bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen Receptor Expression in Prostate Cancer Cells Is Suppressed by Activation of Epidermal Growth Factor Receptor and ErbB2
Authors: Cai Changmeng , Portnoy David C. , Wang Hongyun , Jiang Xinnong , Chen Shaoyong , Balk Steven P. 
Published: June 2009

AbstractProstate cancers (PCa) that relapse after androgen deprivation therapies [castration-resistant PCa (CRPC)] express high levels of androgen receptor (AR) and androgen-regulated genes, and evidence from several groups indicates that ErbB family receptor tyrosine kinases [epidermal growth factor (EGF) receptor (EGFR) and ErbB2] may contribute to enhancing this AR activity. We found that activation of these kinases with EGF and heregulin-β1 rapidly (within 8 hours) decreased expression of endogenous AR and androgen-regulated PSA in LNCaP PCa cells. AR expression was similarly decreased in LAPC4 and C4-2 cells, but not in the CWR22Rv1 PCa cell line. The rapid decrease in AR was not due to increased AR protein degradation and was not blocked by phosphatidylinositol 3-kinase (LY294002) or MEK (UO126) inhibitors. Significantly, AR mRNA levels in LNCaP cells were markedly decreased by EGF and heregulin-β1, and experiments with actinomycin D to block new mRNA synthesis showed that AR mRNA degradation was increased. AR mRNA levels were still markedly decreased by EGF and heregulin-β1 in LNCaP cells adapted to growth in androgen-depleted medium, although AR protein levels did not decline due to increased AR protein stability. These findings show that EGFR and ErbB2 can negatively regulate AR mRNA and may provide an approach to suppress AR expression in CRPC. [Cancer Res 2009;69(12):5202–9]
PUMA Suppresses Intestinal Tumorigenesis in Mice
Authors: Qiu Wei , Carson-Walter Eleanor B. , Kuan Shih Fan , Zhang Lin , Yu Jian 
Published: June 2009

Abstract
Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of β-catenin hotspot mutations. The absence of PUMA led to a significantly elevated incidence of precursor lesions induced by AOM. AOM was found to induce p53-dependent PUMA expression and PUMA-dependent apoptosis in the colonic crypts and stem cell compartment. Furthermore, PUMA deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of APCMin/+ mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice. [Cancer Res 2009;69(12):4999–5006]
Extracellular Engagement of α6 Integrin Inhibited Urokinase-Type Plasminogen Activator–Mediated Cleavage and Delayed Human Prostate Bone Metastasis
Authors: Ports Michael O. , Nagle Ray B. , Pond Gerald D. , Cress Anne E. 
Published: June 2009

Abstract
Expression of α6 integrin, a laminin receptor, on tumor cell surfaces is associated with reduced patient survival and increased metastasis in a variety of tumors. In prostate cancer, tumor extracapsular escape occurs in part via laminin-coated nerves and vascular dissemination, resulting in clinically significant bone metastases. We previously identified a novel form of α6 integrin, called α6p, generated by urokinase-type plasminogen activator-dependent cleavage of the laminin-binding domain from the tumor cell surface. Cleavage increased laminin-dependent migration. Currently, we used the known conformation sensitivity of integrin function to determine if engagement of the extracellular domain inhibited integrin cleavage and the extravasation step of metastasis. We show that α6 integrin was present on prostate carcinoma escaping the gland via nerves. Both endogenous and inducible levels of α6p were inhibited by engaging the extracellular domain of α6 with monoclonal antibody J8H. J8H inhibited tumor cell invasion through Matrigel. A severe combined immunodeficient mouse model of extravasation and bone metastasis produced detectable, progressive osteolytic lesions within 3 weeks of intracardiac injections. Injection of tumor cells, pretreated with J8H, delayed the appearance of metastases. Validation of the α6 cleavage effect on extravasation was confirmed through a genetic approach using tumor cells transfected with uncleavable α6 integrin. Uncleavable α6 integrin significantly delayed the onset and progression of osseous metastases out to six weeks post-injection. The results suggest that α6 integrin cleavage permits extravasation of human prostate cancer cells from circulation to bone and can be manipulated to prevent metastasis. [Cancer Res 2009;69(12):5007–14]
Epithelial Phenotype Confers Resistance of Ovarian Cancer Cells to Oncolytic Adenoviruses
Authors: Strauss Robert , Sova Pavel , Liu Ying , Li Zong Yi , Tuve Sebastian , Pritchard David , Brinkkoetter Paul , Möller Thomas , Wildner Oliver , Pesonen Sari , Hemminki Akseli , Urban Nicole , Drescher Charles , Lieber André 
Published: June 2009

Abstract
We studied the susceptibility of primary ovarian cancer cells to oncolytic adenoviruses. Using gene expression profiling of cancer cells either resistant or susceptible to viral oncolysis, we discovered that the epithelial phenotype of ovarian cancer represents a barrier to infection by commonly used oncolytic adenoviruses targeted to coxsackie-adenovirus receptor or CD46. Specifically, we found that these adenovirus receptors were trapped in tight junctions and not accessible for virus binding. Accessibility to viral receptors was critically linked to depolarization and the loss of tight and adherens junctions, both hallmarks of epithelial-to-mesenchymal transition (EMT). We showed that specific, thus far little-explored adenovirus serotypes (Ad3, Ad7, Ad11, and Ad14) that use receptor(s) other than coxsackie-adenovirus receptor and CD46 were able to trigger EMT in epithelial ovarian cancer cells and cause efficient oncolysis. Our studies on ovarian cancer cultures and xenografts also revealed several interesting cancer cell biology features. Tumors in situ as well as tumor xenografts in mice mostly contained epithelial cells and cells that were in a hybrid stage where they expressed both epithelial and mesenchymal markers (epithelial/mesenchymal cells). These epithelial/mesenchymal cells are the only xenograft-derived cells that can be cultured and with passaging undergo EMT and differentiate into mesenchymal cells. Our study provides a venue for improved virotherapy of cancer as well as new insights into cancer cell biology. [Cancer Res 2009;69(12):5115–25]
Direct Targeting of the Mucin 1 Oncoprotein Blocks Survival and Tumorigenicity of Human Breast Carcinoma Cells
Authors: Raina Deepak , Ahmad Rehan , Joshi Maya Datt , Yin Li , Wu Zekui , Kawano Takeshi , Vasir Baldev , Avigan David , Kharbanda Surender , Kufe Donald 
Published: June 2009

Abstract
The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed by ∼90% of human breast cancers. However, there are no effective agents that directly inhibit MUC1 and induce death of breast cancer cells. We have synthesized a MUC1 inhibitor (called GO-201) that binds to the MUC1 cytoplasmic domain and blocks the formation of MUC1 oligomers in cells. GO-201, and not an altered version, attenuates targeting of MUC1 to the nucleus of human breast cancer cells, disrupts redox balance, and activates the DNA damage response. GO-201 also arrests growth and induces necrotic death. By contrast, the MUC1 inhibitor has no effect on cells null for MUC1 expression or nonmalignant mammary epithelial cells. Administration of GO-201 to nude mice bearing human breast tumor xenografts was associated with loss of tumorigenicity and extensive necrosis, which results in prolonged regression of tumor growth. These findings show that targeting the MUC1 oncoprotein is effective in inducing death of human breast cancer cells in vitro and in tumor models. [Cancer Res 2009;69(12):5133–41]
Reciprocal Effects of STAT5 and STAT3 in Breast Cancer
Authors: Walker Sarah R. , Nelson Erik A. , Zou Lihua , Chaudhury Mousumi , Signoretti Sabina , Richardson Andrea , Frank David A. 
Published: June 2009

Abstract
Breast cancer is often associated with inappropriate activation of transcription factors involved in normal mammary development. Two related transcription factors, signal transducer and activator of transcription (STAT) 5 and STAT3, play important and distinct roles in mammary development and both can be activated in breast cancer. However, the relative contribution of these STATs to mammary tumorigenesis is unknown. We have found that primary human breast tumors displaying activation of both STATs are more differentiated than those with STAT3 activation alone and display more favorable prognostic characteristics. To understand this difference, we have analyzed the effect of these STATs on gene regulation and phenotype of mammary carcinoma cells. STAT5 and STAT3 mediate opposing effects on several key target genes, with STAT5 exerting a dominant role. Using a model system of paired breast cancer cell lines, we found that coactivation of STAT5 and STAT3 leads to decreased proliferation and increased sensitivity to the chemotherapeutic drugs paclitaxel and vinorelbine compared with cells that have only STAT3 activation. Thus, STAT5 can modify the effects of STAT3 from the level of gene expression to cellular phenotype and analysis of the activation state of both STAT5 and STAT3 may provide important diagnostic and prognostic information in breast cancer. (Mol Cancer Res 2009;7(6):966–76)
Tropical Storm Development from African Easterly Waves in the Eastern Atlantic: A Comparison of Two Successive Waves Using a Regional Model as Part of NASA AMMA 2006
Authors: Vizy Edward K. , Cook Kerry H. 
Published: June 2009

Abstract
Two successive African easterly waves (AEWs) from August 2006 are analyzed utilizing observational data, the European Centre for Medium-Range Weather Forecasts reanalysis, and output from the National Center for Atmospheric Research–National Oceanic and Atmospheric Administration Weather Research and Forecasting model (WRF) to understand why the first wave does not develop over the eastern Atlantic while the second wave does. The first AEW eventually forms Hurricane Ernesto over the Caribbean Sea, but genesis does not occur over the eastern Atlantic. The second wave, although weaker than the first over land, leaves the West African coast and quickly intensifies into Tropical Storm Debby west of the Cape Verde islands. This study shows that the environmental conditions associated with the first AEW’s passage inhibited development. These conditions include strong low- and midtropospheric vertical wind shear owing to a stronger than normal African easterly jet, lower than normal relative humidity, and increased atmospheric stability. All of these are characteristics of an intensification of the Saharan air layer (SAL), or SAL outbreak, over the eastern Atlantic. The environmental conditions were more favorable for genesis 2½ days later when the second wave left the African coast. Additionally, a strong low-level southwesterly surge develops over the eastern North Atlantic in the wake of the passage of the first wave. This westerly surge is associated with an enhancement of the low-level westerly flow, low-level cyclonic vorticity, large-scale low-level wind convergence, and vertical motion conducive for development over the region. While the initial westerly surge is likely associated with the passage of the first wave, over time (i.e., by 1600 UTC 20 August 2006) the development of the second wave becomes influential in maintaining the low-level westerly surge. Although SAL outbreaks are also associated with the addition of dust, the different cyclogenesis histories of the two systems are simulated without including dust in the regional model.
Modeling Mesoscale Cellular Structures and Drizzle in Marine Stratocumulus. Part II: The Microphysics and Dynamics of the Boundary Region between Open and Closed Cells
Authors: Wang Hailong , Feingold Graham 
Published: June 2009

Abstract
This is the second of two companion papers on modeling of mesoscale cellular structures and drizzle in marine stratocumulus. In the first, aerosol–cloud–precipitation interactions and dynamical feedbacks were investigated to study the formation and evolution of open and closed cellular structures separately. In this paper, coexisting open and closed cells and how they influence one another are examined in a model domain of 180 × 60 × 1.5 km3. Simulations show that gradients in aerosol at the open–closed-cell boundary cause gradients in precipitation that generate a mesoscale circulation. The circulation promotes precipitation in the polluted closed cells but suppresses it in open cells by transporting water vapor to the closed-cell regime and carrying drier air and aerosol back to the open cells. The strength of this circulation depends on the contrast in precipitation under clean and polluted conditions at the boundary. Ship plumes emitted into clean, precipitating regions, simulated as a special case of a clean–polluted boundary, develop a similar circulation. Drizzle in the ship track is first suppressed by the increase in aerosol particles but later recovers and becomes even stronger because the local circulation enhances liquid water path owing to the convergence of water vapor from the region adjacent to the track. This circulation modifies the transport and mixing of ship plumes and enhances their dispersal. Finally, results show that whereas ship emissions do increase cloud albedo in regions of open cells, even the addition of very large aerosol concentrations cannot transform an open cellular structure to a closed one, for the case considered.
How Much Do Tropical Cyclones Affect Seasonal and Interannual Rainfall Variability over the Western North Pacific?
Authors: Kubota Hisayuki , Wang Bin 
Published: June 2009

Abstract
The authors investigate the effects of tropical cyclones (TCs) on seasonal and interannual rainfall variability over the western North Pacific (WNP) by using rainfall data at 22 stations. The TC-induced rainfall at each station is estimated by using station data when a TC is located within the influential radius (1000 km) from the station. The spatial–temporal variability of the proportion of TC rainfall is examined primarily along the east–west island chain near 10°N (between 7° and 13°N) and the north–south island chain near 125°E (between 120° and 130°E).
Along 10°N the seasonality of total rainfall is mainly determined by non-TC rainfall that is influenced by the WNP monsoon trough. The proportion of the TC rain is relatively low. During the high TC season from July to December, TC rainfall accounts for 30% of the total rainfall in Guam, 15%–23% in Koror and Yap, and less than 10% at other stations. In contrast, along 125°E where the WNP subtropical high is located, the TC rainfall accounts for 50%–60% of the total rainfall between 18° and 26°N during the peak TC season from July to October. In Hualien of Taiwan, TC rainfall exceeds 60% of the total rainfall.
The interannual variability of the TC rainfall and total rainfall is primarily modulated by El Niño–Southern Oscillation (ENSO). Along 10°N, the ratio of TC rainfall versus total rainfall is higher than the climatology during developing and mature phases of El Niño (from March to the following January), whereas the ratio is below the climatology during the decaying phase of El Niño. The opposite is true for La Niña, except that the impact of La Niña is shorter in duration. Furthermore, in summer of El Niño developing years, the total seasonal rainfall increases primarily because of the increase of TC rainfall. In the ensuing autumn, an anticyclonic anomaly develops over the Philippine Sea and TC rainfall shifts eastward; as a result, the total rainfall over the Philippines and Taiwan decreases. The total rainfall to the east of 140°E, however, changes little, because the westward passage of TCs enhances TC rainfall, which offsets the decrease of non-TC rainfall. Along the meridional island chain between 120° and 130°E, the total rainfall anomaly is affected by ENSO starting from the autumn to the following spring, and the variation in TC rainfall dominates the total rainfall variation only in autumn (August–November) of ENSO years.
The results from this study suggest that in the tropical WNP and subtropical East Asian monsoon regions (east of 120°E), the seasonal and interannual variations of rainfall are controlled by changes in nonlocal circulations. These changes outside the monsoon domain may substantially affect summer monsoon rainfall by changing TC genesis and tracks.
Classifying North Atlantic Tropical Cyclone Tracks by Mass Moments*
Authors: Nakamura Jennifer , Lall Upmanu , Kushnir Yochanan , Camargo Suzana J. 
Published: June 2009

AbstractA new method for classifying tropical cyclones or similar features is introduced. The cyclone track is considered as an open spatial curve, with the wind speed or power information along the curve considered to be a mass attribute. The first and second moments of the resulting object are computed and then used to classify the historical tracks using standard clustering algorithms. Mass moments allow the whole track shape, length, and location to be incorporated into the clustering methodology. Tropical cyclones in the North Atlantic basin are clustered with K-means by mass moments, producing an optimum of six clusters with differing genesis locations, track shapes, intensities, life spans, landfalls, seasonal patterns, and trends. Even variables that are not directly clustered show distinct separation between clusters. A trend analysis confirms recent conclusions of increasing tropical cyclones in the basin over the past two decades. However, the trends vary across clusters.
Probabilistic Estimation of Multivariate Streamflow Using Independent Component Analysis and Climate Information
Authors: Westra Seth , Sharma Ashish 
Published: June 2009

Abstract
A statistical estimation approach is presented and applied to multiple reservoir inflow series that form part of Sydney’s water supply system. The approach involves first identifying sources of interannual and interdecadal climate variability using a combination of correlation- and wavelet-based methods, then using this information to construct probabilistic, multivariate seasonal estimates using a method based on independent component analysis (ICA). The attraction of the ICA-based approach is that, by transforming the multivariate dataset into a set of independent time series, it is possible to maintain the parsimony of univariate statistical methods while ensuring that both the spatial and temporal dependencies are accurately captured.
Based on a correlation analysis of the reservoir inflows with the original sea surface temperature anomaly data, the principal sources of variability in Sydney’s reservoir inflows appears to be a combination of the El Niño–Southern Oscillation (ENSO) phenomenon and the Pacific decadal oscillation (PDO). A multivariate ICA-based estimation model was then used to capture this variability, and it was shown that this approach performed well in maintaining the temporal dependence while also accurately maintaining the spatial dependencies that exist in the 11-dimensional historical reservoir inflow dataset.
Top-of-Atmosphere Radiance-to-Flux Conversion in the SW Domain for the ScaRaB-3 Instrument on Megha-Tropiques
Authors: Viollier Michel , Standfuss Carsten , Chomette Olivier , Quesney Arnaud 
Published: June 2009

Abstract
The earth radiation budget (ERB) is the difference between the solar absorbed flux and the terrestrial emitted flux. These fluxes are calculated from satellite measurements of outgoing shortwave (SW) and longwave (LW) radiances using empirical or theoretical models of the radiation anisotropy, which are called angular distribution models (ADMs). Owing to multidirectional measurement analyses and synergy with multispectral information at subpixel scale, the ADM developed for the NASA Clouds and the Earth’s Radiant Energy System (CERES) mission is presently the best knowledge and has to be taken into account for future ERB missions, such as the Indian–French Megha-Tropiques mission to be launched in 2010. This mission will carry an ERB instrument called the Scanner for Radiation Budget (ScaRaB). To prepare the algorithms for the ScaRaB ADM retrievals, the artificial neural network (ANN) method described by the CERES team has been adopted and improved by replacing the broadband (BB) radiances by narrowband (NB) radiances from the auxiliary channels of ScaRaB as input variables of the ANN. This article is restricted to the SW domain, the most critical case, and shows that the flux error is reduced by 60% compared to the former ERB Experiment–like model. The rms differences with the CERES fluxes are around 8.4 W m−2. ScaRaB/Megha-Tropiques measurements have a 4 times lower spatial resolution than those of the CERES/Tropical Rainfall Measuring Mission (TRMM). The impact of this spatial degradation has also been explored. There is a small systematic bias of about 1.5 W m−2 (or an absolute albedo error of 0.0015) and the rms differences are less than 3 W m−2; this is not significant compared to the overall error budget. For the radiance-to-flux conversion in the SW domain, the BB and NB ANN methods will be implemented in the ScaRaB/Megha-Tropiques data processing in order to provide SW flux estimates with an accuracy that is as consistent as possible with CERES results.
Acoustical Measurement of Nonlinear Internal Waves Using the Inverted Echo Sounder
Authors: Li Qiang , Farmer David M. , Duda Timothy F. , Ramp Steve 
Published: June 2009

Abstract
The performance of pressure sensor–equipped inverted echo sounders for monitoring nonlinear internal waves is examined. The inverted echo sounder measures the round-trip acoustic travel time from the sea floor to the sea surface and thus acquires vertically integrated information on the thermal structure, from which the first baroclinic mode of thermocline motion may be inferred. This application of the technology differs from previous uses in that the wave period (∼30 min) is short, requiring a more rapid transmission rate and a different approach to the analysis. Sources of error affecting instrument performance include tidal effects, barotropic adjustment to internal waves, ambient acoustic noise, and sea surface roughness. The latter two effects are explored with a simulation that includes surface wave reconstruction, acoustic scattering based on the Kirchhoff approximation, wind-generated noise, sound propagation, and the instrument’s signal processing circuitry. Bias is introduced as a function of wind speed, but the simulation provides a basis for bias correction.
The assumption that the waves do not significantly affect the mean stratification allows for a focus on the dynamic response. Model calculations are compared with observations in the South China Sea by using nearby temperature measurements to provide a test of instrument performance. After applying corrections for ambient noise and surface roughness effects, the inverted echo sounder exhibits an RMS variability of approximately 4 m in the estimated depth of the eigenfunction maximum in the wind speed range 0 ≤ U10 ≤ 10 m s−1. This uncertainty may be compared with isopycnal excursions for nonlinear internal waves of 100 m, showing that the observational approach is effective for measurements of nonlinear internal waves in this environment.