bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Specific Methylation in Saliva: A Promising Biomarker for Early Detection of Head and Neck Cancer Recurrence
Authors: Righini Christian Adrien , de Fraipont Florence , Timsit Jean-François , Faure Claire , Brambilla Elisabeth , Reyt Emile , Favrot Marie-Christine 
Published: February 2007

Abstract
Purpose: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse.
Experimental Design: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series.
Results: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in &gt;75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[18F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed.
Conclusions: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.
Important Therapeutic Targets in Chronic Myelogenous Leukemia
Authors: Kantarjian Hagop M. , Giles Francis , Quintás-Cardama Alfonso , Cortes Jorge 
Published: February 2007

Abstract
Purpose: Review the state-of-art knowledge of the biology and therapy of chronic myelogenous leukemia (CML).
Experimental Design: A review of the literature was undertaken to summarize current information on the pathophysiology of CML and to update data of imatinib mesylate therapy, mechanisms of resistance, and in vitro and clinical data with the new tyrosine kinase inhibitors.
Results: Imatinib, which targets the ABL kinase activity of BCR-ABL, has prolonged survival in CML. Despite the efficacy of imatinib, some patients in chronic phase and more in advanced phases of CML develop resistance, frequently as a result of BCR-ABL tyrosine kinase domain mutants that impair imatinib binding but retain enzymatic activity. New tyrosine kinase inhibitors inhibit BCR-ABL more potently than imatinib and maintain activity against an array of imatinib-resistant BCR-ABL mutants. The IC50 values of nilotinib and dasatinib are at least 10- to 100-fold lower for BCR-ABL compared with imatinib. Phase I-II trials of nilotinib and dasatinib showed high activity in imatinib-resistant CML and Philadelphia chromosome–positive ALL. Dasatinib also inhibits members of the Src family of kinases (SFKs); nilotinib does not. Whether SFKs have a critical role in imatinib resistance or BCR-ABL–mediated oncogenesis is unresolved. Agents that target signals downstream of BCR-ABL (e.g. Ras/Raf and phosphatidylinositol 3-kinase) are under investigation.
Conclusions: Understanding the pathophysiology of CML and mechanisms of resistance has produced effective targeted strategies for imatinib-resistant CML.
Docetaxel-Induced Apoptosis of Human Melanoma Is Mediated by Activation of c-Jun NH2-Terminal Kinase and Inhibited by the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 1/2 Pathway
Authors: Mhaidat Nizar M. , Zhang Xu Dong , Jiang Chen Chen , Hersey Peter 
Published: February 2007

Abstract
Purpose: Our studies have shown variable sensitivity of cultured melanoma cells to docetaxel. To better understand this response, we studied the role of signal transduction pathways in modulating docetaxel-induced melanoma killing.
Experimental Design: Involvement of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt signaling was studied by evaluating their extent of activation in melanoma cells after treatment with docetaxel. The effect of their activation on docetaxel-induced apoptosis was assessed using biochemical inhibitors of the pathways and Western blot analysis of proteins involved.
Results: Docetaxel induced activation of both JNK and ERK1/2 but not p38 mitogen-activated protein kinase or Akt kinases. Apoptosis was dependent on activation of JNK and mediated through activation of caspase-2 and caspase-dependent changes in Bax and Bak. The levels of activated JNK in individual lines showed a close correlation with the levels of apoptosis. In contrast, activation of ERK1/2 by docetaxel inhibited apoptosis and the levels of activation in individual lines were inversely correlated to the degree of apoptosis. Studies on the Bcl-2 family proteins seemed to reflect changes induced by activation of JNK and ERK1/2 pathways. Docetaxel-induced JNK activation was required for Bcl-2 phosphorylation as well as caspase-2–dependent activation of Bax and Bak and subsequent mitochondrial release of apoptosis-inducing factor and cytochrome c. In contrast, activation of ERK1/2 resulted in degradation of BH3-only protein Bim and phosphorylation of Bad.
Conclusions: These studies provide further insights into sensitivity of melanoma cells to taxanes and provide a basis for the current rationale of combining taxanes with inhibitors of the Raf-ERK1/2 pathway.
Nuclear Factor-κB in Development, Prevention, and Therapy of Cancer
Authors: Van Waes Carter 
Published: February 2007

AbstractNuclear factor-κB (NF-κB) is a signal transcription factor that has emerged as an important modulator of altered gene programs and malignant phenotype in development of cancer. Major carcinogens and oncogenic viruses induce NF-κB activation, and a variety of subsequent oncogenic events contribute to a progressive increase in constitutive NF-κB activation as an important common pathway in most forms of cancer. NF-κB target genes promote tumor cell proliferation, survival, migration, inflammation, and angiogenesis. Inhibition of NF-κB has been found to be an important mechanism of action of steroids, nonsteroidal anti-inflammatory drugs, and natural and synthetic compounds that show therapeutic and preventive activity. Newer agents targeting the proteasome, inhibitor-κB kinase, and other upstream kinases involved in NF-κB activation have shown anticancer activity in clinical or preclinical studies.
Circulating Tumor Cells as Prognostic Factor for Distant Metastases and Survival in Patients with Primary Uveal Melanoma
Authors: Schuster Ronny , Bechrakis Nikolaos E. , Stroux Andrea , Busse Antonia , Schmittel Alexander , Scheibenbogen Carmen , Thiel Eckhard , Foerster Michael H. , Keilholz Ulrich 
Published: February 2007

Abstract
Purpose: The aim of this study was to determine in patients with high-risk primary uveal melanoma whether the detection of circulating tumor cells by quantitative reverse transcription-PCR (RT-PCR) is of prognostic relevance.
Experimental Design: Blood samples from 110 patients with high-risk nonmetastatic uveal melanoma were collected on the occasion of primary treatment or follow-up visit. mRNA expression of tyrosinase and MelanA/MART1 were analyzed by real-time RT-PCR and compared with clinical data at presentation and follow-up by univariate and multivariate analyses.
Results: The RT-PCR assay yielded a positive result in 11 of 110 patients, with five positive findings for tyrosinase and five for MelanA/MART1, and one sample positive for both markers. At a median follow-up of 22 months, 25% of patients had developed metastases and 15% had died. Univariate statistical analysis revealed RT-PCR and the largest tumor diameter as important prognostic factors for the development of metastases and for survival. In a Cox proportional hazard model, RT-PCR result and largest tumor diameter predicted metastases (hazard ratios 7.3 and 2.6, respectively), whereas PCR result, largest tumor diameter, and Karnofsky performance status were significant variables for disease-specific survival (hazard ratios 22.6, 4.7, and 6.0, respectively). Analysis of individual RT-PCR results revealed both tyrosinase and MelanA/MART1 transcripts as independent prognostic factors.
Conclusion: The presence of tyrosinase or MelanA/MART1 transcripts is an independent prognostic factor in patients with high-risk primary uveal melanoma for subsequent development of metastases and for survival and can be used to select patients for adjuvant treatment studies.
CORRIGENDUM
Authors: Legg T. P. , Mylne K. R. 
Published: February 2007

Abstract
In an earlier paper the authors described the use of ensemble information for the generation of early warnings of defined severe-weather events within the United Kingdom. A comprehensive verification of the system was also included in this study. However, an error was later found within the verification code for relative operating characteristic and reliability, which affects most of the results (though the Brier skill scores were not affected). The purpose of the present corrigendum is to provide amended verification results. Briefly, what was found before was that skill appeared to exhibit a maximum for these severe-weather events at 4 days ahead, but, although the results for day 4 remain good, the authors underestimated the skill at other days and so the 4-day skill maximum is no longer clear; instead, skill is useful at days 1–4, and tails off only slowly at days 5–6.
Reliable Probabilistic Quantitative Precipitation Forecasts from a Short-Range Ensemble Forecasting System
Authors: Stensrud David J. , Yussouf Nusrat 
Published: February 2007

Abstract
A simple binning technique is developed to produce reliable 3-h probabilistic quantitative precipitation forecasts (PQPFs) from the National Centers for Environmental Prediction (NCEP) multimodel short-range ensemble forecasting system obtained during the summer of 2004. The past 12 days’ worth of forecast 3-h accumulated precipitation amounts and observed 3-h accumulated precipitation amounts from the NCEP stage-II multisensor analyses are used to adjust today’s 3-h precipitation forecasts. These adjustments are done individually to each of ensemble members for the 95 days studied. Performance of the adjusted ensemble precipitation forecasts is compared with the raw (original) ensemble predictions. Results show that the simple binning technique provides significantly more skillful and reliable PQPFs of rainfall events than the raw forecast probabilities. This is true for the base 3-h accumulation period as well as for accumulation periods up to 48 h. Brier skill scores and the area under the relative operating characteristics curve also indicate that this technique yields skillful probabilistic forecasts. The performance of the adjusted forecasts also progressively improves with the increased accumulation period. In addition, the adjusted ensemble mean QPFs are very similar to the raw ensemble mean QPFs, suggesting that the method does not significantly alter the ensemble mean forecast. Therefore, this simple postprocessing scheme is very promising as a method to provide reliable PQPFs for rainfall events without degrading the ensemble mean forecast.
Effective Storm-Relative Helicity and Bulk Shear in Supercell Thunderstorm Environments
Authors: Thompson Richard L. , Mead Corey M. , Edwards Roger 
Published: February 2007

Abstract
A sample of 1185 Rapid Update Cycle (RUC) model analysis (0 h) proximity soundings, within 40 km and 30 min of radar-identified discrete storms, was categorized by several storm types: significantly tornadic supercells (F2 or greater damage), weakly tornadic supercells (F0–F1 damage), nontornadic supercells, elevated right-moving supercells, storms with marginal supercell characteristics, and nonsupercells. These proximity soundings served as the basis for calculations of storm-relative helicity and bulk shear intended to apply across a broad spectrum of thunderstorm types. An effective storm inflow layer was defined in terms of minimum constraints on lifted parcel CAPE and convective inhibition (CIN). Sixteen CAPE and CIN constraint combinations were examined, and the smallest CAPE (25 and 100 J kg−1) and largest CIN (−250 J kg−1) constraints provided the greatest probability of detecting an effective inflow layer within an 835-supercell subset of the proximity soundings. Effective storm-relative helicity (ESRH) calculations were based on the upper and lower bounds of the effective inflow layer. By confining the SRH calculation to the effective inflow layer, ESRH values can be compared consistently across a wide range of storm environments, including storms rooted above the ground. Similarly, the effective bulk shear (EBS) was defined in terms of the vertical shear through a percentage of the “storm depth,” as defined by the vertical distance from the effective inflow base to the equilibrium level associated with the most unstable parcel (maximum θe value) in the lowest 300 hPa. ESRH and EBS discriminate strongly between various storm types, and between supercells and nonsupercells, respectively.
Foehn Winds That Produced Large Temperature Differences near the Southern Appalachian Mountains
Authors: Gaffin David M. 
Published: February 2007

Abstract
A 30-yr (1971–2000) study was conducted to 1) determine the typical characteristics and synoptic conditions of foehn wind events that produced large temperature differences near the southern Appalachian Mountains and 2) further examine those events that produced dewpoint rises. Foehn wind events were identified on both the western and eastern sides of the southern Appalachians by comparing temperatures between a station immediately adjacent to the southern Appalachians (foehn station) and two nearby stations located farther from the mountains (nonfoehn station). A foehn wind event occurred when the following criteria were met: the daily maximum or minimum temperature at the foehn station was at least 3°C (∼5°F) higher than the nonfoehn station, winds of at least 2.5 m s−1 (∼5 kt) at the foehn station must have been from a downslope direction, and warming of at least 3°C (∼5°F) must have occurred during the period of downslope winds. Foehn wind events on the western side typically occurred as southeasterly winds developed ahead of a low pressure system over the mid–Mississippi River valley, while foehn wind events on the eastern side were typically the result of northwesterly winds behind the passage of a shallow cold front. The relatively warm 850-hPa air mass, which was only a couple of degrees cooler than the surface temperatures, was likely the source region of the foehn winds on both sides, although additional flow through gaps likely contributed to the less than theoretically possible warming observed at the foehn stations. Composite soundings of the foehn wind events revealed a vertical temperature and wind profile that was conducive to large-amplitude mountain wave formation, especially on the western side of the southern Appalachians. An interesting (and possibly unique) finding observed with these southern Appalachian foehn wind events (compared with other documented foehn wind events) was the rise in surface dewpoints at the foehn stations during nearly three-fourths of the events on the western side and around one-third of the events on the eastern side. A comparison of the dewpoint-rise composites to the composites from all foehn wind events near the southern Appalachians revealed that the rise in surface dewpoints was mainly the result of a drier initial surface air mass (compared with the 850-hPa air mass) and not necessarily a more moist 850-hPa air mass.
Evaluation of GFDL and Simple Statistical Model Rainfall Forecasts for U.S. Landfalling Tropical Storms
Authors: Tuleya Robert E. , DeMaria Mark , Kuligowski Robert J. 
Published: February 2007

Abstract
To date, little objective verification has been performed for rainfall predictions from numerical forecasts of landfalling tropical cyclones. Until 2001, digital output from the operational version of the Geophysical Fluid Dynamics Laboratory (GFDL) hurricane forecast model was available only on a 1° grid. The GFDL model was rerun or reanalyzed for 25 U.S. landfalling tropical cyclones from 1995 to 2002 to obtain higher resolution (1/3°) output. Several measures of forecast quality were used to evaluate the predicted rainfall from these runs, using daily rain gauge data as ground truth. The overall quality was measured by the mean error and bias averaged over all the gauge sites. An estimate of the quality of the forecasted pattern was obtained through the correlation coefficient of the model versus gauge values. In addition, more traditional precipitation verification scores were calculated including equitable threat and bias scores. To evaluate the skill of the rainfall forecasts, a simple rainfall climatology and persistence (R-CLIPER) model was developed, where a climatological rainfall rate is accumulated along either the forecasted or observed storm track. Results show that the R-CLIPER and GFDL forecasts had comparable mean absolute errors of ∼0.9 in. (23 mm) for the 25 cases. The GFDL model exhibited a higher pattern correlation with observations than R-CLIPER, but still only explained ∼30% of the spatial variance. The GFDL model also had higher equitable threat scores than R-CLIPER, partially because of a low bias of R-CLIPER for rainfall amounts larger than 0.5 in. (13 mm). A large case-to-case variability was found that was dependent on both synoptic conditions and track error.
Evaluation of a Mesoscale Short-Range Ensemble Forecast System over the Northeast United States
Authors: Jones Matthew S. , Colle Brian A. , Tongue Jeffrey S. 
Published: February 2007

Abstract
A short-range ensemble forecast system was constructed over the northeast United States down to 12-km grid spacing using 18 members from the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). The ensemble consisted of 12 physics members with varying planetary boundary layer schemes and convective parameterizations as well as seven different initial conditions (ICs) [five National Centers for Environmental Prediction (NCEP) Eta-bred members at 2100 UTC and the 0000 UTC NCEP Global Forecast System (GFS) and Eta runs]. The full 18-member ensemble (ALL) was verified at the surface for the warm (May–September 2003) and cool (October 2003–March 2004) seasons. A randomly chosen subset of seven physics (PHS) members at each forecast hour was used to quantitatively compare with the seven IC members. During the warm season, the PHS ensemble predictions for surface temperature and wind speed had more skill than the IC ensemble and a control (shared PHS and IC member) run initialized 12 h later (CTL12). During the cool and warm seasons, a 14-day running-mean bias calibration applied to the ALL ensemble (ALLBC) added 10%–30% more skill for temperature, wind speed, and sea level pressure, with the ALLBC far outperforming the CTL12. For the 24-h precipitation, the PHS ensemble had comparable probabilistic skill to the IC ensemble during the warm season, while the IC subensemble was more skillful during the cool season. All ensemble members had large diurnal surface biases, with ensemble variance approximating ensemble uncertainty only for wind direction. Selection of ICs was also important, because during the cool season the NCEP-bred members introduced large errors into the IC ensemble for sea level pressure, while none of the subensembles (PHS, IC, or ALL) outperformed the GFS–MM5 for sea level pressure.
Assessment of Aircraft Icing Potential and Maximum Icing Altitude from Geostationary Meteorological Satellite Data
Authors: Ellrod Gary P. , Bailey Andrew A. 
Published: February 2007

Abstract
A satellite product that displays regions of aircraft icing potential, along with corresponding cloud-top heights, has been developed using data from the Geostationary Operational Environmental Satellite (GOES) imager and sounder. The icing product, referred to as the Icing Enhanced Cloud-top Altitude Product (ICECAP), is created hourly for the continental United States and southern Canada, and is color coded to show cloud-top altitudes in 1.9-km (6000 ft) intervals. Experimental ICECAP images became routinely available on the Internet during the spring of 2004. Verification of separate ICECAP components (imager icing potential and sounder cloud-top heights) using aircraft pilot reports (PIREPs) indicates that the product provides useful guidance on the spatial coverage and maximum altitude of current icing conditions, but not icing intensity, stratification, or minimum altitude. The imager icing potential component of ICECAP was compared with the operational 40-km resolution National Weather Service (NWS) current icing potential and NWS Airman’s Meteorological Advisories via the NOAA Real-Time Verification System, while GOES cloud-top heights were compared with altitudes of moderate or greater icing from PIREPs. Benefits and deficiencies of the GOES icing product are discussed.
Estimating Hurricane Wind Structure in the Absence of Aircraft Reconnaissance
Authors: Kossin James P. , Knaff John A. , Berger Howard I. , Herndon Derrick C. , Cram Thomas A. , Velden Christopher S. , Murnane Richard J. , Hawkins Jeffrey D. 
Published: February 2007

Abstract
New objective methods are introduced that use readily available data to estimate various aspects of the two-dimensional surface wind field structure in hurricanes. The methods correlate a variety of wind field metrics to combinations of storm intensity, storm position, storm age, and information derived from geostationary satellite infrared (IR) imagery. The first method estimates the radius of maximum wind (RMW) in special cases when a clear symmetric eye is identified in the IR imagery. The second method estimates RMW, and the additional critical wind radii of 34-, 50-, and 64-kt winds for the general case with no IR scene–type constraint. The third method estimates the entire two-dimensional surface wind field inside a storm-centered disk with a radius of 182 km. For each method, it is shown that the inclusion of infrared satellite data measurably reduces error. All of the methods can be transitioned to an operational setting or can be used as a postanalysis tool.