ISLSCP II Surface Radiation Budget (SRB) Radiation Data

Data.gov (United States)

National Aeronautics and Space Administration — ABSTRACT: This data set contains global Surface Radiation Budget (SRB) and a few top-of-atmosphere (TOA) radiation budget parameters on a 1-degree x 1-degree spatial...

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

Use of a GCM to Explore Sampling Issues in Connection with Satellite Remote Sensing of the Earth Radiation Budget

Science.gov (United States)

Fowler, Laura D.; Wielicki, Bruce A.; Randall, David A.; Branson, Mark D.; Gibson, Gary G.; Denn, Fredrick M.

2000-01-01

Collocated in time and space, top-of-the-atmosphere measurements of the Earth radiation budget (ERB) and cloudiness from passive scanning radiometers, and lidar- and radar-in-space measurements of multilayered cloud systems, are the required combination to improve our understanding of the role of clouds and radiation in climate. Experiments to fly multiple satellites "in formation" to measure simultaneously the radiative and optical properties of overlapping cloud systems are being designed. Because satellites carrying ERB experiments and satellites carrying lidars- or radars-in space have different orbital characteristics, the number of simultaneous measurements of radiation and clouds is reduced relative to the number of measurements made by each satellite independently. Monthly averaged coincident observations of radiation and cloudiness are biased when compared against more frequently sampled observations due, in particular, to the undersampling of their diurnal cycle, Using the Colorado State University General Circulation Model (CSU GCM), the goal of this study is to measure the impact of using simultaneous observations from the Earth Observing System (EOS) platform and companion satellites flying lidars or radars on monthly averaged diagnostics of longwave radiation, cloudiness, and its cloud optical properties. To do so, the hourly varying geographical distributions of coincident locations between the afternoon EOS (EOS-PM) orbit and the orbit of the ICESAT satellite set to fly at the altitude of 600 km, and between the EOS PM orbit and the orbits of the PICASSO satellite proposed to fly at the altitudes of 485 km (PICA485) or 705 km (PICA705), are simulated in the CSU GCM for a 60-month time period starting at the idealistic July 1, 2001, launch date. Monthly averaged diagnostics of the top-of-the-atmosphere, atmospheric, and surface longwave radiation budgets and clouds accumulated over grid boxes corresponding to satellite overpasses are compared against

Nimbus-7 Earth radiation budget calibration history. Part 2: The Earth flux channels

Science.gov (United States)

Kyle, H. Lee; Hucek, Douglas Richard R.; Ardanuy, Philip E.; Hickey, John R.; Maschhoff, Robert H.; Penn, Lanning M.; Groveman, Brian S.; Vallette, Brenda J.

1994-01-01

Nine years (November 1978 to October 1987) of Nimbus-7 Earth radiation budget (ERB) products have shown that the global annual mean emitted longwave, absorbed shortwave, and net radiation were constant to within about + 0.5 W/sq m. Further, most of the small annual variations in the emitted longwave have been shown to be real. To obtain this measurement accuracy, the wide-field-of-view (WFOV) Earth-viewing channels 12 (0.2 to over 50 micrometers), 13 (0.2 to 3.8 micrometers), and 14 (0.7 to 2.8 micrometers) have been characterized in their satellite environment to account for signal variations not considered in the prelaunch calibration equations. Calibration adjustments have been derived for (1) extraterrestrial radiation incident on the detectors, (2) long-term degradation of the sensors, and (3) thermal perturbations within the ERB instrument. The first item is important in all the channels; the second, mainly in channels 13 and 14, and the third, only in channels 13 and 14. The Sun is used as a stable calibration source to monitor the long-term degradation of the various channels. Channel 12, which is reasonably stable to both thermal perturbations and sensor degradation, is used as a reference and calibration transfer agent for the drifting sensitivities of the filtered channels 13 and 14. Redundant calibration procedures were utilized. Laboratory studies complemented analyses of the satellite data. Two nearly independent models were derived to account for the thermal perturbations in channels 13 and 14. The global annual mean terrestrial shortwave and longwave signals proved stable enough to act as secondary calibration sources. Instantaneous measurements may still, at times, be in error by as much as a few Wm(exp -2), but the long-term averages are stable to within a fraction of a Wm(exp -2).

Radiation budget measurement/model interface

Science.gov (United States)

Vonderhaar, T. H.; Ciesielski, P.; Randel, D.; Stevens, D.

1983-01-01

This final report includes research results from the period February, 1981 through November, 1982. Two new results combine to form the final portion of this work. They are the work by Hanna (1982) and Stevens to successfully test and demonstrate a low-order spectral climate model and the work by Ciesielski et al. (1983) to combine and test the new radiation budget results from NIMBUS-7 with earlier satellite measurements. Together, the two related activities set the stage for future research on radiation budget measurement/model interfacing. Such combination of results will lead to new applications of satellite data to climate problems. The objectives of this research under the present contract are therefore satisfied. Additional research reported herein includes the compilation and documentation of the radiation budget data set a Colorado State University and the definition of climate-related experiments suggested after lengthy analysis of the satellite radiation budget experiments.

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

Science.gov (United States)

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

1995-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2000-07-01

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

Radiative effects of clouds and cryosphere in the Antarctic

Directory of Open Access Journals (Sweden)

Takashi Yamanouchi

1997-03-01

Full Text Available Examination of the effects of clouds, ice sheet and sea ice on the radiation budget in the Antarctic using Earth Radiation Budget Experiment (ERBE data were reported. The continental ice sheet affects not only the albedo, but also the surface temperature because of elevation, and hence the OLR. Sea ice, which is a critical climate feedback factor, appears to have less impact on radiation than do clouds. However, these surfaces lie underneath clouds, and it was found that the independent effect of sea ice is as large as that of clouds, and clouds are masking the radiative effect of sea ice by more than half. The radiation budget at the top of the atmosphere from satellite observation and that at the surface from the surface radiation measurements at Syowa and South Pole Stations were compared. Cloud radiative forcing at both stations for the surface, atmosphere and top of the atmosphere was derived.

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.

GEWEX Surface Radiation Budget (SRB)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NASA/GEWEX Surface Radiation Budget (SRB) Release-3.0 data sets contains global 3-hourly, daily, monthly/3-hourly, and monthly averages of surface and top-of...

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....

Reactor safety and radiation protection. Draft of the BMU deparmental budget 16 of the 1998 German federal budget

International Nuclear Information System (INIS)

Anon.

1997-01-01

The expenditures earmarked for reactor safety and radiation protection in the 1998 budget of the German Federal Ministry for the Environment, Nature Conservation, and Reactor Safety (BMU) total DM 101 million. The expenditures of the German Federal Office for Radiation Protection (BfS) are to amount to a total of DM 579 million. These are the figures included in departmental budget 16 of the 1998 federal budget, which was discussed by the Federal Parliament in September 1997. The atw compilation singles out a number of significant items of the departmental budget. (orig.) [de

A history of presatellite investigations of the earth's radiation budget

Science.gov (United States)

Hunt, G. E.; Kandel, R.; Mecherikunnel, A. T.

1986-01-01

The history of radiation budget studies from the early twentieth century to the advent of the space age is reviewed. By the beginning of the 1960's, accurate radiative models had been developed capable of estimating the global and zonally averaged components of the radiation budget, though great uncertainty in the derived parameters existed due to inaccuracy of the data describing the physical parameters used in the model, associated with clouds, the solar radiation, and the gaseous atmospheric absorbers. Over the century, the planetary albedo estimates had reduced from 89 to 30 percent.

Radiation budget measurement/model interface research

Science.gov (United States)

Vonderhaar, T. H.

1981-01-01

The NIMBUS 6 data were analyzed to form an up to date climatology of the Earth radiation budget as a basis for numerical model definition studies. Global maps depicting infrared emitted flux, net flux and albedo from processed NIMBUS 6 data for July, 1977, are presented. Zonal averages of net radiation flux for April, May, and June and zonal mean emitted flux and net flux for the December to January period are also presented. The development of two models is reported. The first is a statistical dynamical model with vertical and horizontal resolution. The second model is a two level global linear balance model. The results of time integration of the model up to 120 days, to simulate the January circulation, are discussed. Average zonal wind, meridonal wind component, vertical velocity, and moisture budget are among the parameters addressed.

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.

Nimbus-7 Solar and Earth Flux Data in Native Binary Format

Data.gov (United States)

National Aeronautics and Space Administration — The NIMBUS7_ERB_SEFDT data set is the Solar and Earth Flux Data Tape (SEFDT) generated from Nimbus-7 Earth Radiation Budget (ERB) instrument data. The main purpose...

Nimbus-7 Earth radiation budget calibration history. Part 1: The solar channels

Science.gov (United States)

Kyle, H. Lee; Hoyt, Douglas V.; Hickey, John R.; Maschhoff, Robert H.; Vallette, Brenda J.

1993-01-01

The Earth Radiation Budget (ERB) experiment on the Nimbus-7 satellite measured the total solar irradiance plus broadband spectral components on a nearly daily basis from 16 Nov. 1978, until 16 June 1992. Months of additional observations were taken in late 1992 and in 1993. The emphasis is on the electrically self calibrating cavity radiometer, channel 10c, which recorded accurate total solar irradiance measurements over the whole period. The spectral channels did not have inflight calibration adjustment capabilities. These channels can, with some additional corrections, be used for short-term studies (one or two solar rotations - 27 to 60 days), but not for long-term trend analysis. For channel 10c, changing radiometer pointing, the zero offsets, the stability of the gain, the temperature sensitivity, and the influences of other platform instruments are all examined and their effects on the measurements considered. Only the question of relative accuracy (not absolute) is examined. The final channel 10c product is also compared with solar measurements made by independent experiments on other satellites. The Nimbus experiment showed that the mean solar energy was about 0.1 percent (1.4 W/sqm) higher in the excited Sun years of 1979 and 1991 than in the quiet Sun years of 1985 and 1986. The error analysis indicated that the measured long-term trends may be as accurate as +/- 0.005 percent. The worse-case error estimate is +/- 0.03 percent.

3D modeling of satellite spectral images, radiation budget and energy budget of urban landscapes

Science.gov (United States)

Gastellu-Etchegorry, J. P.

2008-12-01

DART EB is a model that is being developed for simulating the 3D (3 dimensional) energy budget of urban and natural scenes, possibly with topography and atmosphere. It simulates all non radiative energy mechanisms (heat conduction, turbulent momentum and heat fluxes, water reservoir evolution, etc.). It uses DART model (Discrete Anisotropic Radiative Transfer) for simulating radiative mechanisms: 3D radiative budget of 3D scenes and their remote sensing images expressed in terms of reflectance or brightness temperature values, for any atmosphere, wavelength, sun/view direction, altitude and spatial resolution. It uses an innovative multispectral approach (ray tracing, exact kernel, discrete ordinate techniques) over the whole optical domain. This paper presents two major and recent improvements of DART for adapting it to urban canopies. (1) Simulation of the geometry and optical characteristics of urban elements (houses, etc.). (2) Modeling of thermal infrared emission by vegetation and urban elements. The new DART version was used in the context of the CAPITOUL project. For that, districts of the Toulouse urban data base (Autocad format) were translated into DART scenes. This allowed us to simulate visible, near infrared and thermal infrared satellite images of Toulouse districts. Moreover, the 3D radiation budget was used by DARTEB for simulating the time evolution of a number of geophysical quantities of various surface elements (roads, walls, roofs). Results were successfully compared with ground measurements of the CAPITOUL project.

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)

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].

Daily Radiation Budget of the Baltic Sea Surface from Satellite Data

Directory of Open Access Journals (Sweden)

Zapadka Tomasz

2015-09-01

Full Text Available Recently developed system for assessment of radiation budget for the Baltic Sea has been presented and verified. The system utilizes data from various sources: satellite, model and in situ measurements. It has been developed within the SatBałtyk project (Satellite Monitoring of the Baltic Sea Environment - www.satbaltyk.eu where the energy radiation budget is one of the key element. The SatBałtyk system generates daily maps of the all components of radiation budget on every day basis. We show the scheme of making daily maps, applied algorithms and empirical data collection within the system. An empirical verification of the system has been carried out based on empirical data collected on the oil rig placed on the Baltic Sea. This verification concerned all the components of the surface radiation budget. The average daily NET products are estimated with statistical error ca. 13 Wm-2. The biggest absolute statistical error is for LWd component and equals 14 Wm-2. The relative error in relation to the average annual values for whole Baltic is the biggest for SWu and reaches 25%. All estimated components have correlation coefficient above 0.91.

The Geostationary Earth Radiation Budget Project.

Science.gov (United States)

Harries, J. E.; Russell, J. E.; Hanafin, J. A.; Brindley, H.; Futyan, J.; Rufus, J.; Kellock, S.; Matthews, G.; Wrigley, R.; Last, A.; Mueller, J.; Mossavati, R.; Ashmall, J.; Sawyer, E.; Parker, D.; Caldwell, M.; Allan, P. M.; Smith, A.; Bates, M. J.; Coan, B.; Stewart, B. C.; Lepine, D. R.; Cornwall, L. A.; Corney, D. R.; Ricketts, M. J.; Drummond, D.; Smart, D.; Cutler, R.; Dewitte, S.; Clerbaux, N.; Gonzalez, L.; Ipe, A.; Bertrand, C.; Joukoff, A.; Crommelynck, D.; Nelms, N.; Llewellyn-Jones, D. T.; Butcher, G.; Smith, G. L.; Szewczyk, Z. P.; Mlynczak, P. E.; Slingo, A.; Allan, R. P.; Ringer, M. A.

2005-07-01

This paper reports on a new satellite sensor, the Geostationary Earth Radiation Budget (GERB) experiment. GERB is designed to make the first measurements of the Earth's radiation budget from geostationary orbit. Measurements at high absolute accuracy of the reflected sunlight from the Earth, and the thermal radiation emitted by the Earth are made every 15 min, with a spatial resolution at the subsatellite point of 44.6 km (north south) by 39.3 km (east west). With knowledge of the incoming solar constant, this gives the primary forcing and response components of the top-of-atmosphere radiation. The first GERB instrument is an instrument of opportunity on Meteosat-8, a new spin-stabilized spacecraft platform also carrying the Spinning Enhanced Visible and Infrared (SEVIRI) sensor, which is currently positioned over the equator at 3.5°W. This overview of the project includes a description of the instrument design and its preflight and in-flight calibration. An evaluation of the instrument performance after its first year in orbit, including comparisons with data from the Clouds and the Earth's Radiant Energy System (CERES) satellite sensors and with output from numerical models, are also presented. After a brief summary of the data processing system and data products, some of the scientific studies that are being undertaken using these early data are described. This marks the beginning of a decade or more of observations from GERB, as subsequent models will fly on each of the four Meteosat Second Generation satellites.

Long Term Measurement of the Earth's Radiation Budget using a constellation of Broadband Radiometers hosted on Iridium NEXT

Science.gov (United States)

Gupta, Om Prakash; Thoma, Donald; Chaloner, Chris; Russell, Jacqueline; Simpson, Bill; Spilling, David; Morris, Nigel; Caldwell, Martin; Oneill, Alan

The WMO called for "bringing new missions to operational status" and that "ERB should be measured through a constellation of sensors". A unique opportu-nity exists to host a set of Earth Radiation Budget (ERB) sensors on the Iridium NEXT (NEXT) LEO constellation in a cost effective manner that can deliver these requirements. The NEXT constellation, with 66 interconnected satellites in 6 near polar orbiting planes, provides a unique platform for hosting a variety of Earth observation missions including ERB. Launches are planned to begin in 2014 through 2016. The ERB both drives and responds to global climate and monitoring it can provide much insight into the climate system and how it might be changing. A climate quality measurement of the ERB requires high absolute accuracy and excellent stability and a long-term (decades) data record in order to inform the debate about global warming. Measurement of the ERB in terms of the broadband reflected solar (0.3 to 4 µm) and emitted thermal (4 to 200 µm) components have been identified as high priority by the WMO for climate observations. High temporal resolution is the key advantage offered by the NEXT platform and can provide a great step forward in accurately monitoring the energy balance of the planet. The sensor we propose will consist of a broad band instrument and associated imager for scene identification and cloud classification. There is the chance to place two such sensors in each of six different orbital planes this will improve the product refresh time from currently 12 hours to 3 hours. The increased temporal resolution will allow direct measure-ment of the changes to the broadband radiances that result from rapidly varying components of the climate such as cloud and aerosol, and avoid the need of relying on narrow band sensors to infer such changes. Considering that the prediction of cloud response to climate change is still a major source of uncertainty; improved measurement of the cloud effect and

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.

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.

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].

Future Flight Opportunities and Calibration Protocols for CERES: Continuation of Observations in Support of the Long-Term Earth Radiation Budget Climate Data Record

Science.gov (United States)

Priestley, Kory J.; Smith, George L.

2010-01-01

The goal of the Clouds and the Earth s Radiant Energy System (CERES) project is to provide a long-term record of radiation budget at the top-of-atmosphere (TOA), within the atmosphere, and at the surface with consistent cloud and aerosol properties at climate accuracy. CERES consists of an integrated instrument-algorithm validation science team that provides development of higher-level products (Levels 1-3) and investigations. It involves a high level of data fusion, merging inputs from 25 unique input data sources to produce 18 CERES data products. Over 90% of the CERES data product volume involves two or more instruments. Continuation of the Earth Radiation Budget (ERB) Climate Data Record (CDR) has been identified as critical in the 2007 NRC Decadal Survey, the Global Climate Observing System WCRP report, and in an assessment titled Impacts of NPOESS Nunn-McCurdy Certification on Joint NASA-NOAA Climate Goals . Five CERES instruments have flown on three different spacecraft: TRMM, EOS-Terra and EOS-Aqua. In response, NASA, NOAA and NPOESS have agreed to fly the existing CERES Flight Model (FM-5) on the NPP spacecraft in 2011 and to procure an additional CERES Sensor with modest upgrades for flight on the JPSS C1 spacecraft in 2014, followed by a CERES follow-on sensor for flight in 2018. CERES is a scanning broadband radiometer that measures filtered radiance in the SW (0.3-5 m), total (TOT) (0.3-200 m) and WN (8-12 m) regions. Pre-launch calibration is performed on each Flight Model to meet accuracy requirements of 1% for SW and 0.5% for outgoing LW observations. Ground to flight or in-flight changes are monitored using protocols employing onboard and vicarious calibration sources. Studies of flight data show that SW response can change dramatically due to optical contamination. with greatest impact in blue-to UV radiance, where tungsten lamps are largely devoid of output. While science goals remain unchanged for ERB Climate Data Record, it is now understood

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.

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].

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.

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

Directory of Open Access Journals (Sweden)

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.

Continental Ice Sheets and the Planetary Radiation Budget

NARCIS (Netherlands)

Oerlemans, J.

1980-01-01

The interaction between continental ice sheets and the planetary radiation budget is potentially important in climate-sensitivity studies. A simple ice-sheet model incorporated in an energybalance climate model provides a tool for studying this interaction in a quantitative way. Experiments in which

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

Science.gov (United States)

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

1983-01-01

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

Radiation budget in green beans crop with and without polyethylene cover

International Nuclear Information System (INIS)

Souza, J.L. de; Escobedo, J.F.

1997-01-01

The radiation budget in agricultural crops is very important on the microclimate characterization, on the water losses determination and on dry matter accumulation of vegetation. This work describes the radiation budget determination in a green beans crop (Phaseolus vulgaris L.), in Botucatu, SP, Brazil (22° 54′S; 48° 27′W; 850 m), under two different conditions: the normal field culture and in a polyethylene greenhouse. The densities of fluxes of radiation were used to construct diurnal curves of the components of global radiation (Rg), reflected radiation (Rr), net radiation (Rn).The arithmetic's relations allowed to obtain the components net short-waves (Rc) and net long-waves (Rl). The analysis of these components related to the leaf area index (LAI) in many phenological phases of the culture showed Rg distributed in 68%, 85%, 17% and 66%, 76%, 10% to Rn, Rc and Rl in the internal and external ambients in a polyethylene greenhouse, respectively [pt

Analysis of the radiation budget in regional climate simulations with COSMO-CLM for Africa

Directory of Open Access Journals (Sweden)

Steffen Kothe

2014-09-01

Full Text Available This study analysed two regional climate simulations for Africa regarding the radiation budgets with particular focus on the contribution of potentially influential parameters on uncertainties in the radiation components. The ERA-Interim driven simulations have been performed with the COSMO-CLM (grid-spacings of 0.44 ° or 0.22 °. The simulated budgets were compared to the satellite-based Global Energy and Water Cycle Experiment Surface Radiation Budget and ERA-Interim data sets. The COSMO-CLM tended to underestimate the net solar radiation and the outgoing long-wave radiation, and showed a regionally varying over- or underestimation in all budget components. An increase in horizontal resolution from 0.44 ° to 0.22 ° slightly reduced the mean errors by up to 5 %. Especially over sea regions, uncertainties in cloud fraction were the main influencing parameter on errors in the simulated radiation fluxes. Compared to former simulations the introduction of a new bare soil albedo treatment reduced the influence of uncertainties in surface albedo significantly. Over the African continent errors in aerosol optical depth and skin temperature were regionally important sources for the discrepancies within the simulated radiation. In a sensitivity test it was shown that the use of aerosol optical depth values from the MACC reanalysis product improved the simulated surface radiation substantially.

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

Long-term monitoring of the earth's radiation budget; Proceedings of the Meeting, Orlando, FL, Apr. 17, 18, 1990

Science.gov (United States)

Barkstrom, Bruce R. (Editor)

1990-01-01

The uses of the broadband flux measurements as well as the improvements in the Earth Radiation Budget Experiment in instrumentation and data reduction are summarized. Scientific uses of earth-radiation budget data are discussed, along with a perspective on the instrumentation giving a new foundation for studies of the radiation budget, with emphasis on calibration and long-term stability. Cloud identification and angular modeling are covered including angular dependence models for radiance to flux conversion and the pattern recognition of clouds and ice in polar regions. The surface-radiation budget and atmospheric radiative flux divergence from the Clouds and Earth Radiant Energy System are covered, and time dependence of the earth's radiation fields, determination of the outgoing longwave radiation and its diurnal variations are considered.

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.

The geostationary Earth radiation budget (GERB) instrument on EUMETSAT's MSG satellite

Science.gov (United States)

Sandford, M. C. W.; Allan, P. M.; Caldwell, M. E.; Delderfield, J.; Oliver, M. B.; Sawyer, E.; Harries, J. E.; Ashmall, J.; Brindley, H.; Kellock, S.; Mossavati, R.; Wrigley, R.; Llewellyn-Jones, D.; Blake, O.; Butcher, G.; Cole, R.; Nelms, N.; DeWitte, S.; Gloesener, P.; Fabbrizzi, F.

2003-12-01

Geostationary Earth radiation budget (GERB) is an Announcement of Opportunity Instrument for EUMETSAT's Meteosat Second Generation (MSG) satellite. GERB will make accurate measurements of the Earth Radiation Budget from geostationary orbit, provide an absolute reference calibration for LEO Earth radiation budget instruments and allow studies of the energetics of atmospheric processes. By operating from geostationary orbit, measurements may be made many times a day, thereby providing essentially perfect diurnal sampling of the radiation balance between reflected and emitted radiance for that area of the globe within the field of view. GERB will thus complement other instruments which operate in low orbit and give complete global coverage, but with poor and biased time resolution. GERB measures infrared radiation in two wavelength bands: 0.32-4.0 and 0.32- 30 μm, with a pixel element size of 44 km at sub-satellite point. This paper gives an overview of the project and concentrates on the design and development of the instrument and ground testing and calibration, and lessons learnt from a short time scale low-budget project. The instrument was delivered for integration on the MSG platform in April 1999 ready for the proposed launch in October 2000, which has now been delayed probably to early 2002. The ground segment is being undertaken by RAL and RMIB and produces near real-time data for meteorological applications in conjunction with the main MSG imager—SEVERI. Climate research and other applications which are being developed under a EU Framework IV pilot project will be served by fully processed data. Because of the relevance of the observations to climate change, it is planned to maintain an operating instrument in orbit for at least 3.5 years. Two further GERB instruments are being built for subsequent launches of MSG.

A Predictor Analysis Framework for Surface Radiation Budget Reprocessing Using Design of Experiments

Science.gov (United States)

Quigley, Patricia Allison

Earth's Radiation Budget (ERB) is an accounting of all incoming energy from the sun and outgoing energy reflected and radiated to space by earth's surface and atmosphere. The National Aeronautics and Space Administration (NASA)/Global Energy and Water Cycle Experiment (GEWEX) Surface Radiation Budget (SRB) project produces and archives long-term datasets representative of this energy exchange system on a global scale. The data are comprised of the longwave and shortwave radiative components of the system and is algorithmically derived from satellite and atmospheric assimilation products, and acquired atmospheric data. It is stored as 3-hourly, daily, monthly/3-hourly, and monthly averages of 1° x 1° grid cells. Input parameters used by the algorithms are a key source of variability in the resulting output data sets. Sensitivity studies have been conducted to estimate the effects this variability has on the output data sets using linear techniques. This entails varying one input parameter at a time while keeping all others constant or by increasing all input parameters by equal random percentages, in effect changing input values for every cell for every three hour period and for every day in each month. This equates to almost 11 million independent changes without ever taking into consideration the interactions or dependencies among the input parameters. A more comprehensive method is proposed here for the evaluating the shortwave algorithm to identify both the input parameters and parameter interactions that most significantly affect the output data. This research utilized designed experiments that systematically and simultaneously varied all of the input parameters of the shortwave algorithm. A D-Optimal design of experiments (DOE) was chosen to accommodate the 14 types of atmospheric properties computed by the algorithm and to reduce the number of trials required by a full factorial study from millions to 128. A modified version of the algorithm was made

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.

Measuring Earth's Radiation Budget from the Vicinity of the Moon

Science.gov (United States)

Swartz, W. H.; Lorentz, S. R.; Erlandson, R. E.; Cahalan, R. F.; Huang, P. M.

2018-02-01

We propose to measure Earth's radiation budget (integrated total and solar-reflected shortwave) using broadband radiometers and other technology demonstrated in space. The instrument is compact, autonomous, and has modest resource requirements.

Radiation budget changes with dry forest clearing in temperate Argentina.

Science.gov (United States)

Houspanossian, Javier; Nosetto, Marcelo; Jobbágy, Esteban G

2013-04-01

Land cover changes may affect climate and the energy balance of the Earth through their influence on the greenhouse gas composition of the atmosphere (biogeochemical effects) but also through shifts in the physical properties of the land surface (biophysical effects). We explored how the radiation budget changes following the replacement of temperate dry forests by crops in central semiarid Argentina and quantified the biophysical radiative forcing of this transformation. For this purpose, we computed the albedo and surface temperature for a 7-year period (2003-2009) from MODIS imagery at 70 paired sites occupied by native forests and crops and calculated the radiation budget at the tropopause and surface levels using a columnar radiation model parameterized with satellite data. Mean annual black-sky albedo and diurnal surface temperature were 50% and 2.5 °C higher in croplands than in dry forests. These contrasts increased the outgoing shortwave energy flux at the top of the atmosphere in croplands by a quarter (58.4 vs. 45.9 W m(-2) ) which, together with a slight increase in the outgoing longwave flux, yielded a net cooling of -14 W m(-2) . This biophysical cooling effect would be equivalent to a reduction in atmospheric CO2 of 22 Mg C ha(-1) , which involves approximately a quarter to a half of the typical carbon emissions that accompany deforestation in these ecosystems. We showed that the replacement of dry forests by crops in central Argentina has strong biophysical effects on the energy budget which could counterbalance the biogeochemical effects of deforestation. Underestimating or ignoring these biophysical consequences of land-use changes on climate will certainly curtail the effectiveness of many warming mitigation actions, particularly in semiarid regions where high radiation load and smaller active carbon pools would increase the relative importance of biophysical forcing. © 2012 Blackwell Publishing Ltd.

History of satellite missions and measurements of the Earth Radiation Budget (1957-1984)

Science.gov (United States)

House, F. B.; Gruber, A.; Hunt, G. E.; Mecherikunnel, A. T.

1986-01-01

The history of satellite missions and their measurements of the earth radiation budget from the beginning of the space age until the present time are reviewed. The survey emphasizes the early struggle to develop instrument systems to monitor reflected shortwave and emitted long-wave exitances from the earth, and the problems associated with the interpretation of these observations from space. In some instances, valuable data sets were developed from satellite measurements whose instruments were not specifically designed for earth radiation budget observations.

Effects of aerosol/cloud interactions on the global radiation budget

International Nuclear Information System (INIS)

Chuang, C.C.; Penner, J.E.

1994-01-01

Aerosols may modify the microphysics of clouds by acting as cloud condensation nuclei (CCN), thereby enhancing the cloud reflectivity. Aerosols may also alter precipitation development by affecting the mean droplet size, thereby influencing cloud lifetimes and modifying the hydrological cycle. Clouds have a major effect on climate, but aerosol/cloud interactions have not been accounted for in past climate model simulations. However, the worldwide steady rise of global pollutants and emissions makes it imperative to investigate how atmospheric aerosols affect clouds and the global radiation budget. In this paper, the authors examine the relationship between aerosol and cloud drop size distributions by using a detailed micro-physical model. They parameterize the cloud nucleation process in terms of local aerosol characteristics and updraft velocity for use in a coupled climate/chemistry model to predict the magnitude of aerosol cloud forcing. Their simulations indicate that aerosol/cloud interactions may result in important increases in reflected solar radiation, which would mask locally the radiative forcing from increased greenhouse gases. This work is aimed at improving the assessment of the effects of anthropogenic aerosols on cloud optical properties and the global radiation budget

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.

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

Impact of cloud microphysics on cloud-radiation interactions in the CSU general circulation model

Energy Technology Data Exchange (ETDEWEB)

Fowler, L.D.; Randall, D.A.

1995-04-01

Our ability to study and quantify the impact of cloud-radiation interactions in studying global scale climate variations strongly relies upon the ability of general circulation models (GCMs) to simulate the coupling between the spatial and temporal variations of the model-generated cloudiness and atmospheric moisture budget components. In particular, the ability of GCMs to reproduce the geographical distribution of the sources and sinks of the planetary radiation balance depends upon their representation of the formation and dissipation of cloudiness in conjunction with cloud microphysics processes, and the fractional amount and optical characteristics of cloudiness in conjunction with the mass of condensate stored in the atmosphere. A cloud microphysics package which encompasses five prognostic variables for the mass of water vapor, cloud water, cloud ice, rain, and snow has been implemented in the Colorado State University General Circulation Model (CSU GCM) to simulate large-scale condensation processes. Convection interacts with the large-scale environment through the detrainment of cloud water and cloud ice at the top of cumulus towers. The cloud infrared emissivity and cloud optical depth of the model-generated cloudiness are interactive and depend upon the mass of cloud water and cloud ice suspended in the atmosphere. The global atmospheric moisture budget and planetary radiation budget of the CSU GCM obtained from a perpetual January simulation are discussed. Geographical distributions of the atmospheric moisture species are presented. Global maps of the top-of-atmosphere outgoing longwave radiation and planetary albedo are compared against Earth Radiation Budget Experiment (ERBE) satellite data.

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.

Determine Daytime Earth's Radiation Budget from DSCOVR

Science.gov (United States)

Su, W.; Thieman, M. M.; Duda, D. P.; Khlopenkov, K. V.; Liang, L.; Sun-Mack, S.; Minnis, P.; SUN, M.

2017-12-01

The Deep Space Climate Observatory (DSCOVR) platform provides a unique perspective for remote sensing of the Earth. With the National Institute of Standards and Technology Advanced Radiometer (NISTAR) and the Earth Polychromatic Imaging Camera (EPIC) onboard, it provides full-disk measurements of the broadband shortwave and total radiances reaching the L1 position. Because the satellite orbits around the L1 spot, it continuously observes a nearly full Earth, providing the potential to determine the daytime radiation budget of the globe at the top of the atmosphere. The NISTAR is a single-pixel instrument that measures the broadband radiance from the entire globe, while EPIC is a spectral imager with channels in the UV and visible ranges. The Level 1 NISTAR shortwave radiances are filtered radiances. To determine the daytime TOA shortwave and longwave radiative fluxes, the NISTAR measured shortwave radiances must be unfiltered first. We will describe the algorithm used to un-filter the shortwave radiances. These unfiltered NISTAR radiances are then converted to the full disk shortwave and daytime longwave fluxes, by accounting for the anisotropic characteristics of the Earth-reflected and emitted radiances. These anisotropy factors are determined by using the scene identifications determined from multiple low Earth orbit and geostationary satellites matched into the EPIC field of view. Time series of daytime radiation budget determined from NISTAR will be presented, and methodology of estimating the fluxes from the small unlit crescent of the Earth that comprises part of the field of view will also be described. The daytime shortwave and longwave fluxes from NISTAR will be compared with CERES dataset.

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

Directory of Open Access Journals (Sweden)

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.

Radiative budget and cloud radiative effect over the Atlantic from ship-based observations

Directory of Open Access Journals (Sweden)

J. Kalisch

2012-10-01

Full Text Available The aim of this study is to determine cloud-type resolved cloud radiative budgets and cloud radiative effects from surface measurements of broadband radiative fluxes over the Atlantic Ocean. Furthermore, based on simultaneous observations of the state of the cloudy atmosphere, a radiative closure study has been performed by means of the ECHAM5 single column model in order to identify the model's ability to realistically reproduce the effects of clouds on the climate system.

An extensive database of radiative and atmospheric measurements has been established along five meridional cruises of the German research icebreaker Polarstern. Besides pyranometer and pyrgeometer for downward broadband solar and thermal radiative fluxes, a sky imager and a microwave radiometer have been utilized to determine cloud fraction and cloud type on the one hand and temperature and humidity profiles as well as liquid water path for warm non-precipitating clouds on the other hand.

Averaged over all cruise tracks, we obtain a total net (solar + thermal radiative flux of 144 W m⁻² that is dominated by the solar component. In general, the solar contribution is large for cirrus clouds and small for stratus clouds. No significant meridional dependencies were found for the surface radiation budgets and cloud effects. The strongest surface longwave cloud effects were shown in the presence of low level clouds. Clouds with a high optical density induce strong negative solar radiative effects under high solar altitudes. The mean surface net cloud radiative effect is −33 W m⁻².

For the purpose of quickly estimating the mean surface longwave, shortwave and net cloud effects in moderate, subtropical and tropical climate regimes, a new parameterisation was created, considering the total cloud amount and the solar zenith angle.

The ECHAM5 single column model provides a surface net cloud effect that is more

Observational evidence for the impact of jet condensation trails upon the earths radiation budget

Energy Technology Data Exchange (ETDEWEB)

Meinert, D. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

1997-12-31

Jet condensation trails have been classified in AVHRR images from a couple of month. It was tried to estimate their impact upon the radiation budget from the observed radiances. This has been performed by direct comparison of contrail image points to neighboring image points, assuming a slowly varying background. The classification method, basing on an artificial neural network for pattern recognition is explained. The details of the estimation of the net impact of contrails upon the radiation budget are shown by one example. (author) 5 refs.

Observational evidence for the impact of jet condensation trails upon the earths radiation budget

Energy Technology Data Exchange (ETDEWEB)

Meinert, D [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

1998-12-31

Jet condensation trails have been classified in AVHRR images from a couple of month. It was tried to estimate their impact upon the radiation budget from the observed radiances. This has been performed by direct comparison of contrail image points to neighboring image points, assuming a slowly varying background. The classification method, basing on an artificial neural network for pattern recognition is explained. The details of the estimation of the net impact of contrails upon the radiation budget are shown by one example. (author) 5 refs.

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

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.

Influence of Ice Cloud Microphysics on Imager-Based Estimates of Earth's Radiation Budget

Science.gov (United States)

Loeb, N. G.; Kato, S.; Minnis, P.; Yang, P.; Sun-Mack, S.; Rose, F. G.; Hong, G.; Ham, S. H.

2016-12-01

A central objective of the Clouds and the Earth's Radiant Energy System (CERES) is to produce a long-term global climate data record of Earth's radiation budget from the TOA down to the surface along with the associated atmospheric and surface properties that influence it. CERES relies on a number of data sources, including broadband radiometers measuring incoming and reflected solar radiation and OLR, high-resolution spectral imagers, meteorological, aerosol and ozone assimilation data, and snow/sea-ice maps based on microwave radiometer data. While the TOA radiation budget is largely determined directly from accurate broadband radiometer measurements, the surface radiation budget is derived indirectly through radiative transfer model calculations initialized using imager-based cloud and aerosol retrievals and meteorological assimilation data. Because ice cloud particles exhibit a wide range of shapes, sizes and habits that cannot be independently retrieved a priori from passive visible/infrared imager measurements, assumptions about the scattering properties of ice clouds are necessary in order to retrieve ice cloud optical properties (e.g., optical depth) from imager radiances and to compute broadband radiative fluxes. This presentation will examine how the choice of an ice cloud particle model impacts computed shortwave (SW) radiative fluxes at the top-of-atmosphere (TOA) and surface. The ice cloud particle models considered correspond to those from prior, current and future CERES data product versions. During the CERES Edition2 (and Edition3) processing, ice cloud particles were assumed to be smooth hexagonal columns. In the Edition4, roughened hexagonal columns are assumed. The CERES team is now working on implementing in a future version an ice cloud particle model comprised of a two-habit ice cloud model consisting of roughened hexagonal columns and aggregates of roughened columnar elements. In each case, we use the same ice particle model in both the

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.

[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

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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

Radiation budget, soil heat flux and latent heat flux at the forest floor in warm, temperate mixed forest

International Nuclear Information System (INIS)

Tamai, K.; Abe, T.; Araki, M.; Ito, H.

1998-01-01

Seasonal changes in the radiation budget and soil heat flux of a forest floor were measured in a mixed forest located in Kyoto, Japan. The basal area at breast height in the survey forest was about 15·82 m 2 ha −1 , for evergreen trees, and 12·46 m 2 ha −1 , for deciduous trees. The sky view factor was 16 and 22% at the survey site in the foliate and defoliate seasons, respectively. The small difference between the sky view factor in the two seasons was reflected in the seasonal change in the radiation budget of the forest floor. Namely, the net long-wave radiation changed rapidly in leafing and falling days, and the rate of net short-wave radiation was highest in April. The distinctive characteristic of the radiation budget was that the rates of available radiation in the daytime and at night were almost equal in September and October. Latent heat flux at the forest floor was estimated to be around 94 MJ m −2 annually, from our measurement with the simulation model. (author)

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.

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

Science.gov (United States)

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

2017-06-01

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

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

Science.gov (United States)

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

2010-01-01

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

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

Science.gov (United States)

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

2014-10-01

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

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

Directory of Open Access Journals (Sweden)

Gulati Michel

2010-03-01

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

Site selection and directional models of deserts used for ERBE validation targets

Science.gov (United States)

Staylor, W. F.

1986-01-01

Broadband shortwave and longwave radiance measurements obtained from the Nimbus 7 Earth Radiation Budget scanner were used to develop reflectance and emittance models for the Sahara, Gibson, and Saudi Deserts. These deserts will serve as in-flight validation targets for the Earth Radiation Budget Experiment being flown on the Earth Radiation Budget Satellite and two National Oceanic and Atmospheric Administration polar satellites. The directional reflectance model derived for the deserts was a function of the sum and product of the cosines of the solar and viewing zenith angles, and thus reciprocity existed between these zenith angles. The emittance model was related by a power law of the cosine of the viewing zenith angle.

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.

Urban Surface Radiative Energy Budgets Determined Using Aircraft Scanner Data

Science.gov (United States)

Luvall, Jeffrey C.; Quattrochi, Dale A.; Rickman, Doug L.; Estes, Maury G.; Arnold, James E. (Technical Monitor)

2002-01-01

the surface energy budget. Knowledge of it is important in any attempt to describe the radiative and mass fluxes which occur at the surface. Use of energy terms in modeling surface energy budgets allows the direct comparison of various land surfaces encountered in a urban landscape, from vegetated (forest and herbaceous) to non-vegetated (bare soil, roads, and buildings). These terms are also easily measured using remote sensing from aircraft or satellite platforms allowing one to examine the spacial variability. The partitioning of energy budget terms depends on the surface type. In natural landscapes, the partitioning is dependent on canopy biomass, leaf area index, aerodynamic roughness, and moisture status, all of which are influenced by the development stage of the ecosystem. In urban landscapes, coverage by man-made materials substantially alters the surface face energy budget. The remotely sensed data obtained from aircraft and satellites, when properly calibrated allows the measurement of important terms in the radiative surface energy budget a urban landscape scale.

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.

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Study on Earth Radiation Budget mission scenarios

Energy Technology Data Exchange (ETDEWEB)

Dlhopolsky, R; Hollmann, R; Mueller, J; Stuhlmann, R [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

1998-12-31

The goal of this study is to study optimized satellite configurations for observation of the radiation balance of the earth. We present a literature survey of earth radiation budget missions and instruments. We develop a parametric tool to simulate realistic multiple satellite mission scenarios. This tool is a modular computer program which models satellite orbits and scanning operation. We use Meteosat data sampled at three hour intervals as a database to simulate atmospheric scenes. Input variables are satellite equatorial crossing time and instrument characteristics. Regional, zonal and global monthly averages of shortwave and longwave fluxes for an ideal observing system and several realistic satellite scenarios are produced. Comparisons show that the three satellite combinations which have equatorial crossing times at midmorning, noon and midafternoon provide the best shortwave monitoring. Crossing times near sunrise and sunset should be avoided for the shortwave. Longwave diurnal models are necessary over and surfaces and cloudy regions, if there are only two measurements made during daylight hours. We have found in the shortwave inversion comparison that at least 15% of the monthly regional errors can be attributed to the shortwave anisotropic models used. (orig.) 68 refs.

Study on Earth Radiation Budget mission scenarios

Energy Technology Data Exchange (ETDEWEB)

Dlhopolsky, R.; Hollmann, R.; Mueller, J.; Stuhlmann, R. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

1997-12-31

The goal of this study is to study optimized satellite configurations for observation of the radiation balance of the earth. We present a literature survey of earth radiation budget missions and instruments. We develop a parametric tool to simulate realistic multiple satellite mission scenarios. This tool is a modular computer program which models satellite orbits and scanning operation. We use Meteosat data sampled at three hour intervals as a database to simulate atmospheric scenes. Input variables are satellite equatorial crossing time and instrument characteristics. Regional, zonal and global monthly averages of shortwave and longwave fluxes for an ideal observing system and several realistic satellite scenarios are produced. Comparisons show that the three satellite combinations which have equatorial crossing times at midmorning, noon and midafternoon provide the best shortwave monitoring. Crossing times near sunrise and sunset should be avoided for the shortwave. Longwave diurnal models are necessary over and surfaces and cloudy regions, if there are only two measurements made during daylight hours. We have found in the shortwave inversion comparison that at least 15% of the monthly regional errors can be attributed to the shortwave anisotropic models used. (orig.) 68 refs.

Radiative Effects of Aerosols Generated from Biomass Burning, Dust Storms, and Forest Fires

Science.gov (United States)

Christopher Sundar A.; Vulcan, Donna V.; Welch, Ronald M.

1996-01-01

Atmospheric aerosol particles, both natural and anthropogenic, are important to the earth's radiative balance. They scatter the incoming solar radiation and modify the shortwave reflective properties of clouds by acting as Cloud Condensation Nuclei (CCN). Although it has been recognized that aerosols exert a net cooling influence on climate (Twomey et al. 1984), this effect has received much less attention than the radiative forcings due to clouds and greenhouse gases. The radiative forcing due to aerosols is comparable in magnitude to current anthropogenic greenhouse gas forcing but opposite in sign (Houghton et al. 1990). Atmospheric aerosol particles generated from biomass burning, dust storms and forest fires are important regional climatic variables. A recent study by Penner et al. (1992) proposed that smoke particles from biomass burning may have a significant impact on the global radiation balance. They estimate that about 114 Tg of smoke is produced per year in the tropics through biomass burning. The direct and indirect effects of smoke aerosol due to biomass burning could add up globally to a cooling effect as large as 2 W/sq m. Ackerman and Chung (1992) used model calculations and the Earth Radiation Budget Experiment (ERBE) data to show that in comparison to clear days, the heavy dust loading over the Saudi Arabian peninsula can change the Top of the Atmosphere (TOA) clear sky shortwave and longwave radiant exitance by 40-90 W/sq m and 5-20 W/sq m, respectively. Large particle concentrations produced from these types of events often are found with optical thicknesses greater than one. These aerosol particles are transported across considerable distances from the source (Fraser et al. 1984). and they could perturb the radiative balance significantly. In this study, the regional radiative effects of aerosols produced from biomass burning, dust storms and forest fires are examined using the Advanced Very High Resolution Radiometer (AVHRR) Local Area

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.

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...

Radiation Budget Instrument (RBI) for JPSS-2

Science.gov (United States)

Georgieva, Elena; Priestley, Kory; Dunn, Barry; Cageao, Richard; Barki, Anum; Osmundsen, Jim; Turczynski, Craig; Abedin, Nurul

2015-01-01

Radiation Budget Instrument (RBI) will be one of five instruments flying aboard the JPSS-2 spacecraft, a polar-orbiting sun-synchronous satellite in Low Earth Orbit. RBI is a passive remote sensing instrument that will follow the successful legacy of the Clouds and Earth's Radiant Energy System (CERES) instruments to make measurement of Earth's short and longwave radiation budget. The goal of RBI is to provide an independent measurement of the broadband reflected solar radiance and Earth's emitted thermal radiance by using three spectral bands (Shortwave, Longwave, and Total) that will have the same overlapped point spread function (PSF) footprint on Earth. To ensure precise NIST-traceable calibration in space the RBI sensor is designed to use a visible calibration target (VCT), a solar calibration target (SCT), and an infrared calibration target (ICT) containing phase change cells (PCC) to enable on-board temperature calibration. The VCT is a thermally controlled integrating sphere with space grade Spectralon covering the inner surface. Two sides of the sphere will have fiber-coupled laser diodes in the UV to IR wavelength region. An electrical substitution radiometer on the integrating sphere will monitor the long term stability of the sources and the possible degradation of the Spectralon in space. In addition the radiometric calibration operations will use the Spectralon diffusers of the SCT to provide accurate measurements of Solar degradation. All those stable on-orbit references will ensure that calibration stability is maintained over the RBI sensor lifetime. For the preflight calibration the RBI will view five calibration sources - two integrating spheres and three CrIS (Cross-track Infrared Sounder ) -like blackbodies whose outputs will be validated with NIST calibration approach. Thermopile are the selected detectors for the RBI. The sensor has a requirement to perform lunar calibration in addition to solar calibration in space in a way similar to CERES

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.

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

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

Directory of Open Access Journals (Sweden)

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.

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

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

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

The radiation budget of stratocumulus clouds measured by tethered balloon instrumentation: Variability of flux measurements

Science.gov (United States)

Duda, David P.; Stephens, Graeme L.; Cox, Stephen K.

1990-01-01

Measurements of longwave and shortwave radiation were made using an instrument package on the NASA tethered balloon during the FIRE Marine Stratocumulus experiment. Radiation data from two pairs of pyranometers were used to obtain vertical profiles of the near-infrared and total solar fluxes through the boundary layer, while a pair of pyrgeometers supplied measurements of the longwave fluxes in the cloud layer. The radiation observations were analyzed to determine heating rates and to measure the radiative energy budget inside the stratocumulus clouds during several tethered balloon flights. The radiation fields in the cloud layer were also simulated by a two-stream radiative transfer model, which used cloud optical properties derived from microphysical measurements and Mie scattering theory.

Dose budget for exposure control

International Nuclear Information System (INIS)

Nair, P.S.

1999-01-01

Dose budget is an important management tool to effectively control the collective dose incurred in a nuclear facility. The budget represents a set of yardsticks or guidelines for use in controlling the internal activities, involving radiation exposure in the organisation. The management, through budget can evaluate the radiation protection performance at every level of the organisation where a number of independent functional groups work on routine and non-routine jobs. The discrepancy between the plan and the actual performance is high lighted through the budgets. The organisation may have to change the course of its operation in a particular area or revise its plan with due focus on appropriate protective measures. (author)

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.

Impacts of Climate Change and Land use Changes on Land Surface Radiation and Energy Budgets

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Land surface radiation and energy budgets are critical to address a variety of scientific and application issues related to climate trends, weather predictions, hydrologic and biogeophysical modeling, and the monitoring of ecosystem health and agricultural crops. This is an introductory paper to t...

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

Impact of biomass burning plume on radiation budget and atmospheric dynamics over the arctic

Science.gov (United States)

Lisok, Justyna; Pedersen, Jesper; Ritter, Christoph; Markowicz, Krzysztof M.; Malinowski, Szymon; Mazzola, Mauro; Udisti, Roberto; Stachlewska, Iwona S.

2018-04-01

The aim of the research was to determine the impact of July 2015 biomass burning event on radiative budget, atmospheric stratification and turbulence over the Arctic using information about the vertical structure of the aerosol load from the ground-based data. MODTRAN simulations indicated very high surface radiative cooling (forcing of -150 Wm-2) and a heating rate of up to 1.8 Kday-1 at 3 km. Regarding LES results, a turbulent layer at around 3 km was clearly seen after 48 h of simulation.

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

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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.

Impact of biomass burning plume on radiation budget and atmospheric dynamics over the arctic

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Lisok Justyna

2018-01-01

Full Text Available The aim of the research was to determine the impact of July 2015 biomass burning event on radiative budget, atmospheric stratification and turbulence over the Arctic using information about the vertical structure of the aerosol load from the ground–based data. MODTRAN simulations indicated very high surface radiative cooling (forcing of –150 Wm–2 and a heating rate of up to 1.8 Kday–1 at 3 km. Regarding LES results, a turbulent layer at around 3 km was clearly seen after 48 h of simulation.

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

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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.

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

2017-08-01

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

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

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Yuki Miyamoto

2017-06-01

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

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

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Agliberto Barbosa de Oliveira

2004-09-01

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

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Effects of stratospheric perturbations on the solar radiation budget

International Nuclear Information System (INIS)

Luther, F.M.

1978-04-01

The changes in solar absorption and in local heating rates due to perturbations to O 3 and NO 2 concentrations caused by stratospheric injection of NO/sub x/ and CFM pollutants are assessed. The changes in species concentration profiles are derived from theoretical calculations using a transport-kinetics model. Because of significant changes in our understanding of stratospheric chemistry during the past year, the assessment of the effect of stratospheric perturbations on the solar radiation budget differs from previous assessments. Previously, a reduction in O 3 due to an NO/sub x/ injection caused a net decrease in the gaseous solar absorption;now the same perturbation leads to a net increase. The implication of these changes on the surface temperature is also discussed

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.

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.

A transitioning Arctic surface energy budget: the impacts of solar zenith angle, surface albedo and cloud radiative forcing

Energy Technology Data Exchange (ETDEWEB)

Sedlar, Joseph; Tjernstroem, Michael; Leck, Caroline [Stockholm University, Department of Meteorology, Stockholm (Sweden); Mauritsen, Thorsten [Max-Planck-Institute for Meteorology, Hamburg (Germany); Shupe, Matthew D.; Persson, P.O.G. [University of Colorado, NOAA-ESRL-PSD, Boulder, CO (United States); Brooks, Ian M.; Birch, Cathryn E. [University of Leeds, School of Earth and Environment, Leeds (United Kingdom); Sirevaag, Anders [University of Bergen, Bjerknes Center for Climate Research, Bergen (Norway); Nicolaus, Marcel [Norwegian Polar Institute, Tromsoe (Norway); Alfred Wegener Institute for Polar and Marine Research, Bremerhaven (Germany)

2011-10-15

Snow surface and sea-ice energy budgets were measured near 87.5 N during the Arctic Summer Cloud Ocean Study (ASCOS), from August to early September 2008. Surface temperature indicated four distinct temperature regimes, characterized by varying cloud, thermodynamic and solar properties. An initial warm, melt-season regime was interrupted by a 3-day cold regime where temperatures dropped from near zero to -7 C. Subsequently mean energy budget residuals remained small and near zero for 1 week until once again temperatures dropped rapidly and the energy budget residuals became negative. Energy budget transitions were dominated by the net radiative fluxes, largely controlled by the cloudiness. Variable heat, moisture and cloud distributions were associated with changing air-masses. Surface cloud radiative forcing, the net radiative effect of clouds on the surface relative to clear skies, is estimated. Shortwave cloud forcing ranged between -50 W m{sup -2} and zero and varied significantly with surface albedo, solar zenith angle and cloud liquid water. Longwave cloud forcing was larger and generally ranged between 65 and 85 W m{sup -2}, except when the cloud fraction was tenuous or contained little liquid water; thus the net effect of the clouds was to warm the surface. Both cold periods occurred under tenuous, or altogether absent, low-level clouds containing little liquid water, effectively reducing the cloud greenhouse effect. Freeze-up progression was enhanced by a combination of increasing solar zenith angles and surface albedo, while inhibited by a large, positive surface cloud forcing until a new air-mass with considerably less cloudiness advected over the experiment area. (orig.)

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

Science.gov (United States)

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

2004-01-01

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

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

Science.gov (United States)

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

2011-03-01

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

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

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Mary E Irwin

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

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

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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

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...

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.

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.

POLDER/Parasol L2 Radiation Budget subset along CloudSat track V001 (PARASOLRB_CPR) at GES DISC

Data.gov (United States)

National Aeronautics and Space Administration — This is the POLDER/Parasol Level-2 Radiation Budget Subset, collocated with the CloudSat track. The subset is processed at the A-Train Data Depot of the GES DISC,...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Observed perturbations of the Earth's Radiation Budget - A response to the El Chichon stratospheric aerosol layer?

Science.gov (United States)

Ardanuy, P. E.; Kyle, H. L.

1986-01-01

The Earth Radiation Budget experiment, launched aboard the Nimbus-7 polar-orbiting spacecraft in late 1978, has now taken over seven years of measurements. The dataset, which is global in coverage, consists of the individual components of the earth's radiation budget, including longwave emission, net radiation, and both total and near-infrared albedos. Starting some six months after the 1982 eruption of the El Chichon volcano, substantial long-lived positive shortwave irradiance anomalies were observed by the experiment in both the northern and southern polar regions. Analysis of the morphology of this phenomena indicates that the cause is the global stratospheric aerosol layer which formed from the cloud of volcanic effluents. There was little change in the emitted longwave in the polar regions. At the north pole the largest anomaly was in the near-infrared, but at the south pole the near UV-visible anomaly was larger. Assuming an exponential decay, the time constant for the north polar, near-infrared anomaly was 1.2 years. At mid- and low latitudes the effect of the El Chichon aerosol layer could not be separated from the strong reflected-shortwave and emitted-longwave perturbations issuing from the El Nino/Southern Oscillation event of 1982-83.

Contrails over the U.S. and their potential impact on the radiation budget

Energy Technology Data Exchange (ETDEWEB)

Minnis, P [National Aeronautics and Space Administration, Hampton, VA (United States). Langley Research Center; Ayers, J K; Doelling, D R [Analytical Services and Materials, Inc., Hampton, VA (United States)

1998-12-31

A methodology for assessing the contrail impact on the radiation budget is developed to use data characterizing the frequency, areal coverage, optical depth, particle size, and altitude of contrails with observations of cloud and surface properties. The method is tested using various scenarios over the United States to estimate contrail-induced albedo changes based on current aircraft fuel usage statistics. The technique can be used for estimating infrared effects and the impact of future fuel-use rates. (author) 11 refs.

Contrails over the U.S. and their potential impact on the radiation budget

Energy Technology Data Exchange (ETDEWEB)

Minnis, P. [National Aeronautics and Space Administration, Hampton, VA (United States). Langley Research Center; Ayers, J.K.; Doelling, D.R. [Analytical Services and Materials, Inc., Hampton, VA (United States)

1997-12-31

A methodology for assessing the contrail impact on the radiation budget is developed to use data characterizing the frequency, areal coverage, optical depth, particle size, and altitude of contrails with observations of cloud and surface properties. The method is tested using various scenarios over the United States to estimate contrail-induced albedo changes based on current aircraft fuel usage statistics. The technique can be used for estimating infrared effects and the impact of future fuel-use rates. (author) 11 refs.

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

Directory of Open Access Journals (Sweden)

Yuriko eIwakura

2013-02-01

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

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

DEFF Research Database (Denmark)

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

2008-01-01

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

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

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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.

Effects of the Mt. Pinatubo eruption on the chemistry, radiative, and transport processes in the stratosphere

International Nuclear Information System (INIS)

Wuebbles, D.J.; Kinnison, D.E.; Grant, K.E.; Connell, P.S.

1992-09-01

Volcanic eruptions can significantly impact trace gas distribution in the upper troposphere and lower stratosphere. Massive eruptions, produce large quantities of SO 2 , H 2 O, chlorine compounds, and particulates. Modeling the effects of these impulsive increases in traces gases and comparing the results with observations from ground and satellite measurements provide unique opportunities to test current multi-dimensional chemical-radiative-transport models of the global atmosphere. Since these models are currently being used in assessment studies for future anthropogenic emissions of trace gases quantitative understanding of the accuracy of these models is essential. In this study, we have used observed data from the Stratospheric Aerosol and Gas Experiment II (SAGE II) aboard the Earth Radiation Budget Satellite (ERBS) to realistically represent both the time dependent change in aerosol surface area density and wavelength dependent extinction values from the Mt. Pinatubo Eruption. Increases in the aerosol loading increase the rate of important heterogeneous chemical reactions converting odd nitrogen in both ClONO 2 and N 2 O 5 to HNO 3 . Radiative effects of increases aerosol optical thickness include changes to net radiative heating rates and to actinic fluxes. Changes to heating rates will indirectly change chemical reaction rates via changes in atmospheric temperatures. changes in actinic fluxes will directly modify photodissociation rates

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.

Observation of The Top of The Atmosphere Outgoing Longwave Radiation Using The Geostationary Earth Radiation Budget Sensor

Science.gov (United States)

Spencer, G.; Llewellyn-Jones, D.

In the summer of 2002 the Meteosat Second Generation (MSG) satellite is due to be launched. On board the MSG satellite is the Geostationary Earth Radiation Budget (GERB) sensor. This is a new radiometer that will be able to observe and measure the outgoing longwave radiation from the top of the atmosphere for the whole ob- served Earth disc, due to its unique position in geostationary orbit. Every 15 minutes the GERB sensor will make a full Earth disc observation, centred on the Greenwich meridian. Thus, the GERB sensor will provide unprecedented coupled temporal and spatial resolution of the outgoing longwave radiation (4.0 to 30.0 microns), by first measuring the broadband radiation (0.32 to 30.0 microns) and then subtracting the measured reflected shortwave solar radiation (0.32 to 4.0 microns), from the earth- atmosphere system. The GERB sensor is able to make measurements to within an accuracy of 1 W/sq. m. A forward model is being developed at Leicester to simulate the data from the GERB sensor for representative geophysical scenes and to investigate key parameters and processes that will affect the top of the atmosphere signal. At the heart of this model is a line-by-line radiative transfer model, the Oxford Reference Forward Model (RFM) that is to be used with model atmospheres generated from ECMWF analysis data. When MSG is launched, cloud data from the Spinning Enhanced Visible and Infrared Imager (SEVIRI), also on board, is to be used in conjunction with GERB data.

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

Quasi-real-time monitoring of SW radiation budget using geostationary satellite for Climate study and Renewable energy. (Invited)

Science.gov (United States)

Takenaka, H.; Nakajima, T. Y.; Kuze, H.; Takamura, T.; Pinker, R. T.; Nakajima, T.

2013-12-01

Solar radiation is the only source of energy that drives the weather and climate of the Earth's surface. Earth is warmed by incoming solar radiation, and emitted energy to space by terrestrial radiation due to its temperature. It has been kept to the organisms viable environment by the effect of heating and cooling. Clouds can cool the Earth by reflecting solar radiation and also can keep the Earth warm by absorbing and emitting terrestrial radiation. They are important in the energy balance at the Earth surface and the Top of the Atmosphere (TOA) and are connected complicatedly into the Earth system as well as other climate feedback processes. Thus it is important to estimate Earth's radiation budget for better understanding of climate and environmental change. We have shared several topics related to climate change. Energy issues close to the climate change, it is an environmental problems. Photovoltaics is one of the power generation method to converts from solar radiation to electric power directly. It does not emit greenhouse gases during power generation. Similarly, drainage, exhaust, vibration does not emit. PV system can be distributed as a small power supply in urban areas and it can installed to near the power demand points. Also solar thermal is heat generator with high efficiency. Therefor it is an effective energy source that the solar power is expected as one of the mitigation of climate change (IPCC Special Report on Renewable Energy Sources and Climate Change Mitigation). It is necessary to real-time-monitoring of the surface solar radiation for safety operation of electric power system. We introduce a fusion analysis of renewable energy and Quasi-real-time analysis of SW radiation budget. Sample of estimated PV power mapping using geostationary satellite.

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

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

Directory of Open Access Journals (Sweden)

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

Evidence for Solar Cycle Influence on the Infrared Energy Budget and Radiative Cooling of the Thermosphere

Science.gov (United States)

Mlynczak, Martin G.; Martin-Torres, F. Javier; Marshall, B. Thomas; Thompson, R. Earl; Williams, Joshua; Turpin, TImothy; Kratz, D. P.; Russell, James M.; Woods, Tom; Gordley, Larry L.

2007-01-01

We present direct observational evidence for solar cycle influence on the infrared energy budget and radiative cooling of the thermosphere. By analyzing nearly five years of data from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument, we show that the annual mean infrared power radiated by the nitric oxide (NO) molecule at 5.3 m has decreased by a factor of 2.9. This decrease is correlated (r = 0.96) with the decrease in the annual mean F10.7 solar index. Despite the sharp decrease in radiated power (which is equivalent to a decrease in the vertical integrated radiative cooling rate), the variability of the power as given in the standard deviation of the annual means remains approximately constant. A simple relationship is shown to exist between the infrared power radiated by NO and the F10.7 index, thus providing a fundamental relationship between solar activity and the thermospheric cooling rate for use in thermospheric models. The change in NO radiated power is also consistent with changes in absorbed ultraviolet radiation over the same time period.

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

Science.gov (United States)

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

1992-01-01

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

The Surface Radiation Budget over Oceans and Continents.

Science.gov (United States)

Garratt, J. R.; Prata, A. J.; Rotstayn, L. D.; McAvaney, B. J.; Cusack, S.

1998-08-01

An updated evaluation of the surface radiation budget in climate models (1994-96 versions; seven datasets available, with and without aerosols) and in two new satellite-based global datasets (with aerosols) is presented. All nine datasets capture the broad mean monthly zonal variations in the flux components and in the net radiation, with maximum differences of some 100 W m2 occurring in the downwelling fluxes at specific latitudes. Using long-term surface observations, both from land stations and the Pacific warm pool (with typical uncertainties in the annual values varying between ±5 and 20 W m2), excess net radiation (RN) and downwelling shortwave flux density (So) are found in all datasets, consistent with results from earlier studies [for global land, excesses of 15%-20% (12 W m2) in RN and about 12% (20 W m2) in So]. For the nine datasets combined, the spread in annual fluxes is significant: for RN, it is 15 (50) W m2 over global land (Pacific warm pool) in an observed annual mean of 65 (135) W m2; for So, it is 25 (60) W m2 over land (warm pool) in an annual mean of 176 (197) W m2.The effects of aerosols are included in three of the authors' datasets, based on simple aerosol climatologies and assumptions regarding aerosol optical properties. They offer guidance on the broad impact of aerosols on climate, suggesting that the inclusion of aerosols in models would reduce the annual So by 15-20 W m2 over land and 5-10 W m2 over the oceans. Model differences in cloud cover contribute to differences in So between datasets; for global land, this is most clearly demonstrated through the effects of cloud cover on the surface shortwave cloud forcing. The tendency for most datasets to underestimate cloudiness, particularly over global land, and possibly to underestimate atmospheric water vapor absorption, probably contributes to the excess downwelling shortwave flux at the surface.

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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

Science.gov (United States)

Skelton, Lara A; Boron, Walter F

2013-12-15

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

Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

Science.gov (United States)

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

2016-03-01

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

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

National Research Council Canada - National Science Library

Duan, Lei

2001-01-01

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

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

Directory of Open Access Journals (Sweden)

Jian Liu

2015-03-01

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

Global Observations of Aerosols and Clouds from Combined Lidar and Passive Instruments to Improve Radiation Budget and Climate Studies

Science.gov (United States)

Winker, David M.

1999-01-01

Current uncertainties in the effects of clouds and aerosols on the Earth radiation budget limit our understanding of the climate system and the potential for global climate change. Pathfinder Instruments for Cloud and Aerosol Spaceborne Observations - Climatologie Etendue des Nuages et des Aerosols (PICASSO-CENA) is a recently approved satellite mission within NASA's Earth System Science Pathfinder (ESSP) program which will address these uncertainties with a unique suite of active and passive instruments. The Lidar In-space Technology Experiment (LITE) demonstrated the potential benefits of space lidar for studies of clouds and aerosols. PICASSO-CENA builds on this experience with a payload consisting of a two-wavelength polarization-sensitive lidar, an oxygen A-band spectrometer (ABS), an imaging infrared radiometer (IIR), and a wide field camera (WFC). Data from these instruments will be used to measure the vertical distributions of aerosols and clouds in the atmosphere, as well as optical and physical properties of aerosols and clouds which influence the Earth radiation budget. PICASSO-CENA will be flown in formation with the PM satellite of the NASA Earth Observing System (EOS) to provide a comprehensive suite of coincident measurements of atmospheric state, aerosol and cloud optical properties, and radiative fluxes. The mission will address critical uncertainties iin the direct radiative forcing of aerosols and clouds as well as aerosol influences on cloud radiative properties and cloud-climate radiation feedbacks. PICASSO-CENA is planned for a three year mission, with a launch in early 2003. PICASSO-CENA is being developed within the framework of a collaboration between NASA and CNES.

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

Directory of Open Access Journals (Sweden)

Orlando Parise Junior

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

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.

Wave energy budget analysis in the Earth's radiation belts uncovers a missing energy.

Science.gov (United States)

Artemyev, A V; Agapitov, O V; Mourenas, D; Krasnoselskikh, V V; Mozer, F S

2015-05-15

Whistler-mode emissions are important electromagnetic waves pervasive in the Earth's magnetosphere, where they continuously remove or energize electrons trapped by the geomagnetic field, controlling radiation hazards to satellites and astronauts and the upper-atmosphere ionization or chemical composition. Here, we report an analysis of 10-year Cluster data, statistically evaluating the full wave energy budget in the Earth's magnetosphere, revealing that a significant fraction of the energy corresponds to hitherto generally neglected very oblique waves. Such waves, with 10 times smaller magnetic power than parallel waves, typically have similar total energy. Moreover, they carry up to 80% of the wave energy involved in wave-particle resonant interactions. It implies that electron heating and precipitation into the atmosphere may have been significantly under/over-valued in past studies considering only conventional quasi-parallel waves. Very oblique waves may turn out to be a crucial agent of energy redistribution in the Earth's radiation belts, controlled by solar activity.

Climate Model Evaluation using New Datasets from the Clouds and the Earth's Radiant Energy System (CERES)

Science.gov (United States)

Loeb, Norman G.; Wielicki, Bruce A.; Doelling, David R.

2008-01-01

There are some in the science community who believe that the response of the climate system to anthropogenic radiative forcing is unpredictable and we should therefore call off the quest . The key limitation in climate predictability is associated with cloud feedback. Narrowing the uncertainty in cloud feedback (and therefore climate sensitivity) requires optimal use of the best available observations to evaluate and improve climate model processes and constrain climate model simulations over longer time scales. The Clouds and the Earth s Radiant Energy System (CERES) is a satellite-based program that provides global cloud, aerosol and radiative flux observations for improving our understanding of cloud-aerosol-radiation feedbacks in the Earth s climate system. CERES is the successor to the Earth Radiation Budget Experiment (ERBE), which has widely been used to evaluate climate models both at short time scales (e.g., process studies) and at decadal time scales. A CERES instrument flew on the TRMM satellite and captured the dramatic 1998 El Nino, and four other CERES instruments are currently flying aboard the Terra and Aqua platforms. Plans are underway to fly the remaining copy of CERES on the upcoming NPP spacecraft (mid-2010 launch date). Every aspect of CERES represents a significant improvement over ERBE. While both CERES and ERBE measure broadband radiation, CERES calibration is a factor of 2 better than ERBE. In order to improve the characterization of clouds and aerosols within a CERES footprint, we use coincident higher-resolution imager observations (VIRS, MODIS or VIIRS) to provide a consistent cloud-aerosol-radiation dataset at climate accuracy. Improved radiative fluxes are obtained by using new CERES-derived Angular Distribution Models (ADMs) for converting measured radiances to fluxes. CERES radiative fluxes are a factor of 2 more accurate than ERBE overall, but the improvement by cloud type and at high latitudes can be as high as a factor of 5

Parameterization of clouds and radiation in climate models

Energy Technology Data Exchange (ETDEWEB)

Roeckner, E. [Max Planck Institute for Meterology, Hamburg (Germany)

1995-09-01

Clouds are a very important, yet poorly modeled element in the climate system. There are many potential cloud feedbacks, including those related to cloud cover, height, water content, phase change, and droplet concentration and size distribution. As a prerequisite to studying the cloud feedback issue, this research reports on the simulation and validation of cloud radiative forcing under present climate conditions using the ECHAM general circulation model and ERBE top-of-atmosphere radiative fluxes.

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.

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.

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

Think the way to measure the Earth Radiation Budget and the Total Solar Irradiance with a small satellites constellation

Science.gov (United States)

Meftah, M.; Keckhut, P.; Damé, L.; Bekki, S.; Sarkissian, A.; Hauchecorne, A.

2018-05-01

Within the past decade, satellites constellations have become possible and practical. One of the interest to use a satellites constellation is to measure the true Earth Radiation Imbalance, which is a crucial quantity for testing climate models and for predicting the future course of global warming. This measurement presents a high interest because the 2001-2010 decade has not shown the accelerating pace of global warming that most models predict, despite the fact that the greenhouse-gas radiative forcing continues to rise. All estimates (ocean heat content and top of atmosphere) show that over the past decade the Earth radiation imbalance ranges between 0.5 to 1W-2. Up to now, the Earth radiation imbalance has not been measured directly. The only way to measure the imbalance with sufficient accuracy is to measure both the incoming solar radiations (total solar irradiance) and the outgoing terrestrial radiations (top of atmosphere outgoing longwave radiations and shortwave radiations) onboard the same satellite, and ideally, with the same instrument. The incoming solar radiations and the outgoing terrestrial radiations are of nearly equal magnitude of the order of 340.5W-2. The objective is to measure these quantities over time by using differential Sun-Earth measurements (to counter calibration errors) with an accuracy better than 0.05Wm-2 at 1σ. It is also necessary to have redundant instruments to track aging in space in order to measure during a decade and to measure the global diurnal cycle with a dozen satellites. Solar irradiance and Earth Radiation Budget (SERB) is a potential first in orbit demonstration satellite. The SERB nano-satellite aims to measure on the same platform the different components of the Earth radiation budget and the total solar irradiance. Instrumental payloads (solar radiometer and Earth radiometers) can acquire the technical maturity for the future large missions (constellation that insure global measurement cover) by flying in a

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...

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

Construction of a Matched Global Cloud and Radiance Product from LEO/GEO and EPIC Observations to Estimate Daytime Earth Radiation Budget from DSCOVR

Science.gov (United States)

Duda, D. P.; Khlopenkov, K. V.; Palikonda, R.; Khaiyer, M. M.; Minnis, P.; Su, W.; Sun-Mack, S.

2016-12-01

With the launch of the Deep Space Climate Observatory (DSCOVR), new estimates of the daytime Earth radiation budget can computed from a combination of measurements from the two Earth-observing sensors onboard the spacecraft, the Earth Polychromatic Imaging Camera (EPIC) and the National Institute of Standards and Technology Advanced Radiometer (NISTAR). Although these instruments can provide accurate top-of-atmosphere (TOA) radiance measurements, they lack sufficient resolution to provide details on small-scale surface and cloud properties. Previous studies have shown that these properties have a strong influence on the anisotropy of the radiation at the TOA, and ignoring such effects can result in large TOA-flux errors. To overcome these effects, high-resolution scene identification is needed for accurate Earth radiation budget estimation. Selected radiance and cloud property data measured and derived from several low earth orbit (LEO, including NASA Terra and Aqua MODIS, NOAA AVHRR) and geosynchronous (GEO, including GOES (east and west), METEOSAT, INSAT-3D, MTSAT-2, and HIMAWARI-8) satellite imagers were collected to create hourly 5-km resolution global composites of data necessary to compute angular distribution models (ADM) for reflected shortwave (SW) and longwave (LW) radiation. The satellite data provide an independent source of radiance measurements and scene identification information necessary to construct ADMs that are used to determine the daytime Earth radiation budget. To optimize spatial matching between EPIC measurements and the high-resolution composite cloud properties, LEO/GEO retrievals within the EPIC fields of view (FOV) are convolved to the EPIC point spread function (PSF) in a similar manner to the Clouds and the Earth's Radiant Energy System (CERES) Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product. Examples of the merged LEO/GEO/EPIC product will be presented, describing the chosen radiance and cloud properties and

Construction of a Matched Global Cloud and Radiance Product from LEO/GEO and EPIC Observations to Estimate Daytime Earth Radiation Budget from DSCOVR

Science.gov (United States)

Duda, David P.; Khlopenkov, Konstantin V.; Thiemann, Mandana; Palikonda, Rabindra; Sun-Mack, Sunny; Minnis, Patrick; Su, Wenying

2016-01-01

With the launch of the Deep Space Climate Observatory (DSCOVR), new estimates of the daytime Earth radiation budget can be computed from a combination of measurements from the two Earth-observing sensors onboard the spacecraft, the Earth Polychromatic Imaging Camera (EPIC) and the National Institute of Standards and Technology Advanced Radiometer (NISTAR). Although these instruments can provide accurate top-of-atmosphere (TOA) radiance measurements, they lack sufficient resolution to provide details on small-scale surface and cloud properties. Previous studies have shown that these properties have a strong influence on the anisotropy of the radiation at the TOA, and ignoring such effects can result in large TOA-flux errors. To overcome these effects, high-resolution scene identification is needed for accurate Earth radiation budget estimation. Selected radiance and cloud property data measured and derived from several low earth orbit (LEO, including NASA Terra and Aqua MODIS, NOAA AVHRR) and geosynchronous (GEO, including GOES (east and west), METEOSAT, INSAT-3D, MTSAT-2, and HIMAWARI-8) satellite imagers were collected to create hourly 5-km resolution global composites of data necessary to compute angular distribution models (ADM) for reflected shortwave (SW) and longwave (LW) radiation. The satellite data provide an independent source of radiance measurements and scene identification information necessary to construct ADMs that are used to determine the daytime Earth radiation budget. To optimize spatial matching between EPIC measurements and the high-resolution composite cloud properties, LEO/GEO retrievals within the EPIC fields of view (FOV) are convolved to the EPIC point spread function (PSF) in a similar manner to the Clouds and the Earth's Radiant Energy System (CERES) Single Scanner Footprint TOA/Surface Fluxes and Clouds (SSF) product. Examples of the merged LEO/GEO/EPIC product will be presented, describing the chosen radiance and cloud properties and

Wave energy budget analysis in the Earth’s radiation belts uncovers a missing energy

Science.gov (United States)

Artemyev, A.V.; Agapitov, O.V.; Mourenas, D.; Krasnoselskikh, V.V.; Mozer, F.S.

2015-01-01

Whistler-mode emissions are important electromagnetic waves pervasive in the Earth’s magnetosphere, where they continuously remove or energize electrons trapped by the geomagnetic field, controlling radiation hazards to satellites and astronauts and the upper-atmosphere ionization or chemical composition. Here, we report an analysis of 10-year Cluster data, statistically evaluating the full wave energy budget in the Earth’s magnetosphere, revealing that a significant fraction of the energy corresponds to hitherto generally neglected very oblique waves. Such waves, with 10 times smaller magnetic power than parallel waves, typically have similar total energy. Moreover, they carry up to 80% of the wave energy involved in wave–particle resonant interactions. It implies that electron heating and precipitation into the atmosphere may have been significantly under/over-valued in past studies considering only conventional quasi-parallel waves. Very oblique waves may turn out to be a crucial agent of energy redistribution in the Earth’s radiation belts, controlled by solar activity. PMID:25975615

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...

Dosimetric and deformation effects of image-guided interventions during stereotactic body radiation therapy of the prostate using an endorectal balloon

International Nuclear Information System (INIS)

Jones, Bernard L.; Gan, Gregory; Diot, Quentin; Kavanagh, Brian; Timmerman, Robert D.; Miften, Moyed

2012-01-01

Purpose: During stereotactic body radiation therapy (SBRT) for the treatment of prostate cancer, an inflatable endorectal balloon (ERB) may be used to reduce motion of the target and reduce the dose to the posterior rectal wall. This work assessed the dosimetric impact of manual interventions on ERB position in patients receiving prostate SBRT and investigated the impact of ERB interventions on prostate shape. Methods: The data of seven consecutive patients receiving SBRT for the treatment of clinical stage T1cN0M0 prostate cancer enrolled in a multi-institutional, IRB-approved trial were analyzed. The SBRT dose was 50 Gy in five fractions to a planning target volume (PTV) that included the prostate (implanted with three fiducial markers) with a 3–5 mm margin. All plans were based on simulation images that included an ERB inflated with 60 cm 3 of air. Daily kilovoltage cone-beam computed tomography (CBCT) imaging was performed to localize the PTV, and an automated fusion with the planning images yielded displacements required for PTV relocalization. When the ERB volume and/or position were judged to yield inaccurate repositioning, manual adjustment (ERB reinflation and/or repositioning) was performed. Based on all 59 CBCT image sets acquired, a deformable registration algorithm was used to determine the dose received by, displacement of, and deformation of the prostate, bladder (BLA), and anterior rectal wall (ARW). This dose tracking methodology was applied to images taken before and after manual adjustment of the ERB (intervention), and the delivered dose was compared to that which would have been delivered in the absence of intervention. Results: Interventions occurred in 24 out of 35 (69%) of the treated fractions. The direct effect of these interventions was an increase in the prostate radiation dose that included 95% of the PTV (D95) from 9.6 ± 1.0 to 10.0 ± 0.2 Gy (p = 0.06) and an increase in prostate coverage from 94.0% ± 8.5% to 97.8% ± 1.9% (p = 0

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.

Global model simulations of the impact of ocean-going ships on aerosols, clouds, and the radiation budget

Directory of Open Access Journals (Sweden)

A. Lauer

2007-10-01

Full Text Available International shipping contributes significantly to the fuel consumption of all transport related activities. Specific emissions of pollutants such as sulfur dioxide (SO₂ per kg of fuel emitted are higher than for road transport or aviation. Besides gaseous pollutants, ships also emit various types of particulate matter. The aerosol impacts the Earth's radiation budget directly by scattering and absorbing the solar and thermal radiation and indirectly by changing cloud properties. Here we use ECHAM5/MESSy1-MADE, a global climate model with detailed aerosol and cloud microphysics to study the climate impacts of international shipping. The simulations show that emissions from ships significantly increase the cloud droplet number concentration of low marine water clouds by up to 5% to 30% depending on the ship emission inventory and the geographic region. Whereas the cloud liquid water content remains nearly unchanged in these simulations, effective radii of cloud droplets decrease, leading to cloud optical thickness increase of up to 5–10%. The sensitivity of the results is estimated by using three different emission inventories for present-day conditions. The sensitivity analysis reveals that shipping contributes to 2.3% to 3.6% of the total sulfate burden and 0.4% to 1.4% to the total black carbon burden in the year 2000 on the global mean. In addition to changes in aerosol chemical composition, shipping increases the aerosol number concentration, e.g. up to 25% in the size range of the accumulation mode (typically >0.1 μm over the Atlantic. The total aerosol optical thickness over the Indian Ocean, the Gulf of Mexico and the Northeastern Pacific increases by up to 8–10% depending on the emission inventory. Changes in aerosol optical thickness caused by shipping induced modification of aerosol particle number concentration and chemical composition lead to a change in the shortwave radiation budget at the top of the

Atmospheric water budget over the South Asian summer monsoon region

Science.gov (United States)

Unnikrishnan, C. K.; Rajeevan, M.

2018-04-01

High resolution hybrid atmospheric water budget over the South Asian monsoon region is examined. The regional characteristics, variability, regional controlling factors and the interrelations of the atmospheric water budget components are investigated. The surface evapotranspiration was created using the High Resolution Land Data Assimilation System (HRLDAS) with the satellite-observed rainfall and vegetation fraction. HRLDAS evapotranspiration shows significant similarity with in situ observations and MODIS satellite-observed evapotranspiration. Result highlights the fundamental importance of evapotranspiration over northwest and southeast India on atmospheric water balance. The investigation shows that the surface net radiation controls the annual evapotranspiration over those regions, where the surface evapotranspiration is lower than 550 mm. The rainfall and evapotranspiration show a linear relation over the low-rainfall regions (forcing (like surface net radiation). The lead and lag correlation of water budget components show that the water budget anomalies are interrelated in the monsoon season even up to 4 months lead. These results show the important regional interrelation of water budget anomalies on south Asian monsoon.

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_PFM+FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM3_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_PFM+FM1_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=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Terra-FM1_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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...

Surface radiation budget in the Clouds and the Earth's Radiant Energy System (CERES) effort and in the Global Energy and Water Cycle Experiment (GEWEX)

Science.gov (United States)

Charlock, Thomas P.; Smith, G. L.; Rose, Fred G.

1990-01-01

The surface radiation budget (SRB) and the atmospheric radiative flux divergence (ARD) are vital components of the weather and climate system. The importance of radiation in a complex international scientific endeavor, the GEWEX of the World Climate Research Programme is explained. The radiative transfer techniques and satellite instrumentation that will be used to retrieve the SRB and ARD later in this decade with the CERES are discussed; CERES is a component of the Earth Observing System satellite program. Examples of consistent SRB and ARD retrievals made with Nimbus-7 and International Satellite Cloud Climatology Project data from July 1983 are presented.

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

Directory of Open Access Journals (Sweden)

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

An Alternative Inter-Satellite Calibration of the UMD HIRS OLR Retrievals

Science.gov (United States)

Robertson, Franklin R.; Lee, Hai-Tien

2012-01-01

Outgoing Longwave Radiation (OLR) at the top-of-atmosphere (TOA) is a fundamental component of Earth's energy balance and represents the heat energy in the thermal bands rejected to space by the planet. Determination of OLR from satellites has a long and storied history, but the observational record remains largely fragmented with gaps in satellite measurements over the past three decades. Perhaps the most semi-continuous set of retrievals comes from the University of Maryland (UMD) algorithm that uses four HIRS (High Resolution Infrared Sounder) channels on the NOAA polar orbiting satellites to estimate OLR. This data set shows great promise in helping to bridge the discontinuous ERBS (Earth Radiation Budget Satellite) and CERES (Clouds and the Earth s Radiant Energy System) measurements. However, significant satellite inter-calibration biases persist with the present UMD data, principally outside the tropics. Difficulties relate to the combination of drift of the satellite equator crossing time through the diurnal cycle and changes in HIRS channel response function design. Here we show how an ad hoc recalibration of the UMD retrievals among the different satellites removes much of the remaining uncertainty due to diurnal drift of the satellite orbit. The adjusted HIRS data (using no other external information) show much better agreement with OLR from the European Center Interim Reanalysis (EC-Int), longer-term signals in the Global Energy and Water Cycle Experiment / Surface Radiation Budget (GEWEX/SRB) retrievals, and also agree well with ERBS and CERES OLR measurements. These results augur well for narrowing the uncertainties in multi-decadal estimates of this important climate variable.

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

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

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

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_TRMM-PFM_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=1998-08-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

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...

Improved Estimates of Clear Sky Longwave Flux and Application to the Tropical Greenhouse Effect

Science.gov (United States)

Collins, W. D.

1997-01-01

The first objective of this investigation is to eliminate the clear-sky offset introduced by the scene-identification procedures developed for the Earth Radiation Budget Experiment (ERBE). Estimates of this systematic bias range from 10 to as high as 30 W/sq m. The initial version of the ScaRaB data is being processed with the original ERBE algorithm. Since the ERBE procedure for scene identification is based upon zonal flux averages, clear scenes with longwave emission well below the zonal mean value are mistakenly classified as cloudy. The erroneous classification is more frequent in regions with deep convection and enhanced mid- and upper-tropospheric humidity. We will develop scene identification parameters with zonal and/or time dependence to reduce or eliminate the bias in the clear- sky data. The modified scene identification procedure could be used for the ScaRaB-specific version of the Earth-radiation products. The second objective is to investigate changes in the clear-sky Outgoing Longwave Radiation (OLR) associated with decadal variations in the tropical and subtropical climate. There is considerable evidence for a shift in the climate state starting in approximately 1977. The shift is accompanied by higher SSTs in the equatorial Pacific, increased tropical convection, and higher values of atmospheric humidity. Other evidence indicates that the humidity in the tropical troposphere has been steadily increasing over the last 30 years. It is not known whether the atmospheric greenhouse effect has increased during this period in response to these changes in SST and precipitable water. We will investigate the decadal-scale fluctuations in the greenhouse effect using Nimbus-7, ERBE, and ScaRaB measurements spaning 1979 to the present. The data from the different satellites will be intercalibrated by comparison with model calculations based upon ship radiosonde observations. The fluxes calculated from the radiation model will also be used for validation of the

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

Tropical Ocean Evaporation/SST Sensitivity and It's Link to Water and Energy Budget Variations During ENSO

Science.gov (United States)

Robertson, Franklin R.; Marshall, Susan; Oglesby, Robert; Roads, John; Sohn, Byung-Ju; Arnold, James E. (Technical Monitor)

2001-01-01

use the da Silva ocean flux data to identify composite structure of departures of latent heat flux from climatology. We also show how these patterns arise out of associated wind and humidity anomaly distributions. Our preliminary work shows that evaporation sensitivity estimates from the da Silva / COADS data, computed for the tropical oceans (30 degrees N/S) are in the neighborhood of 5 to 6 W/square m K. Model estimates are also quite close to this figure. This rate is only slightly less than a rate corresponding to constant relative humidity; however, substantial regional departures from constant relative humidity are present. These patterns are robust and we relate the associated wind and humidity fluctuations noted in previous investigations to the derived evaporation anomalies. Finally, these results are interpreted with other data from the Earth radiation Budget Experiment (ERBE), Global Precipitation Climatology Project (GPCP) and NASA's Surface Radiation Budget (SRB) data set to characterize the tropical energetics of ENSO-related climate variability.

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

Directory of Open Access Journals (Sweden)

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)

Earth Radiation Imbalance from a Constellation of 66 Iridium Satellites: Climate Science Aspects

Science.gov (United States)

Wiscombe, W.; Chiu, CJ. Y.

2012-01-01

The "global warming hiatus" since the 1998 El Nino, highlighted by Meehl et al., and the resulting "missing energy" problem highlighted by Trenberth et al., has opened the door to a more fundamental view of climate change than mere surface air temperature. That new view is based on two variables which are strongly correlated: the rate of change of ocean heat content d(OHC)/dt; and Earth Radiation Imbalance (ERI) at the top of the atmosphere, whose guesstimated range is 0.4 to 0.9 Watts per square meters (this imbalance being mainly due to increasing CO2). The Argo float array is making better and better measurements of OHC. But existing satellite systems cannot measure ERI to even one significant digit. So, climate model predictions of ERI are used in place of real measurements of it, and the satellite data are tuned to the climate model predictions. Some oceanographers say "just depend on Argo for understanding the global warming hiatus and the missing energy", but we don't think this is a good idea because d(OHC)/dt and ERI have different time scales and are never perfectly correlated. We think the ERB community needs to step up to measuring ERI correctly, just as oceanographers have deployed Argo to measure OHC correctly. This talk will overview a proposed constellation of 66 Earth radiation budget instruments, hosted on Iridium satellites, that will actually be able to measure ERI to at least one significant digit, thus enabling a crucial test of climate models. This constellation will also be able to provide ERI at two-hourly time scales and 500-km spatial scales without extrapolations from uncalibrated narrowband geostationary instruments, using the highly successful methods of GRACE to obtain spatial resolution. This high time resolution would make ERI a synoptic variable like temperature, and allow studies of ERI's response to fast-evolving phenomena like dust storms and hurricanes and even brief excursions of Total Solar Irradiance. Time permitting, we

CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_Aqua-FM3_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 (CER_ES9_Terra-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=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 (CER_ES9_PFM+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=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_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

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

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

7 CFR 3402.14 - Budget and budget narrative.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Budget and budget narrative. 3402.14 Section 3402.14... GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Preparation of an Application § 3402.14 Budget and budget narrative. Applicants must prepare the Budget, Form CSREES-2004, and a budget narrative...

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

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)

Targeted therapies and radiation for the treatment of head and neck cancer

International Nuclear Information System (INIS)

Kim, Gwi Eon

2004-01-01

The purpose of this review is to provide an update on novel radiation treatments for head and neck cancer. Despite the remarkable advances in chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) is an appealing target for novel therapies in head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuximab) and tyrosine kinase inhibitors (ZD1839 and OSI-774) have been assessed and have been most extensively studied in preclinical models and clinical trials. Additional TKIs in clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted in rapid translation into the clinic. Results from initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or in combination with chemotherapy. In this review, we begin with a brief summary of erbB-mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinical and clinical data on the role of EGFR antagonists alone or in combination with radiation in the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR blockade and efforts in the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2

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...

Studies of the Earth Energy Budget and Water Cycle Using Satellite Observations and Model Analyses

Science.gov (United States)

Campbell, G. G.; VonderHarr, T. H.; Randel, D. L.; Kidder, S. Q.

1997-01-01

During this research period we have utilized the ERBE data set in comparisons to surface properties and water vapor observations in the atmosphere. A relationship between cloudiness and surface temperature anomalies was found. This same relationship was found in a general circulation model, verifying the model. The attempt to construct a homogeneous time series from Nimbus 6, Nimbus 7 and ERBE data is not complete because we are still waiting for the ERBE reanalysis to be completed. It will be difficult to merge the Nimbus 6 data in because its observations occurred when the average weather was different than the other periods, so regression adjustments are not effective.

The RAVAN CubeSat Mission: A Pathfinder for a New Measurement of Earth's Radiation Budget

Science.gov (United States)

Swartz, W.; Lorentz, S. R.; Huang, P. M.; Smith, A. W.; Deglau, D.; Reynolds, E.; Carvo, J.; Papadakis, S.; Wu, D. L.; Wiscombe, W. J.; Dyrud, L. P.

2016-12-01

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat is a pathfinder for a constellation to measure the Earth's radiation imbalance (ERI), which is the single most important quantity for predicting the course of climate change over the next century. RAVAN demonstrates a small, accurate radiometer that measures top-of-the-atmosphere Earth-leaving fluxes of total and solar-reflected radiation. Coupled with knowledge of the incoming radiation from the Sun, a constellation of such measurements would aim to determine ERI directly. Our objective with RAVAN is to establish that a compact radiometer that is absolutely calibrated to climate accuracy can be built and operated in space for low cost. The radiometer, hosted on a 3U CubeSat, relies on two key technologies. The first is the use of vertically aligned carbon nanotubes (VACNTs) as the radiometer absorber. VACNT forests are some of the blackest materials known and have an extremely flat spectral response over a wide wavelength range. The second key technology is a gallium fixed-point blackbody calibration source, embedded in RAVAN's sensor head contamination cover, that serves as a stable and repeatable reference to track the long-term degradation of the sensor. Absolute calibration is also maintained by regular solar and deep space views. We present the scientific motivation for the NASA-funded mission, design and characterization of the spacecraft, and mission operations concept. Pending a successful launch in fall 2016, we will also present the first results on-orbit. RAVAN will help enable the development of an Earth radiation budget constellation mission that can provide the measurements needed for superior predictions of future climate change.

Seasonal and annual heat budgets offshore the Hanko Peninsula, Gulf of Finland

Energy Technology Data Exchange (ETDEWEB)

Merkouriadi, I.; Lepparanta, M. [Helsinki Univ. (Finland). Dept. of Physics], Email: ioanna.merkouriadi@helsinki.fi; Shirasawa, K. [Hokkaido Univ., Sapporo (Japan). Pan-Okhotsk Research Center, Inst. of Low Temperature Science

2013-06-01

A joint Finnish-Japanese sea-ice experiment 'Hanko-9012' carried out offshore the Hanko Peninsula included seasonal monitoring and intensive field campaigns. Ice, oceanographic and meteorological data were collected to examine the structure and properties of the Baltic Sea brackish ice, heat budget and solar radiation transfer through the ice cover. Here, the data from two years (2000 and 2001) are used for the estimation of the seasonal and annual heat budgets. Results present the surface heat balance, and the heat budget of the ice sheet and the waterbody. The ice cover acted as a good control measure of the net surface heat exchange. Solar radiation had a strong seasonal cycle with a monthly maximum at 160 and a minimum below 10 W m{sup -2}, while net terrestrial radiation was mostly between -40 and -60 W m{sup -2}. Latent heat exchange was much more important than sensible heat exchange, similar the net terrestrial radiation values in summer and autumn. A comparison between the latent heat flux released or absorbed by the ice and the net surface heat fluxes showed similar patterns, with a clearly better fit in 2001. The differences can be partly explained by the oceanic heat flux to the lower ice boundary. (orig.)

The accuracy of dynamic attitude propagation

Science.gov (United States)

Harvie, E.; Chu, D.; Woodard, M.

1990-01-01

Propagating attitude by integrating Euler's equation for rigid body motion has long been suggested for the Earth Radiation Budget Satellite (ERBS) but until now has not been implemented. Because of limited Sun visibility, propagation is necessary for yaw determination. With the deterioration of the gyros, dynamic propagation has become more attractive. Angular rates are derived from integrating Euler's equation with a stepsize of 1 second, using torques computed from telemetered control system data. The environmental torque model was quite basic. It included gravity gradient and unshadowed aerodynamic torques. Knowledge of control torques is critical to the accuracy of dynamic modeling. Due to their coarseness and sparsity, control actuator telemetry were smoothed before integration. The dynamic model was incorporated into existing ERBS attitude determination software. Modeled rates were then used for attitude propagation in the standard ERBS fine-attitude algorithm. In spite of the simplicity of the approach, the dynamically propagated attitude matched the attitude propagated with good gyros well for roll and yaw but diverged up to 3 degrees for pitch because of the very low resolution in pitch momentum wheel telemetry. When control anomalies significantly perturb the nominal attitude, the effect of telemetry granularity is reduced and the dynamically propagated attitudes are accurate on all three axes.

The early summertime Saharan heat low: sensitivity of the radiation budget and atmospheric heating to water vapour and dust aerosol

Science.gov (United States)

Alamirew, Netsanet K.; Todd, Martin C.; Ryder, Claire L.; Marsham, John H.; Wang, Yi

2018-01-01

The Saharan heat low (SHL) is a key component of the west African climate system and an important driver of the west African monsoon across a range of timescales of variability. The physical mechanisms driving the variability in the SHL remain uncertain, although water vapour has been implicated as of primary importance. Here, we quantify the independent effects of variability in dust and water vapour on the radiation budget and atmospheric heating of the region using a radiative transfer model configured with observational input data from the Fennec field campaign at the location of Bordj Badji Mokhtar (BBM) in southern Algeria (21.4° N, 0.9° E), close to the SHL core for June 2011. Overall, we find dust aerosol and water vapour to be of similar importance in driving variability in the top-of-atmosphere (TOA) radiation budget and therefore the column-integrated heating over the SHL (˜ 7 W m-2 per standard deviation of dust aerosol optical depth - AOD). As such, we infer that SHL intensity is likely to be similarly enhanced by the effects of dust and water vapour surge events. However, the details of the processes differ. Dust generates substantial radiative cooling at the surface (˜ 11 W m-2 per standard deviation of dust AOD), presumably leading to reduced sensible heat flux in the boundary layer, which is more than compensated by direct radiative heating from shortwave (SW) absorption by dust in the dusty boundary layer. In contrast, water vapour invokes a radiative warming at the surface of ˜ 6 W m-2 per standard deviation of column-integrated water vapour in kg m-2. Net effects involve a pronounced net atmospheric radiative convergence with heating rates on average of 0.5 K day-1 and up to 6 K day-1 during synoptic/mesoscale dust events from monsoon surges and convective cold-pool outflows (haboobs). On this basis, we make inferences on the processes driving variability in the SHL associated with radiative and advective heating/cooling. Depending on the

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

Impacts of cloud overlap assumptions on radiative budgets and heating fields in convective regions

Science.gov (United States)

Wang, XiaoCong; Liu, YiMin; Bao, Qing

2016-01-01

Impacts of cloud overlap assumptions on radiative budgets and heating fields are explored with the aid of a cloud-resolving model (CRM), which provided cloud geometry as well as cloud micro and macro properties. Large-scale forcing data to drive the CRM are from TRMM Kwajalein Experiment and the Global Atmospheric Research Program's Atlantic Tropical Experiment field campaigns during which abundant convective systems were observed. The investigated overlap assumptions include those that were traditional and widely used in the past and the one that was recently addressed by Hogan and Illingworth (2000), in which the vertically projected cloud fraction is expressed by a linear combination of maximum and random overlap, with the weighting coefficient depending on the so-called decorrelation length Lcf. Results show that both shortwave and longwave cloud radiative forcings (SWCF/LWCF) are significantly underestimated under maximum (MO) and maximum-random (MRO) overlap assumptions, whereas remarkably overestimated under the random overlap (RO) assumption in comparison with that using CRM inherent cloud geometry. These biases can reach as high as 100 Wm- 2 for SWCF and 60 Wm- 2 for LWCF. By its very nature, the general overlap (GenO) assumption exhibits an encouraging performance on both SWCF and LWCF simulations, with the biases almost reduced by 3-fold compared with traditional overlap assumptions. The superiority of GenO assumption is also manifested in the simulation of shortwave and longwave radiative heating fields, which are either significantly overestimated or underestimated under traditional overlap assumptions. The study also pointed out the deficiency of constant assumption on Lcf in GenO assumption. Further examinations indicate that the CRM diagnostic Lcf varies among different cloud types and tends to be stratified in the vertical. The new parameterization that takes into account variation of Lcf in the vertical well reproduces such a relationship and

Feasibility of modifying the high resolution infrared radiation sounder (HIRS/2) for measuring spectral components of Earth radiation budget

Science.gov (United States)

Koenig, E. W.; Holman, K. A.

1980-01-01

The concept of adding four spectral channels to the 20 channel HIRS/2 instrument for the purpose of determining the origin and profile of radiant existence from the Earth's atmosphere is considered. Methods of addition of three channels at 0.5, 1.0 and 1.6 micron m to the present 0.7 micron m visible channel and an 18-25 micron m channel to the present 19 channels spaced from 3.7 micron m to 15 micron m are addressed. Optical components and physical positions were found that permit inclusion of these added channels with negligible effect on the performance of the present 20 channels. Data format changes permit inclusion of the ERB data in the 288 bits allocated to HIRS for each scan element. A lamp and collimating optic assembly may replace one of the on board radiometric black bodies to provide a reference source for the albedo channels. Some increase in instrument dimensions, weight and power will be required to accommodate the modifications.

A New Approach in Public Budgeting: Citizens' Budget

Science.gov (United States)

Bilge, Semih

2015-01-01

Change and transformation in the understanding and definition of citizenship has led to the emergence of citizen-oriented public service approach. This approach also raised a new term and concept in the field of public budgeting because of the transformation in the processes of public budgeting: citizens' budget. The citizens' budget which seeks…

FY 1996 Congressional budget request: Budget highlights

Energy Technology Data Exchange (ETDEWEB)

1995-02-01

The FY 1996 budget presentation is organized by the Department`s major business lines. An accompanying chart displays the request for new budget authority. The report compares the budget request for FY 1996 with the appropriated FY 1995 funding levels displayed on a comparable basis. The FY 1996 budget represents the first year of a five year plan in which the Department will reduce its spending by $15.8 billion in budget authority and by $14.1 billion in outlays. FY 1996 is a transition year as the Department embarks on its multiyear effort to do more with less. The Budget Highlights are presented by business line; however, the fifth business line, Economic Productivity, which is described in the Policy Overview section, cuts across multiple organizational missions, funding levels and activities and is therefore included in the discussion of the other four business lines.

Comparing a Carbon Budget for the Amazon Basin Derived from Aircraft Observations

Science.gov (United States)

Chow, V. Y.; Dayalu, A.; Wofsy, S. C.; Gerbig, C.

2015-12-01

We present and compare a carbon budget for the Brazilian Amazon Basin based on the Balanço Atmosférico Regional de Carbono na Amazônia (BARCA) aircraft program, which occurred in November 2008 & May 2009, to other published carbon budgets. In particular, we compare our budget and analysis to others also derived from aircraft observations. Using mesoscale meteorological fields from ECMWF and WRF, we drive the Stochastic Time-Inverted Lagrangian Transport (STILT) model and couple the footprint, or influence, to a biosphere model represented by the Vegetation Photosynthesis Respiration Model (VPRM). Since it is the main driver for the VPRM, we use observed shortwave radiation from towers in Brazil and French Guyana to examine the modeled shortwave radiation data from GL 1.2 (a global radiation model based on GOES 8 visible imagery), ECMWF, and WRF to determine if there are any biases in the modeled shortwave radiation output. We use WRF-STILT and ECMWF-STILT, GL 1.2 shortwave radiation, temperature, and vegetation maps (IGBP and SYNMAP) updated by landuse scenarios modeled by Sim Amazonia 2 and Sim Brazil, to compute hourly a priori CO2 fluxes by calculating Gross Ecosystem Exchange and Respiration for the 4 significant vegetation types across two (wet and dry) seasons as defined by 10-years of averaged TRIMM precipitation data. SF6 from stations and aircraft observations are used to determine the anthropogenic CO2 background and the lateral boundary conditions are taken from CarbonTracker2013B. The BARCA aircraft mixing ratios are then used as a top down constraint in an inversion framework that solves for the parameters controlling the fluxes for each vegetation type. The inversion provides scaling factors for GEE and R for each vegetation type in each season. From there, we derive a budget for the Basin and compare/contrast with other published basinwide CO2 fluxes.

Under Secretary of Defense (Comptroller) > Budget Materials > Budget1998

Science.gov (United States)

functionalStatements OUSD(C) History FMR Budget Materials Budget Execution Financial Management Improving Financial Performance Reports Regulations banner DoD Budget Request 2019 | 2018 | 2017 |2016 | 2015 | 2014 | 2013 | 2012 President's Budget request for the Department of Defense sustains the President's commitment to invest in

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

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.

Large differences in the diabatic heat budget of the tropical UTLS in reanalyses

Science.gov (United States)

Wright, J. S.; Fueglistaler, S.

2013-04-01

We present the time mean heat budgets of the tropical upper troposphere (UT) and lower stratosphere (LS) as simulated by five reanalysis models: MERRA, ERA-Interim, CFSR, JRA-25/JCDAS, and NCEP/NCAR. The simulated diabatic heat budget in the tropical UTLS differs significantly from model to model, with substantial implications for representations of transport and mixing. Large differences are apparent both in the net heat budget and in all comparable individual components, including latent heating, heating due to radiative transfer, and heating due to parameterised vertical mixing. We describe and discuss the most pronounced differences. Although they may be expected given difficulties in representing moist convection in models, the discrepancies in latent heating are still disturbing. We pay particular attention to discrepancies in radiative heating (which may be surprising given the strength of observational constraints on temperature and tropospheric water vapour) and discrepancies in heating due to turbulent mixing (which have received comparatively little attention).

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.

Budget Options

National Research Council Canada - National Science Library

2000-01-01

This volume-part of the Congressional Budget Office's (CBO's) annual report to the House and Senate Committees on the Budget-is intended to help inform policymakers about options for the federal budget...

1981 research programme and budget of Hahn-Meitner-Institut fuer Kernforschung Berlin

International Nuclear Information System (INIS)

Anon.

1981-01-01

Hahn-Meitner-Institut fuer Kernforschung Berlin (HMI) is one of the twelve large research centers of the Federal Republic of Germany; like the other centers, it has to present a combined research programme and budget (programme budget) every year. In these programme budgets, as in the medium-term financial planning in the federal budget, planning for the current year is combined with a medium-term plan for the three next years. For the year 1981, the budget of HMI includes a total expenditure of about DM 85 million, DM 71.2 million of which are direct R + D expenditures. This R + D programme is carried by 396 of the total staff of 705. Research is done in the following fields (approximate figures): Heavy ion physics DM 23.0 million. Radiation- and photochemistry DM 11.4 million. Solid state research DM 20.9 million. Nuclear chemistry DM 8.9 million. Data processing/electronics DM 7.0 million. (orig./UA) [de

[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.

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

The Budget as a Management Tool: Zero Base Budgeting, Panacea ...

African Journals Online (AJOL)

Nigeria has been experiencing difficulties in Budget implementation. The objective of this article is to present alternative forms of budgeting and after exposition on them, to recommend one that could mitigate budget implementation problem for Nigeria. Two types of budgeting addressed are incremental and zero-base.

Molecular characterization of thymidine kinase mutants of human cells induced by densely ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Kronenberg, A; Little, J B

1989-04-01

In order to characterize the nature of mutants induced by densely ionizing radiations at an autosomal locus, the authors have isolated a series of 99 thymidine kinase (tk) mutants of human TK6 lymphoblastoid cells iraadiated with either fast neutrons or accelerated argon ions. Individual muant clones were examined for alterations in their restriction fragment pattern after hybridization with a human cDNA probe for tk. A restriction fragment length polymorphism (RFLP) allowed identification of the active tk allele. Among the neutron-induced mutants, 34/52 exhibited loss of the previously active allele while 6/52 exhibited intragenic rearrangements. Among the argon-induced mutants 27/46 exhibited allele loses and 10/46 showed rearrangements within the tk locus. The remaining mutants had restriction patterns indistinguishable from the TK6 parent. Each of the mutant clones was further examined for structural alterations within the c-erbAl locus which has been localized to chromosome 17q11-q22, at some unknown distance from the human tk locus at chromosome 17q21-q22. A substantial proportion (54%) of tk mutants induced by densely ionizing radiation showed loss of the c-erb locus on the homologous chromosome, suggesting that the mutations involve large-scale genetic changes. (author). 51 refs.; 2 figs.; 6 tabs.

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

Directory of Open Access Journals (Sweden)

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.

Measurement of small antenna reflector losses for radiometer calibration budget

DEFF Research Database (Denmark)

Skou, Niels

1997-01-01

Antenna reflector losses play an important role in the calibration budget for a microwave radiometer. If the losses are small, they are difficult to measure by traditional means. However, they can be assessed directly by radiometric means using the sky brightness temperature as incident radiation...

Do budget balance rules anchor budget balance expectations? -- Some international evidence

OpenAIRE

Rülke, Jan-Christoph; Frenkel, Michael; Lis, Eliza

2013-01-01

This is the first study that analyzes whether budget balance expectations are anchored and whether budget balance rules effectively anchor expectations. To this end, we use a unique data set which covers budget balance expectations in 17 countries that implemented a budget balance rules. While our results are mixed concerning the general impact of budget balance rules on anchoring expectations, we do find that specific features of budget balance rules are important to successfully anchor budg...

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

Surface Radiation Budget (SURFRAD) Network 1-Hour Observations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Radiation measurements at SURFRAD stations cover the range of the electromagnetic spectrum that affects the earth/atmosphere system. Direct solar radiation is...

Is Zero-Based Budgeting Different from Planning--Programming--Budgeting Systems?

Science.gov (United States)

Hentschke, Guilbert C.

1977-01-01

Successful adoption of zero-base budgeting (ZBB) will be greater than that of planning-programming-budgeting-systems (PPBS) because perceived problems inherent in PPBS are largely missing in ZBB; ZBB appears to fit current school district budgeting behavior; and ZBB seems to improve communication about the need for budget reform. (Author/IRT)

The increased use of radiation requires enhanced activities regarding radiation safety control

International Nuclear Information System (INIS)

Lee, Yun Jong; Lee, Jin Woo; Jeong, Gyo Seong

2015-01-01

More recently, companies that have obtained permission to use radioactive materials or radiation device and registered radiation workers have increased by 10% and 4% respectively. The increased use of radiation could have an effect on radiation safety control. However, there is not nearly enough manpower and budget compared to the number of workers and facilities. This paper will suggest a counteroffer thought analyzing pending issues. The results of this paper indicate that there are 47 and 31.3 workers per radiation protection officer in educational and research institutes, respectively. There are 20.1 persons per RPO in hospitals, even though there are 2 RPOs appointed. Those with a special license as a radioisotope handler were ruled out as possible managers because medical doctors who have a special license for radioisotope handling normally have no experience with radiation safety. The number of staff members and budget have been insufficient for safety control at most educational and research institutes. It is necessary to build an optimized safety control system for effective Radiation Safety Control. This will reduce the risk factor of safety, and a few RPOs can be supplied for efficiency and convenience

The increased use of radiation requires enhanced activities regarding radiation safety control

Energy Technology Data Exchange (ETDEWEB)

Lee, Yun Jong; Lee, Jin Woo; Jeong, Gyo Seong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

2015-05-15

More recently, companies that have obtained permission to use radioactive materials or radiation device and registered radiation workers have increased by 10% and 4% respectively. The increased use of radiation could have an effect on radiation safety control. However, there is not nearly enough manpower and budget compared to the number of workers and facilities. This paper will suggest a counteroffer thought analyzing pending issues. The results of this paper indicate that there are 47 and 31.3 workers per radiation protection officer in educational and research institutes, respectively. There are 20.1 persons per RPO in hospitals, even though there are 2 RPOs appointed. Those with a special license as a radioisotope handler were ruled out as possible managers because medical doctors who have a special license for radioisotope handling normally have no experience with radiation safety. The number of staff members and budget have been insufficient for safety control at most educational and research institutes. It is necessary to build an optimized safety control system for effective Radiation Safety Control. This will reduce the risk factor of safety, and a few RPOs can be supplied for efficiency and convenience.

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.

Home - House Budget Committee

Science.gov (United States)

Initiatives Hearings Full Menu About Toggle Links Members History Staff Rules & Budget Law News Toggle Links Press Releases Budget Digests HBC Publications Op-Eds Speeches & Statements Budgets Toggle Links FY 2018 Budget FY 2017 Budget FY 2017 Reconciliation FY 2016 Budget FY 2016 Reconciliation FY 2015

Late Budgets

DEFF Research Database (Denmark)

Andersen, Asger Lau; Lassen, David Dreyer; Nielsen, Lasse Holbøll Westh

are negative rather than positive; and when there is divided government. We test the hypotheses of the model using a unique data set of late budgets for US state governments, based on dates of budget approval collected from news reports and a survey of state budget o¢ cers for the period 1988...

Zero-based budgeting: Pathway to sustainable budget implementation in Nigeria

Directory of Open Access Journals (Sweden)

Udeh Francis Nnoli

2017-10-01

Full Text Available This paper investigates the application of Zero-Based Budgeting (ZBB system to budget implementation by the Federal Government of Nigeria by ascertaining among others, the relationship between ZBB approach and budget performance indices in Nigeria. To achieve the above, primary data were obtained through questionnaires that were specifically designed for this study. The data obtained were analysed with the SPSS version 21. The statistical tools employed were Analysis of Variance (ANOVA and Pearson Correlation Coefficiant (PCC. The Cronbach’s Alpha reliability test was used to test the internal consistency/reliability of the instrument used for the study. On the basis of the analysis, we found that there is significant difference in the effectiveness of ZBB in terms of budget implementation compared to the Traditional Budgeting System (TBS. It was also found that the application of ZBB tend to be performance-driven and is able to detect the redundant programmes/projects and staff, thereby recommending either realignment, discharge, transfer or redeployment of projects or resources. The study therefore, recommends among others that ZBB should be encouraged as a good means of budget implementation and also close monitoring of budget execution should be enshrined in work ethics at every stage of budget preparation and implementation in the country. This is believed would go a long way to strengthen measures aimed at mitigating poor budget implementation in the country.

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

California Budget Simulation

Science.gov (United States)

Mallinson, Daniel J.

2018-01-01

The California Budget Challenge produced by Next10 provides a useful and intuitive tool for instructors to introduce students to public budgeting. Students will reason through a series of budgeting decisions using information provided on the fiscal and practical implications of their choices. The Challenge is updated with each budget cycle, so it…

Budgeting for School Media Centers.

Science.gov (United States)

Drott, M. Carl

1978-01-01

Describes various forms of budgets and discusses concepts in budgeting useful to supervisors of school media centers: line item budgets, capital budgets, creating budgets, the budget calendar, innovations, PPBS (Planning, Programing, Budgeting System), zero-based budgeting, cost-benefit analysis, benefits, benefit guidelines, and budgeting for the…

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

Directory of Open Access Journals (Sweden)

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.

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

Entropy Budget for Hawking Evaporation

Directory of Open Access Journals (Sweden)

Ana Alonso-Serrano

2017-07-01

Full Text Available Blackbody radiation, emitted from a furnace and described by a Planck spectrum, contains (on average an entropy of 3 . 9 ± 2 . 5 bits per photon. Since normal physical burning is a unitary process, this amount of entropy is compensated by the same amount of “hidden information” in correlations between the photons. The importance of this result lies in the posterior extension of this argument to the Hawking radiation from black holes, demonstrating that the assumption of unitarity leads to a perfectly reasonable entropy/information budget for the evaporation process. In order to carry out this calculation, we adopt a variant of the “average subsystem” approach, but consider a tripartite pure system that includes the influence of the rest of the universe, and which allows “young” black holes to still have a non-zero entropy; which we identify with the standard Bekenstein entropy.

DCS Budget Tracking System

Data.gov (United States)

Social Security Administration — DCS Budget Tracking System database contains budget information for the Information Technology budget and the 'Other Objects' budget. This data allows for monitoring...

The effect of motivation profile and participative budgeting on budget goal commitment

DEFF Research Database (Denmark)

Sandalgaard, Niels; Bukh, Per Nikolaj; Poulsen, Carsten Stig

2009-01-01

The effect of participative budgeting on motivation is often considered in management accounting research. In this study we focus on dispositional factors of motivation rooted in personality that affect budgeting. Especially we focus on the effect of personality traits in the form of achievement......, power and affiliation motives on budget goal commitment in interaction with participative budgeting. The study is based on a survey among bank managers at different organizational levels of a Scandinavian regional bank and the results indicate that the effect of participative budgeting on budget goal...... commitment is moderated by the implicit power motivation of the bank manager....

Air temperature, radiation budget and area changes of Quisoquipina glacier in the Cordillera Vilcanota (Peru)

Science.gov (United States)

Suarez, Wilson; Macedo, Nicolás; Montoya, Nilton; Arias, Sandro; Schauwecker, Simone; Huggel, Christian; Rohrer, Mario; Condom, Thomas

2015-04-01

The Peruvian Andes host about 71% of all tropical glaciers. Although several studies have focused on glaciers of the largest glaciered mountain range (Cordillera Blanca), other regions have received little attention to date. In 2011, a new program has been initiated with the aim of monitoring glaciers in the centre and south of Peru. The monitoring program is managed by the Servicio Nacional de Meteorología e Hidrología del Perú (SENAMHI) and it is a joint project together with the Universidad San Antonio Abad de Cusco (UNSAAC) and the Autoridad Nacional del Agua (ANA). In Southern Peru, the Quisoquipina glacier has been selected due to its representativeness for glaciers in the Cordillera Vilcanota considering area, length and orientation. The Cordillera Vilcanota is the second largest mountain range in Peru with a glaciated area of approximately 279 km2 in 2009. Melt water from glaciers in this region is partly used for hydropower in the dry season and for animal breeding during the entire year. Using Landsat 5 images, we could estimate that the area of Quisoquipina glacier has decreased by approximately 11% from 3.66 km2 in 1990 to 3.26 km2 in 2010. This strong decrease is comparable to observations of other tropical glaciers. In 2011, a meteorological station has been installed on the glacier at 5180 m asl., measuring air temperature, wind speed, relative humidity, net short and longwave radiation and atmospheric pressure. Here, we present a first analysis of air temperature and the radiation budget at the Quisoquipina glacier for the first three years of measurements. Additionally, we compare the results from Quisoquipina glacier to results obtained by the Institut de recherche pour le développement (IRD) for Zongo glacier (Bolivia) and Antizana glacier (Ecuador). For both, Quisoquipina and Zongo glacier, net shortwave radiation may be the most important energy source, thus indicating the important role of albedo in the energy balance of the glacier

Energy budget of the volcano Stromboli, Italy

Science.gov (United States)

Mcgetchin, T. R.; Chouet, B. A.

1979-01-01

The results of the analyses of movies of eruptions at Stromboli, Italy, and other available data are used to discuss the question of its energy partitioning among various energy transport mechanisms. Energy is transported to the surface from active volcanoes in at least eight modes, viz. conduction (and convection) of the heat through the surface, radiative heat transfer from the vent, acoustical radiation in blast and jet noise, seismic radiation, thermal energy of ejected particles, kinetic energy of ejected particles, thermal energy of ejected gas, and kinetic energy of ejected gas. Estimated values of energy flux from Stromboli by these eight mechanisms are tabulated. The energy budget of Stromboli in its normal mode of activity appears to be dominated by heat conduction (and convection) through the ground surface. Heat carried by eruption gases is the most important of the other energy transfer modes. Radiated heat from the open vent and heat carried by ejected lava particles also contribute to the total flux, while seismic energy accounts for about 0.5% of the total. All other modes are trivial by comparison.

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

Solar Radiation and Cloud Radiative Forcing in the Pacific Warm Pool Estimated Using TOGA COARE Measurements

Science.gov (United States)

Chou, Ming-Dah; Chou, Shu-Hsien; Zhao, Wenzhong

1999-01-01

The energy budget of the tropical western Pacific (TWP) is particularly important because this is one of the most energetic convection regions on the Earth. Nearly half of the solar radiation incident at the top of atmosphere is absorbed at the surface and only about 22% absorbed in the atmosphere. A large portion of the excess heat absorbed at the surface is transferred to the atmosphere through evaporation, which provides energy and water for convection and precipitation. The western equatorial Pacific is characterized by the highest sea surface temperature (SST) and heaviest rainfall in the world ocean. A small variation of SST associated with the eastward shift of the warm pool during El-Nino/Souther Oscillation changes the atmospheric circulation pattern and affects the global climate. In a study of the TWP surface heat and momentum fluxes during the Tropical Ocean and Global Atmosphere Coupled Ocean-Atmosphere Response Experiment (TOGA COARE) Intensive observing period (IOP) from November 1992 to February have found that the solar radiation is the most important component of the surface energy budget, which undergoes significant temporal and spatial variation. The variations are influenced by the two 40-50 days Madden Julian Oscillations (MJOs) which propagated eastward from the Indian Ocean to the Central Pacific during the IOP. The TWP surface solar radiation during the COARE IOP was investigated by a number of studies. In addition, the effects of clouds on the solar heating of the atmosphere in the TWP was studied using energy budget analysis. In this study, we present some results of the TWP surface solar shortwave or SW radiation budget and the effect of clouds on the atmospheric solar heating using the surface radiation measurements and Japan's Geostationary Meteorological Satellite 4 radiance measurements during COARE IOP.

BEYOND BUDGETING

Directory of Open Access Journals (Sweden)

Edo Cvrkalj

2015-12-01

Full Text Available Traditional budgeting principles, with strictly defined business goals, have been, since 1998, slowly growing into more sophisticated and organization-adjusted alternative budgeting concepts. One of those alternative concepts is the “Beyond budgeting” model with an implemented performance effects measuring process. In order for the model to be practicable, budget planning and control has to be reoriented to the “bottom up” planning and control approach. In today’s modern business surroundings one has to take both present and future opportunities and threats into consideration, by valorizing them in a budget which would allow a company to realize a whole pallet of advantages over the traditional budgeting principles which are presented later in the article. It is essential to emphasize the importance of successfully implementing the new budgeting principles within an organization. If the implementation has been lacking and done without a higher goal in mind, it is easily possible that the process has been implemented without coordination, planning and control framework within the organization itself. Further in the article we present an overview of managerial techniques and instruments within the “Beyond budgeting” model such as balanced scorecard, rolling forecast, dashboard, KPI and other supporting instruments. Lastly we define seven steps for implementing the “Beyond budgeting” model and offer a comparison of “Beyond budgeting” model against traditional budgeting principles which lists twelve reasons why “Beyond budgeting” is better suited to modern and market-oriented organizations. Each company faces those challenges in their own characteristic way but implementing new dynamic planning models will soon become essential for surviving in the market.

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.

Public Budgeting: The Compromises Among the Sound Budgeting Principles in Contingency Funding

Science.gov (United States)

2017-06-01

funding for major aircraft using supplemental appropriations in place of incremental funding as intended for normal budgeting practices. This was a prime... incrementally funded on an annual basis. This change in budgeting practices lacked predictability because it allowed last-minute budget requests with low...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release. Distribution is unlimited. PUBLIC BUDGETING

Understanding the Budget Process

Directory of Open Access Journals (Sweden)

Mesut Yalvaç

2000-03-01

Full Text Available Many different budgeting techniques can be used in libraries, and some combination of these will be appropriate for almost any individual situation. Li-ne-item, program, performance, formula, variable, and zero-base budgets all have features that may prove beneficial in the preparation of a budget. Budgets also serve a variety of functions, providing for short-term and long-term financial planning as well as for cash management over a period of time. Short-term plans are reflected in the operating budget, while long-term plans are reflected in the capital budget. Since the time when cash is available to an organization does not usually coincide with the time that disbursements must be made, it is also important to carefully plan for the inflow and outflow of funds by means of a cash budget.      During the budget process an organization selects its programs and activities by providing the necessary funding; the library, along with others in the organization, must justify its requests. Because of the cyclical nature of the budget process, it is possible continually to gather information and evaluate alternatives for the next budget period so that the library may achieve its maximum potential for service to its patrons.

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

Library Budget Primer.

Science.gov (United States)

Warner, Alice Sizer

1993-01-01

Discusses the advantages and disadvantages of six types of budgets commonly used by many different kinds of libraries. The budget types covered are lump-sum; formula; line or line-item; program; performance or function; and zero-based. Accompanying figures demonstrate the differences between four of the budget types. (three references) (KRN)

The Agency's budget

International Nuclear Information System (INIS)

1964-01-01

A total Agency Budget of $10 406 000 for 1965 was approved by the General Conference at its session of September 1964; the Budget for the year 1964 amounted to $9 812 000. The consolidated Budget figures are shown in the table at the end of this article. The Budget falls into two parts - the Regular Budget and the Operational Budget. The Regular Budget provides for the ordinary administrative expenses of the Agency, and for expert panels, special missions, symposia and conferences, distribution of information, and scientific and technical services. In conformity with the Agency's Statute, these expenses are met by contributions made according to Voluntary contributions are paid initially into a General Fund established for this purpose, and money for operations is transferred to the respective Operating Funds as appropriate, and as approved by the Board of Governors. The scale of assessments for 1965 is based on the United Nations scale for 1964. The assessments are estimated to yield $7 713 000 - an increase of 6.8 per cent; however, more than three quarters of this increase will be offset by credits which Member States will receive as a result of a cash surplus brought forward. The Operational Budget is financed by voluntary contributions and is divided into two parts - Operating Fund I, devoted to certain laboratory and research projects, and Operating Fund II, for technical assistance, training and research contracts.

Budget Analysis: Review of the Governor's Proposed Budget, 1999-00.

Science.gov (United States)

New York State Office of the Comptroller, Albany.

This report provides an overview of the 1999-2000 executive budget for New York State. The budget calls for $72.7 billion in all funds spending and proposes that a $1.8 billion surplus from the 1998-99 fiscal year be used to fill budget gaps in fiscal years 2000-01 and 2001-02. The report focuses on spending for education, health and social…

Plan Your Advertising Budget.

Science.gov (United States)

Britt, Steuart-Henderson

1979-01-01

Methods for establishing an advertising budget are reviewed. They include methods based on percentage of sales or profits, unit of sales, and objective and task. Also discussed are ways to allocate a promotional budget. The most common breakdowns are: departmental budgets, total budget, calendar periods, media, and sales area. (JMD)

Budgeting and Beyond

DEFF Research Database (Denmark)

Rohde, Carsten

Budgets and budget control has been known since the early 19th century1. However the use of budget control was until the beginning of the 1920ies in US primarily related to governmental units and states and to a minor extent to business units in practice. At that time James McKinsey describes...

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

Top of Atmosphere Radiation MVIRI/SEVIRI Data Record within the Climate Monitoring SAF

Science.gov (United States)

Urbain, Manon; Clerbaux, Nicolas; Ipe, Alessandro; Tornow, Florian; Hollmann, Rainer; Baudrez, Edward; Velazquez Blazquez, Almudena; Moreels, Johan; Trentmann, Jörg

2017-04-01

The CM SAF Top of Atmosphere (TOA) Radiation MVIRI/SEVIRI Data Record provides a homogeneous satellite-based climatology of the TOA Reflected Solar (TRS) and Emitted Thermal (TET) radiation in all-sky conditions. The continuous monitoring of these two components of the Earth Radiation Budget is of prime importance to study climate variability and change. The Meteosat Visible and InfraRed Imager (MVIRI - from 1983 until 2004) and the Spinning Enhanced Visible and Infrared Imager (SEVIRI - from 2004 onward) on board the Meteosat First and Second Generation satellites are combined to generate a long Thematic Climate Data Record (TCDR). Combining MVIRI and SEVIRI allows an unprecedented temporal (30 minutes / 15 minutes) and spatial (2.5 km / 3 km) resolution compared to the Clouds and the Earth's Radiant Energy System (CERES) products. This is a step forward as it helps to increase the knowledge of the diurnal cycle and the small-scale spatial variations of radiation. The MVIRI/SEVIRI Data Record covers a 32 years time period from 1 February 1983 to 30 April 2015. The TOA radiation products are provided as daily mean, monthly mean and monthly averages of the hourly integrated values (diurnal cycle). To ensure consistency with other CM SAF products, the data is provided on a regular grid at a spatial resolution of 0.05 degrees (i.e. about 5.5 km) and covers the region between +/- 70° longitude and +/- 70° latitude. Validation of the MVIRI/SEVIRI Data Record has been performed by intercomparison with several references such as the CERES products (EBAF, SYN1deg-Day and SYN1deg-M3Hour), the HIRS OLR Climate Data Record (Daily and Monthly), the reconstructed ERBS WFOV-CERES (or DEEP-C) dataset and the ISCCP FD products. CERES is considered as the best reference from March 2000 onward. The quality of the early part of the Data Record is verified against the other references. In general, the stability of all the TOA radiation products is estimated to be better than 4 W.m-2

Budgeting Approaches in Community Colleges

Science.gov (United States)

Palmer, James C.

2014-01-01

Several budgeting approaches have been initiated as alternatives to the traditional, incremental process. These include formula budgeting; zero-base budgeting; planning, programming, and budgeting systems; and responsibility center budgeting. Each is premised on assumptions about how organizations might best make resource allocation decisions.…

Empirical model of the high-latitude boundary of the Earth's outer radiation belt at altitudes of up to 1000 km

Science.gov (United States)

Kalegaev, V. V.; Barinova, W. O.; Myagkova, I. N.; Eremeev, V. E.; Parunakyan, D. A.; Nguyen, M. D.; Barinov, O. G.

2018-01-01

An empirical model of the high-latitude boundary of the outer Earth's radiation belt (ERB) has been presented, which is based on the measurement data of electron fluxes on the polar low-orbit CORONAS-Photon, Meteor-M1, and Meteor-M2 satellites. The boundary was determined by a sharp decrease to the background level of the flux of trapped electrons with energies of 100 or 200 keV in the polar part of the profile of the outer radiation belt. A numerical algorithm has been implemented to determine the time moment, when the fastest flux changes are recorded. The primary search was carried out, first, on 30 s averaged data, then repeated on data with a higher resolution. A functional dependence was obtained in order to approximate the obtained set of intersections of the boundary by elliptical curve. The empirical model constructed using the CORONAS-Photon measurement data in the epoch of anomalously low geomagnetic activity reflects the longitude structure of the high-latitude boundary of the outer radiation belt associated with the internal Earth's magnetic field (MF), as well as its dependence on the universal time. Based on the data of intersections of the high-latitude boundary of the outer ERB (OERB) in the epoch of 2014-2016, the latitudinal shift of the boundary to the equator dependent on geomagnetic activity has been determined, as well as the nightside shift of the boundary due to the diurnal rotation of the Earth.

Zero-based budgeting: Pathway to sustainable budget implementation in Nigeria

OpenAIRE

Udeh Francis Nnoli; Sopekan Sam Adeyemi; Oraka Azubuike Onuora

2017-01-01

This paper investigates the application of Zero-Based Budgeting (ZBB) system to budget implementation by the Federal Government of Nigeria by ascertaining among others, the relationship between ZBB approach and budget performance indices in Nigeria. To achieve the above, primary data were obtained through questionnaires that were specifically designed for this study. The data obtained were analysed with the SPSS version 21. The statistical tools employed were Analysis of Variance (ANOVA) and ...

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

dos linfonodos axilares tem pior prognóstico, em relação ao intervalo livre de doença, quando apresentam associação de tumor pouco diferenciado com RE negativo, p53 positivo e c-erbB-2 positivo.Purpose: to evaluate the prognostic value of estrogen receptor and p53 and c-erbB-2 proteins in lymph node-negative breast cancer. Methods: an immunohistochemical study was made in paraffin-embedded tissues from the file of the Instituto de Pesquisas Cito-Oncológicas of the Fundação Faculdade Federal de Ciências Médicas de Porto Alegre of fifty cases of postmenopausal women, who were treated at the Irmandade da Santa Casa de Misericórdia de Porto Alegre and at the Santa Rita Hospital from 1990 to 1994. For statistical analysis c² with Yates correction, as well as exact Fisher tests were used and Kaplan Meier curves compared with log-rank test. The mean follow-up of the patients was 3.6 years (3.1-4.5. Of the 50 cases, 14 showed recurrence during the period of follow-up. Results: the mean age was 61 years (46-78. Modified radical mastectomy was performed in 35 patients (70% and 15 (30% were submitted to lumpectomy/axillary dissection and postoperative radiation therapy. Fifty percent of the patients who showed recurrence did it in the first three years after the diagnosis. The mean size of the tumor was 2.8 cm (1.98-3.13 and the most frequent histological type was invasive ductal carcinoma of no special type (92%, according to the Bloom and Richardson graduation, 3 being stage I (6.6%, 35 stage II (76% and 8 stage III (17.4%. In the tumors with recurrence, there was no grade I, 9 stage II (25.7% and 3 stage III (37.5%. In relation to the prognosis, the disease-free interval was less when there was association of a poorly differentiated tumor with negative estrogen receptor (p = 0.006, positive p53 (p = 0.006 and positive c-erbB-2 (p = 0.001. Conclusion: postmenopausal women with lymph node-negative breast cancer showed worse prognosis in relation to disease

A study of Monte Carlo radiative transfer through fractal clouds

Energy Technology Data Exchange (ETDEWEB)

Gautier, C.; Lavallec, D.; O`Hirok, W.; Ricchiazzi, P. [Univ. of California, Santa Barbara, CA (United States)] [and others

1996-04-01

An understanding of radiation transport (RT) through clouds is fundamental to studies of the earth`s radiation budget and climate dynamics. The transmission through horizontally homogeneous clouds has been studied thoroughly using accurate, discreet ordinates radiative transfer models. However, the applicability of these results to general problems of global radiation budget is limited by the plane parallel assumption and the fact that real clouds fields show variability, both vertically and horizontally, on all size scales. To understand how radiation interacts with realistic clouds, we have used a Monte Carlo radiative transfer model to compute the details of the photon-cloud interaction on synthetic cloud fields. Synthetic cloud fields, generated by a cascade model, reproduce the scaling behavior, as well as the cloud variability observed and estimated from cloud satellite data.

Budgeting Time to Teach about the School Budget

Science.gov (United States)

Weiss, Dale

2011-01-01

As a teacher in the Milwaukee Public Schools (MPS) for the past 16 years, the author has grown used to dismal budget cut news arriving each February. Although cuts are always frustrating and their results burdensome, the school has been able to "hang on" reasonably well. This year, however, the budget cuts were extreme. In this article,…

STATE BUDGET APPROPRIATION MANAGERS AS THE SUBJECTS OF BUDGET PLANNING IN THE REPUBLIC OF LITHUANIA

Directory of Open Access Journals (Sweden)

Bronius Sudavicius

2017-01-01

Full Text Available The subject. The article deals with the problem of legal status of the state budget appropriation managers in the process of budget planning in the Republic of Lithuania.The purpose of the article is evaluation of state budget appropriation managers’ role in the process of budget planning in the Republic of Lithuania.The methodology of research is the analysis of the budgetary legislation of the Republic of Lithuania and the scientific literature, using the methods of logical and systematic analysis and other methods of scientific researchMain results, and scope of it’s application. The legal definition and the system of state budget appropriation managers is analyzed in the article. Particular attention is given to the question of role of state budget appropriation managers in the process of budget framework. The role of the Government and Parliament, as well as a special body of management of public finances (in the Republic of Lithuania, the Ministry of Finance – legislative and executive authorities – is emphasized in the scientific literature. But it is often not mentioned what an important place in this process other participants of budgetary relations – state budget appropriation managers – takes. The main participation of state budget appropriation managers in the budget planning process related to the planning of the budget expenditures.Preparation of strategic plans and programmes of budgetary funds by state budget appropriation managers can be considered part of governance activities in general. For budget planning drawn up draft budgets of the programs by state budget appropriation managers is particularly important.Conclusions. The efficiency of the use of state funds depends on the spending of funds, the quality and validity of the developed programmes of activities led by their agencies. State budget appropriation managers are involved, along with other entities, on each stage of the budget planning. They provide the

Public Budget Database - Budget Authority and offsetting receipts 1976-Current

Data.gov (United States)

Executive Office of the President — This file contains historical budget authority and offsetting receipts for 1976 through the current budget year, as well as four years of projections. It can be used...

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

Automated Budget System -

Data.gov (United States)

Department of Transportation — The Automated Budget System (ABS) automates management and planning of the Mike Monroney Aeronautical Center (MMAC) budget by providing enhanced capability to plan,...

THE POSITION BUDGETS OF ADMINISTRATIVE AND TERRITORIAL UNITS IN GENERAL CONSOLIDATED BUDGET

Directory of Open Access Journals (Sweden)

CHIRCULESCU MARIA FELICIA

2017-12-01

Full Text Available The budget is a tool of territorial administrative units of financial and budgetary policy in which the state intervenes in the economy at the local level, having a major impact on general government.Through the decentralization processes that are increasingly debated and applied, the paper aims to highlight the importance of the territorial administrative unit budgets in the consolidated budget in Romania.Thus, the work comprises both theoretical notions concerning the presentation of the consolidated state budget and the budget of the territorial administrative units. The relevance of the work lies in the importance of general government in the regulation of macroeconomic balances by sizing or macroeconomic imbalances, with modern methods that analyze the possibilities and effects of new types of deficits or surpluses in the public sector.

Operational budgeting using fuzzy goal programming

OpenAIRE

Saeed Mohammadi; Kamran Feizi; Ali Khatami Firouz Abadi

2013-01-01

Having an efficient budget normally has different advantages such as measuring the performance of various organizations, setting appropriate targets and promoting managers based on their achievements. However, any budgeting planning requires prediction of different cost components. There are various methods for budgeting planning such as incremental budgeting, program budgeting, zero based budgeting and performance budgeting. In this paper, we present a fuzzy goal programming to estimate oper...

Teaching the Federal Budget, National Debt, and Budget Deficit: Findings from High School Teachers

Science.gov (United States)

Marri, Anand R.; Ahn, Meesuk; Crocco, Margaret Smith; Grolnick, Maureen; Gaudelli, William; Walker, Erica N.

2011-01-01

The issues surrounding the federal budget, national debt, and budget deficit are complex, but not beyond the reach of young students. This study finds scant treatment of the federal budget, national debt, and budget deficit in high schools today. It is hardly surprising that high school teachers spend so little time discussing these topics in…

Preparing the operating budget.

Science.gov (United States)

Williams, R B

1983-12-01

The process of preparing a hospital pharmacy budget is presented. The desired characteristics of a budget and the process by which it is developed and approved are described. Fixed, flexible, and zero-based budget types are explained, as are the major components of a well-developed budget: expense, workload, productivity, revenue, and capital equipment and other expenditures. Specific methods for projecting expenses and revenues, based on historical data, are presented along with a discussion of variables that must be considered in order to achieve an accurate and useful budget. The current shift in emphasis away from revenue capture toward critical analysis of pharmacy costs underscores the importance of budgetary analysis for hospital pharmacy managers.

Between Bedside and Budget

NARCIS (Netherlands)

J.L.T. Blank; E. Eggink

1998-01-01

Original title: Tussen bed en budget. The report Between bedside and budget (Tussen bed en budget) describes an extensive empirical study of the efficiency of general and university hospitals in the Netherlands. A policy summary recaps the main findings of the study. Those findings

Operational budgeting using fuzzy goal programming

Directory of Open Access Journals (Sweden)

Saeed Mohammadi

2013-10-01

Full Text Available Having an efficient budget normally has different advantages such as measuring the performance of various organizations, setting appropriate targets and promoting managers based on their achievements. However, any budgeting planning requires prediction of different cost components. There are various methods for budgeting planning such as incremental budgeting, program budgeting, zero based budgeting and performance budgeting. In this paper, we present a fuzzy goal programming to estimate operational budget. The proposed model uses fuzzy triangular as well as interval number to estimate budgeting expenses. The proposed study of this paper is implemented for a real-world case study in province of Qom, Iran and the results are analyzed.

Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

International Nuclear Information System (INIS)

Deville, Curtiland; Both, Stefan; Bui, Viet; Hwang, Wei-Ting; Tan, Kay-See; Schaer, Mattia; Tochner, Zelig; Vapiwala, Neha

2012-01-01

Our purpose was to report acute gastrointestinal (GI) and genitourinary (GU) toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT) with a daily endorectal water-filled balloon (ERB H2O ), and assess associations with planning parameters and pretreatment clinical characteristics. The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERB H2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0) were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Mean age was 68 (range 51–88). Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV) rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps < 0.05). Maximum acute GU toxicity was grade 0, 1, and 2 for 17%, 41%, and 42% of patients, respectively. Infield bladder V20 (P = 0.03) and pretreatment International Prostate Symptom Scale (IPSS) (P = 0.003) were associated with grade 2 GU toxicity. Prostate IG-IMRT using a daily ERB H2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities

Understanding the Budget Process

OpenAIRE

Mesut Yalvaç

2000-01-01

Many different budgeting techniques can be used in libraries, and some combination of these will be appropriate for almost any individual situation. Li-ne-item, program, performance, formula, variable, and zero-base budgets all have features that may prove beneficial in the preparation of a budget. Budgets also serve a variety of functions, providing for short-term and long-term financial planning as well as for cash management over a period of time. Short-term plans are reflected in the oper...

An aerosol optical depth climatology for NOAA's national surface radiation budget network (SURFRAD)

Science.gov (United States)

Augustine, John A.; Hodges, Gary B.; Dutton, Ellsworth G.; Michalsky, Joseph J.; Cornwall, Christopher R.

2008-06-01

A series of algorithms developed to process spectral solar measurements for aerosol optical depth (AOD) for the National Oceanic and Atmospheric Administration's (NOAA) national surface radiation budget network (SURFRAD) is summarized, and decadal results are presented. AOD is a measure of the extinction of the Sun's beam due to aerosols. Daily files of AOD for five spectral measurements in the visible and near-infrared have been produced for 1997-2006. Comparisons of SURFRAD daily AOD averages to NASA's Aerosol Robotic Network product at two of the stations were generally good. An AOD climatology for each SURFRAD station is presented as an annual time series of composite monthly means that represents a typical intra-annual AOD variation. Results are similar to previous U.S. climatologies in that the highest AOD magnitude and greatest variability occur in summer, the lowest AOD levels are in winter, and geographically, the highest-magnitude AOD is in the eastern United States. Springtime Asian dust intrusions show up as a secondary maximum at the western stations. A time series of nationwide annual means shows that 500-nm AOD has decreased over the United States by about 0.02 AOD units over the 10-year period. However, this decline is not statistically significant nor geographically consistent within the country. The eastern U.S. stations and westernmost station at Desert Rock, Nevada, show decreasing AOD, whereas the other two western stations show an increase that is attributed to an upsurge in wildfire activity in the last half of the decade.

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...

System Budgets

DEFF Research Database (Denmark)

Jeppesen, Palle

1996-01-01

The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers.......The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers....

The 'People's Budget' and Budget Effectiveness:The Case of Local ...

African Journals Online (AJOL)

All over the world, participatory budgeting is being advocated. This is based on the belief that stakeholders' participation in the budgeting process improves transparency, accountability and service delivery. Using evidence from 105 Civil Society Organisations (CSOs) in Kabalore and Kamwenge district local governments ...

42 CFR 457.140 - Budget.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Budget. 457.140 Section 457.140 Public Health... Child Health Insurance Programs and Outreach Strategies § 457.140 Budget. The State plan, or plan amendment that has a significant impact on the approved budget, must include a budget that describes the...

Environmental budget and policy goal

Energy Technology Data Exchange (ETDEWEB)

Noh, Sang Hwan [Korea Environment Institute, Seoul (Korea)

1998-12-01

The assigned budget for environmental sector is quite insufficient to meet enormous environmental demand. Under this circumstance, there is only one way to solve environmental problems efficiently, i.e. to use a given budget efficiently. Therefore, the study on efficient utilization of a given environmental invested finance is needed by customizing a diagnosis of present condition on the operation of environmental budget and environmental investment analysis. In this respect, an entire national budget of 1999 and environmental budget were analyzed in this study. By analyzing economic efficiency of sewage disposal program, integrated septic tank system, VOC regulation, incinerator construction program, food waste disposal program, and recycling program, an efficient budget policy was presented. 19 refs., 18 figs., 169 tabs.

Baseline budgeting for continuous improvement.

Science.gov (United States)

Kilty, G L

1999-05-01

This article is designed to introduce the techniques used to convert traditionally maintained department budgets to baseline budgets. This entails identifying key activities, evaluating for value-added, and implementing continuous improvement opportunities. Baseline Budgeting for Continuous Improvement was created as a result of a newly named company president's request to implement zero-based budgeting. The president was frustrated with the mind-set of the organization, namely, "Next year's budget should be 10 to 15 percent more than this year's spending." Zero-based budgeting was not the answer, but combining the principles of activity-based costing and the Just-in-Time philosophy of eliminating waste and continuous improvement did provide a solution to the problem.

Law 15.809 National budget of ressources and expenditure, it approve for the actually government period

International Nuclear Information System (INIS)

1986-01-01

The articles 340,341,342,343 of the budget law 115.809 treat the following topics: creation of the National Commission of Atomic Energy with the National Direction of Nuclear Technology in the Uruguay,duties, radiation protection taxs

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

Budget institutions and taxation

DEFF Research Database (Denmark)

Aaskoven, Lasse

2018-01-01

While a number of different studies have explored the effects of budgetary procedures and the centralization of the budget process on government debt, deficits and spending, few of them have explored whether such fiscal institutions matter for public revenue. This article argues that centralizing...... the budget process raises the levels of taxation by limiting the ability of individual government officials to veto tax increases in line with common-pool-problem arguments regarding public finances. Using detailed data on budgetary procedures from 15 EU countries, the empirical analysis shows that greater...... centralization of the budget process increases taxation as a share of GDP and that both the type of budget centralization and level of government fractionalization matter for the size of this effect. The results suggest that further centralizing the budget process limits government debt and deficits...

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

‘FLEXIBLE’ BUDGETS ARE ALREADY BUDGETING PROCESS ANALYSIS OF PRODUCTION COSTS FOR OIL AND FAT ENTERPRISES

Directory of Open Access Journals (Sweden)

V. Shvetz’

2013-10-01

Full Text Available The problems of methodological fundamentals of managerial accounting of manufacturing costs in information provision for budgeting, not only at the enterprise level, but also as it is required by current conditions of advanced control, in the context of structural production units of “responsibility centers” using “flexible” budgets, which are prepared during the manufacturing process are examined. Unlike a simple comparison of the regular budgets (scheduled amount of work divided by regulatory costs per unit, “flexible” budget makes adjustments to the planned budget because it represents the actual amount of work divided by regulatory costs, which is included with the comparison of the amount of work that are not fulfilled, or carried to a greater or lesser extent compared with the expected budget. Thus, “Flexible” budgets reveal the actual extent of the changes compared with the expected budget.

Development of multi-sensor global cloud and radiance composites for earth radiation budget monitoring from DSCOVR

Science.gov (United States)

Khlopenkov, Konstantin; Duda, David; Thieman, Mandana; Minnis, Patrick; Su, Wenying; Bedka, Kristopher

2017-10-01

The Deep Space Climate Observatory (DSCOVR) enables analysis of the daytime Earth radiation budget via the onboard Earth Polychromatic Imaging Camera (EPIC) and National Institute of Standards and Technology Advanced Radiometer (NISTAR). Radiance observations and cloud property retrievals from low earth orbit and geostationary satellite imagers have to be co-located with EPIC pixels to provide scene identification in order to select anisotropic directional models needed to calculate shortwave and longwave fluxes. A new algorithm is proposed for optimal merging of selected radiances and cloud properties derived from multiple satellite imagers to obtain seamless global hourly composites at 5-km resolution. An aggregated rating is employed to incorporate several factors and to select the best observation at the time nearest to the EPIC measurement. Spatial accuracy is improved using inverse mapping with gradient search during reprojection and bicubic interpolation for pixel resampling. The composite data are subsequently remapped into EPIC-view domain by convolving composite pixels with the EPIC point spread function defined with a half-pixel accuracy. PSF-weighted average radiances and cloud properties are computed separately for each cloud phase. The algorithm has demonstrated contiguous global coverage for any requested time of day with a temporal lag of under 2 hours in over 95% of the globe.

Commensurate comparisons of models with energy budget observations reveal consistent climate sensitivities

Science.gov (United States)

Armour, K.

2017-12-01

Global energy budget observations have been widely used to constrain the effective, or instantaneous climate sensitivity (ICS), producing median estimates around 2°C (Otto et al. 2013; Lewis & Curry 2015). A key question is whether the comprehensive climate models used to project future warming are consistent with these energy budget estimates of ICS. Yet, performing such comparisons has proven challenging. Within models, values of ICS robustly vary over time, as surface temperature patterns evolve with transient warming, and are generally smaller than the values of equilibrium climate sensitivity (ECS). Naively comparing values of ECS in CMIP5 models (median of about 3.4°C) to observation-based values of ICS has led to the suggestion that models are overly sensitive. This apparent discrepancy can partially be resolved by (i) comparing observation-based values of ICS to model values of ICS relevant for historical warming (Armour 2017; Proistosescu & Huybers 2017); (ii) taking into account the "efficacies" of non-CO2 radiative forcing agents (Marvel et al. 2015); and (iii) accounting for the sparseness of historical temperature observations and differences in sea-surface temperature and near-surface air temperature over the oceans (Richardson et al. 2016). Another potential source of discrepancy is a mismatch between observed and simulated surface temperature patterns over recent decades, due to either natural variability or model deficiencies in simulating historical warming patterns. The nature of the mismatch is such that simulated patterns can lead to more positive radiative feedbacks (higher ICS) relative to those engendered by observed patterns. The magnitude of this effect has not yet been addressed. Here we outline an approach to perform fully commensurate comparisons of climate models with global energy budget observations that take all of the above effects into account. We find that when apples-to-apples comparisons are made, values of ICS in models are

Atmospheric components of the surface energy budget over young sea ice: Results from the N-ICE2015 campaign

Science.gov (United States)

Walden, Von P.; Hudson, Stephen R.; Cohen, Lana; Murphy, Sarah Y.; Granskog, Mats A.

2017-08-01

The Norwegian young sea ice campaign obtained the first measurements of the surface energy budget over young, thin Arctic sea ice through the seasonal transition from winter to summer. This campaign was the first of its kind in the North Atlantic sector of the Arctic. This study describes the atmospheric and surface conditions and the radiative and turbulent heat fluxes over young, thin sea ice. The shortwave albedo of the snow surface ranged from about 0.85 in winter to 0.72-0.80 in early summer. The near-surface atmosphere was typically stable in winter, unstable in spring, and near neutral in summer once the surface skin temperature reached 0°C. The daily average radiative and turbulent heat fluxes typically sum to negative values (-40 to 0 W m-2) in winter but then transition toward positive values of up to nearly +60 W m-2 as solar radiation contributes significantly to the surface energy budget. The sensible heat flux typically ranges from +20-30 W m-2 in winter (into the surface) to negative values between 0 and -20 W m-2 in spring and summer. A winter case study highlights the significant effect of synoptic storms and demonstrates the complex interplay of wind, clouds, and heat and moisture advection on the surface energy components over sea ice in winter. A spring case study contrasts a rare period of 24 h of clear-sky conditions with typical overcast conditions and highlights the impact of clouds on the surface radiation and energy budgets over young, thin sea ice.

Radiation closure and diurnal cycle of the clear-sky dust instantaneous direct radiative forcing over Arabian Peninsula

KAUST Repository

Osipov, Sergey; Stenchikov, Georgiy L.; Brindley,  Helen; Banks,  Jamie

2015-01-01

Spinning Enhanced Visible and Infrared Imager (SEVIRI) aerosol optical depth. Results are compared with Geostationary Earth Radiation Budget (GERB) derived top of the atmosphere climatological forcing over the Red Sea.

Zero-Base Budgeting:; An Institutional Experience.

Science.gov (United States)

Alexander, Donald L.; Anderson, Roger C.

Zero-base budgeting as it is used at Allegany College is described. Zero-based budgeting is defined as a budgeting and planning approach that requires the examination of every item in a budget request as if the request were being proposed for the first time. Budgets (decision packages) are first made up for decision units (i.e., a course for the…

Development of models for thermal infrared radiation above and within plant canopies

Science.gov (United States)

Paw u, Kyaw T.

1992-01-01

Any significant angular dependence of the emitted longwave radiation could result in errors in remotely estimated energy budgets or evapotranspiration. Empirical data and thermal infrared radiation models are reviewed in reference to anisotropic emissions from the plant canopy. The biometeorological aspects of linking longwave models with plant canopy energy budgets and micrometeorology are discussed. A new soil plant atmosphere model applied to anisotropic longwave emissions from a canopy is presented. Time variation of thermal infrared emission measurements is discussed.

Revisiting the radiative vertical velocity paradigm in the TTL

Science.gov (United States)

Bolot, Maximilien; Moyer, Elisabeth

2015-04-01

We demonstrate that uplift rates in the TTL (tropical tropopause layer) may be commonly overestimated. The mass balance of any tracer in the TTL depends on the vertical speed of large-scale uplift and the rate of convective detrainment from overshoots. Generally, uplift velocity is retrieved from the conservation of energy, assuming that the only significant factor is radiative heating.1,2 The detrainment rate is then computed from the convergence of the uplift flux, with the assumption that detrainment dominates over entrainment in the TTL. We show that this commonly calculated 'radiative vertical velocity' and the associated rate of detrainment are necessarily flawed for either of two mutually exclusive reasons. If radiative heating is the sole diabatic term in the energy budget, then significant convective entrainment must occur at TTL levels. If detrainment dominates over entrainment, then the heat budget must include the cooling rate from the export of sensible heat deficit in overshooting convection. We illustrate the calculations using tropical values of radiative heating rates and large-scale divergence fluxes from ERA-Interim reanalysis. For undilute convection, the export of heat deficit in detrained overshoots would substantially offset radiative heating, lowering the resulting assumed vertical velocity at 16 km by a factor of three. The computed detrainment rate at this altitude also increases significantly, by a factor of five. Because these changes would alter interpretation of tracer profiles, it is important to include all terms in the heat budget in tracer studies. Conversely, tracer transport properties can be used to help constrain the impact of convection on the TTL heat budget.3 [1] Folkins, I. et al., J. Geophys. Res., 111, D23304, (2006). [2] Read, W. G. et al., Atmos. Chem. Phys., 8, 6051-6067, (2008). [3] Kuang, Z. and Bretherton, C. S., J. Atmos. Sci., 61, 2919-2927, (2004)

Under Secretary of Defense (Comptroller) > Budget

Science.gov (United States)

functionalStatements OUSD(C) History FMR Budget Materials Budget Execution Financial Management Improving Financial Performance Reports Regulations Press Release | Budget Briefing | Transcripts: David L. Norquist, Under PDF document. Click on Excel icon for Excel document Overview - FY2019 Defense Budget Performance

Budget goal commitment, clinical managers' use of budget information and performance.

Science.gov (United States)

Macinati, Manuela S; Rizzo, Marco G

2014-08-01

Despite the importance placed on accounting as a means to influence performance in public healthcare, there is still a lot to be learned about the role of management accounting in clinical managers' work behavior and their link with organizational performance. The article aims at analyzing the motivational role of budgetary participation and the intervening role of individuals' mental states and behaviors in influencing the relationship between budgetary participation and performance. According to the goal-setting theory, SEM technique was used to test the relationships among variables. The data were collected by a survey conducted in an Italian hospital. The results show that: (i) budgetary participation does not directly influence the use of budget information, but the latter is encouraged by the level of budget goal commitment which, as a result, is influenced by the positive motivational consequences of participative budgeting; (ii) budget goal commitment does not directly influence performance, but the relationship is mediated by the use of budget information. This study contributes to health policy and management accounting literature and has significant policy implications. Mainly, the findings prove that the introduction of business-like techniques in the healthcare sector can improve performance if attitudinal and behavioral variables are adequately stimulated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Quantifying Diurnal Cloud Radiative Effects by Cloud Type in the Tropical Western Pacific

Energy Technology Data Exchange (ETDEWEB)

Burleyson, Casey D.; Long, Charles N.; Comstock, Jennifer M.

2015-06-01

Cloud radiative effects are examined using long-term datasets collected at the three Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facilities in the tropical western Pacific. We quantify the surface radiation budget, cloud populations, and cloud radiative effects by partitioning the data by cloud type, time of day, and as a function of large scale modes of variability such as El Niño Southern Oscillation (ENSO) phase and wet/dry seasons at Darwin. The novel facet of our analysis is that we break aggregate cloud radiative effects down by cloud type across the diurnal cycle. The Nauru cloud populations and subsequently the surface radiation budget are strongly impacted by ENSO variability whereas the cloud populations over Manus only shift slightly in response to changes in ENSO phase. The Darwin site exhibits large seasonal monsoon related variations. We show that while deeper convective clouds have a strong conditional influence on the radiation reaching the surface, their limited frequency reduces their aggregate radiative impact. The largest source of shortwave cloud radiative effects at all three sites comes from low clouds. We use the observations to demonstrate that potential model biases in the amplitude of the diurnal cycle and mean cloud frequency would lead to larger errors in the surface energy budget compared to biases in the timing of the diurnal cycle of cloud frequency. Our results provide solid benchmarks to evaluate model simulations of cloud radiative effects in the tropics.

Comparison and evaluation of gridded radiation products across northern Eurasia

International Nuclear Information System (INIS)

Troy, T J; Wood, E F

2009-01-01

Northern Eurasia is a region experiencing documented changes in temperature and large-scale streamflow, yet little attention has been focused on the large-scale energy budgets over the region. We compare station data and gridded radiation products from reanalysis and remote sensing to evaluate the radiative fluxes across northern Eurasia. On annual timescales, we find that the downward shortwave radiation products, with the exception of those of the NCEP/NCAR reanalysis, compare well with long-term station observations, but that this agreement breaks down with smaller timescales and for downward longwave and upward shortwave and longwave radiation. Of the six gridded products, the Surface Radiation Budget data set performs the best as compared to observations. Differences in radiative fluxes are on the order of 15-20 W m -2 on seasonal timescales, averaged across the region, with larger variations spatially and at smaller timescales. The resulting uncertainty in net radiation has implications for climate and hydrologic analyses that seek to understand changes in northern Eurasia climate and its hydrologic cycle.

BUDGET PLANNING IN FINANCIAL MANAGEMENT

Directory of Open Access Journals (Sweden)

Nataliya Melnichuk

2015-11-01

Full Text Available The purpose of the paper is to determine the nature, targets, functions, principles and methods of budget planning and development of classifications due to its types. The essence of budget planning presented by various authors, is own interpretation (the process of developing a plan of formation, distribution and redistribution of financial funds according to budget system units during the reporting period based on budgetary purposes and targets defined by socio-economic development strategy is proposed. Methodology. The following methods such as cognition, induction, deduction, analysis and synthesis have been used in the process of survey. Results of the survey proves that budget planning plays an essential role in the financial management. On condition business environment changing even the best management system can become obsolete. The immediate reaction to the new trends in the financial system as a whole, in the industry is possible with budget planning as well. It also allows to make appropriate adjustments to the plans. Adjustment of long-term, medium-term and short-term plans makes it possible, without changing goals, to change ways of their achievement and thus to raise the level of efficiency of budget funds formation and use. It is necessary to revise the whole system plans, including their mission and goals in the case of global changes in the external and internal environment. Practical implications. The proposed approach to the classification of budget planning types allows to cope with the shortcomings of modern planning in the public sector (the development of the targets according to the state budget expenditures in Ukraine remains a formality and it rarely complies with realities. Value/originality is specified in the proposed interpretation which differs from existing ones that provides clarification of budget planning purpose in financial management; classification of budget planning principles, which differs from previous

Scientific and theoretical principles of personnel costs’ budgeting

Directory of Open Access Journals (Sweden)

O.P. Gutsal

2015-06-01

Full Text Available The object of this article is to determine the main purpose of company’s budgeting, to study its functions in terms of personnel management, to identify the main advantages and disadvantages of budgeting and to determine the stages of realization budgeting in the company. There have been considered the purpose and aim of budgeting. The main functions of budgeting, which include such ones as: planning, forecasting, information and analysis function, motivational, coordinative, control and involvement function have been identified (determined. In terms of defined functions of budgeting their essence in budgeting personnel costs has been outlined. The main advantages and disadvantages of budgeting have been found. There has been determined the implementing and realization company’s budgeting. The process of budgeting is realized according to the following consecutive stages: preparatory and analytical stage; definition of budget constraints; drafting up the budget; discussion and adjustment of budget indicators; adoption of budget; analysis and control of the budget. There also has been considered budget organization structure which includes budget committee, budget planning and analysis department, financial responsibility center.

THE BUDGETING PROCESS IN ROMANIA

Directory of Open Access Journals (Sweden)

TURCIN MARIUS CATALIN

2015-08-01

Full Text Available This paper presents the stages of the budgeting process in Romania and the institutions involved in its carry out, having regard to the recent legislative amendments in the field. The study describes the importance of some state institutions in achieving the economic and social policy objectives. According to practice, the institution specializing in drafting the budget bill is the Government, who submits the budget bill annually to the Parliament for adopting the national budget, accompanied by the explanatory statement, annexes and interpretative calculations. The preparatory works are fulfilled by the Ministry of Public Finance and in parallel, by the ministries, authorities, local administrations or other public institutions to prepare their own drafts budget.

Fiscal Year 2015 Budget

Data.gov (United States)

Montgomery County of Maryland — This dataset includes the Fiscal Year 2015 Council-approved operating budget for Montgomery County. The dataset does not include revenues and detailed agency budget...

Soft Budget Constraints in Public Hospitals.

Science.gov (United States)

Wright, Donald J

2016-05-01

A soft budget constraint arises when a government is unable to commit to not 'bailout' a public hospital if the public hospital exhausts its budget before the end of the budget period. It is shown that if the political costs of a 'bailout' are relatively small, then the public hospital exhausts the welfare-maximising budget before the end of the budget period and a 'bailout' occurs. In anticipation, the government offers a budget to the public hospital that may be greater than or less than the welfare-maximising budget. In either case, the public hospital treats 'too many' elective patients before the 'bailout' and 'too few' after. The introduction of a private hospital reduces the size of any 'bailout' and increases welfare. Copyright © 2015 John Wiley & Sons, Ltd.

Cycle-Based Budgeting Toolkit: A Primer

Science.gov (United States)

Yan, Bo

2016-01-01

At the core, budgeting is about distributing and redistributing limited financial resources for continuous improvement. Incremental budgeting is limited in achieving the goal due to lack of connection between outcomes and budget decisions. Zero-based budgeting fills the gap, but is cumbersome to implement, especially for large urban school…

Optical and radiative properties of aerosols over Abu Dhabi in the ...

Indian Academy of Sciences (India)

Introduction. Atmospheric aerosols strongly influence the radiation budget of ... the radiative balance of the earth–atmosphere sys- tem due to ... resources modelling for photo voltaic (PV) and .... scene information (e.g., cloud and aerosol prop-.

The prevalence of Beyond Budgeting in Denmark

DEFF Research Database (Denmark)

Sandalgaard, Niels

  The annual budget has been criticised in recent years. The critics claim, among other things, that the annual budget is not suitable for today's business environment, that annual budgets stimulate dysfunctional behaviour and furthermore that the use of budgets is too costly. This paper examines...... this critique as well as the current status of the traditional annual budget in a contingency perspective by using data from a survey among the largest Danish companies. The conclusion is that only 4% of the companies claim to have abandoned the traditional, annual budget, 2% have decided or are in the process...... of doing so and 11% are considering abandoning it. These "Beyond Budgeting" companies are more critical towards the traditional budget than other companies. The study also shows that the critical attitude towards annual budgets as well as the decision of abandoning the budget cannot be associated...

7 CFR 906.33 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 906.33 Section 906.33 Agriculture Regulations... GRANDE VALLEY IN TEXAS Order Regulating Handling Expenses and Assessments § 906.33 Budget. At the... budget of income and expenditures necessary for the administration of this part. The committee shall...

The sea ice mass budget of the Arctic and its future change as simulated by coupled climate models

Energy Technology Data Exchange (ETDEWEB)

Holland, Marika M. [National Center for Atmospheric Research, Boulder, CO (United States); Serreze, Mark C.; Stroeve, Julienne [University of Colorado, National Snow and Ice Data Center, Cooperative Institute for Research in Environmental Sciences, Boulder, CO (United States)

2010-02-15

Arctic sea ice mass budgets for the twentieth century and projected changes through the twenty-first century are assessed from 14 coupled global climate models. Large inter-model scatter in contemporary mass budgets is strongly related to variations in absorbed solar radiation, due in large part to differences in the surface albedo simulation. Over the twenty-first century, all models simulate a decrease in ice volume resulting from increased annual net melt (melt minus growth), partially compensated by reduced transport to lower latitudes. Despite this general agreement, the models vary considerably regarding the magnitude of ice volume loss and the relative roles of changing melt and growth in driving it. Projected changes in sea ice mass budgets depend in part on the initial (mid twentieth century) ice conditions; models with thicker initial ice generally exhibit larger volume losses. Pointing to the importance of evolving surface albedo and cloud properties, inter-model scatter in changing net ice melt is significantly related to changes in downwelling longwave and absorbed shortwave radiation. These factors, along with the simulated mean and spatial distribution of ice thickness, contribute to a large inter-model scatter in the projected onset of seasonally ice-free conditions. (orig.)

Coastal polynyas in the southern Weddell Sea: Variability of the surface energy budget

Science.gov (United States)

Renfrew, Ian A.; King, John C.; Markus, Thorsten

2002-06-01

The surface energy budget of coastal polynyas in the southern Weddell Sea has been evaluated for the period 1992-1998 using a combination of satellite observations, meteorological data, and simple physical models. The study focuses on polynyas that habitually form off the Ronne Ice Shelf. The coastal polynya areal data are derived from an advanced multichannel polynya detection algorithm applied to passive microwave brightness temperatures. The surface sensible and latent heat fluxes are calculated via a fetch-dependent model of the convective-thermal internal boundary layer. The radiative fluxes are calculated using well-established empirical formulae and an innovative cloud model. Standard meteorological variables that are required for the flux calculations are taken from automatic weather stations and from the National Centers for Environmental Production/National Center for Atmospheric Research reanalyses. The 7 year surface energy budget shows an overall oceanic warming due to the presence of coastal polynyas. For most of the period the summertime oceanic warming, due to the absorption of shortwave radiation, is approximately in balance with the wintertime oceanic cooling. However, the anomalously large summertime polynya of 1997-1998 allowed a large oceanic warming of the region. Wintertime freezing seasons are characterized by episodes of high heat fluxes interspersed with more quiescent periods and controlled by coastal polynya dynamics. The high heat fluxes are primarily due to the sensible heat flux component, with smaller complementary latent and radiative flux components. The average freezing season area-integrated energy exchange is 3.48 × 1019 J, with contributions of 63, 22, and 15% from the sensible, latent, and radiative components, respectively. The average melting season area-integrated energy exchange is -5.31 × 1019 J, almost entirely due to the radiative component. There is considerable interannual variability in the surface energy budget

7 CFR 1744.64 - Budget adjustment.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Budget adjustment. 1744.64 Section 1744.64... Disbursement of Funds § 1744.64 Budget adjustment. (a) If more funds are required than are available in a budget account, the borrower may request RUS's approval of a budget adjustment to use funds from another...

Motion and shape change when using an endorectal balloon during prostate radiation therapy

International Nuclear Information System (INIS)

Court, Laurence E.; D'Amico, Anthony V.; Kadam, Dnyanesh; Cormack, Robert

2006-01-01

Purpose: To investigate motion and shape change when using an endorectal balloon (ERB) in patients receiving radiotherapy for prostate cancer. Methods: In nine patients treated for prostate cancer using an ERB, the anterior wall of the ERB was contoured on right lateral images taken immediately before irradiation, and on left lateral images taken immediately after irradiation. Changes in the contours were used to calculate inter-fraction shape change and inter-imaging motion and shape change. Inter-imaging motion describes changes that occur after the right lateral image is taken that are seen in the left lateral image. Results: Eighty-six percent of all inter-imaging shifts of the anterior wall of the ERB were in the posterior direction (mean: 1.8 mm, 1 SD: 1.8 mm, maximum posterior shift: 2.8-7.2 mm). The inter-fraction shape change (1 SD) of the anterior wall was equivalent to a change in the angle of the balloon of 2.5-5.7 deg., with a range of 8-20 deg., depending on the patient. Inter-imaging shape changes were similar in size. Conclusions: The inter-imaging motion and shape changes may be explained by the patient relaxing some time after insertion of the ERB, indicating that it could be reduced by a waiting period after insertion before irradiation. Development of image-guided localization strategies should consider intra-fraction motion and also inter- and intra-fraction shape change

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.

7 CFR 956.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 956.41 Section 956.41 Agriculture Regulations... OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Expenses and Assessments § 956.41 Budget. Prior to each fiscal period and as may be necessary thereafter, the committee shall prepare an estimated budget of...

7 CFR 945.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 945.41 Section 945.41 Agriculture Regulations... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Budget, Expenses and Assessments § 945.41 Budget. At the beginning of each fiscal period, and as may be necessary thereafter, the...

7 CFR 958.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 958.41 Section 958.41 Agriculture Regulations... Budget. Prior to each fiscal period, and as may be necessary thereafter the committee shall prepare a budget of estimated income and expenditures necessary for the administration of this part. The committee...

7 CFR 966.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 966.41 Section 966.41 Agriculture Regulations... Handling Expenses and Assessments § 966.41 Budget. At the beginning of each fiscal period and as may be necessary thereafter, the committee shall prepare an estimated budget of income and expenditures necessary...

7 CFR 948.76 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 948.76 Section 948.76 Agriculture Regulations... Regulating Handling Expenses and Assessments § 948.76 Budget. As soon as practicable after the beginning of... budget of income and expenditures necessary for its administration of this part. Each area committee may...

7 CFR 959.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 959.41 Section 959.41 Agriculture Regulations... Handling Expenses and Assessments § 959.41 Budget. As soon as practicable after the beginning of each fiscal period and as may be necessary thereafter, the committee shall prepare an estimated budget of...

Motivation in Beyond Budgeting: A Motivational Paradox?

DEFF Research Database (Denmark)

Sandalgaard, Niels; Bukh, Per Nikolaj

In this paper we discuss the role of motivation in relation to budgeting and we analyse how the Beyond Budgeting model functions compared with traditional budgeting. In the paper we focus on budget related motivation (and motivation in general) and conclude that the Beyond Budgeting model...

The Influence of Anthropogenic Greenhouse Gases and Aerosols on the Surface Heat and Moisture Budgets.

Science.gov (United States)

Ramaswamy, V.; Freidenreich, S.; Ginoux, P. A.; Ming, Y.; Paynter, D.; Persad, G.; Schwarzkopf, M. D.

2017-12-01

Emissions of greenhouse gases and aerosols alter atmospheric composition and `force' major perturbations in the radiative fluxes at the top-of-the-atmosphere and surface. In this paper, we discuss the radiative changes caused by anthropogenic greenhouse gases and aerosols at the surface, and its importance in the context of effects on the global hydrologic cycle. An important characteristic of imbalances forced by radiative species is the tendency for responses to occur in the non-radiative components, in order for the surface energy and moisture budgets to re-establish equilibrium. Using the NOAA/ GFDL global climate models used in CMIP3 and CMIP5, and to be used in CMIP6, we investigate how the surface energy balance has evolved with time under the action of the emissions, and the manner of changes in the surface radiative, sensible and latent heat components. We diagnose the relative importance of the forcings on the global and continental scales, the differing mechanisms due to greenhouse gases and aerosols on surface heat and moisture budgets, and the relative roles of the atmospheric constituents on precipitation and evaporation. Scattering and absorbing properties of aerosols can have contrasting effects on precipitation, with the aerosol indirect effect presenting another complication owing to the uncertainty in its magnitude. We compare the modeled surface flux changes against observations made from multiple platforms over the 20th and the early period of the 21st centuries, and asses the models' strengths and weaknesses. We also explore the consequences for the surface balance and precipitation in the 21st century under various emission scenarios.

Simulations of the effect of intensive biomass burning in July 2015 on Arctic radiative budget

Science.gov (United States)

Markowicz, K. M.; Lisok, J.; Xian, P.

2017-12-01

The impact of biomass burning (BB) on aerosol optical properties and radiative budget in the polar region following an intense boreal fire event in North America in July 2015 is explored in this paper. Presented data are obtained from the Navy Aerosol Analysis and Prediction System (NAAPS) reanalysis and the Fu-Liou radiative transfer model. NAAPS provides particle concentrations and aerosol optical depth (AOD) at 1° x 1° spatial and 6-hourly temporal resolution, its AOD and vertical profiles were validated with field measurements for this event. Direct aerosol radiative forcings (ARF) at the surface, the top of the atmosphere (TOA) and within the atmosphere are calculated for clear-sky and all-sky conditions, with the surface albedo and cloud properties constrained by satellite retrievals. The mean ARFs at the surface, the TOA, and within the atmosphere averaged for the north pole region (latitudes north of 75.5N) and the study period (July 5-15, 2015) are -13.1 ± 2.7, 0.3 ± 2.1, and 13.4 ± 2.7 W/m2 for clear-sky and -7.3 ± 1.8, 5.0 ± 2.6, and 12.3 ± 1.6 W/m2 for all-sky conditions respectively. Local ARFs can be a several times larger e.g. the clear-sky surface and TOA ARF reach over Alaska -85 and -30 W/m2 and over Svalbard -41 and -20 W/m2 respectively. The ARF is found negative at the surface (almost zero over high albedo region though) with the maximum forcing over the BB source region, and weaker forcing under all-sky conditions compared to the clear-sky conditions. Unlike the ARFs at the surface and within the atmosphere, which have consistent forcing signs all over the polar region, the ARF at the TOA changes signs from negative (cooling) over the source region (Alaska) to positive (heating) over bright surfaces (e.g., Greenland) because of strong surface albedo effect. NAAPS simulations also show that the transported BB particle over the Arctic are in the low-to-middle troposphere and above low-level clouds, resulting in little difference in ARFs

NASA/GEWEX Surface Radiation Budget: Integrated Data Product With Reprocessed Radiance, Cloud, and Meteorology Inputs, and New Surface Albedo Treatment

Science.gov (United States)

Cox, Stephen J.; Stackhouse, Paul W., Jr.; Gupta, Shashi K.; Mikovitz, J. Colleen; Zhang, Taiping

2016-01-01

The NASA/GEWEX Surface Radiation Budget (SRB) project produces shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. Spatial resolution is 1 degree. The current release 3.0 (available at gewex-srb.larc.nasa.gov) uses the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This product is subsampled to 30 km. ISCCP is currently recalibrating and recomputing their entire data series, to be released as the H product, at 10km resolution. The ninefold increase in pixel number will allow SRB a higher resolution gridded product (e.g. 0.5 degree), as well as the production of pixel-level fluxes. In addition to the input data improvements, several important algorithm improvements have been made. Most notable has been the adaptation of Angular Distribution Models (ADMs) from CERES to improve the initial calculation of shortwave TOA fluxes, from which the surface flux calculations follow. Other key input improvements include a detailed aerosol history using the Max Planck Institut Aerosol Climatology (MAC), temperature and moisture profiles from HIRS, and new topography, surface type, and snow/ice. Here we present results for the improved GEWEX Shortwave and Longwave algorithm (GSW and GLW) with new ISCCP data, the various other improved input data sets and the incorporation of many additional internal SRB model improvements. As of the time of abstract submission, results from 2007 have been produced with ISCCP H availability the limiting factor. More SRB data will be produced as ISCCP reprocessing continues. The SRB data produced will be released as part of the Release 4.0 Integrated Product, recognizing the interdependence of the radiative fluxes with other GEWEX products providing estimates of the Earth's global water and energy cycle (I.e., ISCCP, SeaFlux, LandFlux, NVAP, etc.).

BUDGET AND PUBLIC DEBT

Directory of Open Access Journals (Sweden)

Morar Ioan Dan

2014-12-01

Full Text Available The issue of public budgeting is an important issue for public policy of the state, for the simple reason that no money from the state budget can not promote public policy. Budgetary policy is official government Doctrine vision mirror and also represents a starting point for other public policies, which in turn are financed by the public budget. Fiscal policy instruments at its disposal handles the public sector in its structure, and the private sector. Tools such as grant, budgetary allocation, tax, welfare under various forms, direct investments and not least the state aid is used by the state through their budgetary policies to directly and indirectly infuence sector, and the private. Fiscal policies can be grouped according to the structure of the public sector in these components, namely fiscal policy, budgeting and resource allocation policies for financing the budget deficit. An important issue is the financing of the budget deficit budgetary policies. There are two funding possibilities, namely, the higher taxes or more axles site and enter the second call to public loans. Both options involve extra effort from taxpayers in the current fiscal year when they pay higher taxes or a future period when public loans will be repaid. We know that by virtue of "fiscal pact" structural deficits of the member countries of the EU are limited by the European Commission, according to the macro structural stability and budget of each Member State. This problem tempers to some extent the governments of the Member States budgetary appetite, but does not solve the problem of chronic budget deficits. Another issue addressed in this paper is related to the public debt, the absolute amount of its relative level of public datoriri, about the size of GDP, public debt financing and its repayment sources. Sources of public debt issuance and monetary impact on the budget and monetary stability are variables that must underpin the justification of budgetary

24 CFR 968.225 - Budget revisions.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Budget revisions. 968.225 Section... Fewer Than 250 Units) § 968.225 Budget revisions. (a) A PHA shall not incur any modernization cost in excess of the total HUD-approved CIAP budget. A PHA shall submit a budget revision, in a form prescribed...

FLEXIBLE BUDGET OF SPORT COMPETITIONS

Directory of Open Access Journals (Sweden)

Dragan Vukasović

2009-11-01

Full Text Available Manager of sport competition has right to decide and also to take responsibility for costs, income and financial results. From economic point of wiev flexible budget and planning cost calculations is top management base for analyzing success level of sport competition. Flexible budget is made before sport competition with few output level, where one is always from static plan-master plan. At the end of competition when we have results, we make report of plan executing and we also analyzing plan variances. Results of comparation between achieved and planning level of static budget can be acceptable if achieved level is approximate to budget level or if we analyzing results from gross or net income. Flexible budget become very important in case of world eco- nomic crises

The impact of cloud inhomogeneities on the Earth radiation budget: the 14 October 1989 I.C.E. convective cloud case study

Directory of Open Access Journals (Sweden)

F. Parol

1994-01-01

Full Text Available Through their multiple interactions with radiation, clouds have an important impact on the climate. Nonetheless, the simulation of clouds in climate models is still coarse. The present evolution of modeling tends to a more realistic representation of the liquid water content; thus the problem of its subgrid scale distribution is crucial. For a convective cloud field observed during ICE 89, Landsat TM data (resolution: 30m have been analyzed in order to quantify the respective influences of both the horizontal distribution of liquid water content and cloud shape on the Earth radiation budget. The cloud field was found to be rather well-represented by a stochastic distribution of hemi-ellipsoidal clouds whose horizontal aspect ratio is close to 2 and whose vertical aspect ratio decreases as the cloud cell area increases. For that particular cloud field, neglecting the influence of the cloud shape leads to an over-estimate of the outgoing longwave flux; in the shortwave, it leads to an over-estimate of the reflected flux for high solar elevations but strongly depends on cloud cell orientations for low elevations. On the other hand, neglecting the influence of cloud size distribution leads to systematic over-estimate of their impact on the shortwave radiation whereas the effect is close to zero in the thermal range. The overall effect of the heterogeneities is estimated to be of the order of 10 W m-2 for the conditions of that Landsat picture (solar zenith angle 65°, cloud cover 70%; it might reach 40 W m-2 for an overhead sun and overcast cloud conditions.

The impact of cloud inhomogeneities on the Earth radiation budget: the 14 October 1989 I.C.E. convective cloud case study

Directory of Open Access Journals (Sweden)

F. Parol

Full Text Available Through their multiple interactions with radiation, clouds have an important impact on the climate. Nonetheless, the simulation of clouds in climate models is still coarse. The present evolution of modeling tends to a more realistic representation of the liquid water content; thus the problem of its subgrid scale distribution is crucial. For a convective cloud field observed during ICE 89, Landsat TM data (resolution: 30m have been analyzed in order to quantify the respective influences of both the horizontal distribution of liquid water content and cloud shape on the Earth radiation budget. The cloud field was found to be rather well-represented by a stochastic distribution of hemi-ellipsoidal clouds whose horizontal aspect ratio is close to 2 and whose vertical aspect ratio decreases as the cloud cell area increases. For that particular cloud field, neglecting the influence of the cloud shape leads to an over-estimate of the outgoing longwave flux; in the shortwave, it leads to an over-estimate of the reflected flux for high solar elevations but strongly depends on cloud cell orientations for low elevations. On the other hand, neglecting the influence of cloud size distribution leads to systematic over-estimate of their impact on the shortwave radiation whereas the effect is close to zero in the thermal range. The overall effect of the heterogeneities is estimated to be of the order of 10 W m^-2 for the conditions of that Landsat picture (solar zenith angle 65°, cloud cover 70%; it might reach 40 W m^-2 for an overhead sun and overcast cloud conditions.

25 CFR 122.7 - Budget.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Budget. 122.7 Section 122.7 Indians BUREAU OF INDIAN... § 122.7 Budget. (a) By August 1 of each year, the Osage Tribal Education Committee will submit a proposed budget to the Assistant Secretary or to his/her designated representative for formal approval...

7 CFR 955.41 - Budget.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Budget. 955.41 Section 955.41 Agriculture Regulations... Assessments § 955.41 Budget. At least 60 days prior to each fiscal period, or such other date as may be... budget of income and expenditures necessary for the administration of this part. The committee may...

Beyond Zero Based Budgeting.

Science.gov (United States)

Ogden, Daniel M., Jr.

1978-01-01

Suggests that the most practical budgeting system for most managers is a formalized combination of incremental and zero-based analysis because little can be learned about most programs from an annual zero-based budget. (Author/IRT)

Zero-base budgeting and the library.

Science.gov (United States)

Sargent, C W

1978-01-01

This paper describes the application of zero-base budgeting to libraries and the procedures involved in setting up this type of budget. It describes the "decision packages" necessary when this systmem is employed, as well as how to rank the packages and the problems which are related to the process. Zero-base budgeting involves the entire staff of a library, and the incentive engendered makes for a better and more realistic budget. The paper concludes with the problems which one might encounter in zero-base budgeting and the major benefits of the system. PMID:626795

FY 1997 congressional budget request: Budget highlights

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

This is an overview of the 1997 budget request for the US DOE. The topics of the overview include a policy overview, the budget by business line, business lines by organization, crosswalk from business line to appropriation, summary by appropriation, energy supply research and development, uranium supply and enrichment activities, uranium enrichment decontamination and decommissioning fund, general science and research, weapons activities, defense environmental restoration and waste management, defense nuclear waste disposal, departmental administration, Office of the Inspector General, power marketing administrations, Federal Energy Regulatory commission, nuclear waste disposal fund, fossil energy research and development, naval petroleum and oil shale reserves, energy conservation, economic regulation, strategic petroleum reserve, energy information administration, clean coal technology and a Department of Energy Field Facilities map.

Building information modeling in budgeting

Directory of Open Access Journals (Sweden)

Strnad, Michal

2017-12-01

Full Text Available Construction activity is one of the financially demanding and ever-changing locations of implementation. The basic idea of the budget is to determine all the possible costs that will arise during construction work. The budget must be a transparent and effective way of communication in the context of supplier-customer relationships. For this reason it is essential to give the budget the structure that is now represented by the price system. It is important to adhere to the principles of budgeting and technical standards. It is necessary to have good documentation for budgeting such as project documentation and much more. However, the construction product range is one of the most extensive, the product group can be changed several times in the investment phase not only materially but also cost-effectively because of the longest production cycle in the construction industry.

Workshop Report on Managing Solar Radiation

Science.gov (United States)

Lane, Lee (Compiler); Caldeira, Ken (Compiler); Chatfield, Robert (Compiler); Langhoff, Stephanie (Compiler)

2007-01-01

The basic concept of managing Earth's radiation budget is to reduce the amount of incoming solar radiation absorbed by the Earth so as to counterbalance the heating of the Earth that would otherwise result from the accumulation of greenhouse gases. The workshop did not seek to decide whether or under what circumstances solar radiation management should be deployed or which strategies or technologies might be best, if it were deployed. Rather, the workshop focused on defining what kinds of information might be most valuable in allowing policy makers more knowledgeably to address the various options for solar radiation management.

Verification of uncertainty budgets

DEFF Research Database (Denmark)

Heydorn, Kaj; Madsen, B.S.

2005-01-01

, and therefore it is essential that the applicability of the overall uncertainty budget to actual measurement results be verified on the basis of current experimental data. This should be carried out by replicate analysis of samples taken in accordance with the definition of the measurand, but representing...... the full range of matrices and concentrations for which the budget is assumed to be valid. In this way the assumptions made in the uncertainty budget can be experimentally verified, both as regards sources of variability that are assumed negligible, and dominant uncertainty components. Agreement between...

The utility of the historical record in assessing future carbon budgets

Science.gov (United States)

Millar, R.; Friedlingstein, P.; Allen, M. R.

2017-12-01

It has long been known that the cumulative emissions of carbon dioxide (CO2) is the most physically relevant determiner of long-lived anthropogenic climate change, with an approximately linear relationship between CO2-induced global mean surface warming and cumulative emissions. The historical observational record offers a way to constrain the relationship between cumulative carbon dioxide emission and global mean warming using observations to date. Here we show that simple regression analysis indicates that the 1.5°C carbon budget would be exhausted after nearly three decades of current emissions, substantially in excess of many estimates from Earth System Models. However, there are many reasons to be cautious about carbon budget assessments from the historical record alone. Accounting for the uncertainty in non-CO2 radiative forcing using a simple climate model and a standard optimal fingerprinting detection attribution technique gives substantial uncertainty in the contribution of CO2 warming to date, and hence the transient climate response to cumulative emissions. Additionally, the existing balance between CO2 and non-CO2 forcing may change in the future under ambitious mitigation scenarios as non-CO2 emissions become more (or less) important to global mean temperature changes. Natural unforced variability can also have a substantial impact on estimates of remaining carbon budgets. By examining all warmings of a given magnitude in both the historical record and past and future ESM simulations we quantify the impact unforced climate variability may have on estimates of remaining carbon budgets, derived as a function of estimated non-CO2 warming and future emission scenario. In summary, whilst the historical record can act as a useful test of climate models, uncertainties in the response to future cumulative emissions remain large and extrapolations of future carbon budgets from the historical record alone should be treated with caution.

Rapid Budget Analysis of the Agricultural Sector for the General Budget Support Annual Review 2010/11

OpenAIRE

Francken, Nathalie; Zorya, S

2010-01-01

The main objective of the budget analysis chapter is to provide an overall assessment of how well the approved budget allocations in 2010-11 align with the strategic objectives and with sector strategic priorities of the Second National Strategy for Growth and Reduction of Poverty (known by its Kiswahili acronym, MKUKUTA II). It also assesses the consistency of the actual spending and approved budget in 2009-10. In evaluating the alignment of the budget and MKUKUTA's strategic objectives and ...

Innovative Concepts of Budgeting in the Enterprises

Directory of Open Access Journals (Sweden)

Adam Bąk

2009-03-01

Full Text Available The article presents the current concepts of budgeting with the special focus on innovative budgets. It includes the evolution of the budgeting concept starting from the traditional one which was applied in the second half of the 20th Century and assumed the budget as the main tool for the achievement of company’s goals. The next presented method is Better Budgeting. It arouse at the nineties as the resposne for the critics of the traditional method which was accused for the fixed assumptions which were no longer matching with the fast changing competitive environment. This method assumed the high level of budget preparation as he opposite to the detailed level as well as shorter planning period. The Beyond Budgeting was the most radical method and eliminated budget as the tool supporting the management; the concept has been used from the nineties until today, by more than seventy multinational companies from beyond budgeting round table. However, Beyond Budgeting was also criticised for not being applied in the industrial sector and too theoretical approach. Therefore, Ronald Gleicha from European Business School, established a working group, which icludes the scientists and managers, in order to create by mid of 2009, the new and opitimal method, which is called Modern Budgeting.

Budget Elements of Economic Security: Specifics of Classification

Directory of Open Access Journals (Sweden)

О. S.

2017-02-01

Full Text Available Theoretical aspects of economic security in conjunction with budget components such as “budget interests” and “budget necessities” are analyzed. Key positions of the categories “budget interests” and “budget necessities” in the theory of economic security in the budgetary area are substantiated given their priority role in setting up its implementation strategy. The category “budget interests” is defined as the system of budget necessities of the interest holders, implemented through budget activities of entities and aimed at seeking benefits through the budget, in order to guarantee functioning and development of the society, the state, legal entities and physical persons. “Budget necessities” are defined as the need in budget funds to achieve and sustain, at a certain level, life activities of individuals, social groups, society, state and legal entities. Classification of budget interests by various criteria is made in the context of their impact on the economic security of the state. It is demonstrated that the four-tier classification of the budget interests by interest holder is essential to guaranteeing economic security in the budgetary area: budget interests of the state: the interests held by central and local power offices; budget interests of legal entities: the interests of profit and non-profit (public, budgetary, party and other organizations; budget interests of individuals: basic necessities of individuals, met by budget transfers, which stand out of the array of public necessities by their individual character.

Polity age and political budget cycles

DEFF Research Database (Denmark)

Aaskoven, Lasse

2018-01-01

Incumbent incentive for competence-signaling and lack of voter information are generally thought to be factors that increase the prevalence of political budget cycles. These mechanisms should be more prevalent in new political units. Since the creation of new political units is rarely exogenous......-experimental to study whether political budget cycles are larger in new political units. Contrary to theoretical predictions, political budget cycles seem to be of a smaller scale in the new municipalities, but only regarding budget cycles in budgetary overruns. The findings are of wider interest for discussions about...... the mechanisms behind context-conditional political budget cycles....

Budgeting in Nonprofit Organizations.

Science.gov (United States)

Kelly, Lauren

1985-01-01

This description of the role of budgets in nonprofit organizations uses libraries as an example. Four types of budgets--legislative, management, cash, and capital--are critiqued in terms of cost effectiveness, implementation, and facilitation of organizational control and objectives. (CLB)

Biological effects of radiation: The induction of malignant transformation and programmed cell death

International Nuclear Information System (INIS)

Servomaa, K.

1991-04-01

In the Chernobyl explosions and fire, powderized nuclear fuel was released from the reactor core, causing an unexpected fallout. X-ray analysis and scanning electron microscopy showed that the isolated single particles were essentially pure uranium. These uranium aerosols contained all of the nonvolatile fission products, including the b-emitters, 95 Zr, 103 Ru, 106 Ru, 141 Ce, and 144 Ce. The hot particles are extremely effective in inducing malignant transformation in mouse fibroblast cells in vitro. The major factor responsible for this effect is focus promotion caused by a wound-mediated permanent increase in cell proliferation (mitogenesis associated with mutagenesis). Transformed foci were analysed for the activation of c-abl, c-erb-A, c-erb-B, c-fms, c-fos, c-myb, c-myc, c-Ha-ras, c-Ki-ras, c-sis, and c-raf oncogenes at the transcriptional level. The pattern of oncogene activation was found to vary from focus to focus. Long interspersed repeated DNA (L1 or LINE makes up a class of mobile genetic elements which can amplify in the cell genome by retroposition. This element is spontaneously transcriptionally activated at a critical population density and later amplified in rat chloroleukaemia cells. UV light and ionizing radiation induce this activation prematurely, and the activation is followed by programmed cell death (apoptosis) in a sequence of events identical to that seen in LIRn activation occurring spontaneously

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.

Political Budget Cycles

DEFF Research Database (Denmark)

Aaskoven, Lasse; Lassen, David Dreyer

2017-01-01

The political budget cycle—how elections affect government fiscal policy—is one of the most studied subjects in political economy and political science. The key theoretical question is whether incumbent governments can time or structure public finances in ways that improve their chances of reelec......The political budget cycle—how elections affect government fiscal policy—is one of the most studied subjects in political economy and political science. The key theoretical question is whether incumbent governments can time or structure public finances in ways that improve their chances...... on political budget cycles have recently focused on conditions under which such cycles are likely to obtain. Much recent research focuses on subnational settings, allowing comparisons of governments in similar institutional environments, and a consensus on the presences of cycles in public finances...

The effect of clouds on the earth's solar and infrared radiation budgets

Science.gov (United States)

Herman, G. F.; Wu, M.-L. C.; Johnson, W. T.

1980-01-01

The effect of global cloudiness on the solar and infrared components of the earth's radiation balance is studied in general circulation model experiments. A wintertime simulation is conducted in which the cloud radiative transfer calculations use realistic cloud optical properties and are fully interactive with model-generated cloudiness. This simulation is compared to others in which the clouds are alternatively non-interactive with respect to the solar or thermal radiation calculations. Other cloud processes (formation, latent heat release, precipitation, vertical mixing) were accurately simulated in these experiments. It is concluded that on a global basis clouds increase the global radiation balance by 40 W/sq m by absorbing longwave radiation, but decrease it by 56 W/sq m by reflecting solar radiation to space. The net cloud effect is therefore a reduction of the radiation balance by 16 W/sq m, and is dominated by the cloud albedo effect. Changes in cloud frequency and distribution and in atmospheric and land temperatures are also reported for the control and for the non-interactive simulations. In general, removal of the clouds' infrared absorption cools the atmosphere and causes additional cloudiness to occur, while removal of the clouds' solar radiative properties warms the atmosphere and causes fewer clouds to form. It is suggested that layered clouds and convective clouds over water enter the climate system as positive feedback components, while convective clouds over land enter as negative components.

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

STATE BUDGET AND BUDGETARY PROCEDURES IN ROMANIA

Directory of Open Access Journals (Sweden)

POPA George Dorel

2013-12-01

Full Text Available In Romania, the budget process is governed by the Constitution and the Law of Public Finance no. 500/2002, act that includes the elaboration of the draft budget, approving the state budget, budget execution and budget control. All these activities are carried out in a legal way and administrative- institutional way, presenting features from country to country. The budget shows many traits in common: it is a decision process, because its essence consists in allocating budgetary resources for public goods such as education, health, national defence and so on. On the other hand is an essentially political process because allocation decisions budgetary resources are determined by the political groups, the mechanism of representation and voting, is a complex process with many participants (schools, hospitals, ministries, etc.. The budgetary process is a cyclic process, as it follows a well-defined calendar as a consequence of yearly and advertising budget. In conclusion, the budget process is a set of consecutive stages of development, approval, execution, control and reporting of the state budget, which ends with the approval of its execution account.

Effects of soil tillage on the energy budget of soybean (Glycine max (L.) Merr.)

International Nuclear Information System (INIS)

Casa, R.; Cascio, B. lo

1997-01-01

The different terms of the energy budget were measured by the Bowen ratio method on soybean (Glycine max (L.) Merr.) grown on a conventional tillage and a direct drilling system. The differences found in the energy budgets varied according to the degree of fractional ground cover and of soil water availability. Soil heat flux was greater for the direct drilling treatment, although soil heating was slower as compared to the conventional tillage. Comparisons for well watered and dry conditions revealed that the conventional tillage system used as latent heat a fraction of net radiation greater than the direct drilling treatment only in well watered conditions. In dry conditions the differences in latent heat fluxes and canopy resistances between the two tillage systems were smaller [it

Defense.gov Special Report: 2013 Fiscal Budget

Science.gov (United States)

Department of Defense Submit Search 2013 Fiscal Budget Published Feb. 13, 2012 Top Stories Budget Proposal Slows Cost Growth, Pentagon Leaders Say The Defense Department's proposed fiscal 2013 budget request Department officials told a Senate panel. Story Officials Seek Construction Funds, More BRAC in Budget

Colorado Children's Budget 2013

Science.gov (United States)

Buck, Beverly; Baker, Robin

2013-01-01

The "Colorado Children's Budget" presents and analyzes investments and spending trends during the past five state fiscal years on services that benefit children. The "Children's Budget" focuses mainly on state investment and spending, with some analysis of federal investments and spending to provide broader context of state…

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.

[The department budget, in the context of the hospital global budget. Initial results in general medicine].

Science.gov (United States)

Besançon, F

1984-02-23

In a general hospital (Hôtel-Dieu, in the center of Paris), run with a global budget, budgets determined for each unit were introduced as an experiment in 1980. Physicians were in charge of certain expenses, mainly: linen, drugs, transportation of patients to and from other hospitals within Paris, and blood fractions. The whole does not exceed 4% of the turnover (FF 20 millions in 1980) of a 67 bed internal medicine unit. Other accounts deal with the stays, admissions, prescriptions of technical acts, laboratory analyses, and X-rays. In 1980, expenses were 11% more than budgeted, but the increase in stays and particularly in admissions was significantly greater. The resulting savings were 8.8% and 18.7% for stays and admissions respectively. Psychic reactions were variable. The subsequent budgets followed the fluctuations of recorded expenses, which were fairly important in both directions. The unit budget may be an advance or a regression, in a restrictive and past-perpetuating context. The coherence between the unit budget and the global hospital budget is questionable. Physicians were willing to take part in accounting and saving. They have good reason for not enlarging their financial responsibilities. Conversely, they may give more attention to diseases of public opinion.

Probabilistic estimates of 1.5-degree carbon budgets based on uncertainty in transient climate response and aerosol forcing

Science.gov (United States)

Partanen, A. I.; Mengis, N.; Jalbert, J.; Matthews, D.

2017-12-01

Nations agreed to limit the increase in global mean surface temperature relative to the preindustrial era below 2 degrees Celsius and pursue efforts to a more ambitious goal of 1.5 degrees Celsius. To achieve these goals, it is necessary to assess the amount of cumulative carbon emissions compatible with these temperature targets, i.e. so called carbon budgets. In this work, we use the intermediate complexity University of Victoria Earth System Climate Model (UVic ESCM) to assess how uncertainty in aerosol forcing and transient climate response transfers to uncertainty in future carbon budgets for burning fossil fuels. We create a perturbed parameter ensemble of model simulations by scaling aerosol forcing and transient climate response, and assess the likelihood of each simulation by comparing the simulated historical cumulative carbon emissions, CO2 concentration and radiative balance to observations. By weighting the results of each simulation with the likelihood of the simulation, the preliminary results give a carbon budget of 48 Pg C to reach 1.5 degree Celsius temperature increase. The small weighted mean is due to large fraction of simulations with strong aerosol forcing and transient climate response giving negative carbon budgets for this time period. The probability of the carbon budget being over 100 Pg C was 38% and 23% for over 200 Pg carbon budget. The carbon budgets after temperature stabilization at 1.5 degrees are even smaller with a weighted mean of -100 Pg C until the year 2200. The main reason for the negative carbon budgets after temperature stabilization is an assumed strong decrease in aerosol forcing in the 21st century. Conversely, simulations with weak aerosol forcing and transient climate response give positive carbon budgets. Our results highlight both the importance of reducing uncertainty in aerosol forcing and transient climate response, and of taking the non-CO2 forcers into account when estimating carbon budgets.

Laboratory administration--capital budgeting.

Science.gov (United States)

Butros, F

1997-01-01

The process of capital budgeting varies among different health-care institutions. Understanding the concept of present value of money, incremental cash flow statements, and the basic budgeting techniques will enable the laboratory manager to make the rational and logical decisions that are needed in today's competitive health-care environment.

Use of Atmospheric Budget to Reduce Uncertainty in Estimated Water Availability over South Asia from Different Reanalyses

Science.gov (United States)

Sebastian, Dawn Emil; Pathak, Amey; Ghosh, Subimal

2016-07-01

Disagreements across different reanalyses over South Asia result into uncertainty in assessment of water availability, which is computed as the difference between Precipitation and Evapotranspiration (P-E). Here, we compute P-E directly from atmospheric budget with divergence of moisture flux for different reanalyses and find improved correlation with observed values of P-E, acquired from station and satellite data. We also find reduced closure terms for water cycle computed with atmospheric budget, analysed over South Asian landmass, when compared to that obtained with individual values of P and E. The P-E value derived with atmospheric budget is more consistent with energy budget, when we use top-of-atmosphere radiation for the same. For analysing water cycle, we use runoff from Global Land Data Assimilation System, and water storage from Gravity Recovery and Climate Experiment. We find improvements in agreements across different reanalyses, in terms of inter-annual cross correlation when atmospheric budget is used to estimate P-E and hence, emphasize to use the same for estimations of water availability in South Asia to reduce uncertainty. Our results on water availability with reduced uncertainty over highly populated monsoon driven South Asia will be useful for water management and agricultural decision making.

Use of Atmospheric Budget to Reduce Uncertainty in Estimated Water Availability over South Asia from Different Reanalyses.

Science.gov (United States)

Sebastian, Dawn Emil; Pathak, Amey; Ghosh, Subimal

2016-07-08

Disagreements across different reanalyses over South Asia result into uncertainty in assessment of water availability, which is computed as the difference between Precipitation and Evapotranspiration (P-E). Here, we compute P-E directly from atmospheric budget with divergence of moisture flux for different reanalyses and find improved correlation with observed values of P-E, acquired from station and satellite data. We also find reduced closure terms for water cycle computed with atmospheric budget, analysed over South Asian landmass, when compared to that obtained with individual values of P and E. The P-E value derived with atmospheric budget is more consistent with energy budget, when we use top-of-atmosphere radiation for the same. For analysing water cycle, we use runoff from Global Land Data Assimilation System, and water storage from Gravity Recovery and Climate Experiment. We find improvements in agreements across different reanalyses, in terms of inter-annual cross correlation when atmospheric budget is used to estimate P-E and hence, emphasize to use the same for estimations of water availability in South Asia to reduce uncertainty. Our results on water availability with reduced uncertainty over highly populated monsoon driven South Asia will be useful for water management and agricultural decision making.

BUDGET PLANNING IN FINANCIAL MANAGEMENT

OpenAIRE

Nataliya Melnichuk

2015-01-01

The purpose of the paper is to determine the nature, targets, functions, principles and methods of budget planning and development of classifications due to its types. The essence of budget planning presented by various authors, is own interpretation (the process of developing a plan of formation, distribution and redistribution of financial funds according to budget system units during the reporting period based on budgetary purposes and targets defined by socio-economic development strategy...

Defense.gov Special Report: 2015 Fiscal Budget

Science.gov (United States)

Department of Defense Submit Search FY 2015 Fiscal Budget News Stories Dempsey Calls for Budget Increase increase its budget, the chairman of the Joint Chiefs of Staff said. Story James: Air Force Grapples with Congress to Fund Readiness The Air Force fiscal 2015 budget request is shrinking because of Congressional

40 CFR 96.140 - State trading budgets.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false State trading budgets. 96.140 Section...) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.140 State trading budgets. The State trading budgets for annual...

Oncogenes, radiation and cancer

International Nuclear Information System (INIS)

Michelin, S.C.

1998-01-01

The discovery of the oncogenic virus and the analysis of its nucleic acid, together with the development of new biochemical technology have permitted the partial knowledge of the molecular mechanisms responsible for the cellular neoplastic transformation. This work, besides describing the discovery of the first oncogenic virus and the experiments to demonstrate the existence of the oncogenes, summarizes its activation mechanisms and its intervention in cellular metabolisms. Ionizing radiation is among the external agents that induce the neoplastic process. Its participation in the genesis of this process and the contribution of oncogenes to the cellular radioresistance are among the topics, which are referred to another topic that makes reference. At the same time as the advancement of theoretical knowledge, lines of investigation for the application of the new concepts in diagnosis, prognosis and therapeutical treatment, were developed. An example of this, is the study of the participation of the oncogen c-erbB-2 in human breast cancer and its implications on the anti tumoral therapy. (author) [es

7 CFR 3015.115 - Budget revisions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Budget revisions. 3015.115 Section 3015.115..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Programmatic Changes and Budget Revisions § 3015.115 Budget revisions. (a) Nonconstruction projects. (1) Except as provided in paragraph (a)(2) of...

Should Corrupt Countries receive Budget Support?

OpenAIRE

Kolstad, Ivar

2005-01-01

Corruption makes budget support ineffective, and sometimes counter-productive. Budget support is particularly unsuitable in partner countries where political corruption is rampant. As donors increase budget support, it is a paradox that corruption is not more of an issue in evaluations and public financial management assessment methods.

The new radiation protection ordinance and its consequences in radiation therapy

International Nuclear Information System (INIS)

Wucherer, M.; Schmidt, T.

2002-01-01

The new radiation protection ordinance (StrlSchV) entails a number of additional or changed instructions. They require that personnel exposed to radiation at work be reclassified, or that personnel not exposed to radiation at work be classified as personnel exposed to radiation at work, that local dosage measurements be taken particularly in radiation therapy, in order to insure that the radiation protection areas prevailing to date can be maintained, that generally accessible areas be examined to determine whether with persons not exposed to radiation in the course of work, in the case of their prolonged presence there, 1 mSv per year is not exceeded, that instructions be put in writing, that at regular 5-year intervals the proficiency of physicians, specialists in medical physics and MTRAs be brought up to date and, that medical positions for radiooncologists be established. The stricter requirements in radiation protection are inevitably connected with greater expenditures and higher costs. These results of the new radiation protection ordinance are in direct opposition to the financial possibilities that are being restricted through budgeting and pressure on hospitals and practices to reduce costs. (orig.) [de

Lean Mean Times--Budgeting for School Media Technology.

Science.gov (United States)

Johnson, Doug

1995-01-01

Discusses budgeting strategies for school media technology programs. Highlights include sources for school funding, school district budget information, control of the budget, how to write an effective budget, working with other community and school groups, local politics, and sidebars that discuss spreadsheets and maintenance budgets. (LRW)