bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid screening and characterization of drug metabolites using a new quadrupole–linear ion trap mass spectrometer
Authors: Hopfgartner Gérard , Husser Christophe , Zell Manfred 
Published: February 2003

AbstractThe application of a new hybrid RF/DC quadrupole–linear ion trap mass spectrometer to support drug metabolism and pharmacokinetic studies is described. The instrument is based on a quadrupole ion path and is capable of conventional tandem mass spectrometry (MS/MS) as well as several high‐sensitivity ion trap MS scans using the final quadrupole as a linear ion trap. Several pharmaceutical compounds, including trocade, remikiren and tolcapone, were used to evaluate the capabilities of the system with positive and negative turbo ionspray, using either information‐dependent data acquisition (IDA) or targeted analysis for the screening, identification and quantification of metabolites. Owing to the MS/MS in‐space configuration, quadrupole‐like CID spectra with ion trap sensitivity can be obtained without the classical low mass cutoff of 3D ion traps. The system also has MS3 capability which allows fragmentation cascades to be followed. The combination of constant neutral loss or precursor ion scan with the enhanced product ion scan was found to be very selective for identifying metabolites at the picogram level in very complex matrices. Owing to the very high cycle time and, depending on the mass range, up to eight different MS experiments could be performed simultaneously without compromising chromatographic performance. Targeted product ion analysis was found to be complementary to IDA, in particular for very low concentrations. Comparable sensitivity was found in enhanced product ion scan and selected reaction monitoring modes. The instrument is particularly suitable for both qualitative and quantitative analysis. Copyright © 2003 John Wiley & Sons, Ltd.
Rapid quantification of HIV protease inhibitors in human plasma by high‐performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry
Authors: Crommentuyn K. M. L. , Rosing H. , Nan‐Offeringa L. G. A. H. , Hillebrand M. J. X. , Huitema A. D. R. , Beijnen J. H. 
Published: February 2003

AbstractHIV protease inhibitors are important antiretroviral drugs which have substantially reduced the morbidity and mortality associated with HIV‐1 infection. Recent data have shown relationships between plasma concentrations of the protease inhibitors and clinical response, which makes therapeutic drug monitoring valuable. We have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of the six licensed protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) and the pharmacologically active nelfinavir metabolite M8 in plasma.The sample pretreatment consisted of protein precipitation with a mixture of methanol and acetronitrile using only 100 µl of plasma. Chromatographic separation was performed on an Inertsil ODS3 column (50 × 2.0 mm i.d., particle size 5 µm), with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.5 ml min−1. The analytical run time was 5.5 min. The use of a 96‐well plate autosampler allowed batch sizes up to 150 patient samples. The triple‐quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges 0.01–10 µg ml−1 for indinavir and saquinavir, 0.1–10 µg ml−1 for amprenavir, 0.05–10 µg ml−1 for nelfinavir and ritonavir, 0.1–20 µg ml−1 for lopinavir and 0.01–5 µg ml−1 for M8. Saquinavir‐d5 and indinavir‐d6 were used as internal standards. The coefficients of variation were always <10% for both intra‐day and inter‐day precisions for each compound. Mean accuracies were also between the designated limits (±15%). The validated concentration ranges proved to be adequate in daily practice. This robust and fast LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring and pharmacokinetic studies in our hospital. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imaging
Authors: Rijpkema M. , Schuuring J. , van der Meulen Y. , van der Graaf M. , Bernsen H. , Boerman R. , van der Kogel A. , Heerschap A. 
Published: February 2003

AbstractOligodendroglial tumors may not be distinguished easily from other brain tumors based on clinical presentation and magnetic resonance imaging (MRI) alone. Identification of these tumors however may have therapeutic consequences. The purpose of this study was to characterize and identify oligodendrogliomas by their metabolic profile as measured by 1H MR spectroscopic imaging (MRSI). Fifteen patients with oligodendroglial tumors (eight high‐grade oligodendrogliomas, seven low‐grade oligodendrogliomas) underwent MRI and short echo time 1H MRSI examinations. Five main metabolites found in brain MR spectra were quantified and expressed as ratios of tumor to contralateral white matter tissue. The level of lipids plus lactate was also assessed in the tumor. For comparison six patients with a low grade astrocytoma were also included in the study. The metabolic profile of oligodendrogliomas showed a decreased level of N‐acetylaspartate and increased levels of choline‐containing compounds and glutamine plus glutamate compared with white matter. The level of glutamine plus glutamate was significantly higher in low‐grade oligodendrogliomas than in low‐grade astrocytomas and may serve as a metabolic marker in diagnosis and treatment planning. In high‐grade oligodendrogliomas large resonances of lipids plus lactate were observed in contrast to low‐grade tumors. Copyright © 2003 John Wiley & Sons, Ltd.
Quantification of the glycogen 13C‐1 NMR signal during glycogen synthesis in perfused rat liver
Authors: Bergans N. , Dresselaers T. , Vanhamme L. , Van Hecke P. , Van Huffel S. , Vanstapel F. 
Published: February 2003

AbstractWe studied glycogen synthesis from glucose in perfused livers of fed (n = 4) and 24 h starved (n = 7) rats. Glycogenolysis was inhibited by BAY R3401 (150 µM) and proglycosyn (100 µM). After 60 min, we replaced 99% 13C‐1 glucose by natural abundance glucose. This pulse‐chase design allowed us to recognize residual ongoing futile glycogen turnover from the release of initially deposited 13C‐label, into the 13C‐free chase medium. Net residual turnover was less than 2 ± 0.7% and 0.6 ± 0.2% of 1‐13C glycogen deposition rates of 0.31 ± 0.04 and 0.99 ± 0.04 µmol glucose g−1 min−1, in starved and fed livers, respectively. The 1‐13C glycogen signal was monitored throughout the experiment with proton‐decoupled 13C NMR spectroscopy and analyzed in the time domain using AMARES. We noticed progressive line‐broadening in any single experiment in the chase phase. One or a sum of two to three overlapping Lorentzians, with different exponential damping factors, were fitted to the signal. When the S/N was better than 40, the fit always delivered a small and a broad component. In the chase phase, the fit with a single Lorentzian resulted in a decline of glycogen signal by about 15 ± 4 and 12 ± 2% in starved and fed rats, respectively. This apparent decline in 1‐13C glycogen signal could not be accounted for by the appearance of equivalent amounts of 13C‐labeled metabolites in the perfusate. The fit with a sum of two Lorentzians resulted in a decline of glycogen signal intensity of 7 ± 5 and 5 ± 3% in starved and fed rats, respectively, which reduced the apparent turnover to 8 ± 9% and 6 ± 4%, respectively. Quantification of the growing 13C‐1 glycogen signal requires a model function that accommodates changes in line shape throughout the period under study. Copyright © 2003 John Wiley & Sons, Ltd.
Solubilization of cellulosomal cellulases by fusion with cellulose‐binding domain of noncellulosomal cellulase engd from Clostridium cellulovorans
Authors: Murashima Koichiro , Kosugi Akihiko , Doi Roy H. 
Published: February 2003

AbstractClostridium cellulovorans produces a cellulase complex (cellulosome) as well as noncellulosomal cellulases. In this study, we determined a factor that affected the solubility of the cellulosomal cellulase EngB and the noncellulosomal EngD when they were expressed in Escherichia coli. The catalytic domains of EngB and EngD formed inclusion bodies when expressed in E. coli. On the other hand, both catalytic domains containing the C‐terminal cellulose‐binding domain (CBD) of EngD were expressed in soluble form. Fusion with the CBD of EngD also helped increased the solubility of cellulosomal cellulase EngL upon expression in E. coli. These results indicate that the CBD of EngD plays an important role in the soluble expression of the catalytic domains of EngB, EngL, and EngD. The possible mechanisms of solubilization by fusion of the catalytic domain with the CBD from EngD are discussed. Proteins 2003;50:620–628. © 2003 Wiley‐Liss, Inc.
The role of electrostatic interaction in the molecular recognition of selective agonists to metabotropic glutamate receptors
Authors: Macchiarulo Antonio , Costantino Gabriele , Sbaglia Robert , Aiello Stefania , Meniconi Mirco , Pellicciari Roberto 
Published: February 2003

AbstractThe influence of electrostatic interactions in determining selectivity for individual subtypes of metabotropic glutamate receptors (mGluRs) is evaluated for a small set of agonists by using the program Delphi and the information thus obtained is compared with docking experiments carried out with AutoDock. The evaluation of the electrostatic component of the free energy of binding for L‐Glu, L‐AP4, or S‐PPG to mGluR1, mGluR2, and mGluR4 subtypes allowed for the detection of subtle differences in the electronic properties of the three subtypes, differences that can account for the observed agonist selectivity. Proteins 2003;50:609–619. © 2003 Wiley‐Liss, Inc.
Crystal structure of a hypothetical protein, TM841 of Thermotoga maritima, reveals its function as a fatty acid–binding protein
Authors: Schulze‐Gahmen Ursula , Pelaschier Joanne , Yokota Hisao , Kim Rosalind , Kim Sung‐Hou 
Published: February 2003

AbstractWe determined the three‐dimensional (3D) crystal structure of protein TM841, a protein product from a hypothetical open‐reading frame in the genome of the hyperthermophile bacterium Thermotoga maritima, to 2.0 Å resolution. The protein belongs to a large protein family, DegV or COG1307 of unknown function. The 35 kDa protein consists of two separate domains, with low‐level structural resemblance to domains from other proteins with known 3D structures. These structural homologies, however, provided no clues for the function of TM841. But the electron density maps revealed clear density for a bound fatty‐acid molecule in a pocket between the two protein domains. The structure indicates that TM841 has the molecular function of fatty‐acid binding and may play a role in the cellular functions of fatty acid transport or metabolism. Proteins 2003;50:526–530. © 2003 Wiley‐Liss, Inc.
Protein local structure prediction from sequence
Authors: Hunter Cornelius G. , Subramaniam Shankar 
Published: February 2003

AbstractA basis set of protein canonical fragments, or centroids, represents the range of local structure found in globular proteins. We develop a methodology to predict centroids from the amino acid sequence. The predictor gives the probability of each centroid in the basis set, at each loci along the backbone. The predictor selects the best‐fit centroid at about 40% of the loci. The predicted probabilities are accurate and can be used to judge the confidence of each centroid prediction. For example, when filtering out centroids with <0.50 probability, the predictor is 65% accurate, although such high‐probability centroids occur at only 28% of the loci. Centroids with high probability can be interpreted as segments that are highly influenced by the amino acid sequence, whereas centroids with low probability can be interpreted as segments that are more likely influenced by tertiary contacts. Low‐resolution, starting point structures, can be generated by fitting the predicted centroids together. Proteins 2003;50:572–579. © 2003 Wiley‐Liss, Inc.
Fine‐grained protein fold assignment by support vector machines using generalized npeptide coding schemes and jury voting from multiple‐parameter sets
Authors: Yu Chin‐Sheng , Wang Jung‐Ying , Yang Jinn‐Moon , Lyu Ping‐Chiang , Lin Chih‐Jen , Hwang Jenn‐Kang 
Published: February 2003

AbstractIn the coarse‐grained fold assignment of major protein classes, such as all‐α, all‐β, α + β, α/β proteins, one can easily achieve high prediction accuracy from primary amino acid sequences. However, the fine‐grained assignment of folds, such as those defined in the Structural Classification of Proteins (SCOP) database, presents a challenge due to the larger amount of folds available. Recent study yielded reasonable prediction accuracy of 56.0% on an independent set of 27 most populated folds. In this communication, we apply the support vector machine (SVM) method, using a combination of protein descriptors based on the properties derived from the composition of n‐peptide and jury voting, to the fine‐grained fold prediction, and are able to achieve an overall prediction accuracy of 69.6% on the same independent set—significantly higher than the previous results. On 10‐fold cross‐validation, we obtained a prediction accuracy of 65.3%. Our results show that SVM coupled with suitable global sequence‐coding schemes can significantly improve the fine‐grained fold prediction. Our approach should be useful in structure prediction and modeling. Proteins 2003;50:531–536. © 2003 Wiley‐Liss, Inc.
Thermal unfolding simulations of apo‐calmodulin using leap‐dynamics
Authors: Kleinjung Jens , Fraternali Franca , Martin Stephen R. , Bayley Peter M. 
Published: February 2003

AbstractThe simulation method leap‐dynamics (LD) has been applied to protein thermal unfolding simulations to investigate domain‐specific unfolding behavior. Thermal unfolding simulations of the 148‐residue protein apo‐calmodulin with implicit solvent were performed at temperatures 290 K, 325 K, and 360 K and compared with the corresponding molecular dynamics trajectories in terms of a number of calculated conformational parameters. The main experimental results of unfolding are reproduced in showing the lower stability of the C‐domain: at 290 K, both the N‐ and C‐domains are essentially stable; at 325 K, the C‐domain unfolds, whereas the N‐domain remains folded; and at 360 K, both domains unfold extensively. This behavior could not be reproduced by molecular dynamics simulations alone under the same conditions. These results show an encouraging degree of convergence between experiment and LD simulation. The simulations are able to describe the overall plasticity of the apo‐calmodulin structure and to reveal details such as reversible folding/unfolding events within single helices. The results show that by using the combined application of a fast and efficient sampling routine with a detailed molecular dynamics force field, unfolding simulations of proteins at atomic resolution are within the scope of current computational power. Proteins 2003;50:648–656. © 2003 Wiley‐Liss, Inc.
Interpolation of geophysical data using continuous global surfaces
Authors: Billings Stephen D. , Beatson Rick K. , Newsam Garry N. 
Published: February 2003

A wide class of interpolation methods, including thin‐plate and tension splines, kriging, sinc functions, equivalent‐source, and radial basis functions, can be encompassed in a common mathematical framework involving continuous global surfaces (CGSs). The difficulty in applying these techniques to geophysical data sets has been the computational and memory requirements involved in solving the large, dense matrix equations that arise. We outline a three‐step process for reducing the computational requirements: (1) replace the direct inversion techniques with iterative methods such as conjugate gradients; (2) use preconditioning to cluster the eigenvalues of the interpolation matrix and hence speed convergence; and (3) compute the matrix–vector product required at each iteration with a fast multipole or fast moment method.We apply the new methodology to a regional gravity compilation with a highly heterogeneous sampling density. The industry standard minimum‐curvature algorithms and several scale‐dependent CGS methods are unable to adapt to the varying data density without introducing spurious artifacts. In contrast, the thin‐plate spline is scale independent and produces an excellent fit. When applied to an aeromagnetic data set with relatively uniform sampling, the thin‐plate spline does not significantly improve results over a standard minimum‐curvature algorithm.
Synthesis of polyaniline using horseradish peroxidase immobilized on plasma‐functionalized polyethylene surfaces as initiator
Authors: Alvarez S. , Manolache S. , Denes F. 
Published: February 2003

AbstractThe doping of semiconducting conjugated polymers (e.g., polyaniline, PANI) can result in the elimination of the bandgap, leading to high electrical conductivities (comparable to metals). Doped PANI is totally insoluble and thus nonprocessable, which considerably limits its practical applications. Synthesis of PANI using immobilized horseradish peroxidase (HRP) as a catalyst in aqueous solutions can open up additional possibilities for applications through the direct synthesis of controlled‐thickness PANI layers on various substrate surfaces. The RF plasma‐enhanced surface functionalization of polyethylene and the covalent immobilization of HRP are discussed, and the polymerization of aniline initiated by immobilized HRP is presented. The nature of plasma‐grafted surface functionalities on the substrate surfaces and the formation of PANI are demonstrated using X‐ray photoelectron spectroscopy and attenuated total reflectance Fourier transform IR spectroscopy. The molecular weight distribution of PANI is evaluated with gel permeation chromatography, and the activity of the immobilized enzyme is monitored using UV spectroscopy. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 369–379, 2003
The characteristic properties of poly(methyl methacrylate)/polystyrene core‐shell composite polymer latex
Authors: Lee Chia‐Fen 
Published: February 2003

AbstractIn this study, the poly(methyl methacrylate/polystyrene (PMMA/PS) core‐shell composite latex was synthesized by the method of soapless seeded emulsion polymerization. The morphology of the PMMA/PS composite latex was core‐shell structure, with PMMA as the core and PS as the shell. The core‐shell morphology of the composite polymer latex was found to be thermally unstable. Under the effect of thermal annealing, the PS shell region first dispersed into the PMMA core region, and later separated out to the outside of the PMMA core region. This was explained on the basis of lowing interfacial tension between the PMMA and PS phases owing to the interpenetration layer. The interpenetration layer, which was located at the interface of the core and shell region, contained graft copolymer and entangled polymer chains. Both the graft copolymer and entangled polymer chains had the ability to lower the interfacial tension between the PMMA and PS phases. Also, the effect of thermal annealing on the morphology of commercial polymer/composite latex polymer blends was examined. The result showed that the core‐shell composite latex had the ability to enhance the compatibility of the components of polymer blends. The compatibilizing ability of the core‐shell composite latex was better than that of a random copolymer. Moreover, the effect of the amount of core‐shell composite latex on the morphology of the polymer blend was investigated. The polymer blends, which contained composite latex above 50% wt, showed the morphology of a double sea‐island structure. In addition, the composite latex was completely dissolved in solvent to destroy the core‐shell structure and release the entangled polymer chains, and then dried to form the entangled free composite polymer. The entangled free composite polymer had the ability to enhance the compatibility of the components of the polymer blend as usual. The weight ratio 3/7 commercial polymer/entangled free composite polymer blend showed the morphology of the phase inversion structure. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 312–321, 2003
Effect of styrene–isoprene–styrene, styrene–butadiene–styrene, and styrene–butadiene–rubber on the mechanical, thermal, rheological, and morphological properties of polypropylene/polystyrene blends
Authors: Raghu P. , Nere C. K. , Jagtap R. N. 
Published: February 2003

AbstractThe mechanical, thermal, rheological, and morphological properties of polypropylene (PP)/polystyrene (PS) blends compatibilized with styrene–isoprene–styrene (SIS), styrene–butadiene–styrene (SBS), and styrene–butadiene–rubber (SBR) were studied. The incompatible PP and PS phases were effectively dispersed by the addition of SIS, SBS, and SBR as compatibilizers. The PP/PS blends were mechanically evaluated in terms of the impact strength, ductility, and tensile yield stress to determine the influence of the compatibilizers on the performance properties of these materials. SIS‐ and SBS‐compatibilized blends showed significantly improved impact strength and ductility in comparison with SBR‐compatibilized blends over the entire range of compatibilizer concentrations. Differential scanning calorimetry indicated compatibility between the components upon the addition of SIS, SBS, and SBR by the appearance of shifts in the melt peak of PP toward the melting range of PS. The melt viscosity and storage modulus of the blends depended on the composition, type, and amount of compatibilizer. Scanning electron microscopy images confirmed the compatibility between the PP and PS components in the presence of SIS, SBS, and SBR by showing finer phase domains. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 266–277, 2003
Surface of cellulosic materials modified with functionalized polyethylene coupling agents
Authors: Li Qingxiu , Matuana Laurent M. 
Published: February 2003

AbstractThe interfacial adhesion between a wood fiber and a plastic matrix strongly influences the performance of wood‐fiber‐reinforced thermoplastic composites. Fiber surface modification with coupling agents is generally needed to induce bond formation between the fiber and polymer matrix. This study investigated the chemical reactions between cellulosic materials and functionalized polyethylene coupling agents. Both wood flour and cotton cellulose powder were treated with acrylic acid‐functionalized polyethylene and maleic anhydride‐functionalized polyethylene (maleated polyethylene) for surface modifications, and chemical changes resulting from these treatments were followed by a study of the Fourier transform infrared and X‐ray photoelectron spectroscopy spectra. Variations in the band intensities, oxygen‐to‐carbon ratios, and concentrations of unoxidized carbon atoms were related to changes that occurred on the surfaces of modified cellulosic materials. The experimental results indicated that chemical bonds between the hydroxyl groups of the cellulosic materials and the functional groups of the coupling agents occurred through esterification reactions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 278–286, 2003