bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong Evidence of a Genetic Determinant for Mammographic Density, a Major Risk Factor for Breast Cancer
Authors: Vachon Celine M. , Sellers Thomas A. , Carlson Erin E. , Cunningham Julie M. , Hilker Christopher A. , Smalley Regenia L. , Schaid Daniel J. , Kelemen Linda E. , Couch Fergus J. , Pankratz V. Shane 
Published: September 2007

AbstractIncreased mammographic density (MD), the proportion of dense tissue visible on a mammogram, is a strong risk factor for breast cancer, common in the population and clusters in families. We conducted the first genome-wide linkage scan to identify genes influencing MD. DNA was obtained from 889 relatives (756 women, 133 men) from 89 families. Percent MD was estimated on 618 (82%) female family members using a validated computer-assisted thresholding method. The genome-wide scan included 403 microsatellite DNA markers with an average spacing of 9 cM. Fine mapping of a region of chromosome 5p (5p13.1-5p15.1) was done using 21 additional closely spaced DNA markers. Linkage analyses were conducted to quantify the evidence for a gene responsible for MD across the genome. The maximum log odds for linkage (LOD) score from the genome-wide scan was on chromosome 5p (LOD = 2.9, supporting linkage by a factor of 102.9 or 794 to 1) with a 1-LOD interval spanning 28.6 cM. Two suggestive regions for linkage were also identified on chromosome 12 (LOD = 2.6, 1-LOD interval of 14.8 cM; and LOD = 2.5, 1-LOD interval of 17.2 cM). Finer mapping of the region surrounding the maximum LOD on chromosome 5p resulted in stronger and statistically significant evidence for linkage (LOD = 4.2) and a narrowed 1-LOD interval (13.4 cM). The putative locus on chromosome 5p is likely to account for up to 22% of variation in MD. Hence, 1 or more of the 45 candidate genes in this region could explain a large proportion of MD and, potentially, breast cancer. [Cancer Res 2007;67(17):8412–8]
Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells
Authors: Wang Zhiwei , Banerjee Sanjeev , Kong Dejuan , Li Yiwei , Sarkar Fazlul H. 
Published: September 2007

Abstract
The Forkhead Box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes involved in cell proliferation, differentiation, and transformation. Overexpression of FoxM1 has been found in a variety of aggressive human carcinomas including pancreatic cancer. However, the precise role and the molecular mechanism of action of FoxM1 in pancreatic cancer remain unclear. To elucidate the cellular and molecular function of FoxM1, we tested the consequences of down-regulation and up-regulation of FoxM1 in pancreatic cancer cells, respectively. Using multiple cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, gene transfection, flow cytometry, real-time reverse transcription-PCR, Western blotting, migration, invasion, and angiogenesis assays, we found that down-regulation of FoxM1 inhibited cell growth, decreased cell migration, and decreased invasion of pancreatic cancer cells. FoxM1 down-regulation also decreased cell population in the S phase. Compared with control, FoxM1 small interfering RNA–transfected cells showed decreased expression of cyclin B, cyclin D1, and Cdk2, whereas p21 and p27 expression was increased. We also found that down-regulation of FoxM1 reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor, resulting in the inhibition of migration, invasion, and angiogenesis. These findings suggest that FoxM1 down-regulation could be a novel 1:49 AM 8/29/2007approach for the inhibition of pancreatic tumor progression. [Cancer Res 2007;67(17):8293–300]
NAC-1 Controls Cell Growth and Survival by Repressing Transcription of Gadd45GIP1, a Candidate Tumor Suppressor
Authors: Nakayama Kentaro , Nakayama Naomi , Wang Tian-Li , Shih Ie-Ming 
Published: September 2007

Abstract
Cancer mortality and morbidity are primarily related to recurrent tumors, and characterization of recurrence-associated genes should illuminate fundamental properties of tumor progression and provide new therapeutic targets. We have previously identified NAC-1, a member of the BTB/POZ gene family and a transcription repressor, as a gene associated with recurrent ovarian carcinomas after chemotherapy. We further showed that homodimerization of NAC-1 proteins is essential for tumor growth and survival. In this study, we applied serial analysis of gene expression and identified growth arrest and DNA-damage–inducible 45-γ interacting protein (Gadd45GIP1) as one of the downstream genes negatively regulated by NAC-1. NAC-1 knockdown in both SKOV3 and HeLa cells that expressed abundant endogenous NAC-1 induced Gadd45GIP1 expression transcriptionally; on the other hand, engineered expression of NAC-1 in NAC-1–negative RK3E and HEK293 cells suppressed endogenous Gadd45GIP1 expression. In NAC-1–expressing tumor cells, induction of dominant negative NAC-1 conferred a growth-inhibitory effect that can be partially reversed by Gadd45GIP1 knockdown. Induced Gadd45GIP1 expression resulted in growth arrest in SKOV3 and HeLa cells both in vitro and in vivo. In summary, NAC-1 contributes to tumor growth and survival by at least inhibiting Gadd45GIP1 expression, which has a tumor suppressor effect in cancer cells. [Cancer Res 2007;67(17):8058–64]
Crystal Structure of the T315I Abl Mutant in Complex with the Aurora Kinases Inhibitor PHA-739358
Authors: Modugno Michele , Casale Elena , Soncini Chiara , Rosettani Pamela , Colombo Riccardo , Lupi Rosita , Rusconi Luisa , Fancelli Daniele , Carpinelli Patrizia , Cameron Alexander D. , Isacchi Antonella , Moll Jürgen 
Published: September 2007

Abstract
Mutations in the kinase domain of Bcr-Abl are the most common cause of resistance to therapy with imatinib in patients with chronic myelogenous leukemia (CML). Second-generation Bcr-Abl inhibitors are able to overcome most imatinib-resistant mutants, with the exception of the frequent T315I substitution, which is emerging as a major cause of resistance to these drugs in CML patients. Structural studies could be used to support the drug design process for the development of inhibitors able to target the T315I substitution, but until now no crystal structure of the T315I Abl mutant has been solved. We show here the first crystal structure of the kinase domain of Abl T315I in complex with PHA-739358, an Aurora kinase inhibitor currently in clinical development for solid and hematologic malignancies. This compound inhibits in vitro the kinase activity of wild-type Abl and of several mutants, including T315I. The cocrystal structure of T315I Abl kinase domain provides the structural basis for this activity: the inhibitor associates with an active conformation of the kinase domain in the ATP-binding pocket and lacks the steric hindrance imposed by the substitution of threonine by isoleucine. [Cancer Res 2007;67(17):7987–90]
A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN-Mutant Glioma
Authors: Fan Qi-Wen , Cheng Christine K. , Nicolaides Theodore P. , Hackett Christopher S. , Knight Zachary A. , Shokat Kevan M. , Weiss William A. 
Published: September 2007

Abstract
We have shown previously that blockade of epidermal growth factor receptor (EGFR) cooperates with a pan-selective inhibitor of phosphoinositide-3-kinase (PI3K) in EGFR-driven glioma. In this communication, we tested EGFR-driven glioma differing in PTEN status, treating with the EGFR inhibitor erlotinib and a novel dual inhibitor of PI3Kα and mTOR (PI-103). Erlotinib blocked proliferation only in PTENwt cells expressing EGFR. Although erlotinib monotherapy showed little effect in PTENmt glioma, PI-103 greatly augmented the antiproliferative efficacy of erlotinib in this setting. To address the importance of PI3K blockade, we showed in PTENmt glioma that combining PI-103 and erlotinib was superior to either monotherapy or to therapy combining erlotinib with either rapamycin (an inhibitor of mTOR) or PIK-90 (an inhibitor of PI3Kα). These experiments show that a dual inhibitor of PI3Kα and mTOR augments the activity of EGFR blockade, offering a mechanistic rationale for targeting EGFR, PI3Kα, and mTOR in the treatment of EGFR-driven, PTEN-mutant glioma. [Cancer Res 2007;67(17):7960–5]
Dynamic Calibration with an Ensemble Kalman Filter Based Data Assimilation Approach for Root-Zone Moisture Predictions
Authors: Montaldo Nicola , Albertson John D. , Mancini Marco 
Published: September 2007

AbstractIn the presence of uncertain initial conditions and soil hydraulic properties, land surface model (LSM) performance can be significantly improved by the assimilation of periodic observations of certain state variables, such as the near-surface soil moisture (θg), as observed from a remote platform. In this paper the possibility of merging observations and the model optimally for providing robust predictions of root-zone soil moisture (θ2) is demonstrated. An assimilation approach that assimilates θg through the ensemble Kalman filter (EnKF) and provides a physics-based update of θ2 is developed. This approach, as with other common soil moisture assimilation approaches, may fail when a key LSM parameter, for example, the saturated hydraulic conductivity (ks), is estimated poorly. This leads to biased model errors producing a violation of a main assumption (model errors with zero mean) of the EnKF. For overcoming this model bias an innovative assimilation approach is developed that accepts this violation in the early model run times and dynamically calibrates all the components of the ks ensemble as a function of the persistent bias in root-zone soil moisture, allowing one to remove the model bias, restore the fidelity to the EnKF requirements, and reduce the model uncertainty. The robustness of the proposed approach is also examined in sensitivity analyses.
A Brief Evaluation of Precipitation from the North American Regional Reanalysis
Authors: Bukovsky Melissa S. , Karoly David J. 
Published: September 2007

Abstract
Several aspects of the precipitation climatology from the North American Regional Reanalysis (NARR) are analyzed and compared with two other reanalyses and one set of gridded observations over a domain encompassing the United States. The spatial distribution, diurnal cycle, and annual cycle of precipitation are explored to establish the reliability of the reanalyses and to judge their usefulness. While the NARR provides a much improved representation of precipitation over that of the other reanalyses examined, some inaccuracies are found and have been highlighted as a warning to potential users of the data.
The Partitioning of Evapotranspiration into Transpiration, Soil Evaporation, and Canopy Evaporation in a GCM: Impacts on Land–Atmosphere Interaction
Authors: Lawrence David M. , Thornton Peter E. , Oleson Keith W. , Bonan Gordon B. 
Published: September 2007

Abstract
Although the global partitioning of evapotranspiration (ET) into transpiration, soil evaporation, and canopy evaporation is not well known, most current land surface schemes and the few available observations indicate that transpiration is the dominant component on the global scale, followed by soil evaporation and canopy evaporation. The Community Land Model version 3 (CLM3), however, does not reflect this global view of ET partitioning, with soil evaporation and canopy evaporation far outweighing transpiration. One consequence of this unrealistic ET partitioning in CLM3 is that photosynthesis, which is linked to transpiration through stomatal conductance, is significantly underestimated on a global basis. A number of modifications to CLM3 vegetation and soil hydrology parameterizations are described that improve ET partitioning and reduce an apparent dry soil bias in CLM3. The modifications reduce canopy interception and evaporation, reduce soil moisture stress on transpiration, increase transpiration through a more realistic canopy integration scheme, reduce within-canopy soil evaporation, eliminate lateral drainage of soil water, increase infiltration of water into the soil, and increase the vertical redistribution of soil water. The partitioning of ET is improved, with notable increases seen in transpiration (13%–41% of global ET) and photosynthesis (65–148 Pg C yr−1). Soils are wetter and exhibit a far more distinct soil moisture annual cycle and greater interseasonal soil water storage, which permits plants to sustain transpiration through the dry season.
The broader influences of improved ET partitioning on land–atmosphere interaction are diverse. Stronger transpiration and reduced canopy evaporation yield an extended ET response to rain events and a shift in the precipitation distribution toward more frequent small- to medium-size rain events. Soil moisture memory time scales decrease particularly at deeper soil levels. Subsurface soil moisture exerts a slightly greater influence on precipitation. These results indicate that partitioning of ET is an important responsibility for land surface schemes, a responsibility that will gain in relevance as GCMs evolve to incorporate ever more complex treatments of the earth’s carbon and hydrologic cycles.
An Improved Gridded Historical Daily Precipitation Analysis for Brazil
Authors: Silva Viviane B. S. , Kousky Vernon E. , Shi Wei , Higgins R. Wayne 
Published: September 2007

Abstract
A gauge-only precipitation data quality control and analysis system has been developed for monitoring precipitation at NOAA’s Climate Prediction Center (CPC). Over the past 10 yr the system has been used to develop and deliver many different precipitation products over the United States, Mexico, and Central and South America. Here the authors describe how the system has been applied to develop improved gridded daily precipitation analyses over Brazil. Consistent with previous studies, comparisons between the the gridded analyses and station observations reveal fewer dry days, a greater number of low precipitation days, and fewer extreme precipitation events in the gridded analyses. Even though the gridded analysis system reduces the number of dry days and increases the number of wet days, there is still a good correlation between time series of the gridpoint precipitation values and observations.
Retrospective analyses are important for computing basic statistics such as mean daily/monthly rainfall, extremes, and probabilities of wet and dry days. The CPC gridded precipitation analyses can be used in hydrologic and climate variability studies dealing with large spatial-scale anomaly patterns, such as those related to ENSO. The analyses can also be used as a benchmark for evaluating model simulations, serve as a basis for real-time monitoring, and provide statistics on the occurrence of large-scale heavy rainfall events and dry periods.
Modeling and Analysis of the Variability of the Water Cycle in the Upper Rio Grande Basin at High Resolution
Authors: Li J. , Gao X. , Sorooshian S. 
Published: September 2007

Abstract
Estimating the water budgets in a small-scale basin is a challenge, especially in the mountainous western United States, where the terrain is complex and observational data in the mountain areas are sparse. This manuscript reports on research that downscaled 5-yr (1999–2004) hydrometeorological fields over the upper Rio Grande basin from a 2.5° NCEP–NCAR reanalysis to a 4-km local scale using a regional climate model [fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5), version 3]. The model can reproduce the terrain-related precipitation distribution—the trend of diurnal, seasonal, and interannual precipitation variability—although poor snow simulation caused it to overestimate precipitation and evapotranspiration in the cold season. The outcomes from the coupled model are also comparable to offline Variable Infiltration Capacity (VIC) and Land Data Assimilation System (LDAS)/Mosaic land surface simulations that are driven by observed and/or analyzed surface meteorological data.
The Influence of Mechanical and Thermal Forcing by the Tibetan Plateau on Asian Climate
Authors: Wu Guoxiong , Liu Yimin , Zhang Qiong , Duan Anmin , Wang Tongmei , Wan Rijin , Liu Xin , Li Weiping , Wang Zaizhi , Liang Xiaoyun 
Published: September 2007

Abstract
This paper attempts to provide some new understanding of the mechanical as well as thermal effects of the Tibetan Plateau (TP) on the circulation and climate in Asia through diagnosis and numerical experiments. The air column over the TP descends in winter and ascends in summer and regulates the surface Asian monsoon flow. Sensible heating on the sloping lateral surfaces appears from the authors’ experiments to be the major driving source. The retarding and deflecting effects of the TP in winter generate an asymmetric dipole zonal-deviation circulation, with a large anticyclone gyre to the north and a cyclonic gyre to the south. Such a dipole deviation circulation enhances the cold outbreaks from the north over East Asia, results in a dry climate in south Asia and a moist climate over the Indochina peninsula and south China, and forms the persistent rainfall in early spring (PRES) in south China. In summer the TP heating generates a cyclonic spiral zonal-deviation circulation in the lower troposphere, which converges toward and rises over the TP. It is shown that because the TP is located east of the Eurasian continent, in summertime the meridional winds and vertical motions forced by the Eurasian continental-scale heating and the TP local heating are in phase over the eastern and central parts of the continent. The monsoon in East Asia and the dry climate in middle Asia are therefore intensified.
Influence of Precipitation Assimilation on a Regional Climate Model’s Surface Water and Energy Budgets
Authors: Nunes Ana M. B. , Roads John O. 
Published: September 2007

Abstract
Initialization of the moisture profiles has been used to overcome the imbalance between analysis schemes and prediction models that generates the so-called spinup problem seen in the hydrological fields. Here precipitation assimilation through moisture adjustment has been proposed as a technique to reduce this problem in regional climate simulations by adjusting the specific humidity according to 3-hourly North American Regional Reanalysis rain rates during two simulated years: 1988 and 1993. A control regional simulation provided the initial condition fields for both simulations. The precipitation assimilation simulation was then compared to the control regional climate simulation, reanalyses, and observations to determine whether assimilation of precipitation had a positive influence on modeled surface water and energy budget terms. In general, rainfall assimilation improved the regional model surface water and energy budget terms over the conterminous United States. Precipitation and runoff correlated better than the control and the global reanalysis fields to the regional reanalysis and available observations. Upward shortwave and downward short- and longwave radiation fluxes had regional seasonal cycles closer to the observed values than the control, and the near-surface temperature anomalies were also improved.
Views and understanding of senior nursing staff in relation to infection control
Authors: Scott AA , Hughes J. , Hall D. 
Published: September 2007

ittle research has been conducted into the broad themes of the factors that encourage nurses to comply with infection control procedures — experimental approaches have dominated previous research. A qualitative study into the views and understanding of senior nurses related to infection control procedures was undertaken at a large district general hospital. This paper looks at a number of themes, which emerged as important bases for compliance with infection control procedures. This included the importance of role models, leadership, efficacy of link groups and communication links.
A study of the factors affecting the likelihood of patients participating in a campaign to improve staff hand hygiene
Authors: Duncanson V. , Pearson LS 
Published: September 2007

his study aimed to seek patient opinion on being asked to participate in a campaign to improve staff compliance with handwashing and to identify factors that may influence the likelihood of patients asking staff to wash their hands. A descriptive survey of 200 patients (150 participants, response rate 75 per cent) about to be discharged from an acute NHS Trust was completed. The age, gender, previous experience, opinions and personality traits of participants were explored. The results showed that 118 (79 per cent) thought they should be involved in helping staff improve hand hygiene and that extraversion was the only personality trait with a significant association with this tendency of wanting to be involved. Age was a significant factor in how likely participants were to ask different groups of staff and how they would feel about asking, with older people being more reluctant. Participants valued measures that facilitated them asking — staff wearing badges was the most popular of these. Groups of patients in this and other studies (National Patient Safety Agency, 2004) indicate that patients want to be involved in helping to improve hand hygiene. In practice, we need to acknowledge the complex nature of involving individuals in challenging staff to improve their own care, and also that hand hygiene is ultimately the responsibility of health professionals.
Solitary pulmonary nodule evaluation with99mTc-methoxy isobutyl isonitrile in a tuberculosis-endemic area
Authors: Schuurmans M. M. , Ellmann A. , Bouma H. , Diacon A. H. , Dyckmans K. , Bolliger C. T. 
Published: September 2007

High prevalence of tuberculosis increases the odds for nonmalignant solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using18F-fluorodeoxyglucose is the method of choice for the identification of malignant SPNs requiring curative surgery. However, PET is not widely available. Technetium-99m methoxy isobutyl isonitrile (MIBI) is inexpensive, widely available and shows increased uptake in malignant SPNs. The aim of the present study was to prospectively evaluate the diagnostic value of MIBI single photon emission computed tomography to distinguish between benign and malignant SPNs in a tuberculosis-endemic area.In total, 49 patients with radiologically indeterminate SPNs (single lesion ≤6 cm in diameter) were prospectively evaluated with MIBI. The final diagnosis was established with bronchoscopy, fine-needle aspiration, surgical resection or clinical follow-up for ≥2 yrs.A total of 12 (92%) out of 13 malignant lesions showed increased uptake of MIBI, while no uptake was observed in 33 (92%) out of 36 benign lesions. MIBI uptake indicated malignancy with a sensitivity and specificity of 92% and a negative predictive value of 97%.In this tuberculosis-endemic area, technetium-99m methoxy isobutyl isonitrile single photon emission computed tomography evaluation of solitary pulmonary nodules had a high negative predictive value. Therefore, it has the potential to prevent unnecessary surgical resections of benign nodules and serve as a low-cost alternative when positron emission tomography is not available.