CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2003-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM2_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2006-10-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM2_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2002-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

Clouds and the Earth's Radiant Energy System (CERES) algorithm theoretical basis document. volume 2; Geolocation, calibration, and ERBE-like analyses (subsystems 1-3)

Science.gov (United States)

Wielicki, B. A. (Principal Investigator); Barkstrom, B. R. (Principal Investigator); Charlock, T. P.; Baum, B. A.; Green, R. N.; Minnis, P.; Smith, G. L.; Coakley, J. A.; Randall, D. R.; Lee, R. B., III

1995-01-01

The theoretical bases for the Release 1 algorithms that will be used to process satellite data for investigation of the Clouds and Earth's Radiant Energy System (CERES) are described. The architecture for software implementation of the methodologies is outlined. Volume 2 details the techniques used to geolocate and calibrate the CERES scanning radiometer measurements of shortwave and longwave radiance to invert the radiances to top-of-the-atmosphere (TOA) and surface fluxes following the Earth Radiation Budget Experiment (ERBE) approach, and to average the fluxes over various time and spatial scales to produce an ERBE-like product. Spacecraft ephemeris and sensor telemetry are used with calibration coefficients to produce a chronologically ordered data product called bidirectional scan (BDS) radiances. A spatially organized instrument Earth scan product is developed for the cloud-processing subsystem. The ERBE-like inversion subsystem converts BDS radiances to unfiltered instantaneous TOA and surface fluxes. The TOA fluxes are determined by using established ERBE techniques. Hourly TOA fluxes are computed from the instantaneous values by using ERBE methods. Hourly surface fluxes are estimated from TOA fluxes by using simple parameterizations based on recent research. The averaging process produces daily, monthly-hourly, and monthly means of TOA and surface fluxes at various scales. This product provides a continuation of the ERBE record.

Top-of-atmosphere radiative fluxes - Validation of ERBE scanner inversion algorithm using Nimbus-7 ERB data

Science.gov (United States)

Suttles, John T.; Wielicki, Bruce A.; Vemury, Sastri

1992-01-01

The ERBE algorithm is applied to the Nimbus-7 earth radiation budget (ERB) scanner data for June 1979 to analyze the performance of an inversion method in deriving top-of-atmosphere albedos and longwave radiative fluxes. The performance is assessed by comparing ERBE algorithm results with appropriate results derived using the sorting-by-angular-bins (SAB) method, the ERB MATRIX algorithm, and the 'new-cloud ERB' (NCLE) algorithm. Comparisons are made for top-of-atmosphere albedos, longwave fluxes, viewing zenith-angle dependence of derived albedos and longwave fluxes, and cloud fractional coverage. Using the SAB method as a reference, the rms accuracy of monthly average ERBE-derived results are estimated to be 0.0165 (5.6 W/sq m) for albedos (shortwave fluxes) and 3.0 W/sq m for longwave fluxes. The ERBE-derived results were found to depend systematically on the viewing zenith angle, varying from near nadir to near the limb by about 10 percent for albedos and by 6-7 percent for longwave fluxes. Analyses indicated that the ERBE angular models are the most likely source of the systematic angular dependences. Comparison of the ERBE-derived cloud fractions, based on a maximum-likelihood estimation method, with results from the NCLE showed agreement within about 10 percent.

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES4_TRMM-PFM_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=1998-08-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

Energy Technology Data Exchange (ETDEWEB)

Okazaki, Shogo [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nakatani, Fumi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Masuko, Kazue; Tsuchihashi, Kenji [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ueda, Shiho; Masuko, Takashi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nagano, Osamu, E-mail: osmna@sb3.so-net.ne.jp [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

2016-01-29

The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

International Nuclear Information System (INIS)

Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

2016-01-01

The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

Characterization of the promoter region of the human c-erbB-2 protooncogene

International Nuclear Information System (INIS)

Ishii, S.; Imamoto, F.; Yamanashi, Y.; Toyoshima, K.; Yamamoto, T.

1987-01-01

Three overlapping genomic clones that contain the 5'-terminal portion of the human c-erbB-2 gene (ERBB2) were isolated. The promoter region was identified by nuclease S1 mapping with c-erbB-2 mRNA. Seven transcriptional start sites were identified. DNA sequence analysis showed that the promoter region contains a TATA box and a CAAT box about 30 and 80 base pairs (bp), respectively, upstream of the most downstream RNA initiation site. Two putative binding sites for transcription factor Sp1 were identified about 50 and 110 bp upstream of the CAAT box, and six GGA repeats were found between the CAAT box and the TATA box. This region had strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into monkey CV-1 cells. These data indicate that the promoter of the human c-erbB-2 protooncogene is different from that of the protooncogene c-erbB-1 (epidermal growth factor receptor gene), which does not contain either a TATA box or a CAAT box. Comparison of the promoter sequences and activities of the two protooncogenes should be helpful in analysis of the regulatory mechanism of expression of their gene products, which are growth-factor receptors

c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.

Science.gov (United States)

Iglesias, T; Llanos, S; López-Barahona, M; Pérez-Aranda, A; Rodríguez-Peña, A; Bernal, J; Höhne, A; Seliger, B; Muñoz, A

1994-07-01

The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential for collocated AGLP and ERBE data for fire, smoke, and radiation budget studies

International Nuclear Information System (INIS)

Christopher, S.A.; Chou, J.

1997-01-01

One month of the Advanced Very High Resolution Radiometer (AVHRR) Global Area Coverage (GAC) Land Pathfinder (AGLP) data from September 1985 are used to examine the spatial and temporal distribution of fires over four major ecosystems in South America. The Earth Radiation Budget Experiment (ERBE) scanner data are used to examine the top of atmosphere (TOA) shortwave and longwave fluxes over smoke generated from biomass burn- ing. The relationship between the AGLP-derived Normalized Difference Vegetation Index (NDVI) and the ERBE-estimated clear sky albedos are also examined as a function of the four ecosystems. This study shows that the grassland areas in South America have the highest number of fires for September 1985, and their corresponding NDVI values are smaller than the tropical rainforest region where the number of fires were comparatively small. Clear sky statistics accumulated during the days when smoke was not present show that clear sky albedos derived from ERBE are higher for grassland areas when compared to the tropical rainforest. The results show that the AGLP can be used to determine the spatial and temporal distribution of fires along with vegetation characteristics, while ERBE data can provide necessary information on broadband albedos and regional top of atmosphere radiative impacts of biomass burning aerosols. Since the AGLP data are available from 1981 to the present day, several climate-related issues can be addressed

ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

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Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

2009-09-25

The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function

DEFF Research Database (Denmark)

Bugge, Anne Skovsø; Feng, Dan; Everett, Logan J

2012-01-01

of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast......-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set...

ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

Energy Technology Data Exchange (ETDEWEB)

Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J; Brugge, Joan S

2001-08-08

Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

Kinesio arm taping as prophylaxis against the development of Erb's Engram.

Science.gov (United States)

ElKhatib, Radwa S; ElNegmy, Emam H; Salem, Amina H; Sherief, AbdelAziz A

2013-11-01

An Erb's Engram is a common debility that develops in recovering children with Erb's palsy. The purpose of this study was to investigate the effect of kinesiotaping over the deltoid and the forearm on the development of proper upper extremity function in children recovering from Erb's palsy. Thirty patients with Erb's palsy participated for 3 months in this study and were equally divided into two groups; control group A and study group B. The two groups received the same designed physical therapy program, while group B along the program, received kinesiotaping over the deltoid and the forearm. The subjects were evaluated, pre and post-treatment, and scored functionally, using the Toronto Active Motion Scale, and objectively, using an EMG device utilized to obtain the percentages of degeneration of the deltoid and the biceps muscles. Post-treatment values of six out of nine measured variables, between the two groups, revealed significant difference in favor of group B. The obtained results strongly support the introduction of kinesiotaping of the deltoid and the forearm as an adjunct to the treatment program of Erb's palsied children.

Auditory ERB like admissible wavelet packet features for TIMIT phoneme recognition

Directory of Open Access Journals (Sweden)

P.K. Sahu

2014-09-01

Full Text Available In recent years wavelet transform has been found to be an effective tool for time–frequency analysis. Wavelet transform has been used as feature extraction in speech recognition applications and it has proved to be an effective technique for unvoiced phoneme classification. In this paper a new filter structure using admissible wavelet packet is analyzed for English phoneme recognition. These filters have the benefit of having frequency bands spacing similar to the auditory Equivalent Rectangular Bandwidth (ERB scale. Central frequencies of ERB scale are equally distributed along the frequency response of human cochlea. A new sets of features are derived using wavelet packet transform's multi-resolution capabilities and found to be better than conventional features for unvoiced phoneme problems. Some of the noises from NOISEX-92 database has been used for preparing the artificial noisy database to test the robustness of wavelet based features.

Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins

Directory of Open Access Journals (Sweden)

Jesus Eliane C.

2005-01-01

Full Text Available PURPOSE: To evaluate the prognostic significance and correlation with staging and degree of cell differentiation of the tumoral expression of the proteins c-erbB-2 and E-cadherin, in patients with colorectal adenocarcinoma. METHODS: The study included 117 patients with an average age of 63.1 years and an average follow-up duration of 28.1 months. The disease-free interval, survival, incidence of recurrence and specific mortality were evaluated. c-erbB-2 anti-oncoprotein antibodies (Dako were utilized via the streptavidin-biotin technique. Samples were considered to be positive for c-erbB-2 if 10% or more of the tumor cell membranes were stained.The anti-E-cadherin antibodies (Dako, evaluated this protein and is considered positive, if 50% or more of the cell membranes were stained. Statistical analysis was performed using Pearson's chi-squared test, Fisher's exact test, Kaplan-Meier's estimator, the log-rank test and Wilcoxon's test (Breslow version, setting the level of statistical significance at 5% (p<0.05. RESULTS: 52 of 108 patients studied for c-erbB-2 were positive (48,1%, 47 of 93 patients studied for E-cadherin were negative (50,5%. These data do not express any correlation with TNM (tumor, node and metastasis staging and the degree of cell differentiation or with the tumor recurrence rate. The disease-free interval among patients who were positive for c-erbB-2 and negative for E-cadherin was 68.0 months and did not differ from those with c-erbB-2 negative and E-cadherin positive ( 55.0 months - p = 0.5510. The average survival among patients positive for c-erbB-2 and negative for E-cadherin was 75 months without statistical significance difference with the other group ( 61 months - p = 0.5256. Specific mortality occurred in 20.0% of the cases and did not correlate with the expression of c-erbB-2 (p=0,446, E-cadherin (p=0,883. CONCLUSION: The tumoral expression of c-erbB-2 and E-cadherin did not demonstrate a correlation with the

Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

Science.gov (United States)

Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

2014-01-01

Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII

DEFF Research Database (Denmark)

Disela, C; Glineur, C; Bugge, T

1991-01-01

The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte...... of this CAII reporter construct could only be suppressed by very high amounts of v-erbA. Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein....

Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

DEFF Research Database (Denmark)

Staberg, Mikkel; Riemer, Christian; Xu, Ruodan

2013-01-01

B1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U...... processing. RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration....... Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation. CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma...

Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.

Science.gov (United States)

Grabinski, Nicole; Ewald, Florian

2014-12-01

Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton's tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer. It is now an FDA-approved drug marketed under the name Imbruvica(TM) (Pharmacyclics, Inc.) and successfully used as an orally administered second-line drug in the treatment of mantle cell lymphoma. Since BTK is predominantly expressed in hematopoietic cells, the sensitivity of solid tumor cells to Ibrutinib has not been analyzed. In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells. Combination indices below 0.25 at 50% inhibition of cell viability were determined by the Chou-Talalay method. Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors. Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.

The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

Science.gov (United States)

Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

2000-01-01

Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

Role of Erbin in ErbB2-dependent breast tumor growth

Science.gov (United States)

Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

2014-01-01

ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

International Nuclear Information System (INIS)

Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

2011-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts.

Science.gov (United States)

Mellinghoff, Ingo K; Tran, Chris; Sawyers, Charles L

2002-09-15

Experiments with human prostate cancer cell lines have shown that forced overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen-independent growth and increases androgen receptor-transcriptional activity in a ligand-independent fashion. To investigate the relationship between ErbB-RTK signaling and androgen in genetically unmanipulated human prostate cancer, we performed biochemical and biological studies with the dual ErbB1/ErbB2 RTK inhibitor PKI-166 using human prostate cancer xenograft models with isogenic sublines reflecting the transition from androgen-dependent to androgen-independent growth. In the presence of low androgen concentrations, PKI-166 showed profound growth-inhibitory effects on tumor growth, which could be partially reversed by androgen add-back. At physiological androgen concentrations, androgen withdrawal greatly enhanced the ability of PKI-166 to retard tumor growth. The level of extracellular signal-regulated kinase activation correlated with the response to PKI-166 treatment, whereas the expression levels of ErbB1 and ErbB2 did not. These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway.

Suppression of atherosclerosis by synthetic REV-ERB agonist

Energy Technology Data Exchange (ETDEWEB)

Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

International Nuclear Information System (INIS)

Schillaci, Roxana; Charreau, Eduardo H; Maronna, Esteban; Roa, Juan C; Elizalde, Patricia V; Guzmán, Pablo; Cayrol, Florencia; Beguelin, Wendy; Díaz Flaqué, María C; Proietti, Cecilia J; Pineda, Viviana; Palazzi, Jorge; Frahm, Isabel

2012-01-01

The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration

Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

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Schillaci Roxana

2012-02-01

Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

1999-2003 Shortwave Characterizations of Earth Radiation Budget Satellite (ERBS)/Earth Radiation Budget Experiment (ERBE) Broadband Active Cavity Radiometer Sensors

Science.gov (United States)

Lee, Robert B., III; Smith, George L.; Wong, Takmeng

2008-01-01

From October 1984 through May 2005, the NASA Earth Radiation Budget Satellite (ERBS/ )/Earth Radiation Budget Experiment (ERBE)ERBE nonscanning active cavity radiometers (ACR) were used to monitor long-term changes in the earth radiation budget components of the incoming total solar irradiance (TSI), earth-reflected TSI, and earth-emitted outgoing longwave radiation (OLR). From September1984 through September 1999, using on-board calibration systems, the ERBS/ERBE ACR sensor response changes, in gains and offsets, were determined from on-orbit calibration sources and from direct observations of the incoming TSI through calibration solar ports at measurement precision levels approaching 0.5 W/sq m , at satellite altitudes. On October 6, 1999, the onboard radiometer calibration system elevation drive failed. Thereafter, special spacecraft maneuvers were performed to observe cold space and the sun in order to define the post-September 1999 geometry of the radiometer measurements, and to determine the October 1999-September 2003 ERBS sensor response changes. Analyses of these special solar and cold space observations indicate that the radiometers were pointing approximately 16 degrees away from the spacecraft nadir and on the anti-solar side of the spacecraft. The special observations indicated that the radiometers responses were stable at precision levels approaching 0.5 W/sq m . In this paper, the measurement geometry determinations and the determinations of the radiometers gain and offset are presented, which will permit the accurate processing of the October 1999 through September 2003 ERBE data products at satellite and top-of-the-atmosphere altitudes.

A peptide antagonist of ErbB receptors, Inherbin3, induces neurite outgrowth from rat cerebellar granule neurons through ErbB1 inhibition

DEFF Research Database (Denmark)

Xu, Ruodan; Pankratova, Stanislava; Christiansen, Søren Hofman

2013-01-01

ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase ac...

Transcriptional profiling of ErbB signalling in mammary luminal epithelial cells - interplay of ErbB and IGF1 signalling through IGFBP3 regulation

International Nuclear Information System (INIS)

Worthington, Jenny; Bertani, Mariana; Chan, Hong-Lin; Gerrits, Bertran; Timms, John F

2010-01-01

Members of the ErbB family of growth factor receptors are intricately linked with epithelial cell biology, development and tumourigenesis; however, the mechanisms involved in their downstream signalling are poorly understood. Indeed, it is unclear how signal specificity is achieved and the relative contribution each receptor has to specific gene expression. Gene expression profiling of a human mammary luminal epithelial cell model of ErbB2-overexpression was carried out using cDNA microarrays with a common RNA reference approach to examine long-term overlapping and differential responses to EGF and heregulin beta1 treatment in the context of ErbB2 overexpression. Altered gene expression was validated using quantitative real time PCR and/or immunoblotting. One gene of interest was targeted for further characterisation, where the effects of siRNA-mediated silencing on IGF1-dependent signalling and cellular phenotype were examined and compared to the effects of loss of ErbB2 expression. 775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e.g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were

ErbB polymorphisms: Insights and implications for response to targeted cancer therapeutics

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Moulay A Alaoui-Jamali

2015-02-01

Full Text Available Advances in high-throughput genomic-scanning have expanded the repertory of genetic variations in DNA sequences encoding ErbB tyrosine kinase receptors in humans, including single nucleotide polymorphisms (SNPs, polymorphic repetitive elements, microsatellite variations, small-scale insertions and deletions. The ErbB family members: EGFR, ErbB2, ErbB3 and ErbB4 receptors are established as drivers of many aspects of tumor initiation and progression to metastasis. This knowledge has provided rationales for the development of an arsenal of anti-ErbB therapeutics, ranging from small molecule kinase inhibitors to monoclonal antibodies. Anti-ErbB agents are becoming the cornerstone therapeutics for the management of cancers that overexpress hyperactive variants of ErbB receptors, in particular ErbB2-positive breast cancer and non-small cell lung carcinomas. However, their clinical benefit has been limited to a subset of patients due to a wide heterogeneity in drug response despite the expression of the ErbB targets, attributed to intrinsic (primary and to acquired (secondary resistance. Somatic mutations in ErbB tyrosine kinase domains have been extensively investigated in preclinical and clinical setting as determinants for either high sensitivity or resistance to anti-ErbB therapeutics. In contrast, only scant information is available on the impact of SNPs, which are widespread in genes encoding ErbB receptors, on receptor structure and activity, and their predictive values for drug susceptibility. This review aims to briefly update polymorphic variations in genes encoding ErbB receptors based on recent advances in deep sequencing technologies, and to address challenging issues for a better understanding of the functional impact of single versus combined SNPs in ErbB genes to receptor topology, receptor-drug interaction, and drug susceptibility. The potential of exploiting SNPs in the era of stratified targeted therapeutics is discussed.

A combination of Trastuzumab and 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation and cytotoxicity in ErbB2-overexpressing breast cancer cells.

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Raja, Srikumar M; Clubb, Robert J; Bhattacharyya, Mitra; Dimri, Manjari; Cheng, Hao; Pan, Wei; Ortega-Cava, Cesar; Lakku-Reddi, Alagarsamy; Naramura, Mayumi; Band, Vimla; Band, Hamid

2008-10-01

ErbB2 (or Her2/Neu) overexpression in breast cancer signifies poorer prognosis, yet it has provided an avenue for targeted therapy as demonstrated by the success of the humanized monoclonal antibody Trastuzumab (Herceptin). Resistance to Trastuzumab and eventual failure in most cases, however, necessitate alternate ErbB2-targeted therapies. HSP90 inhibitors such as 17-allylaminodemethoxygeldanamycin (17-AAG), potently downregulate the cell surface ErbB2. While the precise mechanisms of Trastuzumab or 17-AAG action remain unclear, ubiquitinylation-dependent proteasomal or lysosomal degradation of ErbB2 appears to play a substantial role. As Trastuzumab and 17-AAG induce the recruitment of distinct E3 ubiquitin ligases, Cbl and CHIP respectively, to ErbB2, we hypothesized that 17-AAG and Trastuzumab combination could induce a higher level of ubiquitinylation and downregulation of ErbB2 as compared to single drug treatments. We present biochemical and cell biological evidence that combined 17-AAG and Trastuzumab treatment of ErbB2-overexpressing breast cancer cell lines leads to enhanced ubiquitinylation, downregulation from the cell surface and lysosomal degradation of ErbB2. Importantly, combined 17-AAG and Trastuzumab treatment induced synergistic growth arrest and cell death specifically in ErbB2-overexpressing but not in ErbB2-low breast cancer cells. Our results suggest the 17-AAG and Trastuzumab combination as a mechanism-based combinatorial targeted therapy for ErbB2-overexpressing breast cancer patients.

A peptide antagonist of the ErbB1 receptor inhibits receptor activation, tumor cell growth and migration in vitro and xenograft tumor growth in vivo

DEFF Research Database (Denmark)

Xu, Ruodan; Povlsen, Gro Klitgaard; Soroka, Vladislav

2010-01-01

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization...... constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced Erb....... Structural studies have revealed that ErbB receptor dimers are stabilized by receptor-receptor interactions, primarily mediated by a region in the second extracellular domain, termed the "dimerization arm". The present study is the first biological characterization of a peptide, termed Inherbin3, which...

Epidermal Growth Factor Cytoplasmic Domain Affects ErbB Protein Degradation by the Lysosomal and Ubiquitin-Proteasome Pathway in Human Cancer Cells

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Aleksandra Glogowska

2012-05-01

Full Text Available The cytoplasmic domains of EGF-like ligands, including EGF cytoplasmic domain (EGFcyt, have important biological functions. Using specific constructs and peptides of human EGF cytoplasmic domain, we demonstrate that EGFcyt facilitates lysosomal and proteasomal protein degradation, and this coincided with growth inhibition of human thyroid and glioma carcinoma cells. EGFcyt and exon 22–23-encoded peptide (EGF22.23 enhanced procathepsin B (procathB expression and procathB-mediated lysosomal degradation of EGFR/ErbB1 as determined by inhibitors for procathB and the lysosomal ATPase inhibitor BafA1. Presence of mbEGFctF, EGFcyt, EGF22.23, and exon 23-encoded peptides suppressed the expression of the deubiqitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1. This coincided with hyperubiquitination of total cellular proteins and ErbB1/2 and reduced proteasome activity. Upon small interfering RNA-mediated silencing of endogenously expressed UCH-L1, a similar hyperubiquitinylation phenotype, reduced ErbB1/2 content, and attenuated growth was observed. The exon 23-encoded peptide region of EGFcyt was important for these biologic actions. Structural homology modeling of human EGFcyt showed that this molecular region formed an exposed surface loop. Peptides derived from this EGFcyt loop structure may aid in the design of novel peptide therapeutics aimed at inhibiting growth of cancer cells.

The Regional Biomass-Energy Agency (ERBE): an opportunity for the biomass-energy development in Wallonia

International Nuclear Information System (INIS)

Lemaire, P.; Menu, J.F.; Belle, J.F. van; Schenkel, Y.

1997-01-01

In 1995, the European Commission (Directorate-General for Energy) and the Walloon government set up a biomass-energy agency (ERBE), to promote and build biomass-energy projects in Wallonia (Belgium). A survey of biomass-energy potential indicates that wood-energy seems to offer the best utilization opportunities. Forest and logging residues, sawmills' and joineries' off-cuts, pallets residues, etc. could be burnt in wood district heating units with a significant social benefit. Consequently, the ERBE Agency is trying to set up projects in this way in Austria (+/- 100 wood heating systems) or in Sweden. It serves to inform industries and municipalities about biomass-energy, to advise them in the building of biomass-energy projects, to identify their energy needs and their biomass resources, to carry out prefeasibility studies, to inform them about financing opportunities, and so on. (author)

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

International Nuclear Information System (INIS)

Dearth, Robert K; Kuiatse, Isere; Wang, Yu-Fen; Liao, Lan; Hilsenbeck, Susan G; Brown, Powel H; Xu, Jianming; Lee, Adrian V

2011-01-01

Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm 3 . For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

Role of ErbB receptors in cancer cell migration and invasion

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Aline eAppert-Collin

2015-11-01

Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

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Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: i.h.madshus@medisin.uio.no [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)

2013-02-01

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

International Nuclear Information System (INIS)

Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke; Rødland, Marianne Skeie; Stang, Espen; Madshus, Inger Helene

2013-01-01

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub 4 ) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub 4 chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub 4 was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub 4 was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub 4 was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3.

Science.gov (United States)

Szymanska, Monika; Fosdahl, Anne Marthe; Raiborg, Camilla; Dietrich, Markus; Liestøl, Knut; Stang, Espen; Bertelsen, Vibeke

2016-06-01

In contrast to other members of the EGF receptor family, ErbB3 is constitutively internalized in a clathrin-dependent manner. Previous studies have shown that ErbB3 does not interact with the coated pit localized adaptor complex 2 (AP-2), and that ErbB3 lacks two AP-2 interacting internalization signals identified in the EGF receptor. Several other clathrin-associated sorting proteins which may recruit cargo into coated pits have, however, been identified, and the study was performed to identify adaptors needed for constitutive internalization of ErbB3. A high-throughput siRNA screen was used to identify adaptor proteins needed for internalization of ErbB3. Upon knock-down of candidate proteins internalization of ErbB3 was identified using an antibody-based internalization assay combined with automatic fluorescence microscopy. Among 29 candidates only knock-down of epsin 1 turned out to inhibit ErbB3. Epsin 1 has ubiquitin interacting motifs (UIMs) and we show that ErbB3 interacts with an epsin 1 deletion mutant containing these UIMs. In support of an ErbB3-epsin 1 UIM dependent interaction, we show that ErbB3 is constitutively ubiquitinated, but that both ubiquitination and the ErbB3-epsin 1 interaction increase upon ligand binding. Altogether the results are consistent with a model whereby both constitutive and ligand-induced internalization of ErbB3 are regulated through interaction with epsin 1. Internalization is an important regulator of growth factor receptor mediated signaling and the current study identify mechanisms regulating plasma membrane turnover of ErbB3. Copyright © 2016 Elsevier B.V. All rights reserved.

Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

International Nuclear Information System (INIS)

Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

2003-01-01

The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

Regionalization of monthly rainfall erosivity patternsin Switzerland

Science.gov (United States)

Schmidt, Simon; Alewell, Christine; Panagos, Panos; Meusburger, Katrin

2016-10-01

One major controlling factor of water erosion is rainfall erosivity, which is quantified as the product of total storm energy and a maximum 30 min intensity (I30). Rainfall erosivity is often expressed as R-factor in soil erosion risk models like the Universal Soil Loss Equation (USLE) and its revised version (RUSLE). As rainfall erosivity is closely correlated with rainfall amount and intensity, the rainfall erosivity of Switzerland can be expected to have a regional characteristic and seasonal dynamic throughout the year. This intra-annual variability was mapped by a monthly modeling approach to assess simultaneously spatial and monthly patterns of rainfall erosivity. So far only national seasonal means and regional annual means exist for Switzerland. We used a network of 87 precipitation gauging stations with a 10 min temporal resolution to calculate long-term monthly mean R-factors. Stepwise generalized linear regression (GLM) and leave-one-out cross-validation (LOOCV) were used to select spatial covariates which explain the spatial and temporal patterns of the R-factor for each month across Switzerland. The monthly R-factor is mapped by summarizing the predicted R-factor of the regression equation and the corresponding residues of the regression, which are interpolated by ordinary kriging (regression-kriging). As spatial covariates, a variety of precipitation indicator data has been included such as snow depths, a combination product of hourly precipitation measurements and radar observations (CombiPrecip), daily Alpine precipitation (EURO4M-APGD), and monthly precipitation sums (RhiresM). Topographic parameters (elevation, slope) were also significant explanatory variables for single months. The comparison of the 12 monthly rainfall erosivity maps showed a distinct seasonality with the highest rainfall erosivity in summer (June, July, and August) influenced by intense rainfall events. Winter months have the lowest rainfall erosivity. A proportion of 62 % of

Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

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Faure Claudine

2007-10-01

Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

Science.gov (United States)

Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2016-01-01

The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_TRMM-PFM_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Digitalisierung des Kulturellen Erbes (Europas)

NARCIS (Netherlands)

Gruber, Marion

2011-01-01

Gruber, M. R. (2011, 13 December). Digitalisierung des Kulturellen Erbes (Europas). Guest lecture at the IPMZ - Institute of Mass Communication and Media Research, Devision Media Change & Innovation, University of Zurich, Switzerland.

Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

Energy Technology Data Exchange (ETDEWEB)

Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cleasby, Mark E. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Millard, Susan; Leong, Gary M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cooney, Gregory J. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Muscat, George E.O., E-mail: g.muscat@imb.uq.edu.au [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia)

2009-10-30

The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

ErbB2 regulates NHEJ repair pathway by affecting erbB1-triggered IR-induced Akt activity

International Nuclear Information System (INIS)

Toulany, Mahmoud; Peter Rodemann, H.

2009-01-01

We have already reported that erbBl-PI3K-AKT signaling is an important pathway in regulating radiation sensitivity and DNA double strand break repair of human tumor cells. In the present study using small interfering RNA and pharmacological inhibitors in non-small cell lung cancer cell lines we investigated the role of Aktl on radiation-induced DNA-PKcs activity and DNA-double strand break (DNA-DSB) repair. Likewise, the function of erbB2 as hetrodimerization partner of erbBl in radiation-induced Akt activity and regulation of DNA-dsb repair through DNA-PKcs was evaluated. In A549 and H460 transfected with AKTl-siRNA radiation-induced phosphorylation of DNA-PKcs the key enzyme regulating NHEJ repair pathway was markedly inhibited. In both cell lines downregulation of Aktl led to a significant enhancement of residual DNA-DSB, i.e. impaired DNA-DSB repair. Interestingly, in cells transfected with DNA-PKcs-siRNA a lack of effect of AKTl-siRNA on enhancement of residual DNA-DSBs was observed. This results indicate that Aktl regulates NHEJ repair in a DNA-PKcs dependent manner

[Bacterial synthesis, purification, and solubilization of transmembrane segments of ErbB family members].

Science.gov (United States)

Goncharuk, M V; Shul'ga, A A; Ermoliuk, Ia S; Tkach, E N; Goncharuk, S A; Pustovalova, Iu E; Mineev, K S; Bocharov, É V; Maslennikov, I V; Arsen'ev, A S; Kirpichnikov, M P

2011-01-01

A family of epidermal growth factor receptors, ErbB, represents an important class of receptor tyrosine kinases, playing a leading role in cellular growth, development and differentiation. Transmembrane domains of these receptors transduce biochemical signals across plasma membrane via lateral homo- and heterodimerization. Relatively small size of complexes of ErbB transmembrane domains with detergents or lipids allows one to study their detailed spatial structure using three-dimensional heteronuclear high-resolution NMR spectroscopy. Here, we describe the effective expression system and purification procedure for preparative-scale production of transmembrane peptides from four representatives of ErbB family, ErbB1, ErbB2, ErbB3, ErbB4, for structural studies. The recombinant peptides were produced in Escherichia coli BL21(DE3)pLysS as C-terminal extensions of thioredoxin A. The fusion protein cleavage was accomplished with the light subunit of human enterokinase. Several (10-30) milligrams of purified isotope-labeled transmembrane peptides were isolated with the use of a simple and convenient procedure, which consists of consecutive steps of immobilized metal affinity chromatography and cation-exchange chromatography. The purified peptides were reconstituted in lipid/detergent environment (micelles or bicelles) and characterized using dynamic light scattering, CD and NMR spectroscopy. The data obtained indicate that the purified ErbB transmembrane peptides are suitable for structural and dynamic studies of their homo- and heterodimer complexes using high resolution NMR spectroscopy.

[Construction of the lentiviral expression vector for anti-p185(erbB2) mouse/human chimeric antibody].

Science.gov (United States)

Liu, Fang; Li, Li; Zhang, Wei; Wang, Qi

2013-04-01

This research was to construct the lentiviral expression vector for anti- p185(erbB2) mouse/human chimeric antibody and to determine the expression of the chimeric antibody gene in 293T cells transfected with this vector. The genes (vL and vH) coding light and heavy chain of variable regions of anti-p185(erbB2) mAb and the constant regions of human IgG1 (kappa and gamma1) were cloned with PCR method. The target genes were assembled by three-primers PCR method to obtain the chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was constructed correctly. Then, it was transfected into 293T cells and after 48h, GFP protein expression in 293T cells were detected by fluorescent microscope and the chimeric antibody expression was detected by RT-PCR and direct ELISA. The results showed that after 293T cells were transfected with recombination plasmid, both light and heavy chains of the chimeric antibody genes could express together. The chimeric antibody expressed could bind to p185(erbB2) specifically. This research may lay a sound foundation for further study of anti-p185(erbB2) engineered antibody.

ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

International Nuclear Information System (INIS)

Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

2012-01-01

Highlights: ► ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ► Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ► Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or γ-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

Comparative immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary craniopharyngiomas

International Nuclear Information System (INIS)

Eshebaa, Gh.E.; Hassan, A.A.

2015-01-01

Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the sellar/parasellar region. CPs have been classified into histopathologically, genetically, clinically and prognostically two distinctive subtypes: adamantinomatous and papillary variants. Aim To determine the immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary CPs. Materials and methods β-Catenin, EGFR, ErbB2, and p63 immunostaining was performed on paraffin embedded tissue sections of 25 CPs including 18 adamantinomatous craniopharyngioma (ACP) and 7 cases of papillary craniopharyngiomas (PCPs). Results 17 cases (94%) of ACP exhibited strong nuclear/cytoplasmic expression of β-catenin. On the contrary, all cases of PCP showed exclusively membranous expression (ρ value <0.0001). Regarding EGFR, 15 (83%) and 5 cases (71%) of APC and PCP respectively were positive. On the other hand, only 3 cases (17%) of APC and none of PCP exhibited positivity for ErbB2. p63 over-expression was observed in 16 cases of ACP (89%) and 6 cases of PCP (86%). However, the distribution of p63 staining was diffuse in ACP, while in PCP; the staining was mainly restricted to the basal cell layer. Conclusion Nuclear accumulation of β-catenin is a diagnostic hallmark of the ACP and is very helpful in the differential diagnosis between both ACP and PCP in the setting of small biopsies. Moreover, the restricted nuclear β-catenin accumulation in the cohesive cell clusters within the whorl-like areas supports that aberrant β-catenin expression may play a role in the morphogenesis of ACP.

Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and reinnervation.

Science.gov (United States)

Morano, Michela; Ronchi, Giulia; Nicolò, Valentina; Fornasari, Benedetta Elena; Crosio, Alessandro; Perroteau, Isabelle; Geuna, Stefano; Gambarotta, Giovanna; Raimondo, Stefania

2018-03-22

Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role.

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-01-01] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-11-01] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.

Science.gov (United States)

Wu, Gang; Liu, Xiu-Xiu; Lu, Nan-Nan; Liu, Qi-Bing; Tian, Yun; Ye, Wei-Feng; Jiang, Guo-Jun; Tao, Rong-Rong; Han, Feng; Lu, Ying-Mei

2017-06-01

The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4 f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. © 2017 John Wiley & Sons Ltd.

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

Science.gov (United States)

Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.

Science.gov (United States)

Eldridge, Sandy; Guo, Liang; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

2014-10-01

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

Science.gov (United States)

Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

2014-11-01

The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

Directory of Open Access Journals (Sweden)

Gulati Michel

2010-03-01

Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

Prognostic impact of p53, c-erbB-2 and epidermal growth factor receptor on head and neck carcinoma

Directory of Open Access Journals (Sweden)

Orlando Parise Junior

Full Text Available CONTEXT: p53, c-erbB-2 and epidermal growth factor receptor (EGFR are cancer-related proteins that are usually expressed in head and neck squamous cell carcinoma (SCC. Their prognostic value remains controversial. OBJECTIVE: To evaluate the prognostic impact of p53, c-erbB-2 and EGFR expression in head and neck SCC. TYPE OF STUDY: Prospective. SETTING: Head and Neck Surgery Department, Hospital AC Camargo, São Paulo. METHODS: Fifty-four patients were studied for p53, c-erbB-2 and EGFR expression in head and neck SCC and adjacent mucosa, via immunohistochemistry. These data were correlated with histoclinical data and survival. RESULTS: There was a direct association of p53 expression in SCC and mucosa (p = 0.001; loss of c-erbB-2 expression (- from normal mucosa to SCC (p = 0.04; lower frequency of association of c-erbB-2 (+ with EGFR (- in SCC (p = 0.02; and a direct association of EGFR (+ expression in SCC and mitotic index (p = 0.03. The 60-month actuarial survival rates for patients presenting lymph node metastasis were higher when there was no capsule rupture by SCC (48.3%; p = 0.02, no more than one positive lymph node (52.3%; p = 0.004 or clear surgical margins (47.0%; p = 0.01, in comparison with patients presenting capsule rupture (20.2%, two or more positive lymph nodes (18.7% or compromised surgical margins (0.0%, respectively. Patients presenting SCC p53 (+ and EGFR (- demonstrated greater survival (75.0%; p = 0.03 than for the remaining group (33.1%. Multivariate analysis confirmed the positive impact of p53 (+ and EGFR (- on survival (p = 0.02. DISCUSSION: Associations were found for p53, c-erbB-2 and EGFR expression with histoclinical data and prognosis. Interestingly, these results suggest that loss of mucosal c-erbB-2 expression could be involved in SCC carcinogenesis; EGFR expression in SCC is related to tumor mitotic index; and presence of p53 with absence of EGFR expression in head and neck SCC may be a prognostic factor for

ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases

Directory of Open Access Journals (Sweden)

Alexandru Filippi

2017-01-01

Full Text Available ErbB proteins overexpression, in both normal and mutated forms, is associated with invasive forms of cancer prone to metastasis and with stronger antiapoptotic mechanisms and therefore more challenging to treat. Downstream effectors of ErbB receptors mediating these phenotypic traits include MAPK, STAT, and PI3K/AKT/mTOR pathways. Various phytochemical compounds were studied for their large number of biological effects including anticancer activity. Among these compounds, epigallocatechin-3-gallate (EGCG, the main catechin from green tea leaves, and curcumin, component of the curry powder, constituted the object of numerous studies. Both compounds were shown to act directly either on ErbB expression, or on their downstream signaling molecules. In this paper we aim to review the involvement of ErbB proteins in cancer as well as the biologic activity of EGCG and curcumin in ErbB expressing and overexpressing malignancies. The problems arising in the administration of the two compounds due to their reduced bioavailability when orally administered, as well as the progress made in this field, from using novel formulations to improved dosing regimens or improved synthetic analogs, are also discussed.

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-09-30] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.

Science.gov (United States)

Elizalde, Patricia V; Cordo Russo, Rosalía I; Chervo, Maria F; Schillaci, Roxana

2016-12-01

Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies. © 2016 Society for Endocrinology.

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

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Anxin Gu

Full Text Available Radiation-induced heart disease (RIHD, which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

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Flores Juana M

2010-07-01

Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

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Tan, Zhibing; Robinson, Heath L; Yin, Dong-Min; Liu, Yu; Liu, Fang; Wang, Hongsheng; Lin, Thiri W; Xing, Guanglin; Gan, Lin; Xiong, Wen-Cheng; Mei, Lin

2018-04-18

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression of oncogen c-erbB-2 (neu/HER-2) in human breast cancer

International Nuclear Information System (INIS)

Michelin, Severino C.; Mayo, Jose

2000-01-01

Breast cancer continues to be one of the leading causes of death from cancer among women and represents the most serious challenge to therapeutic control. Amplification and overexpression of the c-erbB-2 proto-oncogene occurs in as many as 30 % of all breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. This gene know as neu, HER-2 or c-erbB-2 in among those most frequently altered in human cancer. It was first identified as a transforming gene activated in chemically induced rat neuroectodermal tumors. Early critical studies linked changes in erbB-2 expression and gene copy number to several human cancer, notably breast, ovarian and gastric cancer. Owing to its accessible location at the cell surface, erbB-2 is now under intensive scrutiny as a therapeutic target. In this review we will summarize the involvement of the c-erbB-2 gene in tumorigenesis. (author)

Expressão imuno-histoquímica de c-erb-B2 e p53 em carcinomas gástricos Imunohistochemical expression of c-erb-B2 and p53 in gastric carcinomas

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Maria Dirlei F. S. Begnami

2005-08-01

Full Text Available INTRODUÇÃO: Em nosso meio, os carcinomas gástricos ainda são neoplasias bastante freqüentes e responsáveis por altas taxas de mortalidade. Recentemente, têm-se demonstrado a expressão de p53 e a amplificação do gene c-erb-B2 nos carcinomas gástricos. A relevância e o significado biológico destas alterações ainda não foram totalmente estabelecidos. OBJETIVO: Estudar as expressões imuno-histoquímicas de p53 e c-erb-B2 em 482 casos de carcinomas gástricos. MATERIAL E MÉTODOS: Foram construídos três blocos de tissue microarray (TMA utilizando-se duplicatas de 482 casos de carcinomas gástricos. Os cortes foram corados por hematoxilina e eosina (HE, tendo sido feita pesquisa para p53 e c-erb-B2. Foram considerados positivos para p53 os casos com marcação nuclear em mais de 10% das células tumorais. Para o c-erb-B2 foram considerados positivos os casos com marcação de membrana completa em mais de 10% das células tumorais. RESULTADOS: A expressão de p53 e c-erb-B2 foi observada em 30% e 12% dos casos, respectivamente. Em relação aos tipos histológicos observou-se correlação entre os carcinomas do tipo intestinal e a expressão de c-erb-B2 (p INTRODUCTION: Gastric cancer is one of the commonest cancers in our country being responsible for a high mortality rate. Recently, the expression of p53 and amplification of c-erb-B2 gene have been described in gastric carcinoma. The relevance and biological significance of these findings are not established yet. OBJECTIVE: The authors investigated p53, c-erb-B2 immunohistochemical expression in 482 cases of gastric carcinomas. MATERIAL AND METHODS: Tissue microarray (TMA blocks were designed using replicate samples of paraffin-embedded tissue from 482 gastric carcinomas. Sections were stained with HE, and antibodies to p53 and c-erb-B2. Cases were considered p53 positive if nuclear staining was detected in > 10% of the tumor cells. Cases were assessed c-erb-B2 positive if the

Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

Energy Technology Data Exchange (ETDEWEB)

Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: federica.cavallo@unito.it [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)

2011-08-10

DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells.

Science.gov (United States)

Zhang, Yingqiu; Zhang, Jinrui; Liu, Congcong; Du, Sha; Feng, Lu; Luan, Xuelin; Zhang, Yayun; Shi, Yulin; Wang, Taishu; Wu, Yue; Cheng, Wei; Meng, Songshu; Li, Man; Liu, Han

2016-11-28

Receptor tyrosine kinase ErbB2/HER2 is frequently observed to be overexpressed in human cancers, leading to over activation of downstream signaling modules. HER2 positive is a major type of breast cancer for which ErbB2 targeting is already proving to be an effective therapeutic strategy. Apart from antibodies against ErbB2, the small molecule tyrosine kinase inhibitor lapatinib has had successful clinical outcomes, and other inhibitors such as neratinib are currently undergoing clinical investigations. In this study we report the effects of lapatinib and neratinib on the mRNA and protein levels of the ErbB2 receptor. We provide evidence that neratinib-induced down regulation of ErbB2 occurs through ubiquitin-mediated endocytic sorting and lysosomal degradation. At the mechanistic level, neratinib treatment leads to HSP90 release from ErbB2 and its subsequent ubiquitylation and endocytic degradation. Our findings provide novel insights into the mechanism of ErbB2 inhibition by neratinib. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer

International Nuclear Information System (INIS)

Staal, O.; Sullivan, S.; Wingren, S.; Skoog, L.; Rutqvist, L.E.; Nordenskjoeld, B.; Carstensen, J.M.

1995-01-01

Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy. (author)

Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

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Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

2006-11-01

A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome

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Ryan D. Welch

2017-07-01

Conclusions: Disrupting Rev-Erb activity in injured muscle accelerates regenerative muscle repair/differentiation through transcriptional de-repression of myogenic programs. Rev-Erb, therefore, may be a potent therapeutic target for a myriad of muscular disorders.

REV-ERB and ROR: therapeutic targets for treating myopathies

Science.gov (United States)

Welch, Ryan D.; Flaveny, Colin A.

2017-08-01

Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

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Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

2013-01-01

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

Science.gov (United States)

Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

2017-08-01

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

Breast cancer metastasis driven by ErbB2 and 14-3-3ξ: A division of labor

OpenAIRE

Wang, Yingqun

2010-01-01

Metastasis remains the leading cause of cancer morbidity and mortality. ErbB2, a metastasis-promoting oncoprotein, is overexpressed in 50–60% of noninvasive ductal carcinoma in situ (DCIS). However, only 25% of invasive breast cancer (IBC) overexpress ErbB2, indicating that ErbB2 alone is not sufficient to drive metastasis and additional risk factors are necessary for the progression of ErbB2-overexpressing DCIS to IBC. A recent study published in Cancer Cell identified 14-3-3ξ as a risk fact...

ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

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Milanesi Elena

2012-09-01

Full Text Available Abstract Background In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD, has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. Methods We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. Results These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models Conclusions Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.

Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

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Hughes, Juliana Bentes; Rødland, Marianne Skeie; Hasmann, Max; Madshus, Inger Helene; Stang, Espen

2012-01-01

ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90) are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only. PMID:24281706

Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

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Juliana Bentes Hughes

2012-06-01

Full Text Available ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90 are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only.

Prognostic value of p53, c-ErbB2 and tunel data in upper urothelial carcinoma associated with Balkan nephropathy

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Savin Marina

2014-01-01

Full Text Available A characteristic tumor suppressor protein 53 (p53 mutational profile of genotoxic action of aristolochic acid was identified in the upper urothelial carcinoma (UUTT associated with Balkan nephropathy (BEN. In the present study, we examined the prognostic value of tissue-based molecular markers in overall-survival (OS risk after surgical treatment of UUTT, adjusted for gender, age and urological characteristics in 32 patients with BEN. Immunohistochemical examination of p53, the proliferation cell nuclear antigen (PCNA, the human epidermal growth factor receptor 2 (c-ErbB2; also known as HER-2/neu proto-oncogene and the in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay for apoptosis detection were used to examine serial tumor sections. The median OS-time was 60 months for UUTT operation; the mortality rate (18.7% was related to (new disease (reoccurrence or invasion in 12-216 months. High-grade (p=0.029, TUNEL>0.36%+ cells (p=0.010, and c-ErbB2+ cells (p=0.014 can define the risk of tumor invasion. Patients with Balkan nephropathy that develop UUTT at a stage greater than pT1 (with apoptosis TUNEL+ cells >0.36% and p53+ cells greater than 10% were at high risk of poor-OS after the tumor surgery (h(x=6.35; p=0.045. The obtained data present evidence for p53, cErbB2 and apoptosis deregulation, as a result of environmental toxin action. This is the first report of molecular biomarker linkage with OS for BEN-associated UUTT.

Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein

DEFF Research Database (Denmark)

Muñoz, A; Zenke, M; Gehring, U

1988-01-01

mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75......To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several......gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone...

Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

Science.gov (United States)

del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia

2013-01-01

Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

ErbB receptors and cell polarity: New pathways and paradigms for understanding cell migration and invasion

International Nuclear Information System (INIS)

Feigin, Michael E.; Muthuswamy, Senthil K.

2009-01-01

The ErbB family of receptor tyrosine kinases is involved in initiation and progression of a number of human cancers, and receptor activation or overexpression correlates with poor patient survival. Research over the past two decades has elucidated the molecular mechanisms underlying ErbB-induced tumorigenesis, which has resulted in the development of effective targeted therapies. ErbB-induced signal transduction cascades regulate a wide variety of cell processes, including cell proliferation, apoptosis, cell polarity, migration and invasion. Within tumors, disruption of these core processes, through cooperative oncogenic lesions, results in aggressive, metastatic disease. This review will focus on the ErbB signaling networks that regulate migration and invasion and identify a potential role for cell polarity pathways during cancer progression

OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.

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Loïc Deleyrolle

Full Text Available The proliferation and differentiation of neural stem cells are tightly controlled by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly recognized as regulators of these processes. Here we report the expression of the olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM during mouse spinal cord development and in neural stem cells cultured as neurospheres. OCAM is also weakly expressed in the dormant adult stem cell niche around the central canal and is overexpressed after spinal cord injury. Both transmembrane (TM and glycosylphosphatidylinositol (GPI-linked isoforms are present in neurospheres. Electron microscopy and internalisation experiments revealed a dynamic trafficking of OCAM between the membrane and intracellular compartments. After differentiation, OCAM remains in neurons and oligodendrocytes whereas no expression is detected in astrocytes. Using OCAM knockout (KO mice, we found that mutant spinal cord stem cells showed an increased proliferation and self-renewal rates although no effect on differentiation was observed. This effect was reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced proliferation of mutant cells. ErbB2 protein expression and phosphorylation level were significantly increased in KO cells whereas no difference was observed at the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also increased their growth while reintroduction of OCAM in mutant cells reduced the level of phosphorylated ErbB2. These results indicate that OCAM exerts a posttranscriptional control on the ErbB2 signalling in spinal cord stem cells. This study adds further support for considering cell adhesion molecules as regulators of the ErbB signalling.

ERBS fuel addendum: Pollution reduction technology program small jet aircraft engines, phase 3

Science.gov (United States)

Bruce, T. W.; Davis, F. G.; Kuhn, T. E.; Mongia, H. C.

1982-01-01

A Model TFE731-2 engine with a low emission, variable geometry combustion system was tested to compare the effects of operating the engine on Commercial Jet-A aviation turbine fuel and experimental referee broad specification (ERBS) fuels. Low power emission levels were essentially identical while the high power NOx emission indexes were approximately 15% lower with the EBRS fuel. The exhaust smoke number was approximately 50% higher with ERBS at the takeoff thrust setting; however, both values were still below the EPA limit of 40 for the Model TFE731 engine. Primary zone liner wall temperature ran an average of 25 K higher with ERBS fuel than with Jet-A. The possible adoption of broadened proprties fuels for gas turbine applications is suggested.

Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

Science.gov (United States)

Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

2012-01-01

First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

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Ronald J Hause

Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

Science.gov (United States)

Burstein, Harold J; Sun, Yan; Dirix, Luc Y; Jiang, Zefei; Paridaens, Robert; Tan, Antoinette R; Awada, Ahmad; Ranade, Anantbhushan; Jiao, Shunchang; Schwartz, Gary; Abbas, Richat; Powell, Christine; Turnbull, Kathleen; Vermette, Jennifer; Zacharchuk, Charles; Badwe, Rajendra

2010-03-10

Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial. Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.

The ErbB family and androgen receptor signaling are targets of Celecoxib in prostate cancer.

Science.gov (United States)

Brizzolara, Antonella; Benelli, Roberto; Venè, Roberta; Barboro, Paola; Poggi, Alessandro; Tosetti, Francesca; Ferrari, Nicoletta

2017-08-01

Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. Western blotting, gene expression analysis, dual-luciferase reporter assay and ELISA were applied to assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and consequent degradation associated with the inhibition of androgenic signaling. By upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently downregulated ErbB3, which is strongly implicated in castration-resistant prostate cancer. Lastly, Celecoxib directly regulated AR transcription and translation independent of ErbB activation by downregulating the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous suppression of ErbB kinases and androgen signaling by Celecoxib represents a novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the primary purpose of undermining their resilient signaling in prostate cancer progression. Our data provide important premises for the chemopreventive use of Celecoxib in the clinical management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Data on the effect of in vivo knockdown using artificial ErbB3 miRNA on Remak bundle structure

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Yuki Miyamoto

2017-06-01

Full Text Available Mature Schwann cells, the peripheral nervous system (PNS glial cells, have two major roles for neuronal axons (Bunge, 1993 [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness. Herein we provide the data regarding the effect of in vivo knockdown of ErbB3 on the thickness between an axon and a neighboring axon in Remak bundle, which is formed by non-myelinating Schwann cells. Since ErbB3 knockout mice are embryonically lethal, Schwann cell lineage-specific transgenic mice transcribing ErbB3 shRNA with an artificial miRNA backbone were generated and used in these experiments (Torii et al., 2014 [2].

Imunoexpressão do c-erbB-2 nas lesões epiteliais proliferativas intraductais da mama de mulheres Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast

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Agliberto Barbosa de Oliveira

2004-09-01

Full Text Available OBJETIVOS: Alterações genéticas são relacionadas à gênese e progressão do câncer. Neoplasias de vários órgãos expressam o oncogene c-erbB-2. Nas proliferações intraductais da mama tem sido avaliado como fator de risco para o desenvolvimento de câncer. Foram avaliadas a imunoexpressão do c-erbB-2 em lesões epiteliais proliferativas intraductais e as possíveis correlações com características anatomopatológicas do carcinoma ductal "in situ" (CDIS. MÉTODOS: Foi utilizado material de arquivo, amostras teciduais fixadas em formalina e incluídas em blocos de parafina de 88 mulheres. Destas, 51 com CDIS e 37 com hiperplasia ductal sem atipias (HDT. A idade variou de 35 a 76 anos. Revisados todos os casos, verificou-se: o grau nuclear, a presença de necrose, o subtipo histológico predominante e sua extensão. Obteve-se material suficiente para o estudo imunohistoquímico do c-erbB-2 de 84 sujeitos do estudo. RESULTADOS: Não foi observada a expressão do oncogene nas hiperplasias sem atipias e nos tecidos adjacentes a todas amostras teciduais. A expressão do c-erbB-2 foi verificada em nove (19,1% dos CDIS (p= 0,0001. A imunoexpressão não se relacionou à extensão das lesões. A imunoexpressão do c-erbB-2 no CDIS correlacionou-se com subtipo histológico (p=0,019, com a presença de necrose (p=0,0066, com o grau nuclear (p=0,0084 e com a Classificação de Van Nuys (p=0,039. CONCLUSÕES: A expressão do c-erbB-2 foi estatisticamente significante nas lesões proliferativas de risco (CDIS e correlacionou-se com características histopatológicas: alto grau nuclear, presença de necrose, subtipo comedo. Não houve expressão nas hiperplasias sem atipias e tecidos adjacentes.OBJECTIVES: Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of

c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

International Nuclear Information System (INIS)

Fritz, Peter; Cabrera, Cristina M; Dippon, Jürgen; Gerteis, Andreas; Simon, Wolfgang; Aulitzky, Walter E; Kuip, Heiko van der

2005-01-01

c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus

DEFF Research Database (Denmark)

Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo

2007-01-01

inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent...

Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients

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Singh Usha

2006-05-01

Full Text Available Abstract Background The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. Methods In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. Results Eight (20% patients of gall bladder cancer were positive for p53 expression and 10 (25% patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. Conclusion Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results.

Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

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Yuh-Shyan Tsai

2012-01-01

Full Text Available The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4 and 1.1 (95% CI: 0.6–1.9, and the risks of mortality were 3.0 (95% CI: 1.6–5.9 and 1.1 (95% CI: 1.0–1.2, respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

Comparison of ERBS orbit determination accuracy using batch least-squares and sequential methods

Science.gov (United States)

Oza, D. H.; Jones, T. L.; Fabien, S. M.; Mistretta, G. D.; Hart, R. C.; Doll, C. E.

1991-10-01

The Flight Dynamics Div. (FDD) at NASA-Goddard commissioned a study to develop the Real Time Orbit Determination/Enhanced (RTOD/E) system as a prototype system for sequential orbit determination of spacecraft on a DOS based personal computer (PC). An overview is presented of RTOD/E capabilities and the results are presented of a study to compare the orbit determination accuracy for a Tracking and Data Relay Satellite System (TDRSS) user spacecraft obtained using RTOS/E on a PC with the accuracy of an established batch least squares system, the Goddard Trajectory Determination System (GTDS), operating on a mainframe computer. RTOD/E was used to perform sequential orbit determination for the Earth Radiation Budget Satellite (ERBS), and the Goddard Trajectory Determination System (GTDS) was used to perform the batch least squares orbit determination. The estimated ERBS ephemerides were obtained for the Aug. 16 to 22, 1989, timeframe, during which intensive TDRSS tracking data for ERBS were available. Independent assessments were made to examine the consistencies of results obtained by the batch and sequential methods. Comparisons were made between the forward filtered RTOD/E orbit solutions and definitive GTDS orbit solutions for ERBS; the solution differences were less than 40 meters after the filter had reached steady state.

Comparison of ERBS orbit determination accuracy using batch least-squares and sequential methods

Science.gov (United States)

Oza, D. H.; Jones, T. L.; Fabien, S. M.; Mistretta, G. D.; Hart, R. C.; Doll, C. E.

1991-01-01

The Flight Dynamics Div. (FDD) at NASA-Goddard commissioned a study to develop the Real Time Orbit Determination/Enhanced (RTOD/E) system as a prototype system for sequential orbit determination of spacecraft on a DOS based personal computer (PC). An overview is presented of RTOD/E capabilities and the results are presented of a study to compare the orbit determination accuracy for a Tracking and Data Relay Satellite System (TDRSS) user spacecraft obtained using RTOS/E on a PC with the accuracy of an established batch least squares system, the Goddard Trajectory Determination System (GTDS), operating on a mainframe computer. RTOD/E was used to perform sequential orbit determination for the Earth Radiation Budget Satellite (ERBS), and the Goddard Trajectory Determination System (GTDS) was used to perform the batch least squares orbit determination. The estimated ERBS ephemerides were obtained for the Aug. 16 to 22, 1989, timeframe, during which intensive TDRSS tracking data for ERBS were available. Independent assessments were made to examine the consistencies of results obtained by the batch and sequential methods. Comparisons were made between the forward filtered RTOD/E orbit solutions and definitive GTDS orbit solutions for ERBS; the solution differences were less than 40 meters after the filter had reached steady state.

Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes

International Nuclear Information System (INIS)

Pentassuglia, Laura; Graf, Michael; Lane, Heidi; Kuramochi, Yukio; Cote, Gregory; Timolati, Francesco; Sawyer, Douglas B.; Zuppinger, Christian; Suter, Thomas M.

2009-01-01

Inhibition of ErbB2 (HER2) with monoclonal antibodies, an effective therapy in some forms of breast cancer, is associated with cardiotoxicity, the pathophysiology of which is poorly understood. Recent data suggest, that dual inhibition of ErbB1 (EGFR) and ErbB2 signaling is more efficient in cancer therapy, however, cardiac safety of this therapeutic approach is unknown. We therefore tested an ErbB1-(CGP059326) and an ErbB1/ErbB2-(PKI166) tyrosine kinase inhibitor in an in-vitro system of adult rat ventricular cardiomyocytes and assessed their effects on 1. cell viability, 2. myofibrillar structure, 3. contractile function, and 4. MAPK- and Akt-signaling alone or in combination with Doxorubicin. Neither CGP nor PKI induced cardiomyocyte necrosis or apoptosis. PKI but not CGP caused myofibrillar structural damage that was additive to that induced by Doxorubicin at clinically relevant doses. These changes were associated with an inhibition of excitation-contraction coupling. PKI but not CGP decreased p-Erk1/2, suggesting a role for this MAP-kinase signaling pathway in the maintenance of myofibrils. These data indicate that the ErbB2 signaling pathway is critical for the maintenance of myofibrillar structure and function. Clinical studies using ErbB2-targeted inhibitors for the treatment of cancer should be designed to include careful monitoring for cardiac dysfunction.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

Science.gov (United States)

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

Overexpression of c-erbB-2 and loss of p16 have molecular diagnostic relevance but no prognostic value in lung cancer.

Science.gov (United States)

Feng, Xiao-li; Li, Ling; Gao, Yan-ning; Zhang, Jian-jun; Xiao, Ting; Ying, Jian-ming; Gao, Ji-dong; Sun, Yun-tian; Cheng, Shu-jun

2011-03-01

This study was designed to evaluate the expression of C-erbB-2 and p16 in lung cancers using tissue microarray technology and to determine their clinical and pathological significance. Immunohistochemical C-erbB-2 and p16 expressions and their associations with clinical and pathological features were analyzed in two tissue microarrays. The membranous and cytoplasmic expression rates of C-erbB-2 were 40.5 and 66.5% in non-small cell lung cancers (NSCLCs), and 0 and 9.5% in small cell lung cancers (SCLCs), respectively. The nuclear and cytoplasmic expression rates of p16 were 11.5 and 32.2% in NSCLs, and 45 and 80% in SCLCs, respectively. The cytoplasmic expression of both C-erbB-2 and p16 was more frequent than the membranous expression of C-erbB-2 and the nuclear expression of p16. The rates of overexpression of C-erbB-2 and loss of p16 expression were significantly higher in NSCLCs than in SCLCs (P < 0.05). Neither C-erbB-2 nor p16 expression was significantly associated with age, tumor grade or stage, presence of lymph node metastasis or survival duration. The abnormal expressions of p16 and C-erbB-2 may play a role in the progression of lung cancers. The variations in the expression patterns of C-erbB-2 and p16 between NSCLCs and SCLCs may aid the molecular classification of lung cancer. The abnormal expression of p16 may be involved in the development of NSCLCs, and the overexpression of C-erbB-2 in NSCLCs indicates that it can be a candidate target for gene therapy.

Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

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Mary E Irwin

Full Text Available The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+ALL is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI that target BCR/ABL, such as imatinib, have improved treatment of Ph(+ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2 is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+ALL as compared to just 4.8% of Ph(-ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM. Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM. Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

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Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel

2012-01-01

Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1.

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Zsebik, Barbara; Citri, Ami; Isola, Jorma; Yarden, Yosef; Szöllosi, János; Vereb, György

2006-04-15

ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in approximately 30-40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5-10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30-40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may

Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

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Dipankar Ray

2011-05-01

Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product

DEFF Research Database (Denmark)

Sap, J; Muñoz, A; Schmitt, J

1989-01-01

Several recent observations, such as the identification of the cellular homologue of the v-erb-A oncogene as a thyroid-hormone receptor, have strongly implicated nuclear oncogenes in transcriptional control mechanisms. The v-erb-A oncogene blocks the differentiation of erythroid cells, and changes...

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

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Morioka, Norimitsu, E-mail: mnori@hiroshima-u.ac.jp; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-01-08

Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

International Nuclear Information System (INIS)

Morioka, Norimitsu; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-01-01

Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American.

Science.gov (United States)

Garaulet, Marta; Smith, Caren E; Gomez-Abellán, Purificación; Ordovás-Montañés, María; Lee, Yu-Chi; Parnell, Laurence D; Arnett, Donna K; Ordovás, José M

2014-04-01

Despite the solid connection between REV-ERB and obesity, the information about whether genetic variations at this locus may be associated with obesity traits is scarce. Therefore our objective was to study the association between REV-ERB-ALPHA1 rs2314339 and obesity in two independent populations. Participants were 2214 subjects from Spanish Mediterranean (n = 1404) and North American (n = 810) populations. Anthropometric, biochemical, dietary, and genotype analyses were performed. We found novel associations between the REV-ERB-ALPHA1 rs2314339 genotype and obesity in two independent populations: in Spanish Mediterranean and North American groups, the frequency of the minor-allele-carriers (AA+ AG) was significantly lower in the "abdominally obese" group than in those of the "nonabdominally obese" group (p obesity than noncarriers, and the effect was of similar magnitude for both populations (OR ≈ 1.50). There were consistent associations between REV-ERB-ALPHA1 genotype and obesity-related traits (p obesity was also detected in the Mediterranean population. This new discovery highlights the importance of REV-ERB-ALPHA1 in obesity and provides evidence for the connection between our biological clock and obesity-related traits. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease.

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Zhang, Heng; Zhang, Ling; Zhou, Dongming; He, Xiao; Wang, Dongpi; Pan, Hongyu; Zhang, Xiaoqin; Mei, Yufei; Qian, Qi; Zheng, Tingting; Jones, Frank E; Sun, Binggui

2017-10-01

Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. Copyright © 2017 Elsevier Inc. All rights reserved.

ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson’s disease

Directory of Open Access Journals (Sweden)

Yuriko eIwakura

2013-02-01

Full Text Available Ligands for ErbB1-4 receptor tyrosine kinases, such as epidermal growth factor (EGF and neuregulins, regulate brain development and function. Thus, abnormalities in their signaling are implicated in the etiology or pathology of schizophrenia and Parkinson’s disease. Among the ErbB receptors, ErbB1 and ErbB4 are expressed in dopamine and GABA neurons, while ErbB1, 2, and/or 3 are mainly present in oligodendrocytes, astrocytes and their precursors. Thus, deficits in ErbB signaling might contribute to schizophrenia neuropathology stemming from these cell types. By incorporating the latest cancer molecular biology as well as our recent progress, we discuss signal cross talk between the ErbB1-4 subunits and their neurobiological functions in each cell type. The potential contribution of virus-derived cytokines (virokines that mimic EGF and neuregulin-1 in brain diseases are also discussed.

Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

DEFF Research Database (Denmark)

Frogne, Thomas; Benjaminsen, Rikke; Sonne-Hansen, Katrine

2008-01-01

cell lines concomitant with inhibition of Erk and unaltered Akt activation. In concert, inhibition of Erk with U0126 preferentially reduced growth of resistant cell lines. Treatment with ErbB3 neutralizing antibodies inhibited ErbB3 activation and resulted in a modest but statistically significant...... activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2...

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients.

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Xu, Yujin; Wang, Liancong; Zheng, Xiao; Liu, Guan; Wang, Yuezhen; Lai, Xiaojing; Li, Jianqiang

2013-05-01

The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration.

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Ketan Mathavan

Full Text Available During development, a multi-potent group of cells known as the cranial neural crest (CNC migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3 is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors.

Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

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Carrasco-Garcia, Estefania; Saceda, Miguel [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gomez-Martinez, Angeles [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Garcia-Morales, Pilar [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Ferragut, Jose A. [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Martinez-Lacaci, Isabel, E-mail: imlacaci@umh.es [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad AECC de Investigacion Traslacional en Cancer, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia (Spain)

2011-06-10

Signaling through the epidermal growth factor receptor (EGFR) is relevant in glioblastoma. We have determined the effects of the EGFR inhibitor AG1478 in glioblastoma cell lines and found that U87 and LN-229 cells were very sensitive to this drug, since their proliferation diminished and underwent a marked G{sub 1} arrest. T98 cells were a little more refractory to growth inhibition and A172 cells did not undergo a G{sub 1} arrest. This G{sub 1} arrest was associated with up-regulation of p27{sup kip1}, whose protein turnover was stabilized. EGFR autophosphorylation was blocked with AG1478 to the same extent in all the cell lines. Other small-molecule EGFR tyrosine kinase inhibitors employed in the clinic, such as gefitinib, erlotinib and lapatinib, were able to abrogate proliferation of glioblastoma cell lines, which underwent a G{sub 1} arrest. However, the EGFR monoclonal antibody, cetuximab had no effect on cell proliferation and consistently, had no effect on cell cycle either. Similarly, cetuximab did not inhibit proliferation of U87 {Delta}EGFR cells or primary glioblastoma cell cultures, whereas small-molecule EGFR inhibitors did. Activity of downstream signaling molecules of EGFR such as Akt and especially ERK1/2 was interrupted with EGFR tyrosine kinase inhibitors, whereas cetuximab treatment could not sustain this blockade over time. Small-molecule EGFR inhibitors were able to prevent phosphorylation of erbB3 and erbB4, whereas cetuximab only hindered EGFR phosphorylation, suggesting that EGFR tyrosine kinase inhibitors may mediate their anti-proliferative effects through other erbB family members. We can conclude that small-molecule EGFR inhibitors may be a therapeutic approach for the treatment of glioblastoma patients.

The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3

International Nuclear Information System (INIS)

Alper, O.; Yamaguchi, K.; Hitomi, J.; Honda, S.; Matsushima, T.; Abe, K.

1990-01-01

The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein

Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

International Nuclear Information System (INIS)

Andolfo, Immacolata; Orditura, Michele; Ciardiello, Fortunato; De Vita, Fernando; Zollo, Massimo; Petrosino, Giuseppe; Vecchione, Loredana; De Antonellis, Pasqualino; Capasso, Mario; Montanaro, Donatella; Gemei, Marica; Troncone, Giancarlo; Iolascon, Achille

2011-01-01

Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression. Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays. The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels. The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer

NOAA-9 Earth Radiation Budget Experiment (ERBE) scanner offsets determination

Science.gov (United States)

Avis, Lee M.; Paden, Jack; Lee, Robert B., III; Pandey, Dhirendra K.; Stassi, Joseph C.; Wilson, Robert S.; Tolson, Carol J.; Bolden, William C.

1994-01-01

The Earth Radiation Budget Experiment (ERBE) instruments are designed to measure the components of the radiative exchange between the Sun, Earth and space. ERBE is comprised of three spacecraft, each carrying a nearly identical set of radiometers: a three-channel narrow-field-of-view scanner, a two-channel wide-field-of-view (limb-to-limb) non-scanning radiometer, a two-channel medium field-of view (1000 km) non-scanning radiometer, and a solar monitor. Ground testing showed the scanners to be susceptible to self-generated and externally generated electromagnetic noise. This paper describes the pre-launch corrective measures taken and the post-launch corrections to the NOAA-9 scanner data. The NOAA-9 scanner has met the mission objectives in accuracy and precision, in part because of the pre-launch reductions of and post-launch data corrections for the electromagnetic noise.

Análise da expressão imuno-histoquímica de c-erbB-2 e EGFR em carcinoma epidermóide de esôfago Immunohistochemical expression of c-erbB-2 and EGFR in esophageal squamous cell carcinoma

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Yukie Sato

2007-08-01

Full Text Available INTRODUÇÃO: O carcinoma epidermóide de esôfago (CEE possui alta incidência em nosso país, com altas taxas de mortalidade. A família dos receptores do fator epitelial de crescimento (EGFR é composta por quatro membros, e muitos estudos têm sido direcionados para a expressão de EGFR e c-erbB-2, com implicações terapêuticas. OBJETIVO: Investigar as expressões imuno-histoquímicas de EGFR e c-erbB-2 e correlacioná-las a aspectos clinicopatológicos em casos de CEE. MATERIAL E MÉTODOS: Para esse estudo, dados clinicopatológicos de 613 CEE foram revistos. A imunoistoquímica foi feita utilizando anticorpo policlonal para c-erbB-2 e monoclonal para EGFR em 597 e 585 casos, respectivamente. Os casos representados por peças cirúrgicas foram distribuídos em três blocos de parafina de tissue microarray (TMA, inseridos em duplicata; aqueles com biópsias foram analisados em corte convencional. Todos foram classificados de acordo com intensidade e padrão de marcação de membrana das células tumorais. RESULTADOS: As expressões de c-erbB-2 e EGFR foram observadas em 42,4% e 77,6% dos casos, respectivamente. Observou-se correlação estatisticamente significativa entre as expressões de c-erbB-2 (p = 0,04 e EGFR (p = 0,01 e grau histológico. Ambos os marcadores foram significativamente mais expressos em casos bem/moderadamente diferenciados do que nos pouco diferenciados/indiferenciados. Embora não tenha sido significativa, houve uma tendência de associação entre superexpressão de c-erbB-2 e sítio do tumor, em que casos positivos ocorreram com mais freqüência no terço médio do esôfago. Nenhuma correlação significativa foi verificada entre essas proteínas e sobrevida global. CONCLUSÃO: Os resultados podem sugerir um papel primordial para essas proteínas na diferenciação tumoral em CEE.INTRODUCTION: Esophageal squamous cell carcinoma (ESCC is highly prevalent in Brazil, and responsible for high mortality index. The

TOA Radiation Balance Study through Reprocessed ERBS WFOV Nonscanner data from 1985 to 1998

Science.gov (United States)

Shrestha, A. K.; Kato, S.; Wong, T.; Stackhouse, P. W., Jr.; Doelling, D. R.; Loughman, R. P.

2017-12-01

Wide-field-of-view (WFOV) nonscanner instrument onboard Earth Radiation Budget Satellite (ERBS) provided broadband irradiances at the top-of-atmosphere (TOA) from 1985 to 1999. However, earlier studies show that the uncertainty in this TOA radiation dataset is significantly higher during the period after the Mt. Pinatubo eruption and battery issue in 1991. In addition, the difference between daytime and nighttime longwave irradiance drifts with time throughout the lifetime of the instrument. We re-processed ERBS WFOV data using the algorithm similar to the one used in the CERES project and calibrated it with CERES-derived irradiances. In addition, the spatial coverage of ERBS irradiances is extended to global from near-global (60°N to 60°S latitudes) using CERES climatological ratio of the near-global to global mean irradiances. The near-global standard deviation of deseasonalized shortwave anomalies computed with Ed4 decreases to 3.2 Wm-2 from 8.0 Wm-2, computed with previous version. In addition, the drift of day-minus-night longwave irradiance is reduced by one third. Similar to the previous version, however, the Ed4 global shortwave irradiance averaged over the 1994 to 1997 period (second period) is smaller by 2.2 Wm-2 compared to that averaged over the 1985 to 1989 period (first period). In addition, the global longwave irradiance in the second period is larger by 0.7 Wm-2 compared to that averaged over the first period. When the difference of two periods is computed (second period minus first period) with the DEEP-C data product (Allan et al. 2014), the difference is 0.5 (-0.3) Wm-2 for shortwave (longwave). The global net imbalance at the TOA computed with ERBS and DEEP-C data sets are, respectively, 0.45 (1.89) Wm-2 and 0.17 (0.96) Wm-2 for the first (second) period. The net imbalance for the CERES period in the 2000s is 0.65 Wm-2. In this presentation, we will further compare Ed4 ERBS-derived TOA net imbalance with ocean heating rates. Re-processed ERBS

A pathological study on overexpression of c-erbB-2, EGFR proteins in human radiation skin ulcer

International Nuclear Information System (INIS)

Zhao Po; Yang Zhixiang; Wang Dewen; Li Guomin; Gao Yabin

1996-01-01

We performed an immunohistochemical study in 25 cases of human radiation skin ulcer by using c-erbB-2, Epidermal growth factor receptor (EGFR), protein antibodies and repairing method of antigen with microwave oven. The results show that the positive rate for overexpression of c-erbB-2 oncoprotein was 92.0% (23/25), and EGFR was 73.7%(14/19). The positive position for overexpression of c-crbB-2 was mainly observed on cell membrane of squamous epithelial cells and cell plasma of fibroblasts, endotheliocytes, and leiomyocytes in media and fibrocytes in adventitia of the arterioles in mesenchyme. It is suggested that the overexpression of c-erbB-2 and EGFR proteins might be related to cancer transformation and poor healing in radiation skin ulcers

Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

DEFF Research Database (Denmark)

Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle

2015-01-01

, the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG...... parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left...... ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes...

Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules.

Science.gov (United States)

Skelton, Lara A; Boron, Walter F

2013-12-15

The renal proximal tubule (PT) is a major site for maintaining whole body pH homeostasis and is responsible for reabsorbing ∼80% of filtered HCO3(-), the major plasma buffer, into the blood. The PT adapts its rate of HCO3(-) reabsorption (JHCO3(-)) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3(-) in response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3(-) concentrations but, surprisingly, not to pH. The response to CO2 concentration can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the present study, we exposed enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific pY (four sites), and ErbB2-specific pY (two sites). We found that each acid-base treatment generated a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance showed that metabolic acidosis (normal CO2 concentration and reduced HCO3(-) concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produced a transient increase. Respiratory acidosis (normal HCO3(-) concentration and elevated CO2 concentration) had little effect on summated pY at 5 min but produced an elevation at 20 min, whereas respiratory alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.

Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

Science.gov (United States)

Mang, Géraldine M; La Spada, Francesco; Emmenegger, Yann; Chappuis, Sylvie; Ripperger, Jürgen A; Albrecht, Urs; Franken, Paul

2016-03-01

The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. © 2016 Associated Professional Sleep Societies, LLC.

A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial

National Research Council Canada - National Science Library

Duan, Lei

2001-01-01

.... Based on these observations, this proposal is investigating the role of Cbl-mediated ubiquitination as a signal for targeting activated ErbB receptors to lysosomes where they undergo degradation...

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

Directory of Open Access Journals (Sweden)

Jian Liu

2015-03-01

Full Text Available Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

Science.gov (United States)

Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

2007-11-01

Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

Science.gov (United States)

Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

2006-10-03

We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation

International Nuclear Information System (INIS)

Diermeier, Simone; Horvath, Gabor; Knuechel-Clarke, Ruth; Hofstaedter, Ferdinand; Szoellosi, Janos; Brockhoff, Gero

2005-01-01

Background: Growth factors and Herceptin specifically and differentially modulate cell proliferation of tumor cells. However, the mechanism of action on erbB-receptor level is incompletely understood. We evaluated Herceptin's capacity to modulate erbB-receptor activation and interaction on the cell surface level and thereby potentially impair cell proliferation of HER2/neu (c-erbB2) overexpressing breast cancer cells, both in the presence and absence of relevant growth factors. Methods: BT474 and SK-BR-3 breast cancer cell lines were treated with Epidermal Growth Factor (EGF), Heregulin, and with Herceptin in different combinations. Kinetics of cell proliferation were evaluated flow cytometrically based on BrdU-labeling. Fluorescence Resonance Energy Transfer, ELISAs and phosphorylation site specific Western Blotting was performed to investigate erbB-receptor interaction and activation. Results: EGF induced EGFR/EGFR and EGFR/c-erbB2 interactions correlate with stimulation of cell proliferation in BT474 cells. Both homo- and heterodimerization are considerably less pronounced in SK-BR-3 cells and heterointeraction is additionally reduced by EGF treatment, causing inhibition of cell proliferation. Heregulin stimulates cell proliferation extensively in both cell lines. Herceptin drives BT474 cells more efficiently into quiescence than it does with SK-BR-3 cells and thereby blocks cell cycle progress. In SK-BR-3 Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248, EGF induces Y877 and Y1112 phosphorylation. The Y1112 phosphorylation site, activated by EGF in SK-BR-3 cell, is bypassed in BT474. In addition the inhibitory capacity of Herceptin on BT474 and SK-BR-3 cell proliferation depends on the presence and absence of growth factors to a various extent. Conclusion: The growth inhibitory effect of Herceptin on c-erbB2 overexpressing breast cancer cells is considerably modulated by EGFR coexpression and consequently EGFR/c-erbB2 homo- and

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.

Science.gov (United States)

Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I; Creighton, Chad J; Kheradmand, Farrah; DeMayo, Francesco J

2015-03-03

Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A holistic approach to the management of Erb's palsy

Science.gov (United States)

Srilakshmi, Dasari; Chaganti, Sreelakshmi

2013-01-01

A 4.5-month-old female baby, presenting with complete paralysis of right upper limb with typical waiter's tip deformity, diagnosed as Erb's palsy was brought to Sri Ganapati Sachchidananda Hospital. Patient was treated with an integrated approach of physiotherapy and Ayurvedic treatment with an intention of aiding faster recovery of the patient to lead a near normal life. As per Ayurvedic classics, this condition can be correlated to Ekangavata (Vata effecting any one part of the body), which is Apatarpana in nature (diseases with deprived growth of body tissue). Hence, the choice of treatment is Santarpana Chikitsa (nourishing treatment). Santarpana Bahyopakramas (nourishing external treatment modalities) such as Ashwagandhabalalakshadi Taila (Ayurvedic medicated oil) Abhyanga (oleation therapy) and Shastikashali Anna Lepa (application of processed rice paste) were administered along with electrical stimulation (physiotherapy modality), both galvanic and faradic current in three sessions. Appreciable results were observed in the form of reduction of disparity in length and mid-arm circumference of right upper limb compared to unaffected left upper limb and the muscle power too improved from zero to four, facilitating patient to near normal movement. PMID:24459391

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats

Science.gov (United States)

Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

2015-01-01

Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats. PMID:25820551

No evidence for c-erbB-2 overexpression in gastric carcinogenesis

NARCIS (Netherlands)

Blok, P.; Craanen, M. E.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

1998-01-01

Conflicting data on c-erbB-2 overexpression in gastric carcinomas can be found in the literature with regard to overall prevalence, prognostic significance and the histological type according to Lauren. The majority of these studies have focused on advanced gastric carcinomas whereas data on

Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

Directory of Open Access Journals (Sweden)

Brown M Scott

2010-12-01

Full Text Available Abstract Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1 mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1, another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield

Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

Science.gov (United States)

2010-01-01

Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield additional insight into the

Novel Peptide/Protein Delivery System Targeting erbB2-Overexpressing Breast Cancer Cells

National Research Council Canada - National Science Library

Yu, Dihua

2002-01-01

.... During this funding year, we focused on the delivery of erbB2 signal-blocking ESP peptides (objective 2) . Because of the complexity of biotin-penetratin-AHNP-ESP, the synthesis was unsuccessful...

Prediction of monthly regional groundwater levels through hybrid soft-computing techniques

Science.gov (United States)

Chang, Fi-John; Chang, Li-Chiu; Huang, Chien-Wei; Kao, I.-Feng

2016-10-01

Groundwater systems are intrinsically heterogeneous with dynamic temporal-spatial patterns, which cause great difficulty in quantifying their complex processes, while reliable predictions of regional groundwater levels are commonly needed for managing water resources to ensure proper service of water demands within a region. In this study, we proposed a novel and flexible soft-computing technique that could effectively extract the complex high-dimensional input-output patterns of basin-wide groundwater-aquifer systems in an adaptive manner. The soft-computing models combined the Self Organized Map (SOM) and the Nonlinear Autoregressive with Exogenous Inputs (NARX) network for predicting monthly regional groundwater levels based on hydrologic forcing data. The SOM could effectively classify the temporal-spatial patterns of regional groundwater levels, the NARX could accurately predict the mean of regional groundwater levels for adjusting the selected SOM, the Kriging was used to interpolate the predictions of the adjusted SOM into finer grids of locations, and consequently the prediction of a monthly regional groundwater level map could be obtained. The Zhuoshui River basin in Taiwan was the study case, and its monthly data sets collected from 203 groundwater stations, 32 rainfall stations and 6 flow stations during 2000 and 2013 were used for modelling purpose. The results demonstrated that the hybrid SOM-NARX model could reliably and suitably predict monthly basin-wide groundwater levels with high correlations (R2 > 0.9 in both training and testing cases). The proposed methodology presents a milestone in modelling regional environmental issues and offers an insightful and promising way to predict monthly basin-wide groundwater levels, which is beneficial to authorities for sustainable water resources management.

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

Science.gov (United States)

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

In silico prediction of ErbB signal activation from receptor expression ...

Indian Academy of Sciences (India)

85

Annals of biomedical engineering 35 1012-1025. Machado D, Costa RS, Rocha M, Ferreira EC, Tidor B, Rocha I 2011 Modeling formalisms in Systems Biology. AMB Express 1 45. McCabe Pryor M, et al. 2015 Orchestration of ErbB3 signaling through heterointeractions and homointeractions. Mol Biol Cell 26 4109-4123.

The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17

DEFF Research Database (Denmark)

Dombernowsky, Sarah Louise; Samsøe-Petersen, Jacob; Petersen, Camilla Hansson

2015-01-01

The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release....... PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduced...

RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

Science.gov (United States)

Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

2018-04-23

The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

Molecularly targeted therapy for the treatment of head and neck cancer: a review of the ErbB family inhibitors

Directory of Open Access Journals (Sweden)

Sacco AG

2016-04-01

Full Text Available Assuntina G Sacco,1 Francis P Worden2 1Department of Internal Medicine, Division of Hematology/Oncology, University of California at San Diego Moores Cancer Center, La Jolla, CA, USA; 2Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, USA Abstract: The majority of patients with head and neck squamous cell carcinoma (HNSCC present with locally advanced disease, which requires site-specific combinations of surgery, radiation, and chemotherapy. Despite aggressive therapy, survival outcomes remain poor, and treatment-related morbidity is not negligible. For patients with recurrent or metastatic disease, therapeutic options are further limited and prognosis is dismal. With this in mind, molecularly targeted therapy provides a promising approach to optimizing treatment efficacy while minimizing associated toxicity. The ErbB family of receptors (ie, epidermal growth factor receptor [EGFR], ErbB2/human epidermal growth factor receptor [HER]-2, ErbB3/HER3, and ErbB4/HER4 is known to contribute to oncogenic processes, such as cellular proliferation and survival. EGFR, specifically, is upregulated in more than 90% of HNSCC, has been implicated in radiation resistance, and correlates with poorer clinical outcomes. The central role of EGFR in the pathogenesis of HNSCC suggests that inhibition of this pathway represents an attractive treatment strategy. As a result, EGFR inhibition has been extensively studied, with the emergence of two classes of drug therapy: monoclonal antibodies and tyrosine kinase inhibitors. While the monoclonal antibody cetuximab is currently the only US Food and Drug Administration–approved EGFR inhibitor for the treatment of HNSCC, numerous investigational drugs are being evaluated in clinical trials. This paper will review the role of the ErbB family in the pathogenesis of HNSCC, as well as the evidence-based data for the use of ErbB family inhibition in clinical

Earth Radiation Budget Experiment (ERBE) Data Sets for Global Environment and Climate Change Studies

Science.gov (United States)

Bess, T. Dale; Carlson, Ann B.; Denn, Fredrick M.

1997-01-01

For a number of years there has been considerable interest in the earth's radiation budget (ERB) or energy balance, and entails making the best measurements possible of absorbed solar radiation, reflected shortwave radiation (RSW), thermal outgoing longwave radiation (OLR), and net radiation. ERB data are fundamental to the development of realistic climate models and studying natural and anthropogenic perturbations of the climate. Much of the interest and investigations in the earth's energy balance predated the age of earth-orbiting satellites (Hunt et al., 1986). Beginning in the mid 1960's earth-orbiting satellites began to play an important role in making measurements of the earth's radiation flux although much effort had gone into measuring ERB parameters prior to 1960 (House et al., 1986). Beginning in 1974 and extending until the present time, three different satellite experiments (not all operating at the same time) have been making radiation budget measurements almost continually in time. Two of the experiments were totally dedicated to making radiation budget measurements of the earth, and the other experiment flown on NOAA sun-synchronous AVHRR weather satellites produced radiation budget parameters as a by-product. The heat budget data from the AVHRR satellites began collecting data in June 1974 and have operated almost continuously for 23 years producing valuable data for long term climate monitoring.

Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments.

Directory of Open Access Journals (Sweden)

Debby D Wang

Full Text Available EGFR mutation-induced drug resistance has become a major threat to the treatment of non-small-cell lung carcinoma. Essentially, the resistance mechanism involves modifications of the intracellular signaling pathways. In our work, we separately investigated the EGFR and ErbB-3 heterodimerization, regarded as the origin of intracellular signaling pathways. On one hand, we combined the molecular interaction in EGFR heterodimerization with that between the EGFR tyrosine kinase and its inhibitor. For 168 clinical subjects, we characterized their corresponding EGFR mutations using molecular interactions, with three potential dimerization partners (ErbB-2, IGF-1R and c-Met of EGFR and two of its small molecule inhibitors (gefitinib and erlotinib. Based on molecular dynamics simulations and structural analysis, we modeled these mutant-partner or mutant-inhibitor interactions using binding free energy and its components. As a consequence, the mutant-partner interactions are amplified for mutants L858R and L858R_T790M, compared to the wild type EGFR. Mutant delL747_P753insS represents the largest difference between the mutant-IGF-1R interaction and the mutant-inhibitor interaction, which explains the shorter progression-free survival of an inhibitor to this mutant type. Besides, feature sets including different energy components were constructed, and efficient regression trees were applied to map these features to the progression-free survival of an inhibitor. On the other hand, we comparably examined the interactions between ErbB-3 and its partners (EGFR mutants, IGF-1R, ErbB-2 and c-Met. Compared to others, c-Met shows a remarkably-strong binding with ErbB-3, implying its significant role in regulating ErbB-3 signaling. Moreover, EGFR mutants corresponding to poor clinical outcomes, such as L858R_T790M, possess lower binding affinities with ErbB-3 than c-Met does. This may promote the communication between ErbB-3 and c-Met in these cancer cells. The

Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

International Nuclear Information System (INIS)

Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

2013-01-01

Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

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Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

2013-11-15

Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

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Maria Teresa de Seixas Alves

2008-04-01

Full Text Available INTRODUÇÃO: Osteossarcoma (OS, o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológicos. A anaplasia, em neoplasias na infância, constitui parâmetro histológico de agressividade tumoral e quimiorresistência. Nos OS primários ou metastáticos, seu significado permanece controverso. Por outro lado, em outras neoplasias humanas, a expressão do c-erb-B2 relaciona-se com p53, grau nuclear e outros parâmetros de agressividade. OBJETIVO: Avaliar a imunoexpressão de p53, c-erb-B2 e P-gp em OS, correlacionando os par��metros entre si e com a presença de anaplasia. MÉTODO: O estudo incluiu 96 biópsias pré-quimioterapia de pacientes com OS de alto grau, diagnosticados entre 1991 e 2000. A pesquisa imuno-histoquímica de p53, P-gp e c-erb-B2 foi feita pela técnica da estreptoavidina-biotina-peroxidase. Foram considerados positivos os casos onde havia imunoexpressão em 10% ou mais das células neoplásicas. Somente colorações membranosa (para cerb-B2 e P-gp e nuclear (para p53 foram consideradas positivas. Anaplasia foi definida como no tumor de Wilms, sendo considerada presente ou ausente. RESULTADOS: Anaplasia pôde ser avaliada em 82/96 casos, estando presente em 29 (35,36%. Imunoexpressão de p53 foi detectada em 25 dos 60 casos (36,23%; de P-gp, em 30 dos 73 casos (41,1%; e de c-erb-B2, em 22 dos 55 casos (40%. Os resultados demonstraram associação entre as imunoexpressões de c-erb-B2 e p53 (p = 0,042, p53 e o parâmetro anaplasia (p = 0,015, anaplasia e Pg (p = 0.034 CONCLUSÕES: A imunoexpressão de p53, c-erb

Regional parametrisation of a monthly hydrological model for estimating discharges in ungaued catchments

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Hlavcova, K.; Szolgay, J.; Kohnova, S.; Kalas, M.

2003-04-01

In the case of the absence of measured runoff optimisation techniques cannot be used to estimate the parameters of monthly rainfall-runoff models. In such a case usually empirical regression methods were used for relating the model parameters to the catchment characteristics in a given region. In the paper a different method for the regional calibration of a monthly water balance model, which can be used for planning purposes, is proposed. Instead of using the regional regression approach a method is proposed, which involves the calibration of a monthly water balance model to gauged sites in the given region simultaneously. A regional objective function was constructed and for the calibration a genetic programming algorithm was employed. It is expected, that the regionally calibrated model parameters can be used in ungauged basins with similar physiographic conditions. The comparison of the performance of such a regional calibration scheme was compared with two single site calibration methods in a region of West Slovakia. The results are based on a study that aimed at computing surface water inflow into a lowland area with valuable groundwater resources. Monthly discharge time series had to be estimated in small ungauged rivers entering the study area.

Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model.

Science.gov (United States)

Luo, Li-Ping; Han, Bin; Yu, Xiao-Ping; Chen, Xiang-Yan; Zhou, Jie; Chen, Wei; Zhu, Yan-Feng; Peng, Xiao-Li; Zou, Qiang; Li, Sui-Yan

2014-01-01

Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

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Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

2009-07-03

Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

Breast cancer cells can switch between estrogen receptor alpha and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance

DEFF Research Database (Denmark)

Sonne-Hansen, Katrine; Norrie, Ida C; Emdal, Kristina Bennet

2010-01-01

circumvent development of resistance. Limited effects were observed when targeting EGFR and ErbB2 with the monoclonal antibodies cetuximab, trastuzumab, and pertuzumab, whereas the pan-ErbB inhibitor CI-1033 selectively inhibited growth of fulvestrant resistant cell lines. CI-1033 inhibited Erk but not Akt...

Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

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Lu Kun

2008-12-01

Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

Science.gov (United States)

Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

2014-01-01

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

The chicken c-erbA alpha-product induces expression of thyroid hormone-responsive genes in 3,5,3'-triiodothyronine receptor-deficient rat hepatoma cells

DEFF Research Database (Denmark)

Muñoz, A; Höppner, W; Sap, J

1990-01-01

To determine the capacity of the chicken c-erbA (cTR-alpha) gene product in regulating expression of known thyroid hormone-responsive genes, both the cTR-alpha and the viral v-erbA genes were expressed in FAO cells, a rat hepatoma cell line defective for functional thyroid hormone receptors. Upon...

Cell cycle synchronization and BrdU incorporation as a tool to study the possible selective elimination of ErbB1 gene in the micronuclei in A549 cells

International Nuclear Information System (INIS)

Lauand, C.; Niero, E.L.; Dias, V.M.; Machado-Santelli, G.M.

2015-01-01

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells

Cell cycle synchronization and BrdU incorporation as a tool to study the possible selective elimination of ErbB1 gene in the micronuclei in A549 cells

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Lauand, C.; Niero, E.L.; Dias, V.M.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-03-06

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells.

Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

International Nuclear Information System (INIS)

Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

2009-01-01

An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

Science.gov (United States)

Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

2016-01-01

The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P oral malignant cancer.

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

Science.gov (United States)

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Evaluation of C-ErbB-2 Overexpression and Her-2/neu Gene Copy Number Heterogeneity in Barrett’s Adenocarcinoma

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Axel Walch

2000-01-01

Full Text Available Amplifiction of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett’s adenocarcinoma (BCA (n = 6 and dysplasia adjacent to the carcinoma (n = 4. In addition, fluorescence in situ hybridisation (FISH was performed in primary BCA (n=5 and dysplastic areas (n=4. For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoural heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogenous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoural gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her‐2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c‐erbB‐2 status in small biopsies and possibly influence the effectiveness of a potential c‐erbB‐2 targeting therapy.

Role of sea surface temperature anomalies in the tropical Indo-Pacific region in the northeast Asia severe drought in summer 2014: month-to-month perspective

Science.gov (United States)

Xu, Zhiqing; Fan, Ke; Wang, HuiJun

2017-09-01

The severe drought over northeast Asia in summer 2014 and the contribution to it by sea surface temperature (SST) anomalies in the tropical Indo-Pacific region were investigated from the month-to-month perspective. The severe drought was accompanied by weak lower-level summer monsoon flow and featured an obvious northward movement during summer. The mid-latitude Asian summer (MAS) pattern and East Asia/Pacific teleconnection (EAP) pattern, induced by the Indian summer monsoon (ISM) and western North Pacific summer monsoon (WNPSM) rainfall anomalies respectively, were two main bridges between the SST anomalies in the tropical Indo-Pacific region and the severe drought. Warming in the Arabian Sea induced reduced rainfall over northeast India and then triggered a negative MAS pattern favoring the severe drought in June 2014. In July 2014, warming in the tropical western North Pacific led to a strong WNPSM and increased rainfall over the Philippine Sea, triggering a positive EAP pattern. The equatorial eastern Pacific and local warming resulted in increased rainfall over the off-equatorial western Pacific and triggered an EAP-like pattern. The EAP pattern and EAP-like pattern contributed to the severe drought in July 2014. A negative Indian Ocean dipole induced an anomalous meridional circulation, and warming in the equatorial eastern Pacific induced an anomalous zonal circulation, in August 2014. The two anomalous cells led to a weak ISM and WNPSM, triggering the negative MAS and EAP patterns responsible for the severe drought. Two possible reasons for the northward movement of the drought were also proposed.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

Science.gov (United States)

Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

2015-06-15

Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was

Monthly Rainfall Erosivity Assessment for Switzerland

Science.gov (United States)

Schmidt, Simon; Meusburger, Katrin; Alewell, Christine

2016-04-01

Water erosion is crucially controlled by rainfall erosivity, which is quantified out of the kinetic energy of raindrop impact and associated surface runoff. Rainfall erosivity is often expressed as the R-factor in soil erosion risk models like the Universal Soil Loss Equation (USLE) and its revised version (RUSLE). Just like precipitation, the rainfall erosivity of Switzerland has a characteristic seasonal dynamic throughout the year. This inter-annual variability is to be assessed by a monthly and seasonal modelling approach. We used a network of 86 precipitation gauging stations with a 10-minute temporal resolution to calculate long-term average monthly R-factors. Stepwise regression and Monte Carlo Cross Validation (MCCV) was used to select spatial covariates to explain the spatial pattern of R-factor for each month across Switzerland. The regionalized monthly R-factor is mapped by its individual regression equation and the ordinary kriging interpolation of its residuals (Regression-Kriging). As covariates, a variety of precipitation indicator data has been included like snow height, a combination of hourly gauging measurements and radar observations (CombiPrecip), mean monthly alpine precipitation (EURO4M-APGD) and monthly precipitation sums (Rhires). Topographic parameters were also significant explanatory variables for single months. The comparison of all 12 monthly rainfall erosivity maps showed seasonality with highest rainfall erosivity in summer (June, July, and August) and lowest rainfall erosivity in winter months. Besides the inter-annual temporal regime, a seasonal spatial variability was detectable. Spatial maps of monthly rainfall erosivity are presented for the first time for Switzerland. The assessment of the spatial and temporal dynamic behaviour of the R-factor is valuable for the identification of more susceptible seasons and regions as well as for the application of selective erosion control measures. A combination with monthly vegetation

A single amino acid substitution is sufficient to modify the mitogenic properties of the epidermal growth factor receptor to resemble that of gp185erbB-2

DEFF Research Database (Denmark)

Di Fiore, P P; Helin, K; Kraus, M H

1992-01-01

The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxtamembrane regio...

Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

Science.gov (United States)

Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

2015-06-28

ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

Correlates and importance of neglect-like symptoms in complex regional pain syndrome.

Science.gov (United States)

Wittayer, Matthias; Dimova, Violeta; Birklein, Frank; Schlereth, Tanja

2018-05-01

Neglect-like symptoms (NLS) are frequently observed in complex regional pain syndrome (CRPS). The clinical meaning of NLS, however, is largely unknown. Therefore, this study sets out to assess the importance of NLS for patient outcome and to explore their clinical correlates. We assessed NLS in a group of 53 patients with CRPS and compared the results to 28 healthy volunteers. To define the origin of the NLS reports, we tested the subjective visual midline, performed a limb-laterality recognition test, and quantitative sensory testing. In addition, psychological and pain assessment scales were completed. Tests were analyzed with univariate and multivariate approaches. After 6 months, patients were reassessed and the influence of NLS on pain outcome was determined. Most patients reported NLS in the questionnaire, whereas subjective visual midline and limb-laterality recognition test in contrast to previous studies did not reveal perceptual disturbances. Neglect-like symptom scores were associated with pain and pain catastrophizing in acute CRPS and anxiety and thermal sensory loss in chronic CRPS. Furthermore, high NLS scores had a negative impact on pain outcome after 6 months. Our results indicate that NLS have a different meaning in acute and chronic CRPS and might be of prognostic value. Possibly, treatment should focus on reducing NLS.

Development of the correlation study between mammographic appearances and expression of estrogen receptor, progesterone receptor and C-erbB-2 in patients with breast cancer

International Nuclear Information System (INIS)

Liu Jie; Liu Peifang

2012-01-01

Breast cancer is one of the most common female malignant tumors. The occurrence and development of breast cancer are often accompanied by abnormal gene expression. It has been well accepted that estrogen receptor (ER), progesterone receptor (PR) and C-erbB-2 (epidermal growth factor receptor-2) are the main reference indexes for clinical endocrine therapy and prognosis prediction. Oncogene expression reflects the malignant biological behavior of breast cancer from different perspectives. Those aggressive behaviors cause a variety of changes in histopathology and thus in imaging. Therefore, the imaging features of breast cancer may indirectly demonstrate the status of ER, PR and C-erbB-2 to a certain extent. Until now, because of its simple operation,low cost and high accuracy, mammography is still the preferred method in breast cancer screening and diagnosis, and has been proposed as a noninvasive technique for prediction of the expression of ER, PR and C-erbB-2. It has potential clinical value in preoperative assessment and non-surgical treatment for those who are not able to perform immunohistochemistry. This review summarized previous related studies and explored mammography as a noninvasive predictor for ER, PR and C-erbB-2. (authors)

Monthly Rainfall Erosivity: Conversion Factors for Different Time Resolutions and Regional Assessments

Directory of Open Access Journals (Sweden)

Panos Panagos

2016-03-01

Full Text Available As a follow up and an advancement of the recently published Rainfall Erosivity Database at European Scale (REDES and the respective mean annual R-factor map, the monthly aspect of rainfall erosivity has been added to REDES. Rainfall erosivity is crucial to be considered at a monthly resolution, for the optimization of land management (seasonal variation of vegetation cover and agricultural support practices as well as natural hazard protection (landslides and flood prediction. We expanded REDES by 140 rainfall stations, thus covering areas where monthly R-factor values were missing (Slovakia, Poland or former data density was not satisfactory (Austria, France, and Spain. The different time resolutions (from 5 to 60 min of high temporal data require a conversion of monthly R-factor based on a pool of stations with available data at all time resolutions. Because the conversion factors show smaller monthly variability in winter (January: 1.54 than in summer (August: 2.13, applying conversion factors on a monthly basis is suggested. The estimated monthly conversion factors allow transferring the R-factor to the desired time resolution at a European scale. The June to September period contributes to 53% of the annual rainfall erosivity in Europe, with different spatial and temporal patterns depending on the region. The study also investigated the heterogeneous seasonal patterns in different regions of Europe: on average, the Northern and Central European countries exhibit the largest R-factor values in summer, while the Southern European countries do so from October to January. In almost all countries (excluding Ireland, United Kingdom and North France, the seasonal variability of rainfall erosivity is high. Very few areas (mainly located in Spain and France show the largest from February to April. The average monthly erosivity density is very large in August (1.67 and July (1.63, while very small in January and February (0.37. This study addresses

78 FR 73586 - Senior Executive Service Performance Review Board (PRB) and Executive Resources Board (ERB...

Science.gov (United States)

2013-12-06

...: Performance Review Board Leland L. Gardner, Chairman Rachel D. Campbell, Member Craig M. Keats, Member Lucille Marvin, Alternate Member Executive Resources Board Rachel D. Campbell, Chairman Lucille Marvin, Member Joseph H. Dettmar, Alternate Member These changes to the PRB and ERB membership are due to the departure...

REGIONAL FIRST ORDER PERIODIC AUTOREGRESSIVE MODELS FOR MONTHLY FLOWS

Directory of Open Access Journals (Sweden)

Ceyhun ÖZÇELİK

2008-01-01

Full Text Available First order periodic autoregressive models is of mostly used models in modeling of time dependency of hydrological flow processes. In these models, periodicity of the correlogram is preserved as well as time dependency of processes. However, the parameters of these models, namely, inter-monthly lag-1 autocorrelation coefficients may be often estimated erroneously from short samples, since they are statistics of high order moments. Therefore, to constitute a regional model may be a solution that can produce more reliable and decisive estimates, and derive models and model parameters in any required point of the basin considered. In this study, definitions of homogeneous region for lag-1 autocorrelation coefficients are made; five parametric and non parametric models are proposed to set regional models of lag-1 autocorrelation coefficients. Regional models are applied on 30 stream flow gauging stations in Seyhan and Ceyhan basins, and tested by criteria of relative absolute bias, simple and relative root of mean square errors.

Generation of Natural Runoff Monthly Series at Ungauged Sites Using a Regional Regressive Model

Directory of Open Access Journals (Sweden)

Dario Pumo

2016-05-01

Full Text Available Many hydrologic applications require reliable estimates of runoff in river basins to face the widespread lack of data, both in time and in space. A regional method for the reconstruction of monthly runoff series is here developed and applied to Sicily (Italy. A simple modeling structure is adopted, consisting of a regression-based rainfall–runoff model with four model parameters, calibrated through a two-step procedure. Monthly runoff estimates are based on precipitation, temperature, and exploiting the autocorrelation with runoff at the previous month. Model parameters are assessed by specific regional equations as a function of easily measurable physical and climate basin descriptors. The first calibration step is aimed at the identification of a set of parameters optimizing model performances at the level of single basin. Such “optimal” sets are used at the second step, part of a regional regression analysis, to establish the regional equations for model parameters assessment as a function of basin attributes. All the gauged watersheds across the region have been analyzed, selecting 53 basins for model calibration and using the other six basins exclusively for validation. Performances, quantitatively evaluated by different statistical indexes, demonstrate relevant model ability in reproducing the observed hydrological time-series at both the monthly and coarser time resolutions. The methodology, which is easily transferable to other arid and semi-arid areas, provides a reliable tool for filling/reconstructing runoff time series at any gauged or ungauged basin of a region.

Development of phonological constancy: 19-month-olds, but not 15-month-olds, identify words in a non-native regional accent.

Science.gov (United States)

Mulak, Karen E; Best, Catherine T; Tyler, Michael D; Kitamura, Christine; Irwin, Julia R

2013-01-01

By 12 months, children grasp that a phonetic change to a word can change its identity (phonological distinctiveness). However, they must also grasp that some phonetic changes do not (phonological constancy). To test development of phonological constancy, sixteen 15-month-olds and sixteen 19-month-olds completed an eye-tracking task that tracked their gaze to named versus unnamed images for familiar words spoken in their native (Australian) and an unfamiliar non-native (Jamaican) regional accent of English. Both groups looked longer at named than unnamed images for Australian pronunciations, but only 19-month-olds did so for Jamaican pronunciations, indicating that phonological constancy emerges by 19 months. Vocabulary size predicted 15-month-olds' identifications for the Jamaican pronunciations, suggesting vocabulary growth is a viable predictor for phonological constancy development. © 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.

ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

Directory of Open Access Journals (Sweden)

Fumitaka Koga

Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with

Speech preference is associated with autistic-like behavior in 18-months-olds at risk for Autism Spectrum Disorder.

Science.gov (United States)

Curtin, Suzanne; Vouloumanos, Athena

2013-09-01

We examined whether infants' preference for speech at 12 months is associated with autistic-like behaviors at 18 months in infants who are at increased risk for autism spectrum disorder (ASD) because they have an older sibling diagnosed with ASD and in low-risk infants. Only low-risk infants listened significantly longer to speech than to nonspeech at 12 months. In both groups, relative preference for speech correlated positively with general cognitive ability at 12 months. However, in high-risk infants only, preference for speech was associated with autistic-like behavior at 18 months, while in low-risk infants, preference for speech correlated with language abilities. This suggests that in children at risk for ASD an atypical species-specific bias for speech may underlie atypical social development.

Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

Science.gov (United States)

Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

2018-04-01

Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen

The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

International Nuclear Information System (INIS)

Wang Xinming; Gao Xiang; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

2006-01-01

Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam

A peptide conjugate of vitamin E succinate targets breast cancer cells with high erbB2 expression

Czech Academy of Sciences Publication Activity Database

Wang, X. F.; Birringer, M.; Dong, L.F.; Vepřek, Pavel; Low, P.; Swettenham, E.; Stantic, M.; Yuan, L. H.; Zobalová, Renata; Wu, K.; Ledvina, Miroslav; Ralph, S.J.; Neužil, Jiří

2007-01-01

Roč. 67, č. 7 (2007), s. 3337-3344 ISSN 0008-5472 R&D Projects: GA MZe QF3115 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : vitamin e E * erbB2 * breast cancer Subject RIV: CC - Organic Chemistry Impact factor: 7.672, year: 2007

Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Chimeric Antigen Receptor

Science.gov (United States)

Schönfeld, Kurt; Sahm, Christiane; Zhang, Congcong; Naundorf, Sonja; Brendel, Christian; Odendahl, Marcus; Nowakowska, Paulina; Bönig, Halvard; Köhl, Ulrike; Kloess, Stephan; Köhler, Sylvia; Holtgreve-Grez, Heidi; Jauch, Anna; Schmidt, Manfred; Schubert, Ralf; Kühlcke, Klaus; Seifried, Erhard; Klingemann, Hans G; Rieger, Michael A; Tonn, Torsten; Grez, Manuel; Wels, Winfried S

2015-01-01

Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant procedures, we generated a stable clonal cell line expressing a humanized CAR based on ErbB2-specific antibody FRP5 harboring CD28 and CD3ζ signaling domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing tumor cells in vitro and exhibited serial target cell killing. Specific recognition of tumor cells and antitumor activity were retained in vivo, resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell carcinoma model, respectively. γ-irradiation as a potential safety measure for clinical application prevented NK cell replication, while antitumor activity was preserved. Our data demonstrate that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as a promising candidate for use in adoptive cancer immunotherapy. PMID:25373520

Florid Granuloma Annulare-Like Reaction in Regional Lymph Nodes After "Regression" of Red Pigment in Tattoos.

Science.gov (United States)

Carter, Michael D; Trites, Jonathan; McNeil, Shelly A; Walsh, Noreen N M; Bullock, Martin J

2018-05-01

A healthy 50-year-old woman had a tattoo performed on the posterior aspect of her neck and another on the dorsum of her left foot. Several weeks later, she noted redness, tenderness, and intense pruritis at both tattoo sites. Treatment with cephalexin and hydrocortisone cream was instituted, without success. Within a few months, the red, but not black, pigment had disappeared from both tattoos and was replaced by pale areas of scarring. Persistently enlarged left supraclavicular and suboccipital lymph nodes were excised 7 and 10 months after receipt of the tattoos, respectively. The nodes were pigmented on gross examination, and on microscopy, a granuloma annulare-like reaction was observed. Normal lymphoid tissue was seen to be replaced by large palisading granulomas with central degenerative change, abundant stromal mucin, and scattered deposits of tattoo pigment. Histochemical stains, tissue culture, and serological studies revealed no evidence of infection. There are rare reports of granuloma annulare-like reactions in tattoos, and these are believed to represent delayed-type hypersensitivity reactions. Our case is unique in the observation of this reaction pattern in regional lymph nodes, and it expands the spectrum of complications known to be associated with tattoos.

ErbB-targeted CAR T-cell immunotherapy of cancer.

Science.gov (United States)

Whilding, Lynsey M; Maher, John

2015-01-01

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

Antibody Responses to Marburg Virus in Egyptian Rousette Bats and Their Role in Protection against Infection.

Science.gov (United States)

Storm, Nadia; Jansen Van Vuren, Petrus; Markotter, Wanda; Paweska, Janusz T

2018-02-10

Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately 4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest that reinfection may only play a minor role in the transmission and maintenance of MARV amongst ERBs in nature.

On exclusive reactions in the time-like region

CERN Document Server

Kroll, P; Schürmann, M; Schweiger, W; Pilsner, Th.

1993-01-01

The electromagnetic form factors of the proton in the time-like region and two-photon annihilations into proton-antiproton are investigated. To calculate these processes at moderately large $s$ we use a variant of the Brodsky-Lepage hard-scattering formalism where diquarks are considered as quasi-elementary constituents of baryons. The proton wave function and the parameters controlling the diquark contributions are determined from fits to space-like data. We also comment on the decay $\\eta_c \\to p\\bar{p}$.

Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 ampersand erbB-2 expression

International Nuclear Information System (INIS)

Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

1994-01-01

One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman's risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185 erbB2 ) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer

The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

International Nuclear Information System (INIS)

Lee, Carol M; Tannock, Ian F

2010-01-01

Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity. Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with ERBB2 (231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2. The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly. Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors

Dim light at night prior to adolescence increases adult anxiety-like behaviors.

Science.gov (United States)

Cissé, Yasmine M; Peng, Juan; Nelson, Randy J

2016-01-01

Dim light at night (dLAN) disrupts circadian organization and influences adult behavior. We examined early dLAN exposure on adult affective responses. Beginning 3 (juvenile) or 5 weeks (adolescent) of age, mice were maintained in standard light-dark cycles or exposed to nightly dLAN (5 lx) for 5 weeks, then anxiety-like and fear responses were assessed. Hypothalami were collected around the clock to assess core clock genes. Exposure to dLAN at either age increased anxiety-like responses in adults. Clock and Rev-ERB expression were altered by exposure to dLAN. In contrast to adults, dLAN exposure during early life increases anxiety and fear behavior.

H II region-like galaxies

International Nuclear Information System (INIS)

French, H.B.

1979-01-01

Line fluxes in the region 3700 to 7100A are presented for 14 galaxies with strong, sharp, H II region-like emission lines. Ten of these galaxies are low luminosity objects (M > -17); the others have M approx. < -20. Ratios of the line fluxes are used to derive electron temperatures and densities, and the abundances of helium, oxygen, nitrogen, neon, and sulfur relative to hydrogen. The low luminosity galaxies are generally found to have oxygen abundances about 30% of normal, while the high luminosity ones generally have about 60% of normal. These galaxies are found to be almost certainly photoionized by hot main sequence stars. The velocity dispersion has been measured for one object; the mass of stars derived for it is several times smaller than the mass of neutral hydrogen which has previously been found in an extended halo around this object. The continuum colors of these galaxies are very blue, and are indistinguishable from those of extragalactic H II regions. No older red population has been convincingly detected. Galactic chemical evolution is investigated through a comparison of the relative abundances in these galaxies with their normal values. It is found that: (i) there is a primary contribution to the nitrogen abundance ((N/O)/sub p = 0.019), but that 80% of the nitrogen in the Galaxy today is of secondary origin; (ii) Ne/O appears to be constant for all objects (Ne/O = 0.23); and (iii) S/O decreases with increasing oxygen abundance, implying that most sulfur is produced in the most massive stars

p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

International Nuclear Information System (INIS)

Tierney, L.A.; Hahn, F.F.; Lechner, J.F.

1996-01-01

Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to 239 PuO 2 and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185 erbB2 ) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and 239 PuO 2 -induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs

Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

International Nuclear Information System (INIS)

Cicenas, Jonas; Urban, Patrick; Vuaroqueaux, Vincent; Labuhn, Martin; Küng, Willy; Wight, Edward; Mayhew, Mark; Eppenberger, Urs; Eppenberger-Castori, Serenella

2005-01-01

Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers. Using a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated (P-S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients. Akt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the significance of this correlation increased (P < 0.001) in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers (e.g. thymidylate synthase), measured using quantitative real-time RT-PCR. Our findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

Science.gov (United States)

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.

Science.gov (United States)

Tang, Xian-ye; Zheng, Wei; Ding, Min; Guo, Kai-jin; Yuan, Feng; Feng, Hu; Deng, Bin; Sun, Wei; Hou, Yang; Gao, Lu

2016-01-01

Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

Directory of Open Access Journals (Sweden)

Kevin A James

Full Text Available The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD motif in the catalytic loop and the Asp-Phe-Gly (DFG motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not

Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway

Czech Academy of Sciences Publication Activity Database

Wang, X.-F.; Witting, P. K.; Salvatore, B.A.; Neužil, Jiří

2005-01-01

Roč. 326, č. 4 (2005), s. 282-289 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E analogs * apoptosis * ErbB2 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

Daily disaggregation of simulated monthly flows using different rainfall datasets in southern Africa

Directory of Open Access Journals (Sweden)

D.A. Hughes

2015-09-01

New hydrological insights for the region: There are substantial regional differences in the success of the monthly hydrological model, which inevitably affects the success of the daily disaggregation results. There are also regional differences in the success of using global rainfall data sets (Climatic Research Unit (CRU datasets for monthly, National Oceanic and Atmospheric Administration African Rainfall Climatology, version 2 (ARC2 satellite data for daily. The overall conclusion is that the disaggregation method presents a parsimonious approach to generating daily flow simulations from existing monthly simulations and that these daily flows are likely to be useful for some purposes (e.g. water quality modelling, but less so for others (e.g. peak flow analysis.

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma

Science.gov (United States)

Bassullu, Nuray; Turkmen, Ilknur; Dayangac, Murat; Yagiz Korkmaz, Pinar; Yasar, Reyhan; Akyildiz, Murat; Yaprak, Onur; Tokat, Yaman; Yuzer, Yildiray; Bulbul Dogusoy, Gulen

2012-01-01

Background Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. Objectives The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. Patients and Methods Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. Results No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). Conclusions c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in

"Rund um die Monti Berici" - Von Villa zu Villa : ein Fahrradtourismuskonzept für die Region Veneto

OpenAIRE

Müller, Evelyn

2002-01-01

Das Konzeptgebiet, die venezianische Ebene in der Region Veneto, bietet ideale Bedingungen für die Entwicklung von Fahrrad- und Bildungstourismus. Es ist flach und landschaftlich reizvoll. Zudem besitzt die Region ein reiches kulturelles Erbe mit vielfältiger Tradition, vornehmlich die venezianische Villa. Die Villen liegen verstreut in der Landschaft auf der ehemaligen "Terraferma". Sie haben das Gesicht der Kulturlandschaft geprägt. Sie waren die Zentralen, von wo aus enorme Meliorationsarb...

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

Science.gov (United States)

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Prognostic value of Laurén classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction

NARCIS (Netherlands)

Polkowski, W.; van Sandick, J. W.; Offerhaus, G. J.; ten Kate, F. J.; Mulder, J.; Obertop, H.; van Lanschot, J. J.

1999-01-01

The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ). Forty-one

Seismic analysis of four solar-like stars observed during more than eight months by Kepler

DEFF Research Database (Denmark)

Mathur, S.; L. Campante, T.; Handberg, R.

2011-01-01

Having started science operations in May 2009, the Kepler photometer has been able to provide exquisite data of solar-like stars. Five out of the 42 stars observed continuously during the survey phase show evidence of oscillations, even though they are rather faint (magnitudes from 10.5 to 12). I......). In this paper, we present an overview of the results of the seismic analysis of 4 of these stars observed during more than eight months....

Seismic Analysis of Four Solar-like Stars Observed during More Than Eight Months by Kepler

Science.gov (United States)

Mathur, S.; Campante, T. L.; Handberg, R.; García, R. A.; Appourchaux, T.; Bedding, T. R.; Mosser, B.; Chaplin, W. J.; Ballot, J.; Benomar, O.; Bonanno, A.; Corsaro, E.; Gaulme, P.; Hekker, S.; Régulo, C.; Salabert, D.; Verner, G.; White, T. R.; Brandão, I. M.; Creevey, O. L.; Dogan, G.; Bazot, M.; Cunha, M. S.; Elsworth, Y.; Huber, D.; Hale, S. J.; Houdek, G.; Karoff, C.; Lundkvist, M.; Metcalfe, T. S.; Molenda-Zakowicz, J.; Monteiro, M. J. P. F. G.; Thompson, M. J.; Stello, D.; Christensen-Dalsgaard, J.; Gilliland, R. L.; Kawaler, S. D.; Kjeldsen, H.; Clarke, B. D.; Girouard, F. R.; Hall, J. R.; Quintana, E. V.; Sanderfer, D. T.; Seader, S. E.

2012-09-01

Having started science operations in May 2009, the Kepler photometer has been able to provide exquisite data for solar-like stars. Five out of the 42 stars observed continuously during the survey phase show evidence of oscillations, even though they are rather faint (magnitudes from 10.5 to 12). In this paper, we present an overview of the results of the seismic analysis of 4 of these stars observed during more than eight months.

A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

National Research Council Canada - National Science Library

Carraway, Kermit

1998-01-01

.... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

National Research Council Canada - National Science Library

Carraway, Kermit

1999-01-01

.... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

High spatial resolution radiation budget for Europe: derived from satellite data, validation of a regional model; Raeumlich hochaufgeloeste Strahlungsbilanz ueber Europa: Ableitung aus Satellitendaten, Validation eines regionalen Modells

Energy Technology Data Exchange (ETDEWEB)

Hollmann, R. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

2000-07-01

Since forty years instruments onboard satellites have been demonstrated their usefulness for many applications in the field of meteorology and oceanography. Several experiments, like ERBE, are dedicated to establish a climatology of the global Earth radiation budget at the top of the atmosphere. Now the focus has been changed to the regional scale, e.g. GEWEX with its regional sub-experiments like BALTEX. To obtain a regional radiation budget for Europe in the first part of the work the well calibrated measurements from ScaRaB (scanner for radiation budget) are used to derive a narrow-to-broadband conversion, which is applicable to the AVHRR (advanced very high resolution radiometer). It is shown, that the accuracy of the method is in the order of that from SCaRaB itself. In the second part of the work, results of REMO have been compared with measurements of ScaRaB and AVHRR for March 1994. The model reproduces the measurements overall well, but it is overestimating the cold areas and underestimating the warm areas in the longwave spectral domain. Similarly it is overestimating the dark areas and underestimating the bright areas in the solar spectral domain. (orig.)

Activation of MAPK overrides the termination of myelin growth and replaces Nrg1/ErbB3 signals during Schwann cell development and myelination

NARCIS (Netherlands)

M.E. Sheean (Maria); E. McShane (Erik); C. Cheret (Cyril); J. Walcher (Jan); T. Müller (Thomas); A. Wulf-Goldenberg (Annika); S. Hoelper (Soraya); A.N. Garratt (Alistair); M. Krüger (Markus); K. Rajewsky (Klaus); D.N. Meijer (Dies); W. Birchmeier (Walter); G.R. Lewin (Gary); M. Selbach (Matthias); C. Birchmeier (Carmen)

2014-01-01

textabstractMyelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin

Reckoning Informal Politics: Expands the Logic of Survival and Failure of Regional Heads

OpenAIRE

Wawan Sobari

2018-01-01

The qualitative research addresses the political logic of why and how the incumbents succeed and fail in direct election for regional heads (pilkada) in emerging democratic Indonesia. De Mesquita et al. (2003) believe that, to survive in office, a leader needs to offer a benefit at least equal to the greatest possible benefit offered by a potential challenger. Particular to the pilkada cases in Indonesia, Erb and Sulistiyanto (2009) elaborate several factors connected to “reward and punishmen...

A SITELLE view of M31's central region - I. Calibrations and radial velocity catalogue of nearly 800 emission-line point-like sources

Science.gov (United States)

Martin, Thomas B.; Drissen, Laurent; Melchior, Anne-Laure

2018-01-01

We present a detailed description of the wavelength, astrometric and photometric calibration plan for SITELLE, the imaging Fourier transform spectrometer attached to the Canada-France-Hawaii telescope, based on observations of a red (647-685 nm) data cube of the central region (11 arcmin × 11 arcmin) of M 31. The first application, presented in this paper is a radial-velocity catalogue (with uncertainties of ∼2-6 km s-1) of nearly 800 emission-line point-like sources, including ∼450 new discoveries. Most of the sources are likely planetary nebulae, although we also detect five novae (having erupted in the first eight months of 2016) and one new supernova remnant candidate.

Exogenous HGF Bypasses the Effects of ErbB Inhibition on Tumor Cell Viability in Medulloblastoma Cell Lines.

Directory of Open Access Journals (Sweden)

Walderik W Zomerman

Full Text Available Recent clinical trials investigating receptor tyrosine kinase (RTK inhibitors showed a limited clinical response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed in the brain, such as HGF and EGF, in relation to the effects of hepatocyte growth factor receptor (MET and epidermal growth factor receptor family (ErbB1-4 inhibition in medulloblastoma cell lines. Medulloblastoma cell lines were treated with tyrosine kinase inhibitors crizotinib or canertinib, targeting MET and ErbB1-4, respectively. Upon treatment, cells were stimulated with VEGF-A, PDGF-AB, HGF, FGF-2 or EGF. Subsequently, we measured cell viability and expression levels of growth factors and downstream signaling proteins. Addition of HGF or EGF phosphorylated MET or EGFR, respectively, and demonstrated phosphorylation of Akt and ERK1/2 as well as increased tumor cell viability. Crizotinib and canertinib both inhibited cell viability and phosphorylation of Akt and ERK1/2. Specifically targeting MET using shRNA's resulted in decreased cell viability. Interestingly, addition of HGF to canertinib significantly enhanced cell viability as well as phosphorylation of Akt and ERK1/2. The HGF-induced bypass of canertinib was reversed by addition of crizotinib. HGF protein was hardly released by medulloblastoma cells itself. Addition of canertinib did not affect RTK cell surface or growth factor expression levels. This manuscript points to the bypassing capacity of exogenous HGF in medulloblastoma cell lines. It might be of great interest to anticipate on these results in developing novel clinical trials with a combination of MET and EGFR inhibitors in medulloblastoma.

Use of the Charge/Discharge (C/D) ratio to aument voltage limit (V sub T) charge control in the ERBS spacecraft

Science.gov (United States)

Halpert, G.

1982-01-01

A 50-ampere hour nickel cadmium cell test pack was operated in a power profile simulating the orbit of the Earth Radiation Budget Satellite (ERBS). The objective was to determine the ability of the temperature compensated voltage limit (V sub T) charge control system to maintain energy balance in the half sine wave-type current profile expected of this mission. The four-cell pack (50 E) was tested at the Naval Weapons Support Center (NWSC) at Crane, Indiana. The ERBS evaluation test consisted of two distinct operating sequences, each having a specific purpose. The first phase was a parametric test involving the effect of V sub T level, temperature, and Beta angle on the charge/discharge (C/D) ratio, an indicator of the amount of overcharge. The second phase of testing made use of the C/D ratio limit to augment the V sub T charge limit control. When the C/D limit was reached, the current was switched from the taper mode to a C/67 (0.75 A) trickle charge. The use of an ampere hour integrator limiting the overcharge to a C/67 rate provided a fine tuning of the charge control technique which eliminated the sensitivity problems noted in the initial operating sequence.

Statistical downscaling of historical monthly mean winds over a coastal region of complex terrain. II. Predicting wind components

Energy Technology Data Exchange (ETDEWEB)

Kamp, Derek van der [University of Victoria, Pacific Climate Impacts Consortium, Victoria, BC (Canada); University of Victoria, School of Earth and Ocean Sciences, Victoria, BC (Canada); Curry, Charles L. [Environment Canada University of Victoria, Canadian Centre for Climate Modelling and Analysis, Victoria, BC (Canada); University of Victoria, School of Earth and Ocean Sciences, Victoria, BC (Canada); Monahan, Adam H. [University of Victoria, School of Earth and Ocean Sciences, Victoria, BC (Canada)

2012-04-15

A regression-based downscaling technique was applied to monthly mean surface wind observations from stations throughout western Canada as well as from buoys in the Northeast Pacific Ocean over the period 1979-2006. A predictor set was developed from principal component analysis of the three wind components at 500 hPa and mean sea-level pressure taken from the NCEP Reanalysis II. Building on the results of a companion paper, Curry et al. (Clim Dyn 2011), the downscaling was applied to both wind speed and wind components, in an effort to evaluate the utility of each type of predictand. Cross-validated prediction skill varied strongly with season, with autumn and summer displaying the highest and lowest skill, respectively. In most cases wind components were predicted with better skill than wind speeds. The predictive ability of wind components was found to be strongly related to their orientation. Wind components with the best predictions were often oriented along topographically significant features such as constricted valleys, mountain ranges or ocean channels. This influence of directionality on predictive ability is most prominent during autumn and winter at inland sites with complex topography. Stations in regions with relatively flat terrain (where topographic steering is minimal) exhibit inter-station consistencies including region-wide seasonal shifts in the direction of the best predicted wind component. The conclusion that wind components can be skillfully predicted only over a limited range of directions at most stations limits the scope of statistically downscaled wind speed predictions. It seems likely that such limitations apply to other regions of complex terrain as well. (orig.)

Valuing Heritage in Macau: On Contexts and Processes of Urban Conservation Kulturelles Erbe in Macau: Zu Rahmenbedingungen und Prozessen städtischer Denkmalpflege

Directory of Open Access Journals (Sweden)

Thomas Chung

2009-04-01

Full Text Available This paper examines the evolving values of urban heritage in Macau in terms of the various conservation approaches and mechanisms employed, and the shifting emphases on heritage and development within the context of continuity and change in Macau. Accumulated over four centuries of cultural interchange, the richly layered Historic Centre of the former Portuguese-administered outpost attained World Heritage status in 2005. After situating the problem pertaining to the multifaceted nature of heritage valorisation, the city’s trajectory of urban conservation leading up to the 1999 retrocession will be traced, and germane issues concerning heritage management vis-à-vis effects of post-handover urban developments assessed. As the latest culmination of value imbalances and conflicts arising from urban change, the Guia Lighthouse controversy will be critically appraised to speculate on a timely re-evaluation of Macau’s heritage conservation process. Der vorliegende Beitrag untersucht die sich wandelnde Haltung in Macau zum eigenen kulturellen Erbe, und zwar mit Blick auf die verschiedenen Konservierungsansätze und die dazu angewandten Methoden sowie auf die unterschiedliche Bedeutung von Kulturellem Erbe und Entwicklung im Kontext von Kontinutät und Wandel in der Stadt.

Month-to-month variability of Indian summer monsoon rainfall in 2016: role of the Indo-Pacific climatic conditions

Science.gov (United States)

Chowdary, Jasti S.; Srinivas, G.; Du, Yan; Gopinath, K.; Gnanaseelan, C.; Parekh, Anant; Singh, Prem

2018-03-01

Indian summer monsoon (ISM) rainfall during 2016 exhibited a prominent month-to-month fluctuations over India, with below normal rainfall in June and August and above normal rainfall in July. The factors determining the month-to-month fluctuations in ISM rainfall during 2016 are investigated with main focus on the Indo-Pacific climatic anomalies. Warm sea surface temperature (SST) anomalies associated with super El Niño 2015 disappeared by early summer 2016 over the central and eastern Pacific. On the other hand, negative Indian Ocean dipole (IOD) like SST anomaly pattern over the equatorial Indian Ocean and anomalous anticyclonic circulation over the western North Pacific (WNP) are reported in summer 2016 concurrently with decaying El Niño/developing La Niña phase. Observations revealed that the low rainfall over central north India in June is due to moisture divergence caused by the westward extension of ridge corresponding to WNP anticyclone and subsidence induced by local Hadley cell partly related to negative IOD. Low level convergence of southeasterly wind from Bay of Bengal associated with weak WNP anticyclone and northwesterly wind corresponding to anticyclonic circulation over the northwest India remarkably contributed to positive rainfall in July over most of the Indian subcontinent. While reduced rainfall over the Indian subcontinent in August 2016 is associated with the anomalous moisture transport from ISM region to WNP region, in contrast to July, due to local cyclogenesis corroborated by number of tropical cyclones in the WNP. In addition to this, subsidence related to strong convection supported by cyclonic circulation over the WNP also resulted in low rainfall over the ISM region. Coupled General Circulation model sensitivity experiments confirmed that strong convective activities associated with cyclonic circulation over the WNP is primarily responsible for the observed negative ISM rainfall anomalies in August 2016. It is noted that the Indo

Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening.

Science.gov (United States)

Giordano, Assunta; Forte, Giovanni; Massimo, Luigia; Riccio, Raffaele; Bifulco, Giuseppe; Di Micco, Simone

2018-04-12

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC 50 on MCF7 cell lines, thus validating IVS in lead repurposing. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Exploring the Links in Monthly to Decadal Variability of the Atmospheric Water Balance Over the Wettest Regions in ERA-20C

Science.gov (United States)

Nogueira, M.

2017-10-01

Monthly-to-decadal variability of the regional precipitation over Intertropical Convergence Zone and north-Atlantic and north-Pacific storm tracks was investigated using ERA-20C reanalysis. Satellite-based precipitation (P) and evaporation (E) climatological patterns were well reproduced by ERA-20C. Regional P and E monthly time series displayed 20% differences, but these decreased rapidly with time scale ( 10% at yearly time scales). Spectral analysis showed good scale-by-scale statistical agreement between ERA-20C and observations. Using ERA-Interim showed no improvement despite the much wider range of information assimilated (including satellites). Remarkably high Detrended Cross-Correlation Analysis coefficients (ρDCCA > 0.7 and often ρDCCA > 0.9) revealed tight links between the nonperiodic variability of P, moisture divergence (DIV), and pressure velocity (ω) at monthly-to-decadal time scales over all the wet regions. In contrast, ρDCCA was essentially nonsignificant between nonperiodic P and E or sea surface temperature (SST). Thus, the nonperiodic monthly-to-decadal variability of precipitation in these regions is almost fully controlled by dynamics and not by local E or SST (suggested by Clausius-Clapeyron relation). Analysis of regional nonperiodic standard deviations and power spectra (and respective spectral exponents, β) provided further robustness to this conclusion. Finally, clear transitions in β for P, DIV, and ω between tropical and storm track regions were found. The latter is dominated by transient storms, with energy accumulation at synoptic scales and β β values (0.2 to 0.4) were found in the tropics, implying longer-range autocorrelations and slower decreasing variability and information creation with time scale, consistent with the important forcing from internal modes of variability (e.g., El Niño-Southern Oscillation).

Model-based global sensitivity analysis as applied to identification of anti-cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network

Science.gov (United States)

Lebedeva, Galina; Sorokin, Anatoly; Faratian, Dana; Mullen, Peter; Goltsov, Alexey; Langdon, Simon P.; Harrison, David J.; Goryanin, Igor

2012-01-01

High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer-related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

Science.gov (United States)

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

The pion-nucleon form factor in space- and time-like regions

International Nuclear Information System (INIS)

Speth, J.; Tegen, R.

1990-01-01

We investigate the pion-nucleon vertex function in space- and time-like regions; these vertex functions appear as internal vertices in nucleon-antinucleon annihilations into n pions (n=2, 3, ..., 6). It is emphasised that only relativistic quark models can account for these vertices where one of the baryons/antibaryons is far off-shell with total energy close to zero. Using a novel 4-momentum projection technique we obtain results which generalize the usual (Breit frame) calculation of G πNN (k 2 ) (space-like) thereby removing completely the discrepancy in the Goldberger-Treiman relation. Our relativistic quark model calculation also explains the empirical suppression of antibaryonic contributions to the vertex functions Gsub(πNanti B) and Gsub(πBanti N) which enter in processes like Nanti N→ππ. (orig.)

Selection for Unequal Densities of Sigma70 Promoter-like Signalsin Different Regions of Large Bacterial Genomes

Energy Technology Data Exchange (ETDEWEB)

Huerta, Araceli M.; Francino, M. Pilar; Morett, Enrique; Collado-Vides, Julio

2006-03-01

The evolutionary processes operating in the DNA regions that participate in the regulation of gene expression are poorly understood. In Escherichia coli, we have established a sequence pattern that distinguishes regulatory from nonregulatory regions. The density of promoter-like sequences, that are recognizable by RNA polymerase and may function as potential promoters, is high within regulatory regions, in contrast to coding regions and regions located between convergently-transcribed genes. Moreover, functional promoter sites identified experimentally are often found in the subregions of highest density of promoter-like signals, even when individual sites with higher binding affinity for RNA polymerase exist elsewhere within the regulatory region. In order to investigate the generality of this pattern, we have used position weight matrices describing the -35 and -10 promoter boxes of E. coli to search for these motifs in 43 additional genomes belonging to most established bacterial phyla, after specific calibration of the matrices according to the base composition of the noncoding regions of each genome. We have found that all bacterial species analyzed contain similar promoter-like motifs, and that, in most cases, these motifs follow the same genomic distribution observed in E. coli. Differential densities between regulatory and nonregulatory regions are detectable in most bacterial genomes, with the exception of those that have experienced evolutionary extreme genome reduction. Thus, the phylogenetic distribution of this pattern mirrors that of genes and other genomic features that require weak selection to be effective in order to persist. On this basis, we suggest that the loss of differential densities in the reduced genomes of host-restricted pathogens and symbionts is the outcome of a process of genome degradation resulting from the decreased efficiency of purifying selection in highly structured small populations. This implies that the differential

Trends and homogeneity of monthly, seasonal, and annual rainfall over arid region of Rajasthan, India

Science.gov (United States)

Meena, Hari Mohan; Machiwal, Deepesh; Santra, Priyabrata; Moharana, Pratap Chandra; Singh, D. V.

2018-05-01

Knowledge of rainfall variability is important for regional-scale planning and management of water resources in agriculture. This study explores spatio-temporal variations, trends, and homogeneity in monthly, seasonal, and annual rainfall series of 62 stations located in arid region of Rajasthan, India using 55 year (1957-2011) data. Box-whisker plots indicate presence of outliers and extremes in annual rainfall, which made the distribution of annual rainfall right-skewed. Mean and coefficient of variation (CV) of rainfall reveals a high inter-annual variability (CV > 200%) in the western portion where the mean annual rainfall is very low. A general gradient of the mean monthly, seasonal, and annual rainfall is visible from northwest to southeast direction, which is orthogonal to the gradient of CV. The Sen's innovative trend test is found over-sensitive in evaluating statistical significance of the rainfall trends, while the Mann-Kendall test identifies significantly increasing rainfall trends in June and September. Rainfall in July shows prominently decreasing trends although none of them are found statistically significant. Monsoon and annual rainfall show significantly increasing trends at only four stations. The magnitude of trends indicates that the rainfall is increasing at a mean rate of 1.11, 2.85, and 2.89 mm year-1 in August, monsoon season, and annual series. The rainfall is found homogeneous over most of the area except for few stations situated in the eastern and northwest portions where significantly increasing trends are observed. Findings of this study indicate that there are few increasing trends in rainfall of this Indian arid region.

Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. [Rezension

OpenAIRE

Mayr, Thomas

2014-01-01

Rezension von Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. 29,90 EUR, ISBN 978-3763936656

OUTFLOWS AND DARK BANDS AT ARCADE-LIKE ACTIVE REGION CORE BOUNDARIES

Energy Technology Data Exchange (ETDEWEB)

Scott, J. T.; Martens, P. C. H.; Tarr, L. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States)

2013-03-10

Observations from the EUV Imaging Spectrometer (EIS) on board Hinode have revealed outflows and non-thermal line broadening in low intensity regions at the edges of active regions (ARs). We use data from Hinode's EIS, Solar Dynamic Observatory's Atmospheric Imaging Assembly and Helioseismic and Magnetic Imager, and the Transition Region and Coronal Explorer instrument to investigate the boundaries of arcade-like AR cores for NOAA ARs 11112, 10978, and 9077. A narrow, low intensity region that is observed at the core's periphery as a dark band shows outflows and increased spectral line broadening. This dark band is found to exist for days and appears between the bright coronal loop structures of different coronal topologies. We find a case where the dark band region is formed between the magnetic field from emerging flux and the field of the pre-existing flux. A magnetic field extrapolation indicates that this dark band is coincident with the spine lines or magnetic separatrices in the extrapolated field. This occurs over unipolar regions where the brightened coronal field is separated in connectivity and topology. This separation does not appear to be infinitesimal and an initial estimate of the minimum distance of separation is found to be Almost-Equal-To 1.5-3.5 Mm.

Prediction of monthly rainfall on homogeneous monsoon regions of India based on large scale circulation patterns using Genetic Programming

Science.gov (United States)

Kashid, Satishkumar S.; Maity, Rajib

2012-08-01

SummaryPrediction of Indian Summer Monsoon Rainfall (ISMR) is of vital importance for Indian economy, and it has been remained a great challenge for hydro-meteorologists due to inherent complexities in the climatic systems. The Large-scale atmospheric circulation patterns from tropical Pacific Ocean (ENSO) and those from tropical Indian Ocean (EQUINOO) are established to influence the Indian Summer Monsoon Rainfall. The information of these two large scale atmospheric circulation patterns in terms of their indices is used to model the complex relationship between Indian Summer Monsoon Rainfall and the ENSO as well as EQUINOO indices. However, extracting the signal from such large-scale indices for modeling such complex systems is significantly difficult. Rainfall predictions have been done for 'All India' as one unit, as well as for five 'homogeneous monsoon regions of India', defined by Indian Institute of Tropical Meteorology. Recent 'Artificial Intelligence' tool 'Genetic Programming' (GP) has been employed for modeling such problem. The Genetic Programming approach is found to capture the complex relationship between the monthly Indian Summer Monsoon Rainfall and large scale atmospheric circulation pattern indices - ENSO and EQUINOO. Research findings of this study indicate that GP-derived monthly rainfall forecasting models, that use large-scale atmospheric circulation information are successful in prediction of All India Summer Monsoon Rainfall with correlation coefficient as good as 0.866, which may appears attractive for such a complex system. A separate analysis is carried out for All India Summer Monsoon rainfall for India as one unit, and five homogeneous monsoon regions, based on ENSO and EQUINOO indices of months of March, April and May only, performed at end of month of May. In this case, All India Summer Monsoon Rainfall could be predicted with 0.70 as correlation coefficient with somewhat lesser Correlation Coefficient (C.C.) values for different

Expression of the clock gene Rev-erbα in the brain controls the circadian organisation of food intake and locomotor activity, but not daily variations of energy metabolism

NARCIS (Netherlands)

Sen, Satish; Dumont, Stéphanie; Sage-Ciocca, Dominique; Reibel, Sophie; de Goede, Paul; Kalsbeek, Andries; Challet, Etienne

2018-01-01

The nuclear receptor REV-ERBα is part of the molecular clock mechanism and is considered to be involved in a variety of biological processes within metabolically active peripheral tissues as well. To investigate whether Rev-erbα (also known as Nr1d1) in the brain plays a role in the daily variations

Areva. Nine-month 2007 sales revenue and data

International Nuclear Information System (INIS)

2007-10-01

The main information concerning the nine-month 2007 financial data of the Areva group is a steady growth of 9-month sales revenue, at euro 8.066 billion (+6.8% like-for-like), including euro 2.692 billion in the 3. quarter, i.e. +7.6% like-for-like. The group confirms its strong sales revenue growth objective for 2007

Monthly hydroclimatology of the continental United States

Science.gov (United States)

Petersen, Thomas; Devineni, Naresh; Sankarasubramanian, A.

2018-04-01

Physical/semi-empirical models that do not require any calibration are of paramount need for estimating hydrological fluxes for ungauged sites. We develop semi-empirical models for estimating the mean and variance of the monthly streamflow based on Taylor Series approximation of a lumped physically based water balance model. The proposed models require mean and variance of monthly precipitation and potential evapotranspiration, co-variability of precipitation and potential evapotranspiration and regionally calibrated catchment retention sensitivity, atmospheric moisture uptake sensitivity, groundwater-partitioning factor, and the maximum soil moisture holding capacity parameters. Estimates of mean and variance of monthly streamflow using the semi-empirical equations are compared with the observed estimates for 1373 catchments in the continental United States. Analyses show that the proposed models explain the spatial variability in monthly moments for basins in lower elevations. A regionalization of parameters for each water resources region show good agreement between observed moments and model estimated moments during January, February, March and April for mean and all months except May and June for variance. Thus, the proposed relationships could be employed for understanding and estimating the monthly hydroclimatology of ungauged basins using regional parameters.

y ERB-2 asociados al pronóstico del cáncer de mama en la población de Barranquilla (2004- 2005

Directory of Open Access Journals (Sweden)

Luz Alba Silvera Arenas

2007-01-01

Full Text Available Objetivo: Estudiar los patrones de expresión de los receptores de estrógenos, progestagenos y erb-2 en 85 pacientes atendidas en dos laboratorios de patología de Barranquilla. De Julio del 2004 a diciembre del 2005. Material y metodos: Estudio Descriptivo de corte. Se utilizaron 85 muestras incluidas en parafina de pacientes con diagnóstico de cáncer de mama para lo cual, se realizaron estudios inmunohistoquimicos con técnicas de peroxidasa – antiperoxidasa, se utilizaron anticuerpos monoclonales Dako contra estrógenos, progestágenos y ebr-2. Resultados: Se observó carcinoma in situ (4, cáncer mesenquimal (1, carcinoma lobulillar (1 y resto carcinomas ductales infiltrantes grados I, II y III. La inmunohistoquímica mostró positividad para estrógeno y progestágeno a nivel intracelular en 73 casos y negativos para erb-2, 11 fueron negativos para estrógeno y progestágeno, uno fue positivo para ebr-2. Conclusiones: 1. El carcinoma ductal infiltrante grado II y III fue la forma histológica que se presentó con mayor frecuencia (80 casos. 2. El 88,23 % de los casos fueron estrógeno y progestágeno positivos. 3. La relación entre el componente histológico y receptores hormonales positivos, sugieren buen pronóstico.

Long-term global distribution of earth's shortwave radiation budget at the top of atmosphere

Directory of Open Access Journals (Sweden)

N. Hatzianastassiou

2004-01-01

Full Text Available The mean monthly shortwave (SW radiation budget at the top of atmosphere (TOA was computed on 2.5° longitude-latitude resolution for the 14-year period from 1984 to 1997, using a radiative transfer model with long-term climatological data from the International Satellite Cloud Climatology Project (ISCCP-D2 supplemented by data from the National Centers for Environmental Prediction – National Center for Atmospheric Research (NCEP-NCAR Global Reanalysis project, and other global data bases such as TIROS Operational Vertical Sounder (TOVS and Global Aerosol Data Set (GADS. The model radiative fluxes at TOA were validated against Earth Radiation Budget Experiment (ERBE S4 scanner satellite data (1985–1989. The model is able to predict the seasonal and geographical variation of SW TOA fluxes. On a mean annual and global basis, the model is in very good agreement with ERBE, overestimating the outgoing SW radiation at TOA (OSR by 0.93 Wm-2 (or by 0.92%, within the ERBE uncertainties. At pixel level, the OSR differences between model and ERBE are mostly within ±10 Wm-2, with ±5 Wm-2 over extended regions, while there exist some geographic areas with differences of up to 40 Wm-2, associated with uncertainties in cloud properties and surface albedo. The 14-year average model results give a planetary albedo equal to 29.6% and a TOA OSR flux of 101.2 Wm-2. A significant linearly decreasing trend in OSR and planetary albedo was found, equal to 2.3 Wm-2 and 0.6% (in absolute values, respectively, over the 14-year period (from January 1984 to December 1997, indicating an increasing solar planetary warming. This planetary SW radiative heating occurs in the tropical and sub-tropical areas (20° S–20° N, with clouds being the most likely cause. The computed global mean OSR anomaly ranges within ±4 Wm-2, with signals from El Niño and La Niña events or Pinatubo eruption, whereas significant negative OSR anomalies, starting from year 1992, are also

Oceanographic Monthly Summary

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Oceanographic Monthly Summary contains sea surface temperature (SST) analyses on both regional and ocean basin scales for the Atlantic, Pacific, and Indian Oceans....

Indicadores de Prognóstico em Câncer de Mama com Axila Negativa: Receptor de Estrógeno e Expressão de P53 e de c-erbB-2 Prognostic Indicators In Lymph Node-Negative Breast Cancer: Estrogen Receptor and P53 and c-erbB-2 Protein Expression

Directory of Open Access Journals (Sweden)

Adriana Harter Teixeira Bolaséll

2000-08-01

Full Text Available Objetivo: avaliar o valor prognóstico do receptor de estrógeno e da expressão das proteínas p53 e c-erbB-2 no câncer de mama com axila negativa. Métodos: foi realizado estudo imuno-histoquímico em material incluido em parafina, do arquivo do Instituto de Pesquisas Cito-Oncológicas (IPCO da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA, de 50 casos de câncer de mama sem comprometimento dos linfonodos axilares, em mulheres menopausadas, tratadas na Irmandade da Santa Casa de Porto Alegre (ISCMPA e no Hospital Santa Rita de Porto Alegre (HSR de janeiro 1990 a dezembro de 1994. Para análise estatística foram utilizados os testes de c² com correção de Yates, teste exato de Fisher e curvas de sobrevida pelo método de Kaplan-Meier comparados pelo teste log rank. O seguimento médio das pacientes foi de 3,6 anos (3,1-4,5. Dos 50 casos, 14 apresentaram recidiva no período observado. Resultados: a média de idade foi 61 anos (variação de 46 a 78 anos. A mastectomia radical modificada (MRM foi realizada em 35 pacientes (70% e 15 (30% foram submetidas a setorectomia com esvaziamento axilar e posterior radioterapia. Metade das pacientes que apresentaram recidiva apresentaram-na nos três primeiros anos após o diagnóstico. O tamanho médio do tumor foi 2,8 cm (1,98-3,13 e o tipo histológico mais freqüente foi o carcinoma ductal infiltrante de tipo histológico não-especial (92%, conforme a graduação histológica de Bloom e Richardson, sendo 3 grau I (6,6%, 35 grau II (76% e 8 grau III (17,4%; nos tumores que recidivaram não houve nenhum grau I, 9 (25,7% eram grau II e 3 (37,5% eram grau III. Em relação ao prognóstico, a taxa de intervalo livre de doença foi menor quando da associação de tumor pouco diferenciado (grau III com receptor de estrógeno negativo (p = 0,006, p53 positivo (p = 0,006 e c-erbB-2 positivo (p = 0,001. Conclusão: mulheres menopausadas com câncer de mama sem comprometimento

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

OpenAIRE

Maria Teresa de Seixas Alves; Luciana Nakao Odashiro Miiji; Larissa Cardoso Marinho; Antonio Sergio Petrilli; Reynaldo Jesus-Garcia; Silvia Caminada Tolledo; Francy Reis da Silva Patricio

2008-01-01

INTRODUÇÃO: Osteossarcoma (OS), o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp) e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológic...

InP based lasers and optical amplifiers with wire-/dot-like active regions

DEFF Research Database (Denmark)

Reithmaier, J. P.; Somers, A.; Deubert, S.

2005-01-01

Long wavelength lasers and semiconductor optical amplifiers based on InAs quantum wire/dot-like active regions were developed on InP substrates dedicated to cover the extended telecommunication wavelength range between 1.4 - 1.65 mm. In a brief overview different technological approaches will be ...

Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

Science.gov (United States)

Traynard, Pauline; Feillet, Céline; Soliman, Sylvain; Delaunay, Franck; Fages, François

2016-11-01

Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favoring the RevErb-α up-regulation hypothesis and on some further predictions of the model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Top-of-Atmosphere Direct Radiative Effect of Aerosols from the Clouds and the Earth's Radiant Energy System Satellite Instrument (CERES)

Science.gov (United States)

Loeb, N. G.; Kato, S.

2002-01-01

Nine months of CERES/TRMM broadband fluxes combined with VIRS high-resolution imager measurements are used to estimate the daily average direct radiative effect of aerosols for clear-sky conditions over the tropical oceans. On average, aerosols have a cooling effect over the tropics of 4.6 +/- 1 W/sq m. The magnitude is approx.2 W/sq m smaller over the southern tropical oceans than it is over northern tropical oceans. The direct effect derived from CERES is highly correlated with coincident aerosol optical depth retrievals inferred from 0.63 microns VIRS radiances (correlation coefficient of 0.96). The slope of the regression line is approx. -32 W/sq m/t over the equatorial Pacific Ocean, but changes both regionally and seasonally, depending on the aerosol characteristics. Near sources of biomass burning and desert dust, the aerosol direct effect reaches -25 W sq m to -30 W/sq m. The direct effect from CERES also shows a dependence on wind speed. The reason for this dependence is unclear-it may be due to increased aerosol (e.g. sea-salt or aerosol transport) or increased surface reflection (e.g. due to whitecaps). The uncertainty in the tropical average direct effect from CERES is approx. 1 W/sq m (approx. 20%) due mainly to cloud contamination, the radiance-to-flux conversion, and instrument calibration. By comparison, uncertainties in the direct effect from the ERBE and CERES "ERBE-Like" products are a factor of 3 to 5 larger.

Determinants of stillbirth among women deliveries at Amhara region, Ethiopia.

Science.gov (United States)

Lakew, Demeke; Tesfaye, Dereje; Mekonnen, Haile

2017-11-13

Stillbirth is one of general medical issues that could contribute significantly to creating nations like Ethiopia. This study aimed to determine the prevalence and related factors of stillbirth among deliveries at Amhara region, Ethiopia. The study used the Ethiopian Mini Demographic and Health Survey (EMDHS) data collected from 2555 eligible Amhara region women in 2014. Bi-variable and multi-variable binary logistic regression analysis was used. The prevalence of stillbirth outcomes became 85 per 1000 (total live birth). Besides, majority of women did not attend any formal education and had no antenatal care follow up. Women whose age at first birth below 18 years were 1859(72.8%) and the mean preceding birth interval were 33.6 months. Even women who attended primary and above education were about 50% and they were less likely to have had stillbirth outcomes than those who had no education (AOR: 0.505, 95% CI 0.311-0.820) and women having higher household wealth index were less likely to have had stillbirth outcomes as it is compared to the reference category. Moreover, women having preceding birth interval above 36 months were about 89% of less likely to end up stillbirth outcomes as compared to women having preceding birth interval below 24 months (AOR: 0.109, 95% CI 0.071-8.0.168). It could be inferred that a stillbirth result is one of the general medical issues in Amhara Region. Among different factors considered in this study, age, age at first birth, wealth index, birth order number and preceding birth interval in months were found to be significantly associated factors for stillbirth. Therefore, more awareness of early birth, widening birth interval, enhancing maternal care (for aged women) and early birth order number could be recommended.

Testing of Haar-Like Feature in Region of Interest Detection for Automated Target Recognition (ATR) System

Science.gov (United States)

Zhang, Yuhan; Lu, Dr. Thomas

2010-01-01

The objectives of this project were to develop a ROI (Region of Interest) detector using Haar-like feature similar to the face detection in Intel's OpenCV library, implement it in Matlab code, and test the performance of the new ROI detector against the existing ROI detector that uses Optimal Trade-off Maximum Average Correlation Height filter (OTMACH). The ROI detector included 3 parts: 1, Automated Haar-like feature selection in finding a small set of the most relevant Haar-like features for detecting ROIs that contained a target. 2, Having the small set of Haar-like features from the last step, a neural network needed to be trained to recognize ROIs with targets by taking the Haar-like features as inputs. 3, using the trained neural network from the last step, a filtering method needed to be developed to process the neural network responses into a small set of regions of interests. This needed to be coded in Matlab. All the 3 parts needed to be coded in Matlab. The parameters in the detector needed to be trained by machine learning and tested with specific datasets. Since OpenCV library and Haar-like feature were not available in Matlab, the Haar-like feature calculation needed to be implemented in Matlab. The codes for Adaptive Boosting and max/min filters in Matlab could to be found from the Internet but needed to be integrated to serve the purpose of this project. The performance of the new detector was tested by comparing the accuracy and the speed of the new detector against the existing OTMACH detector. The speed was referred as the average speed to find the regions of interests in an image. The accuracy was measured by the number of false positives (false alarms) at the same detection rate between the two detectors.

Development of a methodology for monthly forecasting of surface fires of Colombia's vegetation cover, an application to north Andean region

International Nuclear Information System (INIS)

Gonzalez Hernandez, Yolanda; Rangel CH, Jesus Orlando

2004-01-01

In the present article a methodology is presented for the forecasting of the monthly risk of surface fires of the vegetation cover in Colombia, based on the analysis of meteorological components and variables of climatic and anthropic variability involved in fire risks of the north Andean region. The methodology enables one to regionalize the country, with fire prediction purposes in mind, into ten sub-regions, in each one of which seven height levels are defined to make up separate regions of study. For each of these, a database is built to feed both the logistic regression models and the Poisson models, which identify the variables independent from, and/or associated with the presence or absence of fires

AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Hua Xie

Full Text Available Despite the initial response to the reversible, ATP-competitive quinazoline inhibitors that target ErbB-family, such a subset of cancer patients almost invariably develop resistance. Recent studies have provided compelling evidence that irreversible ErbB inhibitors have the potential to override this resistance. Here, we found that AST1306, a novel anilino-quinazoline compound, inhibited the enzymatic activities of wild-type epidermal growth factor receptor (EGFR and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. Importantly, AST1306 functions as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. Further studies showed that AST1306 inactivated pathways downstream of these receptors and thereby inhibited the proliferation of a panel of cancer cell lines. Although the activities of EGFR and ErbB2 were similarly sensitive to AST1306, ErbB2-overexpressing cell lines consistently exhibited more sensitivity to AST1306 antiproliferative effects. Consistent with this, knockdown of ErbB2, but not EGFR, decreased the sensitivity of SK-OV-3 cells to AST1306. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts. Tumor growth inhibition induced by a single dose of AST1306 in the SK-OV-3 xenograft model was accompanied by a rapid (within 2 h and sustained (≥24 h inhibition of both EGFR and ErbB2, consistent with an irreversible inhibition mechanism. Taken together, these results establish AST1306 as a selective, irreversible ErbB2 and EGFR inhibitor whose growth-inhibitory effects are more potent in ErbB2-overexpressing cells.

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Directory of Open Access Journals (Sweden)

Stephanie E Westcot

Full Text Available Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP, an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish. In vivo selection for skin-specific expression of gene-break transposon (GBT mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a revealed a novel requirement for a Neuregulin 2a (Nrg2a-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Science.gov (United States)

Westcot, Stephanie E; Hatzold, Julia; Urban, Mark D; Richetti, Stefânia K; Skuster, Kimberly J; Harm, Rhianna M; Lopez Cervera, Roberto; Umemoto, Noriko; McNulty, Melissa S; Clark, Karl J; Hammerschmidt, Matthias; Ekker, Stephen C

2015-01-01

Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape

Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression.

Science.gov (United States)

Moshe, Hagar; Gal, Ram; Barnea-Ygael, Noam; Gulevsky, Tatiana; Alyagon, Uri; Zangen, Abraham

2016-01-01

Approximately one third of all major depression patients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this Depressive Rat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors. To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats. SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in human patients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements. SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions. Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuity of Earth Radiation Budget Observations

Science.gov (United States)

Loeb, N. G.; Su, W.; Wong, T.; Priestley, K.

2017-12-01

successive satellite missions flying ERB instruments must overlap with one another for at least one year. We also discuss the tremendous challenges associated with alternate observing systems to CERES-like scanner instruments proposed recently to extend the ERB record (e.g., nonscanner broadband instruments on small satellites).

Statistical downscaling of historical monthly mean winds over a coastal region of complex terrain. I. Predicting wind speed

Energy Technology Data Exchange (ETDEWEB)

Curry, Charles L. [Canadian Centre for Climate Modelling and Analysis, Environment Canada, University of Victoria, Victoria, BC (Canada); School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada); Kamp, Derek van der [School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada); Pacific Climate Impacts Consortium, University of Victoria, Victoria, BC (Canada); Monahan, Adam H. [School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada)

2012-04-15

Surface wind speed is a key climatic variable of interest in many applications, including assessments of storm-related infrastructure damage and feasibility studies of wind power generation. In this work and a companion paper (van der Kamp et al. 2011), the relationship between local surface wind and large-scale climate variables was studied using multiple regression analysis. The analysis was performed using monthly mean station data from British Columbia, Canada and large-scale climate variables (predictors) from the NCEP-2 reanalysis over the period 1979-2006. Two regression-based methodologies were compared. The first relates the annual cycle of station wind speed to that of the large-scale predictors at the closest grid box to the station. It is shown that the relatively high correlation coefficients obtained with this method are attributable to the dominant influence of region-wide seasonality, and thus contain minimal information about local wind behaviour at the stations. The second method uses interannually varying data for individual months, aggregated into seasons, and is demonstrated to contain intrinsically local information about the surface winds. The dependence of local wind speed upon large-scale predictors over a much larger region surrounding the station was also explored, resulting in 2D maps of spatial correlations. The cross-validated explained variance using the interannual method was highest in autumn and winter, ranging from 30 to 70% at about a dozen stations in the region. Reasons for the limited predictive skill of the regressions and directions for future progress are reviewed. (orig.)

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

Science.gov (United States)

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Regional and monthly and clear-sky aerosol direct radiative effect (and forcing derived from the GlobAEROSOL-AATSR satellite aerosol product

Directory of Open Access Journals (Sweden)

G. E. Thomas

2013-01-01

Full Text Available Using the GlobAEROSOL-AATSR dataset, estimates of the instantaneous, clear-sky, direct aerosol radiative effect and radiative forcing have been produced for the year 2006. Aerosol Robotic Network sun-photometer measurements have been used to characterise the random and systematic error in the GlobAEROSOL product for 22 regions covering the globe. Representative aerosol properties for each region were derived from the results of a wide range of literature sources and, along with the de-biased GlobAEROSOL AODs, were used to drive an offline version of the Met Office unified model radiation scheme. In addition to the mean AOD, best-estimate run of the radiation scheme, a range of additional calculations were done to propagate uncertainty estimates in the AOD, optical properties, surface albedo and errors due to the temporal and spatial averaging of the AOD fields. This analysis produced monthly, regional estimates of the clear-sky aerosol radiative effect and its uncertainty, which were combined to produce annual, global mean values of (−6.7 ± 3.9 W m⁻² at the top of atmosphere (TOA and (−12 ± 6 W m⁻² at the surface. These results were then used to give estimates of regional, clear-sky aerosol direct radiative forcing, using modelled pre-industrial AOD fields for the year 1750 calculated for the AEROCOM PRE experiment. However, as it was not possible to quantify the uncertainty in the pre-industrial aerosol loading, these figures can only be taken as indicative and their uncertainties as lower bounds on the likely errors. Although the uncertainty on aerosol radiative effect presented here is considerably larger than most previous estimates, the explicit inclusion of the major sources of error in the calculations suggest that they are closer to the true constraint on this figure from similar methodologies, and point to the need for more, improved estimates of both global aerosol loading and aerosol optical properties.

The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

Science.gov (United States)

Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

2007-01-01

Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

Câncer de boca: expressão imuno-histoquímica de c-erbB-2, Bcl-2 e EGFR - estudo comparativo com leucoplasia e hiperplasia inflamatória = Oral cancer: immunohistochemical expression of c-erbB-2, Bcl-2 and EGFR – study with leukoplakia and inflammatory hyperplasia

Directory of Open Access Journals (Sweden)

Barros, Rosana M. G.

2005-01-01

Full Text Available Anormalidades em genes que regulam a proliferação e morte celular podem provocar inúmeras doenças entre elas o carcinoma epidermóide de boca. Tem sido relatado que alterações genéticas nas células tumorais predizem a agressividade biológica dos tumores. Marcadores genéticos como c-erbB-2, Bcl-2 e EGFR são considerados indicadores promissores de prognósticos para as lesões cancerizáveis e as neoplasias. Objetivo: Avaliar a expressão imunohistoquímica das proteínas c-erbB-2, Bcl-2 e EGFR (oncoproteínas envolvidas nas vias de proliferação celular Material e Métodos: cento e cinco blocos e parafina contendo fragmentos de biopsias incisionais, sendo 54 de carcinomas epidermóides, 25 blocos de leucoplasias e 26 blocos de hiperlasias obtidos do Laboratório de Patologia de Boca da Universidade Federal de Mato Grosso do Sul (UFSM. A expressão das proteínas foi verificada através da técnica imunohistoquímica utilizando a estreptoavidina-biotina-peroxidase no Laboratório de Patologia da Universidade de Brasília (UNB. Resultados: Os resultados revelaram diferença estatisticamente significante da proteína EGFR para os carcinomas epidermóides de boca e para as demais proteínas não houve diferença estatisticamente significante entre as lesões. Conclusões: Os resultados sugerem que o EGFR pode ser utilizado como marcador em carcinoma de boca podendo contribuir para a progressão da neoplasia, porém sendo insuficiente na predição da carcinogênese. Abnormalities in genes that regulate the proliferation and cell death can provoke many lesions as oral epidermal carcinoma. It has been related that genetic alterations in tumoral cells predict the biologic agressivity in the tumors. Genetic markers as cerbB-2, Bcl-2 and EGFR are considered indicators of prognostic to the pre-malignant lesions and neoplasias. Objective: to study in the fragments of incisional biopsy the expression of c-erbB-2, Bcl-2 and EGFR proteins

The effect of ambient air temperature and precipitation on monthly counts of salmonellosis in four regions of Kazakhstan, Central Asia, in 2000-2010.

Science.gov (United States)

Grjibovski, A M; Kosbayeva, A; Menne, B

2014-03-01

We studied associations between monthly counts of laboratory-confirmed cases of salmonellosis, ambient air temperature and precipitation in four settings in Kazakhstan. We observed a linear association between the number of cases of salmonellosis and mean monthly temperature during the same months only in Astana: an increase of 1°C was associated with a 5·5% [95% confidence interval (CI) 2·2-8·8] increase in the number of cases. A similar association, although not reaching the level of significance was observed in the Southern Kazakhstan region (3·5%, 95% CI -2·1 to 9·1). Positive association with precipitation with lag 2 was found in Astana: an increase of 1 mm was associated with a 0·5% (95% CI 0·1-1·0) increase in the number of cases. A similar association, but with lag 0 was observed in Southern Kazakhstan region (0·6%, 95% CI 0·1-1·1). The results may have implications for the future patterns of salmonellosis in Kazakhstan with regard to climate change.

LBA Regional Monthly Climatology for the 20th Century (New et al.)

Data.gov (United States)

National Aeronautics and Space Administration — ABSTRACT: This data set is a subset of "Global Monthly Climatology for the 20th Century (New et al.)" (2000a). This subset characterizes mean monthly surface climate...

LBA Regional Monthly Climatology for the 20th Century (New et al.)

Data.gov (United States)

National Aeronautics and Space Administration — This data set is a subset of "Global Monthly Climatology for the 20th Century (New et al.)" (2000a). This subset characterizes mean monthly surface climate over the...

Origins of the Xylella fastidiosa prophage-like regions and their impact in genome differentiation.

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Alessandro de Mello Varani

Full Text Available Xylella fastidiosa is a Gram negative plant pathogen causing many economically important diseases, and analyses of completely sequenced X. fastidiosa genome strains allowed the identification of many prophage-like elements and possibly phage remnants, accounting for up to 15% of the genome composition. To better evaluate the recent evolution of the X. fastidiosa chromosome backbone among distinct pathovars, the number and location of prophage-like regions on two finished genomes (9a5c and Temecula1, and in two candidate molecules (Ann1 and Dixon were assessed. Based on comparative best bidirectional hit analyses, the majority (51% of the predicted genes in the X. fastidiosa prophage-like regions are related to structural phage genes belonging to the Siphoviridae family. Electron micrograph reveals the existence of putative viral particles with similar morphology to lambda phages in the bacterial cell in planta. Moreover, analysis of microarray data indicates that 9a5c strain cultivated under stress conditions presents enhanced expression of phage anti-repressor genes, suggesting switches from lysogenic to lytic cycle of phages under stress-induced situations. Furthermore, virulence-associated proteins and toxins are found within these prophage-like elements, thus suggesting an important role in host adaptation. Finally, clustering analyses of phage integrase genes based on multiple alignment patterns reveal they group in five lineages, all possessing a tyrosine recombinase catalytic domain, and phylogenetically close to other integrases found in phages that are genetic mosaics and able to perform generalized and specialized transduction. Integration sites and tRNA association is also evidenced. In summary, we present comparative and experimental evidence supporting the association and contribution of phage activity on the differentiation of Xylella genomes.

A xeroradiographic study of the developing equine foredigit and metacarpophalangeal region from birth to six months of age

International Nuclear Information System (INIS)

Smallwood, J.E.; Albright, S.M.; Metcalf, M.R.; Thrall, D.E.; Harrington, B.D.

1989-01-01

The purpose of the project was to provide a reference for radiographic anatomy of the developing equine foredigit and metacarpophalangeal region. Using xeroradiographic techniques, both foredigits and meta-carpophalangeal regions of six Quarter Horse foals were radiographed at one day of age and at two-week intervals until the foals were six weeks old. The foals were then radiographed at four-week intervals until they were 12 months old. This report deals specifically with the first six months of postnatal development. Lateromedial and dorsopalmar xeroradiographs of each foredigit and metacarpophalangeal region and a dorsal 65° proximal-palmarodistal oblique view of the distal part of the digit were made for each examination. The foals were weighed and measured at the withers immediately prior to each examination. Representative xeroradiographs were selected and appropriately labeled to demonstrate normal radio-graphic anatomy of these regions. First radiographic appearance of distal epiphyseal ossification in metacarpal 2 and metacarpal 4 was extremely variable and ranged from four to 38 weeks. Radiographic closure of the proximal physis of the middle phalanx ranged from 18 to 30 weeks (mean = 26 weeks). Radiographic closure of the proximal physis of the proximal phalanx ranged from 22 to 38 weeks (mean = 30 weeks). Radiographic closure of the distal physis of metacarpal 3 ranged from 18 to 38 weeks (mean = 29 weeks). When xeroradiographic physeal closure times were compared with scintigraphic closure times from a companion study, results correlated very well. A crena marginis solearis was observed in ten of 12 forelimbs (83.3%); its first radiographic appearance ranged from four to 22 weeks (mean = 11–12 weeks). A consistent groove in the hoof wall, which formed near the time of birth and moved distally at about 3 mm per week, was noted. The groove's distance from the proximal hoof border may be useful in age estimation of foals less than 18–20 weeks old

Analyses of the performance of the ASTRID-like TRU burners in regional scenario studies - 5136

International Nuclear Information System (INIS)

Vezzoni, B.; Gabrielli, F.; Rineiski, A.

2015-01-01

In the past, large Sodium Fast Reactors systems (earlier CAPRA/CADRA, later ESFR and ESFR-like systems) and Accelerator Driven Systems (ADS-EFIT) were considered and extensively studied in Europe for managing MAs/Pu within regional or national scenario studies. After the ASTRID system was proposed in France, ASTRID-like burners could be considered as further options to be investigated. Low conversion ratio (CR) ASTRID-like burner cores (1200 MWth) have been considered at KIT by introducing few modifications with respect to the original French ASTRID design. These modifications allow keeping almost unchanged the main characteristics of the system (e.g. thermal power) and avoiding a strong deterioration of safety parameters (such as sodium void effect) after introduction of large amounts of Pu (more than 20%) and MAs (2-12%) in the fuel. These cores have already been studied at KIT for phase-out scenarios. A constant energy production case, relevant for a European or another regional scenario is considered in the paper. Cases with different shares (from 10 to 30%) of ASTRID-like burners in the nuclear energy fleet are compared. The results show that the ASTRID-like burners allow the use of all TRUs compositions foreseen in the fuel cycle with a proper choice of the MAs to Pu ratios and of the U/TRUs fractions either in phasing-out and on-going nuclear energy utilization conditions. The results show that a mixed fleet composed of 11% burners and 89% ESFR is able to stabilize the MAs in the cycle. The same stabilization is obtained with a fleet composed by 33% burner in combination with LWRs only

Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months.

Science.gov (United States)

Lenz, Melanie; Uçeyler, Nurcan; Frettlöh, Jule; Höffken, Oliver; Krumova, Elena K; Lissek, Silke; Reinersmann, Annika; Sommer, Claudia; Stude, Philipp; Waaga-Gasser, Ana M; Tegenthoff, Martin; Maier, Christoph

2013-10-01

There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

Science.gov (United States)

Awada, A; Dirix, L; Manso Sanchez, L; Xu, B; Luu, T; Diéras, V; Hershman, D L; Agrapart, V; Ananthakrishnan, R; Staroslawska, E

2013-01-01

Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

Multivariate analysis applied to monthly rainfall over Rio de Janeiro state, Brazil

Science.gov (United States)

Brito, Thábata T.; Oliveira-Júnior, José F.; Lyra, Gustavo B.; Gois, Givanildo; Zeri, Marcelo

2017-10-01

Spatial and temporal patterns of rainfall were identified over the state of Rio de Janeiro, southeast Brazil. The proximity to the coast and the complex topography create great diversity of rainfall over space and time. The dataset consisted of time series (1967-2013) of monthly rainfall over 100 meteorological stations. Clustering analysis made it possible to divide the stations into six groups (G1, G2, G3, G4, G5 and G6) with similar rainfall spatio-temporal patterns. A linear regression model was applied to a time series and a reference. The reference series was calculated from the average rainfall within a group, using nearby stations with higher correlation (Pearson). Based on t-test ( p River (G5) and the metropolitan area of the city of Rio de Janeiro (G6). The driest months in all regions were June, July and August, while November, December and January were the rainiest months. Sharp transitions occurred when considering monthly accumulated rainfall: from January to February, and from February to March, likely associated with episodes of "veranicos", i.e., periods of 4-15 days of duration with no rainfall.

Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

LENUS (Irish Health Repository)

Toomey, Sinead

2017-07-27

The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K\\/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.

Electric power monthly

Energy Technology Data Exchange (ETDEWEB)

Smith, Sandra R.; Johnson, Melvin; McClevey, Kenneth; Calopedis, Stephen; Bolden, Deborah

1992-05-01

The Electric Power Monthly is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the national, Census division, and State levels for net generation, fuel consumption, fuel stocks, quantity and quality of fuel, cost of fuel, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fuel are also displayed for the North American Electric Reliability Council (NERC) regions. Additionally, statistics by company and plant are published in the EPM on capability of new plants, new generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fuel.

Some reciprocity-like relations in multi-group neutron diffusion and transport theory over bare homogeneous regions

International Nuclear Information System (INIS)

Modak, R.S.; Sahni, D.C.

1996-01-01

Some simple reciprocity-like relations that exist in multi-group neutron diffusion and transport theory over bare homogeneous regions are presented. These relations do not involve the adjoint solutions and are directly related to numerical schemes based on an explicit evaluation of the fission matrix. (author)

Electric power monthly, April 1993

Energy Technology Data Exchange (ETDEWEB)

1993-05-07

The Electric Power Monthly is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions.

Electric power monthly, May 1993

Energy Technology Data Exchange (ETDEWEB)

1993-05-25

The Electric Power Monthly (EPM) is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions.

Electric power monthly, April 1994

Energy Technology Data Exchange (ETDEWEB)

1994-04-01

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. This publication provides monthly statistics at the U.S., Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. This April 1994 issue contains 1993 year-end data and data through January 1994.

Re-annotation of the physical map of Glycine max for polyploid-like regions by BAC end sequence driven whole genome shotgun read assembly

Directory of Open Access Journals (Sweden)

Shultz Jeffry

2008-07-01

Full Text Available Abstract Background Many of the world's most important food crops have either polyploid genomes or homeologous regions derived from segmental shuffling following polyploid formation. The soybean (Glycine max genome has been shown to be composed of approximately four thousand short interspersed homeologous regions with 1, 2 or 4 copies per haploid genome by RFLP analysis, microsatellite anchors to BACs and by contigs formed from BAC fingerprints. Despite these similar regions,, the genome has been sequenced by whole genome shotgun sequence (WGS. Here the aim was to use BAC end sequences (BES derived from three minimum tile paths (MTP to examine the extent and homogeneity of polyploid-like regions within contigs and the extent of correlation between the polyploid-like regions inferred from fingerprinting and the polyploid-like sequences inferred from WGS matches. Results Results show that when sequence divergence was 1–10%, the copy number of homeologous regions could be identified from sequence variation in WGS reads overlapping BES. Homeolog sequence variants (HSVs were single nucleotide polymorphisms (SNPs; 89% and single nucleotide indels (SNIs 10%. Larger indels were rare but present (1%. Simulations that had predicted fingerprints of homeologous regions could be separated when divergence exceeded 2% were shown to be false. We show that a 5–10% sequence divergence is necessary to separate homeologs by fingerprinting. BES compared to WGS traces showed polyploid-like regions with less than 1% sequence divergence exist at 2.3% of the locations assayed. Conclusion The use of HSVs like SNPs and SNIs to characterize BACs wil improve contig building methods. The implications for bioinformatic and functional annotation of polyploid and paleopolyploid genomes show that a combined approach of BAC fingerprint based physical maps, WGS sequence and HSV-based partitioning of BAC clones from homeologous regions to separate contigs will allow reliable de

INTERDEPENDENCE BETWEEN DRY DAYS AND TEMPERATURE OF SYLHET REGION: CORRELATION ANALYSIS

Directory of Open Access Journals (Sweden)

Syed Mustakim Ali Shah

2016-01-01

Full Text Available Climate change can have profound impact on weather conditions around the world such as heavy rainfall, drought, global warming and so on. Understanding and predicting these natural variations is now a key research challenge for disaster-prone country like Bangladesh. This study focuses on the north eastern part of Bangladesh which is a hilly region, plays an important role in the ecological balance of the country along with socio-economic development. Present study analyses the behavior of maximum temperature and dry days using different statistical tools. Pearson’s correlation matrix and Man-Kendall’s tau are used to correlate monthly dry days with monthly maximum temperature, and also their annual trend. A moderate correlation was found mostly in dry summer months. In addition, a positive trend was observed in Man Kendall’s trend test of yearly temperature which might be an indication of global warming in this region.

Regional neural tube closure defined by the Grainy head-like transcription factors.

Science.gov (United States)

Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

2010-09-15

Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

Atypical dengue meningitis in Makkah, Saudi Arabia with slow resolving, prominent migraine like headache, phobia, and arrhythmia

Directory of Open Access Journals (Sweden)

Kalakatawi H Mamdouh

2013-01-01

Full Text Available Although dengue meningitis is a rare presentation of dengue infection, our aim is to focus on atypical presentation of dengue meningitis that may appear in dengue endemic area like the Makkah region. We report two cases of clinical meningitis with positive dengue virus (DENV IgM in cerebrospinal fluid, followed for minimal 3 months for their prominent attacks of migraine like headache, phobia, and arrhythmia. With special consideration to attack time, type, severity, and respond to classical therapy, using regular ECG monitoring, visual analog pain score and neuropsychological assessments were done. Both cases showed resistant migraine like headaches to classic anti-migraine therapy except for strong NSAID and narcotics with tendency to have severe to extreme severe daily migraine like headache on early to late afternoon time, associated with non-fatal arrhythmias and extreme death phobia, that resolve slowly in a minimal 3 month period. In conclusion, dengue meningitis in the endemic area may present atypically.

Forecasting monthly peak demand of electricity in India—A critique

International Nuclear Information System (INIS)

Rallapalli, Srinivasa Rao; Ghosh, Sajal

2012-01-01

The nature of electricity differs from that of other commodities since electricity is a non-storable good and there have been significant seasonal and diurnal variations of demand. Under such condition, precise forecasting of demand for electricity should be an integral part of the planning process as this enables the policy makers to provide directions on cost-effective investment and on scheduling the operation of the existing and new power plants so that the supply of electricity can be made adequate enough to meet the future demand and its variations. Official load forecasting in India done by Central Electricity Authority (CEA) is often criticized for being overestimated due to inferior techniques used for forecasting. This paper tries to evaluate monthly peak demand forecasting performance predicted by CEA using trend method and compare it with those predicted by Multiplicative Seasonal Autoregressive Integrated Moving Average (MSARIMA) model. It has been found that MSARIMA model outperforms CEA forecasts both in-sample static and out-of-sample dynamic forecast horizons in all five regional grids in India. For better load management and grid discipline, this study suggests employing sophisticated techniques like MSARIMA for peak load forecasting in India. - Highlights: ► This paper evaluates monthly peak demand forecasting performance by CEA. ► Compares CEA forecasts it with those predicted by MSARIMA model. ► MSARIMA model outperforms CEA forecasts in all five regional grids in India. ► Opportunity exists to improve the performance of CEA forecasts.

The Na⁺/H⁺ exchanger NHE1, but not the Na⁺, HCO₃^- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

DEFF Research Database (Denmark)

Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine

2012-01-01

We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2...

Electric power monthly, August 1993

Energy Technology Data Exchange (ETDEWEB)

1993-08-13

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. The EPM is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions.

Electric power monthly, September 1993

Energy Technology Data Exchange (ETDEWEB)

1993-09-17

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. The EPM is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions.

A 21-Year Record of Arctic Sea Ice Extents and Their Regional, Seasonal, and Monthly Variability and Trends

Science.gov (United States)

Parkinson, Claire L.; Cavalieri, Donald J.; Zukor, Dorothy J. (Technical Monitor)

2001-01-01

Satellite passive-microwave data have been used to calculate sea ice extents over the period 1979-1999 for the north polar sea ice cover as a whole and for each of nine regions. Over this 21-year time period, the trend in yearly average ice extents for the ice cover as a whole is -32,900 +/- 6,100 sq km/yr (-2.7 +/- 0.5 %/decade), indicating a reduction in sea ice coverage that has decelerated from the earlier reported value of -34,000 +/- 8,300 sq km/yr (-2.8 +/- 0.7 %/decade) for the period 1979-1996. Regionally, the reductions are greatest in the Arctic Ocean, the Kara and Barents Seas, and the Seas of Okhotsk and Japan, whereas seasonally, the reductions are greatest in summer, for which season the 1979-1999 trend in ice extents is -41,600 +/- 12,900 sq km/ yr (-4.9 +/- 1.5 %/decade). On a monthly basis, the reductions are greatest in July and September for the north polar ice cover as a whole, in September for the Arctic Ocean, in June and July for the Kara and Barents Seas, and in April for the Seas of Okhotsk and Japan. Only two of the nine regions show overall ice extent increases, those being the Bering Sea and the Gulf of St. Lawrence.For neither of these two regions is the increase statistically significant, whereas the 1079 - 1999 ice extent decreases are statistically significant at the 99% confidence level for the north polar region as a whole, the Arctic Ocean, the Seas of Okhotsk and Japan, and Hudson Bay.

Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation.

Science.gov (United States)

Ghanaati, Shahram; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin; Stuebinger, Stefan; Korzinskas, Tadas; Obreja, Karina; Landes, Constantin; Kirkpatrick, Charles J; Sader, Robert A

2013-12-01

In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into the most cranial parts of the augmented region. There was no statistically significant difference in new bone formation after 3 and 6 months (24.89 ± 10.22% vs 31.29 ± 2.29%), respectively. Within the limits of the present study and according to previously published data, implant insertion in regions augmented with this bone substitute material could be considered already after 3 months. Further clinical studies with bone substitute materials are necessary to validate these findings. © 2012 Wiley Periodicals, Inc.

Electric power monthly

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-08-01

The Energy Information Administration (EIA) prepares the Electric Power Monthly (EPM) for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. This publication provides monthly statistics for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. The EIA publishes statistics in the EPM on net generation by energy source, consumption, stocks, quantity, quality, and cost of fossil fuels; and capability of new generating units by company and plant. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead.

Poisson-like shape and shoulder structure of hadron multiplicity distributions in e+e- annihilation at Z0 energy region

International Nuclear Information System (INIS)

Xie Yigang; Chai Yong

1994-01-01

The charged multiplicity distributions of hadron final states in the e + e - annihilation at the 91.2 GeV Z 0 energy region are fitted with Poisson shape in different rapidity windows for double and single hemisphere. The multiplicities which are in Poisson-like shapes can be got according to the parameter /D and fitting qualities are compared with the results derived from the relevant theoretical models. The relationship between the Poisson-like shape and KNO scaling is discussed. The connection between the parameters expressing the deviation from the Poisson shape and non-independent particle emission and multiplicity correlation strength is analyzed. The 'shoulder structure' is observed in the central rapidity region and analyzed with multi-jets by using the JADE jet analysis algorithm

Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants

DEFF Research Database (Denmark)

Damsgaard, Camilla T.; Harsløf, Laurine B. S.; Andersen, Anders D.

2016-01-01

Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months...... of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA...... intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (PIGF-1 in the total population, but a sex×group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95 % CI 0·4, 21·8;P=0...

The molecular environment of the pillar-like features in the H II region G46.5-0.2

Science.gov (United States)

Paron, S.; Celis Peña, M.; Ortega, M. E.; Fariña, C.; Petriella, A.; Rubio, M.; Ashley, R. P.

2017-10-01

At the interface of H II regions and molecular gas, peculiar structures appear, some of them with pillar-like shapes. Understanding their origin is important for characterizing triggered star formation and the impact of massive stars on the interstellar medium. In order to study the molecular environment and influence of radiation on two pillar-like features related to the H II region G46.5-0.2, we performed molecular line observations with the Atacama Submillimeter Telescope Experiment and spectroscopic optical observations with the Isaac Newton Telescope. From the optical observations, we identified the star that is exciting the H II region as spectral type O4-6. The molecular data allowed us to study the structure of the pillars and an HCO+ cloud lying between them. In this HCO+ cloud, which has no well-defined 12CO counterpart, we found direct evidence of star formation: two molecular outflows and two associated near-IR nebulosities. The outflow axis orientation is perpendicular to the direction of the radiation flow from the H II region. Several Class I sources are also embedded in this HCO+ cloud, showing that it is usual that young stellar objects (YSOs) form large associations occupying a cavity bounded by pillars. On the other hand, it was confirmed that the radiation-driven implosion (RDI) process is not occurring in one of the pillar tips.

Statistical theory for estimating sampling errors of regional radiation averages based on satellite measurements

Science.gov (United States)

Smith, G. L.; Bess, T. D.; Minnis, P.

1983-01-01

The processes which determine the weather and climate are driven by the radiation received by the earth and the radiation subsequently emitted. A knowledge of the absorbed and emitted components of radiation is thus fundamental for the study of these processes. In connection with the desire to improve the quality of long-range forecasting, NASA is developing the Earth Radiation Budget Experiment (ERBE), consisting of a three-channel scanning radiometer and a package of nonscanning radiometers. A set of these instruments is to be flown on both the NOAA-F and NOAA-G spacecraft, in sun-synchronous orbits, and on an Earth Radiation Budget Satellite. The purpose of the scanning radiometer is to obtain measurements from which the average reflected solar radiant exitance and the average earth-emitted radiant exitance at a reference level can be established. The estimate of regional average exitance obtained will not exactly equal the true value of the regional average exitance, but will differ due to spatial sampling. A method is presented for evaluating this spatial sampling error.

Mapping White Matter Microstructure in the One Month Human Brain.

Science.gov (United States)

Dean, D C; Planalp, E M; Wooten, W; Adluru, N; Kecskemeti, S R; Frye, C; Schmidt, C K; Schmidt, N L; Styner, M A; Goldsmith, H H; Davidson, R J; Alexander, A L

2017-08-29

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Electric Power Monthly, July 1990

Energy Technology Data Exchange (ETDEWEB)

1990-10-12

The Electric Power Monthly (EPM) is prepared by the Electric Power Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the national, Census division, and State levels for net generation, fuel consumption, fuel stocks, quantity and quality of fuel, cost of fuel, electricity sales, and average revenue per kilowatthour of electricity sold. Data on net generation are also displayed at the North American Electric Reliability Council (NERC) region level. Additionally, company and plant level information are published in the EPM on capability of new plants, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost in fuel. Quantity, quality, and cost of fuel data lag the net generation, fuel consumption, fuel stocks, electricity sales, and average revenue per kilowatthour data by 1 month. This difference in reporting appears in the national, Census division, and State level tables. However, at the plant level, all statistics presented are for the earlier month for the purpose of comparison. 12 refs., 4 figs., 48 tabs.

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia

OpenAIRE

Alves,Maria Teresa de Seixas; Miiji,Luciana Nakao Odashiro; Marinho,Larissa Cardoso; Petrilli,Antonio Sergio; Jesus-Garcia,Reynaldo; Tolledo,Silvia Caminada; Patricio,Francy Reis da Silva

2008-01-01

INTRODUÇÃO: Osteossarcoma (OS), o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp) e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológic...

Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

DEFF Research Database (Denmark)

Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

2017-01-01

, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild......-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels...... of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice...

Diurnal, monthly and seasonal variation of mean winds in the MLT region observed over Kolhapur using MF radar

Science.gov (United States)

Sharma, A. K.; Gaikwad, H. P.; Ratnam, M. Venkat; Gurav, O. B.; Ramanjaneyulu, L.; Chavan, G. A.; Sathishkumar, S.

2018-04-01

Medium Frequency (MF) radar located at Kolhapur (16.8°N, 74.2°E) has been upgraded in August 2013. Since then continuous measurements of zonal and meridional winds are obtained covering larger altitudes from the Mesosphere and Lower Thermosphere (MLT) region. Diurnal, monthly and seasonal variation of these mean winds is presented in this study using four years (2013-2017) of observations. The percentage occurrence of radar echoes show maximum between 80 and 105 km. The mean meridional wind shows Annual Oscillation (AO) between 80 and 90 km altitudes with pole-ward motion during December solstice and equatorial motion during June solstice. Quasi-biennial oscillation (QBO) with weaker amplitudes are also observed between 90 and 104 km. Zonal winds show semi-annual oscillation (SAO) with westward winds during equinoxes and eastward winds during solstices between 80 and 90 km. AO with eastward winds during December solstice and westward wind in the June solstice is also observed in the mean zonal wind between 100 and 110 km. These results match well with that reported from other latitudes within Indian region between 80 and 90 km. However, above 90 km the results presented here provide true mean background winds for the first time over Indian low latitude region as the present station is away from equatorial electro-jet and are not contaminated by ionospheric processes. Further, the results presented earlier with an old version of this radar are found contaminated due to unknown reasons and are corrected in the present work. This upgraded MF radar together with other MLT radars in the Indian region forms unique network to investigate the vertical and lateral coupling.

Monthly Electrical Energy Overview Mars 2017

International Nuclear Information System (INIS)

2017-04-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for March 2017. With 2 deg. C over the normal average temperature, March 2017 was the hottest March recorded over the period 1900-2017. Therefore, gross French power demand fell by 9.4% compared to March 2016. A new record instantaneous balance in favour of exports was reached at over 17 GW. Gross demand was down compared to March 2016, due to milder temperatures. RE generation excluding hydraulic rose after 4 months of falls, driven by favourable weather conditions. The maximum coverage rate of demand by wind power generation reached a new record (18.2%) benefiting from the presence of windy conditions over the country in March. The monthly regional coverage rate of demand by generation of renewable origin exceeded 23% in the Occitanie, Auvergne-Rhone-Alpes, Grand-Est, Provence-Alpes-Cote d'Azur and Nouvelle-Aquitaine regions. The fall in prices continued throughout Europe. On 30 March at 19.30 a new record instantaneous balance in favour of exports was recorded at over 17 GW. 1 new installation went into service in March 2017

Litterfall production under pine plantations in the southern Andes region of Ecuador

Directory of Open Access Journals (Sweden)

Pablo Quichimbo

2016-09-01

Full Text Available Litterfall research is an interesting aspect in environmental studies due to its significance in nutrient cycling specially in regions like the Andes where the interactions between biomass production and its decomposition is poorly understood. This study is focusing in the litterfall biomass production under pine plantations in southern Ecuador. The litterfall production was studied for five months at two-week intervals in three pine forest sites located in the southern Andes region of Ecuador. Monthly litterfall production ranged between 1067-1907 kg ha-1, in comparison with other coniferous stands around the world, this study revealed a higher litterfall production for tropical areas and particularly the highest production under pine plantations in the Andes region. This high litterfall production highlights the upmost importance of this forest component as a potential nutrient reservoir involved in the global nutrient cycling under landscapes dominated by this exotic forest specie in the tropical Andes.

78 FR 54743 - National Preparedness Month, 2013

Science.gov (United States)

2013-09-06

... like hurricanes, tornadoes, and floods to shootings, cyber incidents, and even acts of terrorism. While... Preparedness Month. I encourage all Americans to recognize the importance of preparedness and work together to enhance our national security, resilience, and readiness. [[Page 54744

Electric Power Monthly, June 1990

Energy Technology Data Exchange (ETDEWEB)

1990-09-13

The EPM is prepared by the Electric Power Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the national, Census division, and State levels for net generation, fuel consumption, fuel stocks, quantity and quality of fuel, electricity sales, and average revenue per kilowatthour of electricity sold. Data on net generation are also displayed at the North American Electric Reliability Council (NERC) region level. Additionally, company and plant level information are published in the EPM on capability of new plants, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fuel. Quantity, quality, and cost of fuel data lag the net generation, fuel consumption, fuel stocks, electricity sales, and average revenue per kilowatthour data by 1 month. This difference in reporting appears in the national, Census division, and State level tables. However, at the plant level, all statistics presented are for the earlier month for the purpose of comparison. 40 tabs.

Uncertainty in regional and zonal monthly mean downward surface irradiances from Edition 4.0 CERES Energy Balanced and Filled (EBAF) data product

Science.gov (United States)

Kato, S.; Rutan, D. A.; Rose, F. G.; Loeb, N. G.

2017-12-01

The surface of the Earth receives solar radiation (shortwave) and emission from the atmosphere (longwave). At a global and annual mean approximately 12% of solar radiation incident on the surface is reflected and the rest is absorbed by the surface. The surface emits radiation proportional to the forth power of the temperature. Although the uncertainty in global and annual mean surface irradiances is estimated in earlier studies (Zhang et al. 1995, 2004; L'Ecuyer et al. 2008; Stephens et al. 2012; Kato et al. 2012), only a few studies estimated the uncertainty in computed surface irradiances at smaller spatial and temporal scales (Zhang et al. 1995, 2004; Kato et al. 2012). We use surface observations at 46 buoys and 36 land sites and newly released the Edition 4.0 Clouds and the Earth's Radiant Energy System (CERES) Energy Balanced and Filled (EBAF)-surface data product to estimate the uncertainty in regional and zonal monthly mean downward shortwave and longwave surface irradiances. The root-mean-square difference of monthly mean computed and observed irradiances is used for the regional uncertainty. The uncertainty is separated into bias and spatially random components. The random component decreases when irradiances are averaged over a larger area, nearly inversely proportional to the number of surface observation sites. The presentation provides the uncertainty in the regional and zonal monthly mean downward surface irradiances over ocean and land. ReferencesKato, S. and N.G.Loeb, D. A.Rutan, F. G. Rose, S. Sun-Mack,W.F.Miller, and Y. Chen, 2012. Surv. Geophys., 33, 395-412, doi:10.1007/s10712-012-9179-x. L'Ecuyer, T. S., N. B. Wood, T. Haladay, G. L. Stephens, and P. W. Stackhouse Jr., 2008, J. Geophys. Res., 113, D00A15, doi:10.1029/2008JD009951. Stephens, G. L. and Coauthors, 2012, Nat. Geosci., 5, 691-696, doi:10.1038/ngeo1580. Zhang, Y., W. B. Rossow, A. A. Lacis, V. Oinas, and M. I. Mishchenko, 2004, J. Geophys. Res., 109, D19105, doi:10.1029/2003JD

Regional Variation of Cost of Care in the Last 12 Months of Life in Switzerland: Small-area Analysis Using Insurance Claims Data.

Science.gov (United States)

Panczak, Radoslaw; Luta, Xhyljeta; Maessen, Maud; Stuck, Andreas E; Berlin, Claudia; Schmidlin, Kurt; Reich, Oliver; von Wyl, Viktor; Goodman, David C; Egger, Matthias; Zwahlen, Marcel; Clough-Gorr, Kerri M

2017-02-01

Health care spending increases sharply at the end of life. Little is known about variation of cost of end of life care between regions and the drivers of such variation. We studied small-area patterns of cost of care in the last year of life in Switzerland. We used mandatory health insurance claims data of individuals who died between 2008 and 2010 to derive cost of care. We used multilevel regression models to estimate differences in costs across 564 regions of place of residence, nested within 71 hospital service areas. We examined to what extent variation was explained by characteristics of individuals and regions, including measures of health care supply. The study population consisted of 113,277 individuals. The mean cost of care during last year of life was 32.5k (thousand) Swiss Francs per person (SD=33.2k). Cost differed substantially between regions after adjustment for patient age, sex, and cause of death. Variance was reduced by 52%-95% when we added individual and regional characteristics, with a strong effect of language region. Measures of supply of care did not show associations with costs. Remaining between and within hospital service area variations were most pronounced for older females and least for younger individuals. In Switzerland, small-area analysis revealed variation of cost of care during the last year of life according to linguistic regions and unexplained regional differences for older women. Cultural factors contribute to the delivery and utilization of health care during the last months of life and should be considered by policy makers.

Monthly Electrical Energy Overview October 2017

International Nuclear Information System (INIS)

2017-11-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for Monthly gross domestic demand fell by 5.2% compared to October 2016, due to above-normal temperatures. The monthly trade balance was in favour of exports. Total demand corrected for climate contingencies remained stable. Demand by heavy industry continued its upward trend. Monthly nuclear generation fell by 3.3% compared to October 2016. The rainfall deficit resulted in a reduction of almost 11% in hydropower production compared to October 2016. Wind power production rose 46.7% compared to October 2016. Photovoltaic production fell by 2.2% compared to October 2016. The solar load factor fell in almost all French regions compared to October 2016. Market prices continued to increase, in particular in Belgium and in France where nuclear availability was strongly reduced. The monthly balance of trade for France was once again positive in October 2017. 15 new installations went into service in October

The Chaschuil region of like corridor of Goods, energy and information; pre hispanic Integration between Puna and the Boston de Flambala

International Nuclear Information System (INIS)

Ratto, Norma; Pla, Rita; Orgaz, Martin; Fuente, Guillermo de la

2001-01-01

In this work the relevance of the chascuil region like corridor of goods of energy circulation are discussed, goods of information from times of the societies agroalfareras until the Inca presence in the region being constituted in one of the multiple roads or circulation routes that integrated the territories of the This with the West, of one and another side of the Andean mountain range of the southern sector of the South American knowledge The NAA is an analytic technique that gathers the basic requirements of sensibility, precision, accuracy and necessary selectivity for the discussion of archaeological problems of origin, contacts, trade exchange and pottery production like likewise to reconstruct the socieconomias Inter. and intra populations of the past

Epidemiological factors in admissions for diarrhoea in 6 - 60-month ...

African Journals Online (AJOL)

Objectives. To describe the diarrhoea admissions and the influencing factors in 6 - 60-month-old children at Morogoro Regional Hospital. Design. A retrospective descriptive study of the type of diarrhoea, patient age, home address, nutritional status, diagnosed infection, month of admission, admission duration and outcome ...

TAIL1: an isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region.

Science.gov (United States)

Rossi, Valeria; Beffagna, Giorgia; Rampazzo, Alessandra; Bauce, Barbara; Danieli, Gian Antonio

2004-06-23

Isthmins represent a novel family of vertebrate secreted proteins containing one copy of the thrombospondin type 1 repeat (TSR), which in mammals is shared by several proteins with diverse biological functions, including cell adhesion, angiogenesis, and patterning of developing nervous system. We have determined the genomic organization of human TAIL1 (thrombospondin and AMOP containing isthmin-like 1), a novel isthmin-like gene encoding a protein that contains a TSR and a C-terminal AMOP domain (adhesion-associated domain in MUC4 and other proteins), characteristic of extracellular proteins involved in adhesion processes. TAIL1 gene encompasses more than 24.4 kb. Analysis of the DNA sequence surrounding the putative transcriptional start region revealed a TATA-less promoter located in a CpG island. Several consensus binding sites for the transcription factors Sp1 and MZF-1 were identified in this promoter region. In humans, TAIL1 gene is located on chromosome 14q24.3 within ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region; preliminary evidence suggests that it is expressed in several tissues, showing multiple alternative splicing.

Electric Power Monthly, August 1990. [Glossary included

Energy Technology Data Exchange (ETDEWEB)

1990-11-29

The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

Bιβλιοκρισία: M. ALTRIPP (Ηrsg., Byzanz in Europa. Europas östliches Erbe. [BYZANTIOS. Studies in Byzantine History and Civilization 2], Turnhout 2011, ISBN 978-2-503-54153-2

Directory of Open Access Journals (Sweden)

Στυλιανός ΛΑΜΠΑΚΗΣ

2014-04-01

Full Text Available Βιβλιοκρισία: M. Altripp (Ηrsg., Byzanz in Europa. Europas östliches Erbe. Akten des Kolloquiums 'Byzanz in Europa' vom 11. bis 15. Dezember 2007 in Greifswald [BYZANTIOS. Studies in Byzantine History and Civilization 2], Turnhout 2011, σελ. X + 502, 79 πίν., ISBN 978-2-503-54153-2 (printed version- 978-2-503-54193-8 (online version.

Simulations of monthly mean nitrate concentrations in precipitation over East Asia

International Nuclear Information System (INIS)

Junling An; Xinjin Cheng; Ueda, Hiromasa; Kajino, Mizuo

2002-01-01

Monthly mean nitrate concentrations in precipitation over East Asia (10-55 o N, 75-155 o E) in April, July, September, and December of 1999 were simulated by using a regional air quality Eulerian model (RAQM) with meteorological fields four times per day taken from National Centers for Environmental Prediction. The distribution of the nitrate concentration in precipitation depends significantly on the emission patterns of nitrogen oxides (NO x =NO+NO 2 ) and volatile organic compound (VOC) and seasonal precipitation variability. The downward trend is also revealed, particularly on July and December. Highest concentrations are found in the industrialized regions, i.e., the coastal area of the Mainland of China, the Bay of the Huanghai Sea and the Bohai Sea, Korea, and Southern Japan. Long-range transport may cause elevated concentrations in remote areas downwind of the industrialized regions under favorable meteorological conditions, e.g., low precipitation. Comparison of observation and simulations indicates that the RAQM model reasonably predicts synoptic-scale changes in different months (seasons) and simulated nitrate levels in 4 months fit observed data with the discrepancy within a factor of 2. Exclusion of liquid chemistry within clouds is feasible for regional (1 o x1 o ) and long-term (monthly) nitrate simulations. The uncertainty originates mainly from that of the emission data and modeled precipitation amounts and initial and boundary conditions. (author)

Empirical models of monthly and annual surface albedo in managed boreal forests of Norway

Science.gov (United States)

Bright, Ryan M.; Astrup, Rasmus; Strømman, Anders H.

2013-04-01

As forest management activities play an increasingly important role in climate change mitigation strategies of Nordic regions such as Norway, Sweden, and Finland -- the need for a more comprehensive understanding of the types and magnitude of biogeophysical climate effects and their various tradeoffs with the global carbon cycle becomes essential to avoid implementation of sub-optimal policy. Forest harvest in these regions reduces the albedo "masking effect" and impacts Earth's radiation budget in opposing ways to that of concomitant carbon cycle perturbations; thus, policies based solely on biogeochemical considerations in these regions risk being counterproductive. There is therefore a need to better understand how human disturbances (i.e., forest management activities) affect important biophysical factors like surface albedo. An 11-year remotely sensed surface albedo dataset coupled with stand-level forest management data for a variety of stands in Norway's most productive logging region are used to develop regression models describing temporal changes in monthly and annual forest albedo following clear-cut harvest disturbance events. Datasets are grouped by dominant tree species and site indices (productivity), and two alternate multiple regression models are developed and tested following a potential plus modifier approach. This resulted in an annual albedo model with statistically significant parameters that explains a large proportion of the observed variation, requiring as few as two predictor variables: i) average stand age - a canopy modifier predictor of albedo, and ii) stand elevation - a local climate predictor of a forest's potential albedo. The same model structure is used to derive monthly albedo models, with models for winter months generally found superior to summer models, and conifer models generally outperforming deciduous. We demonstrate how these statistical models can be applied to routine forest inventory data to predict the albedo

Comparison of the observed and calculated clear sky greenhouse effect - Implications for climate studies

Science.gov (United States)

Kiehl, J. T.; Briegleb, B. P.

1992-01-01

The clear sky greenhouse effect is defined in terms of the outgoing longwave clear sky flux at the top of the atmosphere. Recently, interest in the magnitude of the clear sky greenhouse effect has increased due to the archiving of the clear sky flux quantity through the Earth Radiation Budget Experiment (ERBE). The present study investigates to what degree of accuracy this flux can be analyzed by using independent atmospheric and surface data in conjunction with a detailed longwave radiation model. The conclusion from this comparison is that for most regions over oceans the analyzed fluxes agree to within the accuracy of the ERBE-retrieved fluxes (+/- 5 W/sq m). However, in regions where deep convective activity occurs, the ERBE fluxes are significantly higher (10-15 W/sq m) than the calculated fluxes. This bias can arise from either cloud contamination problems or variability in water vapor amount. It is argued that the use of analyzed fluxes may provide a more consistent clear sky flux data set for general circulation modeling validation. Climate implications from the analyzed fluxes are explored. Finally, results for obtaining longwave surface fluxes over the oceans are presented.

Atlas of albedo and absorbed solar radiation derived from Nimbus 7 earth radiation budget data set, November 1985 to October 1987

Science.gov (United States)

Smith, G. Louis; Rutan, David; Bess, T. Dale

1992-01-01

An atlas of monthly mean global contour maps of albedo and absorbed solar radiation is presented for 21 months from Nov. 1985 to Oct. 1987. These data were retrieved from measurements made by the shortwave wide-field-of-view radiometer of the Earth Radiation Budget (ERB) instrument aboard the Nimbus 7 spacecraft. Profiles of zonal mean albedos and absorbed solar radiation were tabulated. These geographical distributions are provided as a resource for researchers studying the radiation budget of the Earth. The El Nino/Southern Oscillation event of 1986-1987 is included in this data set. This atlas of albedo and absorbed solar radiation extends to 12 years the period covered by two similar atlases: NASA RP-1230 (Jul. 1975 - Oct. 1978) and NASA RP-1231 (Nov. 1978 - Oct. 1985). These three compilations complement the atlases of outgoing longwave radiation by Bess and Smith in NASA RP-1185, RP-1186, and RP-1261, which were also based on the Nimbus 6 and 7 ERB data.

[Results of statistical analysis of the dynamics of ionizing radiation dose fields in the service module of the International Space Station in 2000-2012].

Science.gov (United States)

Mitrikas, V G

2014-01-01

The on-going 24th solar cycle (SC) is distinguished from the previous ones by low activity. On the contrary, levels of proton fluxes from galactic cosmic rays (GCR) are high, which increases the proton flow striking the Earth's radiation belts (ERB). Therefore, at present the absorbed dose from ERB protons should be calculated with consideration of the tangible increase of protons intensity built into the model descriptions based on experimental measurements during the minimum between cycles 19 and 20, and the cycle 21 maximum. The absorbed dose from GCR and ERB protons copies galactic protons dynamics, while the ERB electrons dose copies SC dynamics. The major factors that determine the absorbed dose value are SC phase, ISS orbital altitude and shielding of the dosimeter readings of which are used in analysis. The paper presents the results of dynamic analysis of absorbed doses measured by a variety of dosimeters, namely, R-16 (2 ionization chambers), DB8-1, DB8-2, DB8-3, DB8-4 as a function of ISS orbit altitude and SC phase. The existence of annual variation in the absorbed dose dynamics has been confirmed; several additional variations with the periods of 17 and 52 months have been detected. Modulation of absorbed dose variations by the SC and GCR amplitudes has been demonstrated.

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

Directory of Open Access Journals (Sweden)

Eiichiro Okazaki

2017-12-01

Full Text Available Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ, posterior-superior (PSQ, anterior-inferior (AIQ, and posterior-inferior (PIQ. Predictive factors and cut-off values of biochemical failure-free survival (BFFS and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4% had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

Directory of Open Access Journals (Sweden)

Hiscox Stephen

2012-10-01

Full Text Available Abstract Background Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. Methods CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression or MCF7 cells (± transfection with the CD44 gene were treated with the CD44 ligand, hyaluronon (HA, or heregulin and their in vitro growth (MTT, migration (Boyden chamber and wound healing and invasion (Matrigel transwell migration determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. Results TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

International Nuclear Information System (INIS)

Hiscox, Stephen; Gee, Julia; Baruha, Bedanta; Smith, Chris; Bellerby, Rebecca; Goddard, Lindy; Jordan, Nicola; Poghosyan, Zaruhi; Nicholson, Robert I; Barrett-Lee, Peter

2012-01-01

Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration

Monthly Rainfall Erosivity: Conversion Factors for Different Time Resolutions and Regional Assessments

DEFF Research Database (Denmark)

Panagos, Panos; Borrelli, Pasquale; Spinoni, Jonathan

2016-01-01

, for the optimization of land management (seasonal variation of vegetation cover and agricultural support practices) as well as natural hazard protection (landslides and flood prediction). We expanded REDES by 140 rainfall stations, thus covering areas where monthly R-factor values were missing (Slovakia, Poland...

GEOGLAM Crop Monitor Assessment Tool: Developing Monthly Crop Condition Assessments

Science.gov (United States)

McGaughey, K.; Becker Reshef, I.; Barker, B.; Humber, M. L.; Nordling, J.; Justice, C. O.; Deshayes, M.

2014-12-01

The Group on Earth Observations (GEO) developed the Global Agricultural Monitoring initiative (GEOGLAM) to improve existing agricultural information through a network of international partnerships, data sharing, and operational research. This presentation will discuss the Crop Monitor component of GEOGLAM, which provides the Agricultural Market Information System (AMIS) with an international, multi-source, and transparent consensus assessment of crop growing conditions, status, and agro-climatic conditions likely to impact global production. This activity covers the four primary crop types (wheat, maize, rice, and soybean) within the main agricultural producing regions of the AMIS countries. These assessments have been produced operationally since September 2013 and are published in the AMIS Market Monitor Bulletin. The Crop Monitor reports provide cartographic and textual summaries of crop conditions as of the 28th of each month, according to crop type. This presentation will focus on the building of international networks, data collection, and data dissemination.

Children aged 6-24 months like to watch YouTube videos but could not learn anything from them.

Science.gov (United States)

Yadav, Savita; Chakraborty, Pinaki; Mittal, Prabhat; Arora, Udit

2018-03-20

Parents sometimes show young children YouTube videos on their smartphones. We studied the interaction of 55 Indian children born between December 2014 and May 2015 who watched YouTube videos when they were 6-24 months old. The children were recruited by the researchers using professional and personal contacts and visited by the same two observers at four ages, for at least 10 minutes. The observers recorded the children's abilities to interact with touch screens and identify people in videos and noted what videos attracted them the most. The children were attracted to music at six months of age and were interested in watching the videos at 12 months. They could identify their parents in videos at 12 months and themselves by 24 months. They started touching the screen at 18 months and could press the buttons that appeared on the screen, but did not understand their use. The children preferred watching dance performances by multiple artists with melodical music, advertisements for products they used and videos showing toys and balloons. Children up to two years of age could be entertained and kept busy by showing them YouTube clips on smartphones, but did not learn anything from the videos. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer.

Science.gov (United States)

Sequist, Lecia V; Besse, Benjamin; Lynch, Thomas J; Miller, Vincent A; Wong, Kwok K; Gitlitz, Barbara; Eaton, Keith; Zacharchuk, Charles; Freyman, Amy; Powell, Christine; Ananthakrishnan, Revathi; Quinn, Susan; Soria, Jean-Charles

2010-06-20

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non-small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M. Patients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with > or = 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naïve patients with adenocarcinoma and light smoking histories (neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR). One-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks. Neratinib had low activity in patients with prior benefit from TKIs and in TKI-naïve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.

Monthly paleostreamflow reconstruction from annual tree-ring chronologies

Science.gov (United States)

Stagge, J. H.; Rosenberg, D. E.; DeRose, R. J.; Rittenour, T. M.

2018-02-01

Paleoclimate reconstructions are increasingly used to characterize annual climate variability prior to the instrumental record, to improve estimates of climate extremes, and to provide a baseline for climate-change projections. To date, paleoclimate records have seen limited engineering use to estimate hydrologic risks because water systems models and managers usually require streamflow input at the monthly scale. This study explores the hypothesis that monthly streamflows can be adequately modeled by statistically decomposing annual flow reconstructions. To test this hypothesis, a multiple linear regression model for monthly streamflow reconstruction is presented that expands the set of predictors to include annual streamflow reconstructions, reconstructions of global circulation, and potential differences among regional tree-ring chronologies related to tree species and geographic location. This approach is used to reconstruct 600 years of monthly streamflows at two sites on the Bear and Logan rivers in northern Utah. Nash-Sutcliffe Efficiencies remain above zero (0.26-0.60) for all months except April and Pearson's correlation coefficients (R) are 0.94 and 0.88 for the Bear and Logan rivers, respectively, confirming that the model can adequately reproduce monthly flows during the reference period (10/1942 to 9/2015). Incorporating a flexible transition between the previous and concurrent annual reconstructed flows was the most important factor for model skill. Expanding the model to include global climate indices and regional tree-ring chronologies produced smaller, but still significant improvements in model fit. The model presented here is the only approach currently available to reconstruct monthly streamflows directly from tree-ring chronologies and climate reconstructions, rather than using resampling of the observed record. With reasonable estimates of monthly flow that extend back in time many centuries, water managers can challenge systems models with a

Electric power monthly, April 1991

International Nuclear Information System (INIS)

1991-01-01

The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national Census division, and State level. The purpose of this publication is to provide energy decision makers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data are given for net generation, fuel consumption, fuel stocks, quantity and quality of fuel, cost of fuel, electricity sales, revenue, and average revenue per kilowatt hour of electricity sold. Data on net generation are also displayed at the North American Electric Reliability Council (NERC) region level. Additionally, statistics at the company and plant level are published in the EPM on capability of new plants, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fuel. 6 figs., 57 tabs

Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

Science.gov (United States)

Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

2015-03-01

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

Regional differences in trait-like characteristics of the waking EEG in early adolescence.

Science.gov (United States)

Benz, Dominik C; Tarokh, Leila; Achermann, Peter; Loughran, Sarah P

2013-10-09

The human waking EEG spectrum shows high heritability and stability and, despite maturational cortical changes, high test-retest reliability in children and teens. These phenomena have also been shown to be region specific. We examined the stability of the morphology of the wake EEG spectrum in children aged 11 to 13 years recorded over weekly intervals and assessed whether the waking EEG spectrum in children may also be trait-like. Three minutes of eyes open and three minutes of eyes closed waking EEG was recorded in 22 healthy children once a week for three consecutive weeks. Eyes open and closed EEG power density spectra were calculated for two central (C3LM and C4LM) and two occipital (O1LM and O2LM) derivations. A hierarchical cluster analysis was performed to determine whether the morphology of the waking EEG spectrum between 1 and 20 Hz is trait-like. We also examined the stability of the alpha peak using an ANOVA. The morphology of the EEG spectrum recorded from central derivations was highly stable and unique to an individual (correctly classified in 85% of participants), while the EEG recorded from occipital derivations, while stable, was much less unique across individuals (correctly classified in 42% of participants). Furthermore, our analysis revealed an increase in alpha peak height concurrent with a decline in the frequency of the alpha peak across weeks for occipital derivations. No changes in either measure were observed in the central derivations. Our results indicate that across weekly recordings, power spectra at central derivations exhibit more "trait-like" characteristics than occipital derivations. These results may be relevant for future studies searching for links between phenotypes, such as psychiatric diagnoses, and the underlying genes (i.e., endophenotypes) by suggesting that such studies should make use of more anterior rather than posterior EEG derivations.

A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

Science.gov (United States)

Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

2012-07-01

Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

Directory of Open Access Journals (Sweden)

Steven N Steinway

Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

Monthly Electrical Energy Overview April 2017

International Nuclear Information System (INIS)

2017-05-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for April 2017. Despite lower than normal temperatures (-0.8 deg. C), April remained milder than that of the previous year, resulting in a slight fall in demand. For the third month in a row, demand fell compared to the same month in the previous year (-6.2%). Hydraulic generation suffered from the dry weather in April with a fall of 35% compared to April 2016. The good amount of sunlight this month as well as the increase in the installed photovoltaic base allowed solar generation to jump by more than 36%. The rainfall deficit over the country affected hydraulic generation with falls of as much as -80% in the Centre-Val de Loire region. Variations in market prices were mixed depending on the countries. The balance of exports was in France's favour on all its borders, with a national export balance greater than 5 TWh. 9 new installations went into service in April

Transitions in Al-like, Mg-like and Na-like Kr and Mo, observed in the JET tokamak

Energy Technology Data Exchange (ETDEWEB)

Jupen, C; Denne, B; Martinson, I [JET Joint Undertaking, Abingdon, Oxon (UK)

1990-05-01

Spectra of highly ionized Kr and Mo, emitted from the JET tokamak plasmas, have been recorded in the region 30-335 A. Detailed analysis of the n=3, {Delta}n=0 transitions in Kr XXIV-XXVI and Mo XXX-XXXII has resulted in a number of new spectral classifications. Some isoelectronic regularities for Al-like and Mg-like ions are discussed. (orig.).

Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling

Energy Technology Data Exchange (ETDEWEB)

Kim, Min-Sung; Saunders, Adam M.; Hamaoka, Brent Y.; Beachy, Philip A.; Leahy, Daniel J. (Stanford-MED); (JHU)

2011-09-20

Glypicans are heparan sulfate proteoglycans that modulate the signaling of multiple growth factors active during animal development, and loss of glypican function is associated with widespread developmental abnormalities. Glypicans consist of a conserved, approximately 45-kDa N-terminal protein core region followed by a stalk region that is tethered to the cell membrane by a glycosyl-phosphatidylinositol anchor. The stalk regions are predicted to be random coil but contain a variable number of attachment sites for heparan sulfate chains. Both the N-terminal protein core and the heparan sulfate attachments are important for glypican function. We report here the 2.4-{angstrom} crystal structure of the N-terminal protein core region of the Drosophila glypican Dally-like (Dlp). This structure reveals an elongated, {alpha}-helical fold for glypican core regions that does not appear homologous to any known structure. The Dlp core protein is required for normal responsiveness to Hedgehog (Hh) signals, and we identify a localized region on the Dlp surface important for mediating its function in Hh signaling. Purified Dlp protein core does not, however, interact appreciably with either Hh or an Hh:Ihog complex.

Application of GRACE to the assessment of model-based estimates of monthly Greenland Ice Sheet mass balance (2003-2012)

Science.gov (United States)

Schlegel, Nicole-Jeanne; Wiese, David N.; Larour, Eric Y.; Watkins, Michael M.; Box, Jason E.; Fettweis, Xavier; van den Broeke, Michiel R.

2016-09-01

Quantifying the Greenland Ice Sheet's future contribution to sea level rise is a challenging task that requires accurate estimates of ice sheet sensitivity to climate change. Forward ice sheet models are promising tools for estimating future ice sheet behavior, yet confidence is low because evaluation of historical simulations is challenging due to the scarcity of continental-wide data for model evaluation. Recent advancements in processing of Gravity Recovery and Climate Experiment (GRACE) data using Bayesian-constrained mass concentration ("mascon") functions have led to improvements in spatial resolution and noise reduction of monthly global gravity fields. Specifically, the Jet Propulsion Laboratory's JPL RL05M GRACE mascon solution (GRACE_JPL) offers an opportunity for the assessment of model-based estimates of ice sheet mass balance (MB) at ˜ 300 km spatial scales. Here, we quantify the differences between Greenland monthly observed MB (GRACE_JPL) and that estimated by state-of-the-art, high-resolution models, with respect to GRACE_JPL and model uncertainties. To simulate the years 2003-2012, we force the Ice Sheet System Model (ISSM) with anomalies from three different surface mass balance (SMB) products derived from regional climate models. Resulting MB is compared against GRACE_JPL within individual mascons. Overall, we find agreement in the northeast and southwest where MB is assumed to be primarily controlled by SMB. In the interior, we find a discrepancy in trend, which we presume to be related to millennial-scale dynamic thickening not considered by our model. In the northwest, seasonal amplitudes agree, but modeled mass trends are muted relative to GRACE_JPL. Here, discrepancies are likely controlled by temporal variability in ice discharge and other related processes not represented by our model simulations, i.e., hydrological processes and ice-ocean interaction. In the southeast, GRACE_JPL exhibits larger seasonal amplitude than predicted by the

Modeling of the Monthly Rainfall-Runoff Process Through Regressions

Directory of Open Access Journals (Sweden)

Campos-Aranda Daniel Francisco

2014-10-01

Full Text Available To solve the problems associated with the assessment of water resources of a river, the modeling of the rainfall-runoff process (RRP allows the deduction of runoff missing data and to extend its record, since generally the information available on precipitation is larger. It also enables the estimation of inputs to reservoirs, when their building led to the suppression of the gauging station. The simplest mathematical model that can be set for the RRP is the linear regression or curve on a monthly basis. Such a model is described in detail and is calibrated with the simultaneous record of monthly rainfall and runoff in Ballesmi hydrometric station, which covers 35 years. Since the runoff of this station has an important contribution from the spring discharge, the record is corrected first by removing that contribution. In order to do this a procedure was developed based either on the monthly average regional runoff coefficients or on nearby and similar watershed; in this case the Tancuilín gauging station was used. Both stations belong to the Partial Hydrologic Region No. 26 (Lower Rio Panuco and are located within the state of San Luis Potosi, México. The study performed indicates that the monthly regression model, due to its conceptual approach, faithfully reproduces monthly average runoff volumes and achieves an excellent approximation in relation to the dispersion, proved by calculation of the means and standard deviations.

Electric power monthly, February 1994

Energy Technology Data Exchange (ETDEWEB)

1994-02-16

The Electric Power Monthly (EMP) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data in this report are presented for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The EIA collected the information in this report to fulfill its data collection and dissemination responsibilities as specified in the Federal Energy Administration Act of 1974 (Public Law 93-275) as amended. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. Statistics by company and plant are published in the EPM on the capability of new generating units, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fossil fuels.

Electric power monthly, January 1994

International Nuclear Information System (INIS)

1994-01-01

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data in this report are presented for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The EIA collected the information in this report to fulfill its data collection and dissemination responsibilities as specified in the Federal Energy Administration Act of 1974 (Public Law 93-275) as amended. This publication provides monthly statistics at the US Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. Statistics by company and plant are published in the EPM on the capability of new generating units, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fossil fuels

Electric power monthly, January 1994

Energy Technology Data Exchange (ETDEWEB)

1994-01-26

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data in this report are presented for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The EIA collected the information in this report to fulfill its data collection and dissemination responsibilities as specified in the Federal Energy Administration Act of 1974 (Public Law 93-275) as amended. This publication provides monthly statistics at the US Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. Statistics by company and plant are published in the EPM on the capability of new generating units, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fossil fuels.

Electric power monthly, October 1993

Energy Technology Data Exchange (ETDEWEB)

1993-10-20

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data in this report are presented for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The EIA collected the information in this report to fulfill its data collection and dissemination responsibilities as specified in the Federal Energy Administration Act of 1974 (Public Law 93-275) as amended. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. Statistics by company and plant are published in the EPM on the capability of new generating units, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fossil fuels.

Exploiting the Modified Colombo-Nyquist Rule for Co-estimating Sub-monthly Gravity Field Solutions from a GRACE-like Mission

Science.gov (United States)

Devaraju, B.; Weigelt, M.; Mueller, J.

2017-12-01

In order to suppress the impact of aliasing errors on the standard monthly GRACE gravity-field solutions, co-estimating sub-monthly (daily/two-day) low-degree solutions has been suggested as a solution. The maximum degree of the low-degree solutions is chosen via the Colombo-Nyquist rule of thumb. However, it is now established that the sampling of satellites puts a restriction on the maximum estimable order and not the degree - modified Colombo-Nyquist rule. Therefore, in this contribution, we co-estimate low-order sub-monthly solutions, and compare and contrast them with the low-degree sub-monthly solutions. We also investigate their efficacies in dealing with aliasing errors.

Reckoning Informal Politics: Expands the Logic of Survival and Failure of Regional Heads

Directory of Open Access Journals (Sweden)

Wawan Sobari

2018-01-01

Full Text Available The qualitative research addresses the political logic of why and how the incumbents succeed and fail in direct election for regional heads (pilkada in emerging democratic Indonesia. De Mesquita et al. (2003 believe that, to survive in office, a leader needs to offer a benefit at least equal to the greatest possible benefit offered by a potential challenger. Particular to the pilkada cases in Indonesia, Erb and Sulistiyanto (2009 elaborate several factors connected to “reward and punishment” logic that may lead to the incumbents’ survival and failure in re-election bids. This study expands the logic by revealing that populism, rivalry, and tangibility are the core strategies for the successful incumbents in retaining their offices in four rural and urban regions in East Java. Particularly, the survival of an incumbent hinges on his capacity to manage rivalry risks, namely the capability to manage support and opposition both from formal and informal actors through fair or unfair means. These strategies, then, foster the success of patronage-based winning tactics to retain public office in the pilkada. To better assessment, it calls for the importance of democratic accountability as a complementary perspective (to consolidology in measuring the progress of democracy in the country. 

Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

International Nuclear Information System (INIS)

Hu Xiaoqu; Su Fengxi; Qin Li; Jia Weijuan; Gong Chang; Yu Fengyan; Guo Jujiang; Song Erwei

2006-01-01

Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy

Estrogen receptor beta in prostate cancer: friend or foe?

Science.gov (United States)

Nelson, Adam W; Tilley, Wayne D; Neal, David E; Carroll, Jason S

2014-08-01

Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research. © 2014 Society for Endocrinology.

Foreshock-like density cavity in the outflow region of magnetotail reconnection

Directory of Open Access Journals (Sweden)

C. L. Cai

2009-08-01

Full Text Available During Cluster spacecraft crossing of the magnetotail, a novel density depleted cavity in association with magnetic compressions in the outflow region of reconnection was observed. It contains intense reflected field-aligned particles, which are produced by a generation mechanism similar to that of the terrestrial foreshock, and hence manifests a foreshock-like morphology. In this cavity, reflected field-aligned proton beams were observed and simultaneously the feature of magnetic-mirror loss-cone proton distributions were found. Magnetic field fluctuations, especially quasi-monochromatic oscillations, were recorded. Both the leading egde and the ULF wave boundary of the ion foreshock are identified from the time sequence of proton and magnetic field observations. Just upstream of the leading egde of the ion foreshock, reflected field-aligned electrons were detected, whose distribution has a narrow bump-on-tail pattern. However, close to the shock front, reflected electrons with a broad bump-on-tail pattern was measured. These two different manifestations of reflected electrons reveal the differences in their microscopic physics of the reflecting process. Moreover, a part of incident ions was further accelerated in the cavity due to trans-time magnetic pumping which provides another possible mechanism in the multi-step acceleration processes in reconnection.

Electric power monthly, July 1994

Energy Technology Data Exchange (ETDEWEB)

1994-07-01

The Electric Power Monthly (EPM) presents monthly electricity statistics. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data in this report are presented for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The EIA collected the information in this report to fulfill its data collection and dissemination responsibilities as specified in the Federal Energy Administration Act of 1974 (Public Law 93-275) as amended. The EPM is prepared by the Survey Management Division; Office of Coal, Nuclear, Electric and Alternate Fuels, Energy Information Administration (EIA), Department of Energy. This publication provides monthly statistics at the US, Census division, and State levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity sales, revenue, and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. Statistics by company and plant are published in the EPM on the capability of new generating units, net generation, fuel consumption, fuel stocks, quantity and quality of fuel, and cost of fossil fuels. Data on quantity, quality, and cost of fossil fuels lag data on net generation, fuel consumption, fuel stocks, electricity sales, and average revenue per kilowatthour by 1 month. This difference in reporting appears in the US, Census division, and State level tables. However, for purposes of comparison, plant-level data are presented for the earlier month.

Regionalizing Africa: Patterns of Precipitation Variability in Observations and Global Climate Models

Science.gov (United States)

Badr, Hamada S.; Dezfuli, Amin K.; Zaitchik, Benjamin F.; Peters-Lidard, Christa D.

2016-01-01

Many studies have documented dramatic climatic and environmental changes that have affected Africa over different time scales. These studies often raise questions regarding the spatial extent and regional connectivity of changes inferred from observations and proxies and/or derived from climate models. Objective regionalization offers a tool for addressing these questions. To demonstrate this potential, applications of hierarchical climate regionalizations of Africa using observations and GCM historical simulations and future projections are presented. First, Africa is regionalized based on interannual precipitation variability using Climate Hazards Group Infrared Precipitation with Stations (CHIRPS) data for the period 19812014. A number of data processing techniques and clustering algorithms are tested to ensure a robust definition of climate regions. These regionalization results highlight the seasonal and even month-to-month specificity of regional climate associations across the continent, emphasizing the need to consider time of year as well as research question when defining a coherent region for climate analysis. CHIRPS regions are then compared to those of five GCMs for the historic period, with a focus on boreal summer. Results show that some GCMs capture the climatic coherence of the Sahel and associated teleconnections in a manner that is similar to observations, while other models break the Sahel into uncorrelated subregions or produce a Sahel-like region of variability that is spatially displaced from observations. Finally, shifts in climate regions under projected twenty-first-century climate change for different GCMs and emissions pathways are examined. A projected change is found in the coherence of the Sahel, in which the western and eastern Sahel become distinct regions with different teleconnections. This pattern is most pronounced in high-emissions scenarios.

Modeling of air currents in the Gulf Region

International Nuclear Information System (INIS)

Sullivan, T.J.; Ellis, J.S.; Foster, C.S.; Foster, K.T.; Baskett, R.L.; Nasstrom, J.S.; Schalk, W.W.

1992-01-01

The Atmospheric Release Advisory Capability modeled the wind flow in the Gulf Region in order to make projections of the Kuwait oil fires pollution dispersion. Extensive meteorological models incorporating explicit terrain influences to the flow fields were routinely employed through a six month international assessment support effort organized by the World Meteorological Organization and US scientific research agencies. Results show generally close agreement with visible imagery of the smoke plumes as detected by meteorological satellites. However, there are some examples of significant disagreement or failure of the meteorological models. These failures are most likely directly linked to missing or unavailable weather observations

Atmospheric water budget over the South Asian summer monsoon region

Science.gov (United States)

Unnikrishnan, C. K.; Rajeevan, M.

2018-04-01

High resolution hybrid atmospheric water budget over the South Asian monsoon region is examined. The regional characteristics, variability, regional controlling factors and the interrelations of the atmospheric water budget components are investigated. The surface evapotranspiration was created using the High Resolution Land Data Assimilation System (HRLDAS) with the satellite-observed rainfall and vegetation fraction. HRLDAS evapotranspiration shows significant similarity with in situ observations and MODIS satellite-observed evapotranspiration. Result highlights the fundamental importance of evapotranspiration over northwest and southeast India on atmospheric water balance. The investigation shows that the surface net radiation controls the annual evapotranspiration over those regions, where the surface evapotranspiration is lower than 550 mm. The rainfall and evapotranspiration show a linear relation over the low-rainfall regions (forcing (like surface net radiation). The lead and lag correlation of water budget components show that the water budget anomalies are interrelated in the monsoon season even up to 4 months lead. These results show the important regional interrelation of water budget anomalies on south Asian monsoon.

Monthly Electrical Energy Overview September 2017

International Nuclear Information System (INIS)

2017-10-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for September 2017. Gross domestic demand increased slightly compared to September 2016, despite a monthly average temperature of less than 3.4 deg. C. The monthly balance of trade was positive (i.e. France was a net exporter) and increased by 73% compared to September 2016. Total demand corrected for climate contingencies remained stable. Demand by large industry continued its upward trend. Nuclear generation was up 11% compared to September 2016 and reached 29.3 TWh. Wind power production increased 66% compared to September 2016. The Greoux-les-Bains photovoltaic plant was connected to the public electricity transmission network. The plant has a generating power of 70 MW. The Grand-Est and Hauts-de-France regions really benefited from the strong winds observed across France. They thus contributed the most to the record levels of solar and wind generation recorded in September. Market prices were up in most European countries despite a notable decline in week 37. The monthly balance of trade remained exporter. 15 new installations went into service in September

Wave like signatures in aerosol optical depth and associated radiative impacts over the central Himalayan region

Energy Technology Data Exchange (ETDEWEB)

Shukla, K. K.; Phanikumar, D. V.; Kumar, K.  Niranjan; Reddy, Kishore; Kotamarthi, V. R.; Newsom, Rob K.; Ouarda, Taha B. M. J.

2015-10-01

Doppler Lidar and Multi-Filter Rotating Shadowband Radiometer (MFRSR) observations are utilized to show wave like signatures in aerosol optical depth (AOD) during daytime boundary layer evolution over the Himalayan region. Fourier analysis depicted 60–80 min periods dominant during afternoon hours, implying that observed modulations could be plausible reason for the AOD forenoon–afternoon asymmetry which was previously reported. Inclusion of wave amplitude in diurnal variation of aerosol radiative forcing estimates showed ~40% additional warming in the atmosphere relative to mean AOD. The present observations emphasize the importance of wave induced variations in AOD and radiation budget over the site.

[Expression of erythroblastic leukemia viral oncogene homolog 3 (ErbB-3) binding protein-1, matrix metalloproteinases, eplthelial cadherin in adenoid cystic carcinoma and correlation analysis].

Science.gov (United States)

Sun, Jian; Yu, You-cheng; Luo, Yi-xi; Tian, Zhen

2012-12-01

To investigate the expression of ErbB-3 binding protein-1 (EBP-1), matrix metalloproteinase 9 (MMP-9) and E-cadherin (E-cad) in adenoid cystic carcinoma and their correlation. Immunohistochemistry(PV6000 method) was used to detect EBP-1, MMP-9 and E-cad expression in 66 cases of adenoid cystic carcinoma tissues and matched para-cancerous normal tissues. In this study all cases were successfully followed up. The positive expression rate of EBP-1 in adenoid cystic carcinoma tissues was 85%. EBP-1 expression was significantly correlated to pathological pattern and clinical stage (P correlation between EBP-1 and E-cad expression, and positive correlation between EBP-1 and MMP-9. EBP-1 and its correlation with MMP-9 and E-cad may be used as useful indicators for clinical assessment of tumor biological behavior and prognosis in patients with adenoid cystic carcinoma.

Detection of blaOXA-23-like and blaNDM-1 in Acinetobacter baumannii from the Eastern Region, Saudi Arabia.

Science.gov (United States)

El-Mahdy, Taghrid S; Al-Agamy, Mohamed H; Al-Qahtani, Ahmed A; Shibl, Atef M

2017-01-01

Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored bla OXA-23-like and ISAba1 and 9 of them also carried bla ADC . Three isolates of 10 harbored bla NDM-1 coding for NDM metallo-β-lactamase (MBL) with coexistence of bla ADC together with either bla GES or bla TEM or both. Those three isolates exhibited negative Etest MBL screening test. Pulsed-field gel electrophoresis revealed the high clonal variability of the isolates, although two isolates were indistinguishable. The risk of dissemination of carbapenem resistance through presence of ISAba1 upstream of OXA-23-like in all isolates raises the concern about emergence of higher carbapenem prevalence rates in the future in our region. This study also demonstrated the importance of molecular surveillance to provide accurate and reliable data about the resistance rates of A. baumannii. Finally, the high incidence of NDM-1 among our isolates requires a routine surveillance to monitor the future prevalence of this enzyme in the region.

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

Science.gov (United States)

Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

2016-01-01

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

Self-organizing map network-based precipitation regionalization for the Tibetan Plateau and regional precipitation variability

Science.gov (United States)

Wang, Nini; Yin, Jianchuan

2017-12-01

A precipitation-based regionalization for the Tibetan Plateau (TP) was investigated for regional precipitation trend analysis and frequency analysis using data from 1113 grid points covering the period 1900-2014. The results utilizing self-organizing map (SOM) network suggest that four clusters of precipitation coherent zones can be identified, including the southwestern edge, the southern edge, the southeastern region, and the north central region. Regionalization results of the SOM network satisfactorily represent the influences of the atmospheric circulation systems such as the East Asian summer monsoon, the south Asian summer monsoon, and the mid-latitude westerlies. Regionalization results also well display the direct impacts of physical geographical features of the TP such as orography, topography, and land-sea distribution. Regional-scale annual precipitation trend as well as regional differences of annual and seasonal total precipitation were investigated by precipitation index such as precipitation concentration index (PCI) and Standardized Anomaly Index (SAI). Results demonstrate significant negative long-term linear trends in southeastern TP and the north central part of the TP, indicating arid and semi-arid regions in the TP are getting drier. The empirical mode decomposition (EMD) method shows an evolution of the main cycle with 4 and 12 months for all the representative grids of four sub-regions. The cross-wavelet analysis suggests that predominant and effective period of Indian Ocean Dipole (IOD) on monthly precipitation is around ˜12 months, except for the representative grid of the northwestern region.

Regional regression equations for the estimation of selected monthly low-flow duration and frequency statistics at ungaged sites on streams in New Jersey

Science.gov (United States)

Watson, Kara M.; McHugh, Amy R.

2014-01-01

Regional regression equations were developed for estimating monthly flow-duration and monthly low-flow frequency statistics for ungaged streams in Coastal Plain and non-coastal regions of New Jersey for baseline and current land- and water-use conditions. The equations were developed to estimate 87 different streamflow statistics, which include the monthly 99-, 90-, 85-, 75-, 50-, and 25-percentile flow-durations of the minimum 1-day daily flow; the August–September 99-, 90-, and 75-percentile minimum 1-day daily flow; and the monthly 7-day, 10-year (M7D10Y) low-flow frequency. These 87 streamflow statistics were computed for 41 continuous-record streamflow-gaging stations (streamgages) with 20 or more years of record and 167 low-flow partial-record stations in New Jersey with 10 or more streamflow measurements. The regression analyses used to develop equations to estimate selected streamflow statistics were performed by testing the relation between flow-duration statistics and low-flow frequency statistics for 32 basin characteristics (physical characteristics, land use, surficial geology, and climate) at the 41 streamgages and 167 low-flow partial-record stations. The regression analyses determined drainage area, soil permeability, average April precipitation, average June precipitation, and percent storage (water bodies and wetlands) were the significant explanatory variables for estimating the selected flow-duration and low-flow frequency statistics. Streamflow estimates were computed for two land- and water-use conditions in New Jersey—land- and water-use during the baseline period of record (defined as the years a streamgage had little to no change in development and water use) and current land- and water-use conditions (1989–2008)—for each selected station using data collected through water year 2008. The baseline period of record is representative of a period when the basin was unaffected by change in development. The current period is

Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer

Directory of Open Access Journals (Sweden)

Richard L. Schroeder

2014-09-01

Full Text Available The human epidermal growth factor receptor 2 (HER2 is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin® and lapatinib (Tyverb/Tykerb®, a monoclonal antibody inhibitor and a dual EGFR/HER2 kinase inhibitor, respectively, are currently used in the treatment of HER2-positive cancers, although issues with high recurrence and acquired resistance still remain. Small molecule tyrosine kinase inhibitors provide attractive therapeutic targets, as they are able to block cell signaling associated with many of the proposed mechanisms for HER2 resistance. In this regard we aim to present a review on the available HER2 tyrosine kinase inhibitors, as well as those currently in development. The use of tyrosine kinase inhibitors as sequential or combinatorial therapeutic strategies with other HER family inhibitors is also discussed.

Solar-like Oscillations in KIC 11395018 and KIC 11234888 from 8 Months of Kepler Data

DEFF Research Database (Denmark)

Mathur, S.; Handberg, Rasmus; Campante, Tiago. L.

2011-01-01

We analyze the photometric short-cadence data obtained with the Kepler mission during the first 8 months of observations of two solar-type stars of spectral types G and F: KIC 11395018 and KIC 11234888, respectively, the latter having a lower signal-to-noise ratio (S/N) compared with the former. ...

Factors Associated with Fatal Outcomes Following Cholera-Like Syndrome in Far North Region of Cameroon: A Community-Based Survey.

Science.gov (United States)

Djouma, Fabrice N; Ateudjieu, Jerome; Ram, Malathi; Debes, Amanda K; Sack, David A

2016-12-07

This study demonstrates that most cholera deaths in this region of Cameroon occur out of hospital. This is a region which is prone to cholera, and interventions are needed to improve access to emergency medical care, especially during cholera outbreaks. Cameroon has experienced 14 cholera epidemics during the last 20 years, and these have had high case fatality rates. This study attempted to assess the effect of delays in seeking care and the locations of care as possible risk factors for cholera mortality. The study used data from a community-based survey regarding the circumstances of 97 fatal cases and 197 control (nonfatal) cases following a cholera-like syndrome in villages with cholera-like diseases during cholera outbreaks in Cameroon during 2009-2011. Deaths occurred in one of four environments: the community, in a temporary community treatment center (TCTC), in transit to a treatment center, or in a hospital (39%, 32%, 5%, and 24%, respectively). Using a case-control analysis, factors associated with deaths included the nonuse of a cholera treatment center, receiving health care in a TCTC instead of a hospital, and greater than 4 hours delay between the onset of symptoms and the decision to go to a treatment center (odds ratios of 17.1 [confidence interval (CI): 7.0-41.8], 2.5 [CI: 1.2-5.0], and 2.2 [CI: 1.0-4.6], respectively). During cholera epidemics, a higher proportion of deaths are still occurring in communities. The nonuse and delays in deciding to go a treatment center, and treatment at TCTC rather than a hospital were risk factors for death among patients with cholera-like syndrome in Cameroon. Informing people on community management of cholera-like syndrome and improving care in all health facilities are needed to reduce deaths during cholera epidemics. © The American Society of Tropical Medicine and Hygiene.

Defined MicroRNAs Induce Aspects of Maturation in Mouse and Human Embryonic-Stem-Cell-Derived Cardiomyocytes

Directory of Open Access Journals (Sweden)

Desy S. Lee

2015-09-01

Full Text Available Pluripotent-cell-derived cardiomyocytes have great potential for use in research and medicine, but limitations in their maturity currently constrain their usefulness. Here, we report a method for improving features of maturation in murine and human embryonic-stem-cell-derived cardiomyocytes (m/hESC-CMs. We found that coculturing m/hESC-CMs with endothelial cells improves their maturity and upregulates several microRNAs. Delivering four of these microRNAs, miR-125b-5p, miR-199a-5p, miR-221, and miR-222 (miR-combo, to m/hESC-CMs resulted in improved sarcomere alignment and calcium handling, a more negative resting membrane potential, and increased expression of cardiomyocyte maturation markers. Although this could not fully phenocopy all adult cardiomyocyte characteristics, these effects persisted for two months following delivery of miR-combo. A luciferase assay demonstrated that all four miRNAs target ErbB4, and siRNA knockdown of ErbB4 partially recapitulated the effects of miR-combo. In summary, a combination of miRNAs induced via endothelial coculture improved ESC-CM maturity, in part through suppression of ErbB4 signaling.

Maternal Education and Diarrhea among Children aged 0-24 Months in Nigeria.

Science.gov (United States)

Desmennu, Adeyimika T; Oluwasanu, Mojisola M; John-Akinola, Yetunde O; Oladunni, Opeyemi; Adebowale, Ayo S

2017-09-01

Childhood diarrhea remains a problem in countries like Nigeria where access to potable water, good hygiene and sanitation are lacking. Maternal education is an important determinant of health status of under-five children. Very few studies have investigated the relationship between maternal education and diarrhea in children in Nigeria. Therefore, this study was implemented to fill the gap. The study design was cross-sectional and 2013 National Survey was used. Children aged 0-24 months were investigated and the dependent variable was diarrhea status of the index child in the last two weeks prior the survey. The main independent variable was maternal education. Data were analyzed using Chi-square and Logistic regression models (α=0.05). Diarrhea prevalence was 13.7% and higher (15.5%) among children of women who have no formal education, and mothers living in the North East region of Nigeria experienced the highest prevalence (26.4%). Children whose mothers had no formal education were 2.69(CI= 1.800-4.015, p education. Maternal education is an important predictor of diarrhea among children aged 0-24 months in Nigeria. Policies to reduce diarrhea among children in Nigeria should target children of the illiterate, less educated mothers and those living in the North-West.

Family planning use and associated factors among pastoralist community of afar region, eastern Ethiopia.

Science.gov (United States)

Alemayehu, Mussie; Lemma, Hailemariam; Abrha, Kidan; Adama, Yohannes; Fisseha, Girmatsion; Yebyo, Henock; Gebeye, Ejigu; Negash, Kassahun; Yousuf, Jemal; Fantu, Tigist; Gebregzabher, Tesfay; Medhanyie, Araya Abrha

2016-07-18

Ethiopia is the second most populous country in Africa with a total fertility rate (TFR) of 4.8 children per a woman and contraceptive prevalence rate (CPR) of 29 %. The overall prevalence of modern family planning in a pastoralist community, like Afar region, is low (9.1 %). This study aimed to assess family planning utilization and associated factors among married women of Afar region, Eastern Ethiopia. A community-based cross-sectional study was conducted from January 10-28, 2013 among 602 women. Multistage sampling technique was used to select the study participants. Descriptive and multiple variable logistic regression analyses were done to isolate independent predictors on utilization of family planning using SPSS 20. The overall prevalence of family planning utilization in Afar region was 8.5 % (6.2-10.7). Majority of the women (92.2 %) had used injectable. The most common reasons mentioned in the non-use of family planning methods were religion-related (85.3 %), desire to have more children (75.3 %), and husband's objection (70.1 %). Women who had a positive attitude towards family planning utilization (AOR = 4.7, 95 % CI: 2.1, 10.3), owning radio (AOR = 1.8, 95 % CI: 1.02, 4.18), and literate (AOR = 4.4, 95 % CI: 1.80, 11.08) were more likely to use family planning methods as compared to their counterparts. The increase of monthly income was also associated with the likelihood of family planning methods utilization. The odds of using family planning methods were higher among those with monthly income of $27-$55.5 (AOR = 2. 0, 95 % CI: 1.9, 4.7) and > $55 (AOR = 4. 6, 95 % CI: 1.23-17.19) as compared to women with the lowest category of monthly income ($27 and less). The low coverage of family planning in the region could be due to the influence of husband, religious and clan leader. Attitude of women towards family planning methods, possession of radio, monthly income, and educational status could influence family

The effect of an endorectal balloon and off-line correction on the interfraction systematic and random prostate position variations: A comparative study

International Nuclear Information System (INIS)

Lin, Emile van; Vight, Lisette van der; Witjes, J. Alfred; Huisman, HenkJan J.; Leer, Jan Willem; Visser, Andries G.

2005-01-01

Purpose: To investigate the effect of an endorectal balloon (ERB) and an off-line correction protocol on the day-to-day, interfraction prostate gland motion, in patients receiving external beam radiotherapy for prostate cancer. Methods and materials: In 22 patients, irradiated with an ERB in situ (ERB group) and in 30 patients without an ERB (No-ERB group), prostate displacements were measured daily in three orthogonal directions with portal images. Implanted gold markers and an off-line electronic portal imaging correction protocol were used for prostate position verification and correction. Movie loops were analyzed to evaluate prostate motion and rectal filling variations. Results: The off-line correction protocol reduced the systematic prostate displacements, equally for the ERB and No-ERB group, to 1.3-1.8 mm (1 SD). The mean 3D displacement was reduced to 2.8 mm and 2.4 mm for the ERB and No-ERB group, respectively. The random interfraction displacements, relative to the treatment isocenter, were not reduced by the ERB and remained nearly unchanged in all three directions: 3.1 mm (1 SD) left-right, 2.6 mm (1 SD) superior-inferior, and 4.7 mm (1 SD) for the anterior-posterior direction. These day-to-day prostate position variations can be explained by the presence of gas and stool beside the ERB. Conclusions: The off-line corrections on the fiducial markers are effective in reducing the systematic prostate displacements. The investigated ERB does not reduce the interfraction prostate motion. Although the overall mean displacement is low, the day-to-day interfraction motion, especially in anterior-posterior direction, remains high compared with the systematic displacements

Wave like signatures in aerosol optical depth and associated radiative impacts over the central Himalayan region

Energy Technology Data Exchange (ETDEWEB)

Shukla, K. K.; Phanikumar, D. V.; Kumar, K.  Niranjan; Reddy, Kishore; Kotamarthi, V. R.; Newsom, Rob K.; Ouarda, Taha B. M. J.

2015-10-01

In this study, we present a case study on 16 October 2011 to show the first observational evidence of the influence of short period gravity waves in aerosol transport during daytime over the central Himalayan region. The Doppler lidar data has been utilized to address the daytime boundary layer evolution and related aerosol dynamics over the site. Mixing layer height is estimated by wavelet covariance transform method and found to be ~ 0.7 km, AGL. Aerosol optical depth observations during daytime revealed an asymmetry showing clear enhancement during afternoon hours as compared to forenoon. Interestingly, Fourier and wavelet analysis of vertical velocity and attenuated backscatter showed similar 50-90 min short period gravity wave signatures during afternoon hours. Moreover, our observations showed that gravity waves are dominant within the boundary layer implying that the daytime boundary layer dynamics is playing a vital role in transporting the aerosols from surface to the top of the boundary layer. Similar modulations are also evident in surface parameters like temperature, relative humidity and wind speed indicating these waves are associated with the dynamical aspects over Himalayan region. Finally, time evolution of range-23 height indicator snapshots during daytime showed strong upward velocities especially during afternoon hours implying that convective processes through short period gravity waves plays a significant role in transporting aerosols from the nearby valley region to boundary layer top over the site. These observations also establish the importance of wave induced daytime convective boundary layer dynamics in the lower Himalayan region.

The Relationships between Tropical Pacific and Atlantic SST and Northeast Brazil Monthly Precipitation.

Science.gov (United States)

Bertacchi Uvo, Cintia; Repelli, Carlos A.; Zebiak, Stephen E.; Kushnir, Yochanan

1998-04-01

The monthly patterns of northeast Brazil (NEB) precipitation are analyzed in relation to sea surface temperature (SST) in the tropical Pacific and Atlantic Oceans, using singular value decomposition. It is found that the relationships between precipitation and SST in both basins vary considerably throughout the rainy season (February-May). In January, equatorial Pacific SST is weakly correlated with precipitation in small areas of southern NEB, but Atlantic SST shows no significant correlation with regional precipitation. In February, Pacific SST is not well related to precipitation, but south equatorial Atlantic SST is positively correlated with precipitation over the northern Nordeste, the latter most likely reflecting an anomalously early (or late) southward migration of the ITCZ precipitation zone. During March, equatorial Pacific SST is negatively correlated with Nordeste precipitation, but no consistent relationship between precipitation and Atlantic SST is found. Atlantic SST-precipitation correlations for April and May are the strongest found among all months or either ocean. Precipitation in the Nordeste is positively correlated with SST in the south tropical Atlantic and negatively correlated with SST in the north tropical Atlantic. These relationships are strong enough to determine the structure of the seasonal mean SST-precipitation correlations, even though the corresponding patterns for the earlier months of the season are quite different. Pacific SST-precipitation correlations for April and May are similar to those for March. Extreme wet (dry) years for the Nordeste occur when both Pacific and Atlantic SST patterns for April and May occur simultaneously. A separate analysis reinforces previous findings in showing that SST in the tropical Pacific and the northern tropical Atlantic are positively correlated and that tropical Pacific-south Atlantic correlations are negligible.Time-lagged analyses show the potential for forecasting either seasonal mean

Petroleum supply monthly, March 1994

Energy Technology Data Exchange (ETDEWEB)

1994-03-30

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the United States and major US geographic regions. The data series describe production, imports and exports, inter-Petroleum Administration for Defense (PAD) District movements, and inventories by the primary suppliers of petroleum products in the United States (50 States and the District of Columbia). The reporting universe includes those petroleum sectors in primary supply. Included are: petroleum refiners, motor gasoline blenders, operators of natural gas processing plants and fractionators, inter-PAD transporters, importers, and major inventory holders of petroleum products and crude oil. When aggregated, the data reported by these sectors approximately represent the consumption of petroleum products in the United States. Data presented in the PSM are divided into two sections: Summary Statistics and Detailed Statistics. The tables and figures in the Summary Statistics section of the PSM present a time series of selected petroleum data on a US level. Most time series include preliminary estimates for one month based on the Weekly Petroleum Supply Reporting System; statistics based on the most recent data from the Monthly Petroleum Supply Reporting System (MPSRS); and statistics published in prior issues of the PSM and PSA. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. In most cases, the statistics are presented for several geographic areas -- the United States (50 States and the District of Columbia), five PAD Districts, and 12 Refining Districts. At the US and PAD District level, the total volume and the daily rate of activities are presented. The statistics are developed from monthly survey forms submitted by respondents to the EIA and from data provided from other sources.

Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1 deficient mice

Directory of Open Access Journals (Sweden)

Lee Myounghee

2008-12-01

Full Text Available Abstract Background The ErbB3 binding protein-1 (Ebp1 belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4 gene. Results Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues. Conclusion These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.

Regional and seasonal analyses of weights in growing Angus cattle.

Science.gov (United States)

Bradford, H L; Fragomeni, B O; Bertrand, J K; Lourenco, D A L; Misztal, I

2016-10-01

This study evaluated the impact of region and season on growth in Angus seed stock. To assess geographic differences, the United States was partitioned into 9 regions based on similar climate and topography related to cow-calf production. Seasonal effects were associated with the month that animals were weighed. The American Angus Association provided growth data, and records were assigned to regions based on the owner's zip code. Most Angus cattle were in the Cornbelt, Lower Plains, Rocky Mountain, Upper Plains, and Upper South regions, with proportionally fewer Angus in Texas compared with the national cow herd. Most calves were born in the spring, especially February and March. Weaning weights (WW; = 49,886) and yearling weights (YW; = 45,168) were modeled with fixed effects of age-of-dam class (WW only), weigh month, region, month-region interaction, and linear covariate of age. Random effects included contemporary group nested within month-region combination and residual. The significant month-region interaction ( Angus seed stock producers have used calving seasons to adapt to the specific environmental conditions in their regions and to optimize growth in young animals.

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

Institute of Scientific and Technical Information of China (English)

HMC Shantha Kumara; David Gaita; Hiromichi Miyagaki; Xiaohong Yan; Sonali AC Hearth; Linda Njoh; Vesna Cekic; Richard L Whelan

2016-01-01

AIM: To assess blood chitinase 3-like 1(CHi3L1) levels for 2 mo after minimally invasive colorectal resection(MICR) for colorectal cancer(CRC). METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative(PreO p), early postoperative(PostO p), and 1 or more late PostO p samples [postoperative day(POD) 7-27] available were included. Plasma CHi3L1 levels(ng/m L) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL(n = 80). Significantly elevated(P < 0.001) median plasma levels(ng/mL) over PreOp levels were detected on POD1(667.7 CI: 495.7, 771.7; n = 79), POD 3(132.6 CI: 95.5, 173.7; n = 76), POD7-13(96.4 CI: 67.7, 136.9; n = 62), POD14-20(101.4 CI: 80.7, 287.4; n = 22), and POD 21-27(98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.

Thermal Orbital Environmental Parameter Study on the Propulsive Small Expendable Deployer System (ProSEDS) Using Earth Radiation Budget Experiment (ERBE) Data

Science.gov (United States)

Sharp, John R.; McConnaughey, Paul K. (Technical Monitor)

2002-01-01

The natural thermal environmental parameters used on the Space Station Program (SSP 30425) were generated by the Space Environmental Effects Branch at NASA's Marshall Space Flight Center (MSFC) utilizing extensive data from the Earth Radiation Budget Experiment (ERBE), a series of satellites which measured low earth orbit (LEO) albedo and outgoing long-wave radiation. Later, this temporal data was presented as a function of averaging times and orbital inclination for use by thermal engineers in NASA Technical Memorandum TM 4527. The data was not presented in a fashion readily usable by thermal engineering modeling tools and required knowledge of the thermal time constants and infrared versus solar spectrum sensitivity of the hardware being analyzed to be used properly. Another TM was recently issued as a guideline for utilizing these environments (NASA/TM-2001-211221) with more insight into the utilization by thermal analysts. This paper gives a top-level overview of the environmental parameters presented in the TM and a study of the effects of implementing these environments on an ongoing MSFC project, the Propulsive Small Expendable Deployer System (ProSEDS), compared to conventional orbital parameters that had been historically used.

Age-and Brain Region-Specific Differences in Mitochondrial ...

Science.gov (United States)

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

Refinement of glucagon-like peptide 1 docking to its intact receptor using mid-region photolabile probes and molecular modeling.

Science.gov (United States)

Miller, Laurence J; Chen, Quan; Lam, Polo C-H; Pinon, Delia I; Sexton, Patrick M; Abagyan, Ruben; Dong, Maoqing

2011-05-06

The glucagon-like peptide 1 (GLP1) receptor is an important drug target within the B family of G protein-coupled receptors. Its natural agonist ligand, GLP1, has incretin-like actions and the receptor is a recognized target for management of type 2 diabetes mellitus. Despite recent solution of the structure of the amino terminus of the GLP1 receptor and several close family members, the molecular basis for GLP1 binding to and activation of the intact receptor remains unclear. We previously demonstrated molecular approximations between amino- and carboxyl-terminal residues of GLP1 and its receptor. In this work, we study spatial approximations with the mid-region of this peptide to gain insights into the orientation of the intact receptor and the ligand-receptor complex. We have prepared two new photolabile probes incorporating a p-benzoyl-l-phenylalanine into positions 16 and 20 of GLP1(7-36). Both probes bound to the GLP1 receptor specifically and with high affinity. These were each fully efficacious agonists, stimulating cAMP accumulation in receptor-bearing CHO cells in a concentration-dependent manner. Each probe specifically labeled a single receptor site. Protease cleavage and radiochemical sequencing identified receptor residue Leu(141) above transmembrane segment one as its site of labeling for the position 16 probe, whereas the position 20 probe labeled receptor residue Trp(297) within the second extracellular loop. Establishing ligand residue approximation with this loop region is unique among family members and may help to orient the receptor amino-terminal domain relative to its helical bundle region.

SNAP Participants' Eating Patterns over the Benefit Month: A Time Use Perspective.

Science.gov (United States)

Hamrick, Karen S; Andrews, Margaret

2016-01-01

Individuals receiving monthly benefits through the U.S. Supplemental Nutrition Assistance Program (SNAP) often fall short of food at the end of the month and some report feelings of hunger. To investigate this situation, we used time diaries from the 2006-08 American Time Use Survey and Eating & Health Module to identify the timing of days where respondents reported no eating occurrences. Analysis includes descriptive statistics, a logit model, and a simulated benefit month. We found that SNAP participants were increasingly more likely than nonparticipants to report a day with no eating occurrences over the benefit issuance cycle. This supports the view that there is a monthly cycle in food consumption associated with the SNAP monthly benefit issuance policy.

A Month of Breastfeeding Associated with Greater Adherence to Pediatric Nutrition Guidelines.

Science.gov (United States)

Khalessi, Ali; Reich, Stephanie M

2013-07-01

Research has shown that both breastfeeding and delaying the introduction of solids or liquids other than breast milk protect against obesity later in early childhood. To compare whether breastfeeding mothers adhere to more of the American Academy of Pediatrics (AAP) feeding recommendations for infants. This longitudinal study compared the breastfeeding knowledge, intentions, and practices as well as complementary feeding choices of 163 ethnically diverse, primiparous women over the first 18 months of motherhood. Although almost all women knew about the health benefits of (98%) breastfeeding and intended to (98%) breastfeed, only 85% initiated and 51% continued beyond 4 weeks. Breastfeeding for longer durations was associated with better feeding choices. Mothers who breastfed for more weeks were more likely to adhere to AAP guidelines on liquids other than breast milk at 4, 6, and 12 months, and introduce solids, liquids other than breast milk, and other complimentary foods at later ages. Furthermore, mothers who breastfed for less than 1 month were more likely to introduce solids by 2 months in comparison to mothers who breastfed for 1 month or more (OR=3.22). Knowledge and intentions do not explain breastfeeding initiation or continuation. However, when women committed to more weeks of breastfeeding, especially more than 4 weeks, they made better nutrition choices for their infants.

Tumors and tumor - like lesions of the oro - facial region at Mayo hospital, Lahore - a five year study

International Nuclear Information System (INIS)

Riaz, N.; Warriach, R.A.

2011-01-01

The oro-facial region including the oral cavity, the maxilla and mandible and related tissues can be the site of a multitude of neoplastic conditions. These tumours have a predilection for the entire facial region; however, odontogenic tumours tend to affect the mandible more than the maxilla. We report results from a retrospective study spanning five years on the frequency, clinical presentation, sites and character of orofacial tumors seen in the main referral hospital of Pakistan. Patients and Methods: Records of consecutive patients of all age and sex seen by the author's team at the Department of Oral and Maxillofacial Surgery, Mayo Hospital with tumours affecting the oro-facial region from January 2005 to December 2009 were retrieved, coded and entered into a database. The data were then analyzed by age, sex, presenting signs and symptoms, site of lesion, and their histology. Results: A total of 237 patients with oro-facial swellings were retrieved from the registry. The complete data set was obtained for 189 patients, comprising 108 (57.9%) males and 81 (42%) females. The most common clinical presenting features were mandibular facial swelling (63%), intra-oral swelling (55%), and ulceration (29%). The tumors were found in the mandible 67 (35%), buccal mucosa 33 (17%), floor of the mouth 22 (11%) and tongue 29 (15%). The remainder making up almost 20% was found in the palate, submandibular region, pre auricular region and lips. Ninety three (49.2%) of the patients presented with lesions that were classified as malignant of which 64 (69%) were diagnosed as squamous cell carcinoma (SCC). seventy (37.0%) had benign odontogenic tumors and twenty six (13.7%) had non-odontogenic tumor - like lesions. Sixty - four (69%) of malignant tumors were squamous cell carcinoma; sixty four (86.4%) of the benign odontogenic tumors were classified as ameloblastoma. The mean age at presentation of all lesions was 40.4 years with over 50% of benign lesions in patients aged

Nutritional status, exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia.

Science.gov (United States)

Oktaria, V; Lee, K J; Bines, J E; Watts, E; Satria, C D; Atthobari, J; Nirwati, H; Kirkwood, C D; Soenarto, Y; Danchin, M H

2017-12-21

Infant morbidity and mortality rates remain high in Indonesia, with acute respiratory illnesses (ARI) and diarrhea the leading two health problems in children under 5 years. We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants from two regions of Indonesia during the first 6 months of life. This study was an observational study conducted in parallel to an immunogenicity and efficacy trial of an oral rotavirus vaccine (RV3-BB) in the Klaten and Yogyakarta regions, Indonesia. Mothers were interviewed at 3 time points: within the first 6 days of their infant's life, and at 8-10 and 22-24 weeks of age. Questions asked included pregnancy history, infant nutritional status, feeding status and health of infants within up to 2 weeks prior to the assessment. Between February 2013 and January 2014, 233 mother-infant pairs were recruited. 60% (136/223) of infants were exclusively breastfed (EBF) until 6 months of age with the strongest support for EBF reported by mothers themselves 70% (101/223) and 25% (36/223) from their partners. At 6 months, 6% (14/223) of infants were underweight and severely underweight; 4% (8/ 223) wasted and severely wasted; and 12% (28/223) were stunted and severely stunted. Non-recommended medication use was high, with 54% (21/39) of infants with reported cough within 2 weeks of an assessment receiving cough medication, 70% (27 /39) an antihistamine, 26% (10/39) a mucolytic and 15% (6 /39) an oral bronchodilator. At age 22-24 week, infants with reported diarrhea within 2 weeks of an assessment had low use of oral rehydration solutions (ORS) (3/21;14%) and zinc therapy (2/ 21;10%). In this unique observational study, breastfeeding rates of 60% at 6 months were below the Indonesian national target of >75%. Adherence to WHO guidelines for management of ARI and diarrhea was poor, with high use of non-recommended cough medications and oral bronchodilators in the first 6 months of life

A Holistic In silico Approach to Develop Novel Inhibitors Targeting ...

African Journals Online (AJOL)

Purpose: To design a dual inhibitor of natural origin capable of targeting ErbB1 and ErbB2 kinases for the treatment of lung cancer. Method: Advanced In silico drug designing techniques were explored in this study. Sequence and structure analysis of ErbB1 and ErbB2 was followed by three dimensional (3D) ...

Monthly Electrical Energy Overview June 2017

International Nuclear Information System (INIS)

2017-07-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for June 2017. Average temperatures in June increased by +2.7 deg. compared to June 2016. Demand in June increased by +1.76% compared to June 2016. Demand in June increased by 1.76% compared to June 2016, due in particular to the heat wave that occurred between 19 and 22. Hydraulic generation was again penalized by the lack of rainfall with a fall of 28.6% compared to June 2016. Solar generation was up by 26.7%, driven by the high amount of sunlight in the month. The heat wave had a strong impact on demand in the regions most affected by the high temperatures: Champagne-Ardenne, Pays de la Loire, Midi-Pyrenees. Market prices increased in the south of Europe. France imported more than it exported via Switzerland. Overall, French exchanges remained in favour of exports in the month. 14 new installations went into service in June

Electric power monthly, March 1998 with data for December 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

The Electric Power Monthly (EPM) provides monthly statistics at the State, Census division, and US levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity retail sales, associated revenue, and average revenue per kilowatthour of electricity sold. In addition, data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. 63 tabs.

The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas

Directory of Open Access Journals (Sweden)

Kandemir Nilufer

2010-02-01

Full Text Available Abstract Background Endometrial carcinoma (EC is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2 gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER and progesterone receptor (PR status. Methods Immunohistochemical (IHC analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. Results We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. Conclusions Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

Electronic cigarettes, quit attempts and smoking cessation: a 6-month follow-up.

Science.gov (United States)

Pasquereau, Anne; Guignard, Romain; Andler, Raphaël; Nguyen-Thanh, Viêt

2017-09-01

There is conflicting evidence that use of e-cigarettes promotes cessation in regular smokers, but contrasting findings may be due to differing definitions of vaping. The aim was to assess whether regular use of e-cigarettes while smoking is associated with subsequent smoking cessation. Baseline internet survey with outcomes measured at 6-month follow-up. All French metropolitan territory. A total of 2057 smokers aged 15-85 years were recruited through an access panel and responded to a 6-month follow-up: 1805 exclusive tobacco smokers and 252 dual users (tobacco plus regular e-cigarette users) at baseline. The three outcomes assessed at 6 months were: a minimum 50% reduction in the number of cigarettes smoked per day, quit attempts of at least 7 days and smoking cessation of at least 7 days at the time of follow-up. Logistic regressions were performed to model the three outcomes according to regular e-cigarette use at baseline, adjusted for socio-economic variables and smoking behaviours. Baseline dual users were more likely than baseline exclusive tobacco smokers to have halved cigarette consumption [25.9 versus 11.2%, P e-cigarette regularly are more likely to try to quit smoking and reduce their cigarette consumption during the next 6 months. It remains unclear whether regular e-cigarette users are also more likely to stop smoking. © 2017 Society for the Study of Addiction.

Electric Power Monthly with data for July 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-10-01

This publication provides monthly statistics at the state, census division, and U.S. levels for net generation; fossil fuel consumption and stocks, quantity, and quality of fossil fuels; cost of fossil fuels; electricity retail sales; associated revenue; and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council regions. Statistics on net generation are published by energy source; consumption, stocks, quantity, quality, and cost of fossil fuels; and capability of new generating units by company and plant. The monthly update is summarized, and industry developments are briefly described. 57 tabs.

Climate change increases the probability of heavy rains in Northern England/Southern Scotland like those of storm Desmond—a real-time event attribution revisited

Science.gov (United States)

Otto, Friederike E. L.; van der Wiel, Karin; van Oldenborgh, Geert Jan; Philip, Sjoukje; Kew, Sarah F.; Uhe, Peter; Cullen, Heidi

2018-02-01

On 4-6 December 2015, storm Desmond caused very heavy rainfall in Northern England and Southern Scotland which led to widespread flooding. A week after the event we provided an initial assessment of the influence of anthropogenic climate change on the likelihood of one-day precipitation events averaged over an area encompassing Northern England and Southern Scotland using data and methods available immediately after the event occurred. The analysis was based on three independent methods of extreme event attribution: historical observed trends, coupled climate model simulations and a large ensemble of regional model simulations. All three methods agreed that the effect of climate change was positive, making precipitation events like this about 40% more likely, with a provisional 2.5%-97.5% confidence interval of 5%-80%. Here we revisit the assessment using more station data, an additional monthly event definition, a second global climate model and regional model simulations of winter 2015/16. The overall result of the analysis is similar to the real-time analysis with a best estimate of a 59% increase in event frequency, but a larger confidence interval that does include no change. It is important to highlight that the observational data in the additional monthly analysis does not only represent the rainfall associated with storm Desmond but also that of storms Eve and Frank occurring towards the end of the month.

Monthly bulletin of electric power market - November 1988

International Nuclear Information System (INIS)

1988-01-01

This bulletin deals with the brazilian electric power consumption in November 1988, containing data about the total consumption, the growth rates, the special tariffs and monthly evolution in each brazilian region. The economic indexes of industrial production, the market and the prices of electric power and petroleum products are also presented. (C.G.C.)

Monthly bulletin of electric power market - July 1988

International Nuclear Information System (INIS)

1988-01-01

This bulletin deals with the brazilian electric power consumption in July 1988, containing data about the total consumption, the growth rates, the special tariffs and monthly evolution in each brazilian region. The economic indexes of industrial production, the market and the prices of electric power and petroleum products are also presented. (C.G.C.)

Monthly bulletin of electric power market - September 1988

International Nuclear Information System (INIS)

1988-01-01

This bulletin deals with the brazilian electric power consumption in September 1988, containing data about the total consumption, the growth rates, the special tariffs and monthly evolution in each brazilian region. The economic indexes of industrial production, the market and the prices of electric power and petroleum products are also presented. (C.G.C.)

Best pictures of the month

CERN Multimedia

Claudia Marcelloni de Oliveira

The last sector of the Big Muon Wheels was brought to the cavern in the morning of September 20... ... installed on one of the Big Muon Wheels during the same afternoon... ... just in time to sqeeze lots of people in between two of the all-completed Big Muon Wheels on the 21st of September to celebrate the installation of the last sector. Installation of the first ATLAS small wheel in building 191 on September 10. Some of the people involved in the construction and installation of the chambers on the first ATLAS small wheel in building 191 celebrating its completion on September 20. After hearing that the rock band The Police played in Geneva last month, Muriel got inspired and decided to become a rock star, just like one of her favorites, Keith Richards from the Rolling Stones. Special accomplishment of the month: (top) Martina Hurwitz (#908) and Monica Dunford (680), both from the Chicago University group, completed the Lausanne Marathon on October 21 in 4h 4...

Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study.

Directory of Open Access Journals (Sweden)

Lisha Zhu

Full Text Available Preeclampsia (PE is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC and 5-hydroxymethylcytosine (5hmC levels in the placentas of late-onset severe PE patients (n = 4 and normal controls (n = 4 using a (hydroxymethylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq, and the results were verified by (hMeDIP-qPCR. The most significant differentially methylated regions (DMRs were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20. Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, p<0.05. Further, only one gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different 5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.

SNAP Participants' Eating Patterns over the Benefit Month: A Time Use Perspective.

Directory of Open Access Journals (Sweden)

Karen S Hamrick

Full Text Available Individuals receiving monthly benefits through the U.S. Supplemental Nutrition Assistance Program (SNAP often fall short of food at the end of the month and some report feelings of hunger. To investigate this situation, we used time diaries from the 2006-08 American Time Use Survey and Eating & Health Module to identify the timing of days where respondents reported no eating occurrences. Analysis includes descriptive statistics, a logit model, and a simulated benefit month. We found that SNAP participants were increasingly more likely than nonparticipants to report a day with no eating occurrences over the benefit issuance cycle. This supports the view that there is a monthly cycle in food consumption associated with the SNAP monthly benefit issuance policy.

SNAP Participants’ Eating Patterns over the Benefit Month: A Time Use Perspective

Science.gov (United States)

2016-01-01

Individuals receiving monthly benefits through the U.S. Supplemental Nutrition Assistance Program (SNAP) often fall short of food at the end of the month and some report feelings of hunger. To investigate this situation, we used time diaries from the 2006–08 American Time Use Survey and Eating & Health Module to identify the timing of days where respondents reported no eating occurrences. Analysis includes descriptive statistics, a logit model, and a simulated benefit month. We found that SNAP participants were increasingly more likely than nonparticipants to report a day with no eating occurrences over the benefit issuance cycle. This supports the view that there is a monthly cycle in food consumption associated with the SNAP monthly benefit issuance policy. PMID:27410962

CERES Monthly TOA and SRB Averages (SRBAVG) data in HDF-EOS Grid (CER_SRBAVG_TRMM-PFM-VIRS_Edition2B)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Monthly TOA/Surface Averages (SRBAVG) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SRBAVG is also produced for combinations of scanner instruments. The monthly average regional flux is estimated using diurnal models and the 1-degree regional fluxes at the hour of observation from the CERES SFC product. A second set of monthly average fluxes are estimated using concurrent diurnal information from geostationary satellites. These fluxes are given for both clear-sky and total-sky scenes and are spatially averaged from 1-degree regions to 1-degree zonal averages and a global average. For each region, the SRBAVG also contains hourly average fluxes for the month and an overall monthly average. The cloud properties from SFC are column averaged and are included on the SRBAVG. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-02-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=1 degree; Longitude_Resolution=1 degree; Horizontal_Resolution_Range=100 km - < 250 km or approximately 1 degree - < 2.5 degrees; Temporal_Resolution=1 month; Temporal_Resolution_Range=Monthly - < Annual].

Monthly, global emissions of carbon dioxide from fossil fuel consumption

Energy Technology Data Exchange (ETDEWEB)

Andres, R. J.; Marland, G.; Boden, T. A. (Environmental Sciences Div., Oak Ridge National Laboratory, Oak Ridge, TN (United States)), e-mail: andresrj@ornl.gov; Gregg, J. S. (Risoe DTU National Laboratory for Sustainable Energy, Roskilde (Denmark)); Losey, L. (Dept. of Space Studies, Univ. of North Dakota, Grand Forks, ND (United States))

2011-07-15

This paper examines available data, develops a strategy and presents a monthly, global time series of fossil-fuel carbon dioxide emissions for the years 1950-2006. This monthly time series was constructed from detailed study of monthly data from the 21 countries that account for approximately 80% of global total emissions. These data were then used in a Monte Carlo approach to proxy for all remaining countries. The proportional-proxy methodology estimates by fuel group the fraction of annual emissions emitted in each country and month. Emissions from solid, liquid and gas fuels are explicitly modelled by the proportional-proxy method. The primary conclusion from this study is the global monthly time series is statistically significantly different from a uniform distribution throughout the year. Uncertainty analysis of the data presented show that the proportional-proxy method used faithfully reproduces monthly patterns in the data and the global monthly pattern of emissions is relatively insensitive to the exact proxy assignments used. The data and results presented here should lead to a better understanding of global and regional carbon cycles, especially when the mass data are combined with the stable carbon isotope data in atmospheric transport models

Forecasting Precipitation over the MENA Region: A Data Mining and Remote Sensing Based Approach

Science.gov (United States)

Elkadiri, R.; Sultan, M.; Elbayoumi, T.; Chouinard, K.

2015-12-01

We developed and applied an integrated approach to construct predictive tools with lead times of 1 to 12 months to forecast precipitation amounts over the Middle East and North Africa (MENA) region. The following steps were conducted: (1) acquire and analyze temporal remote sensing-based precipitation datasets (i.e. Tropical Rainfall Measuring Mission [TRMM]) over five main water source regions in the MENA area (i.e. Atlas Mountains in Morocco, Southern Sudan, Red Sea Hills of Yemen, and Blue Nile and White Nile source areas) throughout the investigation period (1998 to 2015), (2) acquire and extract monthly values for all of the climatic indices that are likely to influence the climatic patterns over the MENA region (e.g., Northern Atlantic Oscillation [NOI], Southern Oscillation Index [SOI], and Tropical North Atlantic Index [TNA]); and (3) apply data mining methods to extract relationships between the observed precipitation and the controlling factors (climatic indices) and use predictive tools to forecast monthly precipitation over each of the identified pilot study areas. Preliminary results indicate that by using the period from January 1998 until August 2012 for model training and the period from September 2012 to January 2015 for testing, precipitation can be successfully predicted with a three-months lead over South West Yemen, Atlas Mountains in Morocco, Southern Sudan, Blue Nile sources and White Nile sources with confidence (Pearson correlation coefficient: 0.911, 0.823, 0.807, 0.801 and 0.895 respectively). Future work will focus on applying this technique for prediction of precipitation over each of the climatically contiguous areas of the MENA region. If our efforts are successful, our findings will lead the way to the development and implementation of sound water management scenarios for the MENA countries.

Acute malnutrition among children aged 6-59 months of the nomadic population in Hadaleala district, Afar region, northeast Ethiopia.

Science.gov (United States)

Gizaw, Zemichael; Woldu, Wondwoson; Bitew, Bikes Destaw

2018-02-07

Acute malnutrition to be a major health burden in the world, particularly in the developing world. Acute malnutrition is associated with more than one third of the global disease burden for children. Malnourished children are physically, emotionally and intellectually less productive and suffer more from chronic illnesses and disabilities. The nature, magnitude and determinants of acute malnutrition are determined among the general populations; however, there is a lack of evidence in the nomadic communities. A cross-sectional study was conducted to assess the magnitude and factors associated with acute malnutrition among children aged 6-59 months in Hadaleala district, Afar Region. A total of 591 under-five children were included in this study, and subjects were recruited by the multistage cluster sampling technique. Data were collected by a pre-tested questionnaire and a simple anthropometric index so called mid-upper arm circumference (MUAC). The multivariable binary logistic regression analysis was used to identify factors associated with acute malnutrition on the basis of adjusted odds ratio (AOR) with 95% confidence interval (CI) and p malnutrition was 11.8% (95% CI = 9.3, 14.8%). The highest prevalence (50%) of acute malnutrition occurred among children aged between 12.0-23.0 months. Childhood acute malnutrition was associated with the presence of two (AOR = 2.49, p childhood diarrheal disease (AOR = 2.72, p malnutrition among children aged 6-59 months was was higher than the national prevalence. The number of children in each household, drinking water sources, latrine availability, hand washing practice before food preparation and child feeding, childhood diarrheal disease, and child vaccination were identified as factors affecting the childhood acute malnutrition in the nomadic community. Protecting drinking water sources from possible contaminants, improving hand washing practices, utilization of latrine, preventing diarrheal diseases

A Different View of Solar Spectral Irradiance Variations: Modeling Total Energy over Six-Month Intervals.

Science.gov (United States)

Woods, Thomas N; Snow, Martin; Harder, Jerald; Chapman, Gary; Cookson, Angela

A different approach to studying solar spectral irradiance (SSI) variations, without the need for long-term (multi-year) instrument degradation corrections, is examining the total energy of the irradiance variation during 6-month periods. This duration is selected because a solar active region typically appears suddenly and then takes 5 to 7 months to decay and disperse back into the quiet-Sun network. The solar outburst energy, which is defined as the irradiance integrated over the 6-month period and thus includes the energy from all phases of active region evolution, could be considered the primary cause for the irradiance variations. Because solar cycle variation is the consequence of multiple active region outbursts, understanding the energy spectral variation may provide a reasonable estimate of the variations for the 11-year solar activity cycle. The moderate-term (6-month) variations from the Solar Radiation and Climate Experiment (SORCE) instruments can be decomposed into positive (in-phase with solar cycle) and negative (out-of-phase) contributions by modeling the variations using the San Fernando Observatory (SFO) facular excess and sunspot deficit proxies, respectively. These excess and deficit variations are fit over 6-month intervals every 2 months over the mission, and these fitted variations are then integrated over time for the 6-month energy. The dominant component indicates which wavelengths are in-phase and which are out-of-phase with solar activity. The results from this study indicate out-of-phase variations for the 1400 - 1600 nm range, with all other wavelengths having in-phase variations.

Behavior of the S parameter in the crossover region between walking and QCD-like regimes of an SU(N) gauge theory

International Nuclear Information System (INIS)

Kurachi, Masafumi; Shrock, Robert

2006-01-01

We consider a vectorial, confining SU(N) gauge theory with a variable number, N f , of massless fermions transforming according to the fundamental representation. Using the Schwinger-Dyson and Bethe-Salpeter equations, we calculate the S parameter in terms of the current-current correlation functions. We focus on values of N f such that the theory is in the crossover region between the regimes of walking behavior and QCD-like (nonwalking) behavior. Our calculations indicate that the contribution to S from a given fermion decreases as one moves from the QCD-like to the walking regimes. The implications of this result for technicolor theories are discussed

Electric power monthly with data for October 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-01-01

This publication provides monthly statistics at the State, Census division, and U.S. levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity retail sales, associated revenue, and average revenue per kilowatthour of electricity sold. In addition, data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council regions. Statistics are published on net generation by energy source; consumption, stocks, quantity, quality, and cost of fossil fuels; and capability of new generating units by company and plant. A monthly utility update and summary of industry developments are also included. 63 tabs., 1 fig.

Electric power monthly with data for August 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

This publication provides monthly statistics at the state, census division, and U.S. levels for net generation; fossil fuel consumption and stocks, quantity, and quality of fossil fuels; cost of fossil fuels; electricity retail sales; associated revenue; and average revenue per kilowatthour of electricity sold. Data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council regions. Statistics on net generation are published by energy source; consumption, stocks, quantity, quality, and cost of fossil fuels; and capability of new generating units by company and plant. The monthly update is summarized, and industry developments are briefly described. 1 fig., 63 tabs.

Characterization of an insulin-like growth factor-I/somatomedin-C radioimmunoassay specific for the C-peptide region

International Nuclear Information System (INIS)

Hintz, R.L.; Liu, F.; Seegan, G.

1982-01-01

Insulin-like growth factor-I (IGF-I) and somatomedin-C (SM-C) have been shown to be functionally identical by a number of criteria. We have synthesized the 12 amino acid C-peptide region of IGF-I (Gly-Tyr-Gly-Ser-Ser-Ser-Arg-Arg-Ala-Pro-Glu-Thr) and developed a RIA based on antibodies against this synthetic peptide. IGF-I and SM-C were indistinguishable in this RIA. No other peptides competed for this antiserum. The SM-C/IGF-I values of acid-chromatographed serum were strongly age dependent. The mean of children 1-5 yr old was 0.67 +/- 0.033 U/ml (mean +/- sD; n = 23), whereas the mean of children 12-17 yr old was 2.01 +/- 0.66 U/ml (n = 39) and the mean of 38 adults 26-85 yr old was 1.05 +/- 0.34. The SM-C/IGF-I values measured by this RIA were also growth hormone dependent. Thus, this region-specific RIA provides a clinically useful assessment of serum SM-C/IGF-I levels

Chlamydia trachomatis Mip-like protein

DEFF Research Database (Denmark)

Lundemose, AG; Rousch, DA; Birkelund, Svend

1992-01-01

venereum (LGV) biovar) is presented. The sequence shows high similarity to the legionella Mip protein and its C-terminal region, like that of the legionella Mip, has high amino acid similarity to eukaryotic and prokaryotic FK506-binding proteins. The chlamydial mip-like gene was detected by polymerase...

Monthly Electrical Energy Overview May 2017

International Nuclear Information System (INIS)

2017-06-01

This publication presents the electricity characteristics and noteworthy developments in France every month: consumption, generation, renewable energies, cross-border trades and transmission system developments, along with feedback on the highlights affecting this data. This issue presents the key figures for May 2017. Demand increased slightly versus May 2016 with higher average temperatures (+1.6 deg.) over this period. Demand rose by 0.9% compared with May 2016. Hydraulic generation was again impacted by the lack of rain with a fall of 12,6% compared with May 2016. Solar generation increased by 20%, driven by the growth of the park and the high amounts of sunshine observed over the month. It is in Auvergne-Rhone-Alpes, Grand-Est, Hauts-de-France, Ile-de-France and Provence-Alpes-Cote d'Azur (PACA) that annual final demand from heavy industry was at its highest for 2016. In these regions, except for Ile-de-France, the chemicals, para-chemicals, metallurgy and steel sectors consumed the most energy. Market prices were relatively stable in most European countries. France had an export balance with all countries outside its borders. With 1.85 TWh, the export balance for monthly trades with Spain reached a new record. 7 new installations went into service in May

Development tendencies of regional disparities in the Slovak Republic

Directory of Open Access Journals (Sweden)

Klamár Radoslav

2016-01-01

Full Text Available Presented paper deals with the issues of regional development and regional disparities in Slovakia in the years 2001-2014. Levelling respectively increase of regional disparities was evaluated through a set of 13 socio-economic indicators (gross birth rate, average monthly wage, monthly labour costs per employee, employment rate, unemployment rate, net monthly income and expenses per capita, completed dwellings, creation of GDP, labour productivity per employee in industry and construction, number of organizations focused on generating profit and number of freelancers which were used in the territorial units at the level of self-governing regions of the Slovak Republic (NUTS III level. In terms of the evaluation and comparison of regional disparities were used the Gini coefficient and the coefficient of variation for mutual comparison and validation of divergent or convergent tendencies of regional disparities in Slovakia.

Trends for monthly changes in days open in Holsteins

NARCIS (Netherlands)

Pszczola, M.J.; Aguilar, I.; Misztal, I.

2009-01-01

A reaction norm approach was used to estimate trends for days open (DO) with a model that indirectly accounted for heat stress. Data included 3.4 million first-parity records of DO of US Holsteins. A fixed effect model included herd-year, month of calving within region (MOC), age class, and

Transient regional osteoporosis

Directory of Open Access Journals (Sweden)

F. Trotta

2011-09-01

Full Text Available Transient osteoporosis of the hip and regional migratory osteoporosis are uncommon and probably underdiagnosed bone diseases characterized by pain and functional limitation mainly affecting weight-bearing joints of the lower limbs. These conditions are usually self-limiting and symptoms tend to abate within a few months without sequelae. Routine laboratory investigations are unremarkable. Middle aged men and women during the last months of pregnancy or in the immediate post-partum period are principally affected. Osteopenia with preservation of articular space and transitory edema of the bone marrow provided by magnetic resonance imaging are common to these two conditions, so they are also known by the term regional transitory osteoporosis. The appearance of bone marrow edema is not specific to regional transitory osteoporosis but can be observed in several diseases, i.e. trauma, reflex sympathetic dystrophy, avascular osteonecrosis, infections, tumors from which it must be differentiated. The etiology of this condition is unknown. Pathogenesis is still debated in particular the relationship with reflex sympathetic dystrophy, with which regional transitory osteoporosis is often identified. The purpose of the present review is to remark on the relationship between transient osteoporosis of the hip and regional migratory osteoporosis with particular attention to the bone marrow edema pattern and relative differential diagnosis.

Estimation of monthly global solar radiation in the eastern Mediterranean region in Turkey by using artificial neural networks

International Nuclear Information System (INIS)

Sahan, Muhittin; Yakut, Emre

2016-01-01

In this study, an artificial neural network (ANN) model was used to estimate monthly average global solar radiation on a horizontal surface for selected 5 locations in Mediterranean region for period of 18 years (1993-2010). Meteorological and geographical data were taken from Turkish State Meteorological Service. The ANN architecture designed is a feed-forward back-propagation model with one-hidden layer containing 21 neurons with hyperbolic tangent sigmoid as the transfer function and one output layer utilized a linear transfer function (purelin). The training algorithm used in ANN model was the Levenberg Marquand back propagation algorith (trainlm). Results obtained from ANN model were compared with measured meteorological values by using statistical methods. A correlation coefficient of 97.97 (~98%) was obtained with root mean square error (RMSE) of 0.852 MJ/m 2 , mean square error (MSE) of 0.725 MJ/m 2 , mean absolute bias error (MABE) 10.659MJ/m 2 , and mean absolute percentage error (MAPE) of 4.8%. Results show good agreement between the estimated and measured values of global solar radiation. We suggest that the developed ANN model can be used to predict solar radiation another location and conditions

CERES Monthly TOA and SRB Averages (SRBAVG) data in HDF-EOS Grid (CER_SRBAVG_Terra-FM1-MODIS_Edition2D)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Monthly TOA/Surface Averages (SRBAVG) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SRBAVG is also produced for combinations of scanner instruments. The monthly average regional flux is estimated using diurnal models and the 1-degree regional fluxes at the hour of observation from the CERES SFC product. A second set of monthly average fluxes are estimated using concurrent diurnal information from geostationary satellites. These fluxes are given for both clear-sky and total-sky scenes and are spatially averaged from 1-degree regions to 1-degree zonal averages and a global average. For each region, the SRBAVG also contains hourly average fluxes for the month and an overall monthly average. The cloud properties from SFC are column averaged and are included on the SRBAVG. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-02-01; Stop_Date=2004-05-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=1 degree; Longitude_Resolution=1 degree; Horizontal_Resolution_Range=100 km - < 250 km or approximately 1 degree - < 2.5 degrees; Temporal_Resolution=1 month; Temporal_Resolution_Range=Monthly - < Annual].

CERES Monthly TOA and SRB Averages (SRBAVG) data in HDF-EOS Grid (CER_SRBAVG_Terra-FM1-MODIS_Edition2C)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Monthly TOA/Surface Averages (SRBAVG) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SRBAVG is also produced for combinations of scanner instruments. The monthly average regional flux is estimated using diurnal models and the 1-degree regional fluxes at the hour of observation from the CERES SFC product. A second set of monthly average fluxes are estimated using concurrent diurnal information from geostationary satellites. These fluxes are given for both clear-sky and total-sky scenes and are spatially averaged from 1-degree regions to 1-degree zonal averages and a global average. For each region, the SRBAVG also contains hourly average fluxes for the month and an overall monthly average. The cloud properties from SFC are column averaged and are included on the SRBAVG. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-02-01; Stop_Date=2003-02-28] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=1 degree; Longitude_Resolution=1 degree; Horizontal_Resolution_Range=100 km - < 250 km or approximately 1 degree - < 2.5 degrees; Temporal_Resolution=1 month; Temporal_Resolution_Range=Monthly - < Annual].

CERES Monthly TOA and SRB Averages (SRBAVG) data in HDF-EOS Grid (CER_SRBAVG_Terra-FM2-MODIS_Edition2C)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The Monthly TOA/Surface Averages (SRBAVG) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The SRBAVG is also produced for combinations of scanner instruments. The monthly average regional flux is estimated using diurnal models and the 1-degree regional fluxes at the hour of observation from the CERES SFC product. A second set of monthly average fluxes are estimated using concurrent diurnal information from geostationary satellites. These fluxes are given for both clear-sky and total-sky scenes and are spatially averaged from 1-degree regions to 1-degree zonal averages and a global average. For each region, the SRBAVG also contains hourly average fluxes for the month and an overall monthly average. The cloud properties from SFC are column averaged and are included on the SRBAVG. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-02-01; Stop_Date=2003-02-28] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=1 degree; Longitude_Resolution=1 degree; Horizontal_Resolution_Range=100 km - < 250 km or approximately 1 degree - < 2.5 degrees; Temporal_Resolution=1 month; Temporal_Resolution_Range=Monthly - < Annual].

Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms

International Nuclear Information System (INIS)

Haselbacher, G.K.; Schwab, M.E.; Pasi, A.; Humbel, R.E.

1985-01-01

Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain

Structural Diversity in Conserved Regions Like the DRY-Motif among Viral 7TM Receptors-A Consequence of Evolutionary Pressure?

DEFF Research Database (Denmark)

Mølleskov-Jensen, Ann-Sofie; Sparre-Ulrich, Alexander Hovard; Davis-Poynter, Nicholas

2012-01-01

Several herpes- and poxviruses have captured chemokine receptors from their hosts and modified these to their own benefit. The human and viral chemokine receptors belong to class A 7 transmembrane (TM) receptors which are characterized by several structural motifs like the DRY-motif in TM3...... and the C-terminal tail. In the DRY-motif, the arginine residue serves important purposes by being directly involved in G protein coupling. Interestingly, among the viral receptors there is a greater diversity in the DRY-motif compared to their endogenous receptor homologous. The C-terminal receptor tail...... constitutes another regulatory region that through a number of phosphorylation sites is involved in signaling, desensitization, and internalization. Also this region is more variable among virus-encoded 7TM receptors compared to human class A receptors. In this review we will focus on these two structural...

Statistical models to predict flows at monthly level in Salvajina

International Nuclear Information System (INIS)

Gonzalez, Harold O

1994-01-01

It thinks about and models of lineal regression evaluate at monthly level that they allow to predict flows in Salvajina, with base in predictions variable, like the difference of pressure between Darwin and Tahiti, precipitation in Piendamo Cauca), temperature in Port Chicama (Peru) and pressure in Tahiti

Petroleum supply monthly, April 1994

Energy Technology Data Exchange (ETDEWEB)

1994-04-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the United States and major US geographical regions. The data series describe production, imports and exports, inter-Petroleum Administration for Defense (PAD) District movements, and inventories by the primary suppliers of petroleum products in the US. The reporting universe includes those petroleum sectors in primary supply. Included are: petroleum refiners, motor gasoline blenders, operators of natural gas processing plants and fractionators, inter-PAD transporters, importers, and major inventory holders of petroleum products and crude oil. When aggregated, the data reported by these sectors approximately represent the consumption of petroleum products in the US.

Monthly CO surface sources inventory based on the 2000-2001 MOPITT satellite data

Science.gov (United States)

Pétron, Gabrielle; Granier, Claire; Khattatov, Boris; Yudin, Valery; Lamarque, Jean-François; Emmons, Louisa; Gille, John; Edwards, David P.

2004-11-01

This paper presents results of the inverse modeling of carbon monoxide surface sources on a monthly and regional basis using the MOPITT (Measurement Of the Pollution In The Troposphere) CO retrievals. The targeted time period is from April 2000 to March 2001. A sequential and time-dependent inversion scheme is implemented to correct an a priori set of monthly mean CO sources. The a posteriori estimates for the total anthropogenic (fossil fuel + biofuel + biomass burning) surface sources of CO in TgCO/yr are 509 in Asia, 267 in Africa, 140 in North America, 90 in Europe and 84 in Central and South America. Inverting on a monthly scale allows one to assess a corrected seasonality specific to each source type and each region. Forward CTM simulations with the a posteriori emissions show a substantial improvement of the agreement between modeled CO and independent in situ observations.

Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions

International Nuclear Information System (INIS)

Irminger, J.C.; Rosen, K.M.; Humble, R.E.; Villa-Komaroff, L.

1987-01-01

The authors have used RNA from human hypothalamus as template for the production of cDNAs encoding insulin-like growth factor II (IGF-II). The prohormone coding sequence of brain IGF-II RNA is identical to that found in liver; however, the 5' untranslated sequence of the brain cDNA has no homology to the 5' untranslated sequence of the previously reported liver cDNAs. By using hybridization to specific probes as well as a method based on the properties of RNase H, they found that the human IGF-II gene has at least three exons that encode alternative 5' untranslated regions and that are expressed in a tissue-specific manner. A probe specific to the brain cDNA 5' untranslated region hybridizes to a 6.0-kilobase transcript present in placenta, hypothalamus, adrenal gland, kidney, Wilms tumor, and a pheochromocytoma. The 5' untranslated sequence of the brain cDNA does not hybridize to a 5.3-kilobase transcript found in liver or to a 5.0-kb transcript found in pheochromocytoma. By using RNase H to specifically fragment the IGF-II transcripts into 3' and 5' fragments, they found that the RNAs vary in size due to differences in the 5' end but not the 3' end

High resolution reconstruction of monthly autumn and winter precipitation of Iberian Peninsula for last 150 years.

Science.gov (United States)

Cortesi, N.; Trigo, R.; González-Hidalgo, J. C.; Ramos, A.

2012-04-01

Precipitation over Iberian Peninsula (IP) presents large values of interannual variability and large spatial contrasts between wet mountainous regions in the north and dry regions in the southern plains. Unlike other European regions, IP was poorly monitored for precipitation during 19th century. Here we present a new approach to fill this gap. A set of 26 atmospheric circulation weather types (Trigo R.M. and DaCamara C.C., 2000) derived from a recent SLP dataset, the EMULATE (European and North Atlantic daily to multidecadal climate variability) Project, was used to reconstruct Iberian monthly precipitation from October to March during 1851-1947. Principal Component Regression Analysis was chosen to develop monthly precipitation reconstruction back to 1851 and calibrated over 1948-2003 period for 3030 monthly precipitation series of high-density homogenized MOPREDAS (Monthly Precipitation Database for Spain and Portugal) database. Validation was conducted over 1920-1947 at 15 key site locations. Results show high model performance for selected months, with a mean coefficient of variation (CV) around 0.6 during validation period. Lower CV values were achieved in western area of IP. Trigo, R. M., and DaCamara, C.C., 2000: "Circulation weather types and their impact on the precipitation regime in Portugal". Int. J. Climatol., 20, 1559-1581.

Association of Neglect-Like Symptoms with Anxiety, Somatization, and Depersonalization in Complex Regional Pain Syndrome.

Science.gov (United States)

Michal, Matthias; Adler, Julia; Reiner, Iris; Wermke, Andreas; Ackermann, Tatiana; Schlereth, Tanja; Birklein, Frank

2017-04-01

Many patients with complex regional pain syndrome (CRPS) report some foreignness of the affected limb, which is referred to as "neglect-like symptoms" (NLS). Despite similarities of the NLS reports to symptoms of body image disturbances in mental disorders, no study has been conducted to examine such associations. We investigated 50 patients with CRPS and 45 pain control patients (N = 27, chronic limb pain; N = 18, migraine headache). NLS, anxiety, depression, depersonalization, and somatization were assessed using validated questionnaires. Seventy-two percent of the CRPS patients reported at least one NLS vs 29.6% and 33.3% in the two patient control groups. In limb pain controls, NLS correlated with pain intensity. In CRPS patients, NLS correlated with anxiety (rho = 0.658, P  psychological studies. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study.

Directory of Open Access Journals (Sweden)

Lamberto Manzoli

Full Text Available To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes, directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both.Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up.Direct contact and structured questionnaires by phone or via internet.Adults (30-75 years were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers, users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers, or smokers of both tobacco and e-cigarettes (dual smokers. Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence.Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily.We used linear and logistic regression, with region as cluster unit.Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%. All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35-8.02, whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall.Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e

Geometric algorithms for delineating geographic regions

NARCIS (Netherlands)

Reinbacher, I.

2006-01-01

Everyone of us is used to geographical regions like the south of Utrecht, the dutch Randstad, or the mountainous areas of Austria. Some of these regions have crisp, fixed boundaries like Utrecht or Austria. Others, like the dutch Randstad and the Austrian mountains, have no such boundaries and are

Petroleum supply monthly, April 1990

Energy Technology Data Exchange (ETDEWEB)

None

1990-06-26

The Petroleum Supply Monthly (PSM) is one of a family of three publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other two publications are the Weekly Petroleum Status Report (WPSR) and the Petroleum Supply Annual (PSA). Data presented in the Petroleum Supply Monthly describe (PSM) the supply and disposition of petroleum products in the United States and major US geographic regions. The data series describe production, imports and exports, inter-Petroleum Administration for Defense (PAD) District movements, and inventories by the primary suppliers of petroleum products in the United States (50 States and the District of Columbia). The reporting universe includes those petroleum sectors in Primary Supply.'' Included are: petroleum refiners, motor gasoline blenders, operators of natural gas processing plants and fractionators, inter-PAD transporters, importers, and major inventory holders of petroleum products and crude oil. When aggregated, the data reported by these sectors approximately represent the consumption of petroleum products in the United States. Data presented in the PSM are divided into two sections: (1) the Summary Statistics and (2) the Detailed Statistics.

Thrombolysis in patients with prior stroke within the last 3 months.

Science.gov (United States)

Heldner, M R; Mattle, H P; Jung, S; Fischer, U; Gralla, J; Zubler, C; El-Koussy, M; Schroth, G; Arnold, M; Mono, M-L

2014-12-01

Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group). In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years). Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0-1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%). In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit-risk ratio. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.

LENUS (Irish Health Repository)

Sequist, Lecia V

2013-09-20

The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR\\/ErbB1), human epidermal growth factor receptor 2 (HER2\\/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

Deciphering heterogeneity in pig genome assembly Sscrofa9 by isochore and isochore-like region analyses.

Directory of Open Access Journals (Sweden)

Wenqian Zhang

Full Text Available BACKGROUND: The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes. Although the isochore has been widely studied in humans and other species, little is known about its distribution in pigs. PRINCIPAL FINDINGS: In this paper, we construct a map of long homogeneous genome regions (LHGRs, i.e., isochores and isochore-like regions, in pigs to provide an intuitive version of GC heterogeneity in each chromosome. The LHGR pattern study not only quantifies heterogeneities, but also reveals some primary characteristics of the chromatin organization, including the followings: (1 the majority of LHGRs belong to GC-poor families and are in long length; (2 a high gene density tends to occur with the appearance of GC-rich LHGRs; and (3 the density of LINE repeats decreases with an increase in the GC content of LHGRs. Furthermore, a portion of LHGRs with particular GC ranges (50%-51% and 54%-55% tend to have abnormally high gene densities, suggesting that biased gene conversion (BGC, as well as time- and energy-saving principles, could be of importance to the formation of genome organization. CONCLUSION: This study significantly improves our knowledge of chromatin organization in the pig genome. Correlations between the different biological features (e.g., gene density and repeat density and GC content of LHGRs provide a unique glimpse of in silico gene and repeats prediction.

Sox2 promotes survival of satellite glial cells in vitro

International Nuclear Information System (INIS)

Koike, Taro; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

2015-01-01

Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling

Radio stimulation and diagnostics of space plasmas. Progress report

International Nuclear Information System (INIS)

Lee, Minchang.

1993-02-01

This report describes the investigation of the small-scale topside ionospheric plasma structures first observed at Millstone Hill, Massachusetts with the 440 MHz incoherent scatter radar. These small-scale obliquely propagating plasma modes occurring in the vicinity of the midlatitude ionospheric trough, have large radar cross-sections and narrow spectral widths. They have, until recently, been dismissed solely as hard target contamination of the incoherent scatter radar. The geophysical conditions associated with the ionospheric trough, such as the field-aligned current activity and steep plasma density gradients, suggest that these recently discovered small-scale topside ionospheric plasmas may also appear in the auroral and polar ionosphere. In fact, this speculation has been corroborated by the preliminary experiments and data analyses at Tromso, Norway and Sondrestromfjord, Greenland. The primary research results are highlighted. Described in Section 3 are the experiments conducted at Arecibo, Puerto Rico in the past summer for simulating the geophysical conditions of generating these topside ionospheric plasma structures. Recommendation for the future research is finally given. Attached as the appendix of this report are several chapters which present the detailed results of research in the concerned topside ionospheric clutter. Highlights of the research results include: (1) causes of the enhanced radar backscatter (ERB) phenomenon; (2) occurrence of the ERB phenomenon; (3) altitudes of the ERB phenomenon; (4) strength of the ERB returns; (5) range of altitudes of the ERB returns; (6) occurrence frequency of the ERB phenomenon; (7) Doppler effect of the ERB phenomenon; (8) persistency of the ERB; and (9) distinction between ERB phenomenon and space object signatures

Sox2 promotes survival of satellite glial cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

2015-08-14

Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

Electric power monthly, August 1998, with data for May 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-08-01

The Electric Power Monthly (EPM) presents monthly electricity statistics for a wide audience including congress, Federal and State agencies, the electric utility industry, and the general public. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. This publication provides monthly statistics at the State, Census division, and US levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity retail sales, associated revenue, and average revenue per kilowatthour of electricity sold. In addition, data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. 9 refs., 57 tabs.

Electric power monthly, March 1999 with data for December 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

The Electric Power Monthly (EPM) presents monthly electricity statistics for a wide audience including Congress, Federal and State agencies, the electric utility industry, and the general public. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be sued in forming various perspectives on electric issues that lie ahead. This publication provides monthly statistics at the State, Census division, and US levels for net generation, fossil fuel consumption and stocks, quantity and quality of fossil fuels, cost of fossil fuels, electricity retail sales, associated revenue, and average revenue per kilowatthour of electricity sold. In addition, data on net generation, fuel consumption, fuel stocks, quantity and cost of fossil fuels are also displayed for the North American Electric Reliability Council (NERC) regions. 63 tabs.

Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice.

Science.gov (United States)

Von Linstow, C U; Severino, M; Metaxas, A; Waider, J; Babcock, A A; Lesch, K P; Gramsbergen, J B; Finsen, B

2017-09-01

Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP SWE /PS1 ΔE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APP SWE /PS1 ΔE9 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

User's guide: Nimbus-7 Earth radiation budget narrow-field-of-view products. Scene radiance tape products, sorting into angular bins products, and maximum likelihood cloud estimation products

Science.gov (United States)

Kyle, H. Lee; Hucek, Richard R.; Groveman, Brian; Frey, Richard

1990-01-01

The archived Earth radiation budget (ERB) products produced from the Nimbus-7 ERB narrow field-of-view scanner are described. The principal products are broadband outgoing longwave radiation (4.5 to 50 microns), reflected solar radiation (0.2 to 4.8 microns), and the net radiation. Daily and monthly averages are presented on a fixed global equal area (500 sq km), grid for the period May 1979 to May 1980. Two independent algorithms are used to estimate the outgoing fluxes from the observed radiances. The algorithms are described and the results compared. The products are divided into three subsets: the Scene Radiance Tapes (SRT) contain the calibrated radiances; the Sorting into Angular Bins (SAB) tape contains the SAB produced shortwave, longwave, and net radiation products; and the Maximum Likelihood Cloud Estimation (MLCE) tapes contain the MLCE products. The tape formats are described in detail.

How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy