bluuebunny/crossref_metadata_2025_split huggingface dataset:
One‐Pot Chemoselective Bis(Suzuki–Miyaura Cross‐Coupling): Efficient Access to 3,9‐Bis[(hetero)aryl]‐4H‐pyrido[1,2‐a]pyrimidin‐4‐one Derivatives Under Microwave Irradiation
Authors: Kabri Youssef , Crozet Maxime D. , Primas Nicolas , Vanelle Patrice 
Published: August 2012

AbstractA one‐pot chemoselective bis(Suzuki–Miyaura cross‐coupling) reaction under microwave irradiation is reported for the 4H‐pyrido[1,2‐a]pyrimidin‐4‐one series. First, we ascertained an initial coupling reaction that was selectively carried out at the C‐3 position of (7,9‐dichloro‐3‐iodo‐4‐oxo‐4H‐pyrido[1,2‐a]pyrimidin‐2‐yl)methyl acetate (4). Next, we developed an extremely efficient one‐pot chemoselective bis(Suzuki–Miyaura cross‐coupling) reaction, allowing us to substitute successively at the 3‐ and then at the 9‐position of compound 4 with various boronic acids.
Identification of the First Alkenyl Chiloglottone Congener
Authors: Poldy Jacqueline , Peakall Rod , Barrow Russell A. 
Published: August 2012

AbstractOrchids of the genus Chiloglottis rely on sexual deception to attract a male thynnine wasp, whereupon a courtship routine results in the deposition and transfer of pollinia and subsequent pollination of the orchid. The chemical cues responsible for this behavior were recognized as a new class of natural products and efforts to synthetically prepare them, to assist in structural identification and to aid in ecological studies, have been ongoing. Most recently the first alkenylated member of this class was proposed based on GC–MS analysis of a physiologically active compound present in an orchid extract. The current work reveals synthetic efforts that provide access to diastereomerically pure unsaturated chiloglottone analogues and in combination with laboratory‐based electrophysiological assays and field‐based studies have unambiguously allowed identification of 5‐allyl‐2‐ethyl‐1,3‐cyclohexanedione (1d, chiloglottone 4) as the first alkenyl congener in the chiloglottone family. Convergent synthetic approaches, involving copper(I)‐mediated conjugate addition to a glutaconic ester converging on cadmium‐mediated desymmetrization of cyclic anhydrides or a Johnson–Claisen rearrangement of a mixed ketene acetal provided the appropriately substituted δ‐keto acids suitable for carbocyclization to furnish the required chiloglottone analogues.
Asymmetric Ion‐Pairing Catalysis of the Reversible Cyclization of 2′‐Hydroxychalcone to Flavanone: Asymmetric Catalysis of an Equilibrating Reaction
Authors: Hintermann Lukas , Dittmer Claudia 
Published: August 2012

AbstractThe asymmetric catalytic cyclization of the simple 2′‐hydroxychalcone (1) to flavanone (2), a model for the chalcone isomerase reaction, has been realized as a catalytic asymmetric ion‐pairing process with chiral quaternary ammonium salts (e.g., 9‐anthracenylmethlycinchoninium chloride; 9‐Am‐CN‐Cl) and NaH as small‐molecule co‐catalyst. In toluene/CHCl3 solution, the process reaches an intrinsic enantioselectivity of up to S = 14.4 (er = 93.5:6.5). The reversible reaction proceeds in two steps: A fast initial reaction approaches a quasi‐equilibrium with KR/S = 4.5, followed by a second, slow racemization phase approaching Krac = 9. A simple mechanistic model featuring a living ion‐pairing catalysis with full reversibility is proposed. Deuterium transfer from co‐solvent CDCl3 to product 2 and isolation of a Michael conjugate formed from 2 and 1 demonstrate the intermediacy of flavanone enolate ion pairs. A kinetic model shows good agreement with the experimentally observed, peculiar, time‐dependent evolution of the species concentrations and the enantiomeric excess of 2. The reaction is a chemical model of the chalcone isomerase enzymatic reaction. Furthermore, it is an ideal model for studying the characteristic behavior of reversible asymmetric catalyses close to their equilibria.
Loss of a single allele for Ku80 leads to progenitor dysfunction and accelerated aging in skeletal muscle
Authors: Didier Nathalie , Hourdé Christophe , Amthor Helge , Marazzi Giovanna , Sassoon David 
Published: August 2012

AbstractMuscle wasting is a major cause of morbidity in the elderly. Ku80 is required for DNA double strand repair and is implicated in telomere maintenance. Complete loss‐of‐function leads to reduced post‐natal growth and severe progeria in mice. We examined the role of Ku80 in age‐related skeletal muscle atrophy. While complete loss of Ku80 leads to pronounced aging in muscle as expected, accompanied by accumulation of DNA damage, loss of a single allele is sufficient to accelerate aging in skeletal muscle although post‐natal growth is normal. Ku80 heterozygous muscle shows no DNA damage accumulation but undergoes premature telomere shortening that alters stem cell self‐renewal through stress response pathways including p53. These data reveal an unexpected requirement for both Ku80 alleles for optimal progenitor function and prevention of early onset aging in muscle, as well as providing a useful model for therapeutic approaches.
Methylsulfonyl polychlorinated biphenyls in fish from an electronic waste-recycling site in South China: Levels, congener profiles, and chiral signatures
Authors: Zhang Ying , Wu Jiang-Ping , Luo Xiao-Jun , She Ya-Zhe , Mo Ling , Mai Bi-Xian 
Published: August 2012

Abstract
Great concerns have been raised about the fate and effects of polychlorinated biphenyls (PCBs) and other organic contaminants contained in electronic waste (e-waste) exported from industrialized countries at midlatitudes to subtropical and tropical regions. Information on the metabolites of these chemicals, for example, methylsulfonyl-PCBs (MeSO2-PCBs) in wildlife from the later regions is scarce. In the present study, 17 MeSO2-PCBs, including five chiral congeners, were detected in the muscle, liver, and brain tissues of two benthic fish species—northern snakehead and mud carp—from a small pond near an electronic waste recycling site in South China. The mean concentrations of the sum of the MeSO2-PCBs ranged from 80 to 340 ng/g lipid weight in the tissues, with relative higher levels in the liver than the muscle and brain tissues. These levels were one order of magnitude greater than the highest levels of MeSO2-PCBs previously reported in fish. The 3′-MeSO2-CB 87, 3′- and 4′-MeSO2-CB 101, 4-MeSO2-CB 110, and 4-MeSO2-CB 149 were dominant, collectively comprising more than 55% of the total MeSO2-PCBs. Except for 4-MeSO2-CB149, all of the investigated chiral MeSO2-PCBs displayed a clear, congener-specific enantiomeric enrichment in the tissues. No tissue-specific enantioselective retention of the enantiomers was observed in the investigated fish. This is the first report on chiral signatures of MeSO2-PCBs in fish tissues. Environ. Toxicol. Chem. 2012; 31: 2507–2512. © 2012 SETAC
Comparative study of implicit and subgrid‐scale model large‐eddy simulation techniques for low‐Reynolds number airfoil applications
Authors: Garmann Daniel J. , Visbal Miguel R. , Orkwis Paul D. 
Published: August 2012

SUMMARYA computational study of a high‐fidelity, implicit large‐eddy simulation (ILES) technique with and without the use of the dynamic Smagorinsky subgrid‐scale (SGS) model is conducted to examine the contributions of the SGS model on solutions of transitional flow over the SD7003 airfoil section. ILES without an SGS model has been shown in the past to produce comparable and sometimes favorable results to traditional SGS‐based large‐eddy simulation (LES) when applied to canonical turbulent flows. This paper evaluates the necessity of the SGS model for low‐Reynolds number airfoil applications to affirm the use of ILES without SGS‐modeling for a broader class of problems such as those pertaining to micro air vehicles and low‐pressure turbines. It is determined that the addition of the dynamic Smagorinsky model does not significantly affect the time‐mean flow or statistical quantities measured around the airfoil section for the spatial resolutions and Reynolds numbers examined in this study. Additionally, the robustness and reduced computational cost of ILES without the SGS model demonstrates the attractiveness of ILES as an alternative to traditional LES. Published 2012. This article is a US Government work and is in the public domain in the USA.
Maté consumption and risk of oral cancer: Case‐control study in Uruguay
Authors: Deneo–Pellegrini Hugo , De Stefani Eduardo , Boffetta Paolo , Ronco Alvaro L. , Acosta Gisele , Correa Pelayo , Mendilaharsu María 
Published: August 2012

AbstractBackgroundIn the period 1990 to 2001, a case‐control study on oral cancer and maté consumption was conducted at the Cancer Institute of Uruguay.MethodsThe study included 696 newly diagnosed cases with squamous cell carcinoma and 696 controls afflicted with nonneoplastic conditions not related to tobacco smoking and alcohol drinking. The participants were matched on age and residence and the study was restricted to men.ResultsIn order to control confounding for tobacco and alcohol, we fitted 2 models. According to model 1, the odds ratio (OR) for maté consumption was 1.15 (95% confidence interval [CI], 0.76–1.73), whereas the results for model 2 showed an OR of 3.47 (95% CI, 1.60–7.52).ConclusionsThe inclusion of a term for the interaction between maté and smoking (or drinking) was rewarding and the ORs were even higher than those observed with the crude estimates. Head Neck, 2013
A ‘Peak‐Box’ approach for supporting interpretation and verification of operational ensemble peak‐flow forecasts
Authors: Zappa Massimiliano , Fundel Felix , Jaun Simon 
Published: August 2012

AbstractUncertainty communication is an important topic within hydrological forecasting. Hydrological ensemble prediction systems are established tools for the generation of forecasts including uncertainty information. The interpretation of such forecasts requires new visualization and verification tools to help forecasters and end‐users in their decision making. While the visualization of hydrographs is important for estimating flood volumes, little support is provided for the interpretation of peak‐flow forecasts. We introduce the ‘Peak‐Box’, a novel visual support that envelops all ensemble peak timings and peak discharge, from which specific verification metrics are defined. A user‐defined metric quantifies the sharpness concerning peak timing and peak discharge and allows communicating a‐priori, if the spread of peak forecasts is acceptable.Eighteen months of ensemble predictions for four basins have been evaluated. A probabilistic verification which relies on the relationships between the spread and the relative operating characteristic area indicates the quality of the ensemble predictions in all basins. A sub‐sample of 485 events was used for exploring the value of the ‘Peak‐Box’. The combined spread of forecast peak time and peak discharge is higher than a tailored reference sharpness for most of the considered events. We show that, depending on the lead time of the forecasts, 30% to 55% of the observed peaks are found outside the predicted range. Most correct forecasts (hits) were obtained for forecasts having a lead time of 2 or more days. Further analyses indicate that the median of the ensemble peak forecast provides reliable estimates on either peak timing or peak discharge in more than 80% of the events evaluated. Finally, a score system was defined in order to combine different verification measures and obtain an overall assessment on the quality of both the peak discharge and peak ‐timing of the ensemble forecasts.We demonstrate that the ‘Peak‐Box’ can be adopted in different ways in order to obtain quantitative and qualitative insights on the quality of peak forecasts. Copyright © 2012 John Wiley & Sons, Ltd.
Suspended sediment causes annual acute fish mortality in the Pilcomayo River (Bolivia)
Authors: Swinkels L. H. , Van de Ven M. W. P. M. , Stassen M. J. M. , Van der Velde G. , Lenders H. J. R. , Smolders A. J. P. 
Published: August 2012

AbstractFish mortality in the middle reaches of the Pilcomayo River (Bolivia), locally called ‘borrachera’, can be observed almost every year at the onset of the rainy season. In order to study the potential causes of the ‘borrachera’, suspended sediment (SS) and selected water quality parameters have been monitored from mid‐September until mid‐December 2010. Gill samples were taken and analysed, before and during the ‘borrachera’ event on December 7th 2010. Data on river discharge were obtained from a database.During the sampling period, the river hydrology changed dramatically. At the day of the ‘borrachera’, heavy rains in upstream reaches of the river catchment changed the river from a quiet stream into a turbulent river with extremely high concentrations of SS (> 100 g l−1). This may be caused by the inundation of the entire riverbed, which causes easily erodible material, left on the riverbanks at the end of the former rainy season, to be transported by the river during the first peak discharges.As concentrations of heavy metals in filtered water samples did not show higher values during the ‘borrachera’, it is concluded that the ‘borrachera’ is unlikely to be caused by heavy metal toxicity. Results showed a strong association between the SS concentration and the ‘borrachera’. Gills of fish collected during the ‘borrachera’ were clogged with sediment to such an extent that oxygen uptake became virtually impossible. High SS concentrations are therefore considered to be the cause of this typical fish mortality phenomenon. Copyright © 2012 John Wiley & Sons, Ltd.
Role and pharmacologic significance of cytochrome P‐450 2D6 in oxidative metabolism of toremifene and tamoxifen
Authors: Kim Juhyun , Coss Christopher C. , Barrett Christina M. , Mohler Michael L. , Bohl Casey E. , Li Chien‐Ming , He Yali , Veverka Karen A. , Dalton James T. 
Published: August 2012

AbstractWe investigated the in vitro metabolism and estrogenic and antiestrogenic activity of toremifene (TOR), tamoxifen (TAM) and their metabolites to better understand the potential effects of cytochrome P‐450 2D6 (CYP2D6) status on the activity of these drugs in women with breast cancer. The plasma concentrations of TOR and its N‐desmethyl (NDM) and 4‐hydroxy (4‐OH) metabolites during steady‐state dosing with TOR were also determined. Unlike TOR, TAM and its NDM metabolite were extensively oxidized to 4‐OH TAM and 4‐OH‐NDM TAM by CYP2D6, and the rate of metabolism was affected by CYP2D6 status. 4‐OH‐NDM TOR concentrations were not measurable at steady state in plasma of subjects taking 80 mg of TOR. Molecular modeling provided insight into the lack of 4‐hydroxylation of TOR by CYP2D6. The 4‐OH and 4‐OH‐NDM metabolites of TOR and TAM bound to estrogen receptor (ER) subtypes with fourfold to 30‐fold greater affinity were 35‐ to 187‐fold more efficient at antagonizing ER transactivation and had antiestrogenic potency that was up to 360‐fold greater than their parent drugs. Our findings suggest that variations in CYP2D6 metabolic capacity may cause significant differences in plasma concentrations of active TAM metabolites (i.e., 4‐OH TAM and 4‐OH‐NDM TAM) and contribute to variable pharmacologic activity. Unlike TAM, the clinical benefits in subjects taking TOR to treat metastatic breast cancer would not likely be subject to allelic variation in CYP2D6 status or affected by coadministration of CYP2D6‐inhibiting medications.
Tumor size, node status, grading, HER2 and estrogen receptor status still retain a strong value in patients with operable breast cancer diagnosed in recent years
Authors: Cortesi Laura , Marcheselli Luigi , Guarneri Valentina , Cirilli Claudia , Braghiroli Barbara , Toss Angela , Sant Milena , Ficarra Guido , Conte Pier Franco , Federico Massimo 
Published: August 2012

AbstractBreast cancer prognosis has improved greatly in recent years. Consequently, a thorough search for sensitive prognostic factors, able to help clinicians offer appropriate therapy, has become a priority in this area. In this study, we considered all new cases of invasive breast cancer diagnosed in the Province of Modena, Italy, between 1997 and 2007, registered by the Modena Cancer Registry. The principal endpoint of this study was relapse‐free survival (RFS). A set of 11 clinic and pathological parameters was investigated. After a median follow‐up of 73 months, 494 relapses were recorded. Tumor size, node status, grading, HER2 and estrogen receptor status were retained as independent factors in a multivariate analysis. Using these variables, a prognostic model was devised to identify three groups at different risk. In the training sample, the 5‐year RFS rates resulted 96.0%, 82.9% and 63.7% in patients at low, intermediate and high risk, respectively (p< 0.0001). In the validation sample, the 5‐year RFS was 96.2%, 85.4% and 66.9%, respectively. To conclude our study demonstrates that a very simple prognostic index based on easily available clinical data may represent a useful tool for the identification of patients at different risk of relapse and may be a notable device to predict who truly benefits from medical treatment.
Androgen deprivation results in time‐dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response
Authors: Ming Louise , Byrne Niall M. , Camac Sarah Nicole , Mitchell Christopher A. , Ward Claire , Waugh David J. , McKeown Stephanie R. , Worthington Jenny 
Published: August 2012

AbstractAndrogen withdrawal induces hypoxia in androgen‐sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time‐dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT‐induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti‐androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide‐treated and vehicle‐only‐treated tumours were re‐established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 ± 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide‐treated tumours were more malignant than vehicle‐treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide‐induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit.
Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer
Authors: Perry Antoinette S. , O'Hurley Gillian , Raheem Omer A. , Brennan Kevin , Wong Simon , O'Grady Anthony , Kennedy Anne‐Marie , Marignol Laure , Murphy Therese M. , Sullivan Linda , Barrett Ciara , Loftus Barbara , Thornhill John , Hewitt Stephen M. , Lawler Mark , Kay Elaine , Lynch Thomas , Hollywood Donal 
Published: August 2012

AbstractAberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled‐Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC‐3 cells with 5‐Aza‐CdR reactivated 39 genes (≥ 2‐fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high‐grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
An experimental investigation of the role of perceived justice in acute pain
Authors: McParland J. , Knussen C. , Lawrie J. , Brodie E. 
Published: August 2012

AbstractBackgroundEmerging research suggests that perceiving injustice can compound the suffering of chronic pain, while perceiving justice serves as a positive psychological resource in this context. However, little more is currently known about the function of justice beliefs, particularly in the context of acute pain. The present study undertook this investigation, using cold pressor methodology to investigate whether trusting in the fairness of the world would help someone to cope with short‐term pain.MethodsSixty‐five men and 65 women completed measures of personal and general just world beliefs and state anxiety before pain induction and measures of the intensity and quality of pain, in addition to state anxiety following pain induction.ResultsThe personal and general beliefs in a just world were negatively correlated with pre‐task anxiety but not with measures of pain induction (threshold, tolerance and sensitivity) or measures of post‐task pain. Gender had a moderating role, whereby men with a stronger general just world belief reported lower post‐task state anxiety and men who had a stronger personal just world belief reported lower pain intensity. However, unexpectedly, women with a stronger personal just world belief reported higher pain intensity.ConclusionThe observed gender differences may be attributed to gender variations in cognitive appraisals of the task. Overall, while perceived injustice may be undesirable and a potential target for intervention, perceived justice is not necessarily a desired cognition in pain. Research is needed to replicate and extend this emerging research.