CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_PFM+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM4_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Terra-FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CERES:CER_ES9_PFM+FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Aqua-FM3_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_FM1+FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2006-09-30] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF ( CER_ES9_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Regional Averages (ES-9) 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-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. 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 ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_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

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

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)

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.

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.

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

Directory of Open Access Journals (Sweden)

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...

ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

Energy Technology Data Exchange (ETDEWEB)

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.

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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 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

Directory of Open Access Journals (Sweden)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

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.

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.

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.

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

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.

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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

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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

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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

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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.

Science.gov (United States)

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.

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

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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

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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.

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

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].

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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.

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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.

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...

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

DEFF Research Database (Denmark)

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...

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

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.

Science.gov (United States)

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

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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

Energy Technology Data Exchange (ETDEWEB)

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

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.

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.

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.

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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.

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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

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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

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...

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

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

Directory of Open Access Journals (Sweden)

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

[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.

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

Energy Technology Data Exchange (ETDEWEB)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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)

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.

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

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

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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

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

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)

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...

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.

Demographic, Seasonal, and Geographic Differences in Emergency Department Visits for Epistaxis.

Science.gov (United States)

Chaaban, Mohamad R; Zhang, Dong; Resto, Vicente; Goodwin, James S

2017-01-01

Objective To determine the demographics and seasonal and geographic variation of epistaxis in the United States. Study Design Retrospective cohort analysis based on data from Medicare claims. Setting Emergency department visits. Subjects and Methods We used a 5% sample of Medicare data from January 2012 to December 2012. Our cohort included patients with an incident diagnosis of epistaxis during a visit to the emergency department, excluding those with a diagnosis in the prior 12 months. Demographics included age, sex, race, and ethnicity. We compared the rate of emergency department visits for epistaxis by geographic division and individual states. Results In the 5% sample of Medicare data, 4120 emergency department visits for incident epistaxis were identified in 2012. Our results showed an increase in the emergency department visits for epistaxis with age. Compared with patients 85 years old were 1.36 (95% confidence interval [95% CI], 1.23-1.50), 2.37 (95% CI, 2.14-2.62), and 3.24 (95% CI, 2.91-3.62) more likely to present with epistaxis, respectively. Men were 1.24 (95% CI, 1.17-1.32) times more likely to present with epistaxis than women. Blacks were 1.23 (95% CI, 1.10-1.36) times more likely to present with epistaxis when compared with non-Hispanic whites. Epistaxis emergency department visits were 40% lower in the summer months versus winter. The seasonal variation was more pronounced in the northern versus southern United States. Conclusion Emergency department visits for epistaxis increase with age and appear to be seasonal, with a more pronounced variation in the northern versus southern United States.

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

Geographic and racial-ethnic differences in satisfaction with and perceived benefits of mental health services.

Science.gov (United States)

Kim, Giyeon; Parton, Jason M; Ford, Katy-Lauren; Bryant, Ami N; Shim, Ruth S; Parmelee, Patricia

2014-12-01

This study examined whether racial-ethnic differences in satisfaction with and perceived benefits from mental health services vary by geographic region among U.S. adults. Drawn from the Collaborative Psychiatric Epidemiology Surveys (CPES), selected samples consisted of 2,160 adults age 18 and older from diverse racial-ethnic groups (Asian, black, Hispanic/Latino, and white) who had used mental health services in the past 12 months. Generalized linear model analysis was conducted for the United States as a whole and separately by geographic region (Northeast, South, Midwest, and West) after adjustment for covariates. In the national sample, no significant main effects of race-ethnicity and geographic region were found in either satisfaction with or perceived benefits from mental health services. In the stratified analyses for geographic regions, however, significant racial-ethnic differences were observed in the West; blacks in the West were significantly more likely to report higher satisfaction and perceived benefits, whereas Hispanics/Latinos in the West were significantly less likely to do so. The findings suggest that there are regional variations of racial-ethnic differences in satisfaction with and perceived benefits from mental health services among U.S. adults and that addressing needs of Hispanics/Latinos in the West may help reduce racial-ethnic disparities in mental health care. Clinical and policy implications are discussed.

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

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

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

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

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.

Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.

Science.gov (United States)

Linton, Anthony; Soeberg, Matthew; Broome, Richard; Kao, Steven; van Zandwijk, Nico

2017-07-01

Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM. We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed. We identified 910 patients (67% residing in major cities; 92% 70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001). This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW. © 2017 Asian Pacific Society of Respirology.

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

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.

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

Estimation of the monthly average daily solar radiation using geographic information system and advanced case-based reasoning.

Science.gov (United States)

Koo, Choongwan; Hong, Taehoon; Lee, Minhyun; Park, Hyo Seon

2013-05-07

The photovoltaic (PV) system is considered an unlimited source of clean energy, whose amount of electricity generation changes according to the monthly average daily solar radiation (MADSR). It is revealed that the MADSR distribution in South Korea has very diverse patterns due to the country's climatic and geographical characteristics. This study aimed to develop a MADSR estimation model for the location without the measured MADSR data, using an advanced case based reasoning (CBR) model, which is a hybrid methodology combining CBR with artificial neural network, multiregression analysis, and genetic algorithm. The average prediction accuracy of the advanced CBR model was very high at 95.69%, and the standard deviation of the prediction accuracy was 3.67%, showing a significant improvement in prediction accuracy and consistency. A case study was conducted to verify the proposed model. The proposed model could be useful for owner or construction manager in charge of determining whether or not to introduce the PV system and where to install it. Also, it would benefit contractors in a competitive bidding process to accurately estimate the electricity generation of the PV system in advance and to conduct an economic and environmental feasibility study from the life cycle perspective.

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.

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

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

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...

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.

Geographic profiling and animal foraging.

Science.gov (United States)

Le Comber, Steven C; Nicholls, Barry; Rossmo, D Kim; Racey, Paul A

2006-05-21

Geographic profiling was originally developed as a statistical tool for use in criminal cases, particularly those involving serial killers and rapists. It is designed to help police forces prioritize lists of suspects by using the location of crime scenes to identify the areas in which the criminal is most likely to live. Two important concepts are the buffer zone (criminals are less likely to commit crimes in the immediate vicinity of their home) and distance decay (criminals commit fewer crimes as the distance from their home increases). In this study, we show how the techniques of geographic profiling may be applied to animal data, using as an example foraging patterns in two sympatric colonies of pipistrelle bats, Pipistrellus pipistrellus and P. pygmaeus, in the northeast of Scotland. We show that if model variables are fitted to known roost locations, these variables may be used as numerical descriptors of foraging patterns. We go on to show that these variables can be used to differentiate patterns of foraging in these two species.

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

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.

Toll-Like Receptor-3 and Geographic Atrophy in Age-Related Macular Degeneration

Science.gov (United States)

Yang, Zhenglin; Stratton, Charity; Francis, Peter J.; Kleinman, Mark E.; Tan, Perciliz L.; Gibbs, Daniel; Tong, Zongzhong; Chen, Haoyu; Constantine, Ryan; Yang, Xian; Chen, Yuhong; Zeng, Jiexi; Davey, Lisa; Ma, Xiang; Hau, Vincent S.; Wang, Chi; Harmon, Jennifer; Buehler, Jeanette; Pearson, Erik; Patel, Shrena; Kaminoh, Yuuki; Watkins, Scott; Luo, Ling; Zabriskie, Norman A.; Bernstein, Paul S.; Cho, Wongil; Schwager, Andrea; Hinton, David R; Klein, Michael L; Hamon, Sara C.; Simmons, Emily; Yu, Beifeng; Campochiaro, Betsy; Sunness, Janet S.; Campochiaro, Peter; Jorde, Lynn; Parmigiani, Giovanni; Zack, Donald J.; Katsanis, Nicholas; Ambati, Jayakrishna; Zhang, Kang

2008-01-01

BACKGROUND Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. Advanced AMD is comprised of geographic atrophy (GA) and choroidal neovascularization (CNV). Specific genetic variants that predispose for GA are largely unknown. METHODS We tested (i) for association between the functional toll-like receptor-3 (TLR3) variant rs3775291 (L412F) and AMD in European Americans and (ii) the effect of TLR3 L and F variants on the viability of human retinal pigment epithelium (RPE) cells in vitro and on RPE cell apoptosis in wildtype and Tlr3−/− mice. RESULTS The F variant (or T allele at single nucleotide polymorphism at rs3775291) was associated with protection against GA (P=0.005); this association was replicated in two independent GA case-control series (P=5.43×10−4 and P=0.002, respectively. We observed no association between TLR3 variants and CNV. The rs377291 variant is probably critical to the function of TLR3, because a prototypic TLR3 ligand induced cell death and apoptosis in human RPE cells with the LL genotype to a greater extent than it did RPE cells with the LF genotype. Moreover, the ligand induced more RPE cell death and apoptosis in wild-type than in Tlr3−/− mice. CONCLUSIONS The TLR3 412F variant confers protection against GA, probably by suppressing RPE cell death. Given that double stranded RNA can activate TLR3-mediated apoptosis, our results suggest a possible role for viral dsRNA transcripts in the development of GA and raise awareness of potential toxicity induced by short interfering RNA (siRNA) therapeutics in the eye. PMID:18753640

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.

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.

[Geographic data for Neotropical bats (Chiroptera)].

Science.gov (United States)

Noguera-Urbano, Elkin A; Escalante, Tania

2014-03-01

The global effort to digitize biodiversity occurrence data from collections, museums and other institutions has stimulated the development of important tools to improve the knowledge and conservation of biodiversity. The Global Biodiversity Information Facility (GBIF) enables and opens access to biodiversity data of 321 million of records, from 379 host institutions. Neotropical bats are a highly diverse and specialized group, and the geographic information about them is increasing since few years ago, but there are a few reports about this topic. The aim of this study was to analyze the number of digital records in GBIF of Neotropical bats with distribution in 21 American countries, evaluating their nomenclatural and geographical consistence at scale of country. Moreover, we evaluated the gaps of information on 1 degrees latitude x 1 degrees longitude grids cells. There were over 1/2 million records, but 58% of them have no latitude and longitude data; and 52% full fit nomenclatural and geographic evaluation. We estimated that there are no records in 54% of the analyzed area; the principal gaps are in biodiversity hotspots like the Colombian and Brazilian Amazonia and Southern Venezuela. In conclusion, our study suggests that available data on GBIF have nomenclatural and geographic biases. GBIF data represent partially the bat species richness and the main gaps in information are in South America.

Geographic segmentation of users and its use in advertising

OpenAIRE

Dolenc, Blaž

2015-01-01

In modern web advertising the goal is not only deliver an ad to a broad number of customers, but to target particular customers who are more likely to be interested in content. If the user location is known, we can estimate click on ad based on previous visitors. The company Zemanta recognized the need for geographic audience segmentation, and they have invited students to solve their challenge. The goal was geographic segmentation of web pages visitors based on the ZIP code they come from a...

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.

Geographic variation and sociodemographic disparity in the use of oxaliplatin-containing chemotherapy in patients with stage III colon cancer.

Science.gov (United States)

Panchal, Janki M; Lairson, David R; Chan, Wenyaw; Du, Xianglin L

2013-06-01

This study examined the geographic variation and sociodemographic disparities in the use of oxaliplatin chemotherapy, which has not been widely studied in the past. Our results suggest that chemotherapy use varies across geographic regions. Patterns of use that relate specifically to oxaliplatin-containing chemotherapy can inform providers and researchers how newer regimens are being used as standard chemotherapy in a real-world setting. According to the National Cancer Comprehensive Network (NCCN), oxaliplatin with 5-fluorouracil and leucovorin (5-FU/LV) is the recommended adjuvant chemotherapy for patients with resected stage III colon cancer. Age and race are considered strong predictors of chemotherapy receipt, whereas geographic disparity has received minimal attention. The purpose of this study was to examine geographic variation and sociodemographic disparity in the use of chemotherapy in patients with stage III colon cancer, focusing specifically on oxaliplatin. A retrospective cohort of 4106 Medicare patients was identified from the Surveillance, Epidemiology and End Results (SEER)/Medicare linked database. Descriptive statistics show how oxaliplatin-containing chemotherapy was used in various geographic regions among different age and racial groups. Multiple logistic regression analysis was performed to examine the relationship between receipt of oxaliplatin-containing chemotherapy and geographic region while adjusting for other sociodemographic and tumor characteristics. Only 49% of the patients with stage III disease received adjuvant chemotherapy within 3 to 6 months of colon cancer-specific surgery. Patients aged 66 to 70 years were 78% more likely to receive chemotherapy than were those aged 80 years and older (Pcancer care to all patients according to their preferences and needs. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Geographic Names

Data.gov (United States)

Minnesota Department of Natural Resources — The Geographic Names Information System (GNIS), developed by the United States Geological Survey in cooperation with the U.S. Board of Geographic Names, provides...

Ontology for cell-based geographic information

Science.gov (United States)

Zheng, Bin; Huang, Lina; Lu, Xinhai

2009-10-01

Inter-operability is a key notion in geographic information science (GIS) for the sharing of geographic information (GI). That requires a seamless translation among different information sources. Ontology is enrolled in GI discovery to settle the semantic conflicts for its natural language appearance and logical hierarchy structure, which are considered to be able to provide better context for both human understanding and machine cognition in describing the location and relationships in the geographic world. However, for the current, most studies on field ontology are deduced from philosophical theme and not applicable for the raster expression in GIS-which is a kind of field-like phenomenon but does not physically coincide to the general concept of philosophical field (mostly comes from the physics concepts). That's why we specifically discuss the cell-based GI ontology in this paper. The discussion starts at the investigation of the physical characteristics of cell-based raster GI. Then, a unified cell-based GI ontology framework for the recognition of the raster objects is introduced, from which a conceptual interface for the connection of the human epistemology and the computer world so called "endurant-occurrant window" is developed for the better raster GI discovery and sharing.

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

Average monthly and annual climate maps for Bolivia

KAUST Repository

Vicente-Serrano, Sergio M.

2015-02-24

This study presents monthly and annual climate maps for relevant hydroclimatic variables in Bolivia. We used the most complete network of precipitation and temperature stations available in Bolivia, which passed a careful quality control and temporal homogenization procedure. Monthly average maps at the spatial resolution of 1 km were modeled by means of a regression-based approach using topographic and geographic variables as predictors. The monthly average maximum and minimum temperatures, precipitation and potential exoatmospheric solar radiation under clear sky conditions are used to estimate the monthly average atmospheric evaporative demand by means of the Hargreaves model. Finally, the average water balance is estimated on a monthly and annual scale for each 1 km cell by means of the difference between precipitation and atmospheric evaporative demand. The digital layers used to create the maps are available in the digital repository of the Spanish National Research Council.

Identifying areas of need relative to liver disease: geographic clustering within a health service district.

Science.gov (United States)

El-Atem, Nathan; Irvine, Katharine M; Valery, Patricia C; Wojcik, Kyle; Horsfall, Leigh; Johnson, Tracey; Janda, Monika; McPhail, Steven M; Powell, Elizabeth E

2017-08-01

Background Many people with chronic liver disease (CLD) are not detected until they present to hospital with advanced disease, when opportunities for intervention are reduced and morbidity is high. In order to build capacity and liver expertise in the community, it is important to focus liver healthcare resources in high-prevalence disease areas and specific populations with an identified need. The aim of the present study was to examine the geographic location of people seen in a tertiary hospital hepatology clinic, as well as ethnic and sociodemographic characteristics of these geographic areas. Methods The geographic locations of hepatology out-patients were identified via the out-patient scheduling database and grouped into statistical area (SA) regions for demographic analysis using data compiled by the Australian Bureau of Statistics. Results During the 3-month study period, 943 individuals from 71 SA Level 3 regions attended clinic. Nine SA Level 3 regions accounted for 55% of the entire patient cohort. Geographic clustering was seen especially for people living with chronic hepatitis B virus. There was a wide spectrum of socioeconomic advantage and disadvantage in areas with high liver disease prevalence. Conclusions The geographic area from which people living with CLD travel to access liver health care is extensive. However, the greatest demand for tertiary liver disease speciality care is clustered within specific geographic areas. Outreach programs targeted to these areas may enhance liver disease-specific health service resourcing. What is known about the topic? The demand for tertiary hospital clinical services in CLD is rising. However, there is limited knowledge about the geographic areas from which people living with CLD travel to access liver services, or the ethnic, socioeconomic and education characteristics of these areas. What does this paper add? The present study demonstrates that a substantial proportion of people living with CLD and

Geographic Media Literacy

Science.gov (United States)

Lukinbeal, Chris

2014-01-01

While the use of media permeates geographic research and pedagogic practice, the underlying literacies that link geography and media remain uncharted. This article argues that geographic media literacy incorporates visual literacy, information technology literacy, information literacy, and media literacy. Geographic media literacy is the ability…

The Effects of Geographic Isolation and Social Support on the Health of Wisconsin Women.

Science.gov (United States)

Tittman, Sarah M; Harteau, Christy; Beyer, Kirsten M M

2016-04-01

Rural residents are less likely to receive preventive health screening, more likely to be uninsured, and more likely to report fair to poor health than urban residents. Social disconnectedness and perceived isolation are known to be negative predictors of self-rated physical health; however, the direct effects of geographic isolation and social support on overall health have not been well elucidated. A cross-sectional survey of women (n = 113) participating in Wisconsin Rural Women's initiative programming was conducted, which included measures of geographic isolation, an assessment of overall health, and social support using the validated Interpersonal Support Evaluation List with 3 subscales, including belonging support, tangible support, and appraisal support. Geographic isolation was shown to be a negative predictor of belonging support (P = .0064) and tangible support (P = .0349); however, geographic isolation was not a statistically significant predictor of appraisal support. A strong and direct relationship was observed between social support and self-perceived health status among this population of Wisconsin women, and hospital access based on geographic proximity was positively correlated (P = .028) with overall health status. The direct relationship between social support and overall health demonstrated here stresses the importance of developing and maintaining strong social support networks, which can be improved through rural support groups that have the unique ability to assist rural residents in fostering social support systems, advocating stress management techniques, and achieving a greater sense of well-being.

Geographic Object-Based Image Analysis: Towards a new paradigm

NARCIS (Netherlands)

Blaschke, T.; Hay, G.J.; Kelly, M.; Lang, S.; Hofmann, P.; Addink, E.A.|info:eu-repo/dai/nl/224281216; Queiroz Feitosa, R.; van der Meer, F.D.|info:eu-repo/dai/nl/138940908; van der Werff, H.M.A.; van Coillie, F.; Tiede, A.

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis – GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature

A cost-effective Geographic Information Systems for Transportation ...

African Journals Online (AJOL)

A cost-effective Geographic Information Systems for Transportation (GIS-T) application for traffic congestion analyses in the Developing World. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like ...

Rule-guided human classification of Volunteered Geographic Information

Science.gov (United States)

Ali, Ahmed Loai; Falomir, Zoe; Schmid, Falko; Freksa, Christian

2017-05-01

During the last decade, web technologies and location sensing devices have evolved generating a form of crowdsourcing known as Volunteered Geographic Information (VGI). VGI acted as a platform of spatial data collection, in particular, when a group of public participants are involved in collaborative mapping activities: they work together to collect, share, and use information about geographic features. VGI exploits participants' local knowledge to produce rich data sources. However, the resulting data inherits problematic data classification. In VGI projects, the challenges of data classification are due to the following: (i) data is likely prone to subjective classification, (ii) remote contributions and flexible contribution mechanisms in most projects, and (iii) the uncertainty of spatial data and non-strict definitions of geographic features. These factors lead to various forms of problematic classification: inconsistent, incomplete, and imprecise data classification. This research addresses classification appropriateness. Whether the classification of an entity is appropriate or inappropriate is related to quantitative and/or qualitative observations. Small differences between observations may be not recognizable particularly for non-expert participants. Hence, in this paper, the problem is tackled by developing a rule-guided classification approach. This approach exploits data mining techniques of Association Classification (AC) to extract descriptive (qualitative) rules of specific geographic features. The rules are extracted based on the investigation of qualitative topological relations between target features and their context. Afterwards, the extracted rules are used to develop a recommendation system able to guide participants to the most appropriate classification. The approach proposes two scenarios to guide participants towards enhancing the quality of data classification. An empirical study is conducted to investigate the classification of grass

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

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

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.

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

Exploring Additional Determinants of Environmentally Responsible Behavior: The Influence of Environmental Literature and Environmental Attitudes

Science.gov (United States)

Mobley, Catherine; Vagias, Wade M.; DeWard, Sarah L.

2010-01-01

It is often assumed that individuals who are knowledgeable and concerned about the environment will engage in environmentally responsible behavior (ERB). We use data from a large scale Web survey hosted on National Geographic's Web site in 2001-2002 to investigate this premise. We examine whether reading three classic environmental books…

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

Socially just publishing: implications for geographers and their journals

Directory of Open Access Journals (Sweden)

Simon Batterbury

2017-12-01

Full Text Available There have been a range of protests against the high journal subscription costs, and author processing charges (APCs levied for publishing in the more prestigious and commercially run journals that are favoured by geographers. But open protests across the sector like the ‘Academic Spring’ of 2012, and challenges to commercial copyright agreements, have been fragmented and less than successful. I renew the argument for ‘socially just’ publishing in geography. For geographers this is not limited to choosing alternative publication venues. It also involves a considerable effort by senior faculty members that are assessing hiring and promotion cases, to read and assess scholarship independently of its place of publication, and to reward the efforts of colleagues that offer their work as a public good. Criteria other than the citation index and prestige of a journal need to be foregrounded. Geographers can also be publishers, and I offer my experience editing the free online Journal of Political Ecology.

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...

Geographical structure and differential natural selection among North European populations

DEFF Research Database (Denmark)

McEvoy, Brian P; Montgomery, Grant W; McRae, Allan F

2009-01-01

polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like...

Integrative real-time geographic visualization of energy resources

International Nuclear Information System (INIS)

Sorokine, A.; Shankar, M.; Stovall, J.; Bhaduri, B.; King, T.; Fernandez, S.; Datar, N.; Omitaomu, O.

2009-01-01

'Full text:' Several models forecast that climatic changes will increase the frequency of disastrous events like droughts, hurricanes, and snow storms. Responding to these events and also to power outages caused by system errors such as the 2003 North American blackout require an interconnect-wide real-time monitoring system for various energy resources. Such a system should be capable of providing situational awareness to its users in the government and energy utilities by dynamically visualizing the status of the elements of the energy grid infrastructure and supply chain in geographic contexts. We demonstrate an approach that relies on Google Earth and similar standard-based platforms as client-side geographic viewers with a data-dependent server component. The users of the system can view status information in spatial and temporal contexts. These data can be integrated with a wide range of geographic sources including all standard Google Earth layers and a large number of energy and environmental data feeds. In addition, we show a real-time spatio-temporal data sharing capability across the users of the system, novel methods for visualizing dynamic network data, and a fine-grain access to very large multi-resolution geographic datasets for faster delivery of the data. The system can be extended to integrate contingency analysis results and other grid models to assess recovery and repair scenarios in the case of major disruption. (author)

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.

Geographic Variations in Cost of Living: Associations with Family and Child Well-Being

Science.gov (United States)

Chien, Nina C.; Mistry, Rashmita S.

2013-01-01

The effects of geographic variations in cost of living and family income on children's academic achievement and social competence in first grade (mean age = 86.9 months) were examined, mediated through material hardship, parental investments, family stress, and school resources. Using data from the Early Childhood Longitudinal Study-Kindergarten…

The Effect of Geographic Units of Analysis on Measuring Geographic Variation in Medical Services Utilization

Directory of Open Access Journals (Sweden)

Agnus M. Kim

2016-07-01

Full Text Available Objectives: We aimed to evaluate the effect of geographic units of analysis on measuring geographic variation in medical services utilization. For this purpose, we compared geographic variations in the rates of eight major procedures in administrative units (districts and new areal units organized based on the actual health care use of the population in Korea. Methods: To compare geographic variation in geographic units of analysis, we calculated the age–sex standardized rates of eight major procedures (coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, surgery after hip fracture, knee-replacement surgery, caesarean section, hysterectomy, computed tomography scan, and magnetic resonance imaging scan from the National Health Insurance database in Korea for the 2013 period. Using the coefficient of variation, the extremal quotient, and the systematic component of variation, we measured geographic variation for these eight procedures in districts and new areal units. Results: Compared with districts, new areal units showed a reduction in geographic variation. Extremal quotients and inter-decile ratios for the eight procedures were lower in new areal units. While the coefficient of variation was lower for most procedures in new areal units, the pattern of change of the systematic component of variation between districts and new areal units differed among procedures. Conclusions: Geographic variation in medical service utilization could vary according to the geographic unit of analysis. To determine how geographic characteristics such as population size and number of geographic units affect geographic variation, further studies are needed.

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.

Beyond redundancy how geographic redundancy can improve service availability and reliability of computer-based systems

CERN Document Server

Bauer, Eric; Eustace, Dan

2012-01-01

"While geographic redundancy can obviously be a huge benefit for disaster recovery, it is far less obvious what benefit is feasible and likely for more typical non-catastrophic hardware, software, and human failures. Georedundancy and Service Availability provides both a theoretical and practical treatment of the feasible and likely benefits of geographic redundancy for both service availability and service reliability. The text provides network/system planners, IS/IT operations folks, system architects, system engineers, developers, testers, and other industry practitioners with a general discussion about the capital expense/operating expense tradeoff that frames system redundancy and georedundancy"--

Geographical information systems

DEFF Research Database (Denmark)

Möller, Bernd

2004-01-01

The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management.......The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management....

Explaining Global Women's Empowerment Using Geographic Inquiry

Science.gov (United States)

Grubbs, Melanie R.

2018-01-01

It is difficult for students who are just being introduced to major geographical concepts to understand how relatively free countries like India or Mali can have such high levels of human rights abuses as child brides, dowry deaths, and domestic violence. Textbooks explain it and video clips show examples, but it still seems surreal to teenagers…

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

Geographic Ontologies, Gazetteers and Multilingualism

Directory of Open Access Journals (Sweden)

Robert Laurini

2015-01-01

Full Text Available Different languages imply different visions of space, so that terminologies are different in geographic ontologies. In addition to their geometric shapes, geographic features have names, sometimes different in diverse languages. In addition, the role of gazetteers, as dictionaries of place names (toponyms, is to maintain relations between place names and location. The scope of geographic information retrieval is to search for geographic information not against a database, but against the whole Internet: but the Internet stores information in different languages, and it is of paramount importance not to remain stuck to a unique language. In this paper, our first step is to clarify the links between geographic objects as computer representations of geographic features, ontologies and gazetteers designed in various languages. Then, we propose some inference rules for matching not only types, but also relations in geographic ontologies with the assistance of gazetteers.

[Geographic variability of Adh-F allele frequency in populations of Drosophila melanogaster].

Science.gov (United States)

Bubliĭ, O A; Imasheva, A G

1997-07-01

Variation of Adh-F allele frequency in seven regions of North and South America, Eurasia, Africa, and Australia was analyzed on the basis of published data. In six regions, regression of Adh-F frequency on latitude was positive; in four regions, slopes of the regression curves were identical. Regression on the average lowest temperature of the coldest month was negative in six regions. No definite trends in regression on the highest temperature of the hottest month and on rainfall in the most humid month and the driest months were found. Geographic differentiation of populations was independent of climatic parameters. Examination of variation in various climatic zones revealed that tropical populations were distinctly different from those from other climatic zones. No climatic differentiation of fixation index FST was detected. These results indicate that Adh polymorphism is maintained by natural selection.

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).

Three-dimensional visualization of geographical terrain data using temporal parallax difference induction

Science.gov (United States)

Mayhew, Christopher A.; Mayhew, Craig M.

2009-02-01

Vision III Imaging, Inc. (the Company) has developed Parallax Image Display (PIDTM) software tools to critically align and display aerial images with parallax differences. Terrain features are rendered obvious to the viewer when critically aligned images are presented alternately at 4.3 Hz. The recent inclusion of digital elevation models in geographic data browsers now allows true three-dimensional parallax to be acquired from virtual globe programs like Google Earth. The authors have successfully developed PID methods and code that allow three-dimensional geographical terrain data to be visualized using temporal parallax differences.

Build Trust Index for Volunteered Geographic Information: A Case Study of Safecast

Science.gov (United States)

Xin, Y.; Cervone, G.

2017-12-01

Volunteered Geographic Information (VGI), defined as geographic information contributed voluntarily by amateurs, have grown exponentially nowadays with the aid of ubiquitous GPS-enabled telecommunication technologies. VGI projects, like Wikimapia, OpenStreetMap, Flickr and Safecast have shown remarkable success on leveraging citizen science to increase our knowledge about the geographic world. However, in spite of its growing popularity, VGI is still facing the most challenging problem of ensuring data quality. In this study, we proposed a methodology to filter outliers in Safecast measurements through cross-reference among volunteers. Based on the outliers filtered, a trust index is generated for each volunteer. The results are validated using official radiation measurements surveyed by Department of Energy. The validation shows that removing the outliers filtered by our methodology, Safecast measurements yield a better correlation with official measurements.

A Geographical Heuristic Routing Protocol for VANETs

Science.gov (United States)

Urquiza-Aguiar, Luis; Tripp-Barba, Carolina; Aguilar Igartua, Mónica

2016-01-01

Vehicular ad hoc networks (VANETs) leverage the communication system of Intelligent Transportation Systems (ITS). Recently, Delay-Tolerant Network (DTN) routing protocols have increased their popularity among the research community for being used in non-safety VANET applications and services like traffic reporting. Vehicular DTN protocols use geographical and local information to make forwarding decisions. However, current proposals only consider the selection of the best candidate based on a local-search. In this paper, we propose a generic Geographical Heuristic Routing (GHR) protocol that can be applied to any DTN geographical routing protocol that makes forwarding decisions hop by hop. GHR includes in its operation adaptations simulated annealing and Tabu-search meta-heuristics, which have largely been used to improve local-search results in discrete optimization. We include a complete performance evaluation of GHR in a multi-hop VANET simulation scenario for a reporting service. Our study analyzes all of the meaningful configurations of GHR and offers a statistical analysis of our findings by means of MANOVA tests. Our results indicate that the use of a Tabu list contributes to improving the packet delivery ratio by around 5% to 10%. Moreover, if Tabu is used, then the simulated annealing routing strategy gets a better performance than the selection of the best node used with carry and forwarding (default operation). PMID:27669254

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

Natural gas monthly, September 1991. [Contains glossary

Energy Technology Data Exchange (ETDEWEB)

1991-10-18

The Natural Gas Monthly highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. Volume and price data are presented each month for natural gas production distribution consumption, and interstate pipeline activities. Producer-related activities and underground storage data are also reported. From time to time, the NGM features articles designed to assist readers in using and interpreting natural gas information. The data in this publication are collected on surveys conducted by the EIA to fulfill its responsibilities for gathering and reporting energy data. Some of the data are collected under the authority of the Federal Energy Regulatory Commission (FERC), an independent commission within the DOE, which has jurisdiction primarily in the regulation of electric utilities and the interstate natural gas industry. Geographic coverage is the 50 States and the District of Columbia.

Petroleum supply monthly, April 1998, with data for February 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-04-01

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. Data presented in the PSM describe the supply and disposition of petroleum products in the US 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 US (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 US. 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 US (50 States and District of Columbia), 5 PAD Districts and 12 Refining Districts. 16 figs., 56 tabs.

GEOGRAPHIC NAMES INFORMATION SYSTEM (GNIS) ...

Science.gov (United States)

The Geographic Names Information System (GNIS), developed by the U.S. Geological Survey in cooperation with the U.S. Board on Geographic Names (BGN), contains information about physical and cultural geographic features in the United States and associated areas, both current and historical, but not including roads and highways. The database also contains geographic names in Antarctica. The database holds the Federally recognized name of each feature and defines the location of the feature by state, county, USGS topographic map, and geographic coordinates. Other feature attributes include names or spellings other than the official name, feature designations, feature class, historical and descriptive information, and for some categories of features the geometric boundaries. The database assigns a unique feature identifier, a random number, that is a key for accessing, integrating, or reconciling GNIS data with other data sets. The GNIS is our Nation's official repository of domestic geographic feature names information.

Fuzzy modeling with spatial information for geographic problems

CERN Document Server

Petry, Frederick E; Cobb, Maria A

2005-01-01

The capabilities of modern technology are rapidly increasing, spurred on to a large extent by the tremendous advances in communications and computing. Automated vehicles and global wireless connections are some examples of these advances. In order to take advantage of such enhanced capabilities, our need to model and manipulate our knowledge of the geophysical world, using compatible representations, is also rapidly increasing. In response to this one fundamental issue of great concern in modern geographical research is how to most effectively capture the physical world around us in systems like geographical information systems (GIS). Making this task even more challenging is the fact that uncertainty plays a pervasive role in the representation, analysis and use of geospatial information. The types of uncertainty that appear in geospatial information systems are not the just simple randomness of observation, as in weather data, but are manifested in many other forms including imprecision, incompleteness and ...

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.

Volunteered Geographic Information in Wikipedia

Science.gov (United States)

Hardy, Darren

2010-01-01

Volunteered geographic information (VGI) refers to the geographic subset of online user-generated content. Through Geobrowsers and online mapping services, which use geovisualization and Web technologies to share and produce VGI, a global digital commons of geographic information has emerged. A notable example is Wikipedia, an online collaborative…

Geographic Names Information System (GNIS) for Lousiana, Geographic NAD83, USGS (2007) [GNIS_LA_USGS_2007

Data.gov (United States)

Louisiana Geographic Information Center — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

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

Sirenomelia in Argentina: Prevalence, geographic clusters and temporal trends analysis.

Science.gov (United States)

Groisman, Boris; Liascovich, Rosa; Gili, Juan Antonio; Barbero, Pablo; Bidondo, María Paz

2016-07-01

Sirenomelia is a severe malformation of the lower body characterized by a single medial lower limb and a variable combination of visceral abnormalities. Given that Sirenomelia is a very rare birth defect, epidemiological studies are scarce. The aim of this study is to evaluate prevalence, geographic clusters and time trends of sirenomelia in Argentina, using data from the National Network of Congenital Anomalies of Argentina (RENAC) from November 2009 until December 2014. This is a descriptive study using data from the RENAC, a hospital-based surveillance system for newborns affected with major morphological congenital anomalies. We calculated sirenomelia prevalence throughout the period, searched for geographical clusters, and evaluated time trends. The prevalence of confirmed cases of sirenomelia throughout the period was 2.35 per 100,000 births. Cluster analysis showed no statistically significant geographical aggregates. Time-trends analysis showed that the prevalence was higher in years 2009 to 2010. The observed prevalence was higher than the observed in previous epidemiological studies in other geographic regions. We observed a likely real increase in the initial period of our study. We used strict diagnostic criteria, excluding cases that only had clinical diagnosis of sirenomelia. Therefore, real prevalence could be even higher. This study did not show any geographic clusters. Because etiology of sirenomelia has not yet been established, studies of epidemiological features of this defect may contribute to define its causes. Birth Defects Research (Part A) 106:604-611, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Changes at the National Geographic Society

Science.gov (United States)

Schwille, Kathleen

2016-01-01

For more than 125 years, National Geographic has explored the planet, unlocking its secrets and sharing them with the world. For almost thirty of those years, National Geographic has been committed to K-12 educators and geographic education through its Network of Alliances. As National Geographic begins a new chapter, they remain committed to the…

Conceptual Model of Dynamic Geographic Environment

Directory of Open Access Journals (Sweden)

Martínez-Rosales Miguel Alejandro

2014-04-01

Full Text Available In geographic environments, there are many and different types of geographic entities such as automobiles, trees, persons, buildings, storms, hurricanes, etc. These entities can be classified into two groups: geographic objects and geographic phenomena. By its nature, a geographic environment is dynamic, thus, it’s static modeling is not sufficient. Considering the dynamics of geographic environment, a new type of geographic entity called event is introduced. The primary target is a modeling of geographic environment as an event sequence, because in this case the semantic relations are much richer than in the case of static modeling. In this work, the conceptualization of this model is proposed. It is based on the idea to process each entity apart instead of processing the environment as a whole. After that, the so called history of each entity and its spatial relations to other entities are defined to describe the whole environment. The main goal is to model systems at a conceptual level that make use of spatial and temporal information, so that later it can serve as the semantic engine for such systems.

Prevalence and geographic variations in asthma symptoms in children and adolescents in Galicia (Spain).

Science.gov (United States)

López-Silvarrey-Varela, Angel; Pértega-Díaz, Sonia; Rueda-Esteban, Santiago; Sánchez-Lastres, Juan Manuel; San-José-González, Miguel Angel; Sampedro-Campos, Manuel; Pérez-Castro, Teresa; Garnelo-Suárez, Luciano; Bamonde-Rodríguez, Luis; López-Silvarrey-Varela, Javier; González-Barcala, Javier

2011-06-01

To determine the prevalence and geographic variations of the symptoms associated with asthma in Galician children and adolescents. A cross-sectional epidemiological study following ISAAC (International Study of Asthma and Allergies in Childhood) methodology, and using a written questionnaire distributed in schools. The study sample included 10,371 6-7 year-old children and 10,372 13-14 year-old adolescents, all of them from Galician Health Areas. A logistic regression model was used to analyse geographic variations. In the 6-7 year-old group, wheezing in the last 12 months varied from 11.4% (Santiago) to 15.7% (Vigo) and in the adolescents varied from 8.8% (Ourense) to 18.8% (Vigo). The distribution by gender showed a predominant significance in 6-7 year-old males (Pchildren and 2.39 (95% CI, 1.82-3.13) for adolescents. The estimated prevalence of asthma in the Autonomous Community of Galicia was 13.6% in younger children and 12.2% in adolescents. The prevalence of wheezing in the last 12 months in the different areas of Galicia is considerably higher than the rest of Spanish ISAAC cities in the 6-7 years group and very similar in the 13-14 years group, except in Vigo where it is considerably higher. We found a clearly defined geographic pattern in the adolescent group, with higher prevalences in coastal areas than in the interior. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Petroleum supply monthly, December 1995: With data for October 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 US (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 US. The tables and figures in the Summary Statistics section of the PSM present a time series of selected petroleum data on a US level. 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 US (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. 16 figs., 6 tabs.

Urethroplasty: a geographic disparity in care.

Science.gov (United States)

Burks, Frank N; Salmon, Scott A; Smith, Aaron C; Santucci, Richard A

2012-06-01

Urethroplasty is the gold standard for urethral strictures but its geographic prevalence throughout the United States is unknown. We analyzed where and how often urethroplasty was being performed in the United States compared to other treatment modalities for urethral stricture. De-identified case logs from the American Board of Urology were collected from certifying/recertifying urologists from 2004 to 2009. Results were categorized by ZIP codes to determine the geographic distribution. Case logs from 3,877 urologists (2,533 recertifying and 1,344 certifying) were reviewed including 1,836 urethroplasties, 13,080 urethrotomies and 19,564 urethral dilations. The proportion of urethroplasty varied widely among states (range 0% to 17%). The ratio of urethroplasty-to-urethrotomy/dilation also varied widely from state to state, but overall 1 urethroplasty was performed for every 17 urethrotomies or dilations performed. Certifying urologists were 3 times as likely to perform urethroplasty as recertifying urologists (12% vs 4%, respectively, pUrethroplasties were performed more commonly in states with residency programs (mean 5% vs 3%). Some states reported no urethroplasties during the observation period (Vermont, North Dakota, South Dakota, Maine and West Virginia). To our knowledge this is the first report on the geographic distribution of urethroplasty for urethral stricture disease. There are large variations in the rates of urethroplasty performed throughout the United States, indicating a disparity of care, especially for those regions in which few or no urethroplasties were reported. This disparity may decrease with time as younger certifying urologists are performing 3 times as many urethroplasties as older recertifying urologists. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Geographic information system for Long Island: An epidemiologic systems approach to identify environmental breast cancer risks on Long Island. Phase 1

Energy Technology Data Exchange (ETDEWEB)

Barancik, J.I.; Kramer, C.F.; Thode, H.C. Jr.

1995-12-01

BNL is developing and implementing the project ``Geographic Information System (GIS) for Long Island`` to address the potential relationship of environmental and occupational exposures to breast cancer etiology on Long Island. The project is divided into two major phases: The four month-feasibility project (Phase 1), and the major development and implementation project (Phase 2). This report summarizes the work completed in the four month Phase 1 Project, ``Feasibility of a Geographic Information System for Long Island.`` It provides the baseline information needed to further define and prioritize the scope of work for subsequent tasks. Phase 2 will build upon this foundation to develop an operational GIS for the Long Island Breast Cancer Study Project (LIBCSP).

Geographic information system for Long Island: An epidemiologic systems approach to identify environmental breast cancer risks on Long Island. Phase 1

International Nuclear Information System (INIS)

Barancik, J.I.; Kramer, C.F.; Thode, H.C. Jr.

1995-01-01

BNL is developing and implementing the project ''Geographic Information System (GIS) for Long Island'' to address the potential relationship of environmental and occupational exposures to breast cancer etiology on Long Island. The project is divided into two major phases: The four month-feasibility project (Phase 1), and the major development and implementation project (Phase 2). This report summarizes the work completed in the four month Phase 1 Project, ''Feasibility of a Geographic Information System for Long Island.'' It provides the baseline information needed to further define and prioritize the scope of work for subsequent tasks. Phase 2 will build upon this foundation to develop an operational GIS for the Long Island Breast Cancer Study Project (LIBCSP)

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.

Bio-geographic classification of the Caspian Sea

Science.gov (United States)

Fendereski, F.; Vogt, M.; Payne, M. R.; Lachkar, Z.; Gruber, N.; Salmanmahiny, A.; Hosseini, S. A.

2014-03-01

Like other inland seas, the Caspian Sea (CS) has been influenced by climate change and anthropogenic disturbance during recent decades, yet the scientific understanding of this water body remains poor. In this study, an eco-geographical classification of the CS based on physical information derived from space and in-situ data is developed and tested against a set of biological observations. We used a two-step classification procedure, consisting of (i) a data reduction with self-organizing maps (SOMs) and (ii) a synthesis of the most relevant features into a reduced number of marine ecoregions using the Hierarchical Agglomerative Clustering (HAC) method. From an initial set of 12 potential physical variables, 6 independent variables were selected for the classification algorithm, i.e., sea surface temperature (SST), bathymetry, sea ice, seasonal variation of sea surface salinity (DSSS), total suspended matter (TSM) and its seasonal variation (DTSM). The classification results reveal a robust separation between the northern and the middle/southern basins as well as a separation of the shallow near-shore waters from those off-shore. The observed patterns in ecoregions can be attributed to differences in climate and geochemical factors such as distance from river, water depth and currents. A comparison of the annual and monthly mean Chl a concentrations between the different ecoregions shows significant differences (Kruskal-Wallis rank test, P qualitative evaluation of differences in community composition based on recorded presence-absence patterns of 27 different species of plankton, fish and benthic invertebrate also confirms the relevance of the ecoregions as proxies for habitats with common biological characteristics.

Geographical National Condition and Complex System

Directory of Open Access Journals (Sweden)

WANG Jiayao

2016-01-01

Full Text Available The significance of studying the complex system of geographical national conditions lies in rationally expressing the complex relationships of the “resources-environment-ecology-economy-society” system. Aiming to the problems faced by the statistical analysis of geographical national conditions, including the disunity of research contents, the inconsistency of range, the uncertainty of goals, etc.the present paper conducted a range of discussions from the perspectives of concept, theory and method, and designed some solutions based on the complex system theory and coordination degree analysis methods.By analyzing the concepts of geographical national conditions, geographical national conditions survey and geographical national conditions statistical analysis, as well as investigating the relationships between theirs, the statistical contents and the analytical range of geographical national conditions are clarified and defined. This investigation also clarifies the goals of the statistical analysis by analyzing the basic characteristics of the geographical national conditions and the complex system, and the consistency between the analysis of the degree of coordination and statistical analyses. It outlines their goals, proposes a concept for the complex system of geographical national conditions, and it describes the concept. The complex system theory provides new theoretical guidance for the statistical analysis of geographical national conditions. The degree of coordination offers new approaches on how to undertake the analysis based on the measurement method and decision-making analysis scheme upon which the complex system of geographical national conditions is based. It analyzes the overall trend via the degree of coordination of the complex system on a macro level, and it determines the direction of remediation on a micro level based on the degree of coordination among various subsystems and of single systems. These results establish

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.

Change in Geographical Proximity: A Qualitative Study of the Experience of Parting

Directory of Open Access Journals (Sweden)

Urvashi Dixit

2017-08-01

Full Text Available The purpose of the present study is to examine the psychological impact on individuals that results from a change in geographic proximity of a close friend, romantic partner and a sibling. The topic was chosen in light of personal experiences, that is, deep affiliation with friends, and the subsequent experience of parting. A total of 6 participants (1 male and 1 female in each of the three categories, aged between 19 to 26 years were selected purposively. Out of these, 2 had experienced change in geographic proximity from a friend and 2 from a romantic partner and 2 from a sibling. The study provides an insight into the experiences of those who deal with the process of a romantic partner, friend or sibling moving away. The participants identified had experienced change in geographic proximity of friend, romantic partner or sibling within a period of 1 to 8 months. The various aspects explored were communication, well-being, loneliness, transition in feelings, coping with stress, significant experiences, etc. The data were collected using a semi structured interview, and was transcribed and analysed through thematic analysis.

Petroleum supply monthly, August 1994

Energy Technology Data Exchange (ETDEWEB)

1994-08-26

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 Effect of Geographic Location on Circannual Adrenocorticotropic Hormone Plasma Concentrations in Horses in Australia.

Science.gov (United States)

Secombe, C J; Tan, R H H; Perara, D I; Byrne, D P; Watts, S P; Wearn, J G

2017-09-01

Longitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere. To longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12-month period. Clinically normal horses horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville. Circannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The measure of success: geographic isolation promotes diversification in Pachydactylus geckos.

Science.gov (United States)

Heinicke, Matthew P; Jackman, Todd R; Bauer, Aaron M

2017-01-11

Geckos of the genus Pachydactylus and their close relatives comprise the most species-rich clade of lizards in sub-Saharan Africa. Many explanations have been offered to explain species richness patterns of clades. In the Pachydactylus group, one possible explanation is a history of diversification via geographic isolation. If geographic isolation has played a key role in facilitating diversification, then we expect species in more species-rich subclades to have smaller ranges than species in less diverse subclades. We also expect traits promoting geographic isolation to be correlated with small geographic ranges. In order to test these expectations, we performed phylogenetic analyses and tested for correlations among body size, habitat choice, range sizes, and diversification rates in the Pachydactylus group. Both body size and habitat use are inferred to have shifted multiple times across the phylogeny of the Pachydactylus group, with large size and generalist habitat use being ancestral for the group. Geographic range size is correlated with both of these traits. Small-bodied species have more restricted ranges than large-bodied species, and rock-dwelling species have more restricted ranges than either terrestrial or generalist species. Rock-dwelling and small body size are also associated with higher rates of diversification, and subclades retaining ancestral conditions for these traits are less species rich than subclades in which shifts to small body size and rocky habitat use have occurred. The phylogeny also illustrates inadequacies of the current taxonomy of the group. The results are consistent with a model in which lineages more likely to become geographically isolated diversify to a greater extent, although some patterns also resemble those expected of an adaptive radiation in which ecological divergence acts as a driver of speciation. Therefore, the Pachydactylus group may represent an intermediate between clades in which radiation is adaptive versus

Petroleum supply monthly

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-10-01

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the 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 blends, 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.

Geographic Gossip: Efficient Averaging for Sensor Networks

Science.gov (United States)

Dimakis, Alexandros D. G.; Sarwate, Anand D.; Wainwright, Martin J.

Gossip algorithms for distributed computation are attractive due to their simplicity, distributed nature, and robustness in noisy and uncertain environments. However, using standard gossip algorithms can lead to a significant waste in energy by repeatedly recirculating redundant information. For realistic sensor network model topologies like grids and random geometric graphs, the inefficiency of gossip schemes is related to the slow mixing times of random walks on the communication graph. We propose and analyze an alternative gossiping scheme that exploits geographic information. By utilizing geographic routing combined with a simple resampling method, we demonstrate substantial gains over previously proposed gossip protocols. For regular graphs such as the ring or grid, our algorithm improves standard gossip by factors of $n$ and $\\sqrt{n}$ respectively. For the more challenging case of random geometric graphs, our algorithm computes the true average to accuracy $\\epsilon$ using $O(\\frac{n^{1.5}}{\\sqrt{\\log n}} \\log \\epsilon^{-1})$ radio transmissions, which yields a $\\sqrt{\\frac{n}{\\log n}}$ factor improvement over standard gossip algorithms. We illustrate these theoretical results with experimental comparisons between our algorithm and standard methods as applied to various classes of random fields.

The application of geographic information system (GIS) in forensics geoscience

OpenAIRE

McKinley, Jennifer

2017-01-01

Advances in technological developments in Geographic Information Systems (GIS) has enabled the application of GIS in landscape mapping, environmental management, natural hazard risk and disaster management. As geographi- cal information becomes more widely available through satel- lite and aerial imagery, the cost of software decreases and GIS expertise expands, it is most likely that the use of GIS will increase. The methodology has practical applications for police, crime scene investigator...

Geographic proximity to treatment for early stage breast cancer and likelihood of mastectomy.

Science.gov (United States)

Boscoe, Francis P; Johnson, Christopher J; Henry, Kevin A; Goldberg, Daniel W; Shahabi, Kaveh; Elkin, Elena B; Ballas, Leslie K; Cockburn, Myles

2011-08-01

Women with early stage breast cancer who live far from a radiation therapy facility may be more likely to opt for mastectomy over breast conserving surgery (BCS). The geographic dimensions of this relationship deserve further scrutiny. For over 100,000 breast cancer patients in 10 states who received either mastectomy or BCS, a newly-developed software tool was used to calculate the shortest travel distance to the location of surgery and to the nearest radiation treatment center. The likelihood of receipt of mastectomy was modeled as a function of these distance measures and other demographic variables using multilevel logistic regression. Women traveling over 75 km for treatment are about 1.4 times more likely to receive a mastectomy than those traveling under 15 km. Geographic barriers to optimal breast cancer treatment remain a valid concern, though most women traveling long distances to receive mastectomies are doing so after bypassing local options. Copyright © 2011 Elsevier Ltd. All rights reserved.

5 CFR 536.303 - Geographic conversion.

Science.gov (United States)

2010-01-01

... after geographic conversion is the employee's existing payable rate of basic pay in effect immediately before the action. (b) Geographic conversion when a retained rate employee's official worksite is changed... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Geographic conversion. 536.303 Section...

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.

Petroleum supply monthly, July 1999, with data for May 1999

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-07-01

The Petroleum Supply Monthly (PSM) is one of a family of four petroleum supply publications produced by the Petroleum Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the PSM describe the supply and disposition of petroleum products in the US 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 US (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 US. Data presented in the PSM are divided into two sections: Summary Statistics and Detailed Statistics. The Detail 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 US (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.

Artificial neural network optimisation for monthly average daily global solar radiation prediction

International Nuclear Information System (INIS)

Alsina, Emanuel Federico; Bortolini, Marco; Gamberi, Mauro; Regattieri, Alberto

2016-01-01

Highlights: • Prediction of the monthly average daily global solar radiation over Italy. • Multi-location Artificial Neural Network (ANN) model: 45 locations considered. • Optimal ANN configuration with 7 input climatologic/geographical parameters. • Statistical indicators: MAPE, NRMSE, MPBE. - Abstract: The availability of reliable climatologic data is essential for multiple purposes in a wide set of anthropic activities and operative sectors. Frequently direct measures present spatial and temporal lacks so that predictive approaches become of interest. This paper focuses on the prediction of the Monthly Average Daily Global Solar Radiation (MADGSR) over Italy using Artificial Neural Networks (ANNs). Data from 45 locations compose the multi-location ANN training and testing sets. For each location, 13 input parameters are considered, including the geographical coordinates and the monthly values for the most frequently adopted climatologic parameters. A subset of 17 locations is used for ANN training, while the testing step is against data from the remaining 28 locations. Furthermore, the Automatic Relevance Determination method (ARD) is used to point out the most relevant input for the accurate MADGSR prediction. The ANN best configuration includes 7 parameters, only, i.e. Top of Atmosphere (TOA) radiation, day length, number of rainy days and average rainfall, latitude and altitude. The correlation performances, expressed through statistical indicators as the Mean Absolute Percentage Error (MAPE), range between 1.67% and 4.25%, depending on the number and type of the chosen input, representing a good solution compared to the current standards.

Potential impacts of climatic change upon geographical distributions of birds

DEFF Research Database (Denmark)

Huntley, Brian; Collingham, Yvonne C.; Green, Rhys E.

2006-01-01

likely to decrease. Species with restricted distributions and specialized species of particular biomes are likely to suffer the greatest impacts. Migrant species are likely to suffer especially large impacts as climatic change alters both their breeding and wintering areas, as well as critical stopover......Potential climatic changes of the near future have important characteristics that differentiate them from the largest magnitude and most rapid of climatic changes of the Quaternary. These potential climatic changes are thus a cause for considerable concern in terms of their possible impacts upon...... biodiversity. Birds, in common with other terrestrial organisms, are expected to exhibit one of two general responses to climatic change: they may adapt to the changed conditions without shifting location, or they may show a spatial response, adjusting their geographical distribution in response...

The Oklahoma Geographic Information Retrieval System

Science.gov (United States)

Blanchard, W. A.

1982-01-01

The Oklahoma Geographic Information Retrieval System (OGIRS) is a highly interactive data entry, storage, manipulation, and display software system for use with geographically referenced data. Although originally developed for a project concerned with coal strip mine reclamation, OGIRS is capable of handling any geographically referenced data for a variety of natural resource management applications. A special effort has been made to integrate remotely sensed data into the information system. The timeliness and synoptic coverage of satellite data are particularly useful attributes for inclusion into the geographic information system.

Fitting monthly Peninsula Malaysian rainfall using Tweedie distribution

Science.gov (United States)

Yunus, R. M.; Hasan, M. M.; Zubairi, Y. Z.

2017-09-01

In this study, the Tweedie distribution was used to fit the monthly rainfall data from 24 monitoring stations of Peninsula Malaysia for the period from January, 2008 to April, 2015. The aim of the study is to determine whether the distributions within the Tweedie family fit well the monthly Malaysian rainfall data. Within the Tweedie family, the gamma distribution is generally used for fitting the rainfall totals, however the Poisson-gamma distribution is more useful to describe two important features of rainfall pattern, which are the occurrences (dry months) and the amount (wet months). First, the appropriate distribution of the monthly rainfall was identified within the Tweedie family for each station. Then, the Tweedie Generalised Linear Model (GLM) with no explanatory variable was used to model the monthly rainfall data. Graphical representation was used to assess model appropriateness. The QQ plots of quantile residuals show that the Tweedie models fit the monthly rainfall data better for majority of the stations in the west coast and mid land than those in the east coast of Peninsula. This significant finding suggests that the best fitted distribution depends on the geographical location of the monitoring station. In this paper, a simple model is developed for generating synthetic rainfall data for use in various areas, including agriculture and irrigation. We have showed that the data that were simulated using the Tweedie distribution have fairly similar frequency histogram to that of the actual data. Both the mean number of rainfall events and mean amount of rain for a month were estimated simultaneously for the case that the Poisson gamma distribution fits the data reasonably well. Thus, this work complements previous studies that fit the rainfall amount and the occurrence of rainfall events separately, each to a different distribution.

COMPARATIVE AND QUANTITATIVE DETERMINATION OF QUERCETIN AND RUTIN IN TRIBULUS TERRESTRIS L. FRUITS FROM DIFFERENT SEASONAL AND GEOGRAPHICAL POPULATIONS OF SOUTH INDIA

OpenAIRE

Suresh Reddy Yanala* and D. Sathyanarayana

2018-01-01

The objective of the present research work was comparative and quantitative determination of quercetin and rutin in Tribulus terrestirs fruits from different geographical regions and seasons by using HPLC. The Tribulus terrestris fruit samples collected from three different geographical regions of south India in June and December months. In the current HPLC analysis flavonoids in Tribulus terrestris Linn fruits were quantified at 360 nm with help of peak area by comparing to a calibration cur...

Plants and geographical names in Croatia.

Science.gov (United States)

Cargonja, Hrvoje; Daković, Branko; Alegro, Antun

2008-09-01

The main purpose of this paper is to present some general observations, regularities and insights into a complex relationship between plants and people through symbolic systems like geographical names on the territory of Croatia. The basic sources of data for this research were maps from atlas of Croatia of the scale 1:100000. Five groups of maps or areas were selected in order to represent main Croatian phytogeographic regions. A selection of toponyms from each of the map was made in which the name for a plant in Croatian language was recognized (phytotoponyms). Results showed that of all plant names recognized in geographical names the most represented are trees, and among them birch and oak the most. Furthermore, an attempt was made to explain the presence of the most represented plant species in the phytotoponyms in the light of general phytogeographical and sociocultural differences and similarities of comparing areas. The findings confirm an expectation that the genera of climazonal vegetation of particular area are the most represented among the phytotoponyms. Nevertheless, there are ample examples where representation of a plant name in the names of human environment can only be ascribed to ethno-linguistic and socio-cultural motives. Despite the reductionist character of applied methodology, this research also points out some advantages of this approach for ethnobotanic and ethnolinguistic studies of greater areas of human environment.

Composing Models of Geographic Physical Processes

Science.gov (United States)

Hofer, Barbara; Frank, Andrew U.

Processes are central for geographic information science; yet geographic information systems (GIS) lack capabilities to represent process related information. A prerequisite to including processes in GIS software is a general method to describe geographic processes independently of application disciplines. This paper presents such a method, namely a process description language. The vocabulary of the process description language is derived formally from mathematical models. Physical processes in geography can be described in two equivalent languages: partial differential equations or partial difference equations, where the latter can be shown graphically and used as a method for application specialists to enter their process models. The vocabulary of the process description language comprises components for describing the general behavior of prototypical geographic physical processes. These process components can be composed by basic models of geographic physical processes, which is shown by means of an example.

Utilization of the emergency room: impact of geographic distance

Directory of Open Access Journals (Sweden)

Jae Eun Lee

2007-05-01

people in these areas are more likely to utilize ER services. Our data suggest that the geographical distance has an impact on ER utilization, especially by reducing utilization in disadvantaged block group areas. Disadvantaged persons living near ER hospitals (<5 miles were found to be more likely to utilize the ER services. Geographic distance should therefore be considered when planning state-wide ER programmes for disadvantaged populations.

Louisiana State Soil Geographic, General Soil Map, Geographic NAD83, NWRC (1998) [statsgo_soils_NWRC_1998

Data.gov (United States)

Louisiana Geographic Information Center — This data set contains vector line map information. The vector data contain selected base categories of geographic features, and characteristics of these features,...

Geographic Information for Analysis of Highway Runoff-Quality Data on a National or Regional Scale in the Conterminous United States

Science.gov (United States)

Smieszek, Tomas W.; Granato, Gregory E.

2000-01-01

Spatial data are important for interpretation of water-quality information on a regional or national scale. Geographic information systems (GIS) facilitate interpretation and integration of spatial data. The geographic information and data compiled for the conterminous United States during the National Highway Runoff Water-Quality Data and Methodology Synthesis project is described in this document, which also includes information on the structure, file types, and the geographic information in the data files. This 'geodata' directory contains two subdirectories, labeled 'gisdata' and 'gisimage.' The 'gisdata' directory contains ArcInfo coverages, ArcInfo export files, shapefiles (used in ArcView), Spatial Data Transfer Standard Topological Vector Profile format files, and meta files in subdirectories organized by file type. The 'gisimage' directory contains the GIS data in common image-file formats. The spatial geodata includes two rain-zone region maps and a map of national ecosystems originally published by the U.S. Environmental Protection Agency; regional estimates of mean annual streamflow, and water hardness published by the Federal Highway Administration; and mean monthly temperature, mean annual precipitation, and mean monthly snowfall modified from data published by the National Climatic Data Center and made available to the public by the Oregon Climate Service at Oregon State University. These GIS files were compiled for qualitative spatial analysis of available data on a national and(or) regional scale and therefore should be considered as qualitative representations, not precise geographic location information.

Geographic access to radiation therapy facilities and disparities of early-stage breast cancer treatment

Directory of Open Access Journals (Sweden)

Yan Lin

2018-05-01

Full Text Available Few studies of breast cancer treatment have focused on the Northern Plains of the United States, an area with a high mastectomy rate. This study examined the association between geographic access to radiation therapy facilities and receipt of breast cancer treatments among early-stage breast cancer patients in South Dakota. Based on 4,209 early-stage breast cancer patients diagnosed between 2001 and 2012 in South Dakota, the study measured geographic proximity to radiation therapy facilities using the shortest travel time for patients to the closest radiation therapy facility. Two-level logistic regression models were used to estimate for early stage cases i the odds of mastectomy versus breast conserving surgery (BCS; ii the odds of not receiving radiation therapy after BCS versus receiving follow-up radiation therapy. Covariates included race/ethnicity, age at diagnosis, tumour grade, tumour sequence, year of diagnosis, census tract-level poverty rate and urban/rural residence. The spatial scan statistic method was used to identify geographic areas with significantly higher likelihood of experiencing mastectomy. The study found that geographic accessibility to radiation therapy facilities was negatively associated with the likelihood of receiving mastectomy after adjustment for other covariates, but not associated with radiation therapy use among patients receiving BCS. Compared with patients travelling less than 30 minutes to a radiation therapy facility, patients travelling more than 90 minutes were about 1.5 times more likely to receive mastectomy (odds ratio, 1.51; 95% confidence interval, 1.08-2.11 and patients travelling more than 120 minutes were 1.7 times more likely to receive mastectomy (odds ratio, 1.70; 95% confidence interval, 1.19-2.42. The study also identified a statistically significant cluster of patients receiving mastectomy who were located in south-eastern South Dakota, after adjustment for other factors. Because

Determinants of Dentists' Geographic Distribution.

Science.gov (United States)

Beazoglou, Tryfon J.; And Others

1992-01-01

A model for explaining the geographic distribution of dentists' practice locations is presented and applied to particular market areas in Connecticut. Results show geographic distribution is significantly related to a few key variables, including demography, disposable income, and housing prices. Implications for helping students make practice…

Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia

Directory of Open Access Journals (Sweden)

Fritzsche Markus

2002-12-01

Full Text Available Abstract Background Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS. As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. Results The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS shows a similar seasonal trend. Conclusion It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP might encourage a new direction of research in molecular epidemiology.

Petroleum Supply Monthly

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-02-01

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the PSM describe the supply and disposition of petroleum products in the United States and major U.S. 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.

Geographical assignment of hospitalists in an urban teaching hospital: feasibility and impact on efficiency and provider satisfaction.

Science.gov (United States)

Bryson, Christine; Boynton, Greta; Stepczynski, Anna; Garb, Jane; Kleppel, Reva; Irani, Farzan; Natanasabapathy, Siva; Stefan, Mihaela S

2017-10-01

To evaluate whether implementation of a geographic model of assigning hospitalists is feasible and sustainable in a large hospitalist program and assess its impact on provider satisfaction, perceived efficiency and patient outcomes. Pre (3 months) - post (12 months) intervention study conducted from June 2014 through September 2015 at a tertiary care medical center with a large hospitalist program caring for patients scattered in 4 buildings and 16 floors. Hospitalists were assigned to a particular nursing unit (geographic assignment) with a goal of having over 80% of their assigned patients located on their assigned unit. Satisfaction and perceived efficiency were assessed through a survey administered before and after the intervention. Geographic assignment percentage increased from an average of 60% in the pre-intervention period to 93% post-intervention. The number of hospitalists covering a 32 bed unit decreased from 8-10 pre to 2-3 post-intervention. A majority of physicians (87%) thought that geography had a positive impact on the overall quality of care. Respondents reported that they felt that geography increased time spent with patient/caregivers to discuss plan of care (p < 0.001); improved communication with nurses (p = 0.0009); and increased sense of teamwork with nurses/case managers (p < 0.001). Mean length of stay (4.54 vs 4.62 days), 30-day readmission rates (16.0% vs 16.6%) and patient satisfaction (79.9 vs 77.3) did not change significantly between the pre- and post-implementation period. The discharge before noon rate improved slightly (47.5% - 54.1%). Implementation of a unit-based model in a large hospitalist program is feasible and sustainable with appropriate planning and support. The geographical model of care increased provider satisfaction and perceived efficiency; it also facilitated the implementation of other key interventions such as interdisciplinary rounds.

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...

Geographic Names Information System (GNIS) Structures

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

The evolution of cooperation on geographical networks

Science.gov (United States)

Li, Yixiao; Wang, Yi; Sheng, Jichuan

2017-11-01

We study evolutionary public goods game on geographical networks, i.e., complex networks which are located on a geographical plane. The geographical feature effects in two ways: In one way, the geographically-induced network structure influences the overall evolutionary dynamics, and, in the other way, the geographical length of an edge influences the cost when the two players at the two ends interact. For the latter effect, we design a new cost function of cooperators, which simply assumes that the longer the distance between two players, the higher cost the cooperator(s) of them have to pay. In this study, network substrates are generated by a previous spatial network model with a cost-benefit parameter controlling the network topology. Our simulations show that the greatest promotion of cooperation is achieved in the intermediate regime of the parameter, in which empirical estimates of various railway networks fall. Further, we investigate how the distribution of edges' geographical costs influences the evolutionary dynamics and consider three patterns of the distribution: an approximately-equal distribution, a diverse distribution, and a polarized distribution. For normal geographical networks which are generated using intermediate values of the cost-benefit parameter, a diverse distribution hinders the evolution of cooperation, whereas a polarized distribution lowers the threshold value of the amplification factor for cooperation in public goods game. These results are helpful for understanding the evolution of cooperation on real-world geographical networks.

Geographical differences in food allergy.

Science.gov (United States)

Bartra, Joan; García-Moral, Alba; Enrique, Ernesto

2016-06-01

Food allergy represents a health problem worldwide and leads to life-threatening reactions and even impairs quality of life. Epidemiological data during the past decades is very heterogeneous because of the use of different diagnostic procedures, and most studies have only been performed in specific geographical areas. The aim of this article is to review the available data on the geographical distribution of food allergies at the food source and molecular level and to link food allergy patterns to the aeroallergen influence in each area. Systematic reviews, meta-analysis, studies performed within the EuroPrevall Project and EAACI position papers regarding food allergy were analysed. The prevalence of food allergy sensitization differs between geographical areas, probably as a consequence of differences among populations, their habits and the influence of the cross-reactivity of aeroallergens and other sources of allergens. Geographical differences in food allergy are clearly evident at the allergenic molecular level, which seems to be directly influenced by the aeroallergens of each region and associated with specific clinical patterns.

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

Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

Science.gov (United States)

Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

2013-04-01

While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p physical activity reduces cancer risk (p physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

The U.S. Geological Survey Monthly Water Balance Model Futures Portal

Science.gov (United States)

Bock, Andrew R.; Hay, Lauren E.; Markstrom, Steven L.; Emmerich, Christopher; Talbert, Marian

2017-05-03

The U.S. Geological Survey Monthly Water Balance Model Futures Portal (https://my.usgs.gov/mows/) is a user-friendly interface that summarizes monthly historical and simulated future conditions for seven hydrologic and meteorological variables (actual evapotranspiration, potential evapotranspiration, precipitation, runoff, snow water equivalent, atmospheric temperature, and streamflow) at locations across the conterminous United States (CONUS).The estimates of these hydrologic and meteorological variables were derived using a Monthly Water Balance Model (MWBM), a modular system that simulates monthly estimates of components of the hydrologic cycle using monthly precipitation and atmospheric temperature inputs. Precipitation and atmospheric temperature from 222 climate datasets spanning historical conditions (1952 through 2005) and simulated future conditions (2020 through 2099) were summarized for hydrographic features and used to drive the MWBM for the CONUS. The MWBM input and output variables were organized into an open-access database. An Open Geospatial Consortium, Inc., Web Feature Service allows the querying and identification of hydrographic features across the CONUS. To connect the Web Feature Service to the open-access database, a user interface—the Monthly Water Balance Model Futures Portal—was developed to allow the dynamic generation of summary files and plots  based on plot type, geographic location, specific climate datasets, period of record, MWBM variable, and other options. Both the plots and the data files are made available to the user for download 

Representations built from a true geographic database

DEFF Research Database (Denmark)

Bodum, Lars

2005-01-01

the whole world in 3d and with a spatial reference given by geographic coordinates. Built on top of this is a customised viewer, based on the Xith(Java) scenegraph. The viewer reads the objects directly from the database and solves the question about Level-Of-Detail on buildings, orientation in relation...... a representation based on geographic and geospatial principles. The system GRIFINOR, developed at 3DGI, Aalborg University, DK, is capable of creating this object-orientation and furthermore does this on top of a true Geographic database. A true Geographic database can be characterized as a database that can cover...

A framework for investigating geographical variation in diseases, based on a study of Legionnaires' disease.

Science.gov (United States)

Bhopal, R S

1991-11-01

Demonstration of geographical variations in disease can yield powerful insight into the disease pathway, particularly for environmentally acquired conditions, but only if the many problems of data interpretation can be solved. This paper presents the framework, methods and principles guiding a study of the geographical epidemiology of Legionnaires' Disease in Scotland. A case-list was constructed and disease incidence rates were calculated by geographical area; these showed variation. Five categories of explanation for the variation were identified: short-term fluctuations of incidence in time masquerading as differences by place; artefact; and differences in host-susceptibility, agent virulence, or environment. The methods used to study these explanations, excepting agent virulence, are described, with an emphasis on the use of previously existing data to test hypotheses. Examples include the use of mortality, census and hospital morbidity data to assess the artefact and host-susceptibility explanations; and the use of ratios of serology tests to disease to examine the differential testing hypothesis. The reasoning and process by which the environmental focus of the study was narrowed and the technique for relating the geographical pattern of disease to the putative source are outlined. This framework allows the researcher to plan for the parallel collection of the data necessary both to demonstrate geographical variation and to point to the likely explanation.

Drug consumption during the first 18 months of life of infants from smoking and non-smoking families.

OpenAIRE

Håkansson, A; Petersson, C

1992-01-01

In a geographically well defined population in southern Sweden, a study was made of the overall consumption of drugs by infants during their first 18 months of life. The study population comprised 240 infants, of whom 90 were from families where tobacco was smoked by one or both parents and 150 were from non-smoking families. The investigation was carried out retrospectively by interviewing the mothers at the routine 18-month check up at the child health clinic, combined with study of the med...

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...

Ecologic and geographic distributions of the vascular plants of southern Nye County, and adjacent parts of Clark, Lincoln, and Esmeralda Counties, Nevada. [Based on collections made in 1970

Energy Technology Data Exchange (ETDEWEB)

Beatley, J. C.

1971-01-01

A catalog is compiled of the vascular plants indiginous to Nye, Clark, Lincoln, and Esmeralda Counties of Nevada based on collections made in 1970. This compilation is an update of previous collections in these areas and is a supplement to report, UCLA--12-705. (ERB)

[Projection of potential geographic distribution of Apocynum venetum under climate change in northern China].

Science.gov (United States)

Yang, Hui-Feng; Zheng, Jiang-Hua; Jia, Xiao-Guang; Li, Xiao-Jin

2017-03-01

Apocynum venetum belongs to apocynaceae and is a perennial medicinal plant, its stem is an important textile raw materials. The projection of potential geographic distribution of A. venetum has an important significance for the protection and sustainable utilization of the plant. This study was conducted to determine the potential geographic distribution of A. venetum and to project how climate change would affect its geographic distribution. The projection geographic distribution of A. venetum under current bioclimatic conditions in northern China was simulated using MaxEnt software based on species presence data at 44 locations and 19 bioclimatic parameters. The future distributions of A. venetum were also projected in 2050 and 2070 under the climate change scenarios of RCP2.6 and RCP8.5 described in 5th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC). The result showed that min air temperature of the coldest month, annual mean air temperature, precipitation of the coldest quarter and mean air temperature of the wettest quarter dominated the geographic distribution of A. venetum. Under current climate, the suitable habitats of A. venetum is 11.94% in China, the suitable habitats are mainly located in the middle of Xinjiang, in the northern part of Gansu, in the southern part of Neimeng, in the northern part of Ningxia, in the middle and northern part of Shaanxi, in the southern part of Shanxi, in the middle and northern part of Henan, in the middle and southern part of Hebei, Shandong, Tianjin, in the southern part of Liaoning and part of Beijing. From 2050 to 2070, the model outputs indicated that the suitable habitats of A. venetum would decrease under the climate change scenarios of RCP2.6 and RCP8.5. Copyright© by the Chinese Pharmaceutical Association.

FENÔMENOS GEOGRÁFICOS ORIGINADOS PELAS ERBS DA TELEFONIA CELULAR

Directory of Open Access Journals (Sweden)

Maurício José Kaczmarech

2011-01-01

Full Text Available During a research that indicate what was the infl uence of the cellular infrastructure on the urban landscape, has been found the occurrence of certain geographic phenomena generated by the presence of Base Transceiver Station (BTS of mobile telephones. We classifi ed the phenomena of geographic concentration, visual alignment, sharing, overlapping and bordering. The height of the towers, their location, the city¿s topography, the vertical growth, position of the largest transit routes, guidelines and legal agreements for the installation of base stations affect the class of phenomena that occur. Each phenomenon prevents or adds new details in the urban landscape, acting in the sense that the observer has to observe the city, being the most common result, the visual pollution. The phenomenon of concentration of base stations, the overlap of these structures on existing alignment and includes new features to the city. The phenomenon of sharing prevents the installation of new towers. And the overlap reduces the visual impact of base stations along the landscape. The study was conducted in the city of Ponta Grossa and serves as a reference for other cities that also have cellular base stations, ie, most of them.

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...

Respiratory infection rates differ between geographically distant paediatric cystic fibrosis cohorts

Directory of Open Access Journals (Sweden)

Kathryn A. Ramsey

2016-09-01

Full Text Available Respiratory infections are a major cause of pulmonary decline in children with cystic fibrosis (CF. We compared the prevalence of infection in early life at geographically distant CF treatment centres participating in the same surveillance programme in Australia. Lower airway microbiology, inflammation and structural lung disease at annual review were evaluated for 260 children 0–8 years old with CF at 1032 visits to CF treatment centres in Melbourne or Perth. Melbourne patients were more likely to be culture-positive for common respiratory pathogens at all age groups (odds ratio (OR 1.85, 95% CI 1.33–2.58. Subjects 5 years old. Patients at both centres had a similar rate of hospitalisations and prescribed antibiotics. No procedural differences were identified that could explain the disparity between pathogen prevalence. Geographical differences in early acquisition of infection may contribute to variability in outcomes between CF centres.

25 CFR 571.10 - Geographical location.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Geographical location. 571.10 Section 571.10 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR COMPLIANCE AND ENFORCEMENT PROVISIONS MONITORING AND INVESTIGATIONS Subpoenas and Depositions § 571.10 Geographical location. The attendance of...

Socioeconomic Development Inequalities among Geographic Units ...

African Journals Online (AJOL)

Socio-economic development inequality among geographic units is a phenomenon common in both the developed and developing countries. Regional inequality may result in dissension among geographic units of the same state due to the imbalance in socio-economic development. This study examines the inequality ...

Geographic range did not confer resilience to extinction in terrestrial vertebrates at the end-Triassic crisis.

Science.gov (United States)

Dunhill, Alexander M; Wills, Matthew A

2015-08-11

Rates of extinction vary greatly through geological time, with losses particularly concentrated in mass extinctions. Species duration at other times varies greatly, but the reasons for this are unclear. Geographical range correlates with lineage duration amongst marine invertebrates, but it is less clear how far this generality extends to other groups in other habitats. It is also unclear whether a wide geographical distribution makes groups more likely to survive mass extinctions. Here we test for extinction selectivity amongst terrestrial vertebrates across the end-Triassic event. We demonstrate that terrestrial vertebrate clades with larger geographical ranges were more resilient to extinction than those with smaller ranges throughout the Triassic and Jurassic. However, this relationship weakened with increasing proximity to the end-Triassic mass extinction, breaking down altogether across the event itself. We demonstrate that these findings are not a function of sampling biases; a perennial issue in studies of this kind.

Patterns of geographic expansion of Aedes aegypti in the Peruvian Amazon.

Directory of Open Access Journals (Sweden)

Sarah Anne Guagliardo

2014-08-01

Full Text Available In the Peruvian Amazon, the dengue vector Aedes aegypti is abundant in large urban centers such as Iquitos. In recent years, it has also been found in a number of neighboring rural communities with similar climatic and socioeconomic conditions. To better understand Ae. aegypti spread, we compared characteristics of communities, houses, and containers in infested and uninfested communities.We conducted pupal-demographic surveys and deployed ovitraps in 34 communities surrounding the city of Iquitos. Communities surveyed were located along two transects: the Amazon River and a 95 km highway. We calculated entomological indices, mapped Ae. aegypti presence, and developed univariable and multivariable logistic regression models to predict Ae. aegypti presence at the community, household, or container level.Large communities closer to Iquitos were more likely to be infested with Ae. aegypti. Within infested communities, houses with Ae. aegypti had more passively-filled containers and were more often infested with other mosquito genera than houses without Ae. aegypti. For containers, large water tanks/drums and containers with solar exposure were more likely to be infested with Ae. aegypti. Maps of Ae. aegypti presence revealed a linear pattern of infestation along the highway, and a scattered pattern along the Amazon River. We also identified the geographical limit of Ae. aegypti expansion along the highway at 19.3 km south of Iquitos.In the Peruvian Amazon, Ae. aegypti geographic spread is driven by human transportation networks along rivers and highways. Our results suggest that urban development and oviposition site availability drive Ae. aegypti colonization along roads. Along rivers, boat traffic is likely to drive long-distance dispersal via unintentional transport of mosquitoes on boats.

How geographic distance and political ideology interact to influence public perception of unconventional oil/natural gas development

International Nuclear Information System (INIS)

Clarke, Christopher E.; Bugden, Dylan; Hart, P. Sol; Stedman, Richard C.; Jacquet, Jeffrey B.; Evensen, Darrick T.N.; Boudet, Hilary S.

2016-01-01

A growing area of research has addressed public perception of unconventional oil and natural gas development via hydraulic fracturing (“fracking”). We extend this research by examining how geographic proximity to such extraction interacts with political ideology to influence issue support. Regression analysis of data from a fall 2013 national telephone survey of United States residents reveals that as respondents’ geographic distance from areas experiencing significant development increases, political ideology becomes more strongly associated with issue support, with the liberal-partisan divide widening. Our findings support construal level theory's central premise: that people use more abstract considerations (like political ideology) the more geographically removed they are from an issue. We discuss implications for studying public opinion of energy development as well as for risk communication. - Highlights: • Conservatives support unconventional oil and gas development (UOGD) more than liberals. • This divide widened as geographic distance from UOGD areas increased • Construal Level Theory may help explain this finding • We discuss implications for energy policy and risk communication

Development Trends of Cartography and Geographic Information Engineering

Directory of Open Access Journals (Sweden)

WANG Jiayao

2010-04-01

Full Text Available Aimed at the problems of cartography and geographic information engineering and increasing demands of national and military infomationization construction, the paper proposes six hotspots on the research of cartography and geographic information engineering for the future on the foundation of analyzing the development track of cartology, which are heterogeneous geospatial data assimilation, transferring from emphasizing geography infor-mation gaining to user-oriented geographic information deep processing, web or grid geographic information service. intelligent spatial data generalization. integration of GIS and VGE. cartography and geographic information engineering theory system with multi-mode(Map,.GlS..VGE spatial-temporal integrated cognition as the core. And discusses the necessity ,existing groundwork and research contents on studying these hotspots.

Using Metadata to Build Geographic Information Sharing Environment on Internet

Directory of Open Access Journals (Sweden)

Chih-hong Sun

1999-12-01

Full Text Available Internet provides a convenient environment to share geographic information. Web GIS (Geographic Information System even provides users a direct access environment to geographic databases through Internet. However, the complexity of geographic data makes it difficult for users to understand the real content and the limitation of geographic information. In some cases, users may misuse the geographic data and make wrong decisions. Meanwhile, geographic data are distributed across various government agencies, academic institutes, and private organizations, which make it even more difficult for users to fully understand the content of these complex data. To overcome these difficulties, this research uses metadata as a guiding mechanism for users to fully understand the content and the limitation of geographic data. We introduce three metadata standards commonly used for geographic data and metadata authoring tools available in the US. We also review the current development of geographic metadata standard in Taiwan. Two metadata authoring tools are developed in this research, which will enable users to build their own geographic metadata easily.[Article content in Chinese

Transport and geographical position of the big and average cities of the Ukrainian Black Sea region

Directory of Open Access Journals (Sweden)

S. O. Shulevskyi

2017-02-01

Full Text Available There were features of the transport and geographical position of large and average cities of the Ukrainian Black Sea region described in the article. The situation of cities in relation to the existing network of main types of transport connections like road, rail, water, aviation was analyzed. The location of cities in relation to regional centers, the regional center of Odessa, the capital of the country and the state border were characterized. The situation of cities in relation to international transport corridors and the international E-road network was examined. The cities with the most and least favorable transport and geographical location in the region were highlighted.

Development of planning level transportation safety tools using Geographically Weighted Poisson Regression.

Science.gov (United States)

Hadayeghi, Alireza; Shalaby, Amer S; Persaud, Bhagwant N

2010-03-01

A common technique used for the calibration of collision prediction models is the Generalized Linear Modeling (GLM) procedure with the assumption of Negative Binomial or Poisson error distribution. In this technique, fixed coefficients that represent the average relationship between the dependent variable and each explanatory variable are estimated. However, the stationary relationship assumed may hide some important spatial factors of the number of collisions at a particular traffic analysis zone. Consequently, the accuracy of such models for explaining the relationship between the dependent variable and the explanatory variables may be suspected since collision frequency is likely influenced by many spatially defined factors such as land use, demographic characteristics, and traffic volume patterns. The primary objective of this study is to investigate the spatial variations in the relationship between the number of zonal collisions and potential transportation planning predictors, using the Geographically Weighted Poisson Regression modeling technique. The secondary objective is to build on knowledge comparing the accuracy of Geographically Weighted Poisson Regression models to that of Generalized Linear Models. The results show that the Geographically Weighted Poisson Regression models are useful for capturing spatially dependent relationships and generally perform better than the conventional Generalized Linear Models. Copyright 2009 Elsevier Ltd. All rights reserved.

Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997 – 2007

Science.gov (United States)

Green, Traci C.; Grau, Lauretta E.; Carver, H. Wayne; Kinzly, Mark; Heimer, Robert

2010-01-01

Background The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths (“overdoses”) in CT over an 11-year period. Methods We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type. Results Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. Conclusions The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts. PMID:21131140

Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997-2007.

Science.gov (United States)

Green, Traci C; Grau, Lauretta E; Carver, H Wayne; Kinzly, Mark; Heimer, Robert

2011-06-01

The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths ("overdoses") in CT over an 11-year period. We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type. Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Geographical Simulation and Optimization System (GeoSOS and Its Application in the Analysis of Geographic National Conditions

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LI Xia

2017-10-01

Full Text Available Since the Chinese first survey on geographic national conditions has completed, an urgent need is to analyze these geographical data, such as mining of spatial distribution patterns, land use transition rules, development trends. The analysis is crucial for extracting the knowledge from these big data about geographic national conditions. The remote sensing interpretation data and land use/cover data generated by these geographic national conditions monitoring projects are the basic data sources for a variety of research and applications in terms of land use change detection, urban dynamic analysis, and urban/land use planning. The information can be used for assisting in the coordination of land resource use and decision making for urban and rural development, ecological environment protection and other issues that depends on spatial intelligent decisions. We proposed the theoretical framework of geographical simulation and optimization system (GeoSOS, which coupled geographic process simulation/prediction and spatial optimization, provides powerful theoretical support and practical tools for above researches. This paper develops the extension of GeoSOS software-GeoSOS for ArcGIS, which is an ArcGIS Add-In runs on ArcGIS platform for facilitating the above analyses. We take the urban expansion and ecological protection research in rapid urbanization area as an example, use the software to tackle a series of urbanization issues in the study area. The simulation results show that the predicted land development intensity of Guangdong Province will exceed the constraint index in 2020 according to the national development plan. However, the urbanization expansion based on the constraints of land development intensity and ecological protection can satisfy these constraints, and obtain a more compact landscape pattern. The analysis has shown that GeoSOS can be a useful tool for assisting in the analysis of geographic national conditions information

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

Geographic Literacy and Moral Formation among University Students

Science.gov (United States)

Bascom, Jonathan

2011-01-01

This study extends analysis of geographic literacy further by examining the relationship of geographic knowledge with the primary goal of geographic educators--cultivation of cultural understanding and moral sensitivity for global citizenry. The main aim is to examine contributors to moral formation during the university years based on a survey…

Geographic Names Information System (GNIS) Transportation Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Historical Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Admin Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Hydrography Lines

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Cultural Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Landform Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Hydrography Points

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Community Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Geographic Names Information System (GNIS) Antarctica Features

Data.gov (United States)

Department of Homeland Security — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Remote sensing research in geographic education: An alternative view

Science.gov (United States)

Wilson, H.; Cary, T. K.; Goward, S. N.

1981-01-01

It is noted that within many geography departments remote sensing is viewed as a mere technique a student should learn in order to carry out true geographic research. This view inhibits both students and faculty from investigation of remotely sensed data as a new source of geographic knowledge that may alter our understanding of the Earth. The tendency is for geographers to accept these new data and analysis techniques from engineers and mathematicians without questioning the accompanying premises. This black-box approach hinders geographic applications of the new remotely sensed data and limits the geographer's contribution to further development of remote sensing observation systems. It is suggested that geographers contribute to the development of remote sensing through pursuit of basic research. This research can be encouraged, particularly among students, by demonstrating the links between geographic theory and remotely sensed observations, encouraging a healthy skepticism concerning the current understanding of these data.

Personality Homophily and Geographic Distance in Facebook.

Science.gov (United States)

Noë, Nyala; Whitaker, Roger M; Allen, Stuart M

2018-05-24

Personality homophily remains an understudied aspect of social networks, with the traditional focus concerning sociodemographic variables as the basis for assortativity, rather than psychological dispositions. We consider the effect of personality homophily on one of the biggest constraints to human social networks: geographic distance. We use the Big five model of personality to make predictions for each of the five facets: Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism. Using a network of 313,669 Facebook users, we investigate the difference in geographic distance between homophilous pairs, in which both users scored similarly on a particular facet, and mixed pairs. In accordance with our hypotheses, we find that pairs of open and conscientious users are geographically further apart than mixed pairs. Pairs of extraverts, on the other hand, tend to be geographically closer together. We find mixed results for the Neuroticism facet, and no significant effects for the Agreeableness facet. The results are discussed in the context of personality homophily and the impact of geographic distance on social connections.

Surveying and Mapping Geographical Information from the Perspective of Geography

Directory of Open Access Journals (Sweden)

LÜ Guonian

2017-10-01

Full Text Available It briefly reviewed the history of geographic information content development since the existence of geographic information system. It pointed out that the current definition of geographic information is always the extension from the "spatial+ attributes" basic mapping framework of geographic information. It is increasingly difficult to adapt to the analysis and application of spatial-temporal big data. From the perspective of geography research subject and content, it summarized systematically that the content and extension of the "geographic information" that geography needs. It put forward that a six-element expression model of geographic information, including spatial location, semantic description, attribute characteristics, geometric form, evolution process, and objects relationship.Under the guidance of the laws of geography, for geographical phenomenon of spatial distribution, temporal pattern and evolution process, the interaction mechanism of the integrated expression, system analysis and efficient management, it designed that a unified GIS data model which is expressed by six basic elements, a new GIS data structure driven by geographical rules and interaction, and key technologies of unstructured spatio-temporal data organization and storage. It provided that a theoretical basis and technical support for the shift from the surveying and mapping geographic information to the scientific geographic information, and it can help improving the organization, management, analysis and expression ability of the GIS of the geographical laws such as geographical pattern, evolution process, and interaction between elements.

Do Surgeons Treat Their Patients Like They Would Treat Themselves?

NARCIS (Netherlands)

Janssen, Stein J.; Teunis, Teun; Guitton, Thierry G.; Ring, David; Spoor, Andy B.; Chauhan, Aakash; Shafritz, Adam B.; Wasterlain, Amy; Terrono, Andrew L.; Neviaser, Andrew S.; Schmidt, Andrew; Nelson, Andy; Miller, Anna N.; Kristan, Anze; Apard, Thomas; Berner, Arne; Ilyas, Asif; Jubel, Axel; Jost, Bernhard; Babis, George; Watkins, Barry; Kreis, Barbara; Nolan, Betsy M.; Crist, Brett D.; Cross, Brian J.; Wills, Brian P. D.; Barreto, Camilo Jose Romero; Ekholm, Carl; Swigart, Carrie; Spath, Catherine; Zalavras, Charalampos; Cassidy, Charles; Garnavos, Christos; Moreno-Serrano, Constanza L.; Rodner, Craig; Klostermann, Cyrus; Osei, Daniel A.; Rikli, Daniel A.; Haverkamp, Daniel; Polatsch, Daniel; Drosdowech, Darren; Edelstein, David M.; Eygendaal, Denise; Verbeek, Diederik O. F.; Doornberg, Job N.; van den Bekerom, Michel P. J.; Schep, Niels; Kloen, Peter; Haverlag, Robert; Schepers, Tim

2015-01-01

There is substantial unexplained geographical and surgeon-to-surgeon variation in rates of surgery. One would expect surgeons to treat patients and themselves similarly based on best evidence and accounting for patient preferences. (1) Are surgeons more likely to recommend surgery when choosing for

Desert locust populations, rainfall and climate change: insights from phenomenological models using gridded monthly data

OpenAIRE

Tratalos, Jamie A.; Cheke, Robert A.; Healey, Richard G.; Stenseth, Nils Chr.

2010-01-01

Using autocorrelation analysis and autoregressive integrated moving average (ARIMA)modelling, we analysed a time series of the monthly number of 1° grid squares infested with desert locust Schistocerca gregaria swarms throughout the geographical range of the species from 1930–1987. Statistically significant first- and higher-order autocorrelations were found in the series. Although endogenous components captured much of the variance, adding rainfall data improved endogenous ARIMA models and r...

Thematic cartography as a geographical application

Directory of Open Access Journals (Sweden)

Drago Perko

2002-12-01

Full Text Available A thematic map may be a geographical application (tool in itself or the basis for some other geographical work. The development of Slovene thematic cartography accelerated considerably following the independence of the country in 1991. From the viewpoint of content and technology, its greatest achievements are the Geographical Atlas of Slovenia and the National Atlas of Slovenia, which are outstanding achievements at the international level and of great significance for the promotion of Slovenia and Slovene geography and cartography. However, this rapid development has been accompanied by numerous problems, for example, the ignoring of various Slovene and international conventions for the preparation of maps including United Nations resolutions, Slovene and international (SIST ISO, and copyright laws.

National Geographic Education. An Interview with Gilbert M. Grosvenor, President and Chairman of the Board, National Geographic Society.

Science.gov (United States)

Jumper, Sidney R.

1991-01-01

Presents an interview with Gilbert Grosvenor, president and chairman of the board of the National Geographic Society. Examines student and public ignorance about geography. Describes the Society's Geography Education Project, Geographic Alliance Project, and Education Foundation. Includes Grosvenor's call for greater emphasis on geography in…

Musings on privacy issues in health research involving disaggregate geographic data about individuals.

Science.gov (United States)

Boulos, Maged N Kamel; Curtis, Andrew J; Abdelmalik, Philip

2009-07-20

This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic) of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association) workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals), including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.

Cartography and Geographic Information Science in Current Contents

Directory of Open Access Journals (Sweden)

Nedjeljko Frančula

2009-12-01

Full Text Available The Cartography and Geographic Information Science (CaGIS journal was published as The American Cartographer from 1974 to 1989, after that as Cartography and Geographic Information System, and since then has been published with its current name. It is published by the Cartography and Geographic Information Society, a member of the American Congress on Surveying and Mapping.

Geographic patterns of networks derived from extreme precipitation over the Indian subcontinent

Science.gov (United States)

Stolbova, Veronika; Bookhagen, Bodo; Marwan, Norbert; Kurths, Juergen

2014-05-01

Complex networks (CN) and event synchronization (ES) methods have been applied to study a number of climate phenomena such as Indian Summer Monsoon (ISM), South-American Monsoon, and African Monsoon. These methods proved to be powerful tools to infer interdependencies in climate dynamics between geographical sites, spatial structures, and key regions of the considered climate phenomenon. Here, we use these methods to study the spatial temporal variability of the extreme rainfall over the Indian subcontinent, in order to filter the data by coarse-graining the network, and to identify geographic patterns that are signature features (spatial signatures) of the ISM. We find four main geographic patterns of networks derived from extreme precipitation over the Indian subcontinent using up-to-date satellite-derived, and high temporal and spatial resolution rain-gauge interpolated daily rainfall datasets. In order to prove that our results are also relevant for other climatic variables like pressure and temperature, we use re-analysis data provided by the National Center for Environmental Prediction and National Center for Atmospheric Research (NCEP/NCAR). We find that two of the patterns revealed from the CN extreme rainfall analysis coincide with those obtained for the pressure and temperature fields, and all four above mentioned patterns can be explained by topography, winds, and monsoon circulation. CN and ES enable to select the most informative regions for the ISM, providing realistic description of the ISM dynamics with fewer data, and also help to infer geographic pattern that are spatial signatures of the ISM. These patterns deserve a special attention for the meteorologists and can be used as markers of the ISM variability.

Geographic Variation in Maternal Smoking during Pregnancy in the Missouri Adolescent Female Twin Study (MOAFTS)

Science.gov (United States)

Lian, Min; Madden, Pamela A.; Lynskey, Michael T.; Colditz, Graham A.; Lessov-Schlaggar, Christina N.; Schootman, Mario; Heath, Andrew C.

2016-01-01

Objective Despite well-known adverse health effects of maternal smoking during pregnancy (MSP), it is still unclear if MSP varies geographically and if neighborhood socioeconomic deprivation (SED) plays an important role in MSP. This study aims to investigate small-area geographic variation in MSP and examine the association of SED with MSP. Methods The Missouri Adolescent Female Twin Study (MOAFTS) is a cohort study of female like-sex twins born in Missouri to Missouri-resident parents during 1975–1985. Biological mothers completed a baseline interview in 1995–1998 and reported MSP with the twins. Residential address of the mother at birth was geocoded. We developed a census tract-level SED index using a common factor approach based on 21 area-level socioeconomic variables from the 1980 Census data. Multilevel logistic regressions estimated geographic heterogeneity (random effect) in MSP and the odds ratios (ORs, fixed effects) of neighborhood SED associated with MSP. Results Of 1658 MOAFTS mothers, 35.2% reported any MSP and 21.9% reported MSP beyond the first trimester. Neighborhood SED was associated with any MSP (the highest vs. the lowest quartile: OR = 1.90, 95% confidence interval [CI] = 1.40–2.57, Ptrendalcohol use, and parents’ cohabitation), neighborhood SED was not associated with MSP, but geographic variation still persisted in MSP (variance = 0.41, P = 0.003) and in MSP beyond the first trimester (variance = 0.82, P<0.001). Conclusions Neighborhood SED was associated with MSP in unadjusted analyses but this association could be explained by individual socioeconomic conditions. Nonetheless, significant geographic variation in MSP persisted and was not accounted for by differences in neighborhood SED. To develop effective interventions to reduce MSP, further studies are necessary to explore underlying reasons for its geographic variation. PMID:27100091

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.

Airports Geographic Information System -

Data.gov (United States)

Department of Transportation — The Airports Geographic Information System maintains the airport and aeronautical data required to meet the demands of the Next Generation National Airspace System....

Geographic Object-Based Image Analysis - Towards a new paradigm.

Science.gov (United States)

Blaschke, Thomas; Hay, Geoffrey J; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis - GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ' per-pixel paradigm ' and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm.

Hierarchical spatial organization of geographical networks

International Nuclear Information System (INIS)

Travencolo, Bruno A N; Costa, Luciano da F

2008-01-01

In this work, we propose a hierarchical extension of the polygonality index as the means to characterize geographical planar networks. By considering successive neighborhoods around each node, it is possible to obtain more complete information about the spatial order of the network at progressive spatial scales. The potential of the methodology is illustrated with respect to synthetic and real geographical networks

First impressions: geographic variation in media messages during the first phase of ACA implementation.

Science.gov (United States)

Gollust, Sarah E; Barry, Colleen L; Niederdeppe, Jeff; Baum, Laura; Fowler, Erika Franklin

2014-12-01

Many Americans will learn about the implementation of the Patient Protection and Affordable Care Act (ACA) through the mass media. We examined geographic variation in the volume and content of mass media during the initial two-week rollout of the new health insurance marketplaces in October 2013 across 210 US media markets, using data from the Wesleyan Media Project. We found substantial geographic variation in the volume and tone of insurance product advertisements, political advertisements, and news coverage of the ACA marketplaces. News coverage of the ACA airing in media markets located in states operating federal or partnership marketplaces was more negative than coverage airing in markets located in states running their own marketplaces. Intrastate variation in media volume and content was also substantial and appears distinguishable from the local political climate. Variation in exposure to media messages likely affects public sentiment regarding the ACA and could contribute to geographic differences in insurance enrollment and public perceptions of US health care options. Researchers and policy makers evaluating the implementation of the ACA-and insurance enrollment in the marketplaces in particular-should consider addressing media influences. Copyright © 2014 by Duke University Press.

[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.

Multiple sclerosis: a geographical hypothesis.

Science.gov (United States)

Carlyle, I P

1997-12-01

Multiple sclerosis remains a rare neurological disease of unknown aetiology, with a unique distribution, both geographically and historically. Rare in equatorial regions, it becomes increasingly common in higher latitudes; historically, it was first clinically recognized in the early nineteenth century. A hypothesis, based on geographical reasoning, is here proposed: that the disease is the result of a specific vitamin deficiency. Different individuals suffer the deficiency in separate and often unique ways. Evidence to support the hypothesis exists in cultural considerations, in the global distribution of the disease, and in its historical prevalence.

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.

Dynamic management of geographic data in a virtual environment

NARCIS (Netherlands)

Jense, G.J.; Donkers, K.

1996-01-01

In order to achieve true 3D user interaction with geographic information, an interface between a virtual environment system and a geographic information system has been designed and implemented. This VE/GIS interface is based on a loose coupling of the underlying geographic database and the virtual

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.

Petroleum supply monthly, May 1999, with data for March 1999

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-05-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 supplies of petroleum products in the US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 72 tabs.

Petroleum supply monthly, June 1999, with data for April 1999

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-06-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Petroleum supply monthly, April 1999, with data for February 1999

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-04-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 72 tabs.

Petroleum supply monthly, November 1998, with data for September 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-11-01

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 Unites 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 72 tabs.

Petroleum supply monthly, December 1997 with data from October 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-01

Data presented in the Petroleum Supply Monthly (PSM) describes the supply and disposition of petroleum products in the US 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 US (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 aggregates, the data reported by these sectors approximately represent the consumption of petroleum products in the US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Petroleum supply monthly, January 1999 with data for November 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-01-01

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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 82 tabs.

Petroleum supply monthly, July 1997 with data from May 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-07-01

Data presented in the Petroleum Supply Monthly (PSM) describes the supply and disposition of petroleum products in the US 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 US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Petroleum supply monthly, February 1999, with data for December 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-02-01

Data presented in the Petroleum Supply Monthly (PSM) describes 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Petroleum supply monthly, August 1998, with data for June 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-08-01

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 US (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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 fig., 66 tabs.

Petroleum supply monthly: July 1998, with data for May 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-07-01

Data presented in the Petroleum Supply Monthly (PSM) describes the supply and disposition of petroleum products in the US 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 US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 56 tabs.

Petroleum supply monthly, January 1997 with data for November 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-01-01

Data presented in the Petroleum Supply Monthly describe the supply and disposition of petroleum products in the US 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 US (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 US. Data are divided into two sections: Summary Statistics and Detailed Statistics. The tables and figures in the Summary Statistics section present a time series of selected petroleum data on a US level. The Detailed Statistics tables present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Petroleum supply monthly, May 1996 with data from March 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 US (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 US. 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. The Detailed Statistics tables of the PSM present statistics for the most current month available as well as year-to-date. 16 figs., 66 tabs.

Geographic variation in body size and its relationship with environmental gradients in the Oriental Garden Lizard, Calotes versicolor.

Science.gov (United States)

Wei, Xiaomei; Yan, Linmiao; Zhao, Chengjian; Zhang, Yueyun; Xu, Yongli; Cai, Bo; Jiang, Ni; Huang, Yong

2018-05-01

Patterns of geographic variation in body size are predicted to evolve as adaptations to local environmental gradients. However, many of these clinal patterns in body size, such as Bergmann's rule, are controversial and require further investigation into ectotherms such as reptiles on a regional scale. To examine the environmental variables (temperature, precipitation, topography and primary productivity) that shaped patterns of geographic variation in body size in the reptile Calotes versicolor , we sampled 180 adult specimens (91 males and 89 females) at 40 locations across the species range in China. The MANOVA results suggest significant sexual size dimorphism in C. versicolor ( F 23,124  = 11.32, p  body size of C. versicolor differed for males and females, but mechanisms related to heat balance and water availability hypotheses were involved in both sexes. Temperature seasonality, precipitation of the driest month, precipitation seasonality, and precipitation of the driest quarter were the most important predictors of variation in body size in males, whereas mean precipitation of the warmest quarter, mean temperature of the wettest quarter, precipitation seasonality, and precipitation of the wettest month were most important for body size variation in females. The discrepancy between patterns of association between the sexes suggested that different selection pressures may be acting in males and females.

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.

Kornati Islands on Old Geographic Maps and Charts

Directory of Open Access Journals (Sweden)

Josip Faričić

2005-09-01

Full Text Available Based on the analysis of cartographic sources, the paper analyses the historical and geographical development of the Kornati islands, the largest group of Croatian islands. The old maps were used first of all as the means of geographic research that, being necessarily correlated to the simultaneous historical written sources and modern topographic and maritime maps, make the basis for creating a research platform for relevant scientific results to be achieved. On the basis of the old maps it is possible, among other things to anticipate that the Kornati islands used to have great geotraffic significance on the eastern Adriatic sailing route. According to the development of geographic concepts and cartographic methods, the geographic vision of the Kornati islands has been gradually clarified ever since the 16th century. The chart from the Carta di cabotaggio del Mare Adriatico edition published by the Military and Geographic Institute from Milan (1822-1824 presents the turning point with the first complete and mostly precise presentation of the Kornati islands group on the basis of hydrographic and topographic field measurements.

Comparison of immunization strategies in geographical networks

Energy Technology Data Exchange (ETDEWEB)

Wang Bing; Aihara, Kazuyuki [Institute of Industrial Science, The University of Tokyo, Tokyo (Japan)] [ERATO Aihara Complexity Modelling Project, JST, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505 (Japan); Kim, Beom Jun, E-mail: beomjun@skku.ed [BK21 Physics Research Division and Department of Energy Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Computational Biology, School of Computer Science and Communication, Royal Institute of Technology, 100 44 Stockholm (Sweden)

2009-10-12

The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time, for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy, especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy, which may have potential applications for preventing the real epidemic spread.

Comparison of immunization strategies in geographical networks

International Nuclear Information System (INIS)

Wang Bing; Aihara, Kazuyuki; Kim, Beom Jun

2009-01-01

The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time, for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy, especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy, which may have potential applications for preventing the real epidemic spread.

Musings on privacy issues in health research involving disaggregate geographic data about individuals

Directory of Open Access Journals (Sweden)

AbdelMalik Philip

2009-07-01

Full Text Available Abstract This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals, including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.

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

a Conceptual Framework for Virtual Geographic Environments Knowledge Engineering

Science.gov (United States)

You, Lan; Lin, Hui

2016-06-01

VGE geographic knowledge refers to the abstract and repeatable geo-information which is related to the geo-science problem, geographical phenomena and geographical laws supported by VGE. That includes expert experiences, evolution rule, simulation processes and prediction results in VGE. This paper proposes a conceptual framework for VGE knowledge engineering in order to effectively manage and use geographic knowledge in VGE. Our approach relies on previous well established theories on knowledge engineering and VGE. The main contribution of this report is following: (1) The concepts of VGE knowledge and VGE knowledge engineering which are defined clearly; (2) features about VGE knowledge different with common knowledge; (3) geographic knowledge evolution process that help users rapidly acquire knowledge in VGE; and (4) a conceptual framework for VGE knowledge engineering providing the supporting methodologies system for building an intelligent VGE. This conceptual framework systematically describes the related VGE knowledge theories and key technologies. That will promote the rapid transformation from geodata to geographic knowledge, and furtherly reduce the gap between the data explosion and knowledge absence.

Geographic information system applied to the estimation of the plant water status

Science.gov (United States)

Castillo, Cristina; de la Rosa, Jose Mª; Temnani, Abdel; Pérez-Pastor, Alejandro

2017-04-01

The importance of Geographic Information Systems (GIS) at handling managing geospatial data is demonstrated in a large number of scientific and professionals disciplines that have an impact on the territory. Thus, in agriculture, it is a transversal tool that includes the recopilation of: (i) geographic information: soil-plant geolocated sensors in experimental fields, water and fertilizers consumption for each irrigation sector, energy consumption and digital surface models (ii) representation and analysis: obtaining temperature maps, aspect models, solar radiation, run-off and salinity, as well as hardware, software and the people who compose it, results in the optimization of resources (goods, energy and workforce) what it makes the farm more efficient and more beneficial for the environment. In addition, in this project, the use of new technologies, such as satellite imagery or drones with multispectral cameras, allow to obtain other parameters that are not observed with the naked eye, like the state of the crop in spectroradiometric terms (remote sensing), stressed crops through indexes like NDVI, that may lead to take decisions like: (i) irrigation variations (ii) early detection of fillings in droppers (iii) affected areas for a pest, helping to distribute the workforce efficiently (pesticide use in an optimal way). The main objective of GIS use in this project is to establish direct relationships between parameters taken from the soil and plant with image processing in four different crops, orange, peach, apricot trees and table grape. In this way, the leaf area index (LAI) can be calculated, assessing how different irrigation management affects: i) Control (CTL), irrigated to ensure non-limiting water conditions (120% of crop evapotranspiration) and ii) Regulated deficit irrigation (RDI) irrigated as CTL during critical periods and decreasing irrigation in non-critical periods. Acknowledgements This work has been funded by the European Union LIFE+ project

Future Prospects for Geographical Education in Slovenia

Science.gov (United States)

Resnic Planinc, Tatjana

2011-01-01

This paper deals with future prospects for geographical education in Slovenia, with special emphasis on the development and aims of the didactics of geography. The author discusses the past development of geographical curricula and of competencies of geography teachers, and the education of future teachers of the subject in Slovenia. Her ideas are…

Petroleum supply monthly, January 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-02-15

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the 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.

Petroleum supply monthly, October 1993

Energy Technology Data Exchange (ETDEWEB)

1993-10-26

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the 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.

Petroleum Supply Monthly, August 1990

Energy Technology Data Exchange (ETDEWEB)

1990-10-30

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 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 (1) the Summary Statistics and (2) the Detailed Statistics.

Petroleum supply monthly, September 1991

Energy Technology Data Exchange (ETDEWEB)

1991-09-30

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 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 Administrations 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. 65 tabs.

Generalisation of geographic information cartographic modelling and applications

CERN Document Server

Mackaness, William A; Sarjakoski, L Tiina

2011-01-01

Theoretical and Applied Solutions in Multi Scale MappingUsers have come to expect instant access to up-to-date geographical information, with global coverage--presented at widely varying levels of detail, as digital and paper products; customisable data that can readily combined with other geographic information. These requirements present an immense challenge to those supporting the delivery of such services (National Mapping Agencies (NMA), Government Departments, and private business. Generalisation of Geographic Information: Cartographic Modelling and Applications provides detailed review

The Costs and Benefits of Collaborating across Geographic Distance and Organizational Boundaries

DEFF Research Database (Denmark)

Mors, Louise; Waguespack, David

to shed further light on the costs of cross-boundary collaborations. In particular, we examine how such collaborations evolve and whether the costs persist over time. We study collaborations in the Internet Engineering Task Force (IETF). In this open innovation community participants collaborate in work....... In fact, the further away authors are from each other the more likely they are to continue collaborating. Yet we find that crossing geographic distance does become more costly over time - perhaps suggesting that low quality projects get sorted from the process. However, crossing organizational boundaries...

Geographical point cloud modelling with the 3D medial axis transform

NARCIS (Netherlands)

Peters, R.Y.

2018-01-01

A geographical point cloud is a detailed three-dimensional representation of the geometry of our geographic environment.
Using geographical point cloud modelling, we are able to extract valuable information from geographical point clouds that can be used for applications in asset management,

Geographic distribution of phlebotomine sandfly species (Diptera: Psychodidae) in Central-West Brazil

Science.gov (United States)

de Almeida, Paulo Silva; de Andrade, Andrey José; Sciamarelli, Alan; Raizer, Josué; Menegatti, Jaqueline Aparecida; Hermes, Sandra Cristina Negreli Moreira; de Carvalho, Maria do Socorro Laurentino; Gurgel-Gonçalves, Rodrigo

2015-01-01

This study updates the geographic distributions of phlebotomine species in Central-West Brazil and analyses the climatic factors associated with their occurrence. The data were obtained from the entomology services of the state departments of health in Central-West Brazil, scientific collections and a literature review of articles from 1962-2014. Ecological niche models were produced for sandfly species with more than 20 occurrences using the Maxent algorithm and eight climate variables. In all, 2,803 phlebotomine records for 127 species were analysed. Nyssomyia whitmani, Evandromyia lenti and Lutzomyia longipalpis were the species with the greatest number of records and were present in all the biomes in Central-West Brazil. The models, which were produced for 34 species, indicated that the Cerrado areas in the central and western regions of Central-West Brazil were climatically more suitable to sandflies. The variables with the greatest influence on the models were the temperature in the coldest months and the temperature seasonality. The results show that phlebotomine species in Central-West Brazil have different geographical distribution patterns and that climate conditions in essentially the entire region favour the occurrence of at least one Leishmania vector species, highlighting the need to maintain or intensify vector control and surveillance strategies. PMID:26018450

GNIS: Geographic Names Information Systems - All features (2013)

Data.gov (United States)

Earth Data Analysis Center, University of New Mexico — The Geographic Names Information System (GNIS) is the Federal standard for geographic nomenclature. The U.S. Geological Survey developed the GNIS for the U.S. Board...

Training for Internationalization through Domestic Geographical Dispersion

DEFF Research Database (Denmark)

Santangelo, Grazia D.; Stucchi, Tamara

Traditionally created to deal with the unfriendly domestic environment, business groups (BGs) are increasingly internationalizing. However, how BGs can reconcile their strictly domestic orientation with an international dimension still remains an open question. Drawing on arguments from...... organizational learning, we seek to solve this puzzle in relation to the internationalization of Indian BGs. In particular, we argue that in heterogeneous domestic emerging markets BG’s geographical dispersion across sub-national states provides training for internationalization. To internationalize successfully......, BGs need to develop the capability of managing geographically dispersed units in institutional heterogeneous contexts. Domestic geographical dispersion would indeed help the BG dealing with different regulations, customers and infrastructures. However, there is less scope for such training as BGs...

USGS Geographic Names (GNIS) Overlay Map Service from The National Map - National Geospatial Data Asset (NGDA) Geographic Names Information System (GNIS)

Data.gov (United States)

U.S. Geological Survey, Department of the Interior — USGS developed The National Map (TNM) Gazetteer as the Federal and national standard (ANSI INCITS 446-2008) for geographic nomenclature based on the Geographic Names...

Use of fundus autofluorescence images to predict geographic atrophy progression.

Science.gov (United States)

Bearelly, Srilaxmi; Khanifar, Aziz A; Lederer, David E; Lee, Jane J; Ghodasra, Jason H; Stinnett, Sandra S; Cousins, Scott W

2011-01-01

Fundus autofluorescence imaging has been shown to be helpful in predicting progression of geographic atrophy (GA) secondary to age-related macular degeneration. We assess the ability of fundus autofluorescence imaging to predict rate of GA progression using a simple categorical scheme. Subjects with GA secondary to age-related macular degeneration with fundus autofluorescence imaging acquired at least 12 months apart were included. Rim area focal hyperautofluorescence was defined as percentage of the 500-μm-wide margin bordering the GA that contained increased autofluorescence. Rim area focal hyperautofluorescence on baseline fundus autofluorescence images was assessed and categorized depending on the extent of rim area focal hyperautofluorescence (Category 1: ≤33%; Category 2: between 33 and 67%; Category 3: ≥67%). Total GA areas at baseline and follow-up were measured to calculate change in GA progression. Forty-five eyes of 45 subjects were included; average duration of follow-up was 18.5 months. Median growth rates differed among categories of baseline rim area focal hyperautofluorescence (P = 0.01 among Categories 1, 2, and 3; P = 0.008 for Category 1 compared with Category 3, Jonckheere-Terpstra test). A simple categorical scheme that stratifies the amount of increased autofluorescence in the 500-μm margin bordering GA may be used to differentiate faster and slower progressors.

Geographic Object-Based Image Analysis – Towards a new paradigm

Science.gov (United States)

Blaschke, Thomas; Hay, Geoffrey J.; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis – GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ‘per-pixel paradigm’ and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm. PMID:24623958

The study of disaster situation awareness based on volunteered geographic information

Science.gov (United States)

Zhao, Qiansheng; Chen, Zi; Li, Shengming; Luo, Nianxue

2015-12-01

As the development of Web 2.0, the social media like microblog, blogs and social network have supplied a bunch of information with locations (Volunteered Geographical Information, VGI).Recent years many cases have shown that, if disaster happened, the cyber citizens will get together very quickly and share the disaster information, this results a bunch of volunteered geographical information about disaster situation which is very valuable for disaster response if this VGIs are used efficiently and properly. This project will take typhoon disaster as case study. In this paper, we study the relations between weibo messages and the real typhoon situation, we proposed an analysis framework for mine the relations between weibo messages distribution and physical space. We found that the number of the weibo messages, key words frequency and spatial temporary distribution of the messages have strong relations with the disaster spread in the real world, and this research results can improve our disaster situation awareness in the future. The achievement of the study will give a method for typhoon disaster situation awareness based on VGI from the bottom up, and will locate the disaster spot and evolution quickly which is very important for disaster response and recover.

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.

Comparison of Turkey’s Geographical Regions in terms of Stand-Alone PV System Design and Cost Parameters

Directory of Open Access Journals (Sweden)

Nevzat Onat

2017-01-01

Full Text Available Stand-alone photovoltaic (SAPV systems are widely used in rural areas where there is no national grid or as a precaution against power outages. In this study, technical and economic analysis of a SAPV system was carried out using meteorological data for 75 province centers in seven geographical regions of Turkey. Obtained results for each province center were separated by geographical area. The averages of the centers for each region are taken as output. A calculation algorithm based on MsExcel has been established for these operations. The analyses made with the developed algorithm are repeated for five different scenarios that they cover periods of time when a constant strong load is active for all seasons (winter, spring, summer, and autumn and all year round. The developed algorithm calculates the life-cycle cost, the unit energy cost, the electrical capacity utilization rate, the amount of generated/excess energy per month, the initial investment/replacement, and operating and maintenance (O&M costs of each element. As a result, geographical regions of Turkey are compared in terms of these outputs graphically. Further investigations may include the sale of excess energy generated, small-scale PV system cost factors parallel to the grid, and the effects of government incentives.

75 FR 33239 - Rangeland Allotment Management Planning on the Fall River West and Oglala Geographic Areas, Fall...

Science.gov (United States)

2010-06-11

...The USDA, Forest Service, will prepare an environmental impact statement (EIS) analyzing the management of rangeland vegetation resources, which includes livestock grazing, on the National Forest System (NFS) lands within the Oglala Geographic Area (OGA) of the Oglala National Grassland on the Pine Ridge Ranger District and the West Geographic Area (WGA) of the Buffalo Gap National Grassland on the Fall River Ranger District of the Nebraska National Forest (Analysis Area) areas as mapped by the 2001 Nebraska National Forest Revised Land and Resource Management Plan (Forest Plan). A Notice of Intent (NOI) for this project was published February 22, 2008 (73 No. 36 FR 9760- 9762). More than six months have elapsed since the projected draft environmental impact statement (DEIS) date in that original NOI. This revised NOI is being issued to update the project schedule. There will be a record of decision (ROD) for each geographic area. Proposed management actions would be implemented beginning in the year 2012. The agency gives notice of the full environmental analysis and decision-making process that will occur on the proposal so interested and affected people may become aware of how they may participate in the process and contribute to the final decision.

Representation of geographic terrain surface using global indexing

DEFF Research Database (Denmark)

Kolar, Jan

2004-01-01

. Unlike cartographic maps, 3D models can capture the geometry of geographic features without flattening the environment, without cartographic projection?can avoid geometric distortion. More interestingly, however, 3D models can be composed into a single model spanning the whole world; it can be navigated...... visually in order to access information and data in the same geometric space as we navigate ourselves in our real environment.   This article attempts to narrow down the overhead of problems in visualization of 3D geographic information and intends to identify fundamental issues common to other systems......A global 3D geographic model a feasible solution for its visualization and management remains a challenging vision. The existence of a reusable platform would provide an unprecedented potential for development of applications related to geography and facilitate comprehension of geographic data...

Geographical data structures supporting regional analysis

International Nuclear Information System (INIS)

Edwards, R.G.; Durfee, R.C.

1978-01-01

In recent years the computer has become a valuable aid in solving regional environmental problems. Over a hundred different geographic information systems have been developed to digitize, store, analyze, and display spatially distributed data. One important aspect of these systems is the data structure (e.g. grids, polygons, segments) used to model the environment being studied. This paper presents eight common geographic data structures and their use in studies of coal resources, power plant siting, population distributions, LANDSAT imagery analysis, and landuse analysis

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

Evolution of research in health geographics through the International Journal of Health Geographics (2002-2015).

Science.gov (United States)

Pérez, Sandra; Laperrière, Vincent; Borderon, Marion; Padilla, Cindy; Maignant, Gilles; Oliveau, Sébastien

2016-01-20

Health geographics is a fast-developing research area. Subjects broached in scientific literature are most varied, ranging from vectorial diseases to access to healthcare, with a recent revival of themes such as the implication of health in the Smart City, or a predominantly individual-centered approach. Far beyond standard meta-analyses, the present study deliberately adopts the standpoint of questioning space in its foundations, through various authors of the International Journal of Health Geographics, a highly influential journal in that field. The idea is to find space as the common denominator in this specialized literature, as well as its relation to spatial analysis, without for all that trying to tend towards exhaustive approaches. 660 articles have being published in the journal since launch, but 359 articles were selected based on the presence of the word "Space" in either the title, or the abstract or the text over 13 years of the journal's existence. From that database, a lexical analysis (tag cloud) reveals the perception of space in literature, and shows how approaches are evolving, thus underlining that the scope of health geographics is far from narrowing.

Geographical Clusters of Rape in the United States: 2000-2012

Science.gov (United States)

Amin, Raid; Nabors, Nicole S.; Nelson, Arlene M.; Saqlain, Murshid; Kulldorff, Martin

2016-01-01

Background While rape is a very serious crime and public health problem, no spatial mapping has been attempted for rape on the national scale. This paper addresses the three research questions: (1) Are reported rape cases randomly distributed across the USA, after being adjusted for population density and age, or are there geographical clusters of reported rape cases? (2) Are the geographical clusters of reported rapes still present after adjusting for differences in poverty levels? (3) Are there geographical clusters where the proportion of reported rape cases that lead to an arrest is exceptionally low or exceptionally high? Methods We studied the geographical variation of reported rape events (2003-2012) and rape arrests (2000-2012) in the 48 contiguous states of the USA. The disease Surveillance software SaTScan™ with its spatial scan statistic is used to evaluate the spatial variation in rapes. The spatial scan statistic has been widely used as a geographical surveillance tool for diseases, and we used it to identify geographical areas with clusters of reported rape and clusters of arrest rates for rape. Results The spatial scan statistic was used to identify geographical areas with exceptionally high rates of reported rape. The analyses were adjusted for age, and in secondary analyses, for both age and poverty level. We also identified geographical areas with either a low or a high proportion of reported rapes leading to an arrest. Conclusions We have identified geographical areas with exceptionally high (low) rates of reported rape. The geographical problem areas identified are prime candidates for more intensive preventive counseling and criminal prosecution efforts by public health, social service, and law enforcement agencies Geographical clusters of high rates of reported rape are prime areas in need of expanded implementation of preventive measures, such as changing attitudes in our society toward rape crimes, in addition to having the criminal

Using rare earth elements for the identification of the geographic origin of food

Science.gov (United States)

Meisel, T.; Bandoniene, D.; Joebstl, D.

2009-04-01

The European Union defined regimes within the Protected Geographical Status (PGS) framework to protect names of regional food specialities. Thus only food produced in a specific geographical area with a specific way of production or quality can be protected by a protected geographical indication (PGI) label. As such Styrian Pumpkin Seed Oil has been approved with this label, but as with many other high priced regional specialities, fraud cannot be excluded or nor identified. Thus the aim of this work is, to develop an analytical method for the control of the geographic origin of pumpkin seed oil and also to test the method for other protected products. The development of such a method is not only of interest for scientists, but also of importance for the consumer wanting to know the origin of the food products and the assurance of the purity and quality. The group of rare earth elements (REE) in plants also have a characteristic distribution pattern similar to upper crustal REE distributions. Since the REE concentrations are extremely low in pumpkin seed oil (ppt to low ppb), ICP-MS was the only sensitive tool able to produce validated results. The carrier of the REE are most likely small particles distributed within the pumpkin seed oil. Unlike, e.g., olive oil, pumpkin seed oil is bottled and sold unfiltered, which makes this Styrian speciality an interesting sampling target. As pumpkin seed oils from different geographic origin show variable trace element and rare earth distribution patterns, is should possible to trace the origin of these oils. In the current project pumpkin seeds from different regions in Austria and from abroad were sampled. The trace element patterns in the extracted oil of these seeds were determined and a preliminary classification with discriminate analysis was successfully done on a statistical basis. In addition to the study of the geographic origin it was demonstrated that REE distribution patterns can also be used for the

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.

The geographical co-distribution and socio-ecological drivers of childhood pneumonia and diarrhoea in Queensland, Australia.

Science.gov (United States)

Xu, Z; Hu, W; Tong, S

2015-04-01

SUMMARY This study aimed to explore the spatio-temporal patterns, geographical co-distribution, and socio-ecological drivers of childhood pneumonia and diarrhoea in Queensland. A Bayesian conditional autoregressive model was used to quantify the impacts of socio-ecological factors on both childhood pneumonia and diarrhoea at a postal area level. A distinct seasonality of childhood pneumonia and diarrhoea was found. Childhood pneumonia and diarrhoea were mainly distributed in the northwest of Queensland. Mount Isa city was the high-risk cluster where childhood pneumonia and diarrhoea co-distributed. Emergency department visits (EDVs) for pneumonia increased by 3% per 10-mm increase in monthly average rainfall in wet seasons. By comparison, a 10-mm increase in monthly average rainfall may cause an increase of 4% in EDVs for diarrhoea. Monthly average temperature was negatively associated with EDVs for childhood diarrhoea in wet seasons. Low socioeconomic index for areas (SEIFA) was associated with high EDVs for childhood pneumonia. Future pneumonia and diarrhoea prevention and control measures in Queensland should focus more on Mount Isa.

Petroleum supply monthly with data from January 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. Data presented in the 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.

Petroleum supply monthly with data for March 1997

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-05-01

The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration reflecting different levels of data timeliness and completeness. Data presented in the PSM describe the supply and disposition of petroleum products in the United States and major U.S. 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.

Geographic Video 3d Data Model And Retrieval

Science.gov (United States)

Han, Z.; Cui, C.; Kong, Y.; Wu, H.

2014-04-01

Geographic video includes both spatial and temporal geographic features acquired through ground-based or non-ground-based cameras. With the popularity of video capture devices such as smartphones, the volume of user-generated geographic video clips has grown significantly and the trend of this growth is quickly accelerating. Such a massive and increasing volume poses a major challenge to efficient video management and query. Most of the today's video management and query techniques are based on signal level content extraction. They are not able to fully utilize the geographic information of the videos. This paper aimed to introduce a geographic video 3D data model based on spatial information. The main idea of the model is to utilize the location, trajectory and azimuth information acquired by sensors such as GPS receivers and 3D electronic compasses in conjunction with video contents. The raw spatial information is synthesized to point, line, polygon and solid according to the camcorder parameters such as focal length and angle of view. With the video segment and video frame, we defined the three categories geometry object using the geometry model of OGC Simple Features Specification for SQL. We can query video through computing the spatial relation between query objects and three categories geometry object such as VFLocation, VSTrajectory, VSFOView and VFFovCone etc. We designed the query methods using the structured query language (SQL) in detail. The experiment indicate that the model is a multiple objective, integration, loosely coupled, flexible and extensible data model for the management of geographic stereo video.

Geographic profiling survey : a preliminary examination of geographic profilers' views and experiences

NARCIS (Netherlands)

Emeno, Karla; Bennell, Craig; Snook, Brent; Taylor, Paul Jonathon

Geographic profiling (GP) is an investigative technique that involves predicting a serial offender?s home location (or some other anchor point) based on where he or she committed a crime. Although the use of GP in police investigations appears to be on the rise, little is known about the procedure

Geographical Tatoos

Directory of Open Access Journals (Sweden)

Valéria Cazetta

2014-08-01

Full Text Available The article deals with maps tattooed on bodies. My interest in studying the corporeality is inserted in a broader project entitled Geographies and (in Bodies. There is several published research on tattoos, but none in particular about tattooed maps. However some of these works interested me because they present important discussions in contemporary about body modification that helped me locate the body modifications most within the culture than on the nature. At this time, I looked at pictures of geographical tattoos available in several sites of the internet.

[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.

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

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.

Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.

Science.gov (United States)

Wong, Wai T; Dresner, Samuel; Forooghian, Farzin; Glaser, Tanya; Doss, Lauren; Zhou, Mei; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y

2013-04-26

To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

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. ...

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.

Geographic variation in gorilla limb bones.

Science.gov (United States)

Jabbour, Rebecca S; Pearman, Tessa L

2016-06-01

Gorilla systematics has received increased attention over recent decades from primatologists, conservationists, and paleontologists. Studies of geographic variation in DNA, skulls, and teeth have led to new taxonomic proposals, such as recognition of two gorilla species, Gorilla gorilla (western gorilla) and Gorilla beringei (eastern gorilla). Postcranial differences between mountain gorillas (G. beringei beringei) and western lowland gorillas (G. g. gorilla) have a long history of study, but differences between the limb bones of the eastern and western species have not yet been examined with an emphasis on geographic variation within each species. In addition, proposals for recognition of the Cross River gorilla as Gorilla gorilla diehli and gorillas from Tshiaberimu and Kahuzi as G. b. rex-pymaeorum have not been evaluated in the context of geographic variation in the forelimb and hindlimb skeletons. Forty-three linear measurements were collected from limb bones of 266 adult gorillas representing populations of G. b. beringei, Gorilla beringei graueri, G. g. gorilla, and G. g. diehli in order to investigate geographic diversity. Skeletal elements included the humerus, radius, third metacarpal, third proximal hand phalanx, femur, tibia, calcaneus, first metatarsal, third metatarsal, and third proximal foot phalanx. Comparisons of means and principal components analyses clearly differentiate eastern and western gorillas, indicating that eastern gorillas have absolutely and relatively smaller hands and feet, among other differences. Gorilla subspecies and populations cluster consistently by species, although G. g. diehli may be similar to the eastern gorillas in having small hands and feet. The subspecies of G. beringei are distinguished less strongly and by different variables than the two gorilla species. Populations of G. b. graueri are variable, and Kahuzi and Tshiaberimu specimens do not cluster together. Results support the possible influence of

LEGAL INSTRUMENT FOR PROTECTION OF GEOGRAPHICAL INDICATION PRODUCT IN INDONESIA

Directory of Open Access Journals (Sweden)

Almusawir Nansa

2013-07-01

Full Text Available As an archipelago country, Indonesia comprises of a large territory where every region is capable of producing distinctive and characterized products due to its geographical, social, and cultural factors, in addition to its higher quality compared to imported products. In the market, goods with distinct characterization as a result of various geographical locations of production regions is known as Geographical Indication Products. Geographical Indication defines as a characterization that indicates the origin of a product, which includes several influencing factors such as geographical factor, natural factor, human factor or the combination of both factors which eventually contribute to establish a certain distinction and quality upon a product. Several geographical indicated products in Indonesia are widely known to have excellent reputation on the market, namely Delinese tobacco, Temanggung tobacco, Ciancur rice, Muntok white pepper, Lampung black pepper, Kerinci cinnamon, Cilembu cassava, Bandanese nutmeg, Proboliggo sweet mango, Balinese Kintamani coffee, Kalosi coffee, Papuan matoa, etc. Those are several richness of goods from certain regions in Indonesia widely known for their characterization. Characterization of goods are resulted by variation of geographic locations of producing regions in Indonesia. These goods possess high quality and high economic value. Consequently, certain instruments are required to provide protection upon the regions producing those goods against the act of counterfeiting.

Geographic disparities of asthma prevalence in south-western United States of America

Directory of Open Access Journals (Sweden)

Lung-Chang Chien

2014-11-01

Full Text Available Asthma is one of the most prevalent chronic diseases in the United States of America (USA, and many of its risk factors have so far been investigated and identified; however, evidence is limited on how spatial disparities impact the disease. The purpose of this study was to provide scientific evidence on the location influence on asthma in the four states of south- western USA (California, Arizona, New Mexico and Texas which, together, include 360 counties. The Behavioral Risk Factor Surveillance System database for these four states covering the period of 2000 to 2011 was used in this analysis, and a Bayesian structured additive regression model was applied to analyse by a geographical information system. After adjusting for individual characteristics, socioeconomic status and health behaviour, this study found higher odds associated with asth- ma and a likely cluster around the Bay Area in California, while lower odds appeared in several counties around the larger cities of Texas, such as Dallas, Houston and San Antonio. The significance map shows 43 of 360 counties (11.9% to be high-risk areas for asthma. The level of geographical disparities demonstrates that the county risk of asthma prevalence varies significantly and can be about 19.9% (95% confidence interval: 15.3-25.8 higher or lower than the overall asthma prevalence. We provide an efficient method to utilise and interpret the existing surveillance data on asthma. Visualisation by maps may help deliver future interventions on targeted areas and vulnerable populations to reduce geographical disparities in the burden of asthma.

Geographic disparities of asthma prevalence in south-western United States of America.

Science.gov (United States)

Chien, Lung-Chang; Alamgir, Hasanat

2014-11-01

Asthma is one of the most prevalent chronic diseases in the United States of America (USA), and many of its risk factors have so far been investigated and identified; however, evidence is limited on how spatial disparities impact the disease. The purpose of this study was to provide scientific evidence on the location influence on asthma in the four states of southwestern USA (California, Arizona, New Mexico and Texas) which, together, include 360 counties. The Behavioral Risk Factor Surveillance System database for these four states covering the period of 2000 to 2011 was used in this analysis, and a Bayesian structured additive regression model was applied to analyse by a geographical information system. After adjusting for individual characteristics, socioeconomic status and health behaviour, this study found higher odds associated with asthma and a likely cluster around the Bay Area in California, while lower odds appeared in several counties around the larger cities of Texas, such as Dallas, Houston and San Antonio. The significance map shows 43 of 360 counties (11.9%) to be high-risk areas for asthma. The level of geographical disparities demonstrates that the county risk of asthma prevalence varies significantly and can be about 19.9% (95% confidence interval: 15.3-25.8) higher or lower than the overall asthma prevalence. We provide an efficient method to utilise and interpret the existing surveillance data on asthma. Visualisation by maps may help deliver future interventions on targeted areas and vulnerable populations to reduce geographical disparities in the burden of asthma.

Geographic Variation in Oxaliplatin Chemotherapy and Survival in Patients With Colon Cancer.

Science.gov (United States)

Panchal, Janki M; Lairson, David R; Chan, Wenyaw; Du, Xianglin L

2016-01-01

Geographic disparity in colon cancer survival has received less attention, despite the fact that health care delivery varied across regions. To examine geographic variation in colon cancer survival and explore factors affecting this variation, including the use of oxaliplatin chemotherapy, we studied cases with resected stage-III colon cancer in 2004-2009, identified from the Surveillance, Epidemiology and End Results-Medicare linked database. Cox proportional hazard model was used to estimate the effect of oxaliplatin-containing chemotherapy on survival across regions. Propensity score adjustments were made to control for potential selection bias and confounding. Rural regions showed lowest 3-year survival, whereas big metro regions showed better 3-year survival rate than any other region (67.3% in rural regions vs. 69.5% in big metro regions). Hazard ratio for patients residing in metro region was comparable with those residing in big metro region (1.27, 95% confidence interval: 0.90-1.80). However, patients residing in urban area were exhibiting lower mortality than those in other regions, although not statistically significant. Patients who received oxaliplatin chemotherapy were 23% significantly less likely to die of cancer than those received 5-fluorouracil only chemotherapy (adjusted hazard ratio = 0.77, 95% confidence interval: 0.63-0.95). In conclusion, there were some differences in survival across geographic regions, which were not statistically significant after adjusting for sociodemographic, tumor, chemotherapy, and other treatment characteristics. Oxaliplatin chemotherapy was associated with improved survival outcomes compared with 5-fluorouracil only chemotherapy across regions. Further studies may evaluate other factors and newer chemotherapy regimens on mortality/survival of older patients.

Utilisation of general practitioner services by socio-economic disadvantage and geographic remoteness.

Science.gov (United States)

Turrell, Gavin; Oldenburg, Brian F; Harris, Elizabeth; Jolley, Damien

2004-04-01

To examine the association between socio-economic status (SES) and GP utilisation across Statistical Local Areas (SLAs) that differed in their geographic remoteness, and to assess whether Indigenous status and GP availability modified the association. Retrospective analysis of Medicare data for all unreferred GP consultations (1996/97) for 952 SLAs comprising the six Australian States. Geographic remoteness was ascertained using the Area Remoteness Index of Australia (ARIA), and SES was measured by grouping SLAs into tertiles based on their Index of Relative Socioeconomic Disadvantage score. Age/sex standardised rates of GP utilisation for each SLA. In SLAs classified as 'highly accessible', rates of GP use were 10.8% higher (95% CI 5.7-16.0) in the most socio-economically disadvantaged tertile after adjustment for Indigenous status and GP availability. A very different pattern of GP utilsation was found in 'remote/very remote' SLAs. After adjustment, rates of GP use in the most socio-economically disadvantaged tertile were 25.3% lower (95% CI 5.9-40.7) than in the most advantaged tertile. People in socio-economically disadvantaged metropolitan SLAs have higher rates of GP utilisation, as would be expected due to their poorer health. This is not true for people living in disadvantaged remote/very remote SLAs: in these areas, those most in need of GP services are least likely to receive them. Australia may lay claim to having a primary health care system that provides universal coverage, but we are still some way from having a system that is economically and geographically accessible to all.

The National Geographic Names Data Base: Phase II instructions

Science.gov (United States)

Orth, Donald J.; Payne, Roger L.

1987-01-01

The Geographic Names Information System is a computer-based information system developed to meet major national needs by providing information for named entities in the United States, its territories, and outlying areas. The National Geographic Names Data Base, a component of the Geographic Names Information System, currently contains most names and associated information recorded on the 1:24,000-scale (or largest scale available) topographic maps of the U.S. Geological Survey. The work involved in this initial compilation of names shown on the topographic-map series, and the development and editing of the National Geographic Names Data Base, is referred to as Phase I. Optimal use and effectiveness of an automated names system require that the names of features

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

Geographic isolation and elevational gradients promote diversification in an endemic shrew on Sulawesi.

Science.gov (United States)

Eldridge, Ryan A; Achmadi, Anang S; Giarla, Thomas C; Rowe, Kevin C; Esselstyn, Jacob A

2018-01-01

Phylogeographic research on endemic primates and amphibians inhabiting the Indonesian island of Sulawesi revealed the existence of seven areas of endemism (AoEs). Here, we use phylogenetic and population genetic analyses of one mitochondrial gene and 15 nuclear loci to assess geographic patterns of genetic partitioning in a shrew (Crocidura elongata) that is endemic to Sulawesi, but occurs across the island. We uncover substantial genetic diversity in this species both between and within AoEs, but we also identify close relationships between populations residing in different AoEs. One of the earliest divergences within C. elongata distinguishes a high-elevation clade from low-elevation clades. In addition, on one mountain, we observe three distinct genetic groups from low, middle, and high elevations, suggesting divergence along a single elevational gradient. In general, our results show that C. elongata, like several other Sulawesi endemic taxa, harbors extensive genetic diversity. This diversity is structured in part by known AoE boundaries, but also by elevational gradients and geographic isolation within AoEs. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavioral and physiological correlates of the geographic distributions of amphibious sea kraits (Laticauda spp.)

Science.gov (United States)

Brischoux, François; Tingley, Reid; Shine, Richard; Lillywhite, Harvey B.

2013-02-01

The physiological costs of living in seawater likely influenced the secondary evolutionary transitions to marine life in tetrapods. However, these costs are alleviated for species that commute between the land and the sea, because terrestrial habitats can provide frequent access to fresh water. Here, we investigate how differences in the ecology and physiology of three sea krait species (Laticauda spp.) interact to determine their environmental tolerances and geographic distributions. These three species vary in their relative use of terrestrial versus marine environments, and they display concomitant adaptations to life on land versus at sea. A species with relatively high dehydration rates in seawater (Laticauda colubrina) occupied oceanic areas with low mean salinities, whereas a species with comparatively high rates of transcutaneous evaporative water loss on land (Laticauda semifasciata) occupied regions with low mean temperatures. A third taxon (Laticauda laticaudata) was intermediate in both of these traits, and yet occupied the broadest geographic range. Our results suggest that the abilities of sea kraits to acquire fresh water on land and tolerate dehydration at sea determine their environmental tolerances and geographic distributions. This finding supports the notion that speciation patterns within sea kraits have been driven by interspecific variation in the degree of reliance upon terrestrial versus marine habitats. Future studies could usefully examine the effects of osmotic challenges on diversification rates in other secondarily marine tetrapod species.

Interoperability of Geographic Information: A Communication Process –Based Prototype

Directory of Open Access Journals (Sweden)

Jean Brodeur

2005-04-01

Full Text Available Since 1990, municipal, state/provincial, and federal governments have developed numerous geographic databases over the years to fulfill organizations' specific needs. As such, same real world topographic phenomena have been abstracted differently, for instance vegetation (surface, trees (surface, wooded area (line, wooded area (point and line, milieu boisé (surface, zone boisée (unknown geometry. Today, information about these geographic phenomena is accessible on the Internet from Web infrastructures specially developed to simplify their access. Early in the nineties, the development of interoperability of geographic information has been undertaken to solve syntactic, structural, and semantic heterogeneities as well as spatial and temporal heterogeneities to facilitate sharing and integration of such data. Recently, we have proposed a new conceptual framework for interoperability of geographic information based on the human communication process, cognitive science, and ontology, and introduced geosemantic proximity, a reasoning methodology to qualify dynamically the semantic similarity between geographic abstractions. This framework could be of interest to other disciplines. This paper presents the details of our framework for interoperability of geographic information as well as a prototype.

Feasibility of Close-Range Photogrammetric Models for Geographic Information System

International Nuclear Information System (INIS)

2011-01-01

The objective of this project was to determine the feasibility of using close-range architectural photogrammetry as an alternative three dimensional modeling technique in order to place the digital models in a geographic information system (GIS) at SLAC. With the available equipment and Australis photogrammetry software, the creation of full and accurate models of an example building, Building 281 on SLAC campus, was attempted. After conducting several equipment tests to determine the precision achievable, a complete photogrammetric survey was attempted. The dimensions of the resulting models were then compared against the true dimensions of the building. A complete building model was not evidenced to be obtainable using the current equipment and software. This failure was likely attributable to the limits of the software rather than the precision of the physical equipment. However, partial models of the building were shown to be accurate and determined to still be usable in a GIS. With further development of the photogrammetric software and survey procedure, the desired generation of a complete three dimensional model is likely still feasible.

The significant surface-water connectivity of "geographically isolated wetlands"

Science.gov (United States)

Calhoun, Aram J.K.; Mushet, David M.; Alexander, Laurie C.; DeKeyser, Edward S.; Fowler, Laurie; Lane, Charles R.; Lang, Megan W.; Rains, Mark C.; Richter, Stephen; Walls, Susan

2017-01-01

We evaluated the current literature, coupled with our collective research expertise, on surface-water connectivity of wetlands considered to be “geographically isolated” (sensu Tiner Wetlands 23:494–516, 2003a) to critically assess the scientific foundation of grouping wetlands based on the singular condition of being surrounded by uplands. The most recent research on wetlands considered to be “geographically isolated” shows the difficulties in grouping an ecological resource that does not reliably indicate lack of surface water connectivity in order to meet legal, regulatory, or scientific needs. Additionally, the practice of identifying “geographically isolated wetlands” based on distance from a stream can result in gross overestimates of the number of wetlands lacking ecologically important surface-water connections. Our findings do not support use of the overly simplistic label of “geographically isolated wetlands”. Wetlands surrounded by uplands vary in function and surface-water connections based on wetland landscape setting, context, climate, and geographic region and should be evaluated as such. We found that the “geographically isolated” grouping does not reflect our understanding of the hydrologic variability of these wetlands and hence does not benefit conservation of the Nation’s diverse wetland resources. Therefore, we strongly discourage use of categorizations that provide overly simplistic views of surface-water connectivity of wetlands fully embedded in upland landscapes.

Geographic Differences in the Earnings of Economics Majors

Science.gov (United States)

Winters, John V.; Xu, Weineng

2014-01-01

Economics has been shown to be a relatively high-earning college major, but geographic differences in earnings have been largely overlooked. The authors of this article use the American Community Survey to examine geographic differences in both absolute earnings and relative earnings for economics majors. They find that there are substantial…

Cosmopolitanism, geographical imaginaries and belonging in North London.

Science.gov (United States)

Devadason, Ranji

2010-01-01

Cosmopolitanism has been described as the cultural habitus of globalisation. It is therefore, albeit defined somewhat loosely, often associated with ethnically diverse, global cities. This paper considers the extent to which London engenders cosmopolitan values amongst its residents. It draws on survey data from the LOCAL MULTIDEM study of minorities' political participation to address these themes. The analysis examines perceptions of respect, belonging and geographical imaginaries - amongst established minorities and the ethnic majority - in north London. It is argued that cosmopolitan ethics are transformative and dialectical and, critically, cannot remain the preserve of the privileged in multi-ethnic neighbourhoods. The analysis presented demonstrates that a sense of belonging and cosmopolitan imaginaries are not evenly accessed by different ethnic groups; notably, that Bangladeshi Londoners who are born and bred in the city are less likely to appropriate these discourses than Caribbean, Indian or White residents.

Geographic disparity in kidney transplantation under KAS.

Science.gov (United States)

Zhou, Sheng; Massie, Allan B; Luo, Xun; Ruck, Jessica M; Chow, Eric K H; Bowring, Mary G; Bae, Sunjae; Segev, Dorry L; Gentry, Sommer E

2017-12-12

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was 1.75 1.81 1.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR =  1.35 1.40 1.45 , P geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Formal Ontologies and Uncertainty. In Geographical Knowledge

Directory of Open Access Journals (Sweden)

Matteo Caglioni

2014-05-01

Full Text Available Formal ontologies have proved to be a very useful tool to manage interoperability among data, systems and knowledge. In this paper we will show how formal ontologies can evolve from a crisp, deterministic framework (ontologies of hard knowledge to new probabilistic, fuzzy or possibilistic frameworks (ontologies of soft knowledge. This can considerably enlarge the application potential of formal ontologies in geographic analysis and planning, where soft knowledge is intrinsically linked to the complexity of the phenomena under study.  The paper briefly presents these new uncertainty-based formal ontologies. It then highlights how ontologies are formal tools to define both concepts and relations among concepts. An example from the domain of urban geography finally shows how the cause-to-effect relation between household preferences and urban sprawl can be encoded within a crisp, a probabilistic and a possibilistic ontology, respectively. The ontology formalism will also determine the kind of reasoning that can be developed from available knowledge. Uncertain ontologies can be seen as the preliminary phase of more complex uncertainty-based models. The advantages of moving to uncertainty-based models is evident: whether it is in the analysis of geographic space or in decision support for planning, reasoning on geographic space is almost always reasoning with uncertain knowledge of geographic phenomena.

Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1 deficient mice

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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.

Geographical Gradients in Argentinean Terrestrial Mammal Species Richness and Their Environmental Correlates

Science.gov (United States)

Márquez, Ana L.; Real, Raimundo; Kin, Marta S.; Guerrero, José Carlos; Galván, Betina; Barbosa, A. Márcia; Olivero, Jesús; Palomo, L. Javier; Vargas, J. Mario; Justo, Enrique

2012-01-01

We analysed the main geographical trends of terrestrial mammal species richness (SR) in Argentina, assessing how broad-scale environmental variation (defined by climatic and topographic variables) and the spatial form of the country (defined by spatial filters based on spatial eigenvector mapping (SEVM)) influence the kinds and the numbers of mammal species along these geographical trends. We also evaluated if there are pure geographical trends not accounted for by the environmental or spatial factors. The environmental variables and spatial filters that simultaneously correlated with the geographical variables and SR were considered potential causes of the geographic trends. We performed partial correlations between SR and the geographical variables, maintaining the selected explanatory variables statistically constant, to determine if SR was fully explained by them or if a significant residual geographic pattern remained. All groups and subgroups presented a latitudinal gradient not attributable to the spatial form of the country. Most of these trends were not explained by climate. We used a variation partitioning procedure to quantify the pure geographic trend (PGT) that remained unaccounted for. The PGT was larger for latitudinal than for longitudinal gradients. This suggests that historical or purely geographical causes may also be relevant drivers of these geographical gradients in mammal diversity. PMID:23028254

Geographical Gradients in Argentinean Terrestrial Mammal Species Richness and Their Environmental Correlates

Directory of Open Access Journals (Sweden)

Ana L. Márquez

2012-01-01

Full Text Available We analysed the main geographical trends of terrestrial mammal species richness (SR in Argentina, assessing how broad-scale environmental variation (defined by climatic and topographic variables and the spatial form of the country (defined by spatial filters based on spatial eigenvector mapping (SEVM influence the kinds and the numbers of mammal species along these geographical trends. We also evaluated if there are pure geographical trends not accounted for by the environmental or spatial factors. The environmental variables and spatial filters that simultaneously correlated with the geographical variables and SR were considered potential causes of the geographic trends. We performed partial correlations between SR and the geographical variables, maintaining the selected explanatory variables statistically constant, to determine if SR was fully explained by them or if a significant residual geographic pattern remained. All groups and subgroups presented a latitudinal gradient not attributable to the spatial form of the country. Most of these trends were not explained by climate. We used a variation partitioning procedure to quantify the pure geographic trend (PGT that remained unaccounted for. The PGT was larger for latitudinal than for longitudinal gradients. This suggests that historical or purely geographical causes may also be relevant drivers of these geographical gradients in mammal diversity.

SCHOOL LINGUISTIC CREATIVITY BASED ON SCIENTIFIC GEOGRAPHICAL TEXTS

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VIORICA BLÎNDĂ

2012-01-01

Full Text Available The analysis and observation of the natural environment and of the social and economic one, observing phenomena, objects, beings, and geographical events are at the basis of producing geographical scientific texts. The symbols of iconotexts and cartotexts are another source of inspiration for linguistic interpretation. The linguistic creations that we selected for our study are the scientific analysis, the commentary, the characterization, the parallel, the synthesis, epitomizing and abstracting, the scientific communication, the essay, and the scientific description. The representations on maps, photos, graphics and profiles are translated into verbal or written expression in order to render geographical scientific information from diagrams and images through diverse discursive procedures. Through school linguistic creations, teachers develop their students’ observation spirit, in a written and oral form, their geographical thinking through metaphors, they develop and stimulate their students’ imagination and fantasy, their cognitive, reflexive and affective sensitivity, their abilities to express themselves, to present and argument in a scientific way according to different criteria (sufficiency, demonstrative reasoning, lineal reasoning, pros and cons, giving examples, inferential deduction through using truth tables, etc.. Trough description, students give names and define geographical objects and beings (plants, animals, and people according to their form and aspect, they explain toponyms and appellatives, they classify and make hierarchies, they define their identity through processes of differentiation, emblematizing, personification, location in time and space.

The application of geographic information system to radiological and nuclear emergency monitoring

International Nuclear Information System (INIS)

Sadaniowski, I.V.; Rodriguez, M.; Rojas, C.A.; Jordan, O.D.

2010-01-01

The Geographic Information System (GIS) implementation for the preparation and response in case of to radiological and nuclear emergencies is being developed in the Emergency Control Center of the Argentina Nuclear Regulatory Authority, since many years ago. Additionals features have been incorporated such as integration with the results of radiological monitoring, improving and expanding its benefits both in the preparation stage and during the work of emergency response. This paper shows the specific application of GIS to radiological monitoring in case of emergency situations such as during the search of orphan sources and the characterization of geographic context around nuclear power plants and atomic centers. The GIS provides essential data cartographic for the monitoring with sophisticated detectors, to integrate with the information received with infrastructure, urban and rural population maps, physical features of the place, satellite images, etc. The monitoring results are analyzed and compared with relevant information for decision making during the response, like evacuation routes, affected population, security forces in the area, radiological characterization, application of protective actions, hospitals, schools, etc. These two integrated tools improve preparedness and response system in case of radiological or nuclear emergency. (authors) [es

NEPR Geographic Zone Map 2015

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This geographic zone map was created by interpreting satellite and aerial imagery, seafloor topography (bathymetry model), and the new NEPR Benthic Habitat Map...

CYBERNETICS AND GEOGRAPHICAL EDUCATION: CYBERNETICS OF LEARNING AND LEARNING OF CYBERNETICS

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M. R. Arpentieva

2017-01-01

Full Text Available Modern geographical education implies a broad implementation of innovative technologies, allowing students to fully and deeply understand the subject and methods of professional activity, and effectively and productively act upon this understanding. Therefore, in the work of modern geographer computer and media technologies occupy a significant place, and geographic education occupies an important place in learning cybernetic disciplines: computer technologies act as an important condition for obtaining high quality professional education, as well as an important tool of professional activity of modern specialist-geographer. The article is devoted to comparing three modern approaches to the study and optimization of training Cybernetics and programming in the framework of geographical education: an approach devoted to the study of “learning styles”; the metacognitive approach to learning computer science and programming; and intersubjective, evergetic or actually cybernetic, approach. It describes their advantages and limitations in the context of geographical education, as well as the internal unity as different forms of study of productivity and conditions of the dialogical interaction between teacher and student in the context of obtaining high-quality geographical education.

Geographic variation in advertisement calls of a Microhylid frog - testing the role of drift and ecology.

Science.gov (United States)

Lee, Ko-Huan; Shaner, Pei-Jen L; Lin, Yen-Po; Lin, Si-Min

2016-05-01

Acoustic signals for mating are important traits that could drive population differentiation and speciation. Ecology may play a role in acoustic divergence through direct selection (e.g., local adaptation to abiotic environment), constraint of correlated traits (e.g., acoustic traits linked to another trait under selection), and/or interspecific competition (e.g., character displacement). However, genetic drift alone can also drive acoustic divergence. It is not always easy to differentiate the role of ecology versus drift in acoustic divergence. In this study, we tested the role of ecology and drift in shaping geographic variation in the advertisement calls of Microhyla fissipes. We examined three predictions based on ecological processes: (1) the correlation between temperature and call properties across M. fissipes populations; (2) the correlation between call properties and body size across M. fissipes populations; and (3) reproductive character displacement (RCD) in call properties between M. fissipes populations that are sympatric with and allopatric to a congener M. heymonsi. To test genetic drift, we examined correlations among call divergence, geographic distance, and genetic distance across M. fissipes populations. We recorded the advertisement calls from 11 populations of M. fissipes in Taiwan, five of which are sympatrically distributed with M. heymonsi. We found geographic variation in both temporal and spectral properties of the advertisement calls of M. fissipes. However, the call properties were not correlated with local temperature or the callers' body size. Furthermore, we did not detect RCD. By contrast, call divergence, geographic distance, and genetic distance between M. fissipes populations were all positively correlated. The comparisons between phenotypic Q st (P st) and F st values did not show significant differences, suggesting a role of drift. We concluded that genetic drift, rather than ecological processes, is the more likely

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.

Like your labels?

Science.gov (United States)

Field, Michele

2010-01-01

The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off.

Petroleum supply monthly, December 1998 with data for October 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-12-01

Data presented in the Petroleum Supply Monthly (PSM) describe the supply and disposition of petroleum products in the US 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 US (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 US. Data presented in the PSM are divided into two sections: Summary Statistics and Detailed Statistics. 82 tabs.

47 CFR 22.911 - Cellular geographic service area.

Science.gov (United States)

2010-10-01

... Cellular Geographic Service Area (CGSA) of a cellular system is the geographic area considered by the FCC... application for modification of the CGSA using FCC Form 601, a depiction of what the carrier believes the CGSA... location and the locus of points where the predicted or measured median field strength finally drops to 32...

Ecoscapes: Geographical Patternings of Relations

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Aimar Ventsel

2012-06-01

Full Text Available Book review of the publication Ecoscapes: Geographical Patternings of Relations. Edited by Gary Backhaus and John Murungi. Lanham, Boulder, New York, Toronto, Oxford, Lexington Books, 2006, xxxiii+241 pp.

Ecoscapes: Geographical Patternings of Relations

Directory of Open Access Journals (Sweden)

Aimar Ventsel

2013-01-01

Full Text Available Book review of the publication Ecoscapes: Geographical Patternings of Relations. Edited by Gary Backhaus and John Murungi. Lanham, Boulder, New York, Toronto, Oxford, Lexington Books, 2006, xxxiii+241 pp.