bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Circulating Tumor Cells in Early-Stage Breast Cancer Metastasis to Axillary Lymph Nodes
Authors: Nakagawa Taku , Martinez Steve R. , Goto Yasufumi , Koyanagi Kazuo , Kitago Minoru , Shingai Tatsushi , Elashoff David A. , Ye Xing , Singer Frederick R. , Giuliano Armando E. , Hoon Dave S.B. 
Published: July 2007

Abstract
Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status.
Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normal healthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status.
Results: CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P &lt; 0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases.
Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.
Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients
Authors: Landen Charles N. , Lin Yvonne G. , Immaneni Anand , Deavers Michael T. , Merritt William M. , Spannuth Whitney A. , Bodurka Diane C. , Gershenson David M. , Brinkley William R. , Sood Anil K. 
Published: July 2007

Abstract
Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence in cell lines, and by immunohistochemistry in patient samples.
Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase expression was strongly associated with supernumerary centrosome count in tumor cells (P &lt; 0.001). Tumors with the greatest Aurora-A overexpression (n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival (P &lt; 0.05) by multivariate analysis.
Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification and poor survival. It may be a useful prognostic marker and target in ovarian cancer.
Polymorphic TP53BP1 and TP53 Gene Interactions Associated with Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Chen Kexin , Hu Zhibin , Wang Li-E , Zhang Wei , El-Naggar Adel K. , Sturgis Erich M. , Wei Qingyi 
Published: July 2007

Abstract
Purpose: Tumor protein 53-binding protein 1 (TP53BP1) and TP53 interact during TP53-mediated transcriptional activation and during checkpoint activation in response to DNA damage. Because suboptimal repair of tobacco-induced DNA damage is associated with risk of squamous cell carcinoma of the head and neck (SCCHN), we hypothesized that potentially functional polymorphisms in TP53BP1 and TP53 may contribute jointly to SCCHN risk.
Experimental Design: In a case-control study, DNA samples from age- and sex-matched SCCHN patients (n = 818) and cancer-free controls (n = 821) were genotyped for the presence of three variants of TP53BP1 (T-885G, Glu353Asp, and Gln1136Lys) and three variants of TP53 (Arg72Pro, PIN3, and MspI). Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).
Results: Although none of these six genetic variants alone was associated with SCCHN risk, the combined TP53BP1 genotypes were associated with a significant, dose response–dependent decrease in SCCHN risk among carriers of TP53Pro72Pro, TP53PIN3del/del, and TP53Msp1AA genotypes (trend test: P = 0.024, 0.016, and 0.016, respectively). Furthermore, TP53BP1 variant haplotype GGC carriers who were also TP53 variant homozygotes had a significantly lower risk of SCCHN than did TP53BP1 haplotype TCA carriers (adjusted OR, 0.48; 95% CI, 0.25-0.94 for TP53Pro72Pro; adjusted OR, 0.17; 95% CI, 0.04-0.69 for TP53PIN3del/de; and adjusted OR, 0.16; 95% CI, 0.04-0.65 for TP53Msp1AA). There was statistical evidence of interaction between TP53BP1 and TP53 diplotypes (P = 0.017).
Conclusion: Our data suggest that TP53BP1 variants may have protective effects on SCCHN risk but such effects were confined to TP53 variant allele/haplotype carriers.
Synergistic Interactions between Vorinostat and Sorafenib in Chronic Myelogenous Leukemia Cells Involve Mcl-1 and p21CIP1 Down-Regulation
Authors: Dasmahapatra Girija , Yerram Nitin , Dai Yun , Dent Paul , Grant Steven 
Published: July 2007

Abstract
Purpose: Interactions between the multikinase inhibitor sorafenib (Bay 43-9006) and the histone deacetylase inhibitor vorinostat were examined in chronic myelogenous leukemia (CML) cells sensitive and resistant to imatinib mesylate.
Experimental Design: K562, LAMA 84, and primary CML patient-derived CD34+ mononuclear cells were exposed to vorinostat followed by sorafenib, after which effects on cell viability and various survival signaling pathways were monitored by flow cytometry, clonogenic assays, and Western blotting. Real-time reverse transcription-PCR was used to monitor gene expression, and the functional contribution of p21CIP1 and Mcl-1 down-regulation were determined in cells transfected with corresponding constructs.
Results: Pretreatment (24 h) with vorinostat followed by sorafenib optimally induced mitochondrial injury and cell death in Bcr/Abl+ cells (e.g., K562 and LAMA 84). Similar results were obtained in imatinib mesylate–resistant cells expressing activated Lyn as well as in primary CD34+ bone marrow cells obtained from CML patients. This regimen also markedly inhibited CML cell colony formation. Combined but not individual treatment of CML cells with vorinostat and sorafenib triggered pronounced mitochondrial dysfunction (i.e., cytochrome c, Smac, and AIF release), caspase activation, poly(ADP-ribose) polymerase cleavage, and down-regulation of Mcl-1. Sorafenib also blocked vorinostat-mediated induction of p21CIP1. Down-regulation of Mcl-1 was caspase and transcription independent, whereas p21CIP1 down-regulation was partially caspase and transcription dependent. Enforced expression of p21CIP1 and particularly Mcl-1 significantly attenuated vorinostat/sorafenib-mediated lethality.
Conclusions: These findings suggest that combined treatment with vorinostat and sorafenib synergistically induces apoptosis in CML cells through a process that involves Mcl-1 down-regulation and inhibition of p21CIP1 induction.
A Lagrangian Objective Analysis Technique for Assimilating In Situ Observations with Multiple-Radar-Derived Airflow
Authors: Ziegler Conrad L. , Buban Michael S. , Rasmussen Erik N. 
Published: July 2007

Abstract
A new Lagrangian analysis technique is developed to assimilate in situ boundary layer measurements using multi-Doppler-derived wind fields, providing output fields of water vapor mixing ratio, potential temperature, and virtual potential temperature from which the lifting condensation level (LCL) and relative humidity (RH) fields are derived. The Lagrangian analysis employs a continuity principle to bidirectionally distribute observed values of conservative variables with the 3D, evolving boundary layer airflow, followed by temporal and spatial interpolation to an analysis grid. Cloud is inferred at any grid point whose height z &gt; zLCL or equivalently where RH ≥ 100%. Lagrangian analysis of the cumulus field is placed in the context of gridded analyses of visible satellite imagery and photogrammetric cloud-base area analyses. Brief illustrative examples of boundary layer morphology derived with the Lagrangian analysis are presented based on data collected during the International H2O Project (IHOP): 1) a dryline on 22 May 2002; 2) a cold-frontal–dryline “triple point” intersection on 24 May 2002. The Lagrangian analysis preserves the sharp thermal gradients across the cold front and drylines and reveals the presence of undulations and plumes of water vapor mixing ratio and virtual potential temperature associated with deep penetrative updraft cells and convective roll circulations. Derived cloud fields are consistent with satellite-inferred cloud cover and cloud-base locations.
A Case Study of Subtropical Frontogenesis during a Blocking Event
Authors: Chen George Tai-Jen , Wang Chung-Chieh , Wang An-Hsiang 
Published: July 2007

Abstract
During 8–14 June 2000, a 500-hPa blocking event occurred over Mongolia and northern China (near 45°N, 108°E), which was the only case over this region in June since 1981. As the block developed, the initially weak low-level mei-yu front over southern China evolved into a system with strong baroclinity and subsequently moved south. The frontal passage over Taiwan caused temperatures to drop by 10°C, the largest in June over two decades. Using gridded analyses, manually analyzed weather maps, and satellite and surface data, the present study investigates the evolution of this mei-yu front under the influence of the block. The 925-hPa frontogenetical function is computed and effects of different processes are discussed. As the blocking event developed, concurrent ridge–trough amplification in the lower–midtroposphere produced a reversed thermal pattern. The lower-tropospheric high moved southward, and large-scale confluence and deformation were enhanced between the northerly flow and the prefrontal southwesterly flow. The location of the block, to the west-southwest of the Okhotsk Sea area, allowed it to affect the front over southern China and caused it to penetrate inside 20°N, unusual for the month of June. The distribution of the frontogenetical function indicated that the mei-yu frontogenesis and the maintenance of the front were attributed to both deformation and convergence. These two processes together counteracted the strong frontolysis along the frontal zone from diabatic effects, caused by evaporative cooling of frontal precipitation on the warm side and stronger sensible heat transfer (and daytime heating over less cloudy areas) on the cold side of the front. When deformation, convergence, and diabatic effects were all combined, the net total frontogenesis peaked slightly ahead of the frontal zone, thus contributing to the southward propagation of the front in addition to the advection by postfrontal cold air in the present case. When the front moved into the South China Sea, the cross-frontal thermal gradient diminished rapidly, mainly due to the frontolytic effect from sensible heat flux over warm waters.
Verification of an Ensemble Prediction System against Observations
Authors: Candille G. , Côté C. , Houtekamer P. L. , Pellerin G. 
Published: July 2007

Abstract
A verification system has been developed for the ensemble prediction system (EPS) at the Canadian Meteorological Centre (CMC). This provides objective criteria for comparing two EPSs, necessary when deciding whether or not to implement a new or revised EPS. The proposed verification methodology is based on the continuous ranked probability score (CRPS), which provides an evaluation of the global skill of an EPS. Its reliability/resolution partition, proposed by Hersbach, is used to measure the two main attributes of a probabilistic system. Also, the characteristics of the reliability are obtained from the two first moments of the reduced centered random variable (RCRV), which define the bias and the dispersion of an EPS. Resampling bootstrap techniques have been applied to these scores. Confidence intervals are thus defined, expressing the uncertainty due to the finiteness of the number of realizations used to compute the scores. All verifications are performed against observations to provide more independent validations and to avoid any local systematic bias of an analysis. A revised EPS, which has been tested at the CMC in a parallel run during the autumn of 2005, is described in this paper. This EPS has been compared with the previously operational one with the verification system presented above. To illustrate the verification methodology, results are shown for the temperature at 850 hPa. The confidence intervals are computed by taking into account the spatial correlation of the data and the temporal autocorrelation of the forecast error. The revised EPS performs significantly better for all the forecast ranges, except for the resolution component of the CRPS where the improvement is no longer significant from day 7. The significant improvement of the reliability is mainly due to a better dispersion of the ensemble. Finally, the verification system correctly indicates that variations are not significant when two theoretically similar EPSs are compared.
Estimation of Predictability with a Newly Derived Index to Quantify Similarity among Ensemble Members
Authors: Yamada Tomohito J. , Koster Randal D. , Kanae Shinjiro , Oki Taikan 
Published: July 2007

Abstract
This study reveals the mathematical structure of a statistical index, Ω, that quantifies similarity among ensemble members in a weather forecast. Previous approaches for quantifying predictability estimate separately the phase and shape characteristics of a forecast ensemble. The diagnostic Ω, on the other hand, characterizes the similarity (across ensemble members) of both aspects together with a simple expression. The diagnostic Ω is thus more mathematically versatile than previous indices.
Climatology of Cyclone Size Characteristics and Their Changes during the Cyclone Life Cycle
Authors: Rudeva Irina , Gulev Sergey K. 
Published: July 2007

Abstract
Climatology of the atmospheric cyclone sizes and their change over the cyclone life cycle is analyzed on the basis of tracking 57 yr of NCEP–NCAR reanalysis sea level pressure data over the Northern Hemisphere. To quantify the atmospheric cyclone sizes a coordinate transform was used, which allows for the collocation of the cyclone center with the virtual pole and for the establishment of a unique coordinate system for the further determination of cyclone geometry. This procedure was incorporated into a numerical cyclone tracking scheme and provided quantitative estimation of cyclone geometry at every stage of the cyclone development. Climatological features of the distribution of the cyclone size characteristics (effective radius, asymmetry) are considered for the cyclones with different central pressure, deepening rate, and lifetime. Mean effective cyclone radius may experience significant changes, ranging from 300–400 km over the continents to more than 900 km over the oceans. There is found to be a strong dependence of the cyclone effective radius on the cyclone lifetime and intensity, implying the largest cyclone sizes for the most intense and long-living transients. Analysis of size changes during the cyclone life cycle implies that the cyclone radius increases during the development stage from 50% to 150%. Size evolution during the cyclone life cycle implies a universal dependence of the normalized cyclone effective radius and the normalized cyclone age. The actual maximum cyclone radius can be determined from these two nondimensional parameters and cyclone central pressure. Further application of the analysis of cyclone size and shape are discussed.
The Prediction of Extratropical Storm Tracks by the ECMWF and NCEP Ensemble Prediction Systems
Authors: Froude Lizzie S. R. , Bengtsson Lennart , Hodges Kevin I. 
Published: July 2007

Abstract
The prediction of extratropical cyclones by the European Centre for Medium-Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) ensemble prediction systems (EPSs) has been investigated using an objective feature tracking methodology to identify and track the cyclones along the forecast trajectories. Overall the results show that the ECMWF EPS has a slightly higher level of skill than the NCEP EPS in the Northern Hemisphere (NH). However in the Southern Hemisphere (SH), NCEP has higher predictive skill than ECMWF for the intensity of the cyclones. The results from both EPSs indicate a higher level of predictive skill for the position of extratropical cyclones than their intensity and show that there is a larger spread in intensity than position. Further analysis shows that the predicted propagation speed of cyclones is generally too slow for the ECMWF EPS and shows a slight bias for the intensity of the cyclones to be overpredicted. This is also true for the NCEP EPS in the SH. For the NCEP EPS in the NH the intensity of the cyclones is underpredicted. There is small bias in both the EPS for the cyclones to be displaced toward the poles. For each ensemble forecast of each cyclone, the predictive skill of the ensemble member that best predicts the cyclone’s position and intensity was computed. The results are very encouraging showing that the predictive skill of the best ensemble member is significantly higher than that of the control forecast in terms of both the position and intensity of the cyclones. The prediction of cyclones before they are identified as 850-hPa vorticity centers in the analysis cycle was also considered. It is shown that an indication of extratropical cyclones can be given by at least 1 ensemble member 7 days before they are identified in the analysis. Further analysis of the ECMWF EPS shows that the ensemble mean has a higher level of skill than the control forecast, particularly for the intensity of the cyclones, from day 3 of the forecast. There is a higher level of skill in the NH than the SH and the spread in the SH is correspondingly larger. The difference between the ensemble mean error and spread is very small for the position of the cyclones, but the spread of the ensemble is smaller than the ensemble mean error for the intensity of the cyclones in both hemispheres. Results also show that the ECMWF control forecast has ½ to 1 day more skill than the perturbed members, for both the position and intensity of the cyclones, throughout the forecast.
The Role of Eddy Diffusivity Profiles on Stratocumulus Liquid Water Path Biases
Authors: de Roode Stephan R. 
Published: July 2007

Abstract
Results from simulations of the stratocumulus-topped boundary layer with one-dimensional versions of general simulation models typically exhibit a wide range of spread in the modeled liquid water path (LWP). These discrepancies are often attributed to differences in the modeled entrainment rate. Results from a large eddy simulation of the First International Satellite Cloud Climatology Project Regional Experiment I stratocumulus case are analyzed. The diagnosed eddy diffusivities for heat and moisture are found to differ by about a factor of 3. Moreover, both have a much larger magnitude than the ones typically applied in boundary layer parameterization schemes. Motivated by these results mean state solutions are analyzed for the specific case in which the vertical fluxes of heat and moisture are prescribed, whereas eddy diffusivity profiles are systematically varied by multiplication with a constant factor. The solutions demonstrate that any value, ranging from zero to a maximum adiabatic value, can be obtained for the LWP. In the subtropical parts over the ocean where horizontally extended stratocumulus fields persist, the surface sensible heat flux is typically small, whereas surface evaporation and entrainment of relatively dry air from above the surface can result in significant moisture fluxes. If the eddy diffusivity values are small, then the mean specific humidity will tend to decrease quite rapidly with height in order to support the humidity flux. This results in erroneous low humidity values in the upper part of the boundary layers causing low LWP values.
Generalization of the Discrete Brier and Ranked Probability Skill Scores for Weighted Multimodel Ensemble Forecasts
Authors: Weigel Andreas P. , Liniger Mark A. , Appenzeller Christof 
Published: July 2007

Abstract
This note describes how the widely used Brier and ranked probability skill scores (BSS and RPSS, respectively) can be correctly applied to quantify the potential skill of probabilistic multimodel ensemble forecasts. It builds upon the study of Weigel et al. where a revised RPSS, the so-called discrete ranked probability skill score (RPSSD), was derived, circumventing the known negative bias of the RPSS for small ensemble sizes. Since the BSS is a special case of the RPSS, a debiased discrete Brier skill score (BSSD) could be formulated in the same way. Here, the approach of Weigel et al., which so far was only applicable to single model ensembles, is generalized to weighted multimodel ensemble forecasts. By introducing an “effective ensemble size” characterizing the multimodel, the new generalized RPSSD can be expressed such that its structure becomes equivalent to the single model case. This is of practical importance for multimodel assessment studies, where the consequences of varying effective ensemble size need to be clearly distinguished from the true benefits of multimodel combination. The performance of the new generalized RPSSD formulation is illustrated in examples of weighted multimodel ensemble forecasts, both in a synthetic random forecasting context, and with real seasonal forecasts of operational models. A central conclusion of this study is that, for small ensemble sizes, multimodel assessment studies should not only be carried out on the basis of the classical RPSS, since true changes in predictability may be hidden by bias effects—a deficiency that can be overcome with the new generalized RPSSD.