bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib
Authors: Serrels Alan , Macpherson Iain R.J. , Evans T.R. Jeffry , Lee Francis Y. , Clark Edwin A. , Sansom Owen J. , Ashton Gabrielle H. , Frame Margaret C. , Brunton Valerie G. 
Published: December 2006

Abstract
Elevated levels of Src kinase expression have been found in a variety of human epithelial cancers. Most notably in colon cancer, elevated Src expression correlates with malignant potential and is also associated with metastatic disease. Dasatinib (BMS-354825) is a novel, orally active, multi-targeted kinase inhibitor that targets Src family kinases and is currently under clinical evaluation for the treatment of solid tumors. However, the effects of dasatinib on epithelial tumors are not fully understood. We show that concentrations of dasatinib that inhibit Src activity do not inhibit proliferation in 10 of 12 colon cancer cells lines. However, inhibition of integrin-dependent adhesion and migration by dasatinib correlated with inhibition of Src activity, suggesting that dasatinib may have anti-invasive or anti-metastatic activity and antiproliferative activity in epithelial tumors. Using phospho-specific antibodies, we show that inhibition of Src activity in colon cancer cell lines correlates with reduced phosphorylation of focal adhesion kinase and paxillin on specific Src-dependent phosphorylation sites. We have validated the use of phospho-specific antibodies against Src Tyr419 and paxillin Tyr118 as biomarkers of dasatinib activity in vivo. Colon carcinoma–bearing mice treated with dasatinib showed a decrease in both phospho-Src Tyr419 and phospho-paxillin Tyr118 in peripheral blood mononuclear cells, which correlated with inhibition of Src activity in the colon tumors. Thus, peripheral blood mononuclear cells may provide a useful surrogate tissue for biomarker studies with dasatinib using inhibition of Src Tyr419 and paxillin Tyr118 phosphorylation as read-outs of Src activity. [Mol Cancer Ther 2006;5(12):3014–22]
The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-κB activation through direct inhibition of IκB kinase β
Authors: Yore Mark M. , Liby Karen T. , Honda Tadashi , Gribble Gordon W. , Sporn Michael B. 
Published: December 2006

AbstractThe synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) is a multifunctional agent with potent anti-inflammatory, antiproliferative, cytoprotective, and apoptotic activities, whose molecular targets are unknown. Using both cell-free and cellular assays, we show that CDDO-Im is a direct inhibitor of IκB kinase (IKK) β and that it thereby inhibits binding of nuclear factor-κB to DNA and subsequent transcriptional activation. Pretreatment of cells with CDDO-Im prevents IκBα phosphorylation and degradation in response to tumor necrosis factor α. The kinetics of this inhibition by CDDO-Im are rapid and occur within 15 min. A biotinylated analogue of CDDO-Im showed that CDDO-Im binds to the IKK signalsome. Furthermore, we show that Cys179 on IKK is a target for CDDO-Im. This is the first report to show that this novel synthetic triterpenoid binds to and inhibits IKKβ directly. [Mol Cancer Ther 2006;5(12):3232–9]
The Effect of Potential Future Climate Change on the Marine Methane Hydrate Stability Zone
Authors: Fyke Jeremy G. , Weaver Andrew J. 
Published: December 2006

Abstract
The marine gas hydrate stability zone (GHSZ) is sensitive to temperature changes at the seafloor, which likely affected the GHSZ in the past and may do so in the future in response to anthropogenic greenhouse gas emissions. A series of climate sensitivity and potential future climate change experiments are undertaken using the University of Victoria Earth System Climate Model (UVic ESCM) with resulting seafloor temperature changes applied to a simple time-dependent methane hydrate stability model. The global GHSZ responds significantly to elevated atmospheric CO2 over time scales of 103 yr with initial decreases of the GHSZ occurring after 200 yr in shallow high-latitude seafloor areas that underlie regions of sea ice loss. The magnitude and rate of GHSZ change is dependent primarily upon the thermal diffusivity of the seafloor and the magnitude and duration of the seafloor temperature increase. Using a simple approximation of the amount of carbon stored as hydrate in the GHSZ, estimates of carbon mobilized due to hydrate dissociation are made for several potential climate change scenarios.
Some Overlooked Features of Tropical Atlantic Climate Leading to a New Niño-Like Phenomenon*
Authors: Okumura Yuko , Xie Shang-Ping 
Published: December 2006

Abstract
The Atlantic Niño, an equatorial zonal mode akin to the Pacific El Niño–Southern Oscillation (ENSO), is phase-locked to boreal summer when the equatorial easterly winds intensify and the thermocline shoals in the Gulf of Guinea. A suite of satellite and in situ observations reveals a new mode of tropical Atlantic variability that displays many characteristics of the zonal mode but instead peaks in November–December (ND). This new mode is found to be statistically independent from both the Atlantic Niño in the preceding summer and the Pacific ENSO. The origin of this ND zonal mode lies in an overlooked aspect of the seasonal cycle in the equatorial Atlantic.
In November the equatorial easterly winds intensify for the second time, increasing upwelling and lifting the thermocline in the Gulf of Guinea. An analysis of high-resolution climatological data shows that these dynamical changes induce a noticeable SST cooling in the central equatorial Atlantic. The shoaling thermocline and increased upwelling enhance the SST sensitivity to surface wind changes, reinvigorating equatorial ocean–atmosphere interaction. The resultant ocean–atmospheric anomalies are organized into patterns that give rise to positive mutual feedback as Bjerknes envisioned for the Pacific ENSO. This ND zonal mode significantly affects interannual rainfall variability in coastal Congo–Angola during its early rainy season. It tends to further evolve into a meridional mode in the following March–April, affecting precipitation in northeast Brazil. Thus it offers potential predictability for climate over the Atlantic sector in early boreal winter, a season for which local ocean–atmosphere variability was otherwise poorly understood.
A Climatology of Tropospheric Zonal-Mean Water Vapor Fields and Fluxes in Isentropic Coordinates
Authors: Schneider Tapio , Smith Karen L. , O’Gorman Paul A. , Walker Christopher C. 
Published: December 2006

Abstract
Based on reanalysis data for the years 1980–2001 from the European Centre for Medium-Range Weather Forecasts (ERA-40 data), a climatology of tropospheric zonal-mean water vapor fields and fluxes in isentropic coordinates is presented. In the extratropical free troposphere, eddy fluxes dominate the meridional flux of specific humidity along isentropes. At all levels, isentropic eddy fluxes transport water vapor from the deep Tropics through the subtropics into the extratropics. Isentropic eddy fluxes of specific humidity diverge near the surface and in the tropical and subtropical free troposphere; they converge in the extratropical free troposphere. Isentropic mean advective fluxes of specific humidity play a secondary role in the meridional water vapor transport in the free troposphere; however, they dominate the meridional flux of specific humidity near the surface, where they transport water vapor equatorward and, in the solstice seasons, across the equator. Cross-isentropic mean advective fluxes of specific humidity are especially important in the Hadley circulation, in whose ascending branches they moisten and in whose descending branches they dry the free troposphere.
Near the minima of zonal-mean relative humidity in the subtropical free troposphere, the divergence of the cross-isentropic mean advective flux of specific humidity in the descending branches of the Hadley circulation is the dominant divergence in the mean specific humidity balance; it is primarily balanced by convergence of cross-isentropic turbulent fluxes that transport water vapor from the surface upward. Although there are significant isentropic eddy fluxes of specific humidity through the region of the subtropical relative humidity minima, their divergence near the minima is generally small compared with the divergence of cross-isentropic mean advective fluxes, implying that moistening by eddy transport from the Tropics into the region of the minima approximately balances drying by eddy transport into the extratropics. That drying by cross-isentropic mean subsidence near the subtropical relative humidity minima is primarily balanced by moistening by upward turbulent fluxes of specific humidity, likely in convective clouds, suggests cloud dynamics may play a central role in controlling the relative humidity of the subtropical free troposphere.
Ancient Austrocedrus Tree-Ring Chronologies Used to Reconstruct Central Chile Precipitation Variability from a.d. 1200 to 2000
Authors: Le Quesne Carlos , Stahle David W. , Cleaveland Malcolm K. , Therrell Matthew D. , Aravena Juan Carlos , Barichivich Jonathan 
Published: December 2006

Abstract
An expanded network of moisture-sensitive tree-ring chronologies has been developed for central Chile from long-lived cypress trees in the Andean Cordillera. A regional ring width chronology of cypress sites has been used to develop well-calibrated and verified estimates of June–December precipitation totals for central Chile extending from a.d. 1200 to 2000. These reconstructions are confirmed in part by historical references to drought in the seventeenth and eighteenth centuries and by nineteenth-century observations on the position of the Río Cipreses glacier. Analyses of the return intervals between droughts in the instrumental and reconstructed precipitation series indicate that the probability of drought has increased dramatically during the late nineteenth and twentieth centuries, consistent with selected long instrumental precipitation records and with the general recession of glaciers in the Andean Cordillera. This increased drought risk has occurred along with the growing demand on surface water resources and may heighten socioeconomic sensitivity to climate variability in central Chile.
A New Globally Complete Monthly Historical Gridded Mean Sea Level Pressure Dataset (HadSLP2): 1850–2004
Authors: Allan Rob , Ansell Tara 
Published: December 2006

AbstractAn upgraded version of the Hadley Centre’s monthly historical mean sea level pressure (MSLP) dataset (HadSLP2) is presented. HadSLP2 covers the period from 1850 to date, and is based on numerous terrestrial and marine data compilations. Each terrestrial pressure series used in HadSLP2 underwent a series of quality control tests, and erroneous or suspect values were either corrected, where possible, or removed. Marine observations from the International Comprehensive Ocean Atmosphere Data Set were quality controlled (assessed against climatology and near neighbors) and then gridded. The final gridded form of HadSLP2 was created by blending together the processed terrestrial and gridded marine MSLP data. MSLP fields were made spatially complete using reduced-space optimal interpolation. Gridpoint error estimates were also produced.HadSLP2 was found to have generally stronger subtropical anticyclones and higher-latitude features across the Northern Hemisphere than an earlier product (HadSLP1). During the austral winter, however, it appears that the pressures in the southern Atlantic and Indian Ocean midlatitude regions are too high; this is seen in comparisons with both HadSLP1 and the 40-yr ECMWF Re-Analysis (ERA-40). Over regions of high altitude, HadSLP2 and ERA-40 showed consistent differences suggestive of potential biases in the reanalysis model, though the region over the Himalayas in HadSLP2 is biased compared with HadSLP1 and improvements are required in this region. Consistent differences were also observed in regions of sparse data, particularly over the higher latitudes of the Southern Ocean and in the southeastern Pacific. Unlike the earlier HadSLP1 product, error estimates are available with HadSLP2 to guide the user in these regions of low confidence.An evaluation of major phenomena in the climate system using HadSLP2 provided further validation of the dataset. Important climatic features/indices such as the North Atlantic Oscillation, Arctic Oscillation, North Pacific index, Southern Oscillation index, Trans-Polar index, Antarctic Oscillation, Antarctic Circumpolar Wave, East Asian Summer Monsoon index, and the Siberian High index have all been resolved in HadSLP2, with extensions back to the mid-nineteenth century.
The Impact of Satellite Winds and Latent Heat Fluxes in a Numerical Simulation of the Tropical Pacific Ocean
Authors: Ayina Ludos-Herve , Bentamy Abderrahim , Mestas-Nuñez Alberto M. , Madec Gurvan 
Published: December 2006

Abstract
Several oceanic operational programs use remotely sensed fluxes to complement atmospheric operational analyses from major national weather prediction centers. The main goal of this study is to evaluate the ability of the ocean model (ORCA) to correctly simulate the dynamic of the tropical Pacific Ocean in 1996–98 when forced by the satellite turbulent fluxes (wind stress and latent heat fluxes). The results are compared with the oceanic response resulting from forcing the model with the European Centre for Medium-Range Weather Forecasts (ECMWF) operational analysis. Three sensitivity simulations forced with satellite and atmospheric analysis fields are performed. The control experiment is forced with the ECMWF fluxes. The solutions of these simulations are compared with data from the Tropical Atmosphere–Ocean (TAO) buoys and from sea surface temperatures analysis by Reynolds and Smith in the equatorial Pacific Ocean. The analysis results indicate that the model reproduces well the major spatial and temporal oceanic structures including the main characteristics of the 1997–98 El Niño. More specifically, the comparisons with buoys indicate that the experiment forced by the winds and the satellite latent heat fluxes is closer to the observations. They provide weak rms difference and strong correlations along the whole 500-m depth column. Furthermore, the correlations with the SST analysis vary between 75% and 95% compared to 65% and 77% for the experiment forced by ECMWF fluxes. The currents in the first 350 m also show a strong sensitivity to satellite turbulent fluxes.
The Effect of Environmental Conditions on Tropical Deep Convective Systems Observed from the TRMM Satellite
Authors: Lin Bing , Wielicki Bruce A. , Minnis Patrick , Chambers Lin , Xu Kuan-Man , Hu Yongxiang , Fan Alice 
Published: December 2006

Abstract
This study uses measurements of radiation and cloud properties taken between January and August 1998 by three Tropical Rainfall Measuring Mission (TRMM) instruments, the Clouds and the Earth’s Radiant Energy System (CERES) scanner, the TRMM Microwave Imager (TMI), and the Visible and Infrared Scanner (VIRS), to evaluate the variations of tropical deep convective systems (DCSs) with sea surface temperature and precipitation. The authors find that DCS precipitation efficiency increases with SST at a rate of ∼2% K−1. Despite increasing rainfall efficiency, the cloud areal coverage rises with SST at a rate of about 7% K−1 in the warm tropical seas. There, the boundary layer moisture supply for deep convection and the moisture transported to the upper troposphere for cirrus anvil cloud formation increase by ∼6.3% and ∼4.0% K−1, respectively. The changes in cloud formation efficiency, along with the increased transport of moisture available for cloud formation, likely contribute to the large rate of increasing DCS areal coverage. Although no direct observations are available, the increase of cloud formation efficiency with rising SST is deduced indirectly from measurements of changes in the ratio of DCS ice water path and boundary layer water vapor amount with SST. Besides the cloud areal coverage, DCS cluster effective sizes also increase with precipitation. Furthermore, other cloud properties, such as cloud total water and ice water paths, increase with SST. These changes in DCS properties will produce a negative radiative feedback for the earth’s climate system due to strong reflection of shortwave radiation by the DCS. These results significantly differ from some previously hypothesized dehydration scenarios for warmer climates, partially support the thermostat hypothesis but indicate a smaller magnitude of the negative feedback, and have great potential in testing current cloud-system-resolving models and convective parameterizations of general circulation models.
Winter North Atlantic Oscillation Hindcast Skill: 1900–2001
Authors: Fletcher Christopher G. , Saunders Mark A. 
Published: December 2006

Abstract
Recent proposed seasonal hindcast skill estimates for the winter North Atlantic Oscillation (NAO) are derived from different lagged predictors, NAO indices, skill assessment periods, and skill validation methodologies. This creates confusion concerning what is the best-lagged predictor of the winter NAO. To rectify this situation, a standardized comparison of NAO cross-validated hindcast skill is performed against three NAO indices over three extended periods (1900–2001, 1950–2001, and 1972–2001). The lagged predictors comprise four previously published predictors involving anomalies in North Atlantic sea surface temperature (SST), Northern Hemisphere (NH) snow cover, and an additional predictor, an index of NH subpolar summer air temperature (TSP). Significant (p &lt; 0.05) NAO hindcast skill is found with May SST 1900–2001, summer/autumn SST 1950–2001, and warm season snow cover 1972–2001. However, the highest and most significant hindcast skill for all periods and all NAO indices is achieved with TSP. Hindcast skill is nonstationary using all predictors and is highest during 1972–2001 with a TSP correlation skill of 0.59 and a mean-squared skill score of 35%. Observational evidence is presented to support a dynamical link between summer TSP and the winter NAO. Summer TSP is associated with a contemporaneous midlatitude zonal wind anomaly. This leads a pattern of North Atlantic SST that persists through autumn. Autumn SSTs may force a direct thermal NAO response or initiate a response via a third variable. These findings suggest that the NH subpolar regions may provide additional winter NAO lagged predictability alongside the midlatitudes and the Tropics.
Bifurcation Structure of Thermohaline Millennial Oscillations
Authors: Colin de Verdière A. , Ben Jelloul M. , Sévellec F. 
Published: December 2006

Abstract
The question of the generation of millennial oscillations by internal ocean dynamics is studied through deliberate use of the simplest geometry and surface forcing, namely a hemispheric ocean with time-independent mixed boundary conditions (autonomous system). The lowest-order model that supports free oscillations has three horizontal and two vertical boxes. The essential ingredients permitting the existence of the oscillations are turbulent mixing and freshwater forcing. The finite amplitude oscillations share the advective–convective–diffusive characteristics of neighboring stable thermal and haline steady states. There are limits to the quantity of precipitation in polar regions for the existence of oscillatory states. When the freshwater forcing amplitude is increased, the system evolves from a stable thermal state through a global bifurcation to a finite amplitude limit cycle. The period of the limit cycle remains constant when freshwater is increased until at a second global bifurcation it becomes infinite with a logarithmic behavior characteristic of a homoclinic bifurcation. For still higher values of freshwater, the system locks into the stable haline steady state. These results are confirmed through the use of a two-dimensional latitude–depth model. A sensitivity study carried out with the latter shows that the period (away from the logarithmic singularity) varies as (vertical mixing)−1/3. The implications of these results for the Dansgaard–Oeschger oscillations of the last glacial period are threefold: First, internal ocean dynamics in a salt-conserving ocean basin and with time-independent boundary conditions are sufficient to allow free transitions between a strong thermal and a weak haline circulation regime provided that the precipitation in polar oceans does not exceed a certain threshold. It is noteworthy that the snow accumulation rates of the last glacial period were about a fourth of Holocene values. Second, the period of the oscillatory state is determined internally, a possible alternative to studies that require external periodic forcing. The range of the periods when estimated with present determinations of oceanic mixing easily accommodates the observations. Third, if the abrupt warming that signals the beginning of a Dansgaard–Oeschger event is interpreted through the present modeling results, its cause is linked to the efficiency of mixing to accumulate heat for a considerable amount of time in the deep ocean when the thermohaline circulation is weak.
Twentieth-Century Surface Air Temperature over China and the Globe Simulated by Coupled Climate Models
Authors: Zhou Tianjun , Yu Rucong 
Published: December 2006

Abstract
This paper examines variations of the surface air temperature (SAT) over China and the globe in the twentieth century simulated by 19 coupled climate models driven by historical natural and anthropogenic forcings. Most models perform well in simulating both the global and the Northern Hemispheric mean SAT evolutions of the twentieth century. The inclusion of natural forcings improves the simulation, in particular for the first half of the century. The reproducibility of the SAT averaged over China is lower than that of the global and hemispheric averages, but it is still acceptable. The contribution of natural forcings to the SAT over China in the first half of the century is not as robust as that to the global and hemispheric averages. No model could successfully produce the reconstructed warming over China in the 1920s. The prescribed natural and anthropogenic forcings in the coupled climate models mainly produce the warming trends and the decadal- to interdecadal-scale SAT variations with poor performances at shorter time scales. The prominent warming trend in the last half of the century over China and its acceleration in recent decades are weakly simulated. There are discrepancies between the simulated and observed regional features of the SAT trend over China. Few models could produce the summertime cooling over the middle part of eastern China (27°–36°N), while two models acceptably produce the meridional gradients of the wintertime warming trends, with north China experiencing larger warming. Limitations of the current state-of-the-art coupled climate models in simulating spatial patterns of the twentieth-century SAT over China cast a shadow upon their capability toward projecting credible geographical distributions of future climate change through Intergovernmental Panel on Climate Change (IPCC) scenario simulations.