bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer
Authors: Prenen Hans , De Schutter Jef , Jacobs Bart , De Roock Wendy , Biesmans Bart , Claes Bart , Lambrechts Diether , Van Cutsem Eric , Tejpar Sabine 
Published: April 2009

AbstractPurpose: It has been reported that activating KRAS mutations negatively affect response to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. The mutation status of signaling molecules downstream of the EGFR target is thus crucial to predict clinical benefit to EGFR-targeted therapies. Other mechanisms of resistance to EGFR inhibitors could involve activating mutations of the other main EGFR effector pathway, i.e., the PI3K/PTEN/AKT pathway.Experimental Design: We analyzed the PIK3CA and KRAS mutation status in a large group (n = 200) of chemorefractory metastatic colorectal cancers treated with cetuximab (Erbitux) in monotherapy or in combination with irinotecan, and correlated the mutation status with outcome.Results: Twenty-three (12%) of the 200 samples carried 1 of the PIK3CA mutations included in our assay. We found no correlation between the presence of a PIK3CA mutation and impaired response to cetuximab.Conclusions: Our findings do not provide any evidence for a strong role of PIK3CA mutations as a single marker in determining response to cetuximab in chemorefractory metastatic colorectal cancer.
An Open-Label, Multicenter, Phase I/II Study of Single-Agent AT-101 in Men with Castrate-Resistant Prostate Cancer
Authors: Liu Glenn , Kelly W. Kevin , Wilding George , Leopold Lance , Brill Kimberli , Somer Bradley 
Published: April 2009

Abstract
Purpose: AT-101 binds and inhibits the antiapoptotic function of Bcl-2, Bcl-xL, Mcl-1, and Bcl-w and is a potent stimulator of proapoptotic proteins. In this multi-institution phase I/II trial, we evaluated the safety and efficacy of single-agent AT-101, in men with chemotherapy naïve, castrate-resistant prostate cancer (CRPC).
Experimental Design: Patients with progressive CRPC were to be treated with escalating doses of AT-101 on a continuous daily basis until the maximally tolerated dose was achieved. At the recommended phase 2 dose, an additional 21 patients were planned to assess for preliminary evidence of efficacy.
Results: Twenty-three patients were enrolled. The phase I starting dose was 30 mg/day on a continuous basis; however, ongoing trials with AT-101 showed increased gastrointestinal toxicity with this daily schedule when given for repetitive cycles. As a result, the phase II starting dose was chosen to be 30 mg/day for 21 of 28 days. The most frequent observed adverse events (any grade) were diarrhea (43.5%), fatigue (34.8%), nausea (21.7%), anorexia (21.7%), and small intestinal obstruction (21.7%). Due to the high incidence of grade 3 small intestinal obstruction (n = 5; 21.7%), a reduction in dose to 20 mg/day for 21 of 28 days was mandated for all patients. Two patients had a confirmed ≥50% posttherapy prostate-specific antigen decline. No objective responses (Response Evaluation Criteria in Solid Tumors) were observed.
Conclusion: AT-101 administered at 20 mg/day for 21 of 28 days was well-tolerated. Evidence of single-agent clinical activity was observed with prostate-specific antigen declines in some patients. Further investigation of AT-101 in prostate cancer is warranted and trials combining AT-101 with androgen deprivation, as well as with docetaxel chemotherapy are ongoing.
Unusually High Differential Attenuation at C Band: Results from a Two-Year Analysis of the French Trappes Polarimetric Radar Data
Authors: Tabary Pierre , Vulpiani Gianfranco , Gourley Jonathan J. , Illingworth Anthony J. , Thompson Robert J. , Bousquet Olivier 
Published: April 2009

Abstract
The differential phase (ΦDP) measured by polarimetric radars is recognized to be a very good indicator of the path integrated by rain. Moreover, if a linear relationship is assumed between the specific differential phase (KDP) and the specific attenuation (AH) and specific differential attenuation (ADP), then attenuation can easily be corrected. The coefficients of proportionality, γH and γDP, are, however, known to be dependent in rain upon drop temperature, drop shapes, drop size distribution, and the presence of large drops causing Mie scattering. In this paper, the authors extensively apply a physically based method, often referred to as the “Smyth and Illingworth constraint,” which uses the constraint that the value of the differential reflectivity ZDR on the far side of the storm should be low to retrieve the γDP coefficient. More than 30 convective episodes observed by the French operational C-band polarimetric Trappes radar during two summers (2005 and 2006) are used to document the variability of γDP with respect to the intrinsic three-dimensional characteristics of the attenuating cells. The Smyth and Illingworth constraint could be applied to only 20% of all attenuated rays of the 2-yr dataset so it cannot be considered the unique solution for attenuation correction in an operational setting but is useful for characterizing the properties of the strongly attenuating cells. The range of variation of γDP is shown to be extremely large, with minimal, maximal, and mean values being, respectively, equal to 0.01, 0.11, and 0.025 dB °−1. Coefficient γDP appears to be almost linearly correlated with the horizontal reflectivity (ZH), differential reflectivity (ZDR), and specific differential phase (KDP) and correlation coefficient (ρHV) of the attenuating cells. The temperature effect is negligible with respect to that of the microphysical properties of the attenuating cells. Unusually large values of γDP, above 0.06 dB °−1, often referred to as “hot spots,” are reported for 15%—a nonnegligible figure—of the rays presenting a significant total differential phase shift (ΔϕDP &gt; 30°). The corresponding strongly attenuating cells are shown to have extremely high ZDR (above 4 dB) and ZH (above 55 dBZ), very low ρHV (below 0.94), and high KDP (above 4° km−1). Analysis of 4 yr of observed raindrop spectra does not reproduce such low values of ρHV, suggesting that (wet) ice is likely to be present in the precipitation medium and responsible for the attenuation and high phase shifts. Furthermore, if melting ice is responsible for the high phase shifts, this suggests that KDP may not be uniquely related to rainfall rate but can result from the presence of wet ice. This hypothesis is supported by the analysis of the vertical profiles of horizontal reflectivity and the values of conventional probability of hail indexes.
The Bias and Error in Moment Estimators for Parameters of Drop Size Distribution Functions: Sampling from Gamma Distributions
Authors: Smith Paul L. , Kliche Donna V. , Johnson Roger W. 
Published: April 2009

AbstractThis paper complements an earlier one that demonstrated the bias in the method-of-moments (MM) estimators frequently used to estimate parameters for drop size distribution (DSD) functions being “fitted” to observed raindrop size distributions. Here the authors consider both the bias and the errors in MM estimators applied to samples from known gamma DSDs (of which the exponential DSD treated in the earlier paper is a special case). The samples were generated using a similar Monte Carlo simulation procedure. The skewness in the sampling distributions of the DSD moments that causes this bias is less pronounced for narrower population DSDs, and therefore the bias problems (and also the errors) diminish as the gamma shape parameter increases. However, the bias still increases with the order of the moments used in the MM procedures; thus it is stronger when higher-order moments (such as the radar reflectivity) are used. The simulation results also show that the errors of the estimates of the DSD parameters are usually larger when higher-order moments are employed. As a consequence, only MM estimators using the lowest-order sample moments that are thought to be well determined should be used. The biases and the errors of most of the MM parameter estimates diminish as the sample size increases; with large samples the moment estimators may become sufficiently accurate for some purposes. Nevertheless, even with some fairly large samples, MM estimators involving high-order moments can yield parameter values that are physically implausible or are incompatible with the input observations. Correlations of the sample moments with the size of the largest drop in a sample (Dmax) are weaker than for the case of sampling from an exponential DSD, as are the correlations of the MM-estimated parameters with Dmax first noted in that case. However, correlations between the estimated parameters remain because functions of the same observations are correlated. These correlations generally strengthen as the sample size increases.
Convection in a Parameterized and Superparameterized Model and Its Role in the Representation of the MJO
Authors: Zhu Hongyan , Hendon Harry , Jakob Christian 
Published: April 2009

Abstract
The behavior of convection and the Madden–Julian oscillation (MJO) is compared in two simulations from the same global climate model but with two very different treatments of convection: one has a conventional parameterization of moist processes and the other replaces the parameterization with a two-dimensional cloud-resolving model, the so-called superparameterization. The different behavior of local convection and the MJO in the two model simulations reveals that the accurate representation of the following characteristics in the modes of convection might contribute to the improvement of the MJO simulations: (i) precipitation should be an exponentially increasing function of the column saturation fraction, (ii) heavy precipitation should be associated with a stratiform diabatic heating profile, and (iii) there should be a positive relationship between precipitation and surface latent heat flux.
Causes of the El Niño and La Niña Amplitude Asymmetry in the Equatorial Eastern Pacific
Authors: Su Jingzhi , Zhang Renhe , Li Tim , Rong Xinyao , Kug J-S. , Hong Chi-Cherng 
Published: April 2009

Abstract
The amplitude asymmetry between El Niño and La Niña is investigated by diagnosing the mixed-layer heat budget during the ENSO developing phase by using the three ocean assimilation products: Simple Ocean Data Assimilation (SODA) 2.0.2, SODA 1.4.2, and the Global Ocean Data Assimilation System (GODAS). It is found that the nonlinear zonal and meridional ocean temperature advections are essential to cause the asymmetry in the far eastern Pacific, whereas the vertical nonlinear advection has the opposite effect. The zonal current anomaly is dominated by the geostrophic current in association with the thermocline depth variation. The meridional current anomaly is primarily attributed to the Ekman current driven by wind stress forcing. The resulting induced anomalous horizontal currents lead to warm nonlinear advection during both El Niño and La Niña episodes and thus strengthen (weaken) the El Niño (La Niña) amplitude. The convergence (divergence) of the anomalous geostrophic mixed-layer currents during El Niño (La Niña) results in anomalous downwelling (upwelling) in the far eastern equatorial Pacific, which leads to a cold nonlinear vertical advection in both warm and cold episodes.
Estimates of North Atlantic Ventilation and Mode Water Formation for Winters 2002–06
Authors: Trossman David S. , Thompson Lu Anne , Kelly Kathryn A. , Kwon Young-Oh 
Published: April 2009

Abstract
Lagrangian estimates for ventilation rates in the Gulf Stream Extension using Argo and World Ocean Circulation Experiment/Atlantic Climate and Circulation Experiment (WOCE/ACCE) float data, scatterometer (QuikSCAT) wind stress satellite observations, and altimetric [Archiving, Validation, and Interpretation of Satellite Oceanographic data (AVISO)] sea surface height (SSH) satellite observations from 2002 to 2006 are presented. Satellite winds and estimates of surface geostrophic currents allow the inclusion of the effects of currents on wind stress as well as their impact on the Ekman pumping. The presence of large surface geostrophic currents decreases the total Ekman pumping, contributing up to 20% where the Gulf Stream makes its two sharpest turns, and increases the total Ekman pumping by 10% or less everywhere else. The ageostrophic currents may be as large as 15% of the geostrophic currents, but only in proximity of the Gulf Stream.
Using currents and mixed layer depths (MLDs) that are either climatological or vary from year to year, obducted water tends to originate along the Gulf Stream, while subducted water tends to originate to its south. However, using time-varying MLDs for each year, subduction varies significantly, sometimes oppositely from obduction. The 18° Water (EDW) subducts in different locations and is distributed differently each year but tends to be located in the Sargasso Sea. Vertical pumping is the only dominant factor in ventilation closer to the coast where MLDs are shallower and lighter parcels are subducted. Vertical pumping contributes up to 20% of the several hundreds of ventilated meters per year around the Gulf Stream and less elsewhere. Using a temperature- or density-based criterion for estimating the MLDs, especially along the coasts and north of 45°N, obduction estimates differ by up to 25%. The horizontal and temporal structure of the MLDs is the primary factor that controls the tens of sverdrups of ventilation (and a few sverdrups of EDW subduction).
Dynamics of Rotating Shallow Gravity Currents Passing through a Channel. Part I: Observation of Transverse Structure
Authors: Umlauf Lars , Arneborg Lars 
Published: April 2009

Abstract
A detailed dataset describing a quasi-stationary bottom gravity current, approximately 10 m thick and 10 km wide, passing through a channel-like constriction in the western Baltic Sea is presented. The data include full-depth, synoptic, and highly resolved transects of stratification and turbulence parameters, as well as detailed velocity transects across the gravity current at different down-channel locations. The velocity data reveal a persistent transverse circulation, creating a characteristic wedge-shaped density structure in the interface. A strong asymmetry was also found in the interior of the gravity current, where the evolution of a dynamically significant transverse density gradient to the right of the down-channel flow was observed. Spectral analysis of the near-bottom velocities showed a surprisingly strong contribution to the bottom stress from low-frequency motions with periods up to 30 min that are possibly related to internal wave effects. Cross-channel transects of shear microstructure were used to investigate the transverse variation of local entrainment rates and bottom stresses. These data indicate that frictional control is essential for this class of gravity currents that are characterized by subcritical Froude numbers, small entrainment, strong rotational effects, and small thickness compared to the bottom Ekman layer.
Dynamics of Rotating Shallow Gravity Currents Passing through a Channel. Part II: Analysis
Authors: Umlauf Lars , Arneborg Lars 
Published: April 2009

Abstract
The physics of frictional control for channelized rotating gravity currents are analyzed using an extensive dataset including hydrographic, current, and microstructure measurements from the western Baltic Sea. Rotational effects in these gravity currents, characterized by Ekman numbers of the order of one and subcritical Froude numbers, induce a complex transverse circulation that strongly affects the internal dynamics. The key component of this circulation is a geostrophically balanced transverse jet in the interface that modifies the entrainment process by (i) laterally draining the interface and (ii) providing additional interfacial shear comparable to the down-channel shear. The recirculation of mixed interfacial fluid into the interior distorts the internal density structure of the gravity current, and creates a thermal wind shear in the interior that is comparable to the observed shear. Using a theoretical model, this effect is shown to be responsible for the three-layer structure of the transverse velocity with the near-bottom velocity and stress directed opposite to the Ekman transport. The analysis confirms the key assumption in available models for frictional control in rotating gravity currents: the transverse Ekman transport is balanced by the geostrophic transport due to the down-channel tilt of the interface.
Observation and Estimation of Lagrangian, Stokes, and Eulerian Currents Induced by Wind and Waves at the Sea Surface
Authors: Ardhuin Fabrice , Marié Louis , Rascle Nicolas , Forget Philippe , Roland Aron 
Published: April 2009

Abstract
The surface current response to winds is analyzed in a 2-yr time series of a 12-MHz (HF) Wellen Radar (WERA) off the west coast of France. Consistent with previous observations, the measured currents, after filtering tides, are on the order of 1.0%–1.8% of the wind speed, in a direction 10°–40° to the right of the wind, and with systematic trends as a function of wind speed. This Lagrangian current can be decomposed as the vector sum of a quasi-Eulerian current UE, representative of the top 1 m of the water column and part of the wave-induced Stokes drift Uss at the sea surface. Here, Uss is estimated with an accurate numerical wave model using a novel parameterization of wave dissipation processes. Using both observed and modeled wave spectra, Uss is found to be very well approximated by a simple function of the wind speed and significant wave height, generally increasing quadratically with the wind speed. Focusing on a site located 100 km from the mainland, the wave-induced contribution of Uss to the radar measurement has an estimated magnitude of 0.6%–1.3% of the wind speed, in the wind direction—a percentage that increases with wind speed. The difference UE of Lagrangian and Stokes contributions is found to be on the order of 0.4%–0.8% of the wind speed and 45°–70° to the right of the wind. This relatively weak, quasi-Eulerian current with a large deflection angle is interpreted as evidence of strong near-surface mixing, likely related to breaking waves and/or Langmuir circulations. Summer stratification tends to increase the UE response by up to a factor of 2 on average, and further increase the deflection angle of UE by 5°–10°. At locations closer to the coast, Uss is smaller and UE is larger with a smaller deflection angle. These results would be transposable to the World Ocean if the relative part of geostrophic currents in UE was weak, which is expected. This decomposition into Stokes drift and quasi-Eulerian current is most important for the estimation of energy fluxes to the Ekman layer.
Variability and Coherence of the Agulhas Undercurrent in a High-Resolution Ocean General Circulation Model
Authors: Biastoch A. , Beal L. M. , Lutjeharms J. R. E. , Casal T. G. D. 
Published: April 2009

Abstract
The Agulhas Current system has been analyzed in a nested high-resolution ocean model and compared to observations. The model shows good performance in the western boundary current structure and the transports off the South African coast. This includes the simulation of the northward-flowing Agulhas Undercurrent. It is demonstrated that fluctuations of the Agulhas Current and Undercurrent around 50–70 days are due to Natal pulses and Mozambique eddies propagating downstream. A sensitivity experiment that excludes those upstream perturbations significantly reduces the variability as well as the mean transport of the undercurrent. Although the model simulates undercurrents in the Mozambique Channel and east of Madagascar, there is no direct connection between those and the Agulhas Undercurrent. Virtual float releases demonstrate that topography is effectively blocking the flow toward the north.
A Scale Interaction Study on East Asian Cyclogenesis Using a General Circulation Model Coupled with an Interactively Nested Regional Model
Authors: Inatsu Masaru , Kimoto Masahide 
Published: April 2009

Abstract
This study newly developed the interactively nested climate model (INCL) using a general circulation model (GCM) interactively nested with a regional atmospheric model (RAM). One interactive experiment with finer RAM topography and another with coarser topography, as well as offline versions of each experiment, were performed to investigate the effects of subsynoptic-scale eddies and subsynoptic-scale mountains in northeast Asia on the larger-scale climate, using the GCM with T42 atmosphere and the RAM with 40-km mesh size in the INCL system. The subsynoptic-scale eddy effect restrictively increased synoptic-scale eddy activity within the RAM domain. In contrast, subsynoptic-scale mountains had the effect of robust anticyclonic circulation around the Sea of Japan and effectively forced larger-scale circulation. The effect was positively fed back to the mean field and amplified the anticyclonic circulation accompanied by suppressed storm activity in northeast Asia. The results suggest that subsynoptic-scale mountains affect not only subsynoptic-scale eddies but also the global climate.
Daytime Sleepiness and Functional Outcomes in Older Adults With Diabetes
Authors: Chasens Eileen R. , Sereika Susan M. , Burke Lora E. 
Published: April 2009

Purpose This secondary analysis examined the effect of excessive sleepiness on daytime function in older adults with diabetes from the National Sleep Foundation's Sleep and Aging poll. Methods Respondents were older adults (N = 1506; age range, 55-84 years) evaluated by telephone survey on their sleep duration, sleep disturbances, daytime functional outcomes, and self-reported height, weight, and comorbidities. Results Approximately 16% (n = 244) of the sample acknowledged a diagnosis of diabetes; they were older, had more comorbidities, had a higher body mass index (BMI), and were more likely to be sleepy during the daytime than nondiabetic respondents (all P < .05). Respondents with diabetes who reported frequent daytime sleepiness (n = 50; 20%) had significantly (P < .05) higher BMI, lower self-rated health, and more sleep disturbances than those who were not sleepy (n = 194). Sleepy respondents with diabetes also reported more frequent feelings of depression, decreased pleasure in life, naps, feeling drowsy, or dozing off while driving (all P < .05). Excessive sleepiness was significantly associated (P < .001) with an increased risk for depressive symptoms while controlling for BMI, age, and number of comorbidities. Conclusions These results indicate that sleep disturbances affect not only sleep quality but also daytime function in older adults with diabetes.
Discouraging citizenship? Young people's reactions to news media coverage of anti-Iraq war protesting in the UK
Authors: Cushion Stephen 
Published: April 2009

Drawing on a survey completed by 699 young people in the UK at the beginning of the 2003 war in Iraq, this article explores young people's reactions to how young anti-war protestors were represented in news media. The survey taps into young people's opinions at a key democratic moment when many school children — to the surprise of many politicians and journalists — took to the streets to demonstrate their opposition to UK foreign policy making. The findings suggest that news coverage of the anti-war protests discouraged some young people from participating in the political public sphere. Many respondents also provided suggestions as to how news media could renew a sense of political efficacy amongst young people in ways that might encourage a greater connection between their political beliefs and key democratic structures.