bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration but not Intensity of Alcohol and Tobacco Exposure Predicts p16INK4A Homozygous Deletion in Head and Neck Squamous Cell Carcinoma
Authors: Kraunz Kim S. , McClean Michael D. , Nelson Heather H. , Peters Edward , Calderon Henry , Kelsey Karl T. 
Published: April 2006

Abstract
In tobacco-associated solid tumors, evidence suggests that the pattern of carcinogen exposure is related to the nature of somatic gene inactivation within crucial pathways, including the retinoblastoma (Rb) pathway. One somatic event in this pathway, homozygous deletion of the p16INK4A gene, is commonly observed in head and neck squamous cell carcinoma (HNSCC). Alcohol and tobacco are both well-established risk factors for HNSCC but there has been little characterization of the relationship of exposure to these carcinogens and inactivation of the p16INK4A gene. Hypothesizing that p16INK4A homozygous deletion is associated with tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The odds ratio (OR) for p16INK4A homozygous deletion among alcohol consumers in the upper tertile (&gt;43 years used) was 5.2 [95% confidence interval (95% CI), 2.1-12.8] as compared with those with ≤43 years of alcohol consumption. Intensity of alcohol exposure, measured as average alcoholic drinks per week, was not associated with gene deletion. When we examined the distribution of duration of tobacco use, the OR for p16INK4A homozygous deletion was 1.3 (95% CI, 0.5-3.0) and 1.9 (95% CI, 0.9-4.0) for 29 to 39 years and &gt;39 years of tobacco smoking, respectively, as compared with those that smoked ≤28 years. As in the case of alcohol use, intensity of tobacco exposure (measured as packs per day) was not associated with gene deletion. Hence, the duration of alcohol use and duration of smoking, but not intensity of either, significantly predicted p16INK4A homozygous deletion in HNSCC. (Cancer Res 2006; 66(8): 4512-5)
Cohypermethylation of p16 and FHIT Promoters as a Prognostic Factor of Recurrence in Surgically Resected Stage I Non–Small Cell Lung Cancer
Authors: Kim Jin Seuk , Kim Jin Wook , Han Joungho , Shim Young Mog , Park Joobae , Kim Duk-Hwan 
Published: April 2006

Abstract
Despite advances in the detection and treatment of lung cancer, the prognosis for patients with lung cancer is poor, partly as a result of recurrences. We retrospectively analyzed the relationship between recurrence and survival in patients with non–small cell lung cancers (NSCLC), and the promoter methylation of p16, GSTP1, FHIT, H-cadherin, and RARβ2 genes to identify a prognostic molecular marker associated with the recurrence of NSCLC. Methylation status from 335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC samples, promoter methylation was detected in 35% for p16, 39% for RARβ2, 42% for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39% (132 of 335) of the patients. Recurrence was significantly associated with histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any single gene was not associated with recurrence in patients. However, cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI), 1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for those without cohypermethylation of both genes. In conclusion, the present study suggests that cohypermethylation of p16 and FHIT genes in patients with stage I NSCLC may be a valuable biomarker for predicting the recurrence-associated prognosis of the disease. (Cancer Res 2006; 66(8): 4049-54)
Adoptive Transfer of Type 1 CTL Mediates Effective Anti–Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10
Authors: Nishimura Fumihiko , Dusak Jill E. , Eguchi Junichi , Zhu Xinmei , Gambotto Andrea , Storkus Walter J. , Okada Hideho 
Published: April 2006

AbstractThe development of effective immunotherapeutic strategies for central nervous system (CNS) tumors requires a firm understanding of factors regulating the trafficking of tumor antigen–specific CTLs into CNS tumor lesions. Using C57BL/6 mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1 or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor–transgenic OT-1 mice. We also tested our hypothesis that intratumoral (i.t.) delivery of dendritic cells that had been transduced with IFN-α cDNA (DC-IFN-α) would enhance the tumor-homing and antitumor effectiveness of adoptively transferred Tc1 via induction of an IFN-γ-inducible protein 10 (IP-10). In vitro, DC-IFN-α induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1. In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. M05 and mediated antitumor responses more effectively than Tc2, and their effect was IP-10 dependent. I.t. injections of DC-IFN-α remarkably enhanced the tumor homing, therapeutic efficacy, and in situ IFN-γ production of i.v. delivered Tc1, resulting in the long-term survival and persistence of systemic ovalbumin-specific immunity. These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment. (Cancer Res 2006; 66(8): 4478-87)
Development of Real-time Subcellular Dynamic Multicolor Imaging of Cancer-Cell Trafficking in Live Mice with a Variable-Magnification Whole-Mouse Imaging System
Authors: Yamauchi Kensuke , Yang Meng , Jiang Ping , Xu Mingxu , Yamamoto Norio , Tsuchiya Hiroyuki , Tomita Katsuro , Moossa Abdool R. , Bouvet Michael , Hoffman Robert M. 
Published: April 2006

Abstract
With the use of dual-color fluorescent cells and a highly sensitive whole-mouse imaging system with both macro-optics and micro-optics, we report here the development of subcellular real-time imaging of cancer cell trafficking in live mice. To observe cytoplasmic and nuclear dynamics in the living mouse, tumor cells were labeled in the nucleus with green fluorescent protein and with red fluorescent protein in the cytoplasm. Dual-color cancer cells were injected by a vascular route in an abdominal skin flap in nude mice. The mice were imaged with an Olympus OV100 whole-mouse imaging system with a sensitive CCD camera and five objective lenses, parcentered and parfocal, enabling imaging from macrocellular to subcellular. We observed the nuclear and cytoplasmic behavior of cancer cells in real time in blood vessels as they moved by various means or adhered to the vessel surface in the abdominal skin flap. During extravasation, real-time dual-color imaging showed that cytoplasmic processes of the cancer cells exited the vessels first, with nuclei following along the cytoplasmic projections. Both cytoplasm and nuclei underwent deformation during extravasation. Different cancer cell lines seemed to strongly vary in their ability to extravasate. With the dual-color cancer cells and the highly sensitive whole-mouse imaging system described here, the subcellular dynamics of cancer metastasis can now be observed in live mice in real time. This imaging technology will enable further understanding of the critical steps of metastasis and provide visible targets for antimetastasis drug development. (Cancer Res 2006; 66(8): 4208-14)
Phase I Trial of a Novel Intradermal Idiotype Vaccine in Patients with Advanced B-Cell Lymphoma: Specific Immune Responses Despite Profound Immunosuppression
Authors: Bertinetti Cristina , Zirlik Katja , Heining-Mikesch Kristina , Ihorst Gabriele , Dierbach Heide , Waller Cornelius F. , Veelken Hendrik 
Published: April 2006

AbstractThe immunoglobulin receptor of B-cell lymphomas constitutes a specific tumor antigen (idiotype) and a target for active immunotherapy. Encouraging results have been reported in phase II trials after s.c. vaccination of follicular lymphoma patients during clinical remission with idiotype produced from eukaryotic cell lines and coupled to an immunogenic carrier macromolecule. We have developed a good manufacturing protocol for rapid expression of idiotype vaccines as recombinant Fab fragments in Escherichia coli. The objectives of this trial were to show safety and feasibility of intradermal immunization with this vaccine and to investigate whether immune responses were induced by this immunization route. Patients (n = 18) with advanced B-cell malignancies received repetitive intradermal vaccinations with 0.5 to 1.65 mg recombinant idiotype Fab fragment mixed with lipid-based adjuvant in combination with 150 μg granulocyte macrophage colony-stimulating factor s.c. at the same location. The patients' immune status was assessed by flow cytometry of peripheral blood lymphocytes and concomitant hepatitis B vaccination. Cellular and humoral immune responses to the vaccine were assessed by enzyme-linked immunospot and ELISA. Side effects of a total of 65 vaccinations were mild and did not affect the immunization schedule. No patient developed hepatitis B surface antibodies (anti-HBs) after two hepatitis B immunizations. Of 17 evaluable patients, five developed specific anti-vaccine antibodies, and eight developed anti-Fab T-cell responses. T-cell reactivity was independent of the cellular immune status and was idiotype specific as shown by statistical regression analysis (P = 0.0024) and epitope mapping studies. Intradermal administration of uncoupled recombinant idiotype with appropriate adjuvants may overcome profound clinical immunosuppression and induce specific immune responses. (Cancer Res 2006; 66(8): 4496-502)
A Hypermutation Phenotype and Somatic MSH6 Mutations in Recurrent Human Malignant Gliomas after Alkylator Chemotherapy
Authors: Hunter Chris , Smith Raffaella , Cahill Daniel P. , Stephens Philip , Stevens Claire , Teague Jon , Greenman Chris , Edkins Sarah , Bignell Graham , Davies Helen , O'Meara Sarah , Parker Adrian , Avis Tim , Barthorpe Syd , Brackenbury Lisa , Buck Gemma , Butler Adam , Clements Jody , Cole Jennifer , Dicks Ed , Forbes Simon , Gorton Matthew , Gray Kristian , Halliday Kelly , Harrison Rachel , Hills Katy , Hinton Jonathon , Jenkinson Andy , Jones David , Kosmidou Vivienne , Laman Ross , Lugg Richard , Menzies Andrew , Perry Janet , Petty Robert , Raine Keiran , Richardson David , Shepherd Rebecca , Small Alexandra , Solomon Helen , Tofts Calli , Varian Jennifer , West Sofie , Widaa Sara , Yates Andy , Easton Douglas F. , Riggins Gregory , Roy Jennifer E. , Levine Kymberly K. , Mueller Wolf , Batchelor Tracy T. , Louis David N. , Stratton Michael R. , Futreal P. Andrew , Wooster Richard 
Published: April 2006

Abstract
Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of 518 protein kinases in each of nine gliomas. Large numbers of somatic mutations were observed in two gliomas recurrent after alkylating agent treatment. The pattern of mutations in these cases showed strong similarity to that induced by alkylating agents in experimental systems. Further investigation revealed inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We propose that inactivating somatic mutations of MSH6 confer resistance to alkylating agents in gliomas in vivo and concurrently unleash accelerated mutagenesis in resistant clones as a consequence of continued exposure to alkylating agents in the presence of defective mismatch repair. The evidence therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents convert from induction of tumor cell death to promotion of neoplastic progression. These observations highlight the potential of large scale sequencing for revealing and elucidating mutagenic processes operative in individual human cancers. (Cancer Res 2006; 66(8): 3987-91)
Sensitivity of High-Resolution Forecasts Using the Adjoint Technique at the 10-km Scale
Authors: Soci Cornel , Fischer Claude , Horányi András 
Published: April 2006

Abstract
This paper provides an experimental framework designed to assess the performance and the evolution of the diabatic Aire Limitée Adaptation Dynamique Développement International (ALADIN) adjoint model at 10-km grid size. Numerical experiments are carried out with the goal of evaluating the adjoint model solutions and the benefit of employing a complex linearized physical parameterization package in the gradient computation. Sensitivity studies with respect to initial conditions at high resolution on real meteorological events are performed. Numerical results obtained in the gradient computations show that, at high resolution, a strong nonlinear flow over complex orography might be a potential source of numerical instability in the absence of a robust dissipative physics employed in the adjoint model. Also, the scheme of the linearized large-scale precipitation is a source of noise in precipitating areas. The results on one particular case suggest that on the one hand the adjoint model is able to capture the dynamically sensitive area, but on the other hand the subsequent sensitivity forecast is more sensitive to the sign and the amplitude of the initial state perturbation rather than the structure of the gradient field.
A Diagnostic Study of a Retreating Mei-Yu Front and the Accompanying Low-Level Jet Formation and Intensification
Authors: Chen George Tai-Jen , Wang Chung-Chieh , Lin Li-Fen 
Published: April 2006

Abstract
During 7–8 June 1998, an organized mesoscale convective system (MCS) formed within the mei-yu frontal cloud band and moved northeastward to produce heavy rain over the island of Taiwan. During this period, the section of the mei-yu front east of Taiwan moved northward, most significantly for about 300 km over 12 h. Meanwhile, a low-level jet (LLJ) developed within the environmental southwesterly flow to the south of the mei-yu front and the MCS.
Observations revealed that the front retreated as low-level meridional wind components over the postfrontal region shifted from northerly to southerly. Using European Centre for Medium-Range Weather Forecasts (ECMWF) analyses with piecewise potential vorticity (PV) inversion technique and other methods, a diagnostic study was carried out to investigate the northward frontal movement and the formation of the LLJ.
Results indicated that diabatic latent heating from the MCS, large enough in scale, generated positive PV and height fall at low levels. The enhanced height gradient induced northwestward-directed ageostrophic winds and the LLJ formed southeast of the MCS through Coriolis torque. The southwesterly flow associated with this diabatic PV perturbation led to rapid retreat of the frontal segment east of Taiwan at a speed of about 25 m s−1, while the movement was dominated by horizontal advection in the present case. During this process of readjustment toward geostrophy, a thermally indirect circulation also appeared over and south of the front, and the LLJ formed within its lower branch at 850 hPa. The enhanced southwesterly winds reached LLJ strength because they were superimposed upon a background monsoon flow at the same direction. To the lee of Taiwan, the topography also played the role in enhancing local wind speed at lower levels and contributed toward the frontal retreat at nearby regions.
The Ability of MM5 to Simulate Ice Clouds: Systematic Comparison between Simulated and Measured Fluxes and Lidar/Radar Profiles at the SIRTA Atmospheric Observatory
Authors: Chiriaco M. , Vautard R. , Chepfer H. , Haeffelin M. , Dudhia J. , Wanherdrick Y. , Morille Y. , Protat A. 
Published: April 2006

Abstract
The ability of the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) to simulate midlatitude ice clouds is evaluated. Model outputs are compared to long-term meteorological measurements by active (radar and lidar) and passive (infrared and visible fluxes) remote sensing collected at an atmospheric observatory near Paris, France. The goal is to understand which of four microphysical schemes is best suited to simulate midlatitude ice clouds. The methodology consists of simulating instrument observables from the model outputs without any profile inversion, which allows the authors to use fewer assumptions on microphysical and optical properties of ice particles.
Among the four schemes compared in the current study, the best observation-to-simulations scores are obtained with Reisner et al. provided that the particles’ sedimentation velocity from Heymsfield and Donner is used instead of that originally proposed. For this last scheme, the model gives results close to the measurements for clouds with medium optical depth of typically 1 to 3, whatever the season. In this configuration, MM5 simulates the presence of midlatitude ice clouds in more than 65% of the authors’ selection of observed cloud cases. In 35% of the cases, the simulated clouds are too persistent whatever the microphysical scheme and tend to produce too much solid water (ice and snow) and not enough liquid water.
Bow Echo Sensitivity to Ambient Moisture and Cold Pool Strength
Authors: James Richard P. , Markowski Paul M. , Fritsch J. Michael 
Published: April 2006

AbstractBow echo development within quasi-linear convective systems is investigated using a storm-scale numerical model. A strong sensitivity to the ambient water vapor mixing ratio is demonstrated. Relatively dry conditions at low and midlevels favor intense cold-air production and strong cold pool development, leading to upshear-tilted, “slab-like” convection for various magnitudes of convective available potential energy (CAPE) and low-level shear. High relative humidity in the environment tends to reduce the rate of production of cold air, leading to weak cold pools and downshear-tilted convective systems, with primarily cell-scale three-dimensionality in the convective region. At intermediate moisture contents, long-lived, coherent bowing segments are generated within the convective line. In general, the scale of the coherent three-dimensional structures increases with increasing cold pool strength.The bowing lines are characterized in their developing and mature stages by segments of the convective line measuring 15–40 km in length over which the cold pool is much stronger than at other locations along the line. The growth of bow echo structures within a linear convective system appears to depend critically on the local strengthening of the cold pool to the extent that the convection becomes locally upshear tilted. A positive feedback process is thereby initiated, allowing the intensification of the bow echo. If the environment favors an excessively strong cold pool, however, the entire line becomes uniformly upshear tilted relatively quickly, and the along-line heterogeneity of the bowing line is lost.
Surface Heat Fluxes over Global Oceans Exclusively from Satellite Observations
Authors: Singh Randhir , Kishtawal C. M. , Pal P. K. , Joshi P. C. 
Published: April 2006

AbstractA new approach is introduced for determining surface latent heat flux (LHF) and sensible heat flux (SHF) over the global oceans exclusively from satellite observations. Measurements of wind speed (U), sea surface temperature (SST), near surface specific humidity (Qa), and air–sea temperature difference (ΔT = SST − Ta) are required for computing these fluxes by bulk formulas. To compute the heat fluxes exclusively from satellite data, U is obtained from Special Sensor Microwave Imager (SSM/I), SST is obtained from Advanced Very High Resolution Radiometer (AVHRR), empirical algorithm proposed earlier is used to compute ΔT, and a new one is developed to estimate Qa. The developed empirical equation for Qa estimations is an extension of the authors’ previous method. Compared to the Comprehensive Ocean–Atmosphere Data Set (COADS), the Qa retrieved by the previous approach had a negative bias of the order of more than 2 g kg−1 over the Gulf Stream and Kuroshio during winter but had a positive bias of more than 2 g kg−1 over the Arabian Sea and the Bay of Bengal during summertime. The new empirical equation takes into account these seasonal biases over the Gulf Stream, Kuroshio, and the Arabian Sea. Compared to COADS observations, the Qa retrieved from the developed empirical equation has global mean root mean square error (rmse), bias, and correlation of the order of 0.55, −0.007, and 0.98 g kg−1, respectively.Compared to COADS, the satellite-derived monthly mean LHF has global mean rmse, bias, and correlation of the order of 20, 6, and 0.97 W m−2, respectively. Likewise, satellite-derived monthly mean SHF has global mean rmse, bias, and correlations of the order of 6, 0.4, and 0.98 W m−2, respectively. The monthly fields show that the spatial patterns and seasonal variability of satellite-derived latent and sensible heat fluxes are generally good in agreement with those of the COADS and earlier satellite-derived fluxes.Sixteen-year (January 1988–December 2003) datasets of surface heat fluxes and basic input parameters over the global oceans have been constructed using SSM/I and AVHRR data. This dataset has a spatial resolution of 1° × 1° latitude–longitude and temporal resolution of one month. This unique dataset is constructed exclusively from satellite observations, and it can be obtained from the Meteorology and Oceanography Group Space Applications Centre.
Dual Catalysts System Based on Nano-manganese Oxide and Multiwall Carbon Nanotube for Four-electron Oxygen Reduction
Authors: Zhang Dun , Sotomura Tadashi , Ohsaka Takeo 
Published: April 2006

Abstract
The dual catalysts system, in which nano-manganese oxide (nano-MnOx) is electrodeposited on multiwall carbon nanotube (MWCNT) modified glassy carbon (GC) electrode, efficiently catalyzes 4-electron O2 reduction in alkaline media through the redox-mediation of O2 to O2− (superoxide ion) by functional quinone groups on the MWCNT surface and the subsequent disproportionations of O2− to O2 and HO2− (hydrogen peroxide) and further HO2− to O2 and OH− catalyzed by nano-MnOx.
Electra
Authors: Falk Eugene H. 
Published: April 2006

In the Aeschylean version of the material with which Sophocles is
dealing in his Electra, there appear a few
important characteristics the awareness of which lends perspective to the
Sophoclean tragedy.
For the purpose of this study, we only need to concern ourselves with
the second part of the Aechylean trilogy, the
Oresteia, namely the
Choephoroe. The first part deals with the
antecedents of the events. Agamemnon, the commander of the Greek forces, who
sacrificed his daughter, Iphigenia, in order to appease the goddess Artemis
and to regain divine favor for the storm-bound fleet at Aulis, returns,
after Troy's destruction, victoriously to his land of Argos where
Clytemnestra, his wife, has been nurturing her hatred of him because of his
consent to Iphigenia's death. She has joined forces with Aegisthus, who, for
savage cruelties committed against his family, is also burning with a desire
for revenge on Agamemnon. Aegisthus not only becomes Clytemnestra's ally,
but dishonors Agamemnon at the same time.