bluuebunny/crossref_metadata_2025 huggingface dataset:
Explicit/implicit partitioning and a new explicit form of the generalized alpha method
Authors: Daniel W. J. T.
Published: November 2003

abstract Most finite element packages use the Newmark algorithm for time integration of structural dynamics. Various algorithms have been proposed to better optimize the high frequency dissipation of this algorithm. Hulbert and Chung proposed both implicit and explicit forms of the generalized alpha method. The algorithms optimize high frequency dissipation effectively, and despite recent work on algorithms that possess momentum conserving/energy dissipative properties in a non‐linear context, the generalized alpha method remains an efficient way to solve many problems, especially with adaptive timestep control. However, the implicit and explicit algorithms use incompatible parameter sets and cannot be used together in a spatial partition, whereas this can be done for the Newmark algorithm, as Hughes and Liu demonstrated, and for the HHT‐αalgorithm developed from it. The present paper shows that the explicit generalized alpha method can be rewritten so that it becomes compatible with the implicit form. All four algorithmic parameters can be matched between the explicit and implicit forms. An element interface between implicit and explicit partitions can then be used, analogous to that devised by Hughes and Liu to extend the Newmark method. The stability of the explicit/implicit algorithm is examined in a linear context and found to exceed that of the explicit partition. The element partition is significantly less dissipative of intermediate frequencies than one using the HHT‐αmethod. The explicit algorithm can also be rewritten so that the discrete equation of motion evaluates forces from displacements and velocities found at the predicted mid‐point of a cycle. Copyright © 2003 John Wiley & Sons, Ltd.
An exploration of corporate attitudes to the significance of environmental information for stakeholders
Authors: Collison David , Lorraine Nathan , Power David
Published: November 2003

This paper reports on a questionnaire survey sent to environmental managers in quoted UK firms from environmentally sensitive sectors. A total of 58 usable responses was received, with most but not all being returned by environmental managers. While contextual information regarding perceptions of their companies' environmental sensitivity and management systems was sought, the main focus of the questionnaire was on respondents' views about stakeholder concerns. There was broad agreement that external stakeholders attached importance to environmental communications. The results indicate that respondents' perceptions of these issues were associated with the formality of their internal management systems and with the role of the respondents within their firms. It was also found that shareholders were thought to be the least interested stakeholder group. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection
Authors: Kawakami Kazuyoshi , Yamamoto Natsuo , Kinjo Yuki , Miyagi Kazuya , Nakasone Chikara , Uezu Kaori , Kinjo Takeshi , Nakayama Toshinori , Taniguchi Masaru , Saito Atsushi
Published: November 2003

The present study was designed to elucidate the role of Vα14+ NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jα281 gene‐disrupted mice (Jα281KO mice) that lacked this lymphocyte subset. In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild‐type (WT) mice. The proportion of Vα14+ NKT cells, detected by an α‐galactosylceramide (α‐GalCer)‐loaded CD1d tetramer, increased in thelung after S. pneumoniae infection. This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)‐1, which was produced in the early phaseof infection in WT mice. In the lungs of Jα281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice. In support of this finding, macrophage inflammatory protein (MIP)‐2 and TNF‐α synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jα281KO mice, compared to WT mice. In addition, treatment of mice with α‐GalCer significantly improved the outcome of this infection. Our results demonstrated MCP‐1‐dependent recruitment of Vα14+ NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.
Bet v 1, the major birch pollen allergen, initiates sensitization to Api g 1, the major allergen in celery: evidence at the T cell level
Authors: Bohle Barbara , Radakovics Astrid , Jahn‐Schmid Beatrice , Hoffmann‐Sommergruber Karin , Fischer Gottfried F. , Ebner Christof
Published: November 2003

Due to IgE cross‐reactivity, birch pollen‐allergic individuals frequently develop type I hypersensitivity reactions to celery tuber. We evaluated the T cell response to the major allergen in celeriac, Api g 1, and the cellular cross‐reactivity with its homologous major allergen in birch pollen, Bet v 1. Api g 1‐specific T cell lines (TCL) and clones (TCC) were established from peripheralblood mononuclear cells of allergic patients. Epitope mapping of Api g 1 with overlapping Api g 1‐derived peptides revealed one dominant T cell‐activating region, Api g 1109–126. TCL and TCC generated with Api g 1 cross‐reacted with the birch pollen allergen and, although initially stimulated with the food allergen, cellular responses to Bet v 1 were stronger than to Api g 1. Epitopemapping with Bet v 1‐derived peptides revealed that T cells specific for several distinct epitopes distributed over the complete Bet v 1 molecule could be activated by Api g 1. Bet v 1109–126 was identified as the most important T cell epitope for cross‐reactivity with Api g 1. This epitope shares 72% amino acid sequence similarity with the major T cell‐activating region of the food allergen, Api g 1109–126. Our data provide evidence that humoral as well as cellular reactivity to the major celery allergen is predominantly based on cross‐reactivity with the major birch pollen allergen. The activation of Bet v 1‐specific Th2 cells by Api g 1, in particular outside the pollen season, may have consequences for birch pollen‐allergic individuals.
A phenotypically distinct subset of immature B cells exhibits partial activation, increased survival, and preferential expression of VhS107
Authors: Wilson Emily L. , Sherwood Erin M. , King Anne M. , Riley Richard L.
Published: November 2003

We have observed that immature B cells (IgMlowIgD–) in the bone marrow of adult BALB/c mice exhibit heterogeneity, with a distinct subpopulation (∼4–10%) expressing the CD43/S7 surface protein. These CD43/S7+ immature B cells often express other surface antigens associated with B cell activation (CD5, CD11b, PD‐1). Generation of optimal numbers of CD43/S7+ immature B cells requires expression of a functional Btk protein, consistent with activation as a requisite for the CD43/S7+ immature B cell phenotype. Like typical CD43/S7– immature B cells, the CD43/S7+ immature B cells are predominantly resting cells, which are derived from cycling bone marrow B cell precursors. The CD43/S7+ immature B cell population exhibits enhanced survival in vivo upon administration of the apoptosis‐inducing corticosteroid, dexamethasone. Finally, CD43/S7+ immature B cells show a fourfold increase in incidence of VhS107 μ heavy chain expression compared to the CD43/S7– immature B cells. Therefore, in adult murine bone marrow, the presence of a phenotypically distinct immature B cellpopulation can be demonstrated which has undergone partial activation leading to increased survival and BCR‐dependent Vh repertoire selection.
Thymic selection does not limit the individual MHC diversity
Authors: Borghans José A. M. , Noest André J. , De Boer Rob J.
Published: November 2003

The number of different major histocompatibility (MHC) molecules expressed per individual is widely believed to represent a trade‐off between maximizing the detection of foreign antigens, and minimizing the loss of T cell clones due to self‐tolerance induction. Using a mathematical model we here show that this argument fails to explain why individuals typically express of the order of 1020 different MHC molecules. Expression of extra MHC types decreases the number of clones surviving negative selection, but increases the number of positively selected clones. Based on experimental parameter estimates, we show that the number of clones in the functional T cell repertoire would in fact increase if the MHC diversity within an individual were to exceed its normal value, until more than one hundred different MHC molecules would be expressed. Since additional MHC types also increase the number of presented pathogen peptides, resistance against pathogens only decreases at unrealistically high MHC diversities exceeding 1,500 different MHC molecules per individual.
Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by vaccination with cross‐reactive, natural HBsAg variants
Authors: Schirmbeck Reinhold , Dikopoulos Nektarios , Kwissa Marcin , Leithäuser Frank , Lamberth Kasper , Buus Soren , Melber Karl , Reimann Jörg
Published: November 2003

Processing exogenous hepatitis B surface antigen (HBsAg) of the hepatitis B virus (HBV) generates the Kb‐binding S208–215 epitope 1; processing endogenous HBsAg generates theKb‐binding S190–197 epitope 2. Cross‐reactive CD8+ T cell responses were primed to epitope 1 but not epitope 2 when mice were immunized with natural HBsAgayw, orHBsAgadw2 variants differing within both epitopes by one or two residues. Expression of HBsAgayw from a transgene in the liver renders (HBs‐tg) mice tolerant to epitope 1 of HBsAgayw. CD8+ T cells specific for epitope 1 could be primed in HBs‐tg mice by HBsAgadw2; these specific CD8+ T cells cross‐reacted with epitope 1 processed from the transgene‐encoded HBsAgayw. The liver of vaccinated HBsAgayw transgenic mice showed severe histopathology and contained functional (IFNγ‐producing), cross‐reactive CD8+ T cells, and vaccinated HBs‐tg mice showed reduced antigenemia. Hence, vaccination with natural HBsAg variants from different HBV sero/genotypes can prime cross‐reactive, specific CD8+ T cellimmunity that breaks tolerance to HBsAg.
Studies in the Cycloproparene Series: Unexpected Products from Peterson Olefinations
Authors: Halton Brian , Boese Roland , Dixon Gareth M.
Published: November 2003

Reaction of tetraphenylcyclopentadienone with anion 8 derived by monodesilylation of 1,1‐bis(trimethylsilyl)cyclopropa[b]naphthalene (10) gives the 1‐(5′‐cyclopentadienyl)‐substituted cycloproparene 17 from simple anion addition to the carbonyl group rather than fulvalene 16 from loss of Me3SiO−. Reactions of anion 8 with p‐(trifluoromethyl)benzaldehyde and thiophene‐2‐carbaldehyde give the expected exocyclic olefins 12a and 12b, respectively. In contrast, the 3,6‐dimethoxy analogue 24, obtained from cycloproparene 20, gives the C1 unsubstituted cycloproparene 19 and the Tishchenko products, p‐(trifluoromethyl)benzyl p‐(trifluoromethyl)benzoate (21) and 2‐thienylmethyl thiophene‐2‐carboxylate (22), respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A New Route for the Total Synthesis of 6,7‐Dihydroeponemycin
Authors: Bennacer Bibia , Rivalle Christian , Grierson David S.
Published: November 2003

A new synthesis of dihydroeponemycin (2), a peptide epoxide with potent cytotoxic and antiangiogenesis activity, has been developed. In the initial steps, Fmoc‐Leu‐Cl was converted into the key amino ketone intermediate 9 by Stille coupling with tributylvinyltin, conjugate addition of PhSAlMe2 to the derived enone, S‐oxidation, and heat‐induced syn elimination. Subsequent reaction of 9 with H2O2 and catalytic Triton B produced the corresponding epoxides as a 1:1 diastereomeric mixture in 89 % yield. These epoxides were separated and individually converted into 2 and(2S)‐epi‐dihydroeponemycin (24) in a four‐step “one‐pot” protocol (77 % overall yield in both cases). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Preparation and Characterization of [5‐13C]‐(2S,4R)‐Leucine and [4‐13C]‐(2S,3S)‐Valine − Establishing Synthetic Schemes to Prepare Any Site‐Directed Isotopomer of L‐Leucine, L‐Isoleucine and L‐Valine
Authors: Siebum Arjan H. G. , Woo Wei Sein , Lugtenburg Johan
Published: November 2003

In this paper a chemo‐enzymatic method has been developed that gives access to any isotopomer of the essential amino acids isoleucine and valine. The method gives the correct introduction of the second chiral center in (2S,3S)‐isoleucine and allows for discrimination between the two prochiral methyl groups in valine as shown by the preparation of (2S,3S)‐[4‐13C] valine. For the preparation of (2S)‐leucine in any isotopomeric form, the O’Donnell method to prepare optically active amino acids has been used. The protected glycine scaffold used in this method has been prepared by a strategy that allows access to any isotopomeric form. The preparation of [5‐13C]‐(2S,4R)‐leucine shows that the O’Donnell method in combination with the Evans method to obtain chiral 2‐methylpropyl iodide leads to a good discrimination between the two prochiral methyl groups. The O’Donnell strategy for the preparation of α‐amino acids is preferred over other methods since the reaction conditions are mild, the chiral auxiliary can be easily recovered and the optically active product can be easily separated. For the preparation of isotopically enriched valine and isoleucine the O’Donnell method is not suitable, because the alkyl substituents involved have a secondary halide substituent which is sterically too hindered to give an effective reaction with the protected glycine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cyclisation of Novel Amino Oxo Esters to Tetramic Acids − Density Functional Theory Study of the Reaction Mechanism
Authors: Detsi Anastasia , Afantitis Antreas , Athanasellis Giorgos , Markopoulos John , Igglessi‐Markopoulou Olga , Skylaris Chris‐Kriton
Published: November 2003

The synthesis of novel N‐urethane‐protected γ‐methylamino‐β‐oxo esters and their use as precursors for the preparation of N‐methyltetramic acids is described. The presence of the bulky urethane protecting group on the nitrogen atom gives rise to rotational isomers detectable in the NMR spectra of the compounds, along with the keto/enol tautomerism. The mechanism of the cyclisation reaction of γ‐amino‐β‐oxo esters to tetramic acids was studied theoretically by the B3LYP hybrid density functional method. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Zn(ClO4)2·6H2O as a Powerful Catalyst for a Practical Acylation of Alcohols with Acid Anhydrides
Authors: Bartoli Giuseppe , Bosco Marcella , Dalpozzo Renato , Marcantoni Enrico , Massaccesi Massimo , Sambri Letizia
Published: November 2003

A new protocol for the acylation of alcohols with anhydrides in the presence of Zn(ClO4)2·6H2O as the catalyst is reported. The activity of Zn(ClO4)2·6H2O has been proven to be superior to that exerted by dry Mg(ClO4)2 and by metal triflates. Its efficiency allows reactions between poorly reactive substrates, such as sterically hindered tertiary alcohols and aromatic anhydrides. All of the reactions were carried out at a 1:1.05 alcohol/anhydride ratio. These conditions are extremely convenient from a practical and economic point of view, since they avoid wasting reagents and allow a simple workup procedure. The catalytic action of Zn(ClO4)2·6H2O is so specific for the activation of the anhydrides, that acid‐sensitive functionalities and the stereochemical configuration of the starting materials remain unaltered in the esterification process. In all cases, the acylated products are quantitatively obtained in pure form. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of New Hydroxy‐2‐styrylchromones
Authors: Santos Clementina M. M. , Silva Artur M. S. , Cavaleiro José A. S.
Published: November 2003

Hydroxy‐2‐styrylchromones 5a−i were prepared by debenzylation of benzyloxy‐2‐styrylchromones 3a−i, which were synthesised by the Baker−Venkataraman method. The last step of this method, the cyclodehydration 5‐aryl‐3‐hydroxy‐1‐(2‐hydroxyaryl)‐2,4‐pentadien‐1‐ones 2a−i, was carried out with a catalytic amount of iodine, or p‐toluenesulfonic acid, in DMSO. Benzyloxy‐3‐cinnamoyl‐2‐styrylchromones 4a−f were obtained as by‐products in both procedures, but the latter procedure gave benzyloxy‐2‐styrylchromones 3a−i in better yields. The structures of all new compounds were established by extensive NMR studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Evaluation Method of Smoothing Algorithms in Voltammetry
Authors: Jakubowska Malgorzata , Piech Robert , Dzierwa Tomasz , Wcislo Jacek , Kubiak Wladyslaw W.
Published: November 2003

The criterion for testing the influence of smoothing algorithms for the relevant parameters considered in analytical experiment is presented. The proposed approach assumes that the improvement of the whole set of measured curves should be considered. The calibration curve parameters with confidence intervals, correlation coefficient, detection limit, signal to noise ratio and parameters of recovery function are utilized for the evaluation. Performance of evaluation method is presented for several kinds of experimental noises.
The essential oils of Boesenbergia stenophylla R. M. Sm. as natural sources of methyl (E)‐cinnamate
Authors: Ahmad Fasihuddin bin , Jantan Ibrahim bin
Published: November 2003

The rhizome and leaf oils of Boesenbergia stenophylla R. M. Sm. were analysed by gas chromatography on two columns of different polarity, retention indices and GC–MS. The oils were found to possess compositional similarities but quantitative differences in the concentration of each component. The oils are natural sources of methyl (E)‐cinnamate, constituting 49.9–53.4% of the oils. They are also rich in sesquiterpenoids (39.8 and 40.3%, respectively) with δ‐elemene, β‐elemene, α‐santalene, α‐humulene, γ‐muurolene, spathulenol, caryophyllene alcohol and kaur‐16‐ene as the main representatives. Copyright © 2003 John Wiley & Sons, Ltd.
Composition of commercial Cape chamomile oil (Eriocephalus punctulatus)
Authors: Mierendorff Hanco‐Gisbert , Stahl‐Biskup Elisabeth , Posthumus Maarten A. , Beek Teris A. van
Published: November 2003

Cape chamomile oil obtained from the herb Eriocephalus punctulatus DC (Asteraceae) was analysed by GC and GC–MS. It was shown to consist of about 50 aliphatic esters, together amounting to more than 50% of the oil. 2‐Methylbutyl 2‐methylpropanoate (21.2%), 2‐methylbutyl 2‐methylbutanoate (5.6%), 2‐methylpropyl 2‐methylpropanoate (5.3%), and 7‐methyl‐2‐octyl acetate (4.5%) were the main components. In the terpenoid portion (about 37%), linalyl acetate (4.4%) and α‐pinene (1.9%) were the major compounds. In the higher boiling fraction, the artedouglasia oxides A–D, several davanones and laciniata furanones, oxygenated sesquiterpenes previously found in Artemisia species, could be detected in amounts of 5.9%, 0.4% and 1.4%, respectively. Commercial samples of different years showed almost identical compositions. Copyright © 2003 John Wiley & Sons, Ltd.
Application of co‐distillation with superheated pentane vapour to the isolation of unstable essential oils
Authors: Mastelić J. , Jerković I.
Published: November 2003

Hydrodistillation is the main method for essential oil isolation from aromatic plants. For unstable essential oils, this method is not suitable. For these cases, we have developed a method of isolation by co‐distillation with superheated pentane vapour. The method was studied using plant materials of Mentha citrata and Salvia sclarea, which contain unstable linalyl acetate as the main component of their essential oils. The essential oils of the same plants were also isolated by hydrodistillation as a standard method. The isolated volatiles (with both methods) were analysed by gas chromatography–mass spectrometry (GC–MS) and the obtained results were compared. Signiﬁcant differences were found in the qualitative and quantitative composition of isolated volatiles. The major components of the volatiles obtained by hydrodistillation and by co‐distillation with superheated pentane vapour, respectively, were linalyl acetate (26.5%, 55.5%), linalool (29.3%, 15.8%), 1,8‐cineole (7.2%, 3.5%), hedycaryol (6.2%, 6.6%) α‐terpineol (5.5%, 0.7%) and geranyl acetate (4.9%, 2.9%) for Mentha citrata; and linalyl acetate (21.2%, 33.4%), linalool (16.6%, 6.0%), myrcene (8.4%, 10.2%), geranyl acetate (7.3%, 6.7%) α‐terpineol (7.6%, 0.0%), trans‐β‐ocimene (4.4%, 6.4%) and geraniol (3.8%, 0%) for Salvia sclarea. The method of co‐distillation enables safe isolation of monoterpenes, but also sesquiterpene compounds as well as hydrodistillation. It is clear that this new method, unlike hydrodistillation, safely and remarkably diminishes artefact generation. Copyright © 2003 John Wiley & Sons, Ltd.
Composition of the essential oils of four medicinal plants from Ecuador
Authors: Malagón Omar , Vila Roser , Iglesias José , Zaragoza Tomás , Cañigueral Salvador
Published: November 2003

The composition of the essential oils from leaves of Lepechinia mutica, Satureja glabrata, Minthostachys mollis and Myrcianthes rhopaloides, four species used in traditional medicine in Loja (Ecuador), was investigated by GC–FID and GC–MS. Monoterpene hydrocarbons were the main group of constituents in the essential oil of L. mutica, especially β‐phellandrene (30%), whereas oxygenated monoterpenes predominated in the oils of M. mollis and M. rhopaloides, menthone (16%) and geranial (34%), respectively, being the major components. Although the oxygenated monoterpenes dominated the essential oil from S. glabrata (44%), the main constituent of this oil was isocaryophyllene (15%), followed by citronellol (14%) and citronellyl acetate (12%). Copyright © 2003 John Wiley & Sons, Ltd.
Cleft palate, transforming growth factor alpha gene variants, and maternal exposures: Assessing gene‐environment interactions in case‐parent triads
Authors: Jugessur Astanand , Lie Rolv T. , Wilcox Allen J. , Murray Jeffrey C. , Taylor Jack A. , Saugstad Ola D. , Vindenes Hallvard A. , Åbyholm Frank E.
Published: November 2003

We have previously reported a threefold risk of cleft palate only (CPO) among children homozygous for the less common allele A2 at the TaqI marker site of the transforming growth factor alpha gene (TGFA) (Jugessur et al. [2003a] Genet. Epidemiol. 24:230–239). Here we assess possible interaction between the child'sTGFATaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use of multivitamins and folic acid. This was done by comparing the strength of genetic associations between strata of exposed and unexposed case‐parent triads. We also looked for possible gene‐gene interaction with the polymorphic variant C677T of the folic acid‐metabolizing geneMTHFR. We analyzed a total of 88 complete CPO triads selected from a population‐based study of orofacial clefts in Norway (May 1996–1998). No evidence of interaction was observed with either smoking or alcohol use. The risk associated with two copies of the A2 allele atTGFATaqI was strong among children whose mothers did not use folic acid (relative risk=4.5, 95% confidence interval=1.3–15.7), and was only marginal among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2–12.7). Although the interaction between the child's genotypes atTGFATaqI andMTHFR‐C677T was not statistically significant, the effect of theTGFATaqI A2A2 genotype appeared to be stronger among children with either one or two copies of the T‐allele at C677T (RR=4.0, 95% CI=1.1–13.9) compared to children homozygous for the C‐allele (RR=1.7, 95% CI=0.2–15.7). In conclusion, we find little evidence of interaction between the child's genotypes atTGFATaqI and various exposures for cleft palate, with the possible exception of folic acid intake.Genet Epidemiol25:367–374, 2003. © 2003 Wiley‐Liss, Inc.
Estimating the relative recurrence risk ratio using a global cross‐ratio model
Authors: Wallace Chris , Clayton David
Published: November 2003

The relative recurrence risk ratio λR (and particularly the sibling recurrence risk ratio, λS ) is often of interest to those wanting to quantify the genetic contribution towards risk of disease or to discriminate between different genetic models. However, estimating λR for complex diseases for which genetic and environmental risk factors are both involved is not straightforward. Ignoring environmental factors may lead to inflated estimates of λR. We present a marginal model which uses a copula function to model the association in cumulative incidence rates between pairs of relatives. This model is applicable to present‐state data and allows estimation of risk of disease in a pair of relatives (and hence λR), given measured environmental covariates. We apply the model to leprosy among sibling pairs from the Karonga district, Malawi. If risk factors are ignored, the apparent λS in this population is over 3. Accounting for known nongenetic risk factors reduces it to just under 2. Genet Epidemiol 25:293–302, 2003. © 2003 Wiley‐Liss, Inc.
Effects of process parameters on heterologous protein production in Aspergillus niger fermentation
Authors: Wang Liping , Ridgway Darin , Gu Tingyue , Moo‐Young Murray
Published: November 2003

Filamentous fungi such as Aspergillus niger are attractive hosts for recombinant DNA technology because of their ability to secrete bioactive proteins with post‐translational processing such as glycosylation. Foreign genes can be incorporated into the chromosomes of the filamentous fungi, providing superior long‐term genetic stability. However, heterologous protein production is often severely hampered by fungal proteases. In this work, a recombinant Aspergillus niger strain AB4.1[pgpdAGLAGFP]#11 which carries a glucoamylase (GLA)‐green fluorescent protein (GFP) fusion gene was selected as a model system to study the effects of bioprocess parameters—agitation intensity, initial glucose concentration, initial yeast extract concentration, and dissolved oxygen tension (DO)—on extracellular protease inhibition and heterologous protein production. Based on previous experimental experience and results, a 24–1 fractional factorial design was applied to the experiments. Each parameter was tested at two levels. It was found that agitation affected the GFP production most significantly. Higher agitation rate resulted in higher GFP production. Protease activity was most influenced by initial glucose concentration and DO. Fungal morphology was also affected by these parameters. The effects of these parameters on pellet size and pellet porosity are discussed. Copyright © 2003 Society of Chemical Industry
Lignin peroxidase‐catalyzed polymerization and detoxification of toxic halogenated phenols
Authors: Ward Gary , Hadar Yitzhak , Dosoretz Carlos G
Published: November 2003

Halogenated phenols and bisphenols are recognized as being recalcitrant in conventional biological treatments. The current research evaluated lignin peroxidase‐catalyzed oxidation and polymerization as a potential alternative for their detoxification. Gel permeation–HPLC analysis demonstrated the formation of dimers, trimers and tetramers upon oxidation of the target substrates. Polymerization was accompanied by effective detoxification of the aqueous phase during oxidation of 2,4‐dibromophenol, the extent of which correlated with the extent of oxidation and polymerization. Steady state kinetic measurements at a saturating concentration of H2O2 revealed high Km values (270–1100 µmol dm−3) for the target substrates, reflecting the strong electron‐withdrawing properties of halogen substituents, which increase the oxidation potential of the phenols, resulting in thermodynamically less favorable reactions. However, kcat values were not dissimilar from non‐halogenated phenols and the rapid oxidation and polymerization suggests that low retention times could be expected in a continuous process for their treatment, in contrast to conventional biological methods. The operational stability of lignin peroxidase was significantly improved by inclusion of redox mediators, which resulted in enhanced oxidation and more rapid reaction rates. However, due to their inherent toxicity, the use of redox mediators impeded toxicity assays. The findings highlight the potential of lignin peroxidase as a possible alternative for the high‐rate treatment of industrial wastewater when conventional methods are ineffective. Copyright © 2003 Society of Chemical Industry
Convenient and efficient deuteration of functionalized aromatics with deuterium oxide: catalysis by cycloocta‐1,5‐dienyliridium(I) 1,3‐dionates
Authors: McAuley B. , Hickey M. J. , Kingston L. P. , Jones J. R. , Lockley W. J. S. , Mather A. N. , Spink E. , Thompson S. P. , Wilkinson D. J.
Published: November 2003

Aromatic compounds bearing an ortho‐directing substituent may be deuterated by exchange with deuterium oxide in the presence of a range of cycloocta‐1,5‐dienyliridium(I)1,3‐dionate catalysts. The exchange takes place in several dipolar aprotic solvents and is directly applicable to the deuteration of polar compounds. Isotope incorporation is efficient and regiospecific. The method is applicable to a wide range of ortho‐directing groups some of which are only weak directors for alternative ortho‐labelling approaches. In addition, the application of microwaves enables labelling within minutes even with sub‐stituents which are poor directors. Copyright © 2003 John Wiley & Sons, Ltd.
The evolution of the apparent diffusion coefficient in the pediatric brain at low and high diffusion weightings
Authors: Jones Richard A. , Palasis Susan , Grattan‐Smith J. Damien
Published: November 2003

Purpose

To evaluate the evolution of the apparent diffusion coefficient (ADC) with age for different degrees of diffusion weighting using a clinically feasible approach.

Materials and Methods

Data was acquired using separate scans with b values in the range typically used for clinical studies (100–900 seconds/mm2) and higher b values (1800–3000 seconds/mm2). The ADC was calculated for each of the data sets by fitting the data to a monoexponential function.

Results

The results from 50 children aged three years and less showed some deviations from literature values derived using a full biexponential fit, with these differences reflecting the approximations inherent in this approach. The values obtained with this technique appear to be reproducible but the resulting “institutional values” are comparable to those from other centers only if identical measurement criteria are used.

Conclusion

A significant decline in both components of the ADC during the first few months of life was observed; in addition, the attenuated slow ADC values seen in adult white matter were only present at birth in early myelinating regions. The subsequent development of the slow ADC in white matter suggests that it is associated with myelination or processes associated with axonal development. J. Magn. Reson. Imaging 2003;18:665–674. © 2003 Wiley‐Liss, Inc.
Using an adaptive semiautomated self‐evaluated registration technique to analyze MRI data for myocardial perfusion assessment
Authors: Delzescaux Thierry , Frouin Frédérique , De Cesare Alain , Philipp‐Foliguet Sylvie , Todd‐Pokropek Andrew , Herment Alain , Janier Marc
Published: November 2003

Purpose

To validate the adaptive semiautomated self‐evaluated registration technique (ASSERT) followed by factor analysis of medical image sequence (FAMIS) for analyzing myocardial perfusion using magnetic resonance imaging (MRI) images.

Materials and Methods

Eleven patients having a significant stenosis of at least one coronary artery detected by coronarography were examined by thallium tomoscintigraphy and perfusion MRI (first‐pass of Gd‐DTPA‐BMA) at rest and under pharmacologic stress. The MRI images were analyzed by ASSERT to correct for rigid motion in the acquisition plane and to reject those images that were severely deformed or acquired outside the slice plane. The images thus obtained were analyzed by FAMIS. The resulting factor images representing myocardial perfusion were read to identify the ischemic territories corresponding to left anterior descending coronary arteries and right coronary arteries.

Results

ASSERT allowed automatic correction for motion and the exclusion of images that could not be registered. The ischemic territories, identified from the factor images of the myocardium, agreed with those identified by coronarography and tomoscintigraphy for 20 of the 22 territories.

Conclusion

The results demonstrate the feasibility of analyzing myocardial perfusion using MRI acquisition and treating the resulting images by ASSERT and FAMIS. Extending this method to multislice examinations will enable evaluation of the perfusion of the whole myocardium. J. Magn. Reson. Imaging 2003;18:681–690. © 2003 Wiley‐Liss, Inc.
N‐(2‐Hydroxypropyl)methacrylamide (HPMA) Copolymer‐Linked Nitroxides: Potential Magnetic Resonance Contrast Agents
Authors: Huang Yuan , Nan Anjan , Rosen Gerald M. , Winalski Carl S. , Schneider Erika , Tsai Pei , Ghandehari Hamidreza
Published: November 2003

N‐(2‐Hydroxypropyl)methacrylamide (HPMA) copolymer‐linked nitroxides were synthesized as macromolecular contrast agents for MR imaging. Molar relaxivities of HPMA copolymer‐linked nitroxides increased linearly in proportion to the number of nitroxides attached per gram of copolymer. HPMA copolymer‐linked nitroxides with 15, 20 and 30 mol‐% nitroxide exhibited higher relaxivities than gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). These results demonstrate the potential of HPMA copolymer‐linked nitroxides as MR contrast agents for solid tumors.

Structure of HPMA copolymer‐linked nitroxides.

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Structure of HPMA copolymer‐linked nitroxides.
Thin Films by Multilayer Build‐Up of Electron Transport Materials
Authors: Mruk Ralf , Prehl Sabine , Zentel Rudolf
Published: November 2003

We present the synthesis and the electrochemical characterization of polymeric electron transport materials, synthesized by polycondensation of substituted triazines and α,ω‐dihaloalkanes. They can be reversibly reduced with the least negative potential at −0.39 V, which is below the reduction potential of oxygen. In addition, the formation of polyelectrolyte multilayers is possible by the electrostatic self‐assembly method. This multilayer formation takes place in a very defined way up to thirty double layers.

An example of one of the polymeric triazine electron transport materials synthesized and a schematic diagram of a self‐assembled multilayer film.

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An example of one of the polymeric triazine electron transport materials synthesized and a schematic diagram of a self‐assembled multilayer film.
Liquid Adsorption Chromatography Separation of Star Poly(methyl methacrylate)s
Authors: Lazzari Massimo , Jančo Miroslav , Kitayama Tatsuki , Hatada Koichi
Published: November 2003

Liquid adsorption chromatography, in combination with full adsorption–desorption and precipitation–redissolution techniques, is a powerful procedure for the fractionation of mixtures in the synthesis of star polymers. An easy separation of 4‐ and 6‐arm star poly(methyl methacrylate)s from their single arm precursors could be carried out by both procedures, with differences of separation efficiency also depending on the molecular weight of the precursor and the number of arms.

Size exclusion chromatograms of retained and eluted fractions obtained by liquid adsorption chromatography/full adsorption–desorption separation with a tetrahydrofuran/cyclohexane eluent system (53:47 wt.‐%) for a crude reaction mixture (dotted line) containing a 4‐arm star PMMA polymer and a single‐arm precursor (solid lines a and b, respectively).

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Size exclusion chromatograms of retained and eluted fractions obtained by liquid adsorption chromatography/full adsorption–desorption separation with a tetrahydrofuran/cyclohexane eluent system (53:47 wt.‐%) for a crude reaction mixture (dotted line) containing a 4‐arm star PMMA polymer and a single‐arm precursor (solid lines a and b, respectively).
Suppression of the transformed phenotype and induction of differentiation‐like characteristics in cultured ovarian tumor cells by chronic treatment with progesterone
Authors: Blumenthal Martina , Kardosh Adel , Dubeau Louis , Borok Zea , Schönthal Axel H.
Published: November 2003

Epidemiological evidence suggests that elevated levels of the pregnancy hormone progesterone might play a role in the reduced risk of women to develop ovarian cancer. In vitro studies have supported this hypothesis by demonstrating negative effects of this hormone on the growth and proliferation of cultured ovarian carcinoma cells. However, little is known about the underlying molecular processes and how progesterone might decrease the risk for ovarian tumors. Therefore, we investigated the effects of chronic hormone treatment on the cell‐cycle and transformed phenotype of ovarian carcinoma cell lines in vitro. We found that long‐term treatment of these cells with progesterone caused a concomitant reduction of cyclin‐dependent kinase (CDK) activity. In parallel, these cells lost their transformed phenotype as indicated by the acquisition of contact inhibition and the loss of anchorage‐independence, as well as the reduced expression of tumor markers such as heat shock protein (HSP) 72 and carcinoma antigen (CA) 125. In addition, progesterone‐treated cells exhibited characteristics that resembled a more differentiated phenotype. Taken together, our data indicated that progesterone was able to suppress the transformed phenotype of ovarian tumor cells. This observation could serve to explain progesterone's alleged protective effect in ovarian carcinogenesis. © 2003 Wiley‐Liss, Inc.
Pure akinesia: An unusual phenotype of Hallervorden‐Spatz syndrome
Authors: Molinuevo José L. , Martí María J. , Blesa Rafael , Tolosa Eduardo
Published: November 2003

Two siblings were seen in our outpatient movement disorders clinic with an indolent clinical picture of a pure akinesia syndrome. Magnetic resonance showed the typical “eye of the tiger” sign, and genetic screening disclosed that both siblings were compound heterozygotes with two missense mutations in the PANK2 gene 734A→G and 1172T→C. This case report highlights the phenotypic diversity of Hallervorden Spatz syndrome and the need for further investigation of adult‐onset pure akinesia syndromes. © 2003 Movement Disorder Society
Treatment of Sydenham chorea with corticosteroids
Authors: Cardoso Francisco , Maia Débora , Cunningham Mauro César Q.S. , Valença Guilherme
Published: November 2003

Despite treatment with valproic acid and neuroleptics, a significant proportion of patients with Sydenham chorea (SC) remain with chorea. We evaluated the effect of intravenous methyl‐prednisolone followed by oral prednisone in patients with SC refractory to conventional treatment. Patients were enrolled in the study if they failed to improve with conventional treatment, despite the development of side effects. Chorea was rated on a 0 to 4 score. Five patients, 3 of them women, were included in the study. The median pretreatment rating score of the chorea was 3 (range, 3–4) and dropped to 1 (range, 0–2) after a median follow‐up of 7 months (range, 3–7 months). Two patients developed Cushing syndrome. Our data suggest that intravenous methyl‐prednisolone followed by oral prednisone is an effective and well‐tolerated treatment of refractory SC. © 2003 Movement Disorder Society
Diagnostic potential of acoustic startle reflex, acoustic blink reflex, and electro‐oculography in progressive supranuclear palsy: A prospective study
Authors: Gironell Alexandre , Kulisevsky Jaime , Roig Carles , Pascual‐Sedano Berta , Rodríguez‐Fornells Antoni , Otermin Pilar
Published: November 2003

We carried out a prospective study to analyze the diagnostic potential of acoustic startle reflex (ASR), acoustic blink reflex (ABR) and electro‐oculography (EOG) in early stages of atypical parkinsonian syndrome. The study was carried out in a consecutive series of 41 patients clinically diagnosed as atypical parkinsonism (mean time from first symptoms of 38 months and follow‐up of 26 months). The three procedures were carried out immediately after the first clinical evaluation. ASR and ABR were elicited by auditory stimuli while the patient was attending to a simple reaction time task. Outcome measures were: ASR (absence/presence, latency), ABR (absence/presence, latency) and EOG (suggestive/not suggestive of progressive supranuclear palsy [PSP]). Final clinical diagnosis was carried out by two neurologists blind to the neurophysiological results. A study of diagnostic sensitivity and odds ratio (OR) calculation for the PSP diagnosis was carried out. Neurophysiological examination showed the following sensitivity/specificity (%) for the diagnosis of PSP: ASR: 100/89; ABR 85/89; EOG 100/72. OR values were: ASR: 0.011; ABR: 0.037; EOG: 0.038. The three tests taken simultaneously showed a sensitivity of 100% and a specificity of 95%. The three neurophysiological tests investigated provided sensitive and specific measures with predictor value in early stages of atypical parkinsonian syndrome. © 2003 Movement Disorder Society
A computer model of rigidity and related motor dysfunction in Parkinson's disease
Authors: Le Cavorzin Philippe , Carrault Guy , Chagneau Francis , Rochcongar Pierre , Allain Hervé
Published: November 2003

This work explores the involvement of spinal circuits in the generation of parkinsonian rigidity and related motor dysfunction. A computer model of spinal proprioceptive input processing, derived from previous work on spasticity modeling, was adapted to the simulation of parkinsonian rigidity. Model parameters were varied to generate simulations reproducing experimental data obtained using the pendulum test of the leg in 10 parkinsonian patients and 3 healthy subjects. Convenient reproductions of experimental traces in rigidity were obtained by the combination of a low reflex gain and a decrease in reflex threshold. These findings are consistent with studies reporting an increase of spinal interneuron excitability and proprioception deficits in Parkinson's disease (PD). Moreover, as the threshold parameter was much lowered, our model generated typical features of parkinsonian resting tremor, endorsing the hypothesis of a participation of a spinal oscillator in this disorder. Finally, tuning the reflex gain during simulations of rigidity resulted in the generation of active movement, opening some hypotheses on pathophysiology of motor dysfunction in PD, and notably, of akinesia. More generally, this work accredits the hypothesis of the involvement of an aperiodic, altered supra‐spinal motor drive in PD, resulting in spinal dysfunction, through specific descending motor pathways. This may lead to a search for new (spinal) pharmacological targets in PD. It emphasizes further the value of computer modeling in understanding motor control in health and disease. © 2003 Movement Disorder Society
Parkin variants in North American Parkinson's disease: Cases and controls
Authors: Lincoln Sarah J. , Maraganore Demetrius M. , Lesnick Timothy G. , Bounds Rebecca , de Andrade Mariza , Bower James H. , Hardy John A. , Farrer Matthew J.
Published: November 2003

We report on an evaluation of coding variants within the parkin gene to assess their frequency in a North American clinical series of 313 Parkinson's disease (PD) cases and 192 unrelated controls. We hypothesized that the carrier frequency of parkin coding mutations, exon deletions, or duplications may be greater in PD cases. However, point mutations and exonic deletions/duplications, reported previously as pathogenic in homozygous or compound heterozygous individuals, occurred in both cases and controls with similar frequencies (3.8% in cases, 3.1% in controls). Furthermore, only stratified subanalyses detected any genetic association between the V380L common coding polymorphism and PD. We discuss the implication of parkin mutations for Parkinson's disease from this population perspective. © 2003 Movement Disorder Society
Severe cervical dystonia in pathologically proven Parkinson's disease and dementia (PDD)
Authors: Cohen Oren , Fahn Stanley , Frucht Steven J.
Published: November 2003

We describe and present a videotape of a patient with parkinsonism and dementia who developed severe cervical dystonia, despite treatment with levodopa and botulinum toxin. The clinical diagnosis of Parkinson's disease and dementia (PDD) was confirmed at autopsy. © 2003 Movement Disorder Society
Dependence of the pure quadrupole resonance frequency on temperature for KBrO3
Authors: Stahl Edward A. , Herzog Siegfried
Published: November 2003

The pure quadrupole resonance frequency of KBrO3 in the temperature range 4.17–300.16 K was determined experimentally and compared with the model developed by Stahl which contains three adjustable constants. Excellent agreement between the experimental data and the model was obtained when considering only the temperature range 4.17–52 K. As a result of the comparison, the following values are suggested for KBrO3: the resonance frequency at 0 K is 179.50373 MHz, the Debye temperature, Θd, is 108 K, and the rotational energy, Iωl2, of each of the first two modes of oscillation of the BrO3 group is 1.707 × 10−18 kg m2. Here I is the moment of inertia and ωl is the lattice vibration frequency. Comparison of model and experimental data over the entire temperature range from 4.17 to 300.16 K shows that the suggested theory reflects very well the general trend of the experimental data but lacks in some detail. Copyright © 2003 John Wiley & Sons, Ltd.
Total assignments of 1H and 13C NMR spectra of biflorin and bis‐biflorin from Capraria biflora
Authors: Fonseca Aluisio M. , Pessoa Otília D. L. , Silveira Edilberto R. , Monte Francisco J. Q. , Braz‐Filho Raimundo , Lemos Telma L. G.
Published: November 2003

Bis‐biflorin, a new o‐naphthoquinone dimer, and biflorin, 6,9‐dimethyl‐3‐(4‐methyl‐3‐pentenyl)naphtho[1,8‐bc]‐pyran‐7,8‐dione, were isolated from roots of Capraria biflora, a medicinal plant from northeast Brazil. Structural elucidation was made on the basis of spectral data, mainly by high‐field NMR and high‐resolution mass spectrometry. Copyright © 2003 John Wiley & Sons, Ltd.