bluuebunny/crossref_metadata_2025_split huggingface dataset:
The G691S RET Polymorphism Increases Glial Cell Line–Derived Neurotrophic Factor–Induced Pancreatic Cancer Cell Invasion by Amplifying Mitogen-Activated Protein Kinase Signaling
Authors: Sawai Hirozumi , Okada Yuji , Kazanjian Kevork , Kim Joseph , Hasan Sascha , Hines Oscar J. , Reber Howard A. , Hoon Dave S.B. , Eibl Guido 
Published: December 2005

AbstractMutations of the RET proto-oncogene are responsible for several inherited human diseases and may function as genetic modifiers of the disease. However, the role of RET mutations in pancreatic cancer has not been studied. Expression of the glial cell line–derived neurotrophic factor (GDNF) receptors RET and GDNF family receptor α1 (GFRα1) in human pancreatic cancer cells was determined by Western blot, immunofluorescence, and flow cytometry. The effect of GDNF on cell proliferation and invasion was assessed. Small interfering RNA and antibodies were used to evaluate the involvement of RET. The G691S RET polymorphism was analyzed by sequencing and restriction analysis. The modifying effect of G691S RET on GDNF-induced invasion and mitogen-activated protein kinase (MAPK) signaling was evaluated. Transfection studies with wild-type and mutated RET determined the functional role of the G691S polymorphism. Pancreatic cancer specimens and matched tissues were analyzed for the presence of the G691S RET polymorphism. GDNF receptors were found on all cell lines. GDNF increased pancreatic cancer cell proliferation and invasion, which was mediated by RET. The effect of GDNF was more profound in cells with the G691S RET polymorphism (P &lt; 0.01). G691S RET correlated with an enhanced activation of the downstream extracellular signal-regulated kinase pathway. Overexpression of G691S RET increased pancreatic cancer cell invasion. The G691S RET polymorphism was also detected in human pancreatic tumors and represented a somatic mutation in some patients. These findings indicate that the G691S RET single nucleotide polymorphism may directly correlate with the aggressive growth of pancreatic cancers and may function as a genetic modifier or even low-penetrance gene. (Cancer Res 2005; 65(24): 11536-44)
Dentin Matrix Protein 1 Enhances Invasion Potential of Colon Cancer Cells by Bridging Matrix Metalloproteinase-9 to Integrins and CD44
Authors: Karadag Abdullah , Fedarko Neal S. , Fisher Larry W. 
Published: December 2005

Abstract
The up-regulation of various matrix metalloproteinases (MMP), certain cell receptors such as integrins and CD44, and the SIBLING family of integrin-binding glycophosphoproteins have been reported separately and in various combinations for many types of tumors. The mechanisms by which these different proteins may be interacting and enhancing the ability of a cancer cell to survive and metastasize have become an interesting issue in cancer biology. Dentin matrix protein 1 (DMP1) has been known for a number of years to bind to CD44 and ArgGlyAsp sequence–dependent integrins. This SIBLING was recently shown to be able to specifically bind and activate proMMP-9 and to make MMP-9 much less sensitive to inhibition by tissue inhibitors of metalloproteinases and synthetic inhibitors. In this study, we used a modified Boyden chamber assay to show that DMP1 enhanced the invasiveness of the MMP-9 expressing colon cancer cell line, SW480, through Matrigel in a dose-dependant manner. DMP1 (100 nmol/L) increased invasion 4-fold over controls (86.1 ± 13.9 versus 22.3 ± 9.8, P &lt; 0.001). The enhanced invasive potential required the presence of MMP-9 and at least one of the cell surface receptors, CD44, αvβ3, or αvβ5 integrin. The bridging of MMP-9 to the cell surface receptors was shown by both pull-down and fluorescence activated cell sorting experiments. Because all of these proteins were also shown by immunohistochemistry to be expressed in serial sections of a colon adenocarcinoma, we have hypothesized that the MMP-9/DMP1/cell surface complexes observed to enhance cell invasion in vitro may be aiding metastatic events in vivo. (Cancer Res 2005; 65(24): 11545-52)
Gold(III) Porphyrin 1a Induced Apoptosis by Mitochondrial Death Pathways Related to Reactive Oxygen Species
Authors: Wang Ying , He Qing-Yu , Sun Raymond Wai-Yin , Che Chi-Ming , Chiu Jen-Fu 
Published: December 2005

Abstract
Apoptosis is a tightly controlled multistep mechanism of cell death, and mitochondria are considered to play a central role in this process. Mitochondria initiate two distinct apoptosis pathways, one caspase-dependent and the other caspase-independent. In addition, mitochondrial production of reactive oxygen species (ROS) seems to play a role in cell death. Most chemotherapeutic agents induce apoptosis through at least one of these pathways. The post-initiation mechanisms of gold(III) porphyrin 1a were investigated in this study. HONE1 cells exposed to gold(III) porphyrin 1a underwent apoptosis after 24 hours. Functional proteomic studies revealed the alteration of several cytoplasmic protein expressions in HONE1 cells after treatment with the drug. These proteins include enzymes participating in energy production and proteins involved in cellular redox balance. There was a quick attenuation of mitochondrial membrane potential (ΔΨm) with the alterations of Bcl-2 family proteins, the release of cytochrome c, and apoptosis-inducing factor (AIF) following gold(III) porphyrin 1a treatment. Cytochrome c in turn activated caspase-9 and caspase-3. Cotreatment with caspase inhibitor (zVAD-fmk) showed that the activated caspases worked in conjunction with AIF-initiated apoptosis pathways. Further study showed that ROS played a part in gold(III) porphyrin 1a–induced apoptosis by regulating ΔΨm. In summary, gold(III) porphyrin 1a induced apoptosis through both caspase-dependent and caspase-independent mitochondrial pathways, and intracellular oxidation affected gold(III) porphyrin 1a–induced apoptosis. These results support a role for gold(III) porphyrin 1a as a promising anticancer drug lead and as a possible novel therapeutic agent directed toward the mitochondria. (Cancer Res 2005; 65(24): 11553-64)
Organ-Specific Increase in Mutation Accumulation and Apoptosis Rate in CuZn-Superoxide Dismutase–Deficient Mice
Authors: Busuttil Rita A. , Garcia Ana Maria , Cabrera Carlos , Rodriguez Armando , Suh Yousin , Kim Woo Ho , Huang Ting-Ting , Vijg Jan 
Published: December 2005

Abstract
Reactive oxygen species have been implicated as a cause of cancer and aging in mammals. Mice deficient for the antioxidant enzyme CuZn-superoxide dismutase (Sod1) have a decreased life span and an elevated incidence of liver cancer. To test the hypothesis that the cancer-prone phenotype in such mice is due to accelerated spontaneous mutation accumulation, we crossed these mutants with mice harboring a neutral lacZ mutation reporter gene. At 2 months of age, the lacZ mutation frequency in the liver of the hybrid animals was already twice as high as in littermate controls of the same age. This difference in mutation frequency increased to &gt;3-fold at 6 months of age, after which it did not increase any further. Characterization of the mutation spectra in liver of the Sod1-null mice indicated mainly GC-to-TA transversions and GC-to-AT transitions, signature mutations of oxidative stress. The accelerated mutation accumulation in liver was accompanied by an increased frequency of apoptotic cells, as indicated by an increase in both terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling– and caspase 3–stained cells at 6 and 12 months of age. In kidney, an elevated mutation frequency above controls of ∼2.5-fold was found not earlier than at 6 months. No increased mutation accumulation was observed in brain or spleen. These results support the hypothesis, that oxidative stress is an important causal factor of cancer in mammals. (Cancer Res 2005; 65(24): 11271-5)
Context-Dependent Hormone-Refractory Progression Revealed through Characterization of a Novel Murine Prostate Cancer Cell Line
Authors: Watson Philip A. , Ellwood-Yen Katharine , King Jennifer C. , Wongvipat John , LeBeau Michelle M. , Sawyers Charles L. 
Published: December 2005

AbstractInsights into the molecular basis of hormone-refractory prostate cancer have principally relied on human prostate cancer cell lines, all of which were derived from patients who had already failed hormonal therapy. Recent progress in developing genetically engineered mouse prostate cancer models provides an opportunity to isolate novel cell lines from animals never exposed to hormone ablation, avoiding any potential bias conferred by the selective pressure of the castrate environment. Here we report the isolation of such a cell line (Myc-CaP) from a c-myc transgenic mouse with prostate cancer. Myc-CaP cells have an amplified androgen receptor gene despite no prior exposure to androgen withdrawal and they retain androgen-dependent transgene expression as well as androgen-dependent growth in soft agar and in mice. Reexpression of c-Myc from a hormone-independent promoter rescues growth in androgen-depleted agar but not in castrated mice, showing a clear distinction between the molecular requirements for hormone-refractory growth in vitro versus in vivo. Myc-CaP cells represent a unique reagent for dissecting discreet steps in hormone-refractory prostate cancer progression and show the general utility of using genetically engineered mouse models for establishing new prostate cancer cell lines. (Cancer Res 2005; 65(24): 11565-71)
A Blueprint for a Human Epigenome Project: The AACR Human Epigenome Workshop
Authors: Jones Peter A. , Martienssen Robert 
Published: December 2005

Abstract
Epigenetic processes control the packaging and function of the human genome and contribute to normal and pathologic states, including cancer. The time is ripe to undertake an international effort to identify all the chemical changes and relationships between chromatin constituents that provide function to the genetic code. A timely workshop of leading experts, convened by the American Association for Cancer Research (AACR), confirmed that the technology is at hand to begin defining human epigenomes at high resolution. (Cancer Res 2005; 65(24): 11241-6)
The Sensitivity of Diel CO2 and H2O Vapor Exchange of a Tropical Transitional Forest to Seasonal Variation in Meteorology and Water Availability
Authors: Vourlitis George L. , de Souza Nogueira José , Filho Nicolau Priante , Hoeger Wander , Raiter Fernando , Biudes Marcelo Sacardi , Arruda Jose Carlos , Capistrano Vinicius Buscioli , Brito de Faria Jorge Luiz , de Almeida Lobo Francisco 
Published: December 2005

AbstractMeasurements of ecosystem gas exchange, meteorology, and hydrology (rainfall and soil moisture) were used to assess the seasonal patterns of, and controls on, average diel (24 h) net ecosystem CO2 exchange (NEE), evapotranspiration (E), and bulk canopy water vapor conductance (Gc) of a tropical transitional (ecotonal) forest in the Brazilian Amazon. Diel trends in E and NEE were almost completely explained by the diel variation in photosynthetic photon flux density (QPPFD), and while the QPPFD response of E varied little over the annual cycle, the QPPFD response of NEE declined substantially during the dry season, and the magnitude of hysteresis in the NEE–QPPFD response increased as well. The magnitude of the residuals for the QPPFD versus NEE response was significantly negatively correlated with total monthly rainfall and surface soil moisture and positively correlated with the maximum daily temperature and atmospheric vapor pressure deficit (V). Average daily Gc was also significantly correlated with average daily V (r = −0.72) and soil moisture (r = 0.62), suggesting strong stomatal control of NEE during drought. However, drought reduced ecosystem CO2 efflux relatively more than CO2 assimilation, suggesting that the seasonal variation in NEE was largely driven by seasonal variation in respiration. When compared with other tropical forests, seasonality in NEE was negatively correlated with annual rainfall and positively correlated with dry-season length. The relatively high sensitivity of NEE to seasonal variation in climate and water availability has profound implications for C cycling dynamics under novel climates resulting from climate and/or land-use change in the Amazon basin.
The Significance of the 1976 Pacific Climate Shift in the Climatology of Alaska
Authors: Hartmann Brian , Wendler Gerd 
Published: December 2005

Abstract
The 1976 Pacific climate shift is examined, and its manifestations and significance in Alaskan climatology during the last half-century are demonstrated. The Pacific Decadal Oscillation index shifted in 1976 from dominantly negative values for the 25-yr time period 1951–75 to dominantly positive values for the period 1977–2001.
Mean annual and seasonal temperatures for the positive phase were up to 3.1°C higher than for the negative phase. Likewise, mean cloudiness, wind speeds, and precipitation amounts increased, while mean sea level pressure and geopotential heights decreased. The pressure decrease resulted in a deepening of the Aleutian low in winter and spring. The intensification of the Aleutian low increased the advection of relatively warm and moist air to Alaska and storminess over the state during winter and spring.
The regime shift is also examined for its effect on the long-term temperature trends throughout the state. The trends that have shown climatic warming are strongly biased by the sudden shift in 1976 from the cooler regime to a warmer regime. When analyzing the total time period from 1951 to 2001, warming is observed; however, the 25-yr period trend analyses before 1976 (1951–75) and thereafter (1977–2001) both display cooling, with a few exceptions. In this paper, emphasis is placed on the importance of taking into account the sudden changes that result from abrupt climatic shifts, persistent regimes, and the possibility of cyclic oscillations, such as the PDO, in the analysis of long-term climate change in Alaska.
Global Daytime Distribution of Overlapping Cirrus Cloud from NOAA’s Advanced Very High Resolution Radiometer
Authors: Heidinger Andrew K. , Pavolonis Michael J. 
Published: December 2005

Abstract
Data from the National Oceanic and Atmospheric Administration’s (NOAA’s) Advanced Very High Resolution Radiometer (AVHRR) instrument are used to provide the mean July and January global daytime distributions of multilayer cloud, where multilayer cloud is defined as cirrus overlapping one or more lower layers. The AVHRR data were taken from multiple years that were chosen to provide data with a constant local equator crossing time of 1430–1500 local time. The cloud overlap detection algorithm is used in NOAA’s Extended Clouds from AVHRR (CLAVR-x) processing system. The results between 60°N and 60°S indicated that roughly 20% of all clouds and roughly 40% of all ice clouds were classified as cirrus overlapping lower cloud (cirrus overlap). The results show a strong July–January pattern that is consistent with the seasonal cycle in convection. In some regions, cirrus overlap is found to be the dominant type of cloud observed. The distributions of overlapping cirrus cloud presented here are compared with results from other studies based on rawinsondes and manual surface observations. Comparisons are also made with another satellite-derived study that used coincident infrared and microwave observations over the tropical oceans during a 6-month period
A Near-Global Climatology of Single-Layer and Overlapped Clouds and Their Optical Properties Retrieved from Terra/MODIS Data Using a New Algorithm
Authors: Chang Fu-Lung , Li Zhanqing 
Published: December 2005

Abstract
Cloud overlapping has been a major issue in climate studies owing to a lack of reliable information available over both oceans and land. This study presents the first near-global retrieval and analysis of single-layer and overlapped cloud vertical structures and their optical properties retrieved by applying a new method to the Moderate Resolution Imaging Spectroradiometer (MODIS) data. Taking full advantage of the MODIS multiple channels, the method can differentiate cirrus overlapping lower water clouds from single-layer clouds. Based on newly retrieved cloud products using daytime Terra/MODIS 5-km overcast measurements sampled in January, April, July, and October 2001, global statistics of the frequency of occurrence, cloud-top pressure/temperature (Pc/Tc), visible optical depth (τVIS), and infrared emissivity (ɛ) are presented and discussed. Of all overcast scenes identified over land (ocean), the MODIS data show 61% (52%) high clouds (Pc &lt; 500 hPa), 39% (48%) lower clouds (Pc &gt; 500 hPa), and an extremely low occurrence (&lt;4%) of Pc between 500 and 600 hPa. A distinct bimodal distribution of Pc is found and peaks at ∼275 and ∼725 hPa for high and low clouds, thus leaving a minimum in cloud in the middle troposphere. Out of the 61% (52%) of high clouds identified by MODIS, retrievals reveal that 41% (35%) are thin cirrus clouds (ɛ &lt; 0.85 and Pc &lt; 500 hPa) and the remaining 20% (17%) are thick high clouds (ɛ ≥ 0.85). Out of the 41% (35%) of thin cirrus, 29% (27%) are found to overlap with lower water clouds and 12% (8%) are single-layer cirrus. Total low-cloud amount (single-layer plus overlapped) out of all overcast scenes is thus 68% (39% + 29%) over land and 75% (48% + 27%) over ocean, which is greater than the cloud amounts reported by the MODIS and the International Satellite Cloud Climatology Project (ISCCP). Both retrieved overlapping and nonoverlapping cirrus clouds show similar mean τVIS of ∼1.5 and mean ɛ of ∼0.5. The optical properties of single-layer cirrus and single-layer water clouds agree well with the MODIS standard retrievals. Because the MODIS retrievals do not differentiate between cirrus and lower water clouds in overlap situations, large discrepancies are found for emissivity, cloud-top height, and optical depth for high cirrus overlapping lower water clouds.
Local and Remote Impacts of Aerosol Climate Forcing on Tropical Precipitation*
Authors: Chou Chia , Neelin J. David , Lohmann Ulrike , Feichter Johann 
Published: December 2005

Abstract
Mechanisms that determine the direct and indirect effects of aerosols on the tropical climate involve moist dynamical processes and have local and remote impacts on regional tropical precipitation. These mechanisms are examined in a climate model of intermediate complexity [quasi-equilibrium tropical circulation model (QTCM)] forced by prescribed aerosol forcing, which is obtained from a general circulation model (ECHAM4). The aerosol reflection is the dominant aerosol forcing, while the aerosol absorption has complex but much weaker influences on the regional tropical precipitation based on the ECHAM4 aerosol forcing. The local effect associated with aerosols contributes negative precipitation anomalies over convective regions by affecting the net energy flux into the atmospheric column. This net energy flux is controlled by the radiative forcing at the top of the atmosphere on time scales where surface heat flux is near equilibrium, balancing anomalous solar radiation by evaporation, longwave radiation, and sensible heat. Considering the aerosol absorption effect alone, the associated precipitation anomalies are slightly negative but small when surface heat fluxes are near equilibrium. Two effects found in global warming, the upped-ante mechanism and the anomalous gross moist stability mechanism, occur with opposite sign in the aerosol case. Both act as remote effects via the widespread cold tropospheric temperature anomalies induced by the aerosol forcing. In the upped-ante mechanism in global warming, a warm troposphere increases the low-level moisture “ante” required for convection, creating spatially varying moisture anomalies that disfavor precipitation on those margins of convective zones where the mean flow imports air from nonconvective regions. In the aerosol case here, a cool troposphere preferentially decreases moisture in convective regions, creating positive precipitation anomalies at inflow margins. In the anomalous gross moist stability mechanism for the aerosol case, the decrease in moisture in convective regions acts to enhance the gross moist stability, so convection and the associated precipitation are reduced. The partitioning between the aerosol local and remote effects on regional tropical precipitation differs spatially. Over convective regions that have high aerosol concentration, such as the South American region, the aerosol local effect contributes more negative precipitation anomalies than the anomalous gross moist stability mechanism in the QTCM simulations. On the other hand, the remote effect is more important over convective regions with small aerosol concentrations, such as the western Pacific Maritime Continent. Remote effects of midlatitude aerosol forcing have a substantial contribution to tropical anomalies.
The Monte Carlo Independent Column Approximation’s Conditional Random Noise: Impact on Simulated Climate
Authors: Räisänen P. , Barker H. W. , Cole J. N. S. 
Published: December 2005

Abstract
The Monte Carlo Independent Column Approximation (McICA) method for computing domain-average radiative fluxes is unbiased with respect to the full ICA, but its flux estimates contain conditional random noise. Results for five experiments are used to assess the impact of McICA-related noise on simulations of global climate made by the NCAR Community Atmosphere Model (CAM). The experiment with the least noise (an order of magnitude below that of basic McICA) is taken as the reference. Two additional experiments help demonstrate how the impact of noise depends on the time interval between calls to the radiation code. Each experiment is an ensemble of seven 15-month simulations.
Experiments with very high noise levels feature significant reductions to cloudiness in the lowermost model layer over tropical oceans as well as changes in highly related quantities. This bias appears immediately, stabilizes after a couple of model days, and appears to stem from nonlinear interactions between clouds and radiative heating. Outside the Tropics, insignificant differences prevail. When McICA sampling is confined to cloudy subcolumns and when, on average, 50% more samples, relative to basic McICA, are drawn for selected spectral intervals, McICA noise is much reduced and the results of the simulation are almost statistically indistinguishable from the reference. This is true both for mean fields and for the nature of fluctuations on scales ranging from 1 day to at least 30 days.
While calling the radiation code once every 3 h instead of every hour allows the CAM additional time to incorporate McICA-related noise, the impact of noise is enhanced only slightly. In contrast, changing the radiative time step by itself produces effects that generally exceed the impact of McICA’s noise.
An Update of U.S. Temperature Trends
Authors: Lu Qi Qi , Lund Robert , Seymour Lynne 
Published: December 2005

Abstract
This note updates the temperature trend study of the contiguous 48 United States by Lund et al. for data observed during the 4-yr period 1997–2000. A parsimonious changepoint parameterization is now used, and the methods for handling missing data are improved. The number of stations with useable data has now increased from 359 to 969, thereby improving the accuracy of the reported spatial patterns in the trends. The average record length of the 969 stations is now 103 yr, with the longest record starting in 1812 and the shortest in 1926. The methodological improvements and additional 4 yr of data produce slightly smaller trend estimate standard errors. Warming is found in the Northeast, West, and northern Midwest, with slight cooling in the Southeast; overall, the trends here suggest more warming than those of the Lund et al. study.