bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin-3 Mediates Nuclear β-Catenin Accumulation and Wnt Signaling in Human Colon Cancer Cells by Regulation of Glycogen Synthase Kinase-3β Activity
Authors: Song Shumei , Mazurek Nachman , Liu Chunming , Sun Yunjie , Ding Qing Qing , Liu Kaifeng , Hung Mien-Chie , Bresalier Robert S. 
Published: February 2009

Abstract
Wnt/β-catenin signaling plays an essential role in colon carcinogenesis. Galectin-3, a β-galactoside–binding protein, has been implicated in Wnt signaling, but the precise mechanisms by which galectin-3 modulates the Wnt pathway are unknown. In the present study, we determined the effects of galectin-3 on the Wnt/β-catenin pathway in colon cancer cells, as well as the mechanisms involved. Galectin-3 levels were manipulated in human colon cancer cells by stable transfection of galectin-3 antisense, short hairpin RNA, or full-length galectin-3 cDNA, and effects on β-catenin levels, subcellular distribution, and Wnt signaling were determined. Galectin-3 levels correlated with β-catenin levels in a variety of colon cancer cell lines. Down-regulation of galectin-3 resulted in decreased β-catenin protein levels but no change in β-catenin mRNA levels, suggesting that galectin-3 modulates β-catenin by another mechanism. Reduction of galectin-3 led to reduced nuclear β-catenin with a concomitant decrease in TCF4 transcriptional activity and expression of its target genes. Conversely, transfection of galectin-3 cDNA into colon cancer cells increased β-catenin expression and TCF4 transcriptional activity. Down-regulation of galectin-3 resulted in AKT and glycogen synthase kinase-3β (GSK-3β) dephosphorylation and increased GSK activity, increasing β-catenin phosphorylation and degradation. Ly294002, an inhibitor of phosphatidylinositol 3-kinase, and dominant-negative AKT, suppressed TCF4 transcriptional activity induced by galectin-3 whereas LiCl, a GSK-3β inhibitor, increased TCF4 activity, mimicking the effects of galectin-3. These results suggest that galectin-3 mediates Wnt signaling, at least in part, by regulating GSK-3β phosphorylation and activity via the phosphatidylinositol 3-kinase/AKT pathway, and, thus, the degradation of β-catenin in colon cancer cells. [Cancer Res 2009;69(4):1343–9]
Integrated Genome-Wide DNA Copy Number and Expression Analysis Identifies Distinct Mechanisms of Primary Chemoresistance in Ovarian Carcinomas
Authors: Etemadmoghadam Dariush , deFazio Anna , Beroukhim Rameen , Mermel Craig , George Joshy , Getz Gad , Tothill Richard , Okamoto Aikou , Raeder Maria B. ,   AOCS Study Group, Harnett Paul , Lade Stephen , Akslen Lars A. , Tinker Anna V. , Locandro Bianca , Alsop Kathryn , Chiew Yoke-Eng , Traficante Nadia , Fereday Sian , Johnson Daryl , Fox Stephen , Sellers William , Urashima Mitsuyoshi , Salvesen Helga B. , Meyerson Matthew , Bowtell David 
Published: February 2009

Abstract
Purpose: A significant number of women with serous ovarian cancer are intrinsically refractory to platinum-based treatment. We analyzed somatic DNA copy number variation and gene expression data to identify key mechanisms associated with primary resistance in advanced-stage serous cancers.
Experimental Design: Genome-wide copy number variation was measured in 118 ovarian tumors using high-resolution oligonucleotide microarrays. A well-defined subset of 85 advanced-stage serous tumors was then used to relate copy number variation to primary resistance to treatment. The discovery-based approach was complemented by quantitative-PCR copy number analysis of 12 candidate genes as independent validation of previously reported associations with clinical outcome. Likely copy number variation targets and tumor molecular subtypes were further characterized by gene expression profiling.
Results: Amplification of 19q12, containing cyclin E (CCNE1), and 20q11.22-q13.12, mapping immediately adjacent to the steroid receptor coactivator NCOA3, was significantly associated with poor response to primary treatment. Other genes previously associated with copy number variation and clinical outcome in ovarian cancer were not associated with primary treatment resistance. Chemoresistant tumors with high CCNE1 copy number and protein expression were associated with increased cellular proliferation but so too was a subset of treatment-responsive patients, suggesting a cell-cycle independent role for CCNE1 in modulating chemoresponse. Patients with a poor clinical outcome without CCNE1 amplification overexpressed genes involved in extracellular matrix deposition.
Conclusions: We have identified two distinct mechanisms of primary treatment failure in serous ovarian cancer, involving CCNE1 amplification and enhanced extracellular matrix deposition. CCNE1 copy number is validated as a dominant marker of patient outcome in ovarian cancer.
Notch1 mediates growth suppression of papillary and follicular thyroid cancer cells by histone deacetylase inhibitors
Authors: Xiao Xueming , Ning Li , Chen Herbert 
Published: February 2009

Abstract
Notch1 is a multifunctional transmembrane receptor that regulates cellular differentiation, development, proliferation, and survival in a variety of contexts. We have previously shown that Notch1 may function as a tumor suppressor and that histone deacetylase (HDAC) inhibitors can induce Notch1 expression in some endocrine cancers. Here, we showed that although there was minimal Notch1 expression in follicular thyroid cancer FTC236 and papillary thyroid cancer DRO cells, transfection of constitutive Notch1 plasmid into these cells led to growth inhibition, down-regulation of cyclin D1, and up-regulation of p21. Treatment of FTC236 cells with HDAC inhibitors valproic acid (1–4 mmol/L) or suberoyl bishydroxamic acid (10–30 μmol/L) induced functional Notch1 protein expression and suppressed cell growth in a dose-dependent manner. Notch1 siRNA interference blocked the antiproliferative effect of HDAC inhibitors. Western blot analysis revealed the reduction of cyclin D1 and the increase of p21 in HDAC inhibitor–treated cells. These results indicate that HDAC inhibitors activate Notch1 signaling in thyroid cancer cells and lead to the suppression of proliferation by cell cycle arrest. Our findings provide the first documentation of the role of Notch1 signaling as a tumor suppressor in DRO and FTC236 cells, suggesting that Notch1 activation may be a potential therapeutic target for papillary and follicular thyroid cancers. [Mol Cancer Ther 2009;8(2):350–6]
Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors
Authors: Forni Claudia , Minuzzo Mario , Virdis Emanuela , Tamborini Elena , Simone Matteo , Tavecchio Michele , Erba Eugenio , Grosso Federica , Gronchi Alessandro , Aman Pierre , Casali Paolo , D'Incalci Maurizio , Pilotti Silvana , Mantovani Roberto 
Published: February 2009

Abstract
Differentiation is a complex set of events that can be blocked by rearrangements of regulatory genes producing fusion proteins with altered properties. In the case of myxoid liposarcoma (MLS) tumors, the causative abnormality is a fusion between the CHOP transcription factor and the FUS or EWS genes. CHOP belongs to and is a negative regulator of the large CAAT/enhancer binding protein family whose α, β,and δ members are master genes of adipogenesis. Recent clinical data indicate a peculiar sensitivity of these tumors to the natural marine compound trabectedin. One hypothesis is that the activity of trabectedin is related to the inactivation of the FUS-CHOP oncogene. We find that trabectedin causes detachment of the FUS-CHOP chimera from targeted promoters. Reverse transcription-PCR and chromatin immunoprecipitation analysis in a MLS line and surgical specimens of MLS patients in vivo show activation of the CAAT/enhancer binding protein–mediated transcriptional program that leads to morphologic changes of terminal adipogenesis. The activity is observed in cells with type 1 but not type 8 fusions. Hence, the drug induces maturation of MLS lipoblasts in vivo by targeting the FUS-CHOP–mediated transcriptional block. These data provide a rationale for the specific activity of trabectedin and open the perspective of combinatorial treatments with drugs acting on lipogenic pathways. [Mol Cancer Ther 2009;8(2):449–57]
The Perception of Prominence Patterns
Authors: Kohler Klaus J. 
Published: February 2009

Abstract
The term ‘stress’ is used to refer to the perceptual salience at certain places in strings of syllables, but it has several different referents: (a) relative syllable salience in an utterance; this is syllable-, not word-oriented; (b) stress in a word; this is part of the lexical phonology; (c) stressing of words in utterances for various aspects of propositional and expressive meaning, often called ‘accent(uation)’. Referents b and c are word- and meaning-oriented. In this article, the terms are more stringently defined. ‘Stress’ is only used to refer to a lexical stress position (referent b), i.e. a syllable in a word that becomes the docking place for various types of ‘accent’ to weight words in utterances (referent c). ‘Stress’ has no physical attributes by itself. ‘Prominence’ refers to the patterns of salience in syllable strings (referent a). The article reports results of an experiment in prominence perception of the logatome baba, in which the physical parameters F0, syllabic duration, and overall acoustic energy were systematically varied across the bisyllable. Sixteen German subjects had to indicate, by pressing buttons of a computerized reaction time device, whether the first or the second syllable was more prominent. F0 was a more powerful cue than the other two. Equal syllable duration on a monotone resulted in more first-syllable judgements, which could be counteracted by a slightly falling F0 contour on the second syllable to reach equal response frequencies for the two syllables. This ties in with Lehiste’s earlier findings that F0 movement increases the perception of duration. Extrapolating from the results, a research programme for prominence perception is developed that will eventually shed new light on the investigation into the nature and manifestation of speech rhythm.
Morning-to-Afternoon Evolution of Marine Stratus Polluted by Underlying Ships: Implications for the Relative Lifetimes of Polluted and Unpolluted Clouds
Authors: Christensen Matthew W. , Coakley James A. , Tahnk William R. 
Published: February 2009

Abstract
Ship tracks appearing in both the morning and afternoon Moderate Resolution Imaging Spectroradiometer (MODIS) imagery for the Pacific Ocean off the west coast of the United States were used to study the morning-to-afternoon evolution of marine stratus polluted by underlying ships and nearby uncontaminated stratus. Analyzed 925-hPa winds were used to predict the afternoon positions of ship tracks found in the morning imagery. Droplet effective radii, visible optical depths, and liquid water amounts were analyzed for morning and afternoon clouds that, based on the low-level winds, were taken to be the same clouds. As found in a previous study by Segrin et al., both morning and afternoon polluted clouds had smaller droplet radii, larger optical depths, and smaller liquid water amounts than the nearby unpolluted clouds. In contrast to the Segrin et al. study, however, the droplet effective radii decreased significantly from morning to afternoon in both the polluted and unpolluted clouds, with the rate of decrease being twice as large for the unpolluted clouds. The larger decrease in the unpolluted clouds is thought to be caused by drizzle, which is probably absent in the polluted clouds. The observations suggest that, with their slower rate of liquid loss, polluted clouds could have longer lifetimes than their unpolluted counterparts. Of interest is that clouds with similar droplet radii but smaller optical depths, and thus smaller droplet number concentrations and liquid water amounts, exhibited higher sensitivities to the effects of elevated particle concentrations and a greater likelihood of appearing in both the morning and afternoon satellite overpasses.
Revisiting the Thermocline Depth in the Equatorial Pacific*
Authors: Yang Haijun , Wang Fuyao 
Published: February 2009

Abstract
The thermocline depth is defined as the depth of the maximum vertical temperature gradient. In the equatorial Pacific, the depth of 20°C isotherm is widely used to represent the thermocline depth. This work proposes that under the circumstance of a significant mean climate shift, it is better to use the original definition of the thermocline depth in studying the long-term changes in mean climate and tropical coupled climate variabilities. For instance, during the transient period of global warming, the tropical thermocline is usually enhanced because the surface layer warms more and faster than the lower layers. The depth of maximum vertical temperature gradient shoals, which is consistent with the enhanced thermocline. However, the 20°C isotherm depth deepens, which suggests a weakened thermocline. This discrepancy exists in both the observations and the future climate simulations of coupled models.
Eddy-Driven Buoyancy Gradients on Eastern Boundaries and Their Role in the Thermocline
Authors: Cessi Paola , Wolfe Christopher L. 
Published: February 2009

Abstract
It is demonstrated that eddy fluxes of buoyancy at the eastern and western boundaries maintain alongshore buoyancy gradients along the coast. Eddy fluxes arise near the eastern and western boundaries because on both coasts buoyancy gradients normal to the boundary are strong. The eddy fluxes are accompanied by mean vertical flows that take place in narrow boundary layers next to the coast where the geostrophic constraint is broken. These ageostrophic cells have a velocity component normal to the coast that balances the geostrophic mean velocity. It is shown that the dynamics in these thin ageostrophic boundary layers can be replaced by effective boundary conditions for the interior flow, relating the eddy flux of buoyancy at the seaward edge of the boundary layers to the buoyancy gradient along the coast. These effective boundary conditions are applied to a model of the thermocline linearized around a mean stratification and a state of rest. The linear model parameterizes the eddy fluxes of buoyancy as isopycnal diffusion. The linear model produces horizontal gradients of buoyancy along the eastern coast on a vertical scale that depends on both the vertical diffusivity and the eddy diffusivity. The buoyancy field of the linear model agrees very well with the mean state of an eddy-resolving computation. Because the east–west difference in buoyancy is related to the zonally integrated meridional velocity, the linear model successfully predicts the meridional overturning circulation.
Combined Effects of Wind, Tide, and Horizontal Density Gradients on Stratification in Estuaries and Coastal Seas
Authors: Burchard Hans 
Published: February 2009

Abstract
The aim of this one-dimensional water column study is to combine modified versions of three characteristic parameters for periodic tidal flow under the influence of a longitudinal buoyancy gradient—the horizontal Richardson number, the inverse Strouhal number, and the inverse Ekman number—into a parameter space study, including constant wind forcing from various directions. It is shown how the underlying dynamical equations can be cast into nondimensional form, depending mainly on these three nondimensional parameters plus the relative wind speed and the wind direction. Idealized model simulations are carried out for the whole realistic range of horizontal Richardson and inverse Strouhal numbers for various latitudes, showing the amplitude of the tidally induced stratification for a wide range of scenarios. It is found that classical threshold values for the horizontal Richardson number, indicating the switch from periodic stratification to permanent stratification, are valid only for special cases, and that this switch also strongly depends on the inverse Strouhal number, the inverse Ekman number, and the wind vector. The transverse residual flow is close to the thermal wind balance for a variety of parameters, and nondimensionalized longitudinal residual flow shows the classical estuarine exchange flow pattern with little variation in the near-bed onshore component. Wind straining is confirmed as an important estuarine and coastal process, enhancing estuarine circulation for offshore (down estuary) winds and vice versa. Agreement with field data from Liverpool Bay is good, including the explanation of a flood tide local maximum of the dissipation rate in the upper half of the water column. An equation for the second time derivative of the potential energy anomaly is derived for quantifying the dynamical processes leading to stratification due to the straining of the horizontal density gradient.
Optimal Noise Filtering for the Ionospheric Correction of GPS Radio Occultation Signals
Authors: Sokolovskiy S. , Schreiner W. , Rocken C. , Hunt D. 
Published: February 2009

Abstract
GPS radio occultation remote sensing of the neutral atmosphere requires ionospheric correction of L1 and L2 signals. The ionosphere-corrected variables derived from radio occultation signals—such as the phase, Doppler, and bending angle—are affected by small-scale ionospheric effects that are not completely eliminated by the ionospheric correction. They are also affected by noise from mainly the L2 signal. This paper introduces a simple method for optimal filtering of the L4 = L1 − L2 signal used to correct the L1 signal, which minimizes the combined effects of both the small-scale ionospheric residual effects and L2 noise on the ionosphere-corrected variables. Statistical comparisons to high-resolution numerical weather models from the European Centre for Medium-Range Weather Forecasts (ECMWF) validate that this increases the accuracy of radio occultation inversions in the stratosphere.
The Retrieval of Land Surface Pressure from MERIS Measurements in the Oxygen A Band
Authors: Lindstrot Rasmus , Preusker Rene , Fischer Jürgen 
Published: February 2009

AbstractMeasurements of the Medium-Resolution Imaging Spectrometer (MERIS) on the Environmental Satellite (Envisat) are used for the retrieval of surface pressure above land and ice surfaces. The algorithm is based on the exploitation of gaseous absorption in the oxygen A band at 762 nm. The strength of absorption is directly related to the average photon pathlength, which in clear-sky cases above bright surfaces is mainly determined by the surface pressure, with minor influences from scattering at aerosols.Sensitivity studies regarding the influences of aerosol optical thickness and scale height and the temperature profile on the measured radiances are presented. Additionally, the sensitivity of the retrieval to the accuracy of the spectral characterization of MERIS is quantified. The algorithm for the retrieval of surface pressure (SPFUB) is presented and validated against surface pressure maps constructed from ECMWF sea level pressure forecasts in combination with digital elevation model data. The accuracy of SPFUB was found to be within 10 hPa above ice surfaces at Greenland and 15 hPa above desert and mountain scenes in northern Africa and southwest Asia. In a case study above Greenland the accuracy of SPFUB could be enhanced to be better than 3 hPa by spatial averaging over areas of 40 km × 40 km.
Blending Sea Surface Temperatures from Multiple Satellites and In Situ Observations for Coastal Oceans
Authors: Chao Yi , Li Zhijin , Farrara John D. , Hung Peter 
Published: February 2009

Abstract
A two-dimensional variational data assimilation (2DVAR) method for blending sea surface temperature (SST) data from multiple observing platforms is presented. This method produces continuous fields and has the capability of blending multiple satellite and in situ observations. In addition, it allows specification of inhomogeneous and anisotropic background correlations, which are common features of coastal ocean flows. High-resolution (6 km in space and 6 h in time) blended SST fields for August 2003 are produced for a region off the California coast to demonstrate and evaluate the methodology. A comparison of these fields with independent observations showed root-mean-square errors of less than 1°C, comparable to the errors in conventional SST observations. The blended SST fields also clearly reveal the finescale spatial and temporal structures associated with coastal upwelling, demonstrating their utility in the analysis of finescale flows. With the high temporal resolution, the blended SST fields are also used to describe the diurnal cycle. Potential applications of this SST blending methodology in other coastal regions are discussed.
Ensemble-Based Estimates of the Predictability of Wind-Driven Coastal Ocean Flow over Topography
Authors: Kim Sangil , Samelson R. M. , Snyder Chris 
Published: February 2009

AbstractThe predictability of coastal ocean circulation over the central Oregon shelf, a region of strong wind-driven currents and variable topography, is studied using ensembles of 50-day primitive equation ocean model simulations with realistic topography, simplified lateral boundary conditions, and forcing from both idealized and observed wind time series representative of the summer upwelling season. The main focus is on the balance, relevant to practical predictability, between deterministic response to known or well-predicted forcing, uncertainty in initial conditions, and sensitivity to instabilities and topographic interactions. Large ensemble and single-simulation variances are found downstream of topographic features, associated with transitions between along-isobath and cross-isobath flow, which are in turn related both to the time-integrated amplitude of upwelling-favorable wind forcing and to the formation of small-scale eddies. Simulated predictability experiments are conducted and model forecasts are verified by standard statistics including anomaly correlation coefficient, and root-mean-square error. A new variant of relative entropy, the forecast relative entropy, is introduced to quantify the predictive information content in the forecast ensemble, relative to the initial ensemble. The results suggest that, even under conditions of relatively weak wind forcing, the deterministic response is stronger than instability growth over the 3–7-day forecast intervals considered here. Consequently, important elements of the coastal circulation should be accessible to predictive, dynamical forecasts on the nominal 7-day predictability time scale of the atmospheric forcing, provided that sufficiently accurate initializations are available. These results on predictability are consistent with inferences drawn from recent modeling studies of coastal ocean circulation along the central Oregon shelf, and should have general validity for other, similar regions.