bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of Neutrophil Gelatinase–Associated Lipocalin by ErbB2 through Nuclear Factor-κB Activation
Authors: Li Shau-Hsuan , Hawthorne Valerie S. , Neal Christopher L. , Sanghera Sartaj , Xu Jia , Yang Jun , Guo Hua , Steeg Patricia S. , Yu Dihua 
Published: December 2009

Abstract
ErbB2 (HER2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. Neutrophil gelatinase–associated lipocalin (NGAL) is a secreted glycoprotein expressed in a variety of cancers, including breast carcinomas. NGAL can inhibit erythroid cell production, leading to anemia. Anemia usually occurs in cancer patients and negatively affects quality of life. However, current treatment for cancer-related anemia has potential complications. ErbB2, NGAL, and anemia have all been associated with increased metastasis and poor prognosis in breast cancer patients, although the relationship between ErbB2 and NGAL expression is not clear. Here, using breast cancer cell lines in vitro and transgenic mice carrying the activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV-neu) in vivo, we show that ErbB2 overexpression leads to NGAL upregulation, which is dependent on nuclear factor-κB (NF-κB) activity. MMTV-neu transgenic mice developed anemia after tumor onset, and anemia progression could be partially arrested by a NF-κB inhibitor and ErbB2-targeted therapy. Taken together, upregulation of NGAL by ErbB2 through NF-κB activation is involved in cancer-related anemia, and the ErbB2, NF-κB, and NGAL pathways may serve as potential therapeutic targets for cancer-related anemia. [Cancer Res 2009;69(24):9163–8]
Cognitive Susceptibility to Smoking: Two Paths to Experimenting among Mexican Origin Youth
Authors: Spelman Amy R. , Spitz Margaret R. , Kelder Steven H. , Prokhorov Alexander V. , Bondy Melissa L. , Frankowski Ralph F. , Wilkinson Anna V. 
Published: December 2009

Abstract
Cognitive susceptibility to smoking, defined as the lack of a firm commitment not to smoke in the future or if offered a cigarette by a friend, begins in childhood and is an early phase in the transition from never to ever smoking. Our objectives were to examine susceptibility to smoking and other psychosocial risk factors for experimentation with cigarettes among Mexican origin adolescents and to determine whether susceptibility status moderates the relationship between established risk factors for experimentation with cigarettes and future experimentation. We examined susceptibility and several psychosocial factors associated with susceptibility as baseline predictors of experimentation after 3 years of follow-up among 964 Mexican origin girls and boys between 11 and 13 years of age from the Houston metropolitan area. Participants were recruited between May 2005 and October 2006 and reported that they had never experimented with cigarettes at baseline. Baseline susceptibility and experimentation rates were 23% and 9%, respectively, whereas the follow-up experimentation rate, among those who had not experimented at baseline, was 22%. Susceptible adolescents at baseline were 2.6 times more likely to have experimented with cigarettes by follow-up. Baseline susceptibility moderated the relationship between experimentation at follow-up and the psychosocial risk factors assessed at baseline. Susceptibility is a valid and strong marker for the transition to experimentation for Mexican origin adolescents. Our results suggest that tailoring primary prevention programs by a youth's susceptibility status may increase the efficacy of prevention efforts among Mexican origin youth.(Cancer Epidemiol Biomarkers Prev 2009;18(12):3459–67)
Exposure to Smoking Imagery in the Movies and Experimenting with Cigarettes among Mexican Heritage Youth
Authors: Wilkinson Anna V. , Spitz Margaret R. , Prokhorov Alexander V. , Bondy Melissa L. , Shete Sanjay , Sargent James D. 
Published: December 2009

Abstract
There is growing evidence that an adolescent's decision to try cigarettes is influenced by level of exposure to movies in which smoking is portrayed. Less is known about how ethnicity affects this process. We examined whether acculturation and/or country of birth influence the relationship between exposure to smoking imagery in the movies and experimenting with cigarettes among Mexican origin youth. We prospectively followed 1,328 Mexican origin adolescents ages 11 to 13 years at baseline. We assessed which of 50 movies (randomly selected from a pool of 250 popular contemporary movies released from 1999 to 2004 and content analyzed for smoking) adolescents had seen. Smoking behavior was assessed at baseline and at 6-month intervals over 24 months. Ten percent of the adolescents had experimented at baseline; 17% tried subsequently. Multivariate analyses revealed, as exposure to smoking imagery in the movies increased, the chances of having ever experimented [adjusted odds ratio (AOR) = 1.27; 95% confidence interval (CI), 1.10-1.48] and of being a new experimenter (AOR = 1.19; 95% CI, 1.01-1.40) increased, equivalent to a 4.2% increased risk of ever and a 3.0% increased risk of new experimenting for each additional quartile of movie exposure. This effect was moderated by country of birth. For Mexican-born youth, exposure to smoking imagery in the movies was the strongest independent predictor of new experimentation (AOR = 1.52; 95% CI, 1.14-2.05). For U.S.-born youth, we observed a ceiling effect: the percent of experimenters increased with increasing exposure, and then flattened. Among Mexican-born youth, exposure to smoking imagery in the movies may be an important part of the acculturation process associated with smoking initiation. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3435–43)
Triterpenoids CDDO-Methyl Ester or CDDO-Ethyl Amide and Rexinoids LG100268 or NRX194204 for Prevention and Treatment of Lung Cancer in Mice
Authors: Liby Karen , Risingsong Renee , Royce Darlene B. , Williams Charlotte R. , Ma Tian , Yore Mark M. , Sporn Michael B. 
Published: December 2009

Abstract
We tested members of two noncytotoxic classes of drugs, synthetic oleanane triterpenoids and rexinoids, both as individual agents and in combination, for the prevention and treatment of carcinogenesis in a highly relevant animal model of lung cancer. Lung adenocarcinomas were induced in A/J mice by injection of the carcinogen vinyl carbamate. Mice were fed drugs in diet, beginning 1 week after the carcinogen challenge for prevention or 8 weeks later for treatment. The number, size, and severity of tumors in the lungs were then evaluated. In the prevention studies, the triterpenoids CDDO-ethyl amide and CDDO-methyl ester reduced the average tumor burden (ATB) in the lungs 86% to 92%, respectively, compared with the controls, and the rexinoid LG100268 (268) reduced ATB by 50%. The combination of CDDO-ethyl amide and 268 reduced ATB by 93%. We show for the first time that these drugs also were highly effective for treatment of experimental lung cancer, and all triterpenoid and rexinoid combinations reduced ATB 85% to 87% compared with the control group. The triterpenoids also potently inhibited proliferation of VC1 mouse lung carcinoma cells and directly interacted with key regulatory proteins in these cells. In contrast, the rexinoids had little antiproliferative activity in VC1 cells but were potent inhibitors of the toll-like receptor pathway in macrophage-like cells. Triterpenoids and rexinoids are multifunctional, well-tolerated drugs that target different signaling pathways and are thus highly effective for prevention and treatment of experimental lung cancer.
Effects of Chlorophyll and Chlorophyllin on Low-Dose Aflatoxin B1 Pharmacokinetics in Human Volunteers
Authors: Jubert Carole , Mata John , Bench Graham , Dashwood Roderick , Pereira Cliff , Tracewell William , Turteltaub Kenneth , Williams David , Bailey George 
Published: December 2009

Abstract
Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats. These findings were partially extended to humans, where CHL reduced excretion of aflatoxin B1 (AFB1)-DNA repair products in Chinese unavoidably exposed to dietary AFB1. However, neither AFB1 pharmacokinetics nor Chla effects were examined. We conducted an unblinded crossover study to establish AFB1 pharmacokinetic parameters among four human volunteers, and to explore possible effects of CHL or Chla cotreatment in three of those volunteers. For protocol 1, fasted subjects received an Institutional Review Board–approved dose of 14C-AFB1 (30 ng, 5 nCi) by capsule with 100 mL water, followed by normal eating and drinking after 2 hours. Blood and cumulative urine samples were collected over 72 hours, and 14C- AFB1 equivalents were determined by accelerator mass spectrometry. Protocols 2 and 3 were similar except capsules also contained 150 mg of purified Chla or CHL, respectively. Protocols were repeated thrice for each volunteer. The study revealed rapid human AFB1 uptake (plasma ka, 5.05 ± 1.10 h−1; Tmax, 1.0 hour) and urinary elimination (95% complete by 24 hours) kinetics. Chla and CHL treatment each significantly impeded AFB1 absorption and reduced Cmax and AUCs (plasma and urine) in one or more subjects. These initial results provide AFB1 pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models.
Intravesical Delivery of Rapamycin Suppresses Tumorigenesis in a Mouse Model of Progressive Bladder Cancer
Authors: Seager Catherine M. , Puzio-Kuter Anna M. , Patel Trushar , Jain Shalini , Cordon-Cardo Carlos , Mc Kiernan James , Abate-Shen Cory 
Published: December 2009

Abstract
Early-stage bladder cancer occurs as two distinct forms: namely, low-grade superficial disease and high-grade carcinoma in situ (CIS), which is the major precursor of muscle-invasive bladder cancer. Although the low-grade form is readily treatable, few, if any, effective treatments are currently available for preventing progression of nonmuscle-invasive CIS to invasive bladder cancer. Based on our previous findings that the mammalian target of Rapamycin (mTOR) signaling pathway is activated in muscle-invasive bladder cancer, but not superficial disease, we reasoned that suppression of this pathway might block cancer progression. To test this idea, we performed in vivo preclinical studies using a genetically engineered mouse model that we now show recapitulates progression from nonmuscle-invasive CIS to muscle-invasive bladder tumors. We find that delivery of Rapamycin, an mTOR inhibitor, subsequent to the occurrence of CIS effectively prevents progression to invasive bladder cancer. Furthermore, we show that intravesical delivery of Rapamycin directly into the bladder lumen is highly effective for suppressing bladder tumorigenesis. Thus, our findings show the potential therapeutic benefit of inhibiting mTOR signaling for treatment of patients at high risk of developing invasive bladder cancer. More broadly, our findings support a more widespread use of intravesical delivery of therapeutic agents for treatment of high-risk bladder cancer patients, and provide a mouse model for effective preclinical testing of potential novel agents.
Is It Time to Advance the Chemoprevention of Environmental Carcinogenesis with Microdosing Trials?
Authors: Kensler Thomas W. , Groopman John D. 
Published: December 2009

Abstract
This perspective on Jubert et al. (beginning on page [1015] in this issue of the journal) discusses the use of microdosing with environmental carcinogens to accelerate the evaluation and optimization of chemopreventive interventions. The need for chemoprevention of environmental carcinogenesis is considered, as are the structure of microdosing, or phase 0, trials, technologies required to conduct microdose studies in this context, and ethical concerns. We also reflect on what microdosing studies have taught us to date.
Synergistic Electrophysiologic and Antiarrhythmic Effects of the Combination of Ranolazine and Chronic Amiodarone in Canine Atria
Authors: Sicouri Serge , Burashnikov Alexander , Belardinelli Luiz , Antzelevitch Charles 
Published: December 2009

Background—Amiodarone and ranolazine have been characterized as inactivated- and activated-state blockers of cardiac sodium channel current (INa), respectively, and shown to cause atrial-selective depression of INa-related parameters. This study tests the hypothesis that their combined actions synergistically depress INa-dependent parameters in atria but not ventricles.Methods and Results—The effects of acute ranolazine (5 to 10 μmol/L) were studied in coronary-perfused right atrial and left ventricular wedge preparations and superfused left atrial pulmonary vein sleeves isolated from chronic amiodarone-treated (40 mg/kg daily for 6 weeks) and untreated dogs. Floating and standard microelectrode techniques were used to record transmembrane action potentials. When studied separately, acute ranolazine and chronic amiodarone caused atrial-predominant depression of INa-dependent parameters. Ranolazine produced a much greater reduction in Vmaxand much greater increase in diastolic threshold of excitation and effective refractory period in atrial preparations isolated from amiodarone-treated versus untreated dogs, leading to a marked increase in postrepolarization refractoriness. The drug combination effectively suppressed triggered activity in pulmonary vein sleeves but produced relatively small changes in INa-dependent parameters in the ventricle. Acetylcholine (0.5 μmol/L) and burst pacing induced atrial fibrillation in 100% of control atria, 75% of ranolazine-treated (5 μmol/L) atria, 16% of atria from amiodarone-treated dogs, and in 0% of atria from amiodarone-treated dogs exposed to 5 μmol/L ranolazine.Conclusions—The combination of chronic amiodarone and acute ranolazine produces a synergistic use-dependent depression of INa-dependent parameters in isolated canine atria, leading to a potent effect of the drug combination to prevent the induction of atrial fibrillation.
River Control, Merchant Philanthropy, and Environmental Change in Nineteenth-Century China
Authors: Kim Nanny 
Published: December 2009

AbstractThis article investigates a series of projects for the improvement of shipping conditions of the Upper Yangzi in 1805-'40. The enterprise was undertaken by two Hankou merchants, one of whom published his 'Brief Account of the Taming of the Rapids'. An analysis of the detailed data of this source provides insights into navigation conditions and rates of environmental change on a major river, and into a major infrastructure project undertaken as merchant philanthropy. This paper proposes a perspective on water transport in pre-industrial China against a wider temporal and cultural backdrop, with a particular reference to private philanthropy as a set item within the moral economy. Cet article examine une série de projets destinés à améliorer les conditions de la batellerie dans le Haut Yangzi entre 1805 et 1840. Cette entreprise fut menée à l'instigation de deux marchands originaires de Hankou, dont l'un publia un « Bref compte-rendu sur la domestication des rapides ». L'analyse des données détaillées que contient ce document offre un aperçu des conditions de navigation et des changements environnementaux affectant un grand fleuve, et permet de mieux comprendre ce vaste projet d'infrastructure conçu comme une forme de philanthropie marchande. Cet article propose de replacer le transport fluvial de la Chine préindustrielle dans un plus large contexte temporel et culturel, en insistant particulièrement sur le rôle de la philanthropie privée, considérée comme un pivot de l'économie morale.
Women and Nation Building: The Case of the United Arab Emirates
Authors: Dhaheri Hissa Al 
Published: December 2009

AbstractThe newly formed United Arab Emirates appears to be making strides towards the empowerment of women, with women becoming visible in public roles—particularly as professional broadcasters in the media and high-ranking ministers in government posts. However, some evidence suggests that in reality, the progress of women may be a patriarchal image created merely for the sake of appearances as part of the emerging nation's political agenda that seeks to convey the image of a 'modern' state. Fundamentally laws are still biased against women and the education system is still embedding gender bias into the minds of youths via the nation's core curriculum. On the positive side, those visible roles given to women as part of nation-state building and cultural identity projects cannot fail to lead to changes in the social perception of women. However, the fear is that the more the state focuses on creating an image; real change at the grass roots level will be sidelined.
A Higher-Order Closure Model with an Explicit PBL Top
Authors: Lappen Cara-Lyn , Randall David , Yamaguchi Takanobu 
Published: December 2009

Abstract
In 2001, the authors presented a higher-order mass-flux model called “assumed distributions with higher-order closure” (ADHOC 1), which represents the large eddies of the planetary boundary layer (PBL) in terms of an assumed joint distribution of the vertical velocity and scalars. In a subsequent version (ADHOC 2) the authors incorporated vertical momentum fluxes and second moments involving pressure perturbations into the framework. These versions of ADHOC, as well as all other higher-order closure models, are not suitable for use in large-scale models because of the high vertical and temporal resolution that is required. This high resolution is needed mainly because higher-order closure (HOC) models must resolve discontinuities at the PBL top, which can occur anywhere on a model’s Eulerian vertical grid. This paper reports the development of ADHOC 3, in which the computational cost of the model is reduced by introducing the PBL depth as an explicit prognostic variable. ADHOC 3 uses a stretched vertical coordinate that is attached to the PBL top. The discontinuous jumps at the PBL top are “hidden” in the layer edge that represents the PBL top. This new HOC model can use much coarser vertical resolution and a longer time step and is thus suitable for use in large-scale models. To predict the PBL depth, an entrainment parameterization is needed. In the development of the model, the authors have been led to a new view of the old problem of entrainment parameterization. The relatively detailed information available in the HOC model is used to parameterize the entrainment rate. The present approach thus borrows ideas from mixed-layer modeling to create a new, more economical type of HOC model that is better suited for use as a parameterization in large-scale models.
Circulation and Water Mass Modification in the Brazil–Malvinas Confluence
Authors: Jullion Loic , Heywood Karen J. , Naveira Garabato Alberto C. , Stevens David P. 
Published: December 2009

Abstract
The confluence between the Brazil Current and the Malvinas Current [the Brazil–Malvinas Confluence (BMC)] in the Argentine Basin is characterized by a complicated thermohaline structure favoring the exchanges of mass, heat, and salt between the subtropical gyre and the Antarctic Circumpolar Current (ACC). Analysis of thermohaline properties of hydrographic sections in the BMC reveals strong interactions between the ACC and subtropical fronts. In the Subantarctic Front, Subantarctic Mode Water (SAMW), Antarctic Intermediate Water (AAIW), and Circumpolar Deep Water (CDW) warm (become saltier) by 0.4° (0.08), 0.3° (0.02), and 0.6°C (0.1), respectively. In the subtropical gyre, AAIW and North Atlantic Deep Water have cooled (freshened) by 0.4° (0.07) and 0.7°C (0.11), respectively.
To quantify those ACC–subtropical gyre interactions, a box inverse model surrounding the confluence is built. The model diagnoses a subduction of 16 ± 4 Sv (1 Sv ≡ 106 m3 s−1) of newly formed SAMW and AAIW under the subtropical gyre corresponding to about half of the total subduction rate of the South Atlantic found in previous studies. Cross-frontal heat (0.06 PW) and salt (2.4 × 1012 kg s−1) gains by the ACC in the BMC contribute to the meridional poleward heat and salt fluxes across the ACC. These estimates correspond to perhaps half of the total cross-ACC poleward heat flux. The authors’ results highlight the BMC as a key region in the subtropical–ACC exchanges.
Simulation of Water Age and Residence Time in New York Bight
Authors: Zhang Weifeng G. , Wilkin John L. , Schofield Oscar M. E. 
Published: December 2009

Abstract
The time scales on which river inflows disperse in the coastal ocean are relevant to a host of biogeochemical and environmental processes. These time scales are examined in a modeling study of the Hudson River plume on its entry to the New York Bight (NYB). Constituent-oriented age and residence-time theory is applied to compute two time scales: mean age, which is calculated from the ratio of two model tracers, and residence time, which is calculated using the adjoint of the tracer conservation equation.
Spatial and temporal variability associated with river discharge and wind is investigated. High river discharge lowers surface water age and shortens residence time in the apex of the NYB. Easterly winds increase surface water age and extend the duration waters along the Long Island coast remain in the NYB apex. Southerly winds increase age along the New Jersey coast but drive a decrease in age of offshore surface waters and prolong the time that surface waters close to the New Jersey coast stay in the NYB apex. Residence time along the Long Island coast is high in spring and summer because of the retention of water north of the Hudson shelf valley.
Patterns of modeled surface water age and an age proxy computed from the ratio of satellite-measured irradiance in two channels show qualitative agreement. A least squares fit gives a statistically significant empirical relationship between the band ratio and modeled mean age for NYB waters.
Long-Term Statistics and Extreme Waves of Sea Storms
Authors: Fedele Francesco , Arena Felice 
Published: December 2009

AbstractA stochastic model of sea storms for describing long-term statistics of extreme wave events is presented. The formulation generalizes Boccotti’s equivalent triangular storm model by describing an actual storm history in the form of a generic power law. The latter permits the derivation of analytical solutions for the return periods of extreme wave events and associated statistical properties. Lastly, the relative validity of the new model and its predictions is assessed by analyzing wave measurements retrieved from two NOAA National Oceanographic Data Center (NODC) buoys in the Atlantic and Pacific Oceans.