). Hematogenous dissemination is the most common route for cancer metastasis, but the role of HGF and c-Met in circulating tumor cells (CTCs) is unknown. We have isolated and established a circulating tumor cell line from the peripheral blood of a mouse HCC model. Our studies show that these CTCs have increased expression of HGF and c-Met in comparison to the primary tumor cells. The CTCs display phenotypic evidence of epithelial-mesenchymal transition (EMT) and the EMT appears to be inducible by HGF. Epigenetic analysis of the c-Met promoter identified significant loss of DNA methylation in CTCs which correlated with overexpression of c-Met and increased expression of HGF. Six specific CpG sites of c-Met promoter demethylation were identified. CTCs show significantly increased tumorigenicity and metastatic potential in a novel orthotopic syngeneic model of metastatic HCC. We conclude that during hematogenous dissemination in HCC, CTCs undergo EMT under the influence of increased HGF. This process also involves up regulation of c-Met via promoter demethylation at 6 CpG sites. Consequently, targeting HGF and c-Met expression by CTCs may be a novel non-invasive approach with potential clinical applications in HCC management. PMID:23723997

  9. 75 FR 15713 - Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a Meeting of the NIH Blue Ribbon... Lewallen, Advisory Committee Coordinator, Office of Biotechnology Activities, Office of Science Policy...

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

    PubMed Central

    2015-01-01

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

  11. Unified implementation of the reference architecture : concept of operations.

    DOT National Transportation Integrated Search

    2015-10-19

    This document describes the Concept of Operations (ConOps) for the Unified Implementation of the Reference Architecture, located in Southeast Michigan, which supports connected vehicle research and development. This ConOps describes the current state...

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

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

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

  13. Rocket experiment METS Microwave Energy Transmission in Space

    NASA Astrophysics Data System (ADS)

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A METS (Microwave Energy Transmission in Space) rocket experiment is being planned by the SPS (Solar Power Satellite) Working Group at the Institute of Space and Astronautical Science (ISAS) in Japan for the forthcoming International Space Year (ISY), 1992. The METS experiment is an advanced version of our MINIX rocket experiment. This paper describes the conceptual design for the METS rocket experiment. Aims are to verify the feasibility of a newly developed microwave energy transmission system designed for use in space and to study nonlinear effects of the microwave energy beam on space plasma. A high power microwave (936 W) will be transmitted by a new phase-array antenna from a mother rocket to a separate target (daughter rocket) through the Earth's ionospheric plasma. The active phased-array system has the capability of being able to focus the microwave energy at any spatial point by individually controlling the digital phase shifters.

  14. Rocket experiment METS - Microwave Energy Transmission in Space

    NASA Astrophysics Data System (ADS)

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A Microwave Energy Transmission in Space (METS) rocket experiment is being planned by the Solar Power Satellite Working Group at the Institute of Space and Astronautical Science in Japan for the forthcoming International Space Year, 1992. The METS experiment is an advanced version of the previous MINIX rocket experiment (Matsumoto et al., 1990). This paper describes a conceptual design of the METS rocket experiment. It aims at verifying a newly developed microwave energy transmission system for space use and to study nonlinear effects of the microwave energy beam in the space plasma environment. A high power microwave of 936 W will be transmitted by the new phased-array antenna from a mother rocket to a separated target (daughter rocket) through the ionospheric plasma. The active phased-array system has a capability of focusing the microwave energy around any spatial point by controlling the digital phase shifters individually.

  15. Medical Response to Haiti Earthquake: Operation Unified Response

    DTIC Science & Technology

    2011-01-24

    NGO’s • 1500 patients seen • 4 tons medical supplies Operation UNIFIED RESPONSE Medical Logistics Support 18 Support to PROMESS Warehouse ... Logistics Advisory Team  Re-organized warehouse  Provided inventory mgmt  Teams at port to organize donations  Forklift support Operation UNIFIED

  16. 75 FR 10293 - Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Office of Biotechnology Activities; Office of Science Policy; Office of the Director; Notice of a Meeting of the NIH Blue Ribbon... Activities, Office of Science Policy, Office of the Director, National Institutes of Health, 6705 Rockledge...

  17. Hepatocyte growth factor sensitizes brain tumors to c-MET kinase inhibition

    PubMed Central

    Zhang, Ying; Farenholtz, Kaitlyn E.; Yang, Yanzhi; Guessous, Fadila; diPierro, Charles G.; Calvert, Valerie S.; Deng, Jianghong; Schiff, David; Xin, Wenjun; Lee, Jae K.; Purow, Benjamin; Christensen, James; Petricoin, Emanuel; Abounader, Roger

    2013-01-01

    Purpose The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not well known molecular determinants that predict responsiveness to c-MET inhibitors, and to explore new strategies for improving inhibitor efficacy in brain tumors. Experimental design We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells (GSCs), and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. Results We found that HGF co-expression is a key predictor of response to c-MET inhibition among the examined factors, and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and non-responsive cells. Surprisingly, we also found that short pre-treatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the anti-tumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGFR small molecule kinase inhibitor. Conclusions These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition, and propose ligand pre-treatment as a potential new strategy for improving the anti-cancer efficacy of RTK inhibitors. PMID:23386689

  18. 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

    ... the California State Implementation Plan, Joaquin Valley Unified Air Pollution Control District AGENCY... the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portions of the California... U.S.C. 804(2). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  19. 49 CFR 800.25 - Delegation to the Directors of Office of Aviation Safety, Office of Railroad Safety, Office of...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Delegation to the Directors of Office of Aviation... Office of Aviation Safety, Office of Railroad Safety, Office of Highway Safety, Office of Marine Safety... Offices of Aviation, Railroad, Highway, Marine, and Pipeline and Hazardous Materials Safety, the authority...

  20. 49 CFR 800.25 - Delegation to the Directors of Office of Aviation Safety, Office of Railroad Safety, Office of...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Delegation to the Directors of Office of Aviation... Office of Aviation Safety, Office of Railroad Safety, Office of Highway Safety, Office of Marine Safety... Offices of Aviation, Railroad, Highway, Marine, and Pipeline and Hazardous Materials Safety, the authority...

  1. 49 CFR 800.25 - Delegation to the Directors of Office of Aviation Safety, Office of Railroad Safety, Office of...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Delegation to the Directors of Office of Aviation... Office of Aviation Safety, Office of Railroad Safety, Office of Highway Safety, Office of Marine Safety... Offices of Aviation, Railroad, Highway, Marine, and Pipeline and Hazardous Materials Safety, the authority...

  2. 49 CFR 800.25 - Delegation to the Directors of Office of Aviation Safety, Office of Railroad Safety, Office of...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Delegation to the Directors of Office of Aviation... Office of Aviation Safety, Office of Railroad Safety, Office of Highway Safety, Office of Marine Safety... Offices of Aviation, Railroad, Highway, Marine, and Pipeline and Hazardous Materials Safety, the authority...

  3. 49 CFR 800.25 - Delegation to the Directors of Office of Aviation Safety, Office of Railroad Safety, Office of...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Office of Aviation Safety, Office of Railroad Safety, Office of Highway Safety, Office of Marine Safety... Offices of Aviation, Railroad, Highway, Marine, and Pipeline and Hazardous Materials Safety, the authority... 49 Transportation 7 2010-10-01 2010-10-01 false Delegation to the Directors of Office of Aviation...

  4. c-Met must translocate to the nucleus to initiate calcium signals.

    PubMed

    Gomes, Dawidson A; Rodrigues, Michele A; Leite, M Fatima; Gomez, Marcus V; Varnai, Peter; Balla, Tamas; Bennett, Anton M; Nathanson, Michael H

    2008-02-15

    Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca(2+) signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin beta1, and formation of Ca(2+) signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.

  5. Reduction of parameters in Finite Unified Theories and the MSSM

    NASA Astrophysics Data System (ADS)

    Heinemeyer, Sven; Mondragón, Myriam; Tracas, Nicholas; Zoupanos, George

    2018-02-01

    The method of reduction of couplings developed by W. Zimmermann, combined with supersymmetry, can lead to realistic quantum field theories, where the gauge and Yukawa sectors are related. It is the basis to find all-loop Finite Unified Theories, where the β-function vanishes to all-loops in perturbation theory. It can also be applied to the Minimal Supersymmetric Standard Model, leading to a drastic reduction in the number of parameters. Both Finite Unified Theories and the reduced MSSM lead to successful predictions for the masses of the third generation of quarks and the Higgs boson, and also predict a heavy supersymmetric spectrum, consistent with the non-observation of supersymmetry so far.

  6. Transcultural nursing as a global care humanizer, diversifier, and unifier.

    PubMed

    Leininger, M M

    1997-01-01

    Three dominant themes of transcultural nursing as a global humanizer, diversifier, and unifier are discussed in relation to their meaning and uses in education, practice, research and consultation. The presenter takes the position that these three dominant themes are essential and imperative to promote, transform, and maintain desired care outcomes which are beneficial, satisfying, and healthy for people of diverse and similar cultures. The three themes are discussed within Leininger's theory of Culture Care Diversity and Universality with focus on the modes of action and decision-making. The author encourages transcultural nurses to take leadership to be an active global humanizer, diversifier, and unifier and transform nursing and health care into the 21st century.

  7. 10 CFR 1.39 - Office of the Chief Human Capital Officer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Office of the Chief Human Capital Officer. 1.39 Section 1... Headquarters Staff Offices § 1.39 Office of the Chief Human Capital Officer. The Office of the Chief Human... effective organization, utilization, and development of the agency's human resources; (b) Provides labor...

  8. LDA-Based Unified Topic Modeling for Similar TV User Grouping and TV Program Recommendation.

    PubMed

    Pyo, Shinjee; Kim, Eunhui; Kim, Munchurl

    2015-08-01

    Social TV is a social media service via TV and social networks through which TV users exchange their experiences about TV programs that they are viewing. For social TV service, two technical aspects are envisioned: grouping of similar TV users to create social TV communities and recommending TV programs based on group and personal interests for personalizing TV. In this paper, we propose a unified topic model based on grouping of similar TV users and recommending TV programs as a social TV service. The proposed unified topic model employs two latent Dirichlet allocation (LDA) models. One is a topic model of TV users, and the other is a topic model of the description words for viewed TV programs. The two LDA models are then integrated via a topic proportion parameter for TV programs, which enforces the grouping of similar TV users and associated description words for watched TV programs at the same time in a unified topic modeling framework. The unified model identifies the semantic relation between TV user groups and TV program description word groups so that more meaningful TV program recommendations can be made. The unified topic model also overcomes an item ramp-up problem such that new TV programs can be reliably recommended to TV users. Furthermore, from the topic model of TV users, TV users with similar tastes can be grouped as topics, which can then be recommended as social TV communities. To verify our proposed method of unified topic-modeling-based TV user grouping and TV program recommendation for social TV services, in our experiments, we used real TV viewing history data and electronic program guide data from a seven-month period collected by a TV poll agency. The experimental results show that the proposed unified topic model yields an average 81.4% precision for 50 topics in TV program recommendation and its performance is an average of 6.5% higher than that of the topic model of TV users only. For TV user prediction with new TV programs, the average

  9. Neurological exclusiveness or unified science inclusiveness: Comment on Schwartz et al. (2016).

    PubMed

    Staats, Arthur W

    2016-12-01

    Schwartz, Lilienfeld, Meca, and Sauvigné (2016) argue effectively and productively that neuroscience is monistic (excludes other fields) in a way that affects negatively psychology department makeup, psychology grant support, and the way students are trained. They conclude, rather, that it is important to effect an inclusion of different fields of psychology. This paper broadens and strengthens their position. However, it also points out that a call for inclusiveness raises a central question. How is inclusiveness to be accomplished? Without stipulation to the contrary the call is for an eclecticism. As Schwartz et al. indicate, unified theory is now rejected because grand theory in the past has been monistic. However, science moves on; there are unified theories today that are inclusive. Thus, development of an area in psychology is needed that studies, evaluates, and advances works that unify inclusively, the present article being an example. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Evaluation of the Unified Compensation and Classification Plan.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL. Office of Educational Accountability.

    The Unified Classification and Compensation Plan of the Dade County (Florida) Public Schools consists of four interdependent activities that include: (1) developing and maintaining accurate job descriptions, (2) conducting evaluations that recommend job worth and grade, (3) developing and maintaining rates of compensation for job values, and (4)…

  11. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption

    PubMed Central

    2014-01-01

    One line summary Metabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems. The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred

  12. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

    PubMed Central

    2012-01-01

    Background Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC. PMID:22962849

  13. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

    PubMed

    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  14. [Met5]Enkephalin content in brain regions of rats treated with lithium.

    PubMed Central

    Gillin, J C; Hong, J S; Yang, H Y; Costa, E

    1978-01-01

    In rats, chronic treatment with lithium elicits a dose-dependent increase in the [Met5]enkephalin content of nucleus caudatus and globus pallidus. A single injection of lithium fails to change the striatal [Met5]enkephalin content. The increase in [Met5]enkephalin caused by chronic lithium is proportional to the serum lithium level. The extent of the increase in striatal [Met5]enkephalin content levels off at a value of about 250% that of untreated rats. This increase has a time latency of 2--3 days and reaches a plateau at 5 days. The increase that was present at 5 days was no longer evident if the treatment was continued for 2 weeks. Lithium also increases striatal [Leu5]enkephalin content by an extent equal to the increase of [Met 5]enkephalin. Based on the characteristics of the lithium-induced increase in [Met6]enkephalin content, it is proposed that lithium may reduce the rate of release of [Met5]enkephalin from the small enkephalinergic neurons that are intrinsic to the striatum; this action may be related to a change in the regulation of striatal neurons. PMID:275866

  15. Office of the Chief Financial Officer Annual Report 2009

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fernandez, Jeffrey

    2009-12-15

    Presented is the 2009 Chief Financial Officer's Annual Report. The data included in this report has been compiled from the Budget Office, the Controller, Procurement and Property Management and the Sponsored Projects Office.

  16. Extraboard performance : TriMet case study.

    DOT National Transportation Integrated Search

    2012-02-01

    This paper examines extraboard operations and management at TriMet, the transit provider for the Portland Oregon metropolitan area. The : extraboard consists of a pool of operators who fill open work resulting from absences and other causes. The pape...

  17. Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

    PubMed

    Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

    2006-03-01

    Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

  18. User's Guide for MetView: A Meteorological Display and Assessment Tool

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Glantz, Clifford S.; Pelton, Mitchell A.; Allwine, K Jerry

    2000-09-27

    MetView Version 2.0 is an easy-to-use model for accessing, viewing, and analyzing meteorological data. MetView provides both graphical and numerical displays of data. It can accommodate data from an extensive meteorological monitoring network that includes near-surface monitoring locations, instrumented towers, sodars, and meteorologist observations. MetView is used operationally for both routine, emergency response, and research applications at the U.S. Department of Energy's Hanford Site. At the Site's Emergency Operations Center, MetView aids in the access, visualization, and interpretation of real-time meteorological data. Historical data can also be accessed and displayed. Emergency response personnel at the Emergency Operations Center use MetViewmore » products in the formulation of protective action recommendations and other decisions. In the initial stage of an emergency, MetView can be operated using a very simple, five-step procedure. This first-responder procedure allows non-technical staff to rapidly generate meteorological products and disseminate key information. After first-responder information products are produced, the Emergency Operations Center's technical staff can conduct more sophisticated analyses using the model. This may include examining the vertical variation in winds, assessing recent changes in atmospheric conditions, evaluating atmospheric mixing rates, and forecasting changes in meteorological conditions. This user's guide provides easy-to-follow instructions for both first-responder and routine operation of the model. Examples, with explanations, are provided for each type of MetView output display. Information is provided on the naming convention, format, and contents of each type of meteorological data file used by the model area. This user's guide serves as a ready reference for experienced MetView users and a training manual for new users.« less

  19. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

    PubMed

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  20. Toward a Unified Theory of Visual Area V4

    PubMed Central

    Roe, Anna W.; Chelazzi, Leonardo; Connor, Charles E.; Conway, Bevil R.; Fujita, Ichiro; Gallant, Jack L.; Lu, Haidong; Vanduffel, Wim

    2016-01-01

    Visual area V4 is a midtier cortical area in the ventral visual pathway. It is crucial for visual object recognition and has been a focus of many studies on visual attention. However, there is no unifying view of V4’s role in visual processing. Neither is there an understanding of how its role in feature processing interfaces with its role in visual attention. This review captures our current knowledge of V4, largely derived from electrophysiological and imaging studies in the macaque monkey. Based on recent discovery of functionally specific domains in V4, we propose that the unifying function of V4 circuitry is to enable selective extraction of specific functional domain-based networks, whether it be by bottom-up specification of object features or by top-down attentionally driven selection. PMID:22500626

  1. Unified Formulation of the Aeroelasticity of Swept Lifting Surfaces

    NASA Technical Reports Server (NTRS)

    Silva, Walter; Marzocca, Piergiovanni; Librescu, Liviu

    2001-01-01

    An unified approach for dealing with stability and aeroelastic response to time-dependent pressure pulses of swept wings in an incompressible flow is developed. To this end the indicial function concept in time and frequency domains, enabling one to derive the proper unsteady aerodynamic loads is used. Results regarding stability in the frequency and time domains, and subcritical aeroelastic response to arbitrary time-dependent external excitation obtained via the direct use of the unsteady aerodynamic derivatives for 3-D wings are supplied. Closed form expressions for unsteady aerodynamic derivatives using this unified approach have been derived and used to illustrate their application to flutter and aeroelastic response to blast and sonic-boom signatures. In this context, an original representation of the aeroelastic response in the phase space was presented and pertinent conclusions on the implications of some basic parameters have been outlined.

  2. 77 FR 5709 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... pollution control, Incorporation by reference, Intergovernmental relations, Nitrogen dioxide, Ozone...

  3. San Francisco Unified School District: 2013 Survey Brief

    ERIC Educational Resources Information Center

    Center for Education Policy Analysis at Stanford University, 2013

    2013-01-01

    Since the 2009-10 school-year, the Center for Education Policy Analysis (CEPA) at Stanford University administered Teacher, Assistant Principal (AP), and Principal surveys as part of San Francisco Unified School District's (SFUSD's) evaluation of the Quality Teacher and Education Act (passed as Proposition A 2008). The findings from these surveys…

  4. Catastrophe Theory: A Unified Model for Educational Change.

    ERIC Educational Resources Information Center

    Cryer, Patricia; Elton, Lewis

    1990-01-01

    Catastrophe Theory and Herzberg's theory of motivation at work was used to create a model of change that unifies and extends Lewin's two separate stage and force field models. This new model is used to analyze the behavior of academics as they adapt to the changing university environment. (Author/MLW)

  5. DataSpread: Unifying Databases and Spreadsheets.

    PubMed

    Bendre, Mangesh; Sun, Bofan; Zhang, Ding; Zhou, Xinyan; Chang, Kevin ChenChuan; Parameswaran, Aditya

    2015-08-01

    Spreadsheet software is often the tool of choice for ad-hoc tabular data management, processing, and visualization, especially on tiny data sets. On the other hand, relational database systems offer significant power, expressivity, and efficiency over spreadsheet software for data management, while lacking in the ease of use and ad-hoc analysis capabilities. We demonstrate DataSpread, a data exploration tool that holistically unifies databases and spreadsheets. It continues to offer a Microsoft Excel-based spreadsheet front-end, while in parallel managing all the data in a back-end database, specifically, PostgreSQL. DataSpread retains all the advantages of spreadsheets, including ease of use, ad-hoc analysis and visualization capabilities, and a schema-free nature, while also adding the advantages of traditional relational databases, such as scalability and the ability to use arbitrary SQL to import, filter, or join external or internal tables and have the results appear in the spreadsheet. DataSpread needs to reason about and reconcile differences in the notions of schema, addressing of cells and tuples, and the current "pane" (which exists in spreadsheets but not in traditional databases), and support data modifications at both the front-end and the back-end. Our demonstration will center on our first and early prototype of the DataSpread, and will give the attendees a sense for the enormous data exploration capabilities offered by unifying spreadsheets and databases.

  6. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    PubMed

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  7. 76 FR 70886 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... CFR Part 52 Environmental protection, Air pollution control, Incorporation by reference...

  8. 77 FR 73322 - Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... the California State Implementation Plan, Monterey Bay Unified Air Pollution Control District AGENCY... approve revisions to the Monterey Bay Unified Air Pollution Control District (MBUAPCD) portion of the... Part 52 Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental...

  9. 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

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve a revision to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of..., Air pollution control, Intergovernmental relations, Ozone, Reporting and recordkeeping requirements...

  10. 76 FR 5276 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... protection, Air pollution control, Incorporation by reference, Intergovernmental relations, Nitrogen dioxide...

  11. Unified phenology model with Bayesian calibration for several European species in Belgium

    NASA Astrophysics Data System (ADS)

    Fu, Y. S. H.; Demarée, G.; Hamdi, R.; Deckmyn, A.; Deckmyn, G.; Janssens, I. A.

    2009-04-01

    Plant phenology is a good bio-indicator for climate change, and this has brought a significant increase of interest. Many kinds of phenology models have been developed to analyze and predict the phenological response to climate change, and those models have been summarized into one kind of unified model, which could be applied to different species and environments. In our study, we selected seven European woody plant species (Betula verrucosa, Quercus robur pedunculata, Fagus sylvatica, Fraxinus excelsior, Symphoricarpus racemosus, Aesculus hippocastanum, Robinia pseudoacacia) occurring in five sites distributed across Belgium. For those sites and tree species, phenological observations such as bud burst were available for the period 1956 - 2002. We also obtained regional downscaled climatic data for each of these sites, and combined both data sets to test the unified model. We used a Bayesian approach to generate distributions of model parameters from the observation data. In this poster presentation, we compare parameter distributions between different species and between different sites for individual species. The results of the unified model show a good agreement with the observations, except for Fagus sylvatica. The failure to reproduce the bud burst data for Fagus sylvatica suggest that the other factors not included in the unified model affect the phenology of this species. The parameter series show differences among species as we expected. However, they also differed strongly for the same species among sites.Further work should elucidate the mechanism that explains why model parameters differ among species and sites.

  12. Unified sensor management in unknown dynamic clutter

    NASA Astrophysics Data System (ADS)

    Mahler, Ronald; El-Fallah, Adel

    2010-04-01

    In recent years the first author has developed a unified, computationally tractable approach to multisensor-multitarget sensor management. This approach consists of closed-loop recursion of a PHD or CPHD filter with maximization of a "natural" sensor management objective function called PENT (posterior expected number of targets). In this paper we extend this approach so that it can be used in unknown, dynamic clutter backgrounds.

  13. Negative Suppressors of Oncogenic Activation of the Met Receptor Tyrosine Kinase

    DTIC Science & Technology

    2007-03-01

    transfected with HA Gab1 , cells were stimulated, fixed with 3% PFA and stained with antibodies against HA (green) and endogenous Met (red). White...oncogenic activation through deregulate endocytosis. My recent work has uncovered a novel role for the Gab1 scaffold in regulating Met internalization and...I show that Gab1 localizes to CDRs and recruits the Met receptor to this plasma membrane compartment where receptors are then internalized into the

  14. 76 FR 37044 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... Glass Manufacturing'', US EPA, June 1994. 7. ``Integrated Pollution Prevention and Control (IPPC...

  15. 77 FR 66429 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... 1994. 11. ``Integrated Pollution Prevention and Control (IPPC) Reference Document on Best Available...

  16. 77 FR 24883 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental...

  17. 76 FR 52623 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental relations...

  18. 76 FR 56706 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental...

  19. 77 FR 35329 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental...

  20. Unifying decoherence and the Heisenberg Principle

    NASA Astrophysics Data System (ADS)

    Janssens, Bas

    2017-08-01

    We exhibit three inequalities involving quantum measurement, all of which are sharp and state independent. The first inequality bounds the performance of joint measurement. The second quantifies the trade-off between the measurement quality and the disturbance caused on the measured system. Finally, the third inequality provides a sharp lower bound on the amount of decoherence in terms of the measurement quality. This gives a unified description of both the Heisenberg uncertainty principle and the collapse of the wave function.

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

    ERIC Educational Resources Information Center

    Alabama State Commission on Higher Education, Montgomery.

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

  2. A Firsthand Comparison of a System Office to a College Office

    ERIC Educational Resources Information Center

    Hom, Willard C.

    2010-01-01

    System offices for community college institutional research differ in many ways from campus offices for community college institutional research. The other chapters in this volume describe salient characteristics of system IR offices, but many readers may want to see a direct comparison of system IR offices to campus IR offices in the community…

  3. HGF/MET-directed therapeutics in gastroesophageal cancer: a review of clinical and biomarker development.

    PubMed

    Hack, Stephen P; Bruey, Jean-Marie; Koeppen, Hartmut

    2014-05-30

    Aberrant activation of the HGF/MET signaling axis has been strongly implicated in the malignant transformation and progression of gastroesophageal cancer (GEC). MET receptor overexpression in tumor samples from GEC patients has been consistently correlated with an aggressive metastatic phenotype and poor prognosis. In preclinical GEC models, abrogation of HGF/MET signaling has been shown to induce tumor regression as well as inhibition of metastatic dissemination. Promising clinical results in patient subsets in which MET is overexpressed have spurned several randomized studies of HGF/MET-directed agents, including two pivotal global Phase III trials. Available data highlight the need for predictive biomarkers in order to select patients most likely to benefit from HGF/MET inhibition. In this review, we discuss the current knowledge of mechanisms of MET activation in GEC, the current status of the clinical evaluation of MET-targeted therapies in GEC, characteristics of ongoing randomized GEC trials and the associated efforts to identify and validate biomarkers. We also discuss the considerations and challenges for HGF/MET inhibitor drug development in the GEC setting.

  4. HGF/MET-directed therapeutics in gastroesophageal cancer: a review of clinical and biomarker development

    PubMed Central

    Hack, Stephen P.; Bruey, Jean-Marie; Koeppen, Hartmut

    2014-01-01

    Aberrant activation of the HGF/MET signaling axis has been strongly implicated in the malignant transformation and progression of gastroesophageal cancer (GEC). MET receptor overexpression in tumor samples from GEC patients has been consistently correlated with an aggressive metastatic phenotype and poor prognosis. In preclinical GEC models, abrogation of HGF/MET signaling has been shown to induce tumor regression as well as inhibition of metastatic dissemination. Promising clinical results in patient subsets in which MET is overexpressed have spurned several randomized studies of HGF/MET-directed agents, including two pivotal global Phase III trials. Available data highlight the need for predictive biomarkers in order to select patients most likely to benefit from HGF/MET inhibition. In this review, we discuss the current knowledge of mechanisms of MET activation in GEC, the current status of the clinical evaluation of MET-targeted therapies in GEC, characteristics of ongoing randomized GEC trials and the associated efforts to identify and validate biomarkers. We also discuss the considerations and challenges for HGF/MET inhibitor drug development in the GEC setting. PMID:24930887

  5. 76 FR 69135 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Incorporation by...

  6. 77 FR 64427 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-22

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the..., Gas, and Geothermal Resources confirmed that in the Ventura County Air Pollution Control District...

  7. 76 FR 16696 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVAPCD) portion of the...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  8. 75 FR 24408 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVAPCD) portion of the...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  9. 75 FR 1715 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVAPCD) portion of the...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  10. 76 FR 68106 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  11. 76 FR 45212 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... proposing to approve San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) Rule 3170... (CAA or Act). EPA is also proposing to approve SJVUAPCD's fee-equivalent program, which includes Rule...

  12. METs in adults while playing active video games: a metabolic chamber study.

    PubMed

    Miyachi, Motohiko; Yamamoto, Kenta; Ohkawara, Kazunori; Tanaka, Shigeho

    2010-06-01

    Active video game systems controlled through arm gestures and motions (Nintendo Wii Sports) and video games controlled through force plate (Wii Fit Plus) are becoming increasingly popular. This study was performed to determine the energy expenditure (EE) during Wii Fit Plus and Wii Sports game activities. Twelve adult men and women performed all the activities of Wii Sports (five activities: golf, bowling, tennis, baseball, and boxing) and Wii Fit Plus (63 activities classified as yoga, resistance, balance, and aerobic exercises). Each activity was continued for at least 8 min to obtain a steady-state EE. Because EE was assessed in an open-circuit indirect metabolic chamber consisting of an airtight room (20,000 or 15,000 L), subjects were freed of apparatus to collect expired gas while playing the games. MET value was calculated from resting EE and steady-state EE during activity. The mean MET values of all 68 activities were distributed over a wide range from 1.3 METs (Lotus Focus) to 5.6 METs (single-arm stand). The mean MET values in yoga, balance, resistance, and aerobic exercise of Wii Fit Plus and Wii Sports were 2.1, 2.0, 3.2, 3.4, and 3.0 METs, respectively. Forty-six activities (67%) were classified as light intensity (<3 METs), and 22 activities (33%) were classified as moderate intensity (3.0-6.0 METs). There were no vigorous-intensity activities (>6.0 METs). Time spent playing one-third of the activities supplied by motion- and gesture-controlled video games can count toward the daily amount of exercise required according to the guidelines provided by the American College of Sports Medicine and the American Heart Association, which focus on 30 min of moderate-intensity daily physical activity 5 d x wk(-1).

  13. Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

    PubMed Central

    Zhang, Yilong; Jain, Rajul K.; Zhu, Min

    2015-01-01

    The hepatocyte growth factor (HGF): MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed. PMID:28536405

  14. A Unified Analysis of Japanese Aspect Marker "te iru."

    ERIC Educational Resources Information Center

    Shinzato, Rumiko

    1993-01-01

    Following Jacobson's 1990 work, this study is another attempt to offer a unified analysis of the Japanese aspect marker "te iru" that touches upon Gestalt psychologists' ideas of figure/ground opposition, Langacker's cognitive grammar, and Kunihiro's cognitive analysis. (Contains 34 references.) (LB)

  15. 10 CFR 1.5 - Location of principal offices and Regional Offices.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Location of principal offices and Regional Offices. 1.5 Section 1.5 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.5 Location of principal offices and Regional Offices. (a) The principal NRC offices are located in the Washington, DC, area. Facilities...

  16. The Unified Database for BM@N experiment data handling

    NASA Astrophysics Data System (ADS)

    Gertsenberger, Konstantin; Rogachevsky, Oleg

    2018-04-01

    The article describes the developed Unified Database designed as a comprehensive relational data storage for the BM@N experiment at the Joint Institute for Nuclear Research in Dubna. The BM@N experiment, which is one of the main elements of the first stage of the NICA project, is a fixed target experiment at extracted Nuclotron beams of the Laboratory of High Energy Physics (LHEP JINR). The structure and purposes of the BM@N setup are briefly presented. The article considers the scheme of the Unified Database, its attributes and implemented features in detail. The use of the developed BM@N database provides correct multi-user access to actual information of the experiment for data processing. It stores information on the experiment runs, detectors and their geometries, different configuration, calibration and algorithm parameters used in offline data processing. An important part of any database - user interfaces are presented.

  17. Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

    PubMed

    Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

    2017-08-15

    The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 26 CFR 1.1502-36 - Unified loss rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... If stock of more than one subsidiary is transferred in the transaction, the election may be made with...) INCOME TAXES Basis, Stock Ownership, and Earnings and Profits Rules § 1.1502-36 Unified loss rule. (a) In general—(1) Scope. This section provides rules for adjusting members' bases in stock of a subsidiary (S...

  19. A Unified Air-Sea Visualization System: Survey on Gridding Structures

    NASA Technical Reports Server (NTRS)

    Anand, Harsh; Moorhead, Robert

    1995-01-01

    The goal is to develop a Unified Air-Sea Visualization System (UASVS) to enable the rapid fusion of observational, archival, and model data for verification and analysis. To design and develop UASVS, modelers were polled to determine the gridding structures and visualization systems used, and their needs with respect to visual analysis. A basic UASVS requirement is to allow a modeler to explore multiple data sets within a single environment, or to interpolate multiple datasets onto one unified grid. From this survey, the UASVS should be able to visualize 3D scalar/vector fields; render isosurfaces; visualize arbitrary slices of the 3D data; visualize data defined on spectral element grids with the minimum number of interpolation stages; render contours; produce 3D vector plots and streamlines; provide unified visualization of satellite images, observations and model output overlays; display the visualization on a projection of the users choice; implement functions so the user can derive diagnostic values; animate the data to see the time-evolution; animate ocean and atmosphere at different rates; store the record of cursor movement, smooth the path, and animate a window around the moving path; repeatedly start and stop the visual time-stepping; generate VHS tape animations; work on a variety of workstations; and allow visualization across clusters of workstations and scalable high performance computer systems.

  20. 77 FR 73392 - Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R09-OAR-2012-0808; FRL-9750-3] Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control District AGENCY... the Monterey Bay Unified Air Pollution Control District (MBUAPCD) portion of the California State...

  1. 76 FR 56134 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... preempt Tribal law. List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  2. 76 FR 53640 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-29

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... section 307(b)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  3. 76 FR 56132 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... approve revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... preempt Tribal law. List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  4. 76 FR 17347 - Revision to the California State Implementation Plan, Great Basin Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-29

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 Revision to the California State Implementation Plan, Great Basin Unified Air Pollution Control District CFR Correction In Title 40 of the Code of.... * * * * * (c) * * * (345) * * * (i) * * * (D) Great Basin Unified Air Pollution Control District (1) Rule 201...

  5. 75 FR 57862 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-23

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of the... section 307(b)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  6. 77 FR 58312 - Revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control District... revisions to the California State Implementation Plan, San Joaquin Valley Unified Air Pollution Control... section 307(b)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  7. Effectiveness of Light Sources on In-Office Dental Bleaching: A Systematic Review and Meta-Analyses.

    PubMed

    SoutoMaior, J R; de Moraes, Sld; Lemos, Caa; Vasconcelos, Bc do E; Montes, Majr; Pellizzer, E P

    2018-06-12

    A systematic review and meta-analyses were performed to evaluate the efficacy of tooth color change and sensitivity of teeth following in-office bleaching with and without light gel activation in adult patients. This review was registered at PROSPERO (CRD 42017060574) and is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic systematic searches of PubMed/MEDLINE, Web of Science, and the Cochrane Library were conducted for published articles. Only randomized clinical trials among adults that compared in-office bleaching with and without light activation with the same bleaching gel concentrations were selected. The outcomes were tooth color change and tooth sensitivity prevalence and intensity. Twenty-three articles from 1054 data sources met the eligibility criteria. After title and abstract screening, 39 studies remained. Sixteen studies were further excluded. Twenty-three studies remained for qualitative analyses and 20 for meta-analyses of primary and secondary outcomes. No significant differences in tooth color change or tooth sensitivity incidence were found between the compared groups; however, tooth sensitivity intensity decreased when light sources were applied. The use of light sources for in-office bleaching is not imperative to achieve esthetic clinical results.

  8. A unified architecture for biomedical search engines based on semantic web technologies.

    PubMed

    Jalali, Vahid; Matash Borujerdi, Mohammad Reza

    2011-04-01

    There is a huge growth in the volume of published biomedical research in recent years. Many medical search engines are designed and developed to address the over growing information needs of biomedical experts and curators. Significant progress has been made in utilizing the knowledge embedded in medical ontologies and controlled vocabularies to assist these engines. However, the lack of common architecture for utilized ontologies and overall retrieval process, hampers evaluating different search engines and interoperability between them under unified conditions. In this paper, a unified architecture for medical search engines is introduced. Proposed model contains standard schemas declared in semantic web languages for ontologies and documents used by search engines. Unified models for annotation and retrieval processes are other parts of introduced architecture. A sample search engine is also designed and implemented based on the proposed architecture in this paper. The search engine is evaluated using two test collections and results are reported in terms of precision vs. recall and mean average precision for different approaches used by this search engine.

  9. Using Research to Improve College Readiness: A Research Partnership Between the Los Angeles Unified School District and the Los Angeles Education Research Institute

    PubMed Central

    Phillips, Meredith; Yamashiro, Kyo; Farrukh, Adina; Lim, Cynthia; Hayes, Katherine; Wagner, Nicole; White, Jeffrey; Chen, Hansheng

    2015-01-01

    The Los Angeles Unified School District (LAUSD) serves a large majority of socioeconomically disadvantaged students who are struggling academically and are underprepared for high school graduation and college. This article describes the partnership between LAUSD and the Los Angeles Education Research Institute, and how this collaboration endeavors to produce accessible and high-quality research to inform pressing problems of practice. The article also presents findings from an ongoing partnership research project analyzing a district policy focused on improving college readiness by aligning high school graduation and college-eligibility requirements. In a cohort that went through high school before the policy became mandatory for all students, less than 1/5 of all students (and 30% of graduates) met the college eligibility criteria. Our findings indicate that academic and behavioral indicators from 8th and 9th grade can help identify for possible intervention students who are not on track to meet these new graduation requirements. PMID:26709340

  10. MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer.

    PubMed

    Zheng, Difan; Wang, Rui; Ye, Ting; Yu, Su; Hu, Haichuan; Shen, Xuxia; Li, Yuan; Ji, Hongbin; Sun, Yihua; Chen, Haiquan

    2016-07-05

    Recurrent MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target. Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC). Twenty-three patients (1.3%) were positive for MET exon 14 skipping. Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age. MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer. Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation. Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping. From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK. Quantitative Real-Time PCR was used to detect MET gene copy number gain. Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping. Clinicopathological characteristics and survival information were analyzed. MET exon 14 skipping was detected in 1.3% (23/1770) of the Chinese patients with NSCLC. MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC.

  11. The Clinical Impact of c-MET Over-Expression in Advanced Biliary Tract Cancer (BTC).

    PubMed

    Heo, Mi Hwa; Kim, Hee Kyung; Lee, Hansang; Kim, Kyoung-Mee; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2017-01-01

    Background : c-MET is a proto-oncogene that encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF). Activation of HGF-c-MET signaling involves cell invasiveness and evokes metastasis through direct involvement of tumor angiogenesis. However, the value of c-MET overexpression is still unknown in metastatic biliary tract cancer (BTC). Methods : We analyzed the incidence and clinicopathologic characteristics of c-MET overexpression in advanced BTC. Moreover, we investigated the value of c-MET overexpression in predicting response to gemicitabine plus cisplatin (GC), a first line standard regimen, and as a prognostic marker in metastatic BTC. Results : The BTC subtype distribution (N=44) was as follows: intrahepatic cholangiocarcinoma (IHCC, n=7), extrahepatic cholangiocarcinoma (EHCC, n=25) and gallbladder cancer (GBC, n=12). Liver (52.3%) was the predominant metastatic site, followed by lymph nodes (36.4%) and bone (15.9%). Among the 44 patients analyzed for c-MET expression, 15 (34.1%) exhibited c-MET overexpression in tumor tissues. There was no significant difference in the prevalence of c-MET overexpression among primary sites in EHCC (7/25, 28.0%), IHCC (3/7, 42.9%), and GBC (5/12, 41.7%). There was also no significant correlation between specific clinicopathologic variables and c-MET expression. Comparing the tumor-response to GC according to c-MET expression (overexpression vs. non-overexpression), there was no significant difference in either RR or DCR (p=0.394 and p >0.999, respectively). The median PFS for all 44 patients was 9.00 months (95% CI, 7.5-10.5 months) and there was no significant difference for PFS between patients with c-MET overexpression and those without (p=0.917). The median OS was 14.4 months (95% CI, 11.9-16.9 months). There was no significant difference in OS between patients with c-MET overexpression compared to those without (13.7 vs. 14.4 months, respectively; p=0.708). Conclusions : c-MET overexpression was detected

  12. Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent.

    PubMed

    Kim, Eun-Mi; Joung, Min-Hee; Lee, Chang-Moon; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Kim, Dong Wook

    2010-07-15

    The mesenchymal-epithelial transition factor (c-Met), which is related to tumor cell growth, angiogenesis and metastases, is known to be overexpressed in several tumor types. In this study, we synthesized technetium-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP) derivatives, prepared by solid phase peptide synthesis and the 'click-to-chelate' protocol for the introduction of tricarbonyl technetium-99m, as a potential c-Met receptor kinase positive tumor imaging agent, and evaluated their in vitro c-Met binding affinity, cellular uptake, and stability. The (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12, [(99m)Tc(CO)(3)]13, and [(99m)Tc(CO)(3)]14) were prepared in 85-90% radiochemical yields. The cold surrogate cMBP derivatives, [Re(CO)(3)]12, [Re(CO)(3)]13, and [Re(CO)(3)]14, were shown to have high binding affinities (0.13 microM, 0.06 microM, and 0.16 microM, respectively) to a purified cMet/Fc chimeric recombinant protein. In addition, the in vitro cellular uptake and inhibition studies demonstrated the high specific binding of these (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12-14) to c-Met receptor positive U87MG cells. 2010 Elsevier Ltd. All rights reserved.

  13. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    PubMed Central

    2013-01-01

    Background The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. Results To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Conclusions Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases. PMID:23731667

  14. The Four Traditions of Geography: A Unified Future Ahead?

    ERIC Educational Resources Information Center

    Marran, James F.

    1985-01-01

    Identifies William Pattison's four traditions of geography (spatial dimension, area studies, people-environment interaction, and earth science); discusses how geography instruction at secondary level has been one dimensional; describes High School Geography Project's efforts to revise geography curriculum by unifying Pattison's traditions (1960s);…

  15. 76 FR 45199 - Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District, CA AGENCY... limited approval and limited disapproval of revisions to the San Joaquin Valley Unified Air Pollution... section 307(b)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  16. Four Courses within a Discipline: UGA Unified Core

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  17. Workplace-Based Interventions for Neck Pain in Office Workers: Systematic Review and Meta-Analysis.

    PubMed

    Chen, Xiaoqi; Coombes, Brooke K; Sjøgaard, Gisela; Jun, Deokhoon; O'Leary, Shaun; Johnston, Venerina

    2018-01-01

    At present, there is no consolidated evidence for workplace-based interventions for the prevention and reduction of neck pain in office workers. The purpose of this review was to investigate the effectiveness of workplace-based interventions for neck pain in office workers. MEDLINE, PEDro, CINAHL, and CENTRAL were searched for trials published since inception and before May 31, 2016. Randomized controlled trials (RCTs) were considered when they met the following criteria: population consisted of office workers, intervention(s) was performed at the workplace, outcome measures included neck and/or neck/shoulder pain intensity and incidence/prevalence, and comparator groups included no/other intervention. Data were extracted by 1 reviewer using predefined data fields and checked by a second reviewer. Risk of bias was assessed by 2 independent reviewers using the 2015 Cochrane Back and Neck Group guidelines. Evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Twenty-seven RCTs were included. There was moderate-quality evidence that neck/shoulder strengthening exercises and general fitness training were effective in reducing neck pain in office workers who were symptomatic, although the effect size was larger for strengthening exercises. Greater effects were observed with greater participation in exercise. Ergonomic interventions were supported by low-quality evidence. Data could not be obtained from some studies for meta-analysis and assessment of risk of bias. Reporting bias might have been present because only studies in the English language were included. Workplace-based strengthening exercises were effective in reducing neck pain in office workers who were symptomatic, and the effect size was larger when the exercises were targeted to the neck/shoulder. Future RCTs of ergonomic interventions targeted at office workers who are symptomatic are required. More research on neck pain prevention is warranted

  18. 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 Central

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

    2016-01-01

    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

  19. Involvement of lipid rafts in adhesion-induced activation of Met and EGFR.

    PubMed

    Lu, Ying-Che; Chen, Hong-Chen

    2011-10-27

    Cell adhesion has been shown to induce activation of certain growth factor receptors in a ligand-independent manner. However, the mechanism for such activation remains obscure. Human epidermal carcinoma A431 cells were used as a model to examine the mechanism for adhesion-induced activation of hepatocyte growth factor receptor Met and epidermal growth factor receptor (EGFR). The cells were suspended and replated on culture dishes under various conditions. The phosphorylation of Met at Y1234/1235 and EGFR at Y1173 were used as indicators for their activation. The distribution of the receptors and lipid rafts on the plasma membrane were visualized by confocal fluorescent microscopy and total internal reflection microscopy. We demonstrate that Met and EGFR are constitutively activated in A431 cells, which confers proliferative and invasive potentials to the cells. The ligand-independent activation of Met and EGFR in A431 cells relies on cell adhesion to a substratum, but is independent of cell spreading, extracellular matrix proteins, and substratum stiffness. This adhesion-induced activation of Met and EGFR cannot be attributed to Src activation, production of reactive oxygen species, and the integrity of the cytoskeleton. In addition, we demonstrate that Met and EGFR are independently activated upon cell adhesion. However, partial depletion of Met and EGFR prevents their activation upon cell adhesion, suggesting that overexpression of the receptors is a prerequisite for their self-activation upon cell adhesion. Although Met and EGFR are largely distributed in 0.04% Triton-insoluble fractions (i.e. raft fraction), their activated forms are detected mainly in 0.04% Triton-soluble fractions (i.e. non-raft fraction). Upon cell adhesion, lipid rafts are accumulated at the cell surface close to the cell-substratum interface, while Met and EGFR are mostly excluded from the membrane enriched by lipid rafts. Our results suggest for the first time that cell adhesion to a

  20. 37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false The United States Patent and Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES International Processing...

  1. Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk.

    PubMed

    Mukamel, Zohar; Konopka, Genevieve; Wexler, Eric; Osborn, Gregory E; Dong, Hongmei; Bergman, Mica Y; Levitt, Pat; Geschwind, Daniel H

    2011-08-10

    Autism spectrum disorder (ASD) is a highly heritable, behaviorally defined, heterogeneous disorder of unknown pathogenesis. Several genetic risk genes have been identified, including the gene encoding the receptor tyrosine kinase MET, which regulates neuronal differentiation and growth. An ASD-associated polymorphism disrupts MET gene transcription, and there are reduced levels of MET protein expression in the mature temporal cortex of subjects with ASD. To address the possible neurodevelopmental contribution of MET to ASD pathogenesis, we examined the expression and transcriptional regulation of MET by a transcription factor, FOXP2, which is implicated in regulation of cognition and language, two functions altered in ASD. MET mRNA expression in the midgestation human fetal cerebral cortex is strikingly restricted, localized to portions of the temporal and occipital lobes. Within the cortical plate of the temporal lobe, the pattern of MET expression is highly complementary to the expression pattern of FOXP2, suggesting the latter may play a role in repression of gene expression. Consistent with this, MET and FOXP2 also are reciprocally expressed by differentiating normal human neuronal progenitor cells (NHNPs) in vitro, leading us to assess whether FOXP2 transcriptionally regulates MET. Indeed, FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk.

  2. A unified view of "how allostery works".

    PubMed

    Tsai, Chung-Jung; Nussinov, Ruth

    2014-02-01

    The question of how allostery works was posed almost 50 years ago. Since then it has been the focus of much effort. This is for two reasons: first, the intellectual curiosity of basic science and the desire to understand fundamental phenomena, and second, its vast practical importance. Allostery is at play in all processes in the living cell, and increasingly in drug discovery. Many models have been successfully formulated, and are able to describe allostery even in the absence of a detailed structural mechanism. However, conceptual schemes designed to qualitatively explain allosteric mechanisms usually lack a quantitative mathematical model, and are unable to link its thermodynamic and structural foundations. This hampers insight into oncogenic mutations in cancer progression and biased agonists' actions. Here, we describe how allostery works from three different standpoints: thermodynamics, free energy landscape of population shift, and structure; all with exactly the same allosteric descriptors. This results in a unified view which not only clarifies the elusive allosteric mechanism but also provides structural grasp of agonist-mediated signaling pathways, and guides allosteric drug discovery. Of note, the unified view reasons that allosteric coupling (or communication) does not determine the allosteric efficacy; however, a communication channel is what makes potential binding sites allosteric.

  3. DataSpread: Unifying Databases and Spreadsheets

    PubMed Central

    Bendre, Mangesh; Sun, Bofan; Zhang, Ding; Zhou, Xinyan; Chang, Kevin ChenChuan; Parameswaran, Aditya

    2015-01-01

    Spreadsheet software is often the tool of choice for ad-hoc tabular data management, processing, and visualization, especially on tiny data sets. On the other hand, relational database systems offer significant power, expressivity, and efficiency over spreadsheet software for data management, while lacking in the ease of use and ad-hoc analysis capabilities. We demonstrate DataSpread, a data exploration tool that holistically unifies databases and spreadsheets. It continues to offer a Microsoft Excel-based spreadsheet front-end, while in parallel managing all the data in a back-end database, specifically, PostgreSQL. DataSpread retains all the advantages of spreadsheets, including ease of use, ad-hoc analysis and visualization capabilities, and a schema-free nature, while also adding the advantages of traditional relational databases, such as scalability and the ability to use arbitrary SQL to import, filter, or join external or internal tables and have the results appear in the spreadsheet. DataSpread needs to reason about and reconcile differences in the notions of schema, addressing of cells and tuples, and the current “pane” (which exists in spreadsheets but not in traditional databases), and support data modifications at both the front-end and the back-end. Our demonstration will center on our first and early prototype of the DataSpread, and will give the attendees a sense for the enormous data exploration capabilities offered by unifying spreadsheets and databases. PMID:26900487

  4. SO(10) supersymmetric grand unified theories

    NASA Astrophysics Data System (ADS)

    Dermisek, Radovan

    The origin of the fermion mass hierarchy is one of the most challenging problems in elementary particle physics. In the standard model fermion masses and mixing angles are free parameters. Supersymmetric grand unified theories provide a beautiful framework for physics beyond the standard model. In addition to gauge coupling unification these theories provide relations between quark and lepton masses within families, and with additional family symmetry the hierarchy between families can be generated. We present a predictive SO(10) supersymmetric grand unified model with D 3 x U(1) family symmetry. The hierarchy in fermion masses is generated by the family symmetry breaking D 3 x U(1) → ZN → nothing. This model fits the low energy data in the charged fermion sector quite well. We discuss the prediction of this model for the proton lifetime in light of recent SuperKamiokande results and present a clear picture of the allowed spectra of supersymmetric particles. Finally, the detailed discussion of the Yukawa coupling unification of the third generation particles is provided. We find a narrow region is consistent with t, b, tau Yukawa unification for mu > 0 (suggested by b → sgamma and the anomalous magnetic moment of the muon) with A0 ˜ -1.9m16, m10 ˜ 1.4m16, m16 ≳ 1200 GeV and mu, M1/2 ˜ 100--500 GeV. Demanding Yukawa unification thus makes definite predictions for Higgs and sparticle masses.

  5. Now, Here's the Weather Forecast...

    ERIC Educational Resources Information Center

    Richardson, Mathew

    2013-01-01

    The Met Office has a long history of weather forecasting, creating tailored weather forecasts for customers across the world. Based in Exeter, the Met Office is also home to the Met Office Hadley Centre, a world-leading centre for the study of climate change and its potential impacts. Climate information from the Met Office Hadley Centre is used…

  6. Voice: Reflections on an Artist-Led Program at the Met

    ERIC Educational Resources Information Center

    Valladares, Maya

    2017-01-01

    This article explores an education project in which artist Fred Wilson, poets from Lincoln Center's Poet-Linc program, and the Met Museum Education Department collaborated to produce a teen-led spoken-word poetry performance in the Met's galleries. Wilson drew from his own knowledge of the collection to facilitate a group dialogue about objects…

  7. 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.

  8. The Development of Cadastral Domain Model Oriented at Unified Real Estate Registration of China Based on Ontology

    NASA Astrophysics Data System (ADS)

    Li, M.; Zhu, X.; Shen, C.; Chen, D.; Guo, W.

    2012-07-01

    With the certain regulation of unified real estate registration taken by the Property Law and the step-by-step advance of simultaneous development in urban and rural in China, it is the premise and foundation to clearly specify property rights and their relations in promoting the integrated management of urban and rural land. This paper aims at developing a cadastral domain model oriented at unified real estate registration of China from the perspective of legal and spatial, which set up the foundation for unified real estate registration, and facilitates the effective interchange of cadastral information and the administration of land use. The legal cadastral model is provided based on the analysis of gap between current model and the demand of unified real estate registration, which implies the restrictions between different rights. Then the new cadastral domain model is constructed based on the legal cadastral domain model and CCDM (van Oosterom et al., 2006), which integrate real estate rights of urban land and rural land. Finally, the model is validated by a prototype system. The results show that the model is applicable for unified real estate registration in China.

  9. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration

    PubMed Central

    Elsen, Gina E.; Choi, Louis Y.; Prince, Victoria E.; Ho, Robert K.

    2009-01-01

    During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders. PMID:19732764

  10. Educational Services Officer

    DTIC Science & Technology

    1988-01-01

    publication is a a recommended reading list. A brief description valuable tool to an ESO when it is available of the subject matter of each is given, and...factors that must be considered in the arrangement of an office. 9. Identify the basic office products. 3. Identify the tools necessary for the...of the office. Personnel served by the tools of the trade; however, if the office this office judge it by the measure of does not provide

  11. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice

    PubMed Central

    Sennino, Barbara; Ishiguro-Oonuma, Toshina; Schriver, Brian J.; Christensen, James G.; McDonald, Donald M.

    2013-01-01

    Inhibition of vascular endothelial growth factor (VEGF) signaling can promote lymph node metastasis in preclinical models, but the mechanism is not fully understood, and successful methods of prevention have not been found. Signaling of hepatocyte growth factor (HGF) and its receptor c-Met can promote the growth of lymphatics and metastasis of some tumors. We sought to explore the contributions of c-Met signaling to lymph node metastasis after inhibition of VEGF signaling. In particular, we examined whether c-Met is upregulated in lymphatics in or near pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice and whether lymph node metastasis can be reduced by concurrent inhibition of VEGF and c-Met signaling. Inhibition of VEGF signaling by anti-VEGF antibody or sunitinib in mice from age 14 to 17 weeks was accompanied by more intratumoral lymphatics, more tumor cells inside lymphatics, and more lymph node metastases. Under these conditions, lymphatic endothelial cells - like tumor cells - had strong immunoreactivity for c-Met and phospho-c-Met. c-Met blockade by the selective inhibitor PF-04217903 significantly reduced metastasis to local lymph nodes. Together, these results indicate that inhibition of VEGF signaling in RIP-Tag2 mice upregulates c-Met expression in lymphatic endothelial cells, increases the number of intratumoral lymphatics and number of tumor cells within lymphatics, and promotes metastasis to local lymph nodes. Prevention of lymph node metastasis by PF-04217903 in this setting implicates c-Met signaling in tumor cell spread to lymph nodes. PMID:23576559

  12. 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.

  13. AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet.

    PubMed

    Jurėnas, Dukas; Chatterjee, Sneha; Konijnenberg, Albert; Sobott, Frank; Droogmans, Louis; Garcia-Pino, Abel; Van Melderen, Laurence

    2017-06-01

    Toxin-antitoxin (TA) loci are prevalent in bacterial genomes. They are suggested to play a central role in dormancy and persister states. Under normal growth conditions, TA toxins are neutralized by their cognate antitoxins, and under stress conditions, toxins are freed and inhibit essential cellular processes using a variety of mechanisms. Here we characterize ataR-ataT, a novel TA system, from enterohemorrhagic Escherichia coli. We show that the toxin AtaT is a GNAT family enzyme that transfers an acetyl group from acetyl coenzyme A to the amine group of the methionyl aminoacyl moiety of initiator tRNA. AtaT specifically modifies Met-tRNA fMet , but no other aminoacyl-tRNAs, including the elongator Met-tRNA Met . We demonstrate that once acetylated, AcMet-tRNA fMet fails to interact with initiation factor-2 (IF2), resulting in disruption of the translation initiation complex. This work reveals a new mechanism of translation inhibition and confirms Met-tRNA fMet as a prime target to efficiently block cell growth.

  14. Activation of the JNK pathway is essential for transformation by the Met oncogene.

    PubMed

    Rodrigues, G A; Park, M; Schlessinger, J

    1997-05-15

    The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.

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

    ERIC Educational Resources Information Center

    Squires, Steven J.

    1993-01-01

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

  16. Substance P-induced release of Met5-enkephalin from striatal and periaqueductal gray slices.

    PubMed

    Del Río, J; Naranjo, J R; Yang, H Y; Costa, E

    1983-11-21

    Substance P(SP), the heptapeptide SP and the stable analogue (p-Glu5-MePhe8-MeGly9) SP (DiMe-C7) induce a Ca2+-dependent release of Met5-enkephalin (MET) from slices of periaqueductal gray matter (PAG) and striatum of rats. The MET release from striatal slices is greater than that from PAG slices because of the higher MET content of striatum. Intraventricular injection of SP and of the two related peptides induce analgesia in the rat, and their analgesic potency is in line with their capacity to release MET. Other neuropeptides which possess antinociceptive activity such as bombesin, neurotensin, vasopressin and somatostatin fail to release MET from PAG slices.

  17. The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells.

    PubMed

    Shintani, Terumichi; Kusuhara, Yoshito; Daizumoto, Kei; Dondoo, Tsogt-Ochir; Yamamoto, Hiroki; Mori, Hidehisa; Fukawa, Tomoya; Nakatsuji, Hiroyoshi; Fukumori, Tomoharu; Takahashi, Masayuki; Kanayama, Hiroomi

    2017-03-01

    To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Microphysics in Multi-scale Modeling System with Unified Physics

    NASA Technical Reports Server (NTRS)

    Tao, Wei-Kuo

    2012-01-01

    Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (1) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, a review of developments and applications of the multi-scale modeling system will be presented. In particular, the microphysics development and its performance for the multi-scale modeling system will be presented.

  19. Unified Quest 2010, Part 1. Warfighter Forum

    DTIC Science & Technology

    2010-01-01

    The Warfighter Forum is one of several analytic events in the Chief of Staff of the Army’s Unified Quest 2010 Campaign of Learning . During the event...and Missile Defense Command/Army Strategic Forces Command (USASMDC/ARSTRAT) conducted a Warfighter Forum devoted to gaining direct insights into...Warfighter Forum event was conducted Dec. 8-9, 2009 in Colorado Springs, Colo., to lever- age the availability of combat units at nearby Fort Carson

  20. The research and implementation of a unified identity authentication in e-government network

    NASA Astrophysics Data System (ADS)

    Feng, Zhou

    Current problem existing in e-government network is that the applications of information system are developed independently by various departments, and each has its own specific set of authentication and access control mechanism. To build a comprehensive information system in favor of sharing and exchanging information, a sound and secure unified e-government authentication system is firstly needed. The paper, combining with practical development of e-government network, carries out a thorough discussion on how to achieve data synchronization between unified authentication system and related application systems.

  1. A unified approach to the analysis and design of elasto-plastic structures with mechanical contact

    NASA Technical Reports Server (NTRS)

    Bendsoe, Martin P.; Olhoff, Niels; Taylor, John E.

    1990-01-01

    With structural design in mind, a new unified variational model has been developed which represents the mechanics of deformation elasto-plasticity with unilateral contact conditions. For a design problem formulated as maximization of the load carrying capacity of a structure under certain constraints, the unified model allows for a simultaneous analysis and design synthesis for a whole range of mechanical behavior.

  2. Targeted deletion of c-Met in thymic epithelial cells leads to an autoimmune phenotype

    PubMed Central

    Su, Min; Hu, Rong; Song, Yinhong; Liu, Yalan; Lai, Laijun

    2017-01-01

    Hepatocyte growth factor (HGF) and its receptor c-Met signaling have been implicated in regulating various types of cells including epithelial cells. We have previously reported that c-Met is expressed by thymic epithelial cells (TECs), and that in vivo administration of hybrid cytokines containing IL-7 and the beta- or alpha-chain of HGF significantly increase the number of TECs. In order to study the role of c-Met signaling in TECs, we generated conditional knockout (cKO) mice in which c-Met was specifically deleted in TECs using a Foxn1-Cre transgene. We show here that c-Met deficiency in TECs results in age-progressive reduction in TEC number and reduced number of regulatory T cells. Consequently, c-Met TEC cKO mice displayed an autoimmune phenotype. Thus, c-Met signaling in TECs is important for the maintenance of TECs and immune self-tolerance. PMID:29363160

  3. In vivo detection of c-Met expression in a rat C6 glioma model.

    PubMed

    Towner, R A; Smith, N; Doblas, S; Tesiram, Y; Garteiser, P; Saunders, D; Cranford, R; Silasi-Mansat, R; Herlea, O; Ivanciu, L; Wu, D; Lupu, F

    2008-01-01

    The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T(1) relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal'brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas.

  4. In vivo detection of c-Met expression in a rat C6 glioma model

    PubMed Central

    Towner, RA; Smith, N; Doblas, S; Tesiram, Y; Garteiser, P; Saunders, D; Cranford, R; Silasi-Mansat, R; Herlea, O; Ivanciu, L; Wu, D; Lupu, F

    2008-01-01

    Abstract The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T1 relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and ‘normal’brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas. PMID:18194445

  5. Strategic Black Officer Capital Investment: Increasing Competitiveness for General Officer

    DTIC Science & Technology

    2010-05-17

    support a discussion between the genders since African American women are completing their degrees at a higher rate than men . There are a many...officers, but this was out of an officer corps that numbered more than 15 150,000 men and women , meaning African Americans still made up less than...senior officers.‖6 My research does not necessarily separate African American men and women officers. However, the most recent graduation trends

  6. 77 FR 25080 - Safety Zones; TriMet Bridge Project, Willamette River, Portland, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ...-AA00 Safety Zones; TriMet Bridge Project, Willamette River, Portland, OR AGENCY: Coast Guard, DHS... trestles and construction cranes involved in the construction of the TriMet Bridge on the Willamette River... project. These safety zones replace the prior safety zones established for the TriMet Bridge construction...

  7. In Search of a Unified Model of Language Contact

    ERIC Educational Resources Information Center

    Winford, Donald

    2013-01-01

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

  8. Skinner-Rusk unified formalism for higher-order systems

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

    The Lagrangian-Hamiltonian unified formalism of R. Skinner and R. Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, first-order and higher-order field theories, and higher-order autonomous systems. In this work we present a generalization of this formalism for higher-order non-autonomous mechanical systems.

  9. 76 FR 56116 - Interim Final Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District AGENCY... on a proposed approval of revisions to the San Joaquin Valley Unified Air Pollution Control District... Part 52 Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental...

  10. 76 FR 56114 - Interim Final Determination to Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... Determination to Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District AGENCY... on a proposed approval of revisions to the San Joaquin Valley Unified Air Pollution Control District... Part 52 Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental...

  11. North Coast Unified Air Quality Management District: PSD Delegation Agreements

    EPA Pesticide Factsheets

    Agreements for Partial Delegation of the Federal Prevention of Significant Deterioration (PSD) Program Set Forth in 40 CPR 52.21 by the United States Environmental Protection Agency, Region 9 to the North Coast Unified Air Quality Management District.

  12. A unified large/small-scale dynamo in helical turbulence

    NASA Astrophysics Data System (ADS)

    Bhat, Pallavi; Subramanian, Kandaswamy; Brandenburg, Axel

    2016-09-01

    We use high resolution direct numerical simulations (DNS) to show that helical turbulence can generate significant large-scale fields even in the presence of strong small-scale dynamo action. During the kinematic stage, the unified large/small-scale dynamo grows fields with a shape-invariant eigenfunction, with most power peaked at small scales or large k, as in Subramanian & Brandenburg. Nevertheless, the large-scale field can be clearly detected as an excess power at small k in the negatively polarized component of the energy spectrum for a forcing with positively polarized waves. Its strength overline{B}, relative to the total rms field Brms, decreases with increasing magnetic Reynolds number, ReM. However, as the Lorentz force becomes important, the field generated by the unified dynamo orders itself by saturating on successively larger scales. The magnetic integral scale for the positively polarized waves, characterizing the small-scale field, increases significantly from the kinematic stage to saturation. This implies that the small-scale field becomes as coherent as possible for a given forcing scale, which averts the ReM-dependent quenching of overline{B}/B_rms. These results are obtained for 10243 DNS with magnetic Prandtl numbers of PrM = 0.1 and 10. For PrM = 0.1, overline{B}/B_rms grows from about 0.04 to about 0.4 at saturation, aided in the final stages by helicity dissipation. For PrM = 10, overline{B}/B_rms grows from much less than 0.01 to values of the order the 0.2. Our results confirm that there is a unified large/small-scale dynamo in helical turbulence.

  13. Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma

    PubMed Central

    Cruickshanks, Nichola; Zhang, Ying; Yuan, Fang; Pahuski, Mary; Gibert, Myron; Abounader, Roger

    2017-01-01

    Glioblastoma (GBM) is a lethal brain tumor with dismal prognosis. Current therapeutic options, consisting of surgery, chemotherapy and radiation, have only served to marginally increase patient survival. Receptor tyrosine kinases (RTKs) are dysregulated in approximately 90% of GBM; attributed to this, research has focused on inhibiting RTKs as a novel and effective therapy for GBM. Overexpression of RTK mesenchymal epithelial transition (MET), and its ligand, hepatocyte growth factor (HGF), in GBM highlights a promising new therapeutic target. This review will discuss the role of MET in cell cycle regulation, cell proliferation, evasion of apoptosis, cell migration and invasion, angiogenesis and therapeutic resistance in GBM. It will also discuss the modes of deregulation of HGF/MET and their regulation by microRNAs. As the HGF/MET pathway is a vital regulator of multiple pro-survival pathways, efforts and strategies for its exploitation for GBM therapy are also described. PMID:28696366

  14. 76 FR 53054 - Safety Zone; TriMet Bridge Project, Willamette River; Portland, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-25

    ...-AA00 Safety Zone; TriMet Bridge Project, Willamette River; Portland, OR AGENCY: Coast Guard, DHS... the TriMet Bridge on the Willamette River, in Portland, OR. This action is necessary to ensure the... Zone: TriMet Bridge Project, Willamette River; Portland, OR in the Federal Register (76 FR 86). We...

  15. Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

    PubMed

    Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

    2018-06-01

    Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

  16. Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

    PubMed

    Tang, Na-Ping; Wang, Lian-Sheng; Yang, Li; Gu, Hai-Juan; Zhu, Huai-Jun; Zhou, Bo; Sun, Qing-Min; Cong, Ri-Hong; Wang, Bin

    2008-01-01

    Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

  17. Reciprocal Activating Crosstalk between c-Met and Caveolin 1 Promotes Invasive Phenotype in Hepatocellular Carcinoma

    PubMed Central

    Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Çokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

    2014-01-01

    c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC. PMID:25148256

  18. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

    PubMed

    Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

    2014-01-01

    c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  19. SO(10) × S 4 grand unified theory of flavour and leptogenesis

    NASA Astrophysics Data System (ADS)

    de Anda, Francisco J.; King, Stephen F.; Perdomo, Elena

    2017-12-01

    We propose a Grand Unified Theory of Flavour, based on SO(10) together with a non-Abelian discrete group S 4, under which the unified three quark and lepton 16-plets are unified into a single triplet 3'. The model involves a further discrete group ℤ 4 R × ℤ 4 3 which controls the Higgs and flavon symmetry breaking sectors. The CSD2 flavon vacuum alignment is discussed, along with the GUT breaking potential and the doublet-triplet splitting, and proton decay is shown to be under control. The Yukawa matrices are derived in detail, from renormalisable diagrams, and neutrino masses emerge from the type I seesaw mechanism. A full numerical fit is performed with 15 input parameters generating 19 presently constrained observables, taking into account supersymmetry threshold corrections. The model predicts a normal neutrino mass ordering with a CP oscillation phase of 260°, an atmospheric angle in the first octant and neutrinoless double beta decay with m ββ = 11 meV. We discuss N 2 leptogenesis, which fixes the second right-handed neutrino mass to be M 2 ≃ 2 × 1011 GeV, in the natural range predicted by the model.

  20. 76 FR 59254 - Interim Final Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District AGENCY... on a proposed approval of revisions to the San Joaquin Valley Unified Air Pollution Control District...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control...

  1. 77 FR 24857 - Interim Final Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... Determination To Stay and Defer Sanctions, San Joaquin Valley Unified Air Pollution Control District AGENCY... on a proposed approval of revisions to the San Joaquin Valley Unified Air Pollution Control District... Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental regulations...

  2. Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer.

    PubMed

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

    2013-01-01

    MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P < 0.001). Overexpression of MET was significantly associated with shortened overall survival in univariate analysis (P < 0.001). Moreover, patients with a MET+/phospho-BAD(Ser-136)+ phenotype had a poorer prognosis than others (P < 0.001). Multivariate Cox proportional hazard analysis confirmed that MET expression is a prognostic factor for NSCLC. MET expression might be correlated with phospho-BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC.

  3. A Unified Approach for Solving Nonlinear Regular Perturbation Problems

    ERIC Educational Resources Information Center

    Khuri, S. A.

    2008-01-01

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

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

    ERIC Educational Resources Information Center

    Anastasi, Anne

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

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

    ERIC Educational Resources Information Center

    Schaefer, Earl S.; And Others

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

  6. MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

    PubMed

    De Bacco, Francesca; D'Ambrosio, Antonio; Casanova, Elena; Orzan, Francesca; Neggia, Roberta; Albano, Raffaella; Verginelli, Federica; Cominelli, Manuela; Poliani, Pietro L; Luraghi, Paolo; Reato, Gigliola; Pellegatta, Serena; Finocchiaro, Gaetano; Perera, Timothy; Garibaldi, Elisabetta; Gabriele, Pietro; Comoglio, Paolo M; Boccaccio, Carla

    2016-05-01

    Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy. We elucidate that MET promotes GSC radioresistance through a novel mechanism, relying on AKT activity and leading to (i) sustained activation of Aurora kinase A, ATM kinase, and the downstream effectors of DNA repair, and (ii) phosphorylation and cytoplasmic retention of p21, which is associated with anti-apoptotic functions. We show that MET pharmacological inhibition causes DNA damage accumulation in irradiated GSCs and their depletion in vitro and in GBMs generated by GSC xenotransplantation. Preclinical evidence is thus provided that MET inhibitors can radiosensitize tumors and convert GSC-positive selection, induced by radiotherapy, into GSC eradication. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  7. Coriolis effect in optics: unified geometric phase and spin-Hall effect.

    PubMed

    Bliokh, Konstantin Y; Gorodetski, Yuri; Kleiner, Vladimir; Hasman, Erez

    2008-07-18

    We examine the spin-orbit coupling effects that appear when a wave carrying intrinsic angular momentum interacts with a medium. The Berry phase is shown to be a manifestation of the Coriolis effect in a noninertial reference frame attached to the wave. In the most general case, when both the direction of propagation and the state of the wave are varied, the phase is given by a simple expression that unifies the spin redirection Berry phase and the Pancharatnam-Berry phase. The theory is supported by the experiment demonstrating the spin-orbit coupling of electromagnetic waves via a surface plasmon nanostructure. The measurements verify the unified geometric phase, demonstrated by the observed polarization-dependent shift (spin-Hall effect) of the waves.

  8. Modulation of the COMT Val(158)Met polymorphism on resting-state EEG power.

    PubMed

    Solís-Ortiz, Silvia; Pérez-Luque, Elva; Gutiérrez-Muñoz, Mayra

    2015-01-01

    The catechol-O-methyltransferase (COMT) Val(158)Met polymorphism impacts cortical dopamine (DA) levels and may influence cortical electrical activity in the human brain. This study investigated whether COMT genotype influences resting-state electroencephalogram (EEG) power in the frontal, parietal and midline regions in healthy volunteers. EEG recordings were conducted in the resting-state in 13 postmenopausal healthy woman carriers of the Val/Val genotype and 11 with the Met/Met genotype. The resting EEG spectral absolute power in the frontal (F3, F4, F7, F8, FC3 and FC4), parietal (CP3, CP4, P3 and P4) and midline (Fz, FCz, Cz, CPz, Pz and Oz) was analyzed during the eyes-open and eyes-closed conditions. The frequency bands considered were the delta, theta, alpha1, alpha2, beta1 and beta2. EEG data of the Val/Val and Met/Met genotypes, brain regions and conditions were analyzed using a general linear model analysis. In the individuals with the Met/Met genotype, delta activity was increased in the eyes-closed condition, theta activity was increased in the eyes-closed and in the eyes-open conditions, and alpha1 band, alpha2 band and beta1band activity was increased in the eyes-closed condition. A significant interaction between COMT genotypes and spectral bands was observed. Met homozygote individuals exhibited more delta, theta and beta1 activity than individuals with the Val/Val genotype. No significant interaction between COMT genotypes and the resting-state EEG regional power and conditions were observed for the three brain regions studied. Our findings indicate that the COMT Val(158)Met polymorphism does not directly impact resting-state EEG regional power, but instead suggest that COMT genotype can modulate resting-state EEG spectral power in postmenopausal healthy women.

  9. Modulation of the COMT Val158Met polymorphism on resting-state EEG power

    PubMed Central

    Solís-Ortiz, Silvia; Pérez-Luque, Elva; Gutiérrez-Muñoz, Mayra

    2015-01-01

    The catechol-O-methyltransferase (COMT) Val158Met polymorphism impacts cortical dopamine (DA) levels and may influence cortical electrical activity in the human brain. This study investigated whether COMT genotype influences resting-state electroencephalogram (EEG) power in the frontal, parietal and midline regions in healthy volunteers. EEG recordings were conducted in the resting-state in 13 postmenopausal healthy woman carriers of the Val/Val genotype and 11 with the Met/Met genotype. The resting EEG spectral absolute power in the frontal (F3, F4, F7, F8, FC3 and FC4), parietal (CP3, CP4, P3 and P4) and midline (Fz, FCz, Cz, CPz, Pz and Oz) was analyzed during the eyes-open and eyes-closed conditions. The frequency bands considered were the delta, theta, alpha1, alpha2, beta1 and beta2. EEG data of the Val/Val and Met/Met genotypes, brain regions and conditions were analyzed using a general linear model analysis. In the individuals with the Met/Met genotype, delta activity was increased in the eyes-closed condition, theta activity was increased in the eyes-closed and in the eyes-open conditions, and alpha1 band, alpha2 band and beta1band activity was increased in the eyes-closed condition. A significant interaction between COMT genotypes and spectral bands was observed. Met homozygote individuals exhibited more delta, theta and beta1 activity than individuals with the Val/Val genotype. No significant interaction between COMT genotypes and the resting-state EEG regional power and conditions were observed for the three brain regions studied. Our findings indicate that the COMT Val158Met polymorphism does not directly impact resting-state EEG regional power, but instead suggest that COMT genotype can modulate resting-state EEG spectral power in postmenopausal healthy women. PMID:25883560

  10. 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…

  11. 28 CFR 0.118 - Office of Chief Administrative Hearing Officer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Officer. 0.118 Section 0.118 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Executive Office for Immigration Review § 0.118 Office of Chief Administrative Hearing... Law Judges in performance of their duties in accordance with 8 U.S.C. 1324 A and B. ...

  12. Designing a more efficient, effective and safe Medical Emergency Team (MET) service using data analysis

    PubMed Central

    Bilgrami, Irma; Bain, Christopher; Webb, Geoffrey I.; Orosz, Judit; Pilcher, David

    2017-01-01

    Introduction Hospitals have seen a rise in Medical Emergency Team (MET) reviews. We hypothesised that the commonest MET calls result in similar treatments. Our aim was to design a pre-emptive management algorithm that allowed direct institution of treatment to patients without having to wait for attendance of the MET team and to model its potential impact on MET call incidence and patient outcomes. Methods Data was extracted for all MET calls from the hospital database. Association rule data mining techniques were used to identify the most common combinations of MET call causes, outcomes and therapies. Results There were 13,656 MET calls during the 34-month study period in 7936 patients. The most common MET call was for hypotension [31%, (2459/7936)]. These MET calls were strongly associated with the immediate administration of intra-venous fluid (70% [1714/2459] v 13% [739/5477] p<0.001), unless the patient was located on a respiratory ward (adjusted OR 0.41 [95%CI 0.25–0.67] p<0.001), had a cardiac cause for admission (adjusted OR 0.61 [95%CI 0.50–0.75] p<0.001) or was under the care of the heart failure team (adjusted OR 0.29 [95%CI 0.19–0.42] p<0.001). Modelling the effect of a pre-emptive management algorithm for immediate fluid administration without MET activation on data from a test period of 24 months following the study period, suggested it would lead to a 68.7% (2541/3697) reduction in MET calls for hypotension and a 19.6% (2541/12938) reduction in total METs without adverse effects on patients. Conclusion Routinely collected data and analytic techniques can be used to develop a pre-emptive management algorithm to administer intravenous fluid therapy to a specific group of hypotensive patients without the need to initiate a MET call. This could both lead to earlier treatment for the patient and less total MET calls. PMID:29281665

  13. Differential transcriptional control of the two tRNA(fMet) genes of Escherichia coli K-12.

    PubMed

    Nagase, T; Ishii, S; Imamoto, F

    1988-07-15

    The metZ gene of Escherichia coli, which encodes the tRNA(f1Met), was cloned. Using the nucleotide sequence, in vitro transcription, and S1 nuclease mapping analyses, we identified the promoter region, transcriptional start point, the two tandem tRNA(f1Met) structural genes separated by an intergenic space of 33 bp, and the two Rho-independent transcriptional termination sites, in that order. We compared the promoter region of the metZ gene with that of the metY gene, which encodes the tRNA(f2Met) and is located in the promoter-proximal portion of the nusA operon. A G + C-rich sequence (5'-GCGCATCCAC-3'), similar to the corresponding sequence of the rrn promoters that are under stringent control, was found between the Pribnow box and the transcriptional start point of the metZ promoter, but not in the metY promoter region. We therefore examined the effect of guanosine 3'-diphosphate, 5'-diphosphate (ppGpp), the chemical mediator of stringent control, and found that ppGpp inhibited the transcription of the metZ gene, but not that of the metY gene. These data suggested that the promoters for metZ and metY have different physiological functions and are regulated by different mechanisms.

  14. Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies.

    PubMed

    Qamsari, Elmira Safaie; Sharifzadeh, Zahra; Bagheri, Salman; Riazi-Rad, Farhad; Younesi, Vahid; Abolhassani, Mohsen; Ghaderi, Sepideh Safaei; Baradaran, Behzad; Somi, Mohammad Hossein; Yousefi, Mehdi

    2017-12-01

    The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers.

  15. A Unified Theoretical Framework for Cognitive Sequencing.

    PubMed

    Savalia, Tejas; Shukla, Anuj; Bapi, Raju S

    2016-01-01

    The capacity to sequence information is central to human performance. Sequencing ability forms the foundation stone for higher order cognition related to language and goal-directed planning. Information related to the order of items, their timing, chunking and hierarchical organization are important aspects in sequencing. Past research on sequencing has emphasized two distinct and independent dichotomies: implicit vs. explicit and goal-directed vs. habits. We propose a theoretical framework unifying these two streams. Our proposal relies on brain's ability to implicitly extract statistical regularities from the stream of stimuli and with attentional engagement organizing sequences explicitly and hierarchically. Similarly, sequences that need to be assembled purposively to accomplish a goal require engagement of attentional processes. With repetition, these goal-directed plans become habits with concomitant disengagement of attention. Thus, attention and awareness play a crucial role in the implicit-to-explicit transition as well as in how goal-directed plans become automatic habits. Cortico-subcortical loops basal ganglia-frontal cortex and hippocampus-frontal cortex loops mediate the transition process. We show how the computational principles of model-free and model-based learning paradigms, along with a pivotal role for attention and awareness, offer a unifying framework for these two dichotomies. Based on this framework, we make testable predictions related to the potential influence of response-to-stimulus interval (RSI) on developing awareness in implicit learning tasks.

  16. A Unified Theoretical Framework for Cognitive Sequencing

    PubMed Central

    Savalia, Tejas; Shukla, Anuj; Bapi, Raju S.

    2016-01-01

    The capacity to sequence information is central to human performance. Sequencing ability forms the foundation stone for higher order cognition related to language and goal-directed planning. Information related to the order of items, their timing, chunking and hierarchical organization are important aspects in sequencing. Past research on sequencing has emphasized two distinct and independent dichotomies: implicit vs. explicit and goal-directed vs. habits. We propose a theoretical framework unifying these two streams. Our proposal relies on brain's ability to implicitly extract statistical regularities from the stream of stimuli and with attentional engagement organizing sequences explicitly and hierarchically. Similarly, sequences that need to be assembled purposively to accomplish a goal require engagement of attentional processes. With repetition, these goal-directed plans become habits with concomitant disengagement of attention. Thus, attention and awareness play a crucial role in the implicit-to-explicit transition as well as in how goal-directed plans become automatic habits. Cortico-subcortical loops basal ganglia-frontal cortex and hippocampus-frontal cortex loops mediate the transition process. We show how the computational principles of model-free and model-based learning paradigms, along with a pivotal role for attention and awareness, offer a unifying framework for these two dichotomies. Based on this framework, we make testable predictions related to the potential influence of response-to-stimulus interval (RSI) on developing awareness in implicit learning tasks. PMID:27917146

  17. A Unifying Theme for General Education in Community Colleges.

    ERIC Educational Resources Information Center

    Blanchard, Bryan

    National attention is currently focusing on the issue of general education in American colleges and universities, bringing to light the need for a unifying purpose and idea. Evidence such as declining test scores, grade inflation, and employer criticisms of college graduates have prompted public laments by academics themselves about the erosion of…

  18. The MetOp second generation 3MI instrument

    NASA Astrophysics Data System (ADS)

    Manolis, Ilias; Grabarnik, Semen; Caron, Jérôme; Bézy, Jean-Loup; Loiselet, Marc; Betto, Maurizio; Barré, Hubert; Mason, Graeme; Meynart, Roland

    2013-10-01

    The MetOp-SG programme is a joint Programme of EUMETSAT and ESA. ESA develops the prototype MetOp-SG satellites (including associated instruments) and procures, on behalf of EUMETSAT, the recurrent satellites (and associated instruments). Two parallel, competitive phase A/B1 studies for MetOp Second Generation (MetOp-SG) have been concluded in May 2013. The implementation phases (B2/C/D/E) are planned to start the first quarter of 2014. ESA is responsible for instrument design of six missions, namely Microwave Sounding Mission (MWS), Scatterometer mission (SCA), Radio Occultation mission (RO), Microwave Imaging mission (MWI), Ice Cloud Imager (ICI) and Multi-viewing, Multi-channel, Multi-polarisation imaging mission (3MI). The paper will present the main performances of the 3MI instrument and will highlight the performance improvements with respect to its heritage derived by the POLDER instrument, such as number of spectral channels and spectral range coverage, swath and ground spatial resolution. The engineering of some key performance requirements (multi-viewing, polarisation sensitivity, straylight etc.) will also be discussed. The results of the feasibility studies will be presented together with the programmatics for the instrument development. Several pre-development activities have been initiated to retire highest risks and to demonstrate the ultimate performances of the 3MI optics. The scope, objectives and current status of those activities will be presented. Key technologies involved in the 3MI instrument design and implementation are considered to be: the optical design featuring aspheric optics, the implementation of broadband Anti Reflection coatings featuring low polarisation and low de-phasing properties, the development and qualification of polarisers with acceptable performances as well as spectral filters with good uniformities over a large clear aperture.

  19. Detection of MET Gene Copy Number in Cancer Samples Using the Droplet Digital PCR Method.

    PubMed

    Zhang, Yanni; Tang, En-Tzu; Du, Zhiqiang

    2016-01-01

    The analysis of MET gene copy number (CN) has been considered to be a potential biomarker to predict the response to MET-targeted therapies in various cancers. However, the current standard methods to determine MET CN are SNP 6.0 in the genomic DNA of cancer cell lines and fluorescence in situ hybridization (FISH) in tumor models, respectively, which are costly and require advanced technical skills and result in relatively subjective judgments. Therefore, we employed a novel method, droplet digital PCR (ddPCR), to determine the MET gene copy number with high accuracy and precision. The genomic DNA of cancer cell lines or tumor models were tested and compared with the MET gene CN and MET/CEN-7 ratio determined by SNP 6.0 and FISH, respectively. In cell lines, the linear association of the MET CN detected by ddPCR and SNP 6.0 is strong (Pearson correlation = 0.867). In tumor models, the MET CN detected by ddPCR was significantly different between the MET gene amplification and non-amplification groups according to FISH (mean: 15.4 vs 2.1; P = 0.044). Given that MET gene amplification is defined as MET CN >5.5 by ddPCR, the concordance rate between ddPCR and FISH was 98.0%, and Cohen's kappa coefficient was 0.760 (95% CI, 0.498-1.000; P <0.001). The results demonstrated that the ddPCR method has the potential to quantify the MET gene copy number with high precision and accuracy as compared with the results from SNP 6.0 and FISH in cancer cell lines and tumor samples, respectively.

  20. VIEW EAST, WEST SIDE OF TWOSTORY OFFICE BUILDING, ONESTORY OFFICE ...

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

    VIEW EAST, WEST SIDE OF TWO-STORY OFFICE BUILDING, ONE-STORY OFFICE BUILDING, AND HEBERTS 1949 HANGAR, AND VIEW OF SOUTH SIDE OF TWO-STORY OFFICE BUILDING AND NORTH SIDE OF HEBERTS 1949 HANGAR - Capital City Airport, Capital City Aviation, North side of Grand River Avenue, Lansing, Ingham County, MI

  1. Unifying concepts in the high school biology curriculum, one or many: An investigation of rural, suburban, and urban schools

    NASA Astrophysics Data System (ADS)

    Brown, Judith Ann

    2000-10-01

    Nine high school biology teachers from rural, suburban, and urban school settings, were interviewed about what idea, topic, or concept, if any, they use to unify their high school biology curriculum. Professional scientists and educational organizations have proposed that high school biology teachers use "biological evolution" as a unifying concept of their curriculum. Interviews, concept maps, and classroom syllabi and outlines were provided as data for these nine case studies. Each teacher was asked what topics were included in their curriculum to determine if a wide enough content was taught to warrant unification. The teachers' responses were compared to content and concepts listed in the National Science Content Standards, the Washington State Essential Academic Learning Requirements for Science, and a paper (Hurd, Bybee, Kahle, and Yager, 1980) that proposed what and how topics should be taught in the high school biology class by the year 2000. The nine teachers were asked to draw a concept map showing how these topics were interrelated and what concept, if any, "unified" them. A unifying concept is defined as a concept introduced early in the year and referred back to whenever new topics are introduced illustrating how the new topic is related to the previous ones through this unifying concept. Seven of the nine teachers did use at least one unifying concept. Two use evolution or natural selection, two use the web of life, two use the characteristics of life, and one uses scientific inquiry. The data collected in this study indicate high school teachers use these concepts such as the web of life and the characteristics of life because they believe they are easily understood by their students and less controversial than the theory of evolution. This study also presents evidence that school setting has minimal influence on what concept teachers use to unify their curriculum and that teachers have a significant amount of academic freedom to choose what they

  2. The utilization of unified protocols in behavioral cognitive therapy in transdiagnostic group subjects: A clinical trial.

    PubMed

    de Ornelas Maia, Ana Claudia Corrêa; Nardi, Antonio Egidio; Cardoso, Adriana

    2015-02-01

    The practicing of protocols based on behavioral cognitive therapy (CBT) have been frequently used in the last decades and adapted to better manage the necessities of patients and providers. The goal is to build a treatment that is evidence-based - for that reason the unified protocol for multiple emotional disorders (transdiagnostics) have been utilized to simplify treatment - without losing scientific traits. The main goal of this study is to evaluate the unified protocol in groups of patients with depression and anxiety disorders. In a pool of 48 subjects, divided in two groups, one was submitted to 12 intervention sessions of the unified protocol while the other was solely given medication. MINI, BAI and BDI were the instruments used at the beginning and at the end of treatment. The results were highly significant (p<0.001) in as much as with the improvement of anxiety and depressive disorders as it was in the group which was treated with the unified protocol compared with the group which was only given medication Limitations of this study were the number of sample participants and the non-randomization of subjects in both groups. Group therapy has not been largely implemented though it is deemed very useful for treatments when the unified protocol is used in transdiagnostic patients. Not only does it allow for emotional stabilizing and socialization but it also enables subjects with an altruistic feeling amongst themselves. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Proposal for a unified CCN nomenclature

    PubMed Central

    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

    2003-01-01

    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

  4. "Met" Made Simple: Building Research-Based Teacher Evaluations. Issue Analysis Report

    ERIC Educational Resources Information Center

    New Teacher Project, 2012

    2012-01-01

    Groundbreaking new findings from the Bill and Melinda Gates Foundation's Measures of Effective Teaching (MET) project hold the potential to answer crucial questions about how to assess teachers' performance. For the past two years, MET researchers have conducted a research project of unprecedented scope, involving 3,000 teachers in six school…

  5. 76 FR 53935 - Delegation Authority for the Office of the Chief Financial Officer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... Office of the Chief Financial Officer AGENCY: Office of the Secretary, HUD. ACTION: Notice of delegation of authority. SUMMARY: In this notice, the Secretary of HUD, pursuant to the Chief Financial Officers Act of 1990 (CFO Act), which established the position of the Chief Financial Officer within HUD, is...

  6. Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

    PubMed

    Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

    2011-10-01

    Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

  7. The MetOp second generation 3MI mission

    NASA Astrophysics Data System (ADS)

    Manolis, Ilias; Caron, Jérôme; Grabarnik, Semen; Bézy, Jean-Loup; Betto, Maurizio; Barré, Hubert; Mason, Graeme; Meynart, Roland

    2017-11-01

    ESA is currently running two parallel, competitive phase A/B1 studies for MetOp Second Generation (MetOp-SG). MetOp-SG is the space segment of EUMETSAT Polar System (EPS-SG) consisting of the satellites and instruments. The Phase A/B1 studies will be completed in the first quarter of 2013. The final implementation phases (B2/C/D) are planned to start 2013. ESA is responsible for instrument design of five missions, namely Microwave Sounding Mission (MWS), Scatterometer mission (SCA), Radio Occultation mission (RO), Microwave Imaging mission (MWI), Ice Cloud Imaging (ICI) mission, and Multiviewing, Multi-channel, Multi-polarization imaging mission (3MI). This paper will present the instrument main design elements of the 3MI mission, primarily aimed at providing aerosol characterization for climate monitoring, Numerical Weather Prediction (NWP), atmospheric chemistry and air quality. The 3MI instrument is a passive radiometer measuring the polarized radiances reflected by the Earth under different viewing geometries and across several spectral bands spanning the visible and short-wave infrared spectrum. The paper will present the main performances of the instrument and will concentrate mainly on the performance improvements with respect to its heritage derived by the POLDER instrument. The engineering of some key performance requirements (multiviewing, polarization sensitivity, etc.) will also be discussed.

  8. A new unified theory of electromagnetic and gravitational interactions

    NASA Astrophysics Data System (ADS)

    Li, Li-Xin

    2016-12-01

    In this paper we present a new unified theory of electromagnetic and gravitational interactions. By considering a four-dimensional spacetime as a hypersurface embedded in a five-dimensional bulk spacetime, we derive the complete set of field equations in the four-dimensional spacetime from the fivedimensional Einstein field equation. Besides the Einstein field equation in the four-dimensional spacetime, an electromagnetic field equation is obtained: ∇a F ab - ξ R b a A a = -4π J b with ξ = -2, where F ab is the antisymmetric electromagnetic field tensor defined by the potential vector A a , R ab is the Ricci curvature tensor of the hypersurface, and J a is the electric current density vector. The electromagnetic field equation differs from the Einstein-Maxwell equation by a curvature-coupled term ξ R b a A a , whose presence addresses the problem of incompatibility of the Einstein-Maxwell equation with a universe containing a uniformly distributed net charge, as discussed in a previous paper by the author [L.-X. Li, Gen. Relativ. Gravit. 48, 28 (2016)]. Hence, the new unified theory is physically different from Kaluza-Klein theory and its variants in which the Einstein-Maxwell equation is derived. In the four-dimensional Einstein field equation derived in the new theory, the source term includes the stress-energy tensor of electromagnetic fields as well as the stress-energy tensor of other unidentified matter. Under certain conditions the unidentified matter can be interpreted as a cosmological constant in the four-dimensional spacetime. We argue that, the electromagnetic field equation and hence the unified theory presented in this paper can be tested in an environment with a high mass density, e.g., inside a neutron star or a white dwarf, and in the early epoch of the universe.

  9. A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peyret, Thomas; Poulin, Patrick; Krishnan, Kannan, E-mail: kannan.krishnan@umontreal.ca

    The algorithms in the literature focusing to predict tissue:blood PC (P{sub tb}) for environmental chemicals and tissue:plasma PC based on total (K{sub p}) or unbound concentration (K{sub pu}) for drugs differ in their consideration of binding to hemoglobin, plasma proteins and charged phospholipids. The objective of the present study was to develop a unified algorithm such that P{sub tb}, K{sub p} and K{sub pu} for both drugs and environmental chemicals could be predicted. The development of the unified algorithm was accomplished by integrating all mechanistic algorithms previously published to compute the PCs. Furthermore, the algorithm was structured in such amore » way as to facilitate predictions of the distribution of organic compounds at the macro (i.e. whole tissue) and micro (i.e. cells and fluids) levels. The resulting unified algorithm was applied to compute the rat P{sub tb}, K{sub p} or K{sub pu} of muscle (n = 174), liver (n = 139) and adipose tissue (n = 141) for acidic, neutral, zwitterionic and basic drugs as well as ketones, acetate esters, alcohols, aliphatic hydrocarbons, aromatic hydrocarbons and ethers. The unified algorithm reproduced adequately the values predicted previously by the published algorithms for a total of 142 drugs and chemicals. The sensitivity analysis demonstrated the relative importance of the various compound properties reflective of specific mechanistic determinants relevant to prediction of PC values of drugs and environmental chemicals. Overall, the present unified algorithm uniquely facilitates the computation of macro and micro level PCs for developing organ and cellular-level PBPK models for both chemicals and drugs.« less

  10. Simulation of Aerosols and Chemistry with a Unified Global Model

    NASA Technical Reports Server (NTRS)

    Chin, Mian

    2004-01-01

    This project is to continue the development of the global simulation capabilities of tropospheric and stratospheric chemistry and aerosols in a unified global model. This is a part of our overall investigation of aerosol-chemistry-climate interaction. In the past year, we have enabled the tropospheric chemistry simulations based on the GEOS-CHEM model, and added stratospheric chemical reactions into the GEOS-CHEM such that a globally unified troposphere-stratosphere chemistry and transport can be simulated consistently without any simplifications. The tropospheric chemical mechanism in the GEOS-CHEM includes 80 species and 150 reactions. 24 tracers are transported, including O3, NOx, total nitrogen (NOy), H2O2, CO, and several types of hydrocarbon. The chemical solver used in the GEOS-CHEM model is a highly accurate sparse-matrix vectorized Gear solver (SMVGEAR). The stratospheric chemical mechanism includes an additional approximately 100 reactions and photolysis processes. Because of the large number of total chemical reactions and photolysis processes and very different photochemical regimes involved in the unified simulation, the model demands significant computer resources that are currently not practical. Therefore, several improvements will be taken, such as massive parallelization, code optimization, or selecting a faster solver. We have also continued aerosol simulation (including sulfate, dust, black carbon, organic carbon, and sea-salt) in the global model to cover most of year 2002. These results have been made available to many groups worldwide and accessible from the website http://code916.gsfc.nasa.gov/People/Chin/aot.html.

  11. Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy.

    PubMed

    Basilico, Cristina; Modica, Chiara; Maione, Federica; Vigna, Elisa; Comoglio, Paolo M

    2018-04-25

    MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET K842E retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET K842E used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience." © 2018 UICC.

  12. Chief Information Officer > Library

    Science.gov Websites

    Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department of Defense Chief Information Officer Home About DoD CIO Bios Organization DCIO C4&IIC DCIO IE

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

    ERIC Educational Resources Information Center

    Chavez, Lisa; Frankenberg, Erica

    2009-01-01

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

  14. When Unified Teacher Pay Scales Meet Differential Alternative Returns

    ERIC Educational Resources Information Center

    Walsh, Patrick

    2014-01-01

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

  15. Efficient construction of unified continuous and discontinuous Galerkin formulations for the 3D Euler equations

    NASA Astrophysics Data System (ADS)

    Abdi, Daniel S.; Giraldo, Francis X.

    2016-09-01

    A unified approach for the numerical solution of the 3D hyperbolic Euler equations using high order methods, namely continuous Galerkin (CG) and discontinuous Galerkin (DG) methods, is presented. First, we examine how classical CG that uses a global storage scheme can be constructed within the DG framework using constraint imposition techniques commonly used in the finite element literature. Then, we implement and test a simplified version in the Non-hydrostatic Unified Model of the Atmosphere (NUMA) for the case of explicit time integration and a diagonal mass matrix. Constructing CG within the DG framework allows CG to benefit from the desirable properties of DG such as, easier hp-refinement, better stability etc. Moreover, this representation allows for regional mixing of CG and DG depending on the flow regime in an area. The different flavors of CG and DG in the unified implementation are then tested for accuracy and performance using a suite of benchmark problems representative of cloud-resolving scale, meso-scale and global-scale atmospheric dynamics. The value of our unified approach is that we are able to show how to carry both CG and DG methods within the same code and also offer a simple recipe for modifying an existing CG code to DG and vice versa.

  16. Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

    PubMed

    Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

    2007-05-01

    Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

  17. 76 FR 53939 - Order of Succession for the Office of the Chief Financial Officer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... Office of the Chief Financial Officer AGENCY: Office of the Secretary, HUD. ACTION: Notice of Order of... Chief Financial Officer. This Order of Succession supersedes all prior Orders of Succession for the Office of the Chief Financial Officer. DATES: Effective Date: August 19, 2011. FOR FURTHER INFORMATION...

  18. Office Careers. Teacher's Guide. Pre-Vocational Office Education.

    ERIC Educational Resources Information Center

    Powell, Theressa

    This guide is intended for use in providing competency-based prevocational instruction in business and office occupations programs. Addressed in the individual units are the following topics: career awareness (career planning, decision making, and educational planning); personal assessment; the business and office cluster (bookkeeper, word…

  19. Medicare Information Office

    Science.gov Websites

    Agencies Alaska Pioneer Homes Behavioral Health Office of Children's Services Office of the Commissioner Office of Substance Misuse and Addiction Prevention Finance & Management Services Health Care Services Juvenile Justice Public Assistance Public Health Seniors & Disabilities Services Boards

  20. Army National Guard and U.S. Army Reserve: Promotion of Commissioned Officers and Warrant Officers Other Than General Officers

    DTIC Science & Technology

    2001-10-24

    Notification of Selection for Promotion—Officers Assigned to Control Group (Dual Component), page 57 Figure 4–15: Memorandum Format for Notification of... Group Standby Reserve (Active Status List) officers. (3) USAR officers released from AD in the grade of COL and below, and not under the jurisdiction...Control Group (Officer Active Duty Obligor) (OADO) or under administrative control of the Control Group (OADO) with concurrent assignment to a Reserve

  1. Framework Design of Unified Cross-Authentication Based on the Fourth Platform Integrated Payment

    NASA Astrophysics Data System (ADS)

    Yong, Xu; Yujin, He

    The essay advances a unified authentication based on the fourth integrated payment platform. The research aims at improving the compatibility of the authentication in electronic business and providing a reference for the establishment of credit system by seeking a way to carry out a standard unified authentication on a integrated payment platform. The essay introduces the concept of the forth integrated payment platform and finally put forward the whole structure and different components. The main issue of the essay is about the design of the credit system of the fourth integrated payment platform and the PKI/CA structure design.

  2. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    PubMed

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  3. The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism

    PubMed Central

    Eagleson, Kathie L.; Xie, Zhihui; Levitt, Pat

    2016-01-01

    People with autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy - the influence of one gene on distinct phenotypes - raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multi-functional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain, and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with ASD, reduces transcription and disrupts socially-relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways, and has a complex protein interactome that is enriched in ASD and other NDD candidates. The interactome is co-regulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, impacting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. PMID:27837921

  4. Annual Report 2008 -- Office of the Chief Financial Officer (OCFO)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fernandez, Jeffrey

    2008-12-22

    It is with great pleasure that I present to you the 2008 Chief Financial Officer's Annual Report. The data included in this report has been compiled from the Budget Office, the Controller, Procurement and Property Management and the Sponsored Projects Office. Also included are some financial comparisons with other DOE Laboratories and a glossary of commonly used acronyms.

  5. 41 CFR 101-25.104 - Acquisition of office furniture and office machines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Acquisition of office furniture and office machines. 101-25.104 Section 101-25.104 Public Contracts and Property Management... PROCUREMENT 25-GENERAL 25.1-General Policies § 101-25.104 Acquisition of office furniture and office machines...

  6. Conservation and functional importance of carbon-oxygen hydrogen bonding in AdoMet-dependent methyltransferases.

    PubMed

    Horowitz, Scott; Dirk, Lynnette M A; Yesselman, Joseph D; Nimtz, Jennifer S; Adhikari, Upendra; Mehl, Ryan A; Scheiner, Steve; Houtz, Robert L; Al-Hashimi, Hashim M; Trievel, Raymond C

    2013-10-16

    S-adenosylmethionine (AdoMet)-based methylation is integral to metabolism and signaling. AdoMet-dependent methyltransferases belong to multiple distinct classes and share a catalytic mechanism that arose through convergent evolution; however, fundamental determinants underlying this shared methyl transfer mechanism remain undefined. A survey of high-resolution crystal structures reveals that unconventional carbon-oxygen (CH···O) hydrogen bonds coordinate the AdoMet methyl group in different methyltransferases irrespective of their class, active site structure, or cofactor binding conformation. Corroborating these observations, quantum chemistry calculations demonstrate that these charged interactions formed by the AdoMet sulfonium cation are stronger than typical CH···O hydrogen bonds. Biochemical and structural studies using a model lysine methyltransferase and an active site mutant that abolishes CH···O hydrogen bonding to AdoMet illustrate that these interactions are important for high-affinity AdoMet binding and transition-state stabilization. Further, crystallographic and NMR dynamics experiments of the wild-type enzyme demonstrate that the CH···O hydrogen bonds constrain the motion of the AdoMet methyl group, potentially facilitating its alignment during catalysis. Collectively, the experimental findings with the model methyltransferase and structural survey imply that methyl CH···O hydrogen bonding represents a convergent evolutionary feature of AdoMet-dependent methyltransferases, mediating a universal mechanism for methyl transfer.

  7. Are pressure measurements effective in the assessment of office chair comfort/discomfort? A review.

    PubMed

    Zemp, Roland; Taylor, William R; Lorenzetti, Silvio

    2015-05-01

    Nowadays, the majority of jobs in the western world involves sitting in an office chair. As a result, a comfortable and supported sitting position is essential for employees. In the literature, various objective methods (e.g. pressure measurements, measurements of posture, EMG etc.) have been used to assess sitting comfort/discomfort, but their validity remains unknown. This review therefore examines the relationship between subjective comfort/discomfort and pressure measurements while sitting in office chairs. The literature search resulted in eight papers that met all our requirements. Four studies identified a relationship between subjective comfort/discomfort and pressure distribution parameters (including correlations of up to r = 0.7 ± 0.13). However, the technique for evaluating subjective comfort/discomfort seems to play an important role on the results achieved, therefore placing their validity into question. The peak pressure on the seat pan, the pressure distribution on the backrest and the pressure pattern changes (seat pan and backrest) all appear to be reliable measures for quantifying comfort or discomfort. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  8. Fatty Acid Synthase Activity as a Target for c-Met Driven Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    to aid future studies. Identification is a highly significant finding with regard to the potential for future therapeutic development targeted at...Met trafficking, stability, and ultimately oncogenic potential . Palmitoylation defective mutants will be used in animal models of c-Met driven tumor...growth (Aim 2). In addition, future work toward identifying the enzyme responsible for palmitoylation of c- Met will provide a new specific target

  9. 20 CFR 402.55 - Materials available at district offices and branch offices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Materials available at district offices and branch offices. 402.55 Section 402.55 Employees' Benefits SOCIAL SECURITY ADMINISTRATION AVAILABILITY OF INFORMATION AND RECORDS TO THE PUBLIC § 402.55 Materials available at district offices and branch offices. (a) Materials available for inspection...

  10. Physician offices marketing: assessing patients' views of office visits.

    PubMed

    Emmett, Dennis; Chandra, Ashish

    2010-01-01

    Physician offices often lack the sense of incorporating appropriate strategies to make their facilities as marketer of their services. The patient experience at a physician's office not only incorporates the care they receive from the physician but also the other non-healthcare related aspects, such as the behavior of non-health professionals as well as the appearance of the facility itself. This paper is based on a primary research conducted to assess what patients assess from a physician office visit.

  11. 12 CFR 1710.17 - Certification of disclosures by chief executive officer and chief financial officer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... officer and chief financial officer. 1710.17 Section 1710.17 Banks and Banking OFFICE OF FEDERAL HOUSING... Corporate Practices and Procedures § 1710.17 Certification of disclosures by chief executive officer and chief financial officer. The chief executive officer and the chief financial officer of an Enterprise...

  12. Unified Plant Growth Model (UPGM). 1. Background, objectives, and vision.

    USDA-ARS?s Scientific Manuscript database

    Since the development of the Environmental Policy Integrated Climate (EPIC) model in 1988, the EPIC-based plant growth code has been incorporated and modified into many agro-ecosystem models. The goals of the Unified Plant Growth Model (UPGM) project are: 1) integrating into one platform the enhance...

  13. The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

    PubMed

    Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

    2017-03-01

    People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Unified Planetary Coordinates System: A Searchable Database of Geodetic Information

    NASA Technical Reports Server (NTRS)

    Becker, K. J.a; Gaddis, L. R.; Soderblom, L. A.; Kirk, R. L.; Archinal, B. A.; Johnson, J. R.; Anderson, J. A.; Bowman-Cisneros, E.; LaVoie, S.; McAuley, M.

    2005-01-01

    Over the past 40 years, an enormous quantity of orbital remote sensing data has been collected for Mars from many missions and instruments. Unfortunately these datasets currently exist in a wide range of disparate coordinate systems, making it extremely difficult for the scientific community to easily correlate, combine, and compare data from different Mars missions and instruments. As part of our work for the PDS Imaging Node and on behalf of the USGS Astrogeology Team, we are working to solve this problem and to provide the NASA scientific research community with easy access to Mars orbital data in a unified, consistent coordinate system along with a wide variety of other key geometric variables. The Unified Planetary Coordinates (UPC) system is comprised of two main elements: (1) a database containing Mars orbital remote sensing data computed using a uniform coordinate system, and (2) a process by which continual maintainance and updates to the contents of the database are performed.

  15. A unified model explains commonness and rarity on coral reefs.

    PubMed

    Connolly, Sean R; Hughes, Terry P; Bellwood, David R

    2017-04-01

    Abundance patterns in ecological communities have important implications for biodiversity maintenance and ecosystem functioning. However, ecological theory has been largely unsuccessful at capturing multiple macroecological abundance patterns simultaneously. Here, we propose a parsimonious model that unifies widespread ecological relationships involving local aggregation, species-abundance distributions, and species associations, and we test this model against the metacommunity structure of reef-building corals and coral reef fishes across the western and central Pacific. For both corals and fishes, the unified model simultaneously captures extremely well local species-abundance distributions, interspecific variation in the strength of spatial aggregation, patterns of community similarity, species accumulation, and regional species richness, performing far better than alternative models also examined here and in previous work on coral reefs. Our approach contributes to the development of synthetic theory for large-scale patterns of community structure in nature, and to addressing ongoing challenges in biodiversity conservation at macroecological scales. © 2017 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  16. A Unified Framework for Analyzing and Designing for Stationary Arterial Networks

    DOT National Transportation Integrated Search

    2017-05-17

    This research aims to develop a unified theoretical and simulation framework for analyzing and designing signals for stationary arterial networks. Existing traffic flow models used in design and analysis of signal control strategies are either too si...

  17. A unified tensor level set for image segmentation.

    PubMed

    Wang, Bin; Gao, Xinbo; Tao, Dacheng; Li, Xuelong

    2010-06-01

    This paper presents a new region-based unified tensor level set model for image segmentation. This model introduces a three-order tensor to comprehensively depict features of pixels, e.g., gray value and the local geometrical features, such as orientation and gradient, and then, by defining a weighted distance, we generalized the representative region-based level set method from scalar to tensor. The proposed model has four main advantages compared with the traditional representative method as follows. First, involving the Gaussian filter bank, the model is robust against noise, particularly the salt- and pepper-type noise. Second, considering the local geometrical features, e.g., orientation and gradient, the model pays more attention to boundaries and makes the evolving curve stop more easily at the boundary location. Third, due to the unified tensor pixel representation representing the pixels, the model segments images more accurately and naturally. Fourth, based on a weighted distance definition, the model possesses the capacity to cope with data varying from scalar to vector, then to high-order tensor. We apply the proposed method to synthetic, medical, and natural images, and the result suggests that the proposed method is superior to the available representative region-based level set method.

  18. Clinical analysis by next-generation sequencing for NSCLC patients with MET amplification resistant to osimertinib.

    PubMed

    Wang, Yubo; Li, Li; Han, Rui; Jiao, Lin; Zheng, Jie; He, Yong

    2018-04-01

    The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as MET amplification. However, cohort studies of osimertinib resistance mechanism, and the correlation of MET and progression-free survival (PFS) after osimertinib resistance have been poorly investigated. This study was carried out to study the acquired MET amplification after osimertinib resistance in advanced lung adenocarcinoma patients, and interrogate the correlation of clinical prognosis and MET amplification. We performed capture-based sequencing on longitudinal plasma and tissue samples obtained before osimertinib treatment and after resistance development from lung adenocarcinoma patients to investigate the underlying resistance mechanism. We also investigated the correlation of MET amplification and patient prognosis after osimertinib resistance using Kaplan-Meier analysis. Paired biopsies before osimertinib treatment and after the resistance development revealed underlying resistance mechanisms. In addition, a cohort of 13 patients who developed disease progression after osimertinib resistance was investigated. Patients with MET amplification after osimertinib resistance commonly had inferior median progression-free survival (mPFS) than patients without MET amplification appearance or increase (3.5 months vs. 9.9 months, p = .117). Patients in MET amplification group also displayed poor median overall survival (mOS) compared to MET amplification negative group (15.6 months vs. 30.7 months, p = .885). Furthermore, combinatorial treatment of first/third-generation EGFR-TKI and crizotinib was efficaciously administrated into two patients with newly acquired MET amplification after osimertinib resistance. Partial responses were achieved by them, both clinically and radiographically. We investigated the osimertinib resistance mechanism in a small cohort of lung adenocarcinoma patients, and demonstrated MET amplification was correlated with inferior PFS

  19. Prevalence of oral cancer self-examination among elderly people treated under Brazil's Unified Health System: household health survey.

    PubMed

    Martins, Andréa Maria Eleutério de Barros Lima; Souza, João Gabriel Silva; Haikal, Desireé Sant'Ana; de Paula, Alfredo Maurício Batista; Ferreira e Ferreira, Efigênia; Pordeus, Isabela Almeida

    2015-04-01

    The aim of this study was to examine the prevalence of oral cancer self-examinationamong the elderly and confirm whether prevalence was higher among users of the dental services provided by Brazil's Unified Health System (SUS, acronym in Portuguese). A transversal study of elderly people aged between 65 and 74 years living in a large-sized Brazilian municipality was conducted using simple random sampling. Logistic regression was conducted and results were corrected for sample design and unequal weighting using the SPSS(r) software. The study assessed 740 individuals. A total of 492 met the inclusion criteria, of which 101 (22.4%) reported having performed an oral cancer self-examination. Prevalence was higher among users of the dental services provided by the SUS, higher-income individuals, people with higher levels of education, individuals that used a removable dental prosthesis, and people who had not experienced discomfort attributed to oral condition, and lower among people who sought regular and periodic dental treatment and individuals who did not have a drinking habit. This type of self-care should be encouraged by public health policies which respond to the needs of the elderly, with emphasis on users of private and philanthropic services, and other services outside the public health network.

  20. Pediatric office emergencies.

    PubMed

    Fuchs, Susan

    2013-10-01

    Pediatricians regularly see emergencies in the office, or children that require transfer to an emergency department, or hospitalization. An office self-assessment is the first step in determining how to prepare for an emergency. The use of mock codes and skill drills make office personnel feel less anxious about medical emergencies. Emergency information forms provide valuable, quick information about complex patients for emergency medical services and other physicians caring for patients. Furthermore, disaster planning should be part of an office preparedness plan. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Next Generation Community Based Unified Global Modeling System Development and Operational Implementation Strategies at NCEP

    NASA Astrophysics Data System (ADS)

    Tallapragada, V.

    2017-12-01

    NOAA's Next Generation Global Prediction System (NGGPS) has provided the unique opportunity to develop and implement a non-hydrostatic global model based on Geophysical Fluid Dynamics Laboratory (GFDL) Finite Volume Cubed Sphere (FV3) Dynamic Core at National Centers for Environmental Prediction (NCEP), making a leap-step advancement in seamless prediction capabilities across all spatial and temporal scales. Model development efforts are centralized with unified model development in the NOAA Environmental Modeling System (NEMS) infrastructure based on Earth System Modeling Framework (ESMF). A more sophisticated coupling among various earth system components is being enabled within NEMS following National Unified Operational Prediction Capability (NUOPC) standards. The eventual goal of unifying global and regional models will enable operational global models operating at convective resolving scales. Apart from the advanced non-hydrostatic dynamic core and coupling to various earth system components, advanced physics and data assimilation techniques are essential for improved forecast skill. NGGPS is spearheading ambitious physics and data assimilation strategies, concentrating on creation of a Common Community Physics Package (CCPP) and Joint Effort for Data Assimilation Integration (JEDI). Both initiatives are expected to be community developed, with emphasis on research transitioning to operations (R2O). The unified modeling system is being built to support the needs of both operations and research. Different layers of community partners are also established with specific roles/responsibilities for researchers, core development partners, trusted super-users, and operations. Stakeholders are engaged at all stages to help drive the direction of development, resources allocations and prioritization. This talk presents the current and future plans of unified model development at NCEP for weather, sub-seasonal, and seasonal climate prediction applications with special

  2. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    PubMed

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  3. A Unified and Coherent Land Surface Emissivity Earth System Data Record

    NASA Astrophysics Data System (ADS)

    Knuteson, R. O.; Borbas, E. E.; Hulley, G. C.; Hook, S. J.; Anderson, M. C.; Pinker, R. T.; Hain, C.; Guillevic, P. C.

    2014-12-01

    Land Surface Temperature and Emissivity (LST&E) data are essential for a wide variety of studies from calculating the evapo-transpiration of plant canopies to retrieving atmospheric water vapor. LST&E products are generated from data acquired by sensors in low Earth orbit (LEO) and by sensors in geostationary Earth orbit (GEO). Although these products represent the same measure, they are produced at different spatial, spectral and temporal resolutions using different algorithms. The different approaches used to retrieve the temperatures and emissivities result in discrepancies and inconsistencies between the different products. NASA has identified a major need to develop long-term, consistent, and calibrated data and products that are valid across multiple missions and satellite sensors. This poster will introduce the land surface emissivity product of the NASA MEASUREs project called A Unified and Coherent Land Surface Temperature and Emissivity (LST&E) Earth System Data Record (ESDR). To develop a unified high spectral resolution emissivity database, the MODIS baseline-fit emissivity database (MODBF) produced at the University of Wisconsin-Madison and the ASTER Global Emissivity Database (ASTER GED) produced at JPL will be merged. The unified Emissivity ESDR will be produced globally at 5km in mean monthly time-steps and for 12 bands from 3.6-14.3 micron and extended to 417 bands using a PC regression approach. The poster will introduce this data product. LST&E is a critical ESDR for a wide variety of studies in particular ecosystem and climate modeling.

  4. Unified formalism for the generalized kth-order Hamilton-Jacobi problem

    NASA Astrophysics Data System (ADS)

    Colombo, Leonardo; de Léon, Manuel; Prieto-Martínez, Pedro Daniel; Román-Roy, Narciso

    2014-08-01

    The geometric formulation of the Hamilton-Jacobi theory enables us to generalize it to systems of higher-order ordinary differential equations. In this work we introduce the unified Lagrangian-Hamiltonian formalism for the geometric Hamilton-Jacobi theory on higher-order autonomous dynamical systems described by regular Lagrangian functions.

  5. Unified Behavior Framework for Discrete Event Simulation Systems

    DTIC Science & Technology

    2015-03-26

    I would like to thank Dr. Hodson for his guidance and direction throughout the AFIT program. I also would like to thank my thesis committee members...SPA Sense-Plan-Act SSL System Service Layer TCA Task Control Architecture TRP Teleo-Reactive Program UAV Unmanned Aerial Vehicle UBF Unified Behavior...a teleo-reactive architecture [11]. Teleo-Reactive Programs ( TRPs ) are composed of a list of rules, where each has a condition and an action. When the

  6. Hydration Status in US Military Officer Students.

    PubMed

    Rogers, Reva; Cole, Renee

    2016-01-01

    Relocation from a cool to a hot climate is a frequent occurrence in military service. Acclimatization requires time and exposure to heat. Nonacclimatized individuals frequently consume inadequate fluid leading to hypohydration, which can quickly result in dehydration with increased risk of heat illness/injury. This descriptive cross-sectional study assessed the hydration status of 196 officers attending the US Army Medical Department's Officer Basic Course (67%) or Captain's Career Course (33%) in San Antonio, Texas, prior to taking the Army Physical Fitness Test (APFT). Consenting Soldiers provided a first morning void urine sample and demographic survey (age, rank, sex, previous geographic location, etc) prior to the APFT. Height, weight, and APFT event scores were collected from a subject-coded, APFT scorecard without personal information data. Binary logistic regression was performed to identify variables that contribute to predicting hypohydration status. The sample population was 54% male, a mean age of 30 years, 5.2 years of military service, and a mean body mass index of 25 kg/m². Nearly one-third met the criteria for hypohydration (≥1.02 urine specific gravity). Soldiers who relocated from a cool environment within 9 days of taking the APFT had 2.1 higher odds of being hypohydrated compared with individuals who had resided in a hot environment for more than 9 days. Women had a 0.5 lower odds of being hypohydrated as compared to males. Significantly more Soldiers were hypohydrated on Monday compared to those tested on Tuesday (33% vs 16%, P=.004). Given these findings, the authors provided 5 recommendations to reduce the number of Soldiers exercising in a hypohydrated state.

  7. Inhibition of EGFR Induces a c-MET Driven Stem Cell Population in Glioblastoma

    PubMed Central

    Jun, Hyun Jung; Bronson, Roderick T.; Charest, Al

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal form of primary brain tumors, characterized by highly invasive and aggressive tumors that are resistant to all current therapeutic options. GBMs are highly heterogeneous in nature and contain a small but highly tumorigenic and self-renewing population of stem or initiating cells (Glioblastoma stem cells or GSCs). GSCs have been shown to contribute to tumor propagation and resistance to current therapeutic modalities. Recent studies of human GBMs have elucidated the genetic alterations common in these tumors, but much remains unknown about specific signaling pathways that regulate GSCs. Here we identify a distinct fraction of cells in a genetically engineered mouse model of EGFR-driven GBM that respond to anti-EGFR therapy by inducing high levels of c-MET expression. The MET positive cells displayed clonogenic potential and long-term self-renewal ability in vitro and are capable of differentiating into multiple lineages. The MET positive GBM cells are resistant to radiation and highly tumorigenic in vivo. Activation of MET signaling led to an increase in expression of the stemness transcriptional regulators Oct4, Nanog and Klf4. Pharmacological inhibition of MET activity in GSCs prevented the activation of Oct4, Nanog and Klf4 and potently abrogated stemness. Finally, the MET expressing cells were preferentially localized in perivascular regions of mouse tumors consistent with their function as GSCs. Together, our findings indicate that EGFR inhibition in GBM induces MET activation in GSCs, which is a functional requisite for GSCs activity and thus represents a promising therapeutic target. PMID:24115218

  8. Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse

    PubMed Central

    Xie, Zhihui; Li, Jing; Baker, Jonathan; Eagleson, Kathie L.; Coba, Marcelo P.; Levitt, Pat

    2016-01-01

    Background Atypical synapse development and plasticity are implicated in many neurodevelopmental disorders (NDDs). NDD-associated, high confidence risk genes have been identified, yet little is known about functional relationships at the level of protein-protein interactions, which are the dominant molecular bases responsible for mediating circuit development. Methods Proteomics in three independent developing neocortical synaptosomal preparations identified putative interacting proteins of the ligand-activated MET receptor tyrosine kinase, an autism risk gene that mediates synapse development. The candidates were translated into interactome networks and analyzed bioinformatically. Additionally, three independent quantitative proximity ligation assays (PLA) in cultured neurons and four independent immunoprecipitation analyses of synaptosomes validated protein interactions. Results Approximately 11% (8/72) of MET-interacting proteins, including SHANK3, SYNGAP1 and GRIN2B, are associated with NDDs. Proteins in the MET interactome were translated into a novel MET interactome network based on human protein-protein interaction databases. High confidence genes from different NDD datasets that encode synaptosomal proteins were analyzed for being enriched in MET interactome proteins. This was found for autism, but not schizophrenia, bipolar disorder, major depressive disorder or attentional deficit hyperactivity disorder. There is correlated gene expression between MET and its interactive partners in developing human temporal and visual neocortices, but not with highly expressed genes that are not in the interactome. PLA and biochemical analyses demonstrate that MET-protein partner interactions are dynamically regulated by receptor activation. Conclusions The results provide a novel molecular framework for deciphering the functional relations of key regulators of synaptogenesis that contribute to both typical cortical development and to NDDs. PMID:27086544

  9. Macroporous hydrogel micropillars for quantifying Met kinase activity in cancer cell lysates.

    PubMed

    Powers, Alicia D; Liu, Bi; Lee, Andrew G; Palecek, Sean P

    2012-09-07

    Overactive and overexpressed kinases have been implicated in the cause and progression of many cancers. Kinase inhibitors offer a targeted approach for treating cancers associated with increased or deregulated kinase activity. Often, however, cancer cells exhibit initial resistance to these inhibitors or evolve to develop resistance during treatment. Additionally, cancers of any one tissue type are typically heterogeneous in their oncogenesis mechanisms, and thus diagnosis of a particular type of cancer does not necessarily provide insight into what kinase therapies may be effective. For example, while some lung cancer cells that overexpress the epidermal growth factor receptor (EFGR) respond to treatment with EGFR kinase inhibitors, overexpression or hyperactivity of Met kinase correlates with resistance to EGFR kinase inhibitors. Here we describe a microfluidic-based assay for quantifying Met kinase activity in cancer cell lysates with the eventual goals of predicting cancer cell responsiveness to kinase inhibitors and monitoring development of resistance to these inhibitors. In this assay, we immobilized a phosphorylation substrate for Met kinase into macroporous hydrogel micropillars. We then exposed the micropillars to a cancer cell lysate and detected substrate phosphorylation using a fluorescently conjugated antibody. This assay is able to quantify Met kinase activity in whole cell lysate from as few as 150 cancer cells. It can also detect cells expressing overactive Met kinase in a background of up to 75% non-cancerous cells. Additionally, the assay can quantify kinase inhibition by the Met-specific kinase inhibitors SU11274 and PHA665752, suggesting predictive capability for cellular response to kinase inhibitors.

  10. 3 CFR - Designation of Officers of the Office of Personnel Management To Act as Director of the Office of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 3 The President 1 2013-01-01 2013-01-01 false Designation of Officers of the Office of Personnel Management To Act as Director of the Office of Personnel Management Presidential Documents Other Presidential... from this memorandum in designating an acting Director. Sec. 3. Prior Memorandum Superseded. This...

  11. 41. BOW SPACES (YN OFFICES, AYN OFFICES & DECK SHOP, ...

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

    41. BOW SPACES (YN OFFICES, AYN OFFICES & DECK SHOP, LAUNDRY & BOS'N STORES), WITH HATCH TO PAINT LOCKER AT LEFT. - U.S. Coast Guard Cutter WHITE HEATH, USGS Integrated Support Command Boston, 427 Commercial Street, Boston, Suffolk County, MA

  12. Unified theory of the exciplex formation/dissipation.

    PubMed

    Khokhlova, Svetlana S; Burshtein, Anatoly I

    2010-11-04

    The natural extension and reformulation of the unified theory (UT) proposed here makes it integro-differential and capable of describing the distant quenching of excitation by electron transfer, accompanied with contact but reversible exciplex formation. The numerical solution of the new UT equations allows specifying the kinetics of the fluorescence quenching and exciplex association/dissociation as well as those reactions' quantum yields. It was demonstrated that the distant electron transfer in either the normal or inverted Marcus regions screens the contact reaction of exciplex formation, especially at slow diffusion.

  13. (1S,2E,4S,7E,11E)-2,7,11-Cembratriene-4,6-diol semisynthetic analogs as novel c-Met inhibitors for the control of c-Met-dependent breast malignancies.

    PubMed

    Ebrahim, Hassan Y; Mohyeldin, Mohamed M; Hailat, Mohammad M; El Sayed, Khalid A

    2016-11-15

    (1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer. Breast cancer is the most diagnosed cancer in women and ranked second female disease killer. The receptor tyrosine kinase c-Met correlates with aggressiveness of certain breast cancer phenotypes and thus considered a valid therapeutic target. This study reports the discovery and optimization of the tobacco-based cembranoid 1 as a novel c-Met inhibitory scaffold using combined structure- and ligand-based approaches. 1 displayed antiproliferative, anti-migratory and anti-invasive effects against the c-Met overexpressing MDA-MB-231 breast cancer cells at moderate μM concentrations. The Z'-LYTE kinase platform and Western blot analysis identified c-Met as a potential macromolecular target. Rationally designed carbamate analogs were proposed to probe additional targeted c-Met interactions and improve the cellular potency. The 6-phenyl carbamate 3 showed enhanced c-Met inhibitory activity. Structure-activity relationships of different substituents on the 3's phenyl moiety were studied. The most active analog 20 showed potent in vitro anticancer activity against the MDA-MB-231 breast cancer cells at low μM concentrations, with minimal toxicity on the non-tumorigenic MCF-10A mammary epithelial cells. Cembranoid 20 potently inhibited the c-Met catalytic activity in Z'-LYTE kinase assay and various cellular c-Met-driven signaling pathways. Furthermore, 20 displayed a robust antitumor activity in a breast cancer xenograft athymic mouse model and thus promoted to the lead rank. Cembranoids are novel c-Met inhibitors appropriate for future use to control c-Met dependent malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus.

    PubMed

    Ukkola, O; Kesäniemi, Y A

    2003-10-01

    The association between the Leu72Met polymorphism of the preproghrelin gene and diabetic complications was examined in patients with type 2 diabetes mellitus. A total of 258 patients with type 2 diabetes mellitus and 522 control subjects were screened. Genotypes were determined by polymerase chain reaction technique. The diagnosis of coronary heart disease was based on clinical and ECG criteria. Laboratory analyses were carried out in the hospital laboratory. No differences in the genotype distributions and allele frequencies of the preproghrelin Leu72Met polymorphism were found between type 2 diabetes mellitus patients and controls. The polymorphism was not associated with macro- or micro-angiopathy or hypertension. However, Leu72Met polymorphism was associated with serum creatinine (P = 0.006) and lipoprotein(a) [Lp(a)] levels (P = 0.006) with Leu72Leu subjects showing the highest values. This association was observed only amongst diabetic group. The Leu72Met polymorphism of the preproghrelin gene was not related to cardiovascular disease in type 2 diabetes mellitus patients. Leu72Met polymorphism was, however, associated with serum creatinine and Lp(a) levels in diabetic patients. The mechanism might be associated with a possible change in ghrelin product and its somatotropic effect.

  15. NARSTO PAC2001 CONVAIR PM OZONE MET DATA

    Atmospheric Science Data Center

    2018-04-09

    NARSTO PAC2001 CONVAIR PM OZONE MET DATA Project Title:  NARSTO Discipline:  Tropospheric Composition Field Campaigns Aerosols ... Temperature Probe Humidity Probe Wind Sensor UV Ozone Detector Optical Counter Location:  Lower Fraser ...

  16. Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.

    PubMed

    Bell, Diana; Ferrarotto, Renata; Fox, Melanie D; Roberts, Dianna; Hanna, Ehab Y; Weber, Randal S; El-Naggar, Adel K

    2015-01-01

    Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types. In this study, we evaluated the expression of c-Met by immunohistochemistry (IHC) in a large cohort of salivary gland ACCs and examined its clinicopathologic implications. Archival formalin-fixed paraffin-embedded blocks from 200 ACC patients were used in this study. Pathologic patterns and phenotypic expression of c-Met were recorded and compared with clinical factors including gender, age, disease stage at diagnosis, and clinical outcomes. Correlations between c-MET expression and clinical characteristics were assessed by Pearson's chi-square test or by the 2-tailed Fisher exact test. Curves describing overall survival were generated by Kaplan-Meier product limit method. Strong c-MET expression was seen in inner ductal and outer myoepithelial cells in 53.2% of the cases. There was no correlation between c-Met overexpression and clinicopathologic parameters or patient's overall survival ( p = .94074). In conclusion, c-MET expression is high in a significant subgroup of ACC patients. While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation.

  17. Unifying physical concepts of reality

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 andmore » 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.« less

  18. A Unified, Transdiagnostic Treatment for Adolescents With Chronic Pain and Comorbid Anxiety and Depression

    PubMed Central

    Allen, Laura B.; Tsao, Jennie C.I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

    2017-01-01

    Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional disorders and suggest the possibility of extending these interventions to chronic pain and pain-related dysfunction. This case report describes the use of a unified protocol for treatment of an adolescent boy with chronic daily headache and social anxiety and an adolescent girl with whole body pain and depression. Following weekly, 50-minute individual treatment sessions, the boy demonstrated notable improvement in emotional symptoms, emotion regulation skills, somatization, and functional disability. The girl showed some improvement on measures of anxiety and depression, although there appeared to be a worsening of pain symptoms and somatization. However, both patients demonstrated improvement over follow-up. This case study illustrates the potential utility of a unified treatment approach targeting pain and emotional symptoms from an emotion regulation perspective in an adolescent population. PMID:28824271

  19. The MetLife Survey of the American Teacher: Preparing Students for College and Careers

    ERIC Educational Resources Information Center

    MetLife, Inc., 2011

    2011-01-01

    "The MetLife Survey of the American Teacher: Preparing Students for College and Careers" was conducted by Harris Interactive and is the twenty-seventh in a series sponsored annually by MetLife since 1984 to give voice to those closest to the classroom. This MetLife Survey examines the priority that all students graduate from high school prepared…

  20. MetNetAPI: A flexible method to access and manipulate biological network data from MetNet

    PubMed Central

    2010-01-01

    Background Convenient programmatic access to different biological databases allows automated integration of scientific knowledge. Many databases support a function to download files or data snapshots, or a webservice that offers "live" data. However, the functionality that a database offers cannot be represented in a static data download file, and webservices may consume considerable computational resources from the host server. Results MetNetAPI is a versatile Application Programming Interface (API) to the MetNetDB database. It abstracts, captures and retains operations away from a biological network repository and website. A range of database functions, previously only available online, can be immediately (and independently from the website) applied to a dataset of interest. Data is available in four layers: molecular entities, localized entities (linked to a specific organelle), interactions, and pathways. Navigation between these layers is intuitive (e.g. one can request the molecular entities in a pathway, as well as request in what pathways a specific entity participates). Data retrieval can be customized: Network objects allow the construction of new and integration of existing pathways and interactions, which can be uploaded back to our server. In contrast to webservices, the computational demand on the host server is limited to processing data-related queries only. Conclusions An API provides several advantages to a systems biology software platform. MetNetAPI illustrates an interface with a central repository of data that represents the complex interrelationships of a metabolic and regulatory network. As an alternative to data-dumps and webservices, it allows access to a current and "live" database and exposes analytical functions to application developers. Yet it only requires limited resources on the server-side (thin server/fat client setup). The API is available for Java, Microsoft.NET and R programming environments and offers flexible query and broad