bluuebunny/crossref_metadata_2025 huggingface dataset:
Least‐squares meshfree method for incompressible Navier–Stokes problems
Authors: Zhang Xiang Kun , Kwon Kie‐Chan , Youn Sung‐Kie
Published: July 2004

A least‐squares meshfree method based on the first‐order velocity–pressure–vorticity formulation for two‐dimensional incompressible Navier–Stokes problem is presented. The convective term is linearized by successive substitution or Newton's method. The discretization of all governing equations is implemented by the least‐squares method. Equal‐order moving least‐squares approximation is employed with Gauss quadrature in the background cells. The boundary conditions are enforced by the penalty method. The matrix‐free element‐by‐element Jacobi preconditioned conjugate method is applied to solve the discretized linear systems. Cavity flow for steady Navier–Stokes problem and the flow over a square obstacle for time‐dependent Navier–Stokes problem are investigated for the presented least‐squares meshfree method. The effects of inaccurate integration on the accuracy of the solution are investigated. Copyright © 2004 John Wiley & Sons, Ltd.
Folate modulates Hox gene‐controlled skeletal phenotypes
Authors: Kappen Claudia , Mello Maria Alice , Finnell Richard H. , Salbaum J. Michael
Published: July 2004

Hox genes are well‐known regulators of pattern formation and cell differentiation in the developing vertebrate skeleton. Although skeletal variations are not uncommon in humans few mutations in human HOX genes have been described. If such mutations are compatible with life, there may be physiological modifiers for the manifestation of Hox gene‐controlled phenotypes, masking underlying mutations. Here we present evidence that the essential nutrient folate modulates genetically induced skeletal defects in Hoxd4 transgenic mice. We also show that chondrocytes require folate for growth and differentiation and that they express folate transport genes, providing evidence for a direct effect of folate on skeletal cells. To our knowledge, this is the first report of nutritional influence on Hox gene‐controlled phenotypes, and implicates gene–environment interactions as important modifiers of Hox gene function. Taken together, our results demonstrate a beneficial effect of folate on skeletal development that may also be relevant to disorders and variations of the human skeleton. genesis 39:155–166, 2004. © 2004 Wiley‐Liss, Inc.
Inner hair cell Cre‐expressing transgenic mouse
Authors: Li Mingyuan , Tian Yong , Fritzsch Bernd , Gao Jiangang , Wu Xudong , Zuo Jian
Published: July 2004

Cochlear hair cells of the inner ear are mechanosensory transducers critical for sound reception in mammals. A mouse with a specific expression of Cre recombinase activity in hair cells is essential for hair cell‐specific gene targeting. Here we report a transgenic mouse in which Cre activity is detected in inner hair cells, not in supporting cells, in the cochlea. The Cre activity was visualized with both X‐gal staining and β‐galactosidase immunostaining in progeny of a cross between our Cre line and the reporter ROSA26R line. In inner hair cells, the Cre activity started at postnatal day 14 and was maintained throughout adulthood. Starting at postnatal day 50, a few outer hair cells in the outermost row of cochlear apical and middle turns displayed the Cre activity. In vestibular hair cells and spiral ganglia, the Cre activity was also detected. Cre activity was present in cells widely distributed throughout brain, testis, and retina, but was absent in many other tissues such as kidney, heart, liver, and intestine. This Cre mouse line can thus be used for conditional gene targeting in mature inner hair cells of the cochlea. genesis 39:173–177, 2004. © 2004 Wiley‐Liss, Inc.
Tissue‐specific and inducible Cre‐mediated recombination in the gut epithelium
Authors: El Marjou Fatima , Janssen Klaus‐Peter , Hung‐Junn Chang Benny , Li Mei , Hindie Valérie , Chan Lawrence , Louvard Daniel , Chambon Pierre , Metzger Daniel , Robine Sylvie
Published: July 2004

We generated two complementary systems for Cre‐mediated recombination of target genes in the mouse digestive epithelium and tested them with a Cre‐reporter mouse strain. Cre was expressed under the control of a 9 kb regulatory region of the murine villin gene (vil‐Cre). Genetic recombination was initiated at embryonic day (E) 9 in the visceral endoderm, and by E12.5 in the entire intestinal epithelium, but not in other tissues. Cre expression was maintained throughout adulthood. Furthermore, transgenic mice bearing a tamoxifen‐dependent Cre recombinase (vil‐Cre‐ERT2) expressed under the control of the villin promoter were created to perform targeted spatiotemporally controlled somatic recombination. After tamoxifen treatment, recombination was detectable throughout the digestive epithelium. The recombined locus persisted for 60 days after tamoxifen administration, despite rapid intestinal cell renewal, indicating that epithelial progenitor cells had been targeted. The villin‐Cre and villin‐Cre‐ERT2 mice provide valuable tools for studies of cell lineage allocation and gene function in the developing and adult intestine. genesis 39:186–193, 2004. © 2004 Wiley‐Liss, Inc.
Thyrocyte‐specific expression of Cre recombinase in transgenic mice
Authors: Kusakabe Takashi , Kawaguchi Akio , Kawaguchi Rumi , Feigenbaum Lionel , Kimura Shioko
Published: July 2004

A transgenic mouse line that expresses Cre recombinase under control of the human thyroid peroxidase (TPO) gene promoter was established. The activity and specificity of the TPO‐driven Cre recombinase were examined by using Northern blotting and by crossing with the ROSA26 reporter transgenic mouse line. In the latter mice, Cre‐mediated recombination occurred only in the thyrocytes, and recombination commenced around embryonic day 14.5, at the time during thyroid organogenesis when TPO expression begins. This study demonstrates that the TPO‐Cre transgenic mouse is a powerful tool to specifically delete loxP‐inserted (floxed) genes in thyrocytes and will be of great value in the study of thyrocyte‐specific genes during development and/or in adult thyroids. genesis 39:212–216, 2004. © 2004 Wiley‐Liss, Inc.
Germline transmission and efficient DNA recombination in mouse embryonic stem cells mediated by adenoviral‐Cre transduction
Authors: Shui Jr‐Wen , Tan Tse‐Hua
Published: July 2004

Following gene targeting, a loxP‐neo‐loxP cassette was introduced into ES cells. The presence of a selectable marker such as neo in the targeted allele may result in gene interference in flox mice or unexpected phenotypes due to genetic ambiguity in direct knockout mice. Typically, the neo cassette is selectively removed by transient expression of the Cre recombinase in targeted ES cell. However, this method involves a tedious process of selecting, expanding, and screening ES cell clones which may compromise germline competency. Here, we describe a novel method of combining adenovirus‐Cre mediated gene recombination with ES gene targeting to facilitate efficient loxP‐neo‐loxP removal in ES cells. We demonstrate that adenovirus‐Cre infected ES cells can retain their germline competency. The procedures described here facilitate a rapid genetic manipulation of ES cells to obtain neo‐free knockout animals, multiple gene targeting, homozygous mutant ES cells ideal for in vitro characterization, or Rag‐deficient blastocyst complementation. genesis 39:217–223, 2004. © 2004 Wiley‐Liss, Inc.
Water resources hazard management system: spatial extension for the assessment of sustainable water use practices in Kenya
Authors: Ochola W. O. , Kerkides P. , Argyrokastritis I. , Kollias V.
Published: July 2004

Water resources attributes can be parameterized into water quality indicators that also describe the impact of agriculture on the biophysical and socio‐economic processes in the environment. This article is a sequel to a previous paper published by the authors that presented a water resources hazard assessment decision support system (DSS). The geographical information system (GIS) functionality of the original DSS has been advanced for mapping, spatial and geostatistical analysis of water resources hazards, water use/management practice classification and best water management practice identification. The interactive mapping potential enables the users to broaden water resource management and investigate spatial and temporal trends in water hazard status. The output includes a host of thematic maps and water use matrices. The improvement of the DSS by integration of GIS has enhanced its ability to support land and water use decision‐making at farm and catchment levels by not only setting best water use guidelines but also suggesting where they are most appropriate. The improved version of the DSS has been recalibrated, tested and applied to land and water use data from the Kusa area in Kenya. The system assists land and water use planning through the evaluation of sustainability of water resources, identifying environmental issues concerning future water use sites and defining the conditions for use of present water resources. It can be used to evaluate hazards and environmental threats to other agricultural land resources. The current paper presents a documentation of the water hazard management system and a description of its application to be a requisite of water hazards in the study area. Copyright © 2004 John Wiley & Sons, Ltd.
A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force‐field parameter sets 53A5 and 53A6
Authors: Oostenbrink Chris , Villa Alessandra , Mark Alan E. , Van Gunsteren Wilfred F.
Published: July 2004

Successive parameterizations of the GROMOS force field have been used successfully to simulate biomolecular systems over a long period of time. The continuing expansion of computational power with time makes it possible to compute ever more properties for an increasing variety of molecular systems with greater precision. This has led to recurrent parameterizations of the GROMOS force field all aimed at achieving better agreement with experimental data. Here we report the results of the latest, extensive reparameterization of the GROMOS force field. In contrast to the parameterization of other biomolecular force fields, this parameterization of the GROMOS force field is based primarily on reproducing the free enthalpies of hydration and apolar solvation for a range of compounds. This approach was chosen because the relative free enthalpy of solvation between polar and apolar environments is a key property in many biomolecular processes of interest, such as protein folding, biomolecular association, membrane formation, and transport over membranes. The newest parameter sets, 53A5 and 53A6, were optimized by first fitting to reproduce the thermodynamic properties of pure liquids of a range of small polar molecules and the solvation free enthalpies of amino acid analogs in cyclohexane (53A5). The partial charges were then adjusted to reproduce the hydration free enthalpies in water (53A6). Both parameter sets are fully documented, and the differences between these and previous parameter sets are discussed. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1656–1676, 2004
A history of Combined‐Integrated doctoral training in psychology
Authors: Beutler Larry E. , Givner Abraham , Mowder Barbara A. , Fisher Daniel , Reeve Ronald E.
Published: July 2004

The history of doctoral training in psychology is reviewed, with special emphasis on the development of training models for applied psychology. Among applied psychology doctoral programs, most label themselves as being one of the three currently recognized practice areas: clinical, counseling, and school psychology; however, since the 1970s, APA also has accredited “combined” programs. The history of the development of the combined model is traced, including information from the programs themselves about the manner in which each evolved. Recently, new interest in the combined category —or Combined‐Integrated (C‐I) as these programs wish to become known—has emerged, and an organization representing these programs has formed. The C‐I model is described, and the potential that the model may serve as a template for the future of professional training in psychology is discussed. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Synthesis of 2H‐ and 3H‐labelled iptakalim hydrochloride
Authors: Zhang Cheng , Yang Rifang , Chen Lanfu , Zhong Bohua , Yun Liuhong , Wang Hai
Published: July 2004

Iptakalim hydrochloride (N‐(1‐methylethyl)‐1,1,2‐trimethyl‐propylamine hydrochloride) is a promising antihypertensive drug discovered and developed by Beijing Institute of Pharmacology and Toxicology. Deuterium‐ and tritium‐labelled compounds were designed and synthesized for pharmacokinetic and pharmacological mechanism studies. A derivatization method has been employed in the synthesis procedure. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, radiosynthesis and preliminary in vivo evaluation of [123I]‐(4‐fluorophenyl) {1‐[2‐(2‐iodophenyl)ethyl]piperidin‐4‐yl}methanone, a potential 5‐HT2A‐antagonist for SPECT brain imaging
Authors: Blanckaert P. , Vandecapelle M. , Staelens L. , Burvenich I. , Dierckx R. A. , Slegers G.
Published: July 2004

Many people suffer from psychiatric illnesses like depression and anorexia. Relevant to these diseases is amongst others a malfunctioning of brain 5‐HT2A‐receptors. To allow in vivo quantification of these receptors with Single Photon Emission Computerized Tomography (SPECT), a radiolabelled ligand with high 5‐HT2A affinity is needed.

This work reports the radiosynthesis of [123I]‐(4‐fluorophenyl) {1‐[2‐(2‐iodophenyl)ethyl]piperidin‐4‐yl}methanone, the synthesis of its precursor, (4‐fluorophenyl) {1‐[2‐(2‐bromophenyl)ethyl]piperidin‐4‐yl}methanone, and the preliminary in vivo evaluation of the tracer. The precursor was synthesized with a total yield of 40%. Radiolabelling was performed using a halogen exchange reaction and the yield was 70%. Radiochemical purity was >95%, and specific activity was at least 2.4 Ci/µmol. Log P was measured to be 2.52. The tracer showed uptake in mice brain (3.5% I.D./g tissue at 3 min post injection) and therefore will be evaluated further by regional brain biodistribution and displacement studies in rabbits. Copyright © 2004 John Wiley & Sons, Ltd.
Novel benzyl rearrangements in electrospray ionization multistage tandem mass spectra of benzyl 2′,3′‐ didehydro‐2′,3′‐dideoxythymidin‐5′‐yl H‐phosphonate
Authors: Chen Yi , Sun Xiaobin , Fu Hua , Liu Xiaohong , Zhao Yufen
Published: July 2004

Several alkyl 2′,3′‐didehydro‐2′,3′‐dideoxythymidin‐5′‐yl H‐phosphonates were synthesized and analyzed by electrospray ionization multistage tandem mass spectrometry (ESI − MSn). Two kinds of novel benzyl rearrangement reactions were observed in ESI − MS2 of [M + H]+, [M + Na]+ and [M + K]+ of benzyl 2′,3′‐didehydro‐2′,3′‐dideoxythymidin‐5′‐yl H‐phosphonate. Results from tandem mass spectrometry, high‐resolution mass spectrometry and control experiments showed that the benzyl migration could undergo a four‐membered cyclic rearrangement reaction, and benzyl was essential in the process. Copyright © 2004 John Wiley & Sons, Ltd.
Study of peptide–sugar non‐covalent complexes by infrared atmospheric pressure matrix‐assisted laser desorption/ionization
Authors: Von Seggern Christopher E. , Cotter Robert J.
Published: July 2004

Infrared atmospheric pressure matrix‐assisted laser desorption/ionization quadrupole ion trap mass spectrometry was applied to the study of siglec binding to oligosaccharide ligands. Peptides were designed to mimic the binding sites of three members of the siglec family: sialoadhesin, MAG and CD22. These peptides were tested for their ability to complex with their carbohydrate ligands 3′‐sialyllactose (3′SL) and 6′‐sialyllactose (6′SL). All peptides demonstrated the ability to bind to the carbohydrates, with the peptide representing sialoadhesin maintaining its binding specificity for 3′SL in preference to 6′SL. This technique can be used to study other protein–sugar interactions and can be expanded to create high‐throughput screening techniques. Copyright © 2004 John Wiley & Sons, Ltd.
Collision‐induced dissociation tandem mass spectrometry of desferrioxamine siderophore complexes from electrospray ionization of UO22+, Fe3+ and Ca2+ solutions
Authors: Groenewold Gary S. , Van Stipdonk Michael J. , Gresham Garold L. , Chien Winnie , Bulleigh Kellis , Howard Angela
Published: July 2004

Desferrioxamine (DEF) is a trihydroxamate siderophore typical of those produced by bacteria and fungi for the purpose of scavenging Fe3+ from environments where the element is in short supply. Since this class of molecules has excellent chelating properties, reaction with metal contaminants such as actinide species can also occur. The complexes that are formed can be mobile in the environment. Because the natural environment is extremely diverse, strategies are needed for the identification of metal complexes in aqueous matrices having a high degree of chemical heterogeneity, and electrospray ionization mass spectrometry (ESI‐MS) has been highly effective for the characterization of siderophore–metal complexes. In this study, ESI‐MS of solutions containing DEF and either UO22+, Fe3+ or Ca2+ resulted in generation of abundant singly charged ions corresponding to [UO2(DEF − H)]+, [Fe(DEF − 2H)]+ and [Ca(DEF − H)]+. In addition, less abundant doubly charged ions were produced. Mass spectrometry/mass spectrometry (MS/MS) studies of collision‐induced dissociation (CID) reactions of protonated DEF and metal–DEF complexes were contrasted and rationalized in terms of ligand structure. In all cases, the most abundant fragmentation reactions involved cleavage of the hydroxamate moieties, consistent with the idea that they are most actively involved with metal complexation. Singly charged complexes tended to be dominated by cleavage of a single hydroxamate, while competitive fragmentation between two hydroxamate moieties increased when the doubly charged complexes were considered. Rupture of amide bonds was also observed, but these were in general less significant than the hydroxamate fragmentations. Several lower abundance fragmentations were unique to the metal examined: abundant loss of H2O occurred only for the singly charged UO22+ complex. Further, NH3 was eliminated only from the singly charged Fe3+ complex; this and fragmentation of CC and CN bonds derived from neither the hydroxamate nor the amide groups suggested that Fe3+ insertion reactions were competing with ligand complexation. In no experiments were coordinating solvent molecules observed, attached either to the intact complexes or to the fragment ions, which indicated that both intact DEF and its fragments were occupying all of the coordination sites around the metal centers. This conclusion was based on previous experiments that showed that undercoordinated UO22+ and Fe3+ readily added H2O and methanol in the ESI quadrupole ion trap mass spectrometer that was used in this study. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative analysis of 5α‐reductase inhibitors in DU145 cells using matrix‐assisted laser desorption/ ionization time‐of‐flight mass spectrometry and high‐performance liquid chromatography/tandem mass spectrometry
Authors: Kang Min‐Jung , Mathur Sonal , Hartmann Rolf W.
Published: July 2004

N‐(Dicyclohexyl)acetylpiperidine‐4‐benzylidene‐4‐carboxylic acid (1) is an excellent in vitro inhibitor of 5α‐reductase (5αR). Compound 1 showed, however, much lower inhibition activity of 5αR in vivo than in vitro, which might be caused by poor membrane permeability. The methyl ester of 1 (1a) was therefore tested as a model prodrug to see if it has better permeability properties than the corresponding acid 1. It was also monitored that this methyl ester was cleaved into the active compound 1 within the DU145 cells. Quantitative matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) and high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) methods were established with reliable linearity factors (0.996 for MALDI‐TOFMS and 0.998 for HPLC/MS/MS) and reproducibility (relative standard deviation = 6.5% for MALDI‐TOFMS and 2.8% for HPLC/MS/MS). The samples for MS analysis were effectively prepared from the cell homogenates using solid‐phase extraction, with a high recovery of 90% on average. The intracellular amount of 1a (1.7 nmol) was much higher than that of 1 (0.032 nmol) in DU145 cells after 6 h of incubation. After incubation with the ester (1a), the cleaved acid (1) was detected within the cells. The concentration of acid 1 (0.045 nmol) in this experiment was higher than the acid content (0.032 nmol) after direct incubation with 1. Surprisingly, high amounts of the cleaved compound 1 were found outside the cells after 6 h of incubation with 1a. Copyright © 2004 John Wiley & Sons, Ltd.
An atmospheric pressure chemical ionization study of the positive and negative ion chemistry of the hydrofluorocarbons 1,1‐difluoroethane (HFC‐152a) and 1,1,1,2‐tetrafluoroethane (HFC‐134a) and of perfluoro‐n‐hexane (FC‐72) in air plasma at atmospheric pressure
Authors: Marotta Ester , Paradisi Cristina , Scorrano Gianfranco
Published: July 2004

A report is given on the ionization/dissociation behavior of the title compounds within air plasmas produced by electrical corona discharges at atmospheric pressure: both positive and negative ions were investigated at different temperatures using atmospheric pressure chemical ionization mass spectrometry (APCI‐MS). CHF2CH3 (HFC‐152a) undergoes efficient ionic oxidation to C2H5O+, in which the oxygen comes from water present in the plasma. In contrast, CF3CH2F (HFC‐134a) does not produce any characteristic positive ion under APCI conditions, its presence within the plasma being revealed only as a neutral ligand in ion–molecule complexes with ions of the background (H3O+ and NO+). Analogously, the perfluorocarbon FC‐72 (n‐C6F14) does not produce significant positive ions at 30 °C: at high temperature, however, it undergoes dissociative ionization to form many product ions including C3F6+, C2F4+, CnF2n+1+ and a few families of oxygen containing cations (CnF2n+1OH2+, CnF2nOH+, CnF2n−1O+, CnF2n−1O2H2+, CnF2n−2O2H+) which are suggested to derive from CnF2n+1+ in a cascade of steps initiated by condensation with water followed by steps of HF elimination and H2O addition. Negative ions formed from the fluoroethanes CHF2CH3 and CF3CH2F (M) include complexes with ions of the background, O2−(M), O3−(M) and some higher complexes involving also water, and complexes of the fluoride ion, F−(H2O), F−(M) and higher complexes with both M and H2O also together. The interesting product O2−(HF) is also formed from 1,1‐difluoroethane. In contrast to the HFCs, perfluoro‐n‐hexane gives stable molecular anions, M−, which at low source temperature or in humidified air are also detected as hydrates, M−(H2O). In addition, in humidified air F−(H2O)n complexes are also formed. The reactions leading to all major positive and negative product ions are discussed also with reference to available thermochemical data and relevant literature reports. The effects on both positive and negative APCI spectra due to ion activation via increasing Vcone are also reported and discussed: several interesting endothermic processes are observed under these conditions. The results provide important information on the role of ionic reactions in non‐thermal plasma processes. Copyright © 2004 John Wiley & Sons, Ltd.
The propionyl cation heat of formation revisited
Authors: Harvey Zoë A. , Traeger John C.
Published: July 2004

The 298 K heat of formation for the propionyl cation (C2H5CO+) has been measured previously by dissociative photoionization mass spectrometry. However, recent theoretical and experimental studies involving methylketene suggest that this may be significantly underestimated, resulting in a methylketene proton affinity that is too high by ∼30 kJ mol−1. In this study, the previous m/z 57 appearance energies were carefully re‐evaluated, with various possible sources of error being investigated. These include factors such as sample purity, carbon‐13 contamination from lower energy m/z 56 processes, kinetic and/or competitive shifts, reverse activation energies, ionizing energy calibration errors and the availability of accurate supplementary thermochemical data. In addition, high‐level ab initio calculations are used to model the relevant unimolecular fragmentation processes for each of the ionized precursor molecules. As a result, it is found that only the 2‐butanone appearance energy can be used to provide a reliable value for the propionyl cation heat of formation. From the 298 K m/z 57 appearance energy of 10.199 ± 0.003 eV for 2‐butanone measured here, a value of 617.8 ± 0.9 kJ mol−1 is derived for $\Delta H^{\circ}_{{\rm f},298}(\hbox{C}_{2}\hbox{H}_{5}\hbox{CO}^{+})$, which corresponds to 845.4 ± 4.8 kJ mol−1 for the proton affinity of methylketene. This is in good agreement with previous theoretical calculations and thermokinetic proton affinity measurements, indicating that a significant upward revision to the propionyl cation heat of formation is warranted. Copyright © 2004 John Wiley & Sons, Ltd.
Matrix‐dependent cationization in MALDI mass spectrometry
Authors: Zhang Juan , Zenobi Renato
Published: July 2004

The matrix dependence in cationization processes, the competition between cationization and protonation and the question of whether gas‐phase cation transfer or attachment of free cations dominates in matrix‐assisted laser desorption/ionization mass spectrometry were studied. Two different sample preparation methods were employed, the dried‐droplet sample preparation and a mixture of solid matrix, analyte and salt. The latter ensures that the formation of cation adducts takes place in the gas phase. By monitoring the suppression of matrix signals for different matrices, it was found that matrices with high gas‐phase metal ion binding energies require high analyte concentrations for matrix suppression to occur. By comparing the mass spectra obtained using sinapinic acid or sinapinic methyl ester as a matrix, a correlation between cationization and deprotonation of matrix molecules was found. It is also demonstrated that attachment of free gas‐phase cations, rather than cation transfer from the cationized matrix, is the predominant process in cationization. Copyright © 2004 John Wiley & Sons, Ltd.
Peptide and protein characterization by high‐rate electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry
Authors: Tsybin Youri O. , Ramström Margareta , Witt Matthias , Baykut Gökhan , Håkansson Per
Published: July 2004

The analytical utility of the electron capture dissociation (ECD) technique, developed by McLafferty and co‐workers, has substantially improved peptide and protein characterization using Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS). The limitations of the first ECD implementations on commercial instruments were eliminated by the employment of low‐energy electron‐injection systems based on indirectly heated dispenser cathodes. In particular, the ECD rate and reliability were greatly increased, enabling the combination of ECD/FTICR‐MS with on‐line liquid separation techniques. Further technique development allowed the combination of two rapid fragmentation techniques, high‐rate ECD and infrared multiphoton dissociation (IRMPD), in a single experimental configuration. Simultaneous and consecutive irradiations of trapped ions with electrons and photons extended the possibilities for ion activation/dissociation and led to improved peptide and protein characterization. The application of high‐rate ECD/FTICR‐MS has demonstrated its power and unique capabilities in top‐down sequencing of peptides and proteins, including characterization of post‐translational modifications, improved sequencing of peptides with multiple disulfide bridges and secondary fragmentation (w‐ion formation). Analysis of peptide mixtures has been accomplished using high‐rate ECD in bottom‐up mass spectrometry based on mixture separation by liquid chromatography and capillary electrophoresis. This paper summarizes the current impact of high‐rate ECD/FTICR‐MS for top‐down and bottom‐up mass spectrometry of peptides and proteins. Copyright © 2004 John Wiley & Sons, Ltd.
Simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of lacidipine in human plasma
Authors: Ramakrishna N. V. S. , Vishwottam K. N. , Puran S. , Manoj S. , Santosh M. , Koteshwara M.
Published: July 2004

A simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method was developed and validated for the quantification of lacidipine in human plasma using its structural analogue, amlodipine, as internal standard (IS). The method involves a simple single‐step liquid–liquid extraction with tert‐butyl methyl ether. The analyte was chromatographed on an Xterra MS C18 reversed‐phase chromatographic column by isocratic elution with 20 mM ammonium acetate buffer–acetonitrile (10 : 90, v/v; pH 6) and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 456.4 → 354.4 and m/z 409.3 → 238.3 were used to measure the analyte and the I.S., respectively. The chromatographic run time was 1.5 min and the weighted (1/x2) calibration curves were linear over the range 0.1–25 ng ml−1. Lacidipine was sensitive to temperature in addition to light. The method was validated in terms of accuracy, precision, absolute recovery, freeze–thaw stability, bench‐top stability and re‐injection reproducibility. The limit of detection and lower limit of quantification in human plasma were 50 and 100 pg ml−1, respectively. The within‐ and between‐batch accuracy and precision were found to be well within acceptable limits (<15%). The analyte was stable after three freeze–thaw cycles (deviation <15%). The average absolute recoveries of lacidipine and amlodipine (IS) from spiked plasma samples were 51.1 ± 1.3 and 50.3 ± 4.9%, respectively. The assay method described here could be applied to study the pharmacokinetics of lacidipine. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative study of degeneration and new growth of axons and synaptic endings in the chinchilla cochlear nucleus after acoustic overstimulation
Authors: Kim J.J. , Gross J. , Morest D.K. , Potashner S.J.
Published: July 2004

To determine if acoustic overstimulation altered synaptic connections in the cochlear nucleus, anesthetized adult chinchillas, with one ear protected by a silicone plug, were exposed for 3 hr to a 108‐dB octave‐band noise, centered at 4 kHz, and allowed to survive for periods up to 32 weeks. This exposure led to cochlear damage in the unprotected ear, mainly in the basal regions of the organ of Corti. The anterior part of the ipsilateral posteroventral cochlear nucleus consistently contained a band of degenerating axons and terminals, in which electron microscopic analysis revealed substantial losses of axons and synaptic terminals with excitatory and inhibitory cytology. The losses were significant after 1 week's survival and progressed for 16–24 weeks after exposure. By 24–32 weeks, a new growth of these structures produced a resurgence in the number of axons and terminals. The net number of excitatory endings fully recovered, but the quantity with inhibitory cytology was only partially recouped. Neuronal somata lost both excitatory and inhibitory endings at first and later recovered a full complement of excitatory but not inhibitory terminals. Dendrites suffered a net loss of both excitatory and inhibitory endings. Excitatory and inhibitory terminals with unidentified postsynaptic targets in the neuropil declined, then increased in number, with excitatory terminals exhibiting a greater recovery. These findings are consistent with a loss and regrowth of synaptic endings and with a reorganization of synaptic connections that favors excitation. © 2004 Wiley‐Liss, Inc.
Fine structure of long‐term changes in the cochlear nucleus after acoustic overstimulation: Chronic degeneration and new growth of synaptic endings
Authors: Kim J.J. , Gross J. , Potashner S.J. , Morest D.K.
Published: July 2004

The companion study showed that acoustic overstimulation of adult chinchillas, with a noise level sufficient to damage the cochlea, led to cytological changes and degeneration of synaptic endings in the cochlear nucleus within 1–16 weeks. In the present study, the same stimulus was used to study the long‐term effects on the fine structure of synaptic endings in the cochlear nucleus. For periods of 6 and 8 months after a single exposure to a damaging noise level, there ensued a chronic, continuing process of neurodegeneration involving excitatory and inhibitory synaptic endings. Electron microscopic observations demonstrated freshly occurring degeneration even as late as 8 months. Degeneration was widespread in the neuropil and included the synapses on the globular bushy cell, which forms part of the main ascending auditory pathway. Neurodegeneration was accompanied by newly formed synaptic endings, which repopulated some of the sites vacated previously by axosomatic endings on globular bushy cells. Many of these synaptic endings must arise from central interneurons. The findings suggest that overstimulation can induce a self‐sustaining condition of progressive neurodegeneration accompanied by a new growth of synaptic endings. Noise‐induced hearing loss thus may progress as a neurodegenerative disease with the capacity for synaptic reorganization within the cochlear nucleus. © 2004 Wiley‐Liss, Inc.
Architecture and evolution of a fjord‐head delta, western Vancouver Island, British Columbia
Authors: Gutsell Jeffrey E. , Clague John J. , Best Melvyn E. , Bobrowsky Peter T. , Hutchinson Ian
Published: July 2004

The architectural framework and Holocene evolution of the Zeballos fjord‐head delta on west‐central Vancouver Island was established through a multidisciplinary field‐based study. The Zeballos delta is a composite feature, consisting of an elevated, incised, late Pleistocene delta and an inset Holocene delta graded to present sea level. Both deltas have a classic Gilbert‐type tripartite architecture, with nearly flat topset and bottomset units and an inclined foreset unit. Time domain electromagnetic (TDEM) and ground‐penetrating radar (GPR) surveys, borehole data, and gravel pit exposures provided information on the internal form, lithologies and substrate of both deltas. Both sets of deltaic deposits coarsen upward from silt in the bottomset unit to gravel in the topset unit. The TDEM survey revealed a highly irregular, buried bedrock surface, ranging from 20 m to 190 m in depth, and it delineated saltwater intrusion into the deltaic sediments.

Late Quaternary sea‐level change at Zeballos was inferred from delta morphology and the GPR survey. The elevated, late Pleistocene delta was constructed when the sea was about 21 m higher relative to the land than it is today. It was dissected when sea‐level fell rapidly as a result of glacio‐isostatic rebound. Relative sea‐level reached a position about 20 m below the present datum during the early Holocene. Foreset beds that overlap and progressively climb in a seaward direction and topset beds that thicken to 26 m landward imply that the delta aggraded and prograded into Zeballos Inlet during the middle and late Holocene transgression. Sea‐level may have risen above the present datum during the middle Holocene, creating a delta plain at about 4 m a.s.l. Remnants of this surface are preserved along the valley margins. Copyright © 2004 John Wiley & Sons, Ltd.
Investigation of the factors that induce analyte peak splitting in capillary electrophoresis
Authors: Chen Xiaofeng , Xie Jianping , Li Cunhong , Hu Zhide , Chen Xingguo
Published: July 2004

Peak splitting has a detrimental effect on analyses by capillary electrophoresis. Many papers have reported it and several mechanisms have been proposed to explain the phenomenon. We investigated the electrophoretic behavior of an amphoteric analyte, levodopa, in phosphate buffer and observed a peak splitting phenomenon at moderate sample concentrations and under general analytical conditions, even without organic solvent. The dependence of effective mobility on pH was taken into account and pKa values of 2.30, 8.11, and 9.92 were obtained for levodopa. Then, we constructed pH‐dependent distribution diagrams of levodopa and phosphate species present in aqueous solution and proposed that the most relevant factors contributing to peak splitting are the presence of ionizable groups in the analyte molecule and the occurrence of ionization, yielding charged species which interacted with buffer electrolyte species in a definite pH range to form complexes. This result is different from those presented in the literature and broadens our understanding of amphoteric analyte peak splitting.
Chiral separation of omeprazole and several related benzimidazoles using supercritical fluid chromatography
Authors: del Nozal M. Jesús , Toribio Laura , Bernal José L. , Alonso Cristina , Jiménez Juan J.
Published: July 2004

A study of the enantiomeric separation of omeprazole and several related benzimidazoles, using supercritical fluid chromatography (SFC), on the amylose based column Chiralpak AD is presented in this work. The effect of the organic modifier as well as temperature on the retention and enantioresolution was investigated. Alcohol‐type modifiers provided the best results, allowing the enantiomeric separation of all the compounds studied with resolutions that were in most cases higher than 2, and analysis times lower than 10 minutes. An investigation of the temperature effect revealed that the isoelution temperature was below the working temperature range in only two cases, and hence it was better to work at the highest temperature permitted.
Hölder continuity for quasilinear subelliptic equations in Carnot Carathéodory spaces
Authors: Di Fazio Giuseppe , Zamboni Pietro
Published: July 2004

In this note we prove the Harnack inequality and the Hölder continuity for weak solutions of quasilinear subelliptic equation of the form

where u belongs to Sobolev spaces with respect to a system of locally Lipschitz vector fields. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Elliptic and parabolic problems in unbounded domains
Authors: Guidotti Patrick
Published: July 2004

We consider elliptic and parabolic problems in unbounded domains. We give general existence and regularity results in Besov spaces and semi‐explicit representation formulas via operator‐valued fundamental solutions which turn out to be a powerful tool to derive a series of qualitative results about the solutions. We give a sample of possible applications including asymptotic behavior in the large, singular perturbations, exact boundary conditions on artificial boundaries and validity of maximum principles. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fredholmness of singular integral operators with discrete subexponentialgroups of shifts on Lebesgue spaces
Authors: Karlovich Yuri , Silbermann Bernd
Published: July 2004

The paper is devoted to an application of a general local method of studying the Fredholmness of nonlocal bounded linear operators to Banach algebras of singular integral operators with piecewise continuous coefficients and discrete subexponential groups of piecewise smooth shifts acting topologically freely on composed contours. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The essential spectrum of a system of singular ordinary differential operators of mixed order. Part III: A strongly singular case
Authors: Möller Manfred
Published: July 2004

We consider a system of ordinary differential operators of mixed order on an interval (0, r0), r0 > 0, where some of the coefficients are singular at 0. A special case has been dealt with by Kako, where the essential spectrum of an operator associated with a linearized magnetohydrodynamic equation was explicitly calculated. Generalizations of this problem have been considered by Hardt, Mennicken, Naboko and Faierman, Mennicken and Möller, where in each case some kind of regularity condition was required. The essential spectrum has been calculated explicitly in terms of the coefficient functions of the system; it is always bounded in these cases. Here we consider a class of problems for which the essential spectrum is unbounded. The essential spectrum is explicitly given as the essential spectrum in the limiting case. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cross‐national differences in proneness to scarcity effects: The moderating roles of familiarity, uncertainty avoidance, and need for cognitive closure
Authors: Jung Jae Min , Kellaris James J.
Published: July 2004

The scarcity effect is a powerful social‐influence principle used by marketers to increase the subjective desirability of products. This study explores cross‐national differences in proneness to the scarcity effect and attempts to explain observed differences in terms of boundary conditions. Results of a shopping simulation experiment show a positive effect of scarcity on purchase intent and a greater proneness to such among participants from a lower‐ (U.S.) versus higher‐ (France) context culture. Moreover, the scarcity effect is moderated by product familiarity, uncertainty avoidance, and need for cognitive closure. Differential familiarity levels may help explain the observed cross‐national differences. Managerial implications concern the conditions under which marketing appeals based on scarcity should be more (versus less) persuasive. © 2004 Wiley Periodicals, Inc.
Redefining functional models of basal ganglia organization: Role for the posteroventral pallidum in linguistic processing?
Authors: Whelan Brooke‐Mai , Murdoch Bruce E. , Theodoros Deborah G. , Darnell Ross , Silburn Peter , Hall Bruce
Published: July 2004

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical–semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high‐level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3‐month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non‐neurologically impaired controls (NC). Nonparametric between‐groups comparisons were conducted and reliable change indices calculated, relative to baseline/3‐month follow‐up difference scores. Group‐wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case‐by‐case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical–semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP. © 2004 Movement Disorder Society
Timing of Plk1 and MPF activation during porcine oocyte maturation
Authors: Anger Martin , Klima Jiri , Kubelka Michal , Prochazka Radek , Motlik Jan , Schultz Richard M.
Published: July 2004

A Polo‐like kinase 1 (Plk1) appears involved in an autocatalytic loop between CDC25C phosphatase and M phase promoting factor (MPF) in Xenopus oocytes and leads to activation of MPF that is required for germinal vesicle breakdown (GVBD). Although similar evidence for such a role of Plk1 in MPF activation during maturation of mammalian oocytes is absent, changes in Plk1 enzyme activity correlate with MPF activation, Plk1 co‐localizes with MPF, and microinjection of antibodies neutralizing Plk1 delays GVBD. In this study, we exploited the prolonged time required for maturation of porcine oocytes to define precisely the timing of Plk1 and MPF activation during maturation. GVBD typically occurs between 24 and 26 hr of culture in vitro and meiotic maturation is completed after 40–44‐hr culture. We find that Plk1 is activated before MPF, which is consistent with its role in activating MPF in mammalian oocytes. Mol. Reprod. Dev. 69: 11–16, 2004. © 2004 Wiley‐Liss, Inc.
Advances in understanding and treatment of immune‐mediated disorders of the peripheral nervous system
Authors: Kieseier Bernd C. , Kiefer Reinhard , Gold Ralf , Hemmer Bernhard , Willison Hugh J. , Hartung Hans‐Peter
Published: July 2004

During recent years, novel insights in basic immunology and advances in biotechnology have contributed to an increased understanding of the pathogenetic mechanisms of immune‐mediated disorders of the peripheral nervous system. This increased knowledge has an impact on the management of patients with this class of disorders. Current advances are outlined and their implication for therapeutic approaches addressed. As a prototypic immune‐mediated neuropathy, special emphasis is placed on the pathogenesis and treatment of the Guillain–Barré syndrome and its variants. Moreover, neuropathies of the chronic inflammatory demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed. This review summarizes recent progress with currently available therapies and—on the basis of present immunopathogenetic concepts—outlines future treatment strategies. Muscle Nerve 30: 131–136, 2004
Role of magnetic resonance neurography in brachial plexus lesions
Authors: Zhou Lan , Yousem David M. , Chaudhry Vinay
Published: July 2004

Magnetic resonance neurography (MRN) is a relatively new imaging technique that is highly sensitive in detecting lesions in the peripheral nerves. We studied six cases of brachial plexopathies in which MRN played a pivotal role in making the correct diagnoses. All patients had clinical, nerve conduction, and electromyographic findings consistent with brachial plexus lesions. Four patients had brachial plexitis and two had multifocal demyelinating neuropathy presenting as brachial plexopathies. MRN in all patients showed edema, thickening, and T2 hyperintensities localized to the brachial plexus region. We conclude that MRN is a useful technique in evaluating patients with brachial plexus lesions, particularly in cases of brachial plexitis, where conventional magnetic resonance imaging is generally normal. Muscle Nerve 30: 305–309, 2004
Disorder resembling Guillain–Barré syndrome on initiation of statin therapy
Authors: Rajabally Yusuf A. , Varakantam Vivek , Abbott Richard J.
Published: July 2004

We report a disorder resembling Guillain–Barré syndrome, occurring on initiation of simvastatin, in a 58‐year‐old man, who had experienced a similar but milder episode after starting pravastatin 6 months earlier. This case suggests that acute polyradiculoneuropathy may represent a rare but serious side‐effect of statin treatment. It also raises the issue of the pathophysiology of acute neuropathy on statin exposure, with a hypersensitivity reaction resulting in an immune‐mediated process being possible instead of the hypothesized mitochondrial dysfunction in chronic cases. Muscle Nerve, 2004