bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation of primary satellite cells improves properties of reinnervated skeletal muscles
Authors: Lazerges Cyril , Daussin Paul‐André , Coulet Bertrand , Boubaker el Andalousi Ramzi , Micallef Jean‐Paul , Chammas Michel , Reyne Yves , Bacou Francis
Published: January 2004

Skeletal muscle demonstrates a force deficit after repair of injured peripheral nerves. We tested the hypothesis that transplantation of satellite cells into reinnervated rabbit tibialis anterior (TA) muscles improves their properties. Adult rabbits underwent transection and immediate suture of the common peroneal nerve. In order to provide an environment favorable for cell transplantation, TA were then made to degenerate by cardiotoxin injection, either immediately or after a 2‐month delay, which is sufficient for muscle reinnervation. In both cases, the injured TA were transplanted with cultured satellite cells 5 days after induction of muscle degeneration. When cells were transferred immediately after nerve repair, drastic morphological and functional muscle alterations were observed. However, when the muscles were allowed to become reinnervated before cell transplantation, muscles were heavier and developed a significantly higher maximal force compared to denervated–reinnervated muscles. Thus, application of the cell therapy protocol improved properties of denervated muscles only when they were allowed to become innervated. These results, which represent the application of cell therapy to improve force recovery of reinnervated muscles, will be of significant interest in certain clinical contexts, particularly after immediate or delayed muscle reinnervation. Muscle Nerve 29: 218–226, 2004
Prediction of aspiration in myasthenia gravis
Authors: Koopman Wilma J. , Wiebe Samuel , Colton‐Hudson Angela , Moosa Tas , Smith Dean , Bach David , Nicolle Michael W.
Published: January 2004

Prediction of the risk of dysphagia and aspiration is important in the management of myasthenia gravis (MG). We assessed the ability of four bedside clinical tools to predict aspiration in 20 MG patients. Patients completed a self‐directed questionnaire, underwent clinical neurological assessment and a bedside speech pathology assessment, and were assessed with the quantitative myasthenia gravis (QMG) score. The ability of these tools to predict aspiration was compared with the results of a modified barium swallow. Seven patients aspirated, 4 silently. The total self‐directed questionnaire score, two specific questions on the self‐directed questionnaire, the prediction based on clinical neurological assessment, and the QMG bulbar subset score all correlated with aspiration. The speech pathology prediction was highly sensitive but less specific. This pilot study shows that simple clinical tools can predict which MG patients are at risk of aspiration. Muscle Nerve 29: 256–260, 2004
Reproducibility of muscle‐fiber conduction velocity estimates using multichannel surface EMG techniques
Authors: Farina Dario , Zagari Domenico , Gazzoni Marco , Merletti Roberto
Published: January 2004

The aim of this study was to assess the reproducibility of muscle‐fiber conduction velocity (MFCV) estimates obtained from multichannel surface electromyographic (EMG) recordings. Surface EMG signals were collected with a matrix of 61 electrodes during isometric, submaximal (50% of the maximal voluntary contraction torque) contractions of the biceps brachii muscle. Conduction velocity was estimated using multichannel maximum likelihood techniques. Reproducibility of MFCV estimates was assessed varying the number of signals (two to seven) used for the estimate and the distance between detection points (5–30 mm). Intraclass correlation coefficient (ICC) of both initial MFCV values and their rates of change with fatigue increased when increasing number of signals and distance between detection points. ICC of initial MFCV was negative using two signals for MFCV estimate, and it increased to approximately 75% with six to seven signals. Thus, reproducibility of MFCV estimates may be improved significantly using advanced multichannel estimation methods with respect to classic two‐channel techniques. Muscle Nerve 29: 282–291, 2004
Effect of static stretch training on neural and mechanical properties of the human plantar‐flexor muscles
Authors: Guissard Nathalie , Duchateau Jacques
Published: January 2004

To determine the contributions of neural and mechanical mechanisms to the limits in the range of motion (ROM) about a joint, we studied the effects of 30 sessions of static stretch training on the characteristics of the plantar‐flexor muscles in 12 subjects. Changes in the maximal ankle dorsiflexion and the torque produced during passive stretching at various ankle angles, as well as maximal voluntary contraction (MVC) and electrically induced contractions, were recorded after 10, 20, and 30 sessions, and 1 month after the end of the training program. Reflex activities were tested by recording the Hoffmann reflex (H reflex) and tendon reflex (T reflex) in the soleus muscle. Training caused a 30.8% (P < 0.01) increase in the maximal ankle dorsiflexion. This improved flexibility was associated (r2 = 0.88; P < 0.001) with a decrease in muscle passive stiffness and, after the first 10 sessions only, with a small increase in passive torque at maximal dorsiflexion. Furthermore, both the H‐ and T‐reflex amplitudes were reduced after training, especially the latter (−36% vs. −14%; P < 0.05). The MVC torque and the maximal rate of torque development were not affected by training. Although the changes in flexibility and passive stiffness were partially maintained 1 month after the end of the training program, reflex activities had already returned to control levels. It is concluded that the increased flexibility results mainly from reduced passive stiffness of the muscle–tendon unit and tonic reflex activity. The underlying neural and mechanical adaptation mechanisms, however, showed different time courses. Muscle Nerve 29: 248–255, 2004
Quadriceps muscle endurance in patients with chronic obstructive pulmonary disease
Authors: Hul Alex Van'T , Harlaar Jaap , Gosselink Rik , Hollander Peter , Postmus Piet , Kwakkel Gert
Published: January 2004

The purpose of this study was to compare quadriceps muscle strength (maximal voluntary contraction, MVC), endurance (TLIM), and dynamic work capacity (WLIM) in 89 patients (57 men and 32 women) with chronic obstructive pulmonary disease (COPD) to 31 healthy controls (20 men and 11 women). Compared with the healthy subjects, COPD patients demonstrated statistically significant (P < 0.05) lower values for MVC, TLIM and WLIM. The MVC was 20–30% lower, whereas TLIM and WLIM were 70–80% lower in the patients. Stepwise multiple regression analysis revealed that pulmonary function variables contributed only partially to the explanation of variance in MVC, TLIM, and WLIM. Our results indicate that in patients with COPD, quadriceps muscle endurance and dynamic work capacity are impaired to a greater extent than is quadriceps muscle strength. For rehabilitation purposes, the findings may lead to more specific exercise programs, further enhancing rehabilitation outcomes in terms of functional abilities and social participation. Muscle Nerve 29: 267–274, 2004
Electrodiagnostic services in the United States
Authors: Dillingham Timothy R. , Pezzin Liliana E. , Rice J. Bradford
Published: January 2004

To identify patterns of service provision in the United States, electrodiagnostic encounters were characterized by analyzing data from the 1998 MarketScan Commercial Claims & Encounters Database (The MEDSTAT Group). Electrodiagnostic‐related claims were identified using CPT codes for nerve conduction studies, electromyography, and somatosensory evoked potentials. Over 130,000 electrodiagnostic claims representing 48,207 separate electrodiagnostic encounters were identified. Neurologists accounted for the highest percentage of physician providers (23.6%), followed closely by physiatrists (22%). Physiatrists performed the services at a higher rate than any other provider (886.3 studies per 100 practicing physiatrists). Electrodiagnostic encounters by nonphysician providers accounted for 16.9% of all studies. Physical therapists were the dominant nonphysician providers of electrodiagnostic services (9.3%), followed by podiatrists (5.5%). Physician providers had a median of three claims per encounter compared with one claim per encounter for nonphysician providers. The relatively large proportion of studies conducted by nonphysicians, as well as their limited extent of testing, raises concerns about the quality of care for these patients. These quality issues should be addressed in future studies. Muscle Nerve 29: 198–204, 2004
A coupling of multi‐zone curved Galerkin BEM with finite elements for independently modelled sub‐domains with non‐matching nodes in elasticity
Authors: Ganguly S. , Layton J. B. , Balakrishna C.
Published: January 2004

When the different parts of a structure are modelled independently by BEM or FEM methods, it is sometimes necessary to put the parts together without remeshing of the nodes along the part interfaces. Frequently the nodes do not match along the interface. In this work, the symmetric Galerkin multi‐zone curved boundary element is a fully symmetric formulation and is the method used for the boundary element part. For BEM–FEM coupling it is then necessary to interpolate the tractions in‐between the non‐matching nodes for the FEM part. Finally, the coupling is achieved by transforming the finite element domains to equivalent boundary element domains in a block symmetric formulation. This system is then coupled with a boundary element domain with non‐matching nodes in‐between. Copyright © 2004 John Wiley & Sons, Ltd.
Perfectly matched layers for transient elastodynamics of unbounded domains
Authors: Basu Ushnish , Chopra Anil K.
Published: January 2004

One approach to the numerical solution of a wave equation on an unbounded domain uses a bounded domain surrounded by an absorbing boundary or layer that absorbs waves propagating outward from the bounded domain. A perfectly matched layer (PML) is an unphysical absorbing layer model for linear wave equations that absorbs, almost perfectly, outgoing waves of all non‐tangential angles‐of‐incidence and of all non‐zero frequencies. In a recent work [Computer Methods in Applied Mechanics and Engineering 2003; 192: 1337–1375], the authors presented, inter alia, time‐harmonic governing equations of PMLs for anti‐plane and for plane‐strain motion of (visco‐) elastic media. This paper presents (a) corresponding time‐domain, displacement‐based governing equations of these PMLs and (b) displacement‐based finite element implementations of these equations, suitable for direct transient analysis. The finite element implementation of the anti‐plane PML is found to be symmetric, whereas that of the plane‐strain PML is not. Numerical results are presented for the anti‐plane motion of a semi‐infinite layer on a rigid base, and for the classical soil–structure interaction problems of a rigid strip‐footing on (i) a half‐plane, (ii) a layer on a half‐plane, and (iii) a layer on a rigid base. These results demonstrate the high accuracy achievable by PML models even with small bounded domains. Copyright © 2004 John Wiley & Sons, Ltd.
XFEM for direct evaluation of mixed mode SIFs in homogeneous and bi‐materials
Authors: Liu X. Y. , Xiao Q. Z. , Karihaloo B. L.
Published: January 2004

The extended finite element method (XFEM) is improved to directly evaluate mixed mode stress intensity factors (SIFs) without extra post‐processing, for homogeneous materials as well as for bimaterials. This is achieved by enriching the finite element (FE) approximation of the nodes surrounding the crack tip with not only the first term but also the higher order terms of the crack tip asymptotic field using a partition of unity method (PUM). The crack faces behind the tip(s) are modelled independently of the mesh by displacement jump functions. The additional coefficients corresponding to the enrichments at the nodes of the elements surrounding the crack tip are forced to be equal by a penalty function method, thus ensuring that the displacement approximations reduce to the actual asymptotic fields adjacent to the crack tip. The numerical results so obtained are in excellent agreement with analytical and numerical results available in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Combined extended and superimposed finite element method for cracks
Authors: Lee Sang‐Ho , Song Jeong‐Hoon , Yoon Young‐Cheol , Zi Goangseup , Belytschko Ted
Published: January 2004

A combination of the extended finite element method (XFEM) and the mesh superposition method (s‐version FEM) for modelling of stationary and growing cracks is presented. The near‐tip field is modelled by superimposed quarter point elements on an overlaid mesh and the rest of the discontinuity is implicitly described by a step function on partition of unity. The two displacement fields are matched through a transition region. The method can robustly deal with stationary crack and crack growth. It simplifies the numerical integration of the weak form in the Galerkin method as compared to the s‐version FEM. Numerical experiments are provided to demonstrate the effectiveness and robustness of the proposed method. Copyright © 2004 John Wiley & Sons, Ltd.
The computation of the J integral with the traction boundary integral equation
Authors: Chen Songying , Wang Leqin , Jiao Lei
Published: January 2004

The solutions of the displacement boundary integral equation (BIE) are not uniquely determined in certain types of boundary conditions. Traction boundary integral equations that have unique solutions in these traction and mixed boundary cases are established. For two‐dimensional linear elasticity problems, the divergence‐free property of the traction boundary integral equation is established. By applying Stokes' theorem, unknown tractions or displacements can be reduced to computation of traction integral potential functions at the boundary points. The same is true of the J integral: it is divergence‐free and the evaluation of the J integral can be inverted into the computation of the J integral potential functions at the boundary points of the cracked body. The J integral can be expressed as the linear combination of the tractions and displacements from the traction BIE on the boundary of the cracked body. Numerical integrals are not needed at all. Selected examples are presented to demonstrate the validity of the traction boundary integral and J integral. Copyright © 2004 John Wiley & Sons, Ltd.
Theoretical study of magnetic coupling interaction in terephthalato‐bridged Ni(II) binuclear systems
Authors: Bi Siwei , Liu Chengbu
Published: January 2004

The density functional theory combined with broken‐symmetry approach has been successfully extended into the study of the long‐range weak coupling interaction in a binuclear Ni(II) complex bridged by terephthalate dianion. The calculated magnetic coupling constant (−0.27 cm−1) is well in agreement with the experimental one (−0.33 cm−1). The relative magnitude of the energies of different spin states has been obtained. The spin delocalization and spin polarization occur between two Ni(II) ions, based on the analysis of the spin density distribution. Weak antiferromagnetic behavior in such a system may result from the competition between spin delocalization and spin polarization where the former is dominant. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Structural analysis of certain linear operators representing chemical network systems via the existence and uniqueness theorems of spectral resolution VII
Authors: Arimoto Shigeru , Spivakovsky Mark , Ohno Hiromu , Zizler Peter , Zuidwijk Rob A. , Taylor Keith F. , Yamabe Tokio , Mezey Paul G.
Published: January 2004

The present Part VII of this series of articles is a direct extension of Part VI, where (1) fundamental methodology in the repeat space theory (RST) and (2) frontier electron theory of reactivity indices were theoretically linked. This part presents an estimate of the size of the regular index set, which was a central notion in Part VI, and two new theorems that are simpler and more powerful than the main theorem in Part VI. The main theorem in this part enables one to globally contextualize the Generalized Alpha Existence Theorem (a theorem essential in the RST and proved in Part V) and the μ Existence Theorem (derived from the main theorem in Part VI) into the star algebra structure of the generalized repeat space 𝒳r(q, d). © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Critical evaluation of the bond order concept with application to thermal hydrogen shifts
Authors: Buck Henk
Published: January 2004

Since Coulson introduced the concept of bond order into the molecular orbital theory its significance has been proven as an important tool for the discussion and calculation of bond strength and bond length. On studying simple π‐conjugated odd‐ and even‐membered carbonhydrogen systems in an open and cyclic geometry, it could be shown that the use of the concept of bond order with respect to bond length in geometric representations for ground or transition states must be handled with caution. This has been concluded from a theoretical study of Okajima and Imafuku on chlorine and hydrogen thermal shifts in (cyclo)pentadiene and cycloheptatriene compounds. The results of their calculations and our previous calculations on the [1,5]‐H shift in cis‐1,3‐pentadiene following a suprafacial transition state compared with a shift of the migrating hydrogen in the plane of the carbon skeleton ask for a critical evaluation. The impact on the result of the π systems under investigation and on the results of others will be disclosed. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Combinatorical analysis of the Rayleigh–Schrödinger perturbation theory based on a circular scale of time
Authors: Olszewski S.
Published: January 2004

Contractions of events examined on a circular scale of time have been applied to combinatorical analysis of the Rayleigh–Schrödinger (RS) perturbation theory. The main practical aim of the analysis was to split any of the RS perturbation terms for energy belonging to an order N into product of RS energy terms belonging to perturbation orders N′, N″, N‴ … lower than N. Solely the perturbation of a nondegenerate state is examined. The analysis is illustrated by the whole ensemble of the RS perturbation terms entering the perturbation orders N = 8, 9, and 10 taken as examples. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Unitarily invariant decomposition of arbitrary Hermitian matrices of physical interest
Authors: Alcoba Diego R.
Published: January 2004

The aim of this article is to report a unitarily invariant decomposition of arbitrary Hermitian second‐order matrices. For the particular cases of antisymmetrical and symmetrical Hermitian second‐order matrices this decomposition reduces to the unitarily invariant decompositions of antisymmetrical and symmetrical Hermitian second‐order matrices reported by Coleman, A. J. In: Erdahl, R. M., ed. Reduced Density Operators with Applications to Physical and Chemical Systems II, Queen's Paper in Pure and Applied Mathematics, vol. 40; Queen's University: Kingston, Ontario, 1974 and Sun et al. Int J Quantum Chem 1984, 25, 1045, respectively. An illustration of physical interest is reported. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Matrix‐assisted laser desorption/ionization mass spectrometry for the evaluation of the C‐terminal lysine distribution of a recombinant monoclonal antibody
Authors: Lazar Alexandru C. , Kloczewiak Marek A. , Mazsaroff Istvan
Published: January 2004

Recombinant monoclonal antibodies produced using mammalian cell lines contain multiple chemical modifications. One specific modification resides on the C‐terminus of the heavy chain. Enzymes inside the cell can cleave the C‐terminal lysine from the heavy‐chain molecules, and variants with and without C‐terminal lysine can be produced. In order to fully characterize the protein, there is a need for analytical methods that are able to account for the different product variants. Conventional analytical methods used for the measurement of the distribution of the two different variants are based on chemical or enzymatic degradation of the protein followed by chromatographic separation of the degradation products. Chromatographic separations with gradient elution have long run times, and analyses of multiple samples are time‐consuming. This paper reports development of a novel method for the determination of the relative amounts of the two C‐terminal heavy‐chain variants based on matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) measurements of the cyanogen bromide degraded recombinant monoclonal antibody products. The distribution of the variants is determined from the MALDI‐TOF mass spectra by measuring the peak areas of the two C‐terminal peptides. The assay was used for the assessment of the C‐terminal lysine distribution in different development lots. The method was able to differentiate between the products obtained using the same cell line as well as between products obtained from different cell lines. Copyright © 2004 John Wiley & Sons, Ltd.
Continuous‐flow isotope analysis of the deuterium/hydrogen ratio in atmospheric hydrogen
Authors: Rhee Tae Siek , Mak John , Röckmann Thomas , Brenninkmeijer Carl A. M.
Published: January 2004

A convenient method is described for analyzing the deuterium/hydrogen (D/H) ratio of atmospheric molecular hydrogen (H2) based on mass spectrometric isotope‐ratio monitoring. The method requires small amounts of air (∼300 mL STP), is operated on‐line, and comprises four steps: (1) the condensation of the air matrix at ∼40 K; (2) the collection of the non‐condensed components of the air sample (H2, Ne, He, and traces of N2) in a 5 Å molecular sieves pre‐concentration trap at ∼63 K; (3) gas chromatographic purification of H2 in a flow of He; and (4) quantification of the D/H ratio in an isotope‐ratio mass spectrometer. The precision of the determination of the D/H ratio is better than 2‰, which is comparable to, or better than, that obtained by conventional duel‐inlet off‐line analysis. There are, however, discrepancies relative to the D/H ratios determined by conventional duel‐inlet analysis. This is due to differences in peak shape between reference and sample air, depending on the amount of H2 injected. Consequently, calibration runs are required. After the calibration of the system, we obtained an accuracy of 1.5‰, so that the accumulated uncertainty is estimated to be less than 4‰. The method also allows determination of the H2 concentration, with an uncertainty estimated to be 2%. Copyright © 2004 John Wiley & Sons, Ltd.
Using dual‐bacterial denitrification to improve δ15N determinations of nitrates containing mass‐independent 17O
Authors: Coplen T. B. , Böhlke J. K. , Casciotti K. L.
Published: January 2004

The bacterial denitrification method for isotopic analysis of nitrate using N2O generated from Pseudomonas aureofaciens may overestimate δ15N values by as much as 1–2‰ for samples containing atmospheric nitrate because of mass‐independent 17O variations in such samples. By analyzing such samples for δ15N and δ18O using the denitrifier Pseudomonas chlororaphis, one obtains nearly correct δ15N values because oxygen in N2O generated by P. chlororaphis is primarily derived from H2O. The difference between the apparent δ15N value determined with P. aureofaciens and that determined with P. chlororaphis, assuming mass‐dependent oxygen isotopic fractionation, reflects the amount of mass‐independent 17O in a nitrate sample. By interspersing nitrate isotopic reference materials having substantially different δ18O values with samples, one can normalize oxygen isotope ratios and determine the fractions of oxygen in N2O derived from the nitrate and from water with each denitrifier. This information can be used to improve δ15N values of nitrates having excess 17O. The same analyses also yield estimates of the magnitude of 17O excess in the nitrate (expressed as Δ17O) that may be useful in some environmental studies. The 1‐σ uncertainties of δ15N, δ18O and Δ17O measurements are ±0.2, ±0.3 and ±5‰, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of derivatized and underivatized theanine enantiomers by high‐performance liquid chromatography/atmospheric pressure ionization‐mass spectrometry
Authors: Desai Meera J. , Armstrong Daniel W.
Published: January 2004

Theanine, a naturally occurring non‐proteinic amino acid found in tea leaves, has demonstrated wide‐ranging physiological activity, from lowering blood pressure to enhancing the anti‐tumor activity of chemotherapeutic drugs. The chiral nature of theanine suggests that enantiospecificity plays a significant role in its various pharmacological functions. Using the Chirobiotic T (teicoplanin) chiral stationary phase, native and derivatized theanine enantiomers were separated and detected via high‐performance liquid chromatography (HPLC) coupled to atmospheric pressure ionization mass spectrometry (API‐MS). With the use of flow rates compatible with each ionization source, native theanine standards achieved excellent sensitivity and detection limits (10 ng/mL) for both atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). Optimum sensitivity and detection limits for derivatized theanine standards were achieved using ESI‐MS. The enantiomeric composition of six commercially available L‐theanine samples was evaluated using the high‐flow APCI‐MS method and confirmed with photodiode array detection. Five of the six products contained significant amounts of D‐theanine. Only one product, SunTheanine®, appeared to contain only the L‐theanine enantiomer. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of mono‐ and polyatomic primary ions for the characterization of organic dye overlayers with static secondary ion mass spectrometry
Authors: Lenaerts Jens , Vaeck Luc Van , Gijbels Renaat , Luppen Jaymes Van
Published: January 2004

Organic carbocyanine dye coatings have been analyzed by time‐of‐flight static secondary ion mass spectrometry (TOF‐S‐SIMS) using three types of primary ions: Ga+ operating at 25 keV, and Xe+ and SF5+ both operating at 9 keV. Secondary ion yields obtained with these three primary ions have been compared for coatings with different layer thickness, varying from (sub)‐monolayer to multilayers, on different substrates (Si, Ag and AgBr cubic microcrystals). For (sub)‐monolayers deposited on Ag, Xe+ and SF5+ primary ions generate similar precursor ion intensities, but with Ga+ slightly lower precursor ion intensities were obtained. Thick coatings on Ag as well as mono‐ and multilayers on Si produce the highest precursor and fragment ion intensities with the polyatomic primary ion. The yield difference between SF5+ and Xe+ can reach a factor of 6. In comparison with Ga+, yield enhancements by up to a factor of 180 are observed with SF5+. For the mass spectrometric analysis of dye layers on AgBr microcrystals, SF5+ again proves to be the primary ion of choice. Copyright © 2004 John Wiley & Sons, Ltd.
Simultaneous determination of the urinary metabolites of benzene, toluene, xylene and styrene using high‐performance liquid chromatography/hybrid quadrupole time‐of‐flight mass spectrometry
Authors: Marchese Stefano , Curini Roberta , Gentili Alessandra , Perret Daniela , Rocca Lucia Mainero
Published: January 2004

A simple and rapid method using reversed‐phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the simultaneous determination of the urinary metabolites of benzene, toluene, xylene and styrene in human urine specimens and standard solutions is described. A hybrid quadrupole/time‐of‐flight (QqTOF) mass spectrometer was compared for the determination of metabolite of aromatic solvents in urine samples. The metabolites selected were: trans,trans‐muconic acid, hippuric acid, o‐, m‐ and p‐methylhippuric acid and phenylglyoxylic acid. The compounds were well separated from each other on narrow‐bore 1‐mm i.d. reversed‐phase LC C‐18 columns. Average recoveries for loading 100 μL of urine samples varied from 88–110% and the quantification limits were less than 30 ng/mL for each analyte (3 ng/mL for trans,trans‐muconic acid). The qualitative information obtained (mass accuracy, resolution and full‐scan spectra) with the QqTOF mass spectrometer allows a secure identification of analytes in biological matrices. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and electrospray ionization mass spectra of AZT/d4T boranophosphates
Authors: Lin Changxue , Fu Hua , Zhao Yufen
Published: January 2004

New anti‐HIV prodrugs, conjugates of AZT and d4T with boranophosphates, were prepared by the H‐phosphonate method. Their structures were determined by negative ion electrospray ionization mass spectrometry (ESI‐MS) in conjunction with tandem mass spectrometry (MS/MS). The fragmentation pathways were investigated, and most of the fragment ions contained the boranophosphate or phosphinate group. Copyright © 2004 John Wiley & Sons, Ltd.
Surface chemistry study of RuO2/IrO2/TiO2 mixed‐oxide electrodes
Authors: Barison Simona , Daolio Sergio , Fabrizio Monica , Battisti Achille De
Published: January 2004

DSA® metal oxide electrodes such as the RuO2/IrO2/TiO2 mixed system are widely studied for their excellent electrocatalytic activity. In order to understand their catalytic properties, the comprehension of the surface chemistry involved during electrochemical treatments is crucial. With this aim, RuO2/IrO2/TiO2 mixed‐oxide electrodes having various noble metal contents were studied by means of secondary ion mass spectrometry (SIMS). In particular, cathodic and anodic polarization and O2 evolution reactions were carried out to test the electrode behaviour and SIMS analyses were performed after all these treatments. In this way, surface changes induced by electrochemical treatments and depending on electrode composition were widely investigated by SIMS, revealing, for example, the presence of hydration or preferential dissolution phenomena induced by electrochemical processing. Copyright © 2004 John Wiley & Sons, Ltd.
Ab initio calculations of proton affinities of glycine, proline, cysteine and phenylalanine: comparison with the experimental values obtained using an electrospray ionisation ion trap mass spectrometer
Authors: Pepe C. , Rochut S. , Paumard J.‐P. , Tabet J.‐C.
Published: January 2004

The proton affinities of four characteristic amino acids, glycine, proline, cysteine and phenylalanine, have been calculated using three different types of wave function, HF, DFT and MP2. These wave functions were combined with several basis sets using the valence double‐ or triple‐ξ with polarisation functions, and included or not a diffuse d function on heavy atoms. Calculations were carried out using Gaussian 98 on a LINUX system (2 GHz, 2 GB of RAM). The calculated results have been compared with the experimental values obtained using Cooks' kinetic method, in particular on an electrospray ionisation ion trap mass spectrometer. An excellent agreement was found between the experimental values and the theoretical results obtained using the B3P86/6‐31+G*//B3LYP/6‐31G* level. Copyright © 2004 John Wiley & Sons, Ltd.
Glass‐chip‐based sample preparation and on‐chip trypic digestion for matrix‐assisted laser desorption/ionization mass spectrometric analysis using a sol–gel/2,5‐dihydroxybenzoic acid hybrid matrix
Authors: Lin Ya‐Shiuan , Yang Chin‐Hsiung , Chen Yu‐Chie
Published: January 2004

A glass‐chip‐based sample preparation method for matrix‐assisted laser desorption/ionization mass spectrometric (MALDI‐MS) analysis of tryptic digests of proteins and intact cells is described. A MALDI matrix, 2,5‐dihydroxybenzoic acid (2,5‐DHB), was hybridized with sol–gels to generate a sol–gel‐derived material. Taking advantage of the characteristics of sol–gels, the sol–gel‐derived material readily adhered to the surface of a glass chip through covalent bonding. Only one step of sample preparation, deposition of the sample solution on the glass chip, was required before MALDI‐MS analysis. Because 2,5‐DHB was homogeneously dispersed on the sol–gel network structure, good spot‐to‐spot reproducibility was obtained in MALDI analysis using this approach and the analyte signals were uniform throughout the chip. The modified glass chips were robust and effective for at least 1 week. This glass‐chip‐based matrix preparation method provides a straightforward approach to developing techniques for analyzing the on‐chip enzymatic digestion of proteins and intact cells of microorganisms. Cytochrome C and Escherichia coli were used as analytes to demonstrate the feasibility of this approach. The products of the on‐chip enzymatic digests were identified through protein database searches. Copyright © 2004 John Wiley & Sons, Ltd.
Rapid screening for S‐adenosylmethionine‐dependent methylation products by enzyme‐transferred isotope patterns analysis
Authors: Wan Wei , Zhao Gang , Al‐Saad Khalid , Siems William F. , Zhou Zhaohui Sunny
Published: January 2004

We report here an isotopic labeling and mass spectrometric method to rapidly identify S‐adenosylmethionine (AdoMet)‐dependent methylation products. In the presence of CH3‐ and CD3‐labeled AdoMet, a methyl transfer product appears as a doublet separated by 3 Da in a mass spectrum, while other compounds show their normal isotopic distribution. Based on this unique isotopic pattern, methylation product(s) can be easily detected even from a mixture of cellular components. To validate our method, the product of human thiopurine methyltransferase (TPMT, EC 2.1.1.67) has been successfully identified from both an in vitro assay and a whole‐cell assay. This method is generally applicable to AdoMet‐dependent transmethylation and other group‐transfer reactions, and constitutes the first example of a general strategy of enzyme‐transferred isotope patterns (ETIPs) analysis. Copyright © 2004 John Wiley & Sons, Ltd.
[2H/H] Isotope ratio analyses of [2H5]cholesterol using high‐temperature conversion elemental analyser isotope‐ratio mass spectrometry: determination of cholesterol absorption in normocholesterolemic volunteers
Authors: Godin Jean‐Philippe , Richelle Myriam , Metairon Sylviane , Fay Laurent‐Bernard
Published: January 2004

This paper validates the use of high‐temperature conversion elemental analyser isotope‐ratio mass spectrometry (TC‐EA/IRMS) for measuring the [2H/H] enrichment of plasma [2H5]cholesterol. From a molecular point of view, the free cholesterol is initially separated from plasma by thin‐layer chromatography (TLC) and then injected onto the TC‐EA reactor which converts cholesterol molecules into CO and H2 gases. The slope of the curve of the experimental mole percent excess (MPE(exp.)) versus MPE(theor.) was very close to 1, demonstrating that no significant isotopic fractionation was observed during all processing of the samples (i.e., isolation of plasma free cholesterol by TLC and pyrolysis in the TC‐EA reactor). Excellent linearity (r2 = 0.9994, n = 4) of δ (‰) of [2H/H] isotopic measurements versus mole percent (MP) was assessed over the range 0 to 0.1 MP. The precision of the [2H/H] measurement, evaluated with two calibration points processed with TLC, was δ2HV‐SMOW = −192.5 ± 3.4‰ and δ2HV‐SMOW = −136.9 ± 2.9‰. The standard deviations of the within‐assay and between‐assay repeatabilities of the analytical process, evaluated using the quality control (QC) of plasma samples, were 4.6 and 6.1‰, respectively. Plant sterols are known to reduce cholesterol absorption and therefore were used as a positive control in a clinical study performed with normocholesterolemic volunteers. This present method produces biological results consistent with those already reported in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Oligomeric carbon and siloxane series observed by matrix‐assisted laser desorption/ionisation and laser desorption/ionisation mass spectrometry during the analysis of soot formed in fuel‐rich flames
Authors: Apicella Barbara , Ciajolo Anna , Millan Marcos , Galmes Carolina , Herod Alan A. , Kandiyoti Rafael
Published: January 2004

Oligomeric carbon and siloxane series have been observed by matrix‐assisted laser desorption/ionisation mass spectrometry (MALDI‐MS), during the analysis of the dichloromethane (DCM)‐soluble fractions of condensable material recovered from fuel‐rich flames. Laser desorption (LD) spectra showed a pattern of oligomeric dimethyl‐siloxane structures with a spacing of 74 u. The siloxane series appears to have originated as contamination of samples by silicone oil used to lubricate connections of polymer tubing. This was confirmed by extracting silicone tubing and silicone grease with DCM followed by MALDI‐MS analysis. A series of peaks with a mass spacing of 24 u was also observed, superimposed on the continuum of unresolved organic ions. This oligomeric series appears to correspond to polycyclic aromatics separated by (mainly) ethylene bridges. Thus LD‐MS appears to have revealed a series of soot precursors, intermediate between polycyclic aromatics and particulate soot, which was not detected by MALDI‐MS. More detailed work is necessary to define these species with precision. Copyright © 2004 John Wiley & Sons, Ltd.
Advantages of derivatization by osmium tetroxide and 2,2′‐bipyridine for matrix‐assisted laser desorption/ionization post‐source decay fragment ion analysis of peptides
Authors: Šedo O. , Novotná K. , Havel J.
Published: January 2004

Matrix‐assisted laser desorption/ionization—post‐source decay (MALDI‐PSD) fragment ion analysis is frequently used for peptide sequence determination. PSD fragmentation is often changed or improved in terms of, e.g., sequence coverage, after derivatization. In this work, the influence of modification by an osmium tetroxide‐bipyridine reagent (Os,bipy) on the MALDI‐PSD behaviour of peptides is studied. The reagent modifies peptides specifically at tryptophan residues and oxidizes methionine to methionine sulfone and cysteine to cysteic acid. As a result the masses of some of the fragments are specifically shifted in case of peptides containing a methionine by +32 Da and, in cases of peptides containing a cysteine residue, by +48 Da. In addition, due to the change in protonation properties of a peptide after oxidation, fragments containing cysteic acid are in most cases totally suppressed. This effect significantly facilitates peptide sequence determination. Improvement of MALDI‐TOFMS and PSD analysis after the reaction with Os,bipy is demonstrated for examples involving derivatives of humanin, a novel neuroprotective peptide. Copyright © 2004 John Wiley & Sons, Ltd.
Formation of [MH]− and [M2H]2− ions in the electrospray ionization mass spectra of dicarboxylated polyethylene glycols
Authors: Frańska Magdalena , Zgoła Agnieszka , Rychłowska Joanna , Szymański Andrzej , Łukaszewski Zenon , Frański Rafał
Published: January 2004

The negative‐ion electrospray mass spectrometric behavior of dicarboxylated polyethylene glycols (CPEGCs) is discussed. Both [MH]− and [M2H]2− ions were observed. It was found that the ratio [M2H]2−/[MH]− is affected by oxyethylene chain length, solvent polarity, analyte concentration and applied cone voltage. Copyright © 2004 John Wiley & Sons, Ltd.
Adaptation to life after surgical removal of the bladder—an application of graphical Markov models for analysing longitudinal data
Authors: Hardt J. , Petrak F. , Filipas D. , Egle U. T.
Published: January 2004

Graphical Markov models have been developed particularly for the analysis of observational data. They allow the control of various background variables when analysing theoretically relevant associations. This paper demonstrates the application and some advantages of graphical Markov models in comparison to conventional statistical analyses. The aim of the study was to identify patients at risk for developing decreased health‐related quality of life (QoL) after cystectomy and to explore the influence of coping on QoL in this situation. Therefore, the method was applied to analyse the data of a prospective study, in which 81 patients with bladder cancer were interviewed pre‐operatively and in a 1‐year follow‐up. QoL was assessed both times, and two basic coping strategies (active and depressive) were measured preoperatively. The explanatory variables of theoretical interest were active and depressive coping strategies. As a result of the analysis, relevant proportions of variance in the development of QoL could be explained by the suggested model (60 per cent in mental component, 40 per cent in physical component of QoL). Active coping was positively related to QoL, depressive coping negatively. These effects were linear in the physical component of QoL, moderated by working status and the type of urinary diversion in the mental component of QoL. Copyright © 2004 John Wiley & Sons, Ltd.
Admissible two‐stage designs for phase II cancer clinical trials
Authors: Jung Sin‐Ho , Lee Taiyeong , Kim KyungMann , George Stephen L.
Published: January 2004

In a typical two‐stage design for a phase II cancer clinical trial for efficacy screening of cytotoxic agents, a fixed number of patients are initially enrolled and treated. The trial may be terminated for lack of efficacy if the observed number of tumour responses after the first stage is too small, thus avoiding treatment of patient with inefficacious regimen. Otherwise, an additional fixed number of patients are enrolled and treated to accumulate additional information on efficacy as well as safety. The minimax and the so‐called ‘optimal’ designs by Simon have been widely used, and other designs have largely been ignored in the past for such two‐stage cancer clinical trials. Recently Jung et al. proposed a graphical method to search for compromise designs with features more favourable than either the minimax or the optimal design. In this paper, we develop a family of two‐stage designs that are admissible according to a Bayesian decision‐theoretic criterion based on an ethically justifiable loss function. We show that the admissible designs include as special cases the Simon's minimax and the optimal designs as well as the compromise designs introduced by Jung et al. We also present a Java program to search for admissible designs that are compromises between the minimax and the optimal designs. Copyright © 2004 John Wiley & Sons, Ltd.
Testing non‐inferiority (and equivalence) between two diagnostic procedures in paired‐sample ordinal data
Authors: Lui Kung‐Jong , Zhou Xiao‐Hua
Published: January 2004

Before adopting a new diagnostic procedure, which is more convenient and less expensive than the standard existing procedure, it is essentially important to assess whether the diagnostic accuracy of the new procedure is non‐inferior (or equivalent) to that of the standard procedure. In this paper, we consider the situation where test responses are on an ordinal scale with more than two categories. We give two definitions of non‐inferiority, one in terms of the probability of correctly identifying the case for a randomly selected pair of a case and a non‐case over all possible cut‐off points, and the other in terms of both the sensitivity and specificity directly. On the basis of large sample theory, we develop two simple test procedures for detecting non‐inferiority. We further conduct Monte Carlo simulation to evaluate the finite sample performance of these test procedures. We note that the two asymptotic test procedures proposed here can actually perform reasonably well in a variety of situations even when the numbers of studied subjects from the diseased and non‐diseased populations are not large. To illustrate the use of the proposed test procedures, we include an example of determining whether the diagnostic accuracy of using a digitized film is non‐inferior to that of using a plain film for screening breast cancer. Finally, we note that the extension of these results to accommodate the case of detecting (two‐sided) equivalence is simply straightforward. Copyright © 2004 John Wiley & Sons, Ltd.
Stochastic model for non‐standard case–cohort design
Authors: Hsiu‐Hsi Chen Tony , Yen Ming‐Fang , Shiu Ming‐Neng , Tung Tao‐Hsin , Wu Hui‐Min
Published: January 2004

Application of case–cohort design to multi‐state disease progression in epidemiological studies has been barely addressed. To estimate multi‐state disease natural history, we proposed non‐homogeneous exponential regression stochastic model to accommodate the data requiring a non‐standard case–cohort design. We allowed transition rates to vary with time by modelling the time of transitions between two states with Weibull distribution. The exponential regression model was used to assess the effect of patient‐specific covariates on multi‐state disease progressions. This method was successfully applied to two epidemiological applications. The first application was to elucidate the effect of betel quids, smoking and alcohol on three‐state disease progression, from normal, through leukoplakia and finally to oral cancer. The second application was to extend the three‐state to a five‐state model to estimate transition rates from normal to diminutive adenoma to small adenoma to large adenoma and finally to invasive carcinoma of the colon and rectum. Finally, an index for assessing the treatment efficacy for pre‐cancerous lesion was developed by comparing transition probabilities derived from the proposed model with the probabilities of malignant transformation after a medical regime. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of testicular cancer data using a frailty modelwith familial dependence
Authors: Moger Tron A. , Aalen Odd O. , Heimdal Ketil , Gjessing Håkon K.
Published: January 2004

Previously published papers have indicated a fairly strong familial dependence intesticular cancer patients. This is particularly evident in brothers. We have applied a frailty model with familial dependence to family data on brothers of testicular cancer patients from the Norwegian Radium Hospital. The model is a two‐level frailty, with variation in susceptibility at both the family and the individual level. Specifically, the frailty variable is assumed to be compound Poisson distributed to allow individuals to be non‐susceptible. The underlying Poisson parameter is gamma distributed to model how testicular cancer is distributed among families. This is an extension of a previous compound Poisson frailty model developed for individual testicular cancer data, and an alternative to traditional modelling of survival time family data. The likelihood construction and ascertainment problems are looked at in detail. To avoid ascertainment bias, the likelihood is based on the probability of observing the disease status for each brother in a family, given that at least one brother is ascertained. The estimated relative risk for brothers is 7.4. This paper expands on a previous analysis of the data by using a frailty model, which makes it possible to examine how the cancer is distributed among families. The estimated gamma‐shaped parameter is 0.151 (95 per cent confidence interval 0.078–0.294), and this indicates that in order to obtain the high relative risks observed for brothers of testicular cancer patients, the distribution of susceptibility has to be strongly skewed among the families. The vast majority of families have a very low risk and a small proportion have a high risk. In addition, a quantity similar to the relative risk is derived to show that the susceptibility is skewly distributed also if the Poisson parameter is Bernoulli or stable distributed. This indicates that the results are valid also if other distributions are used to model familial dependence in the compound Poisson frailty model. Copyright © 2004 John Wiley & Sons, Ltd.