bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence-Dependent MutSα Dysfunction Attenuates Mismatch Repair
Authors: Chang In-Youb , Jin Ming , Yoon Sang Pil , Youn Cha-Kyung , Yoon Young , Moon Sung-Pyo , Hyun Jin-Won , Jun Jae Yeoul , You Ho Jin 
Published: June 2008

Abstract
DNA damage and mutations in the genome increase with age. To determine the potential mechanisms of senescence-dependent increases in genomic instability, we analyzed DNA mismatch repair (MMR) efficiency in young and senescent human colonic fibroblast and human embryonic lung fibroblast. It was found that MMR activity is significantly reduced in senescent cells. Western blot and immunohistochemistry analysis revealed that hMSH2 and MSH6 protein (MutSα complex), which is a known key component in the MMR pathway, is markedly down-regulated in senescent cells. Moreover, the addition of purified MutSα to extracts from senescent cells led to the restoration of MMR activity. Semiquantitative reverse transcription-PCR analysis exhibited that MSH2 mRNA level is reduced in senescent cells. In addition, a decrease in E2F transcriptional activity in senescent cells was found to be crucial for MSH2 suppression. E2F1 small interfering RNA expression reduced hMSH2 expression and MMR activity in young human primary fibroblast cells. Importantly, expression of E2F1 in quiescent cells restored the MSH2 expression as well as MMR activity, whereas E2F1-infected senescent cells exhibited no restoration of MSH2 expression and MMR activity. These results indicate that the suppression of E2F1 transcriptional activity in senescent cells lead to stable repression of MSH2, followed by a induction of MutSα dysfunction, which results in a reduced cellular MMR capacity in senescent cells. (Mol Cancer Res 2008;6(6):978–89)
Multiple Signaling Pathways Are Responsible for Prostaglandin E2–Induced Murine Keratinocyte Proliferation
Authors: Ansari Kausar M. , Rundhaug Joyce E. , Fischer Susan M. 
Published: June 2008

Abstract
Although prostaglandin E2 (PGE2) has been shown by pharmacologic and genetic studies to be important in skin cancer, the molecular mechanism(s) by which it contributes to tumor growth is not well understood. In this study, we investigated the mechanisms by which PGE2 stimulates murine keratinocyte proliferation using in vitro and in vivo models. In primary mouse keratinocyte cultures, PGE2 activated the epidermal growth factor receptor (EGFR) and its downstream signaling pathways as well as increased cyclic AMP (cAMP) production and activated the cAMP response element binding protein (CREB). EGFR activation was not significantly inhibited by pretreatment with a c-src inhibitor (PP2), nor by a protein kinase A inhibitor (H-89). However, PGE2-stimulated extracellularly regulated kinase 1/2 (ERK1/2) activation was completely blocked by EGFR, ERK1/2, and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors. In addition, these inhibitors attenuated the PGE2-induced proliferation, nuclear factor-κB, activator protein-1 (AP-1), and CREB binding to the promoter regions of the cyclin D1 and vascular endothelial growth factor (VEGF) genes and expression of cyclin D1 and VEGF in primary mouse keratinocytes. Similarly, in vivo, we found that WT mice treated with PGE2 and untreated cyclooxygenase-2–overexpressing transgenic mice had higher levels of cell proliferation and expression of cyclin D1 and VEGF, as well as higher levels of activated EGFR, nuclear factor-κB, AP-1, and CREB, than vehicle-treated WT mice. Our findings provide evidence for a link between cyclooxygenase-2 overexpression and EGFR-, ERK-, PI3K-, cAMP-mediated cell proliferation, and the tumor-promoting activity of PGE2 in mouse skin. (Mol Cancer Res 2008;6(6):1003–16)
Familiarity or Conceptual Priming: Event-related Potentials in Name Recognition
Authors: Stenberg Georg , Hellman Johan , Johansson Mikael , Rosén Ingmar 
Published: June 2008

AbstractRecent interest has been drawn to the separate components of recognition memory, as studied by event-related potentials (ERPs). In ERPs, recollection is usually accompanied by a late, parietal positive deflection. An earlier, frontal component has been suggested to be a counterpart, accompanying recognition by familiarity. However, this component, the FN400, has alternatively been suggested to reflect a form of implicit memory, conceptual priming. The present study examined the ERP components of recognition memory using an episodic memory task with a stimulus material consisting of names, half of which were famous. Along a different dimension, the names varied in how rare or common they were. These dimensions, frequency and fame, exerted powerful effects on memory accuracy, and dissociated the two recognition processes, such that frequency gave rise to familiarity and fame fostered recollection, when the receiver operating characteristics data were analyzed with Yonelinas' dual-process signal detection model. The ERPs corresponded fully to the behavioral data because frequency affected the frontal component exclusively, and fame affected the parietal component exclusively. Moreover, a separate behavioral experiment showed that conceptual priming was sensitive to fame, but not to frequency. Our data therefore indicate that the FN400 varies jointly with familiarity, but independently of conceptual priming.
The Influence of Soil and Vegetation Parameters on Atmospheric Variables Relevant for Convection in the Sahel
Authors: Lauwaet D. , De Ridder K. , van Lipzig N. P. M. 
Published: June 2008

Abstract
A key issue in modeling the Sahelian climate is to correctly predict the energy fluxes between the land surface and the atmosphere. A problem faced by land surface models in the Sahel is the horizontal heterogeneity of soil and vegetation properties in the region, where measured data are scarce. Experiments have been designed to evaluate a land surface model both in offline mode and coupled to the Advanced Regional Prediction System (ARPS), a mesoscale atmospheric model. For the evaluation in offline mode, an observational dataset of 58 days from the Hydrological and Atmospheric Pilot Experiment in the Sahel (HAPEX-Sahel) is gathered to interpret the results. For the evaluation in the coupled mode, boundary layer development is simulated for 4 individual days. The model is able to reproduce the observations close to measurement errors. Sensitivity experiments are conducted to identify the most important parameters that affect the simulation of the convective available potential energy (CAPE) and the equivalent potential temperature (θe), two variables closely linked to convection and rainfall in the Sahel. During the selected cases, model results depend significantly on the soil moisture conditions. When bare soil evaporation is dominant, the soil parameters have the most impact on CAPE and θe, whereas in dry soil conditions, the vegetation parameters gain in importance. Differences due to the change of one parameter can reach 400 J kg−1 for CAPE and 4 K for θe, which is large enough to affect local convection.
Linkages between Orographic Forcing and the Scaling Properties of Convective Rainfall in Mountainous Regions
Authors: Nykanen Deborah K. 
Published: June 2008

Abstract
Heavy rainfall over mountainous terrain often results in catastrophic flooding and presents a great challenge for forecasters. Statistical downscaling methods provide a way to bridge across the scale gap between rainfall forecasts from numerical weather prediction models and the high-resolution needs of hydrologic models for flash flood prediction. In this study, multiscale statistical analysis was used to analyze several heavy convective rainfall events that produced catastrophic flooding in the Appalachian Mountains and Front Range of the Rocky Mountains with the motivation of developing predictive relationships for a priori parameter estimation needed in downscaling applications. The multiscale behavior of the rainfall was analyzed over time and linked to underlying topographic elevation and predominate orographic forcing. It was found that in storms located on the leeward side (i.e., the side of the mountain facing away from the upper-level winds), one of the parameters increased with increasing topographic elevation. An opposite trend was found for this parameter in storms located on the windward side (i.e., the side of the mountain facing toward the direction of the upper-level winds). These trends held across different geographical regions and both upslope and downslope directions of storm motion. The interaction between orographic and meteorological forcings was found to be important in developing predictive relationships for the multiscale statistical parameters.
Short-Range Precipitation Forecasts from Time-Lagged Multimodel Ensembles during the HMT-West-2006 Campaign
Authors: Yuan Huiling , McGinley John A. , Schultz Paul J. , Anderson Christopher J. , Lu Chungu 
Published: June 2008

Abstract
High-resolution (3 km) time-lagged (initialized every 3 h) multimodel ensembles were produced in support of the Hydrometeorological Testbed (HMT)-West-2006 campaign in northern California, covering the American River basin (ARB). Multiple mesoscale models were used, including the Weather Research and Forecasting (WRF) model, Regional Atmospheric Modeling System (RAMS), and fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). Short-range (6 h) quantitative precipitation forecasts (QPFs) and probabilistic QPFs (PQPFs) were compared to the 4-km NCEP stage IV precipitation analyses for archived intensive operation periods (IOPs). The two sets of ensemble runs (operational and rerun forecasts) were examined to evaluate the quality of high-resolution QPFs produced by time-lagged multimodel ensembles and to investigate the impacts of ensemble configurations on forecast skill. Uncertainties in precipitation forecasts were associated with different models, model physics, and initial and boundary conditions. The diabatic initialization by the Local Analysis and Prediction System (LAPS) helped precipitation forecasts, while the selection of microphysics was critical in ensemble design. Probability biases in the ensemble products were addressed by calibrating PQPFs. Using artificial neural network (ANN) and linear regression (LR) methods, the bias correction of PQPFs and a cross-validation procedure were applied to three operational IOPs and four rerun IOPs. Both the ANN and LR methods effectively improved PQPFs, especially for lower thresholds. The LR method outperformed the ANN method in bias correction, in particular for a smaller training data size. More training data (e.g., one-season forecasts) are desirable to test the robustness of both calibration methods.
A New Parsimonious Methodology of Mapping the Spatial Variability of Annual Maximum Rainfall in Mountainous Environments
Authors: Boni G. , Parodi A. , Siccardi F. 
Published: June 2008

Abstract
The estimation of rare frequency rainfall is an essential prerequisite for the design of engineering structures and to determine risk areas. Index-based methods are among the most applied for regional frequency analysis of hydrological variables such as discharge and rainfall and comprise two stages: the mapping of a scale or “index” factor and the derivation of rainfall growth curves. The underlying hypothesis of these methods is that cumulative distribution functions of a certain random variable can be assumed homogeneous on a given region, except for the index factor, which varies spatially in that region and is often represented by the expected value of the random variable itself at a given location. Methods either to single out homogeneous regions or to evaluate the index factor can be purely statistical and physically based.
In this paper a robust and transferable physically based methodology is proposed to estimate the index factor for rainfall in mountainous regions referred to in the following text as “index rainfall.” Index rainfall is defined as the expected value of annual rainfall maxima recorded in a fixed time window: a time window of 1 h is used. Reliable estimates of the index rainfall are obtained at ungauged sites by applying a relationship, based on a multivariate linear regression obtained at gauged sites, of rainfall and selected synthetic descriptors for atmospheric climate and orography. An extended and general set of descriptors is chosen from parameters that are considered in the literature to affect rainfall intensity. The relevant relief descriptors, defining slope, elevation, orientation, etc., at a given location, are extracted from digital elevation models (DEMs). A 2D Fourier series analysis of the DEM is performed and a spectral analysis is carried out to single out the components with the highest morphological information content. The synthetic relief descriptors are evaluated along different cross sections of the 2D truncated Fourier series to single out the role of the prevailing convection direction of extreme rainfall-producing meteorological patterns. The optimal descriptor subset for the study area is then extracted to maximize transferability of the method. Application to the Italian and French Alps and the Apennines shows encouraging results. Descriptor subset extraction has been tested and validated on independent subsets of index rainfall estimates in the regions. Results demonstrate that the proposed method is robust, transferable, and reliable for the evaluation of the index rainfall in ungauged sites.
A New Metric for Estimating the Influence of Evaporation on Seasonal Precipitation Rates
Authors: Anderson Bruce T. , Salvucci Guido , Ruane Alex C. , Roads John O. , Kanamitsu Masao 
Published: June 2008

Abstract
The objective of this paper is to introduce a diagnostic metric—termed the local-convergence ratio—that can be used to quantify the contribution of evaporation (and transpiration) to the atmospheric hydrologic cycle, and precipitation in particular, over a given region. Previous research into regional moisture (or precipitation) recycling has produced numerous methods for estimating the contributions of “local” (i.e., evaporated) moisture to climatological precipitation and its variations. In general, these metrics quantify the evaporative contribution to the mass of precipitable water within an atmospheric column by comparing the vertically integrated atmospheric fluxes of moisture across a region with the fluxes via evaporation. Here a new metric is proposed, based on the atmospheric moisture tendency equation, which quantifies the evaporative contribution to the rate of precipitation by comparing evaporative convergence into the column with large-scale moisture-flux convergence. Using self-consistent, model-derived estimates of the moisture-flux fields and the atmospheric moisture tendency terms, the authors compare estimates of the flux-based moisture-recycling ratio with the newly introduced local-convergence ratio. Differences between the two ratios indicate that they can be considered complementary, but independent, descriptors of the atmospheric hydroclimatology for a given region.
An Investigation of the Thermal and Energy Balance Regimes of Great Slave and Great Bear Lakes
Authors: Rouse Wayne R. , Blanken Peter D. , Bussières Normand , Walker Anne E. , Oswald Claire J. , Schertzer William M. , Spence Christopher 
Published: June 2008

Abstract
Great Slave Lake and Great Bear Lake have large surface areas, water volumes, and high latitudinal positions; are cold and deep; and are subject to short daylight periods in winter and long ones in summer. They are dissimilar hydrologically. Great Slave Lake is part of the Mackenzie Basin flowthrough system. Great Bear Lake is hydrologically isolated in its own relatively small drainage basin and all of its inflow and outflow derive from its immediate watershed. Great Slave Lake’s outflow into the Mackenzie River is more than 8 times that from Great Bear Lake. Input from the south via the Slave River provides 82% of this outflow volume. These hydrological differences exert pronounced effects on the thermodynamics, hydrodynamics, and surface climates of each lake. The quantitative results in this study are based on limited datasets from different years that are normalized to allow comparison between the two lakes. They indicate that both lakes have regional annual air temperatures within 2°C of one another, but Great Slave Lake exhibits a much longer open-water period with higher temperatures than Great Bear Lake. During the period when the lakes are warming, each lake exerts a substantial overlake atmospheric cooling, and in the period when the lakes are cooling, each exerts a strong overlake warming. This local cooling and warming cycle is greatest over Great Bear Lake. Temperature and humidity inversions are frequent early in the lake-warming season and very strong lapse gradients occur late in the lake-cooling season. Annually, for both lakes, early ice breakup is matched with late freeze-up. Conversely, late breakup is matched with early freeze-up. The magnitudes of midlake latent heat fluxes (evaporation) and sensible heat fluxes from Great Slave Lake are substantially larger than those from Great Bear Lake during their respective open-water periods. The hypothesis that because they are both large and deep, and are located in high latitudes, Great Slave Lake and Great Bear Lake will exhibit similar surface and near-surface climates that are typical of large lakes in the high latitudes proves invalid because their different hydrological systems impose very different thermodynamic regimes on the two lakes. Additionally, such an extensive north-flowing river system as the Mackenzie is subjected to latitudinally variable meteorological regimes that will differentially influence the hydrology and energy balance of these large lakes. Great Slave Lake is very responsive to climatic variability because of the relation between lake ice and absorbed solar radiation in the high sun season and we expect that Great Bear Lake will be affected in a similar fashion.
Empirical Correction of the NCEP Global Forecast System
Authors: Yang Xiaosong , DelSole Timothy , Pan Hua-Lu 
Published: June 2008

Abstract
This paper examines the extent to which an empirical correction method can improve forecasts of the National Centers for Environmental Prediction (NCEP) operational Global Forecast System. The empirical correction is based on adding a forcing term to the prognostic equations equal to the negative of the climatological tendency errors. The tendency errors are estimated by a least squares method using 6-, 12-, 18-, and 24-h forecast errors. Tests on independent verification data show that the empirical correction significantly reduces temperature biases nearly everywhere at all lead times up to at least 5 days but does not significantly reduce biases in forecast winds and humidity. Decomposing mean-square error into bias and random components reveals that the reduction in total mean-square error arises solely from reduction in bias. Interestingly, the empirical correction increases the random error slightly, but this increase is argued to be an artifact of the change in variance in the forecasts. The empirical correction also is found to reduce the bias more than traditional “after the fact” corrections. The latter result might be a consequence of the very different sample sizes available for estimation, but this difference in sample size is unavoidable in operational situations in which limited calibration data are available for a given forecast model.
Energy Recovering in Active Vibration Isolation System — Results of Experimental Research
Authors: Kowal Janusz , Pluta Janusz , Konieczny Jarosław , Kot Andrzej 
Published: June 2008

Studies of systems with energy regeneration have been carried out for years, because they primarily cover the assemblies with electrodynamic actuators. This paper addresses the issue of active reduction of mechanical vibration using an electrohydraulic actuator. The testing procedure aims to assess the potential use of those assemblies in a different frequency band and force range than in electrodynamic actuators. The paper explains the operating principle of the system, and the findings of laboratory tests are presented. The tested vibration reducing system is the physical model of a 2 degree-of-freedom (DOF) suspension. An initial analysis has been conducted to explore the potential use of the energy produced by the vibration of unsprung mass in the first degree of the suspension system, for power supply to the active component incorporated in the second suspension degree. The energy recuperated from the first suspension DOF is transferred by a dedicated hydraulic system and stored in an accumulator. Results of the experiments revealed that the mechanical parameters of the system can be selected in such a way that for specific interfering signals the accumulated energy should be at least equal to the energy used up by the system.
DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication
Authors: Whitman Susan P. , Hackanson Björn , Liyanarachchi Sandya , Liu Shujun , Rush Laura J. , Maharry Kati , Margeson Dean , Davuluri Ramana , Wen Jing , Witte Tatiana , Yu Li , Liu Chunhui , Bloomfield Clara D. , Marcucci Guido , Plass Christoph , Caligiuri Michael A. 
Published: June 2008

Abstract
Posttranslationally modified histones and DNA hypermethylation frequently interplay to deregulate gene expression in cancer. We report that acute myeloid leukemia (AML) with an aberrant histone methyltransferase, the mixed lineage leukemia partial tandem duplication (MLL-PTD), exhibits increased global DNA methylation versus AML with MLL-wildtype (MLL-WT; P = .02). Among the differentially methylated genes, the SLC5A8 tumor suppressor gene (TSG) was more frequently hypermethylated (P = .003). In MLL-PTD+ cell lines having SLC5A8 promoter hypermethylation, incubation with decitabine activated SLC5A8 expression. Ectopic SLC5A8 expression enhanced histones H3 and H4 acetylation in response to the histone deacetylase inhibitor, valproate, consistent with the encoded protein—SMCT1—short-chain fatty acid transport function. In addition, enhanced cell death was observed in SMCT1-expressing MLL-PTD+ AML cells treated with valproate. Within the majority of MLL-PTD AML is a mechanism in which DNA hypermethylation silences a TSG that, together with MLL-PTD, can contribute further to aberrant chromatin remodeling and altered gene expression.
Silencing of T lymphocytes by antigen-driven programmed death in recombinant adeno-associated virus vector–mediated gene therapy
Authors: Velazquez Victoria M. , Bowen David G. , Walker Christopher M. 
Published: June 2008

AbstractRecombinant adeno-associated virus (rAAV) vectors are considered promising for human gene replacement because they facilitate stable expression of therapeutic proteins in transduced tissues. Whether the success of gene therapy will be influenced by cellular immune responses targeting transgene-encoded proteins that are potentially immunogenic is unknown. Here we characterized CD8+ T-cell activity against β-galactosidase and enhanced green fluorescent protein, model antigens containing major histocompatibility complex (MHC) class I epitopes that are constitutively produced in murine skeletal muscle after rAAV vector transduction. Antigen-specific CD8+ T cells were detected in the spleen and liver of mice within 7 days of muscle transduction. CD8+ T-cell frequencies in these organs were stable, and effector functions were intact for months despite ongoing antigen production in muscle. CD8+ T cells also infiltrated transduced muscle, where frequencies were at least 5-fold higher than in untransduced spleen and liver. Significantly, the majority of antigen-specific CD8+ T cells in vector-transduced muscle were not functional. Loss of function in the muscle was associated with programmed death of the effector cells. Stable gene expression therefore depended on selective death of CD8+ T cells at the site of antigen production, an effective mechanism for subverting immunity that is also potentially reversible.