bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Prostate Cancer Prevention Trial Risk calculator in a high‐risk screening population
Authors: Kaplan David J. , Boorjian Stephen A. , Ruth Karen , Egleston Brian L. , Chen David Y. T. , Viterbo Rosalia , Uzzo Robert G. , Buyyounouski Mark K. , Raysor Susan , Giri Veda N. 
Published: August 2009

Study Type – Diagnostic (exploratory cohort)  Level of Evidence 2bOBJECTIVETo evaluate the Prostate Cancer Prevention Trial (PCPT) risk calculator in a screening cohort of young, racially diverse, high‐risk men with a low baseline prostate‐specific antigen (PSA) level and enrolled in the Prostate Cancer Risk Assessment Program (PRAP). The PCPT calculator provides an assessment of prostate cancer risk based on age, PSA level, race, previous biopsy, and family history.PATIENTS AND METHODSEligibility for PRAP includes men aged 35–69 years who are African‐American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates.RESULTSIn all, 624 participants were evaluated, including 382 (61.2%) African‐American men and 242 (38.7%) men with a family history of prostate cancer; the median (range) age was 49.0 (34.0–69.0) years and the median PSA level 0.9 (0.1–27.2) ng/mL. The PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, vs 14.2% in patients not diagnosed with prostate cancer (P < 0.001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer vs 15.2% in all other participants (P < 0.001).CONCLUSIONThe PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African‐American men with a low baseline PSA level. These results support further evaluation of this predictive tool for assessing the risk of prostate cancer in high‐risk men.
Ductal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical management
Authors: Aydin Hakan , Zhang Jun , Samaratunga Hemamali , Tan Nelly , Magi‐Galluzzi Cristina , Klein Eric , Jones J. Stephen , Zhou Ming 
Published: August 2009

Study Type – Prognosis (case series)  Level of Evidence 4OBJECTIVETo report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA).PATIENTS AND METHODSThe presence of DCP in transrectal ultrasonography‐guided prostate biopsy (TRUSB) is associated with adverse pathological findings at radical prostatectomy (RP) and clinical outcomes, and the significance of detecting DCP initially in transurethral biopsy (UB) or transurethral resection (TURP) in the present era of screening with prostate‐specific antigen (PSA) is unclear. The study included 23 cases of pure DCP without acinar PA diagnosed on UB or TURP. Demographic information, serum PSA level, follow‐up surgical procedures (RP, TURP or TRUSB) and outcome data were collected.RESULTSThe mean age of the men was 67.5 years and the mean PSA level before the procedure was 12.5 ng/mL; 14 cases were detected on UB and nine were diagnosed on TURP. The mean (range) follow‐up was 4 (1–23) months after the initial procedure. In all, 21 (89%) patients had DCP or PA in follow‐up procedures. Two (11%) patients had no residual cancer, one on RP and the other on two repeat TURPs. DCP or PA was found in 12 RP cases; four patients had Gleason score 7 PA, three of which were organ‐confined, and eight had Gleason score ≥8 PA. Extraprostatic extension, seminal vesicle invasion and regional lymph node metastasis were present in seven, six and two cases, respectively.CONCLUSIONSMost DCP diagnosed on UB or TURP in this contemporary series was associated with aggressive PA, but a subset presented as a small periurethral tumour with no concomitant acinar PA, and was eradicated by the initial biopsy/TURP alone. We recommend that patients with a diagnosis of DCP on UB or TURP undergo follow‐up TURP and TRUSB before radical surgery is offered.
Multinational Firms’ Heterogeneity in Tax Responsiveness: The Role of Transfer Pricing
Authors: Azémar Céline , Corcos Gregory 
Published: August 2009

AbstractIn this paper we show that the ability of multinational firms to manipulate transfer prices affects the tax sensitivity of foreign direct investment (FDI). We offer a model of international capital allocation where firms are heterogeneous in their ability to manipulate transfer prices. Perhaps paradoxically, we show that the ability to shift profits can make parent companies’ investment more sensitive to host‐country tax rates, as long as investors expect fiscal authorities to use price and profit detection methods. We then offer a comprehensive empirical study to test our predictions in the case of Japanese FDI. We exploit the finding that the unobservable ability to manipulate transfer prices is correlated with whole ownership of affiliates and R&D expenditure. Based on country, parent firm and sector characteristics, we estimate an investment equation on a sample of 3,614 Japanese affiliates in 49 emerging countries. We obtain a greater semi‐elasticity of investment to the statutory tax rate in affiliates that are wholly‐owned and that have R&D‐intensive parents. We interpret these results as indirect evidence that abusive transfer pricing is one of the determinants of FDI activity.
Estimation Uncertainty and the Equity Premium*
Authors: YAN HONG 
Published: August 2009

ABSTRACTThis paper studies a dynamic equilibrium model of asset prices in a partially observable exchange economy. It shows that the precautionary savings motive in response to estimation uncertainty can dominate the risk aversion effect, resulting in the reduction of the equity premium over short horizons. This exacerbates the equity premium puzzle. Over longer holding horizons, however, estimation uncertainty does induce higher risk premiums on equity over risk‐free coupon bonds of matching maturities, as long‐term bond yields are lowered due to the precautionary savings effect.
Short Rate Dynamics and Regime Shifts*
Authors: LI HAITAO , XU YUEWU 
Published: August 2009

ABSTRACTWe characterize the dynamics of the US short‐term interest rate using a Markov regime‐switching model. Using a test developed by Garcia, we show that there are two regimes in the data: In one regime, the short rate behaves like a random walk with low volatility; in another regime, it exhibits strong mean reversion and high volatility. In our model, the sensitivity of interest rate volatility to the level of interest rate is much lower than what is commonly found in the literature. We also show that the findings of nonlinear drift in Aït‐Sahalia and Stanton, using nonparametric methods, are consistent with our regime‐switching model.
Rapid Na, Cu exchange between synthetic fluid inclusions and external aqueous solutions: evidence from LA‐ICP‐MS analysis
Authors: LI Y. , AUDÉTAT A. , LERCHBAUMER L. , XIONG X. L. 
Published: August 2009

AbstractThree sets of equilibration experiments (Set 1 to Set 3) were performed in cold‐seal pressure vessels to investigate the compositional modification of quartz‐hosted fluid inclusions after entrapment. Each set of experiment consisted of two stages. In a pre‐run, fluid inclusions containing 5–10 wt% NaCl and selected trace elements were synthesized at 700°C/140–200 MPa. These samples were then loaded into new capsules together with Cu‐bearing solutions and some mineral buffers, and re‐equilibrated at 600–800°C and 70–140 MPa for 6–8 days. LA‐ICP‐MS analysis of individual fluid inclusions reveals that in re‐equilibration experiments in which the outer fluid was composed of KCl (±FeCl2) up to 83% of the original Na content of pre‐existing fluid inclusions were lost, and up to 5660 ppm Cu were gained. Other elements with larger ionic radii (i.e. K, Fe, Ba, Sr) were not exchanged, demonstrating that the inclusions remained physically intact and that Na and Cu were transported through quartz by diffusion. The observed Na loss from pre‐existing fluid inclusions correlates positively with Cu gain, with about 1 Cu atom being gained per 10 Na atoms lost. Thus, Na and Cu (plus probably H) were exchanged by interdiffusion. Remarkably, this processes resulted in up to 10 times higher Cu concentrations in re‐equilibrated inclusions than were present in the outer fluid, i.e. Cu diffused ‘uphill’. Large variations of Cu concentrations relative to the concentration of other elements are common also in natural fluid inclusion assemblages. However, no evidence for a correlation between Cu content and Na content was found so far, suggesting that Cu diffusion in natural samples may be dominated by processes other than Na–Cu interdiffusion.
Hydrogeochemical modelling of CO2 equilibria and mass transfer induced by organic–inorganic interactions in siliciclastic petroleum reservoirs
Authors: Van BERK W. , SCHULZ H.‐M. , FU Y. 
Published: August 2009

AbstractDifferent feldspar types control complex hydrogeochemical processes in hydrocarbon‐bearing siliciclastic reservoirs, which have undergone different degrees of degradation. To test such processes generically, carbon dioxide equilibria and mass transfers induced by organic–inorganic interactions have been modelled for different hydrogeochemical scenarios. The approach is based on and compared with data from the Norwegian continental shelf (Smith & Ehrenberg 1989) and assumes local thermodynamic equilibrium among solids and fluids. Equilibrating mineral assemblages (different feldspar types, quartz, kaolinite, calcite) are based on the primary reservoir composition. Equilibration and coupled mass transfer were triggered by the addition and reaction of different amounts of CO2, CH4 and H2 (plus acetic acid) at temperatures between 50 and 95°C (323 and 368 K). These components occur in oil fields as products of anaerobic bacterial degradation, hydrolytic disproportionation of hydrocarbons and/or thermal maturation of kerogen. We apply two different computer codes and two different thermodynamic data bases to calculate the results. Reaction of 0.32–0.6 mol CO2, 0.16–0.3 mol CH4 and 0.8–1.5 mol H2 with K‐feldspar, quartz, kaolinite and calcite in 1 l of pore water results in modelled values of 0.3–2.3 mol% CO2 in a multicomponent gas phase that resembles measured data (0.2–1.5 mol%). Similar CO2 contents result from acetic acid addition (CO2, CH4, H2 + 0.016 mol CH3COOH). Equilibration with albite or anorthite reduces the release of CO2 into the multicomponent gas phase dramatically, by 1 or 4 orders of magnitude compared with the equilibration with K‐feldspar. Minor differences in the modelled CO2 content (0.1–0.2 mol%) result from calculations with different computer codes if the same thermodynamic data base is applied. Relevant differences (up to 1.9 mol% CO2) result from calculations using different thermodynamic data bases.
Mechanisms of strain‐rate‐ and reaction‐dependent permeability in the mid‐crust of the Southern Alps: insight from three‐dimensional mechanical models
Authors: UPTON P. , CRAW D. 
Published: August 2009

AbstractWe used three‐dimensional mechanical modelling to explore the interplay of rheology, modes of permeability creation and fluid flow in the mid‐crust of an oblique orogen. We used the central Southern Alps and the Otago Schist of New Zealand to constrain our models. We also compared our models with the magnetotelluric survey along the Rangitata–Whataroa rivers that imaged a U‐shaped zone of high conductivity, interpreted as interconnected fluids, beneath the central Southern Alps. Modelling was carried out using the numerical code FLAC3D. We used a number of simple assumptions: an initially homogeneous starting material, deformation boundary conditions based on the tectonics of the South Island, the capability of the modelled material to develop an anisotropic permeability structure, strain rate and reaction‐induced permeability increases, initial saturation and lithostatic pore pressures as a basis for our models. The initial isotropic permeability was 10−18 m2. We modelled two possible mechanisms of permeability increase: (i) strain‐rate dependent and (ii) reaction dependent. For a strong mid‐crust, the models showed enhanced permeability and hence fluid interconnectivity in a symmetric region beneath the model main divide, both ends were turned up towards the brittle–ductile transition and fluid flow was the greatest in the across strike direction. For a weak mid‐crust, the region of enhanced permeability was asymmetric and turned up towards the brittle–ductile regime close to the Alpine Fault. The strong mid‐crust model reproduces the features that are common to all interpretations of the MT soundings and is our preferred model for the central Southern Alps.
Chronic adrenaline treatment fails to down‐regulate the Del301–303‐α2B‐adrenoceptor in neuronal cells
Authors: Salim S , Desai AN , Taneja M , Eikenburg DC 
Published: August 2009

Background and purpose:  A polymorphism of the human α2B‐adrenoceptor (Del301–303‐α2B‐adrenoceptor) has been described, and this receptor exhibits reduced G‐protein‐coupled receptor kinase (GRK) phosphorylation and impaired short‐term desensitization. Expression of the Del301–303‐α2B‐adrenoceptor also is associated with an increased risk for myocardial infarction in humans. Recent evidence from our laboratory suggests a quantitative relationship between cellular GRK3 expression levels and the sensitivity of the α2B‐adrenoceptor to agonist‐induced down‐regulation. Therefore, the present study was undertaken to study agonist‐induced down‐regulation of the wild‐type (WT)‐ and Del301–303‐α2B‐adrenoceptor in a neuronal cell model.Experimental approach:  Haemagglutinin (HA) epitope‐tagged WT‐ and Del301–303‐α2B‐adrenoceptor containing plasmids were constructed and the receptors were stably or transiently transfected in neuroblastoma/glioma hybrid NG108 cells. The expression levels in stable transfects were ∼50 fmol·mg−1. These cells were used to examine agonist‐induced down‐regulation and phosphorylation of the WT‐ and Del301–303‐α2B‐adrenoceptor.Key results:  The Del301–303‐α2B‐adrenoceptor, compared with the WT‐α2B‐adrenoceptor, displayed reduced adrenaline‐stimulated (20 µM) phosphorylation and did not down‐regulate in response to adrenaline (20–1000 µM). Using immunofluorescence labelling, we observed that transiently transfected WT‐α2B‐adrenoceptors internalized upon adrenaline treatment whereas the Del301–303‐α2B‐adrenoceptor did not. Finally, we determined the effect of adrenaline on the Del301–303‐α2B‐adrenoceptor in cells stably over‐expressing GRK3 3‐fold. In spite of the GRK3 over‐expression, 20–1000 µM ADR failed to down‐regulate or to increase phosphorylation of the Del301–303‐α2B‐adrenoceptor in these cells.Conclusions and implications:  The results suggest that the 301–303 deletion mutation of the α2B‐adrenoceptor eliminates agonist‐induced down‐regulation, an effect that cannot be overcome by increasing agonist concentration or by modest GRK3 over‐expression.
Cross‐regulation between β1‐ and β3‐adrenoceptors following chronic β‐adrenergic stimulation in neonatal rat cardiomyocytes
Authors: Ufer Christoph , Germack Renée 
Published: August 2009

Background and purpose: We have previously shown that β‐adrenoceptors continuously stimulated with noradrenaline induces an increase in β3‐adrenoceptors (GαiPCRs) and a decrease in β1‐adrenoceptors (GαsPCRs) at functional, genomic and protein levels. This compensatory modification induced by noradrenaline is probably one of the consequences of cardiac depression observed in heart disease. Therefore, we investigated further the interaction between β1‐ and β3‐adrenoceptors in neonatal rat cardiomyocytes.Experimental approach: Functional studies were performed by cyclic adenosine monophosphate (cAMP) accumulation assays in cells untreated or treated with dobutamine and ICI 118551 (β1‐adrenoceptor) or CL‐3162436243 (β3‐adrenoceptor) for 24 h in the presence or absence of protein kinase inhibitors. β‐adrenoceptor and protein kinase expression was monitored by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) and by Western blotting, respectively.Key results: Chronic β1‐ or β3‐adrenoceptor stimulation reduced β1‐adrenoceptor‐mediated cAMP accumulation in association with a decrease in β1‐adrenoceptor mRNA and protein levels through protein kinase C (PKC), phosphoinositide 3‐kinase (PI3K) and p38 mitogen‐activated protein kinase (p38MAPK) activation. In contrast, both treatments induced an increase in β3‐adrenoceptor expression and β3‐adrenoceptor‐inhibited forskolin response through PKC, extracellular‐signal‐regulated kinases 1 and 2 (ERK1/2) and p38MAPK phosphorylation, although no β3‐adrenoceptor response was observed in untreated cells. ERK1/2 and p38MAPK were activated by both treatments. The modulation of β1‐ or β3‐adrenoceptor function did not require stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) although chronic β1‐adrenoceptor stimulation activated SAPK/JNK. β3‐adrenoceptor treatment activated Akt although PI3K was not involved in β3‐adrenoceptor up‐regulation.Conclusion and implications: We show for the first time that chronic β1‐ or β3‐adrenoceptor stimulation leads to the modulation of β1‐ and β3‐adrenoceptors by a cross‐regulation involving PKC, PI3K p38MAPK and MEK/ERK1/2 pathway, and through protein kinase A when β1‐adrenoceptors are chronically activated.
Novel antagonists for proteinase‐activated receptor 2: inhibition of cellular and vascular responsesin vitroandin vivo
Authors: Kanke T , Kabeya M , Kubo S , Kondo S , Yasuoka K , Tagashira J , Ishiwata H , Saka M , Furuyama T , Nishiyama T , Doi T , Hattori Y , Kawabata A , Cunningham MR , Plevin R 
Published: August 2009

Background and purpose: Proteinase‐activated receptor 2 (PAR2) is a G‐protein coupled receptor associated with many pathophysiological functions. To date, the development of PAR2antagonists has been limited. Here, we identify a number of novel peptide‐mimetic PAR2antagonists and demonstrate inhibitory effects on PAR2‐mediated intracellular signalling pathways and vascular responses.Experimental approach: The peptide‐mimetic compound library based on the structures of PAR2agonist peptides were screened for inhibition of PAR2‐induced calcium mobilisation in human keratinocytes. Representative compounds were further evaluated by radioligand binding and inhibition of NFκB transcriptional activity and IL‐8 production. The vascular effects of the antagonists were assessed usingin vitroandin vivomodels.Key results: Two compounds, K‐12940 and K‐14585, significantly reduced SLIGKV‐induced Ca2+mobilisation in primary human keratinocytes. Both K‐12940 and K‐14585 exhibited competitive inhibition for the binding of a high‐affinity radiolabelled PAR2‐ligand, [3H]‐2‐furoyl‐LIGRL‐NH2, to human PAR2with Kivalues of 1.94 and 0.627 µM respectively. NFκB reporter activity and IL‐8 production were also significantly reduced. Furthermore, relaxation of rat‐isolated aorta induced by SLIGRL‐NH2was inhibited competitively by K‐14585. K‐14585 also significantly lowered plasma extravasation in the dorsal skin of guinea pigs and reduced salivation in mice.Conclusions and implications: K‐12940 and K‐14585 antagonized PAR2competitively, resulting in inhibition of PAR2‐mediated signalling and physiological responses bothin vitroandin vivo. These peptide‐mimetic PAR2antagonists could be useful in evaluating PAR2‐mediated biological events and might lead to a new generation of therapeutically useful antagonists.
The signal transduction cascade regulating the expression of the gap junction protein connexin43 by β‐adrenoceptors
Authors: Salameh A , Krautblatter S , Karl S , Blanke K , Gomez D Rojas , Dhein S , Pfeiffer D , Janousek J 
Published: August 2009

Background and purpose:  In mammalian heart, connexin43 (Cx43) represents the predominant connexin in the working myocardium. As the β‐adrenoceptor is involved in many cardiac diseases, we wanted to clarify the pathway by which β‐adrenoceptor stimulation may control Cx43 expression.Experimental approach:  Cultured neonatal rat cardiomyocytes were stimulated with isoprenaline. Cx43 expression as well as activation of p38 mitogen‐activated protein kinase (MAPK), p42/44 MAPK, JUN NH2‐terminal kinase (JNK) and nuclear translocation of the transcription factors activator protein 1 (AP1) and CRE‐binding protein (CREB) were investigated. Additionally, we assessed Cx43 expression and distribution in left ventricular biopsies from patients without any significant heart disease, and from patients with either congestive heart failure [dilated cardiomyopathy (DCM)] or hypertrophic cardiomyopathy (HCM).Key results:  Isoprenaline exposure caused about twofold up‐regulation of Cx43 protein with a pEC50 of 7.92 ± 0.11, which was inhibited by propranolol, SB203580 (4‐(4‐fluorophenyl)‐2‐(4‐methylsulphinylphenyl)‐5‐(4‐pyridyl)‐1H‐imidazole) (p38 inhibitor), PD98059 2‐(2‐amino‐3‐methoxyphenyl)‐4H‐1‐benzopyran‐4‐one) (MAPK 1 kinase inhibitor) (Alexis Biochemicals, San Diego, CA, USA) or cyclosporin A. Similar findings were obtained for Cx43 mRNA. Furthermore, Cx43 up‐regulation was accompanied by phosphorylation of p38, p42/44 and JNK, and by translocation of AP1 and CREB to the nucleus. Analysis of Cx43 protein and mRNA in ventricular biopsies revealed that in patients with DCM, Cx43 content was significantly lower, and in patients with HCM, Cx43 content was significantly higher, relative to patients without any cardiomyopathy. More importantly, Cx43 distribution also changed with more Cx43 being localized at the lateral border of the cardiomyocytes.Conclusion and implication:  β‐adrenoceptor stimulation up‐regulated cardiac Cx43 expression via a protein kinase A and MAPK‐regulated pathway, possibly involving AP1 and CREB. Cardiomyopathy altered Cx43 expression and distribution.
Helicobacters and Extragastric Diseases
Authors: Pellicano Rinaldo , Franceschi Francesco , Saracco Giorgio , Fagoonee Sharmila , Roccarina Davide , Gasbarrini Antonio 
Published: August 2009

AbstractFor two decades, Helicobacter pylori has been considered as the culprit in many extragastric manifestations. However, for several of these supposed associations the hypothesis of an etiological role has not yet been fully investigated. This may be due to a series of factors linked to the epidemiological features of the studies and to the diseases investigated. This review attempts to highlight the main reported associations of H. pylori with extragastric manifestations during the last year. The most convincing data arise in the field of idiopathic thrombocytopenic purpura (ITP) and sideropenic anemia. Long‐term follow‐up studies have shown that 50% of subjects with ITP maintain a hematological response after H. pylori eradication. There is also growing evidence of the role of H. pylori in other diseases, including ischemic heart disease even though results are not conclusive.