bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipase Congeners Designed by Genetic Code Engineering
Authors: Hoesl Michael G. , Acevedo‐Rocha Carlos G. , Nehring Sebastian , Royter Marina , Wolschner Christina , Wiltschi Birgit , Budisa Nediljko , Antranikian Garabed 
Published: October 2010

AbstractClassical enzyme optimization exploits the chemistry confined to the 20 canonical amino acids encoded by the standard genetic code. ‘Genetic code engineering’ allows the global substitution of particular residues with synthetic analogues, endowing proteins with chemical diversity not found in nature. These proteins are congeners of the parent protein because they originate from the same gene sequence, but contain a fraction of noncanonical amino acids. Global substitutions of methionine, proline, phenylalanine, and tyrosine have been carried out with related analogues in Thermoanaerobacter thermohydrosulfuricus lipase. This study represents the first extensive report of an important biocatalyst substituted with a high number of noncanonical amino acids. The generated lipase congeners displayed special features such as enhanced activation, elevated enzyme activity (by up to 25 %) and substrate tolerance (by up to 40 %), and changes in optimal temperature (by up to 20 °C) and pH (by up to 3). These emergent features achieved by genetic code engineering might be important not only for academic research, but also for numerous economical applications in the food, detergent, chemical, pharmaceutical, leather, textile, cosmetic, and paper industries.
The Heck Reaction of Allylic Alcohols Catalyzed by Palladium Nanoparticles in Water: Chemoenzymatic Synthesis of (R)‐(−)‐Rhododendrol
Authors: Boffi Alberto , Cacchi Sandro , Ceci Pierpaolo , Cirilli Roberto , Fabrizi Giancarlo , Prastaro Alessandro , Niembro Sandra , Shafir Alexandr , Vallribera Adelina 
Published: October 2010

AbstractThe use of phosphine‐free perfluoro‐tagged palladium nanoparticles immobilized on fluorous silica gel (FSG), either through fluorous–fluorous interactions or covalent bonding, in the Heck reaction of aryl iodides with allylic alcohols under aerobic conditions in water is described. 4‐(4‐Methoxyphenyl)‐butan‐2‐one, an important fine chemical, is readily accessed by this procedure. A two‐step one‐pot process, involving a Heck reaction followed by an enantioselective enzyme‐catalyzed reduction, to form chiral alcohols is applied to the synthesis of (R)‐(−)‐rhododendrol. The palladium catalysts can be recycled several times, both in the Heck reaction and in the one‐pot chemoenzymatic process.
Structures and H2 Adsorption Properties of Porous Scandium Metal–Organic Frameworks
Authors: Ibarra Ilich A. , Lin Xiang , Yang Sihai , Blake Alexander J. , Walker Gavin S. , Barnett Sarah A. , Allan David R. , Champness Neil R. , Hubberstey Peter , Schröder Martin 
Published: October 2010

AbstractTwo new three‐dimensional ScIII metal–organic frameworks {[Sc3O(L1)3(H2O)3]⋅Cl0.5(OH)0.5(DMF)4(H2O)3}∞ (1) (H2L1=1,4‐benzene‐dicarboxylic acid) and {[Sc3O(L2)2(H2O)3](OH)(H2O)5(DMF)}∞ (2) (H3L2=1,3,5‐tris(4‐carboxyphenyl)benzene) have been synthesised and characterised. The structures of both 1 and 2 incorporate the trinuclear trigonal planar [Sc3(O)(O2CR)6] building block featuring three ScIII centres joined by a central μ3‐O2− donor. Each ScIII centre is further bound by four oxygen donors from four different bridging carboxylate anions, and a molecule of water located trans to the μ3‐O2− donor completes the six coordination at the metal centre. Frameworks 1 and 2 show high thermal stability with retention of crystallinity up to 350 °C. The desolvated materials 1 a and 2 a, in which the solvent has been removed from the pores but with water or hydroxide remaining coordinated to ScIII, show BET surface areas based upon N2 uptake of 634 and 1233 m2 g−1, respectively, and pore volumes calculated from the maximum N2 adsorption of 0.25 cm3 g−1 and 0.62 cm3 g−1, respectively. At 20 bar and 78 K, the H2 isotherms for desolvated 1 a and 2 a confirm 2.48 and 1.99 wt % total H2 uptake, respectively. The isosteric heats of adsorption were estimated to be 5.25 and 2.59 kJ mol−1 at zero surface coverage for 1 a and 2 a, respectively. Treatment of 2 with acetone followed by thermal desolvation in vacuo generated free metal coordination sites in a new material 2 b. Framework 2 b shows an enhanced BET surface area of 1511 m2 g−1 and a pore volume of 0.76 cm3 g−1, with improved H2 uptake capacity and a higher heat of H2 adsorption. At 20 bar, H2 capacity increases from 1.99 wt % in 2 a to 2.64 wt % for 2 b, and the H2 adsorption enthalpy rises markedly from 2.59 to 6.90 kJ mol−1.
Total Syntheses of the Thiopeptides Amythiamicin C and D
Authors: Ammer Carolin , Bach Thorsten 
Published: October 2010

AbstractThe thiopeptides amythiamicin C and D were synthesized by employing amide bond formation, a Stille cross‐coupling reaction, and two Negishi cross‐coupling reactions as key transformations. The central 2,3,6‐trisubstituted pyridine ring of the target compounds was introduced as a 2,6‐dibromo‐3‐iodopyridine, which was selectively metalated at the 3‐position and connected to the complete Southern fragment of the amythiamicins by a Negishi cross‐coupling. For the synthesis of amythiamicin C, this step was followed by a Negishi cross‐coupling at C‐6 of the pyridine core. Subsequent attachment of the Eastern fragment was achieved by amide bond formation and macrolactam ring closure by a Stille cross‐coupling at C‐2. The Eastern bithiazole fragment of the amythiamins was constructed also by regioselective metalation and cross‐coupling reactions. The pivotal step involved the diastereoselective addition of 4‐bromothiazole‐2‐magnesium bromide to a chiral sulfinyl imine. For the synthesis of amythiamicin D, the order of cross‐coupling at C‐6, amide bond formation, and cross‐coupling at C‐2 was changed. The amide bond formation to the Eastern fragment was performed first and it was subsequently attempted to close the macrolactam by an intramolecular regioselective Stille cross‐coupling at C‐2. Despite the low regioselectivity of this reaction it paved the way to the immediate completion of the amythiamicin D synthesis when followed by a Negishi cross‐coupling at C‐6 with 2‐zincated methyl thiazole‐5‐carboxylate.
Mean squared error estimators of small area means using survey weights
Authors: Torabi Mahmoud , Rao Jon N. K. 
Published: October 2010

AbstractUsing survey weights, You & Rao [You and Rao, The Canadian Journal of Statistics 2002; 30, 431–439] proposed a pseudo‐empirical best linear unbiased prediction (pseudo‐EBLUP) estimator of a small area mean under a nested error linear regression model. This estimator borrows strength across areas through a linking model, and makes use of survey weights to ensure design consistency and preserve benchmarking property in the sense that the estimators add up to a reliable direct estimator of the mean of a large area covering the small areas. In this article, a second‐order approximation to the mean squared error (MSE) of the pseudo‐EBLUP estimator of a small area mean is derived. Using this approximation, an estimator of MSE that is nearly unbiased is derived; the MSE estimator of You & Rao [You and Rao, The Canadian Journal of Statistics 2002; 30, 431–439] ignored cross‐product terms in the MSE and hence it is biased. Empirical results on the performance of the proposed MSE estimator are also presented. The Canadian Journal of Statistics 38: 598–608; 2010 © 2010 Statistical Society of Canada
Positive quadrant dependence tests for copulas
Authors: Gijbels Irène , Omelka Marek , Sznajder Dominik 
Published: October 2010

AbstractIn this paper the interest is in testing the null hypothesis of positive quadrant dependence (PQD) between two random variables. Such a testing problem is important since prior knowledge of PQD is a qualitative restriction that should be taken into account in further statistical analysis, for example, when choosing an appropriate copula function to model the dependence structure. The key methodology of the proposed testing procedures consists of evaluating a “distance” between a nonparametric estimator of a copula and the independence copula, which serves as a reference case in the whole set of copulas having the PQD property. Choices of appropriate distances and nonparametric estimators of copula are discussed, and the proposed methods are compared with testing procedures based on bootstrap and multiplier techniques. The consistency of the testing procedures is established. In a simulation study the authors investigate the finite sample size and power performances of three types of test statistics, Kolmogorov–Smirnov, Cramér–von‐Mises, and Anderson–Darling statistics, together with several nonparametric estimators of a copula, including recently developed kernel type estimators. Finally, they apply the testing procedures on some real data. The Canadian Journal of Statistics 38: 555–581; 2010 © 2010 Statistical Society of Canada
Atrioventricular Reverse Remodeling After Valve Repair for Chronic Severe Mitral Regurgitation: 1‐Year Follow‐Up
Authors: Song Bong Gun , On Young Keun , Jeon Eun‐Seok , Kim Duk‐Kyung , Lee Sang‐Chol , Park Seung Woo , Oh Jae K. , Sung Ki Ick , Park PyoWon 
Published: October 2010

AbstractBackground:Chronic severe mitral regurgitation is associated with poor clinical outcome because chronic volume overload leads to hemodynamic changes and left ventricular and left atrial remodeling. Few data are available regarding left atrial volume index regression (LAVIR) and left ventricular mass index regression (LVMIR) after valve surgery for mitral regurgitation. We aimed to identify predictive correlates of LAVIR and LVMIR and to assess the relationship between these regressions.Hypothesis:Volume overload in chronic severe mitral regurgitation may influence left atrial and ventricular remodeling and reverse remodeling.Methods:Eighty‐five patients who underwent valve repair for severe chronic mitral regurgitation were consecutively enrolled. Plasma N‐terminal fragment of the prohormone brain natriuretic peptide (NT‐proBNP) and echocardiographic measurements were performed before surgery, before discharge, and at 12 months after surgery. LAVIR and LVMIR were assessed using serial echocardiography.Results:There were significant decreases in left ventricular mass index (LVMI; from 125.9 ± 31.3 g/m2 to 94.8 ± 28.6 g/m2, P = 0.001) and left atrial volume index (LAVI; from 75.3 ± 33.5 mL/m2 to 41.7 ± 16.0 mL/m2, P = 0.001) after surgery. Preoperative LAVI positively correlated with preoperative LVMI (r = 0.437, P = 0.001) and LAVIR positively correlated with LVMIR (r = 0.347, P = 0.001). In multivariate stepwise linear regression analysis, preoperative LAVI, age, hypertension, and atrial fibrillation were independently predictive of LAVIR, and preoperative LVMI, hypertension, and NT‐proBNP were independently predictive of LVMIR.Conclusions:Volume overload in chronic severe mitral regurgitation may influence left ventricular remodeling and reverse remodeling, as well as left atrial remodeling and reverse remodeling. Preoperative lower LAVI, younger age, absence of hypertension, and absence of atrial fibrillation may predict LAVIR, and preoperative lower LVMI, lower NT‐proBNP levels, and absence of hypertension may predict LVMIR after surgery for chronic severe mitral regurgitation. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.
Positive Vasodilator Stress ECG With Normal Myocardial Perfusion Imaging and Its Correlation With Coronary Angiographic Findings in African Americans and Hispanics
Authors: Paladugu Neelima , Shaqra Hussein , Blum Steve , Bhalodkar Narendra C. 
Published: October 2010

AbstractBackground:Ischemic electrocardiographic (ECG) changes during vasodilator stress testing (VST) in the presence of abnormal myocardial perfusion imaging (MPI) are uncommon and are associated with presence of multivessel coronary artery disease (CAD). However, there is a paucity of data regarding the significance of ischemic ECG changes during VST with normal MPI in general, and especially among African Americans and Hispanics.Hypothesis:Ischemic changes during VST with normal MPI are associated with significant CAD.Methods:A retrospective review was done of 2945 patients undergoing VST.Results:Only 20 patients (0.7%) had positive ECG changes with normal MPI. Their demographics were: 60% Hispanic, 40% African American; 85% female; mean age 63 ± 11 years; history of hypertension 80%, diabetes 50%, and dyslipidemia 75%; smokers 30%; atypical chest pain 60%, and typical chest pain 40%. Of these 20 patients, 12 patients underwent coronary angiography. All 12 had significant CAD; nine (75%) had multivessel disease and 3 (25%) had single‐vessel disease. Prevalence of clinical variables and risk factors for CAD were similar among both the groups who did and did not undergo coronary angiography.Conclusions:Among African Americans and Hispanics, ischemic ECG changes during VST with normal MPI are likely to be associated with significant CAD and may warrant coronary angiography to assess presence and extent of CAD. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.
Association of Left Atrial Myocardial Function With Left Ventricular Diastolic Dysfunction in Subjects With Preserved Systolic Function: A Strain Rate Imaging Study
Authors: Guan Zhiqiang , Zhang Di , Huang Rongjie , Zhang Fang , Wang Qingrong , Guo Shenglan 
Published: October 2010

AbstractBackground:The purpose of this study was to investigate the relationship between left atrial (LA) myocardial function and left ventricular (LV) diastolic dysfunction in subjects with preserved LV ejection fraction (LVEF).Methods:The study included a group of 118 hypertensive patients and normal subjects. LV diastolic dysfunction was classified into 4 groups: none, mild, moderate, and severe. Peak strain rates in systole (S‐Sr), early diastole (E‐Sr), and late diastole (A‐Sr) were obtained from Doppler‐derived strain rate imaging to evaluate LA myocardial deformation.Results:No significant difference in LA dimension was observed in subjects with different degrees of LV diastolic dysfunction, although LA myocardial strain rate parameters were all significantly different across the 4 groups (all with P < 0.001). Compared with patients of normal diastolic function, the mild diastolic dysfunction group had significantly lower E‐Sr (0.62 ± 0.18 s−1 vs 1.20 ± 0.38 s−1, P < 0.001) and S‐Sr (0.78 ± 0.16 s−1 vs 0.94 ± 0.22 s−1, P < 0.001) but increased A‐Sr (1.14 ± 0.29 s−1 vs 1.00 ± 0.23 s−1, P = 0.05).Conclusions:By using strain rate imaging, significant changes of LA deformation in response to different stages of LV diastolic dysfunction were detected in subjects with preserved LVEF. Quantification of LA myocardial function rather than LA size may have the potential to predict early LV diastolic dysfunction in subjects with preserved LVEF. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.
Combination Rosuvastatin Plus Fenofibric Acid in a Cohort of Patients 65 Years or Older With Mixed Dyslipidemia: Subanalysis of Two Randomized, Controlled Studies
Authors: Pepine Carl J. , Jacobson Terry A. , Carlson Dawn M. , Kelly Maureen T. , Setze Carolyn M. , Gold Alex , Stolzenbach James C. , Williams Laura A. 
Published: October 2010

AbstractBackgroundCoronary heart disease risk increases with advancing age and is further increased in patients with mixed dyslipidemia, characterized by elevated low‐density lipoprotein cholesterol (LDL‐C), low high‐density lipoprotein cholesterol (HDL‐C), and high triglycerides (TG). Combination lipid therapy is an option; however, efficacy and safety data among elderly patients are lacking.HypothesisThe combination of rosuvastatin and fenofibric acid (R + FA) results in more comprehensive lipid improvements than corresponding‐dose monotherapies, without additional safety concerns, in elderly patients with mixed dyslipidemia.MethodsThis post‐hoc analysis evaluated data from patients age ≥ 65 years (n = 401) with mixed dyslipidemia (LDL‐C ≥ 130 mg/dL, HDL‐C < 40 mg/dL [men] or < 50 mg/dL [women], and TG ≥ 150 mg/dL) in 2 randomized studies. Patients included in this analysis received either monotherapy (as R 5, 10, or 20 mg or FA 135 mg), or combination therapy with R (5, 10, or 20 mg) + FA 135 mg, for 12 weeks. Data were pooled and analyzed, and mean/median percent changes in multiple lipid parameters and biomarkers were compared.ResultsCombination therapy decreased LDL‐C by 31.8%–47.2% vs 10.6% with FA monotherapy (P < 0.001). Combination therapy also increased HDL‐C by 21.9%–27.0% vs 5.9%–9.9% with R monotherapy (P < 0.001), and decreased TG by 48.3%–53.5% vs 20.7%–32.8% with R monotherapy (P < 0.001). In general, safety profiles were consistent between combination therapy and individual monotherapies.ConclusionsIn these elderly patients with mixed dyslipidemia, R 5, 10, or 20 mg in combination with FA 135 mg improved the overall lipid profile, without new or unexpected safety issues. Copyright © 2010 Wiley Periodicals, Inc.Financial support for the studies was provided by Abbott and AstraZeneca. Dr. Pepine has served as a consultant for Abbott, Angioblast, Eli Lilly, Forest, Medtelligence, NicOx, Novartis, Sanofi‐Aventis, and SLACK, Inc.; has received research grants from Baxter, Bioheart, Inc., GlaxoSmithKline, and Pfizer; and has received unrestricted educational grants from AstraZeneca, AtCor Medical, Daiichi Sankyo, Eli Lilly, Pfizer, sanofi aventis, and Schering Plough. Dr. Jacobson is a consultant for Abbott, AstraZeneca, GlaxoSmithKline, Merck, and Schering Plough. Dr. Carlson, Dr. Kelly, Ms. Setze, Dr. Stolzenbach, and Dr. Williams are Abbott employees and stockholders. Dr. Gold is an AstraZeneca employee and stockholder.
Spironolactone Use in Heart Failure Patients With End‐Stage Renal Disease on Hemodialysis: Is It Safe?
Authors: Chua Doson , Lo Anita , Lo Chris 
Published: October 2010

AbstractBackground:Spironolactone is used in the treatment of cardiovascular disease, but is contraindicated in renal dysfunction due to the risk of hyperkalemia. It is not known if patients with end‐stage renal disease (ESRD) on hemodialysis are at the same risk for hyperkalemia. The objective of this study was to systematically review the evidence evaluating the incidence of hyperkalemia with spironolactone use in ESRD patients on hemodialysis.Hypothesis:Spironolactone use in ESRD patients on hemodialysis may not lead to greater incidence of hyperkalemia.Methods:We searched the MEDLINE, Embase, CINAHL, Cochrane, and PubMed databases up to January 2010 for English‐language, human‐subject clinical trials that evaluated the rate of hyperkalemia with spironolactone use in ESRD patients on hemodialysis. Search terms included were “spironolactone,” “eplerenone,” “aldosterone antagonist,” “heart failure,” “kidney failure,” “hemodialysis,” “dialysis,” and “renal replacement therapy.”Results:Six prospective trials demonstrated that spironolactone use was safe in ESRD patients on hemodialysis. The incidence of hyperkalemia with spironolactone treatment in these studies was similar to control groups. The studies involved a small population of compliant subjects who were at low risk for hyperkalemia.Conclusions:Small pilot studies demonstrated that spironolactone treatment in ESRD patients on hemodialysis did not result in higher hyperkalemia rates. Larger studies are needed to confirm these preliminary results before spironolactone is routinely considered in hemodialysis patients. Copyright © 2010 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.
Screening, risk assessment, and the approach to therapy in patients with prostate cancer
Authors: Freedland Stephen J. 
Published: October 2010

AbstractThe major challenge in prostate cancer is to identify patients at higher risk of death and to distinguish them from those more likely to die from other causes. Stratification of patients into risk groups can be used to guide management decisions at each disease stage. This review discusses the measures, tools, and nomograms available for risk assessment in prostate cancer. For patients with localized hormone‐sensitive disease, the choice is between active surveillance and radical treatment, with focal therapy an emerging option. Current guidelines recommend treatment of patients with a life expectancy ≥10 years, although active surveillance is being used with increasing frequency for low‐risk patients, even with a long life expectancy. A number of risk stratification methods have been devised to assess the risk of biochemical recurrence (BCR) after treatment, with prostate‐specific antigen (PSA) level, Gleason score, clinical stage, and tumor mass/volume all shown to be predictive of BCR. Among men with BCR after treatment, PSA doubling time (PSADT) was the best predictor of further progression. Although studies in patients with castration‐resistant prostate cancer have shown that PSA level and PSADT are associated with a risk of developing metastatic disease, there is currently no clear surrogate for disease progression or overall survival for this patient group and no standard second‐ or third‐line therapy after progression on first‐line chemotherapy. The use of newly developed risk‐stratification models and markers of disease progression should assist in the earlier identification of disease progression, allowing the optimal treatment of such patients. Cancer 2011. © 2010 American Cancer Society.
Tumor response and progression‐free survival as potential surrogate endpoints for overall survival in extensive stage small‐cell lung cancer
Authors: Foster Nathan R. , Qi Yingwei , Shi Qian , Krook James E. , Kugler John W. , Jett James R. , Molina Julian R. , Schild Steven E. , Adjei Alex A. , Mandrekar Sumithra J. 
Published: October 2010

AbstractBACKGROUND:The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression‐free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.METHODS:Individual patient data from 870 untreated extensive stage small‐cell lung cancer patients participating in 6 single‐arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient‐level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial‐level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial‐level surrogacy measures included:R2from weighted least squares regression model, Spearman correlation coefficient, andR2from bivariate survival model (CopulaR2).RESULTS:Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1‐10.0) and 5.5 (95% CI, 5.2‐5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient‐level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35‐0.51; concordance index 0.63;P< .01), with 6‐month PFS being the strongest (HR, 0.41; 95% CI, 0.35‐0.49; concordance index, 0.66,P< .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squaresR2= 0.79; CopulaR2= 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squaresR2≤0.48).CONCLUSIONS:PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials. Cancer 2011. © 2010 American Cancer Society.