bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential inhibitory effects of proton pump inhibitors on the metabolism and antiplatelet activities of clopidogrel and prasugrel
Authors: Chen Chia‐Hao , Yang Jyh‐Chin , Uang Yow‐Shieng , Lin Chun‐Jung 
Published: May 2012

ABSTRACTThe interaction between proton pump inhibitors (PPIs) and clopidogrel/prasugrel was investigated. The IC50 values of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole on the metabolic ratios of 2‐oxo‐clopidogrel/clopidogrel, H4 (the active metabolite of clopidogrel)/2‐oxo‐clopidogrel and R‐138727 (the active metabolite of prasugrel)/prasugrel thiolactone in human liver microsomes were determined. The antiplatelet activities of clopidogrel and prasugrel were measured with or without PPIs. As a result, most PPIs (except for pantoprazole) inhibited the formation of 2‐oxo‐clopidogrel with IC50 values of 20–32 μm and inhibited the formation of H4 with IC50 values of 6–20 μm. PPIs inhibited the formation of R‐138727 with IC50 values of 9–25 μm. Among the tested PPIs, omeprazole exhibited the highest inhibitory potency on the formation of H4. Omeprazole, esomeprazole and rabeprazole exhibited the highest inhibitory potencies on the formation of R‐138727. For platelet aggregation, omeprazole and lansoprazole show higher inhibitory effects on the antiplatelet activity of clopidogrel. On the other hand, omeprazole, esomeprazole and rabeprazole significantly decreased the antiplatelet activity of prasugrel thiolactone. These data indicate that PPIs differ in their effects of inhibiting the metabolism and antiplatelet activities of clopidogrel and prasugrel. Copyright © 2012 John Wiley & Sons, Ltd.
About the structural role of disulfide bridges in serum albumins: Evidence from protein simulated unfolding
Authors: Paris Guillaume , Kraszewski Sebastian , Ramseyer Christophe , Enescu Mironel 
Published: May 2012

AbstractThe role of the 17 disulfide (SS) bridges in preserving the native conformation of human serum albumin (HSA) is investigated by performing classical molecular dynamics (MD) simulations on protein structures with intact and, respectively, reduced SS bridges. The thermal unfolding simulations predict a clear destabilization of the protein secondary structure upon reduction of the SS bridges as well as a significant distortion of the tertiary structure that is revealed by the changes in the protein native contacts fraction. The effect of the SS bridges reduction on the protein compactness was tested by calculating Gibbs free energy profiles with respect to the protein gyration radius. The theoretical results obtained using the OPLS‐AA and the AMBER ff03 force fields are in agreement with the available experimental data. Beyond the validation of the simulation method, the results here reported provide new insights into the mechanism of the protein reductive/oxidative unfolding/folding processes. It is predicted that in the native conformation of the protein, the thiol (SH) groups belonging to the same reduced SS bridge are located in potential wells that maintain them in contact. The SH pairs can be dispatched by specific conformational transitions of the peptide chain located in the neighborhood of the cysteine residues. © 2012 Wiley Periodicals, Inc. Biopolymers 97:889–898, 2012.
High‐titer n‐butanol production by clostridium acetobutylicum JB200 in fed‐batch fermentation with intermittent gas stripping
Authors: Xue Chuang , Zhao Jingbo , Lu Congcong , Yang Shang‐Tian , Bai Fengwu , Tang I.‐Ching 
Published: May 2012

AbstractAcetone–butanol–ethanol (ABE) fermentation with a hyper‐butanol producing Clostridium acetobutylicum JB200 was studied for its potential to produce a high titer of butanol that can be readily recovered with gas stripping. In batch fermentation without gas stripping, a final butanol concentration of 19.1 g/L was produced from 86.4 g/L glucose consumed in 78 h, and butanol productivity and yield were 0.24 g/L h and 0.21 g/g, respectively. In contrast, when gas stripping was applied intermittently in fed‐batch fermentation, 172 g/L ABE (113.3 g/L butanol, 49.2 g/L acetone, 9.7 g/L ethanol) were produced from 474.9 g/L glucose in six feeding cycles over 326 h. The overall productivity and yield were 0.53 g/L h and 0.36 g/g for ABE and 0.35 g/L h and 0.24 g/g for butanol, respectively. The higher productivity was attributed to the reduced butanol concentration in the fermentation broth by gas stripping that alleviated butanol inhibition, whereas the increased butanol yield could be attributed to the reduced acids accumulation as most acids produced in acidogenesis were reassimilated by cells for ABE production. The intermittent gas stripping produced a highly concentrated condensate containing 195.9 g/L ABE or 150.5 g/L butanol that far exceeded butanol solubility in water. After liquid–liquid demixing or phase separation, a final product containing ∼610 g/L butanol, ∼40 g/L acetone, ∼10 g/L ethanol, and no acids was obtained. Compared to conventional ABE fermentation, the fed‐batch fermentation with intermittent gas stripping has the potential to reduce at least 90% of energy consumption and water usage in n‐butanol production from glucose. Biotechnol. Bioeng. 2012; 109: 2746–2756. © 2012 Wiley Periodicals, Inc.
Systematic review and meta-analysis of outcomes after intraoperative pancreatic duct stent placement during pancreaticoduodenectomy
Authors: Xiong J J , Altaf K , Mukherjee R , Huang W , Hu W M , Li A , Ke N W , Liu X B 
Published: May 2012

AbstractBackgroundPostoperative pancreatic leakage after pancreaticoduodenectomy is often serious. Although some studies have suggested that stenting the anastomosis can reduce the incidence of this complication, the value of stenting in the setting of pancreaticoduodenectomy remains unclear.MethodsStudies comparing outcomes of stent versus no stent, and internal versus external stent placement for pancreaticoduodenectomy were eligible for inclusion. Pooled odds ratios (ORs) with 95 per cent confidence intervals were calculated using fixed- or random-effects models.ResultsFrom a search of the literature published between January 1973 and September 2011, five randomized clinical trials (RCTs) and 11 non-randomized observational clinical studies (OCS) involving 1726 patients were selected for inclusion in this review. Meta-analysis of RCTs revealed that placing a stent in the pancreatic duct did not reduce the incidence of postoperative pancreatic fistula. External stents had no advantage over internal stents in terms of clinical outcome. Subgroup analyses revealed that use of an external stent significantly reduced the incidence of pancreatic fistula (RCTs: OR 0·42, 0·24 to 0·76, P = 0·004; OCS: OR 0·43, 0·27 to 0·68, P &lt; 0·001), delayed gastric emptying (RCTs: OR 0·41, 0·19 to 0·87, P = 0·02) and postoperative morbidity (RCTs: OR 0·55, 0·34 to 0·89, P = 0·02) compared with no stent.ConclusionPancreatic duct stenting did not reduce the incidence of pancreatic fistula and other complications in pancreaticoduodenectomy compared with no stenting. Although no difference was found between external and internal stents in terms of efficacy, external stents seemed to reduce the incidence of pancreatic fistula compared with control.
Real-time monitoring of liver damage during experimental ischaemia–reperfusion using a nitric oxide sensor
Authors: Nakagawa A , Yokoyama Y , Suzuki H , Shoji K , Watanabe Y , Imamura A , Kokuryo T , Nagino M 
Published: May 2012

Abstract

Background
Hepatic ischaemia–reperfusion (IR) injury may lead to liver damage during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role in this context. The aim of this study was to demonstrate real-time changes in intrahepatic NO concentration during IR and to correlate potential hepatic NO production with liver damage using a selective NO sensor.

Methods
Wistar rats were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which changes in intrahepatic NO levels were measured using an NO sensor. Additionally, rats were exposed to five successive periods of IR, each consisting of 15 min ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated by blood tests and histological examination. Hepatic expression of Akt, phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS was examined at different time points during and after IR by western blot and immunohistochemical analysis.

Results
During ischaemia, intrahepatic NO levels increased and reached a plateau at approximately 10 min. Repeated 15 min ischaemia–5 min reperfusion cycles reduced the maximum amount of NO produced during ischaemia gradually, and almost no NO production was observed during the fifth period of ischaemia. NO production following repeated ischaemia was proportional to the degree of hepatic viability. Phosphorylated eNOS was upregulated and correlated with the level of NO production during hepatic ischaemia.

Conclusion
Intrahepatic NO levels decrease during repeated IR in rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction of IR-related liver injury during experimental liver surgery.
Development and validation of a liquid chromatography–tandem mass spectrometry method for the determination of febuxostat in human plasma
Authors: Wang Haidong , Deng Pan , Chen Xiaoyan , Guo Lixia , Zhong Dafang 
Published: May 2012

ABSTRACTA rapid and sensitive analytical method based on liquid chromatography coupled to tandem mass spectrometry detection with positive ion electrospray ionization was developed for the determination of febuxostat in human plasma using d7‐febuxostat as the internal standard (IS). A simple protein precipitation was performed using acetonitrile. The analyte and IS were subjected to chromatographic analysis on a Capcell PAK C18 column (4.6 × 100 mm, 5 µm) using acetonitrile–5 mm ammonium acetate–formic acid (85:15:0.015, v/v/v) as the mobile phase at a flow rate of 0.6 mL/min. An Agilent 6460 electrospray tandem mass spectrometer was operated in the multiple reaction monitoring mode. The precursor‐to‐product ion transitions m/z 317 → m/z 261 (febuxsotat) and m/z 324 → m/z (261 + 262) (d7‐febuxostat, IS) were used for quantitation. The results were linear over the studied range (10.0–5000 ng/mL), and the total analysis time for each chromatograph was 3 min. The intra‐ and inter‐day precisions were less than 7.9 and 7.2%, respectively, and the accuracy was within ±4.2%. No evidence of analyte instability in human plasma was observed storage at −20°C for 31 days. This method was successfully applied in the determination of febuxostat concentrations in plasma samples from healthy Chinese volunteers. Copyright © 2012 John Wiley & Sons, Ltd.
Validation and application of a liquid chromatography‐tandem mass spectrometric method for the determination of GDC‐0152 in human plasma using solid‐phase extraction
Authors: Shin Young G. , Jones Steve A. , Murakami Stan C. , Budha Nageshwar , Ware Joseph , Wong Harvey , Buonarati Michael H. , Dean Brian , Hop Cornelis E. C. A. 
Published: May 2012

ABSTRACTA liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method was developed and validated for the determination of GDC‐0152 in human plasma to support clinical development. The method consisted of a solid‐phase extraction for sample preparation and LC‐MS/MS analysis in the positive ion mode using TurboIonSprayTM for analysis. d7‐GDC‐0152 was used as the internal standard. A linear regression (weighted 1/concentration2) was used to fit calibration curves over the concentration range of 0.02–10.0 ng/mL for GDC‐0152. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of 13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between‐run %CV was ≤8.64. Between‐run percentage accuracy ranged from 98.2 to 99.6%. GDC‐0152 was stable in human plasma for 363 days at −20°C and for 659 days at −70°C storage. GDC‐0152 was stable in human plasma at room temperature for up to 25 h and through three freeze–thaw cycles. In whole blood, GDC‐0152 was stable for 12 h at 4°C and at ambient temperature. This validated LC‐MS/MS method for determination of GDC‐0152 was used to support clinical studies. Copyright © 2012 John Wiley & Sons, Ltd.
Development and validation of LC‐MS/MS method for the estimation of β‐hydroxy‐β‐methylbutyrate in rat plasma and its application to pharmacokinetic studies
Authors: Deshpande Parag , Jie Zhang , Subbarayan Ramesh , Mamidi Vijay Kumar , Chunduri Raja Haranadha Babu , Das Tapas , Shreeram Sathyavageeswaran 
Published: May 2012

ABSTRACTA simple, sensitive and specific high‐performance liquid chromatography mass spectrometry (LC‐MS/MS) method was developed and validated for the quantification of β‐hydroxy‐β‐methyl butyrate (HMB) in small volumes of rat plasma using warfarin as an internal standard (IS). The API‐4000 LC‐MS/MS was operated under the multiple reaction‐monitoring mode using the electrospray ionization technique. A simple liquid–liquid extraction process was used to extract HMB and IS from rat plasma. The total run time was 3 min and the elution of HMB and IS occurred at 1.48 and 1.75 min respectively; this was achieved with a mobile phase consisting of 0.1% formic acid in a water–acetonitrile mixture (15:85, v/v) at a flow rate of 1.0 mL/min on a Agilent Eclipse XDB C8 (150 × 4.6, 5 µm) column. The developed method was validated in rat plasma with a lower limit of quantitation of 30.0 ng/mL for HMB. A linear response function was established for the range of concentrations 30–4600 ng/mL (r > 0.998) for HMB. The intra‐ and inter‐day precision values for HMB were acceptable as per Food and Drug Administration guidelines. HMB was stable in the battery of stability studies, viz. bench‐top, autosampler freeze–thaw cycles and long‐term stability for 30 days in plasma. The developed assay method was applied to a bioavailability study in rats. Copyright © 2012 John Wiley & Sons, Ltd.
A universal surrogate peptide to enable LC‐MS/MS bioanalysis of a diversity of human monoclonal antibody and human Fc‐fusion protein drug candidates in pre‐clinical animal studies
Authors: Furlong Michael T. , Ouyang Zheng , Wu Steven , Tamura James , Olah Timothy , Tymiak Adrienne , Jemal Mohammed 
Published: May 2012

ABSTRACTFor the development of human antibody Fc (fraction crystallizable) region‐containing therapeutic protein candidates, which can be either monoclonal antibodies (mAbs) or pharmacologically active proteins/peptides fused to the Fc region of human Immunoglobulin G (IgG), reliable quantification of these proteins in animal pharmacokinetic study plasma samples is critical. LC‐MS/MS has emerged as a promising assay platform for this purpose. LC‐MS/MS assays used for bioanalysis of human antibody Fc region‐containing therapeutic protein candidates frequently rely upon quantification of a ‘signature’ surrogate peptide whose sequence is unique to the protein analyte of interest. One drawback of the signature peptide approach is that a new LC‐MS/MS assay must be developed for each new human Fc region‐containing therapeutic protein. To address this issue, we propose an alternative ‘universal surrogate peptide’ approach for the quantification of human antibody Fc region‐containing therapeutic protein candidates in plasma samples from all nonclinical species. A single surrogate tryptic peptide was identified in the Fc region of most human antibody Fc‐containing therapeutic protein candidates. An LC‐MS‐MS method based upon this peptide was shown to be capable of supporting bioanalysis of a diversity of human Fc region‐containing therapeutic protein candidates in plasma samples of all commonly used animal species. Copyright © 2012 John Wiley & Sons, Ltd.
A unified structure for crowd simulation
Authors: Jund Thomas , Kraemer Pierre , Cazier David 
Published: May 2012

ABSTRACTRealistic simulation of crowds is an important issue for the production of virtual worlds for games, entertainment or architectural and urban planning. Difficult issues need to be addressed such as collision avoidance and the handling of dynamic environments. In this paper, we present a unified structure for the simulation of crowds in complex urban environments. We propose a topological multiresolution model supporting different levels of details, allowing efficient proximity querying and compatible with real‐time rendering and hierarchical path planning. A fine exploitation of the multiscale aspect of the underlying model allows to achieve the same efficiency as the fastest existing methods. The generality of the approach allows the simulation to be executed on any two manifold, and the unified approach eases the handling of dynamic environments. Copyright © 2012 John Wiley & Sons, Ltd.
Perceptually plausible formations for virtual conversers
Authors: Ennis Cathy , O'Sullivan Carol 
Published: May 2012

ABSTRACTRecent progress in real‐time simulations has led to a higher demand for believability from virtual characters. Background characters are becoming a more integral part of games, with emphasis being placed in particular on interactions between them. Conversing groups can play a significant role in adding plausibility, or a sense of presence, to a real‐time simulation. However, it is not obvious how best to generate and vary these kinds of groups. In this paper, using anthropological standards for interacting distances and formations, we conduct a series of experiments to examine how these parameters inherent in human conversation are perceived for virtual characters. Our results show that, although participants were sensitive to both distance and orientation changes between talkers and listeners in a virtual conversation, they were not as sensitive to anomalous gesturing behaviours across different distances. Copyright © 2012 John Wiley & Sons, Ltd.
Silver‐coated copper nanowires with improved anti‐oxidation property as conductive fillers in low‐density polyethylene
Authors: Luo Xiaoxiong , Gelves Genaro A. , Sundararaj Uttandaraman , Luo Jing‐Li 
Published: May 2012

AbstractSilver‐coated copper nanowires (AgCuNWs) are prepared by chemical plating method with copper nanowires (CuNWs) and Ag‐amine reagent. The prepared AgCuNWs with silver content of 66.52 wt.%, diameter 28–33 nm exhibited improved anti‐oxidation behaviour. The silver coating on AgCuNWs can effectively reduce the formation of copper oxide under room temperature. The temperature at which nanowires begin to gain weight can be improved from 85 to 230°C and the maximum weight gain can be decreased from 20.3% to 3.2% by applying silver coating. The volume electrical resistivity of the AgCuNWs filled low‐density polyethylene nanocomposites is lower than that of the CuNWs filled low‐density polyethylene nanocomposites with same volume percentage of fillers because the silver content in the AgCuNWs is not oxidised during compression moulding. © 2012 Canadian Society for Chemical Engineering
The Role of octopamine and tyramine in Drosophila larval locomotion
Authors: Selcho Mareike , Pauls Dennis , el Jundi Basil , Stocker Reinhard F. , Thum Andreas S. 
Published: May 2012

AbstractThe characteristic crawling behavior of Drosophila larvae consists of a series of rhythmic waves of peristalsis and episodes of head swinging and turning. The two biogenic amines octopamine and tyramine have recently been shown to modulate various parameters of locomotion, such as muscle contraction, the time spent in pausing or forward locomotion, and the initiation and maintenance of rhythmic motor patterns. By using mutants having altered octopamine and tyramine levels and by genetic interference with both systems we confirm that signaling of these two amines is necessary for larval locomotion. We show that a small set of about 40 octopaminergic/tyraminergic neurons within the ventral nerve cord is sufficient to trigger proper larval locomotion. Using single‐cell clones, we describe the morphology of these neurons individually. Given various potential roles of octopamine and tyramine in the larval brain, such as locomotion, learning and memory, stress‐induced behaviors or the regulation of the energy state, functions that are often not easy to discriminate, we dissect here for the first time a subset of this complex circuit that modulates specifically larval locomotion. Thus, these data will help to understand—for a given neuronal modulator—how specific behavioral functions are executed within distinct subcircuits of a complex neuronal network. J. Comp. Neurol. 520:3764–3785, 2012. © 2012 Wiley Periodicals, Inc.
Electromagnetism‐like method tuned constant modulus algorithm for blind detector in multicarrier CDMA system
Authors: Hung Ho‐Lung 
Published: May 2012

SUMMARYThis paper presents an efficient meta‐heuristic algorithm based on electromagnetism‐like method, which has been successfully implemented in multiuser detection problems. The contribution revisits blind multiuser detection for multicarrier code division multiple access systems using a novel combined adaptive step‐size constant modulus algorithm (CMA) and electromagnetism‐like method scheme. To work around potentially computational intractability and improved the capability of suppressing multiple access interference (MAI) for Multicarrier CDMA System, the proposed scheme exploits heuristics in consideration of both global and local exploration of the step size of the CMA. Simulation results obtained confirm that faster convergence and desirable BER performance with low computational complexity can be achieved with electromagnetism‐like method based CMA scheme, compared with the previous step‐size CMA scheme, genetic algorithm, and particle swarm optimization with CMA scheme. Copyright © 2012 John Wiley & Sons, Ltd.
Urine cytomorphology of micropapillary urothelial carcinoma
Authors: Zhu Bing , Rohan Stephen M. , Lin Xiaoqi 
Published: May 2012

AbstractMicropapillary urothelial carcinoma (MPUC) is a rare subtype of urothelial carcinoma (UC) with an aggressive clinical course. The cytomorphologic features of MPUC in urine cytology have not been well described. In this study, 23 urine specimens (11 voided urines and 12 bladder washings) from 23 patients with MPUC on follow‐up surgical material and 28 specimens (14voided urines and 14 bladder washings) from 28 patients with high‐grade UCs (HGUC) were retrieved. Cytologic features (nuclear grade, cytoplasmic characteristics), architectural features (single cell pattern, true papillary structures, flat sheets/nests, three dimensional clusters, micropapillary (inside‐out, acinar‐like, or cauliflower with nuclei located peripherally)), and necrosis were evaluated. Clinical follow‐up was obtained by chart review. Two findings, micropapillae and cytoplasmic vacuoles, were seen more frequently in MPUC compared to HGUC, 81.0% vs. 14.3%, and 57.1% vs. 14.3%, respectively. The combination of these two findings had a sensitivity of 78%, a specificity of 86%, a positive predictive value of 82%, and a negative predictive value of 83% for the diagnosis of MPUC on subsequent biopsy. MPUC and HGUC can both exhibit a single cell pattern, papillary structures, flat sheets/nests, three dimensional clusters, high‐nuclear grade, and necrosis, thus these findings are not useful in distinguishing these entities. Chart review revealed that patients with MPUC had a higher rate of metastasis to lymph nodes and distant organs than HGUC, 57% vs. 4%. Therefore, the findings of cytoplasmic vacuoles and micropapillary structures in UC from a urine cytology specimen are associated with MPUC on subsequent biopsy. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.