bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat Prolactinoma Cell Growth Regulation by Epidermal Growth Factor Receptor Ligands
Authors: Vlotides George , Siegel Emily , Donangelo Ines , Gutman Shiri , Ren Song-Guang , Melmed Shlomo 
Published: August 2008

Abstract
Epidermal growth factor (EGF) regulates pituitary development, hormone synthesis, and cell proliferation. Although ErbB receptor family members are expressed in pituitary tumors, the effects of EGF signaling on pituitary tumors are not known. Immunoprecipitation and Western blot confirmed EGF receptor (EGFR) and p185c-neu protein expression in GH3 lacto-somatotroph but not in adrenocorticotropic hormone–secreting AtT20 pituitary tumor cells. EGF (5 nmol/L) selectively enhanced baseline (∼4-fold) and serum-induced (&gt;6-fold) prolactin (PRL) mRNA levels, whereas gefitinib, an EGFR antagonist, suppressed serum-induced cell proliferation and Pttg1 expression, blocked PRL gene expression, and reversed EGF-mediated somatotroph-lactotroph phenotype switching. Downstream EGFR signaling by ERK, but not phosphoinositide-3-kinase or protein kinase C, mediated the gefitinib response. Tumors in athymic mice implanted s.c. with GH3 cells resulted in weight gain accompanied by increased serum PRL, growth hormone, and insulin growth factor 1. Gefitinib decreased tumor volumes and peripheral hormone levels by ∼30% and restored normal mouse body weight patterns. Mice treated with gefitinib exhibited decreased tumor tissue ERK1/2 phosphorylation and down-regulated tumor PRL and Pttg1 mRNA abundance. These results show that EGFR inhibition controls tumor growth and PRL secretion in experimental lacto-somatotroph tumors. EGFR inhibitors could therefore be useful for the control of PRL secretion and tumor load in prolactinomas resistant to dopaminergic treatment, or for those prolactinomas undergoing rare malignant transformation. [Cancer Res 2008;68(15):6377–86]
Targeting Cancer Stem Cells through L1CAM Suppresses Glioma Growth
Authors: Bao Shideng , Wu Qiulian , Li Zhizhong , Sathornsumetee Sith , Wang Hui , McLendon Roger E. , Hjelmeland Anita B. , Rich Jeremy N. 
Published: August 2008

AbstractMalignant gliomas are lethal cancers that display striking cellular heterogeneity. A highly tumorigenic glioma tumor subpopulation, termed cancer stem cells or tumor-initiating cells, promotes therapeutic resistance and tumor angiogenesis. Therefore, targeting cancer stem cells may improve patient survival. We interrogated the role of a neuronal cell adhesion molecule, L1CAM, in glioma stem cells as L1CAM regulates brain development and is expressed in gliomas. L1CAM+ and CD133+ cells cosegregated in gliomas, and levels of L1CAM were higher in CD133+ glioma cells than normal neural progenitors. Targeting L1CAM using lentiviral-mediated short hairpin RNA (shRNA) interference in CD133+ glioma cells potently disrupted neurosphere formation, induced apoptosis, and inhibited growth specifically in glioma stem cells. We identified a novel mechanism for L1CAM regulation of cell survival as L1CAM knockdown decreased expression of the basic helix-loop-helix transcription factor Olig2 and up-regulated the p21WAF1/CIP1 tumor suppressor in CD133+ glioma cells. To determine if targeting L1CAM was sufficient to reduce glioma stem cell tumor growth in vivo, we targeted L1CAM in glioma cells before injection into immunocompromised mice or directly in established tumors. In each glioma xenograft model, shRNA targeting of L1CAM expression in vivo suppressed tumor growth and increased the survival of tumor-bearing animals. Together, these data show that L1CAM is required for maintaining the growth and survival of CD133+ glioma cells both in vitro and in vivo, and L1CAM may represent a cancer stem cell–specific therapeutic target for improving the treatment of malignant gliomas and other brain tumors. [Cancer Res 2008;68(15):6043–8]
Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy
Authors: Hingorani Mohan , White Christine L. , Zaidi Shane , Merron Andrew , Peerlinck Inge , Gore Martin E. , Nutting Christopher M. , Pandha Hardev S. , Melcher Alan A. , Vile Richard G. , Vassaux Georges , Harrington Kevin J. 
Published: August 2008

Abstract
Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)–mediated 131I therapy with EBRT.
Experimental Design: Expression of reporter genes [NIS, green fluorescent protein (GFP), β-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc.
Results: EBRT increased NIS, GFP, and β-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin αv) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors.
Conclusions: Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.
Prospective Study of the Accuracy of EGFR Mutational Analysis by High-Resolution Melting Analysis in Small Samples Obtained from Patients with Non–Small Cell Lung Cancer
Authors: Fukui Tomoya , Ohe Yuichiro , Tsuta Koji , Furuta Koh , Sakamoto Hiromi , Takano Toshimi , Nokihara Hiroshi , Yamamoto Noboru , Sekine Ikuo , Kunitoh Hideo , Asamura Hisao , Tsuchida Takaaki , Kaneko Masahiro , Kusumoto Masahiko , Yamamoto Seiichiro , Yoshida Teruhiko , Tamura Tomohide 
Published: August 2008

Abstract
Purpose: Epidermal growth factor receptor (EGFR) mutations, especially in-frame deletions in exon 19 (DEL) and a point mutation in exon 21 (L858R), predict gefitinib sensitivity in patients with non–small cell lung cancer (NSCLC). In this study, we verified the accuracy of EGFR mutation analysis in small samples by high-resolution melting analysis (HRMA), which is a rapid method using PCR amplification with a dye to analyze the melting curves in NSCLC.
Experimental Design: We designed a prospective study to compare the sensitivity and specificity of HRMA and DNA sequencing with laser capture microdissection. Eligible patients with lung lesions were screened by bronchoscopy or percutaneous needle biopsy to histologically confirm the diagnosis, followed by surgical resection of the NSCLC. Small diagnostic specimens were analyzed for EGFR mutations by HRMA, and the surgically resected specimens were examined for mutations by HRMA and DNA sequencing.
Results: The analyses for EGFR mutations were conducted in 52 eligible cases of the 92 enrolled patients. EGFR mutations were detected in 18 (34.6%) patients. The results of HRMA from surgically resected specimens as well as DNA sequencing revealed 100% sensitivity and specificity. On the other hand, the sensitivity and specificity of HRMA from the small diagnostic specimens were 83.3% and 100%, respectively.
Conclusions: In this study, we showed that HRMA is a highly accurate method for detecting DEL and L858R mutations in patients with NSCLC, although it is necessary to consider the identification of patients with a false-negative result when the analysis is conducted using small samples.
Telomere Maintenance in Laser Capture Microdissection–Purified Barrett's Adenocarcinoma Cells and Effect of Telomerase Inhibition In vivo
Authors: Shammas Masood A. , Qazi Aamer , Batchu Ramesh B. , Bertheau Robert C. , Wong Jason Y.Y. , Rao Manjula Y. , Prasad Madhu , Chanda Diptiman , Ponnazhagan Selvarangan , Anderson Kenneth C. , Steffes Christopher P. , Munshi Nikhil C. , De Vivo Immaculata , Beer David G. , Gryaznov Sergei , Weaver Donald W. , Goyal Raj K. 
Published: August 2008

Abstract
Purpose: The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of telomerase inhibition in cancer cells in vitro and in vivo.
Experimental Design: Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by β-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L.
Results: Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model.
Conclusions: We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo.
A 5-yr 40-km-Resolution Global Climatology of Superrefraction for Ground-Based Weather Radars
Authors: Lopez Philippe 
Published: August 2008

Abstract
The propagation of electromagnetic waves emitted from ground-based meteorological radars is determined by the stratification of the atmosphere. In extreme superrefractive situations characterized by strong temperature inversions or strong vertical gradients of moisture, the radar beam can be deflected toward the ground (ducting or trapping). This phenomenon often results in spurious returned echoes and misinterpretation of radar images such as erroneous precipitation detection. In this work, a 5-yr global climatology of the frequency of superrefractive and ducting conditions and of trapping-layer base height has been produced using refractivity computations from ECMWF temperature, moisture, and pressure analyses at a 40-km horizontal resolution. The aim of this climatology is to better document how frequent such events are, which is a prerequisite for fully benefiting from radar data information for the multiple purposes of model validation, precipitation analysis, and data assimilation. First, the main climatological features are summarized for the whole globe: high- and midlatitude oceans seldom experience superrefraction or ducting whereas tropical oceans are strongly affected, especially in regions where the trade wind inversion is intense and lying near the surface. Over land, seasonal averages of superrefraction (ducting) frequencies reach 80% (40%) over tropical moist areas year-round but remain below 40% (15%) in most other regions. A particular focus is then laid on Europe and the United States, where extensive precipitation radar networks already exist. Seasonal statistics exhibit a pronounced diurnal cycle of ducting occurrences, with averaged frequencies peaking at 60% in summer late afternoon over the eastern half of the United States, the Balkans, and the Po Valley but no ducts by midday. Similarly high ducting frequencies are found over the southwestern coast of the United States at night. A potentially strong reduction of ducting occurrences with increased radar height (especially in midlatitude summer late afternoon) is evidenced by initiating refractivity vertical gradient computations from either the lowest or the second lowest model level. However, installing radar on tall towers also brings other problems, such as a possible amplification of sidelobe clutter echoes.
On the Origin of the Standardization Sensitivity in RegEM Climate Field Reconstructions*
Authors: Smerdon Jason E. , Kaplan Alexey , Chang Diana 
Published: August 2008

Abstract
The regularized expectation maximization (RegEM) method has been used in recent studies to derive climate field reconstructions of Northern Hemisphere temperatures during the last millennium. Original pseudoproxy experiments that tested RegEM [with ridge regression regularization (RegEM-Ridge)] standardized the input data in a way that improved the performance of the reconstruction method, but included data from the reconstruction interval for estimates of the mean and standard deviation of the climate field—information that is not available in real-world reconstruction problems. When standardizations are confined to the calibration interval only, pseudoproxy reconstructions performed with RegEM-Ridge suffer from warm biases and variance losses. Only cursory explanations of this so-called standardization sensitivity of RegEM-Ridge have been published, but they have suggested that the selection of the regularization (ridge) parameter by means of minimizing the generalized cross validation (GCV) function is the source of the effect. The origin of the standardization sensitivity is more thoroughly investigated herein and is shown not to be associated with the selection of the ridge parameter; sets of derived reconstructions reveal that GCV-selected ridge parameters are minimally different for reconstructions standardized either over both the reconstruction and calibration interval or over the calibration interval only. While GCV may select ridge parameters that are different from those that precisely minimize the error in pseudoproxy reconstructions, RegEM reconstructions performed with truly optimized ridge parameters are not significantly different from those that use GCV-selected ridge parameters. The true source of the standardization sensitivity is attributable to the inclusion or exclusion of additional information provided by the reconstruction interval, namely, the mean and standard deviation fields computed for the complete modeled dataset. These fields are significantly different from those for the calibration period alone because of the violation of a standard EM assumption that missing values are missing at random in typical paleoreconstruction problems; climate data are predominantly missing in the preinstrumental period when the mean climate was significantly colder than the mean of the instrumental period. The origin of the standardization sensitivity therefore is not associated specifically with RegEM-Ridge, and more recent attempts to regularize the EM algorithm using truncated total least squares could theoretically also be susceptible to the problems affecting RegEM-Ridge. Nevertheless, the principal failure of RegEM-Ridge arises because of a poor initial estimate of the mean field, and therefore leaves open the possibility that alternative methods may perform better.
Artificial Skill due to Predictor Screening
Authors: DelSole Timothy , Shukla Jagadish 
Published: August 2008

AbstractThis paper shows that if predictors are selected preferentially because of their strong correlation with a prediction variable, then standard methods for validating prediction models derived from these predictors will be biased. This bias is demonstrated by screening random numbers and showing that regression models derived from these random numbers have apparent skill, in a cross-validation sense, even though the predictors cannot possibly have the slightest predictive usefulness. This result seemingly implies that random numbers can give useful predictions, since the sample being predicted is separate from the sample used to estimate the regression model. The resolution of this paradox is that, prior to cross validation, all of the data had been used to evaluate correlations for selecting predictors. This situation differs from real-time forecasts in that the future sample is not available for screening. These results clarify the fallacy in assuming that if a model performs well in cross-validation mode, then it will perform well in real-time forecasts. This bias appears to afflict several forecast schemes that have been proposed in the literature, including operational forecasts of Indian monsoon rainfall and number of Atlantic hurricanes. The cross-validated skill of these models probably would not be distinguishable from that of a no-skill model if prior screening were taken into account.
Pressure transient identification of depleted appliance trap seals: a sinusoidal wave technique
Authors: Kelly DA , Swaffield JA , Jack LB , Campbell DP , Gormley M. 
Published: August 2008

Depleted appliance trap seals were shown to be a causal factor in the spread of the SARS virus at the Amoy Gardens housing complex in Hong Kong in 2003. This serious health risk has emphasised the requirement for an effective maintenance regime to ensure trap seals do not again facilitate the spread of infection and disease. This paper introduces a remote and non-invasive technique to identify depleted trap seals through analysis of the system response to an applied sinusoidal pressure wave. The pressure signal will be analysed in both the time domain and the frequency domain to determine system status. Results obtained from laboratory experiments will be used to confirm the practicality of this technique while a Method of Characteristic based numerical model will validate the methodology. Practical application: The transients generated within the building drainage system as a result of normal system operation continue to pose a threat to the integrity of the appliance trap seal. The technique outlined in this paper will help to quickly identify defective trap seals to ensure that cross-contamination is minimised. However, it is important that this transient-based technique does not itself introduce an additional risk to trap integrity. A sinusoidal pressure wave offers a completely non-invasive testing option that will not only be of great advantage to facility managers but also to the building users due to the reduced risk of cross-contamination.
Suitability of time domain reflectometry for monitoring moisture in building materials
Authors: Phillipson MC , Baker PH , Davies M. , Ye Z. , Galbraith GH , McLean RC 
Published: August 2008

Time Domain Reflectometry (TDR) has been used since the 1980s for measuring the moisture content of soils. The principle of TDR is based on measuring the reflection time of an electromagnetic signal sent down a set of waveguides that are inserted into the material. This paper reports research work examining the suitability of TDR for measuring the moisture content of building materials. Results suggest that TDR is an effective way of monitoring relative changes in the moisture content. Measurement of absolute moisture content is more complicated as it requires a calibration function, and the existing empirical relationships used in the soil sciences consistently overestimate the moisture content. A semi-empirical calibration relationship has been found to offer a better approach to absolute moisture content evaluation with TDR. Practical application: This paper reports research work examining the suitability of TDR for application to the measurement of the moisture content of building materials. It finds that TDR can rapidly identify changes in the relative moisture content and may therefore be suited to monitoring the long-term moisture behaviour of a building material in situ. Application of the technique to the measurement of the absolute moisture content is more difficult; further work is needed to address the accuracy of absolute measurements.
Investigating the effect of indoor water canal on the cooling load estimation and condensation issues of Venetian Macao
Authors: Lu L. , Han J. , Yang HX 
Published: August 2008

This paper reports the influence of the presence of a water canal on the cooling load calculation for an air-conditioned recreation centre in Macao, and investigates the condensation issue of lower floor ceiling caused by the relatively low temperature of canal water. Different canal surface water activities (water activity factor) cause different evaporation rates of canal water and result in the changes of cooling load. It is found that the design of the large indoor water canal leads to the increase of design cooling load of the upper floor of the centre, for example 304 kW (when water temperature is 20°C and surface activity factor equals 1, which is the function of evaporation rate), and condensation of the lower floor ceiling under canal occurs after an operation break of the air-conditioning system. To minimise the cooling load increase due to the presence of a water canal, the water activity of the canal should be lowered as much as possible, and several energy saving measures are recommended. Furthermore, to avoid the possible condensation phenomena and issue of water drop from the ceiling under the canal, the air humidity of the space under the water canal should be controlled strictly according to the design conditions. Practical application: Heat and mass transfer between the large water surface and the air-conditioned space results in the change of space cooling load in the spaces with large indoor water canal. The influences of the presence of the water canal, due to its evaporation and heat loss, on the cooling load estimation of the space should be investigated for accurately evaluating the cooling load and properly sizing the air conditioning systems in such types of buildings with large interior water facilities. As the evaporation rate changes due to the water activity level of the canal, the change of cooling load should be estimated considering the water activity levels. On the other hand, for the air-conditioned spaces under the canal, there is the arising issue of condensation due to the low temperature of the canal water. Condensation will occur when the external surface temperature of canal wall is lower than the dew point temperature of the nearby air. The process of the possible condensation issues of the lower floor has been analysed and recommendations are proposed according to the simulation results. This paper is useful in the design of air conditioning system for such types of complexes.