bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of permethylated oligosaccharides using electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry and deutero‐reduction
Authors: Morelle Willy , Faid Valegh , Michalski Jean‐Claude
Published: September 2004

Deutero‐reduced permethylated oligosaccharides were analyzed by electrospray ionization mass spectrometry (ESI‐MS) and tandem mass spectrometry (MS/MS) using a hybrid quadrupole orthogonal acceleration time‐of‐flight mass spectrometer, fitted with a nanoflow ESI source. Under these ionization conditions such derivatives preferentially form sodiated molecular species in addition to protonated molecular species. Under collision‐induced dissociation, protonated and sodiated molecular species yield simple and predictable fragment mass spectra. A systematic study was conducted on a series of deutero‐reduced permethylated glycans to allow rationalization of the fragmentation processes. MS/MS spectra were characterized by fragments resulting from the cleavage of glycosidic bonds. These fragments originating from both the reducing and the non‐reducing ends of the glycan yield information on sequence and branching. Furthermore, the substituent 3‐linked to a HexNAc unit was readily eliminated. Special attention was devoted to a systematic study of fucosylated glycans. The fucosylated deutero‐reduced permethylated glycans were submitted to an acidic hydrolysis, releasing specifically the fucosyl residues. The nascent free hydroxyl groups were subsequently CD3‐labelled in order to determine the positions initially bearing the fucosyl residues along the oligosaccharide backbone. This methodology was finally applied to characterize a glycan pool enzymatically released from glycoproteins. The present data show that structural elucidation can be achieved at the 50 fmol level. Copyright © 2004 John Wiley & Sons, Ltd.
Automated interpretation of mass spectra of complex mixtures by matching of isotope peak distributions
Authors: Fernández‐de‐Cossio Jorge , Gonzalez Luis Javier , Satomi Yoshinori , Betancourt Lazaro , Ramos Yassel , Huerta Vivian , Besada Vladimir , Padron Gabriel , Minamino Naoto , Takao Toshifumi
Published: September 2004

Mass spectrometry is now firmly established as a powerful technique for the identification and characterization of proteins when used in conjunction with sequence databases. Various approaches involving stable‐isotope labeling have been developed for quantitative comparisons between paired samples in proteomic expression analysis by mass spectrometry. However, interpretation of such mass spectra is far from being fully automated, mainly due to the difficulty of analyzing complex patterns resulting from the overlap of multiple peaks arising from the assortment of natural isotopes. In order to facilitate the interpretation of a complex mass spectrum of such a mixture, such as an MS spectrum of a stable‐isotope‐enriched ion species, we report on the development of a software application, ‘Matching’ (web accessible), that enables the automatic matching of theoretical isotope envelopes to multiple ion peaks in a raw spectrum. It is particularly useful for resolving the relative abundances of narrow‐split paired peaks caused by enrichment with a stable isotope, such as 18O, 13C, 2H, or 15N. Copyright © 2004 John Wiley & Sons, Ltd.
Nanospray ‘taxation’ and how to avoid it
Authors: Chernushevich I. V. , Bahr U. , Karas M.
Published: September 2004

In mass spectrometric analysis with nanospray ionization, some analytes were found to appear in spectra with a delay of tens of minutes, while a few others could not be detected at all. The effect was found to be related to cation‐exchange chromatography with negative charge on the glass surface, and with the most affected peptide or protein ions having strong localization of positive charge in blocks of two or more adjacent basic amino acid residues (e.g. melittin). The ‘affinity’ to the glass surface was studied with a peptide mixture and bovine serum albumin (BSA) tryptic digest solutions at sub‐micromolar concentration. About 20% fewer tryptic peptides could be identified from spectra recorded with a glass nanospray capillary compared to those acquired with either conventional 1 μL/min electrospray or a quartz nanospray capillary. Protein identification studies are not likely to be seriously affected by this loss, but other protein applications, such as investigations of mutations or post‐translational modifications, may suffer due to reduced sequence coverage. Ways to avoid losses of useful ions are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Dynamic identification of phosphopeptides using immobilized metal ion affinity chromatography enrichment, subsequent partial β‐elimination/chemical tagging and matrix‐assisted laser desorption/ionization mass spectrometric analysis
Authors: Ahn Yeong Hee , Park Eun Jung , Cho Kun , Kim Jin Young , Ha Sang Hoon , Ryu Sung Ho , Yoo Jong Shin
Published: September 2004

The enrichment of phosphopeptides using immobilized metal ion affinity chromatography (IMAC) and subsequent mass spectrometric analysis is a powerful protocol for detecting phosphopeptides and analyzing their phosphorylation state. However, nonspecific binding peptides, such as acidic, nonphosphorylated peptides, often coelute and make analyses of mass spectra difficult. This study used a partial chemical tagging reaction of a phosphopeptide mixture, enriched by IMAC and contaminated with nonspecific binding peptides, following a modified β‐elimination/Michael addition method, and dynamic mass analysis of the resulting peptide pool. Mercaptoethanol was used as a chemical tag and nitrilotriacetic acid (NTA) immobilized on Sepharose beads was used for IMAC enrichment. The time‐dependent dynamic mass analysis of the partially tagged reaction mixture detected intact phosphopeptides and their mercaptoethanol‐tagged derivatives simultaneously by their mass difference (–20 Da for each phosphorylation site). The number of new peaks appearing with the mass shift gave the number of multiply phosphorylated sites in a phosphopeptide. Therefore, this partial chemical tagging/dynamic mass analysis method can be a powerful tool for rapid and efficient phosphopeptide identification and analysis of the phosphorylation state concurrently using only MS analysis data. Copyright © 2004 John Wiley & Sons, Ltd.
Remedial options for chlorinated volatile organics in a partially anaerobic aquifer
Authors: Qiu Xiujin , Stock Melinda K. , Davis John W.
Published: September 2004

A laboratory study was conducted for the selection of appropriate remedial technologies for a partially anaerobic aquifer contaminated with chlorinated volatile organics (VOCs). Evaluation of in situ bioremediation demonstrated that the addition of electron donors to anaerobic microcosms enhanced biological reductive dechlorination of tetrachloroethene (PCE), trichloroethene (TCE), and 1,1,1‐trichloroethane (1,1,1‐TCA) with half‐lives of 20, 22, and 41 days, respectively. Nearly complete reductions of PCE, TCE, 1,1,1‐TCA, and the derivative cis‐dichloroethene were accompanied by a corresponding increase in chloride concentrations. Accumulation of vinyl chloride, ethene, and ethane was not observed; however, elevated levels of 14CO2 (from 14C‐TCE spiked) were recovered, indicating the occurrence of anaerobic oxidation. In contrast, very little degradation of 1,2‐dichloropropane (1,2‐DCP) and 1,1‐dichlorethane (1,1‐DCA) was observed in the anaerobic microcosms, but nutrient addition enhanced their degradation in the aerobic biotic microcosms. The aerobic degradation half‐lives for 1,2‐DCP and 1,1‐DCA were 63 and 56 days, respectively. Evaluation of in situ chemical oxidation (ISCO) demonstrated that chelate‐modified Fenton's reagent was effective in degrading aqueous‐phase PCE, TCE, 1,1,1‐TCA, 1,2‐DCP, etc.; however, this approach had minimal effects on solid‐phase contaminants. The observed oxidant demand was 16 g‐H2O2/L‐groundwater. The oxidation reaction rates were not highly sensitive to the molar ratio of H2O2:Fe2+:citrate. A ratio of 60:1:1 resulted in slightly faster removal of chemicals of concern (COCs) than those of 12:1:1 and 300:1:1. This treatment resulted in increases in dissolved metals (Ca, Cr, Mg, K, and Mn) and a minor increase of vinyl chloride. Treatment with zero‐valent iron (ZVI) resulted in complete dechlorination of PCE, and TCE to ethene and ethane. ZVI treatment reduced 1,1,1‐TCA only to 1,1‐DCA and chloroethane (CA) but had little effect on reducing the levels of 1,2‐DCP, 1,1‐DCA, and CA. The longevity test showed that one gram of 325‐mesh iron powder was exhausted in reaction with > 22 mL of groundwater. The short life of ZVI may be a barrier to implementation. The ZVI surface reaction rates (ksa) were 1.2 × 10−2 Lm−2h−1, 2 × 10−3 Lm−2h−1, and 1.2 × 10−3 Lm−2h−1 for 1,1,1‐TCA, TCE, and PCE, respectively. Based upon the results of this study, in situ bioremediation appeared to be more suitable than ISCO and ZVI for effectively treating the groundwater contamination at the site. © 2004 Wiley Periodicals, Inc.
Using wind to power a groundwater circulation well—preliminary results
Authors: Elmore Andrew Curtis , Gallagher Ron , Drake K. David
Published: September 2004

In areas of the country where the U.S. Department of Energy has classified the available wind resources as Class 3 or greater, the use of wind turbines to provide power to relatively small remediation systems such as groundwater circulation wells may be technically and economically feasible. Groundwater circulation wells are a good candidate technology to couple with renewable energy, because the remediation system removes contamination from the subject aquifer with no net loss of the groundwater resource, while the wind turbine does not create potentially harmful air emissions. Wind data collected in the vicinity of the former Nebraska Ordnance Plant Superfund site were used to select a wind turbine system to provide a portion of the energy necessary to power a groundwater circulation well located in an area of high trichloroethylene groundwater contamination. Because utility power was already installed at the remediation system, a 10 kW grid inter‐tie wind turbine system supplements the utility system without requiring batteries for energy storage. The historical data from the site indicate that the quantity of energy purchased correlates poorly with the quantity of groundwater treated. Preliminary data from the wind turbine system indicate that the wind turbine provides more energy than the remediation system treatment components and the well submersible pump require on a monthly average. The preliminary results indicate that the coupling of wind turbines and groundwater circulation wells may be an attractive alternative in terms of the system operation time, cost savings, and contaminant mass removal. © 2004 Wiley Periodicals, Inc.
Kinetic study of permanganate oxidation of tetrachloroethylene at a high pH under acidic conditions
Authors: Dai Qunli , Reitsma Stanley
Published: September 2004

Since carbon compounds are the main component of dense nonaqueous phase liquids (DNAPLs), the end products of all in situ chemical oxidation (ISCO) will include carbon dioxide. If the production rate of carbon dioxide exceeds the capacity of water to remove the carbon dioxide, degassing will occur. The uncontrolled carbon dioxide gas may change the flow patterns, remobilize the pooled DNAPL, transport DNAPL vapor, and reduce the relative permeability to the aqueous phase. Under high pH buffered conditions, most of the carbon dioxide will be dissolved in water. In this study, potassium permanganate oxidation of tetrachloroethylene (PCE) was conducted using a sodium carbonate buffered solution (1 g/L, pH = 10.6 ± 0.1) at three different temperatures (5, 10, and 20°C) and three potassium permanganate concentrations (0.2, 1, and 5 g/L). Extensive kinetic studies suggest that the overall oxidation is a second‐order reaction and pseudo‐first‐order with respect to PCE and potassium permanganate, respectively. The second‐order rate constant and the activation energy were 0.028 ± 0.001 M−1s−1 at 20°C and 43.9 ± 2.85 kJ/M, respectively. This study provides a base for further experimental and field studies on potassium permanganate oxidation of PCE under natural or artificial high pH buffered conditions. © 2004 Wiley Periodicals, Inc.
Study of the future land use of a contaminated site: Preferences versus potential use
Authors: Burger Joanna
Published: September 2004

Worldwide, agencies with high levels of contamination are faced with decisions about remediation and restoration. These decisions should be informed by future land use and long‐term stewardship goals. In the United States, the Department of Energy has lands in some 34 states that require cleanup. They are involved in massive remediation and restoration efforts on lands from the Cold War legacy and wish to reduce their overall footprint. Understanding future land use preferences is essential for determining the nature and degree of remediation and restoration. The objective of this study was to examine future land use preferences for the Department of Energy's Los Alamos National Laboratory as a function of ethnicity for attendees at the Los Alamos Gun Show in New Mexico (1999), and to determine whether their own activity influences future land use preferences. The highest preferred future land uses for Los Alamos National Laboratory were hiking, camping, National Environmental Research Park, and birdwatching, followed by hunting and fishing. Increased nuclear waste storage and building homes and factories were rated the lowest. Further, hiking and camping were rated higher than at two other DOE sites. There were few ethnic differences, although American Indians rated camping, hiking, building houses, and returning the land to American Indians higher than did others, and Hispanics rated using it for a preserve as a higher preferred land use than all others. The differences, however, were not great. Relative ratings for using the land for hunting and fishing were directly related to individual frequency of hunting and fishing for both whites and Hispanics, indicating that people perceive the importance of land use by how they want to use it. Ratings for hiking and camping were not related to the number of days people hiked and camped, suggesting these are general preferences overall. © 2004 Wiley Periodicals, Inc.
The potential of foliar treatments for enhanced phytoextraction of heavy metals from contaminated soil
Authors: Meers Erik , Tack Filip
Published: September 2004

Phytoextraction is the plant‐based removal of inorganic contaminants from the soil by root absorption and subsequent translocation to harvestable plant parts. The efficiency of this technique is limited by the phytoavailability of these contaminants in the soil and the root‐to‐shoot transport. To enhance the phytoextraction efficiency, the use of soil amendments has been widely investigated. Potential risks such as increased ecotoxicological effects and leaching of mobilized contaminants caution against the use of persistent mobilizing agents. The potential use of foliar amendments to enhance mineral absorption and/or translocation offers prospects for complementing or substituting soil amendments for enhanced phytoextraction purposes. This study presents an explorative screening to evaluate the feasibility of this approach. Helianthus annuus giganteus plants were grown in moderately contaminated dredged sediment for ten weeks, with daily foliar treatments from week six onward: (1) distilled water (control), (2) magnesium‐ethylenediaminetetraacetic acid (Mg‐EDTA), (3) diethylenetriaminepentaacetic acid (DTPA), (4) nitrilotriacetic acid (NTA), (5) citric acid, (6) oxalic acid, (7) calcium acetate, (8) ammonium thiocyanate (NH4SCN), and (9) cystein. Applied doses varied between treatments based on plant tolerance: 15 μmol per plant for cystein, 60 μmol per plant for DTPA and NH4SCN, 180 μmol per plant for Mg‐EDTA and NTA and 400 μmol per plant for the organic acids. At the end of the experiment, shoot accumulation of cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc was evaluated. © 2004 Wiley Periodicals, Inc.
A resource‐based analysis of peer‐to‐peer technology
Authors: Pavlov Oleg V. , Saeed Khalid
Published: September 2004

Peer‐to‐peer technology allowed massive free music ﬁle sharing, which led to much controversy, legal debate, and a great deal of speculation about the technology's business viability. Operation of a peer‐to‐peer (P2P) network depends on the content and bandwidth contributions from its users. Many users free ride by contributing fewer resources than they use. Research found that free riding intensiﬁes with crowding. These salient features suggest that the underlying template describing a P2P system may be the limits to growth archetype. We expand on this idea by building a system dynamics model, which captures complex causal interactions between private provision of common resources, free riding, network performance, and membership dynamics. Base runs conﬁrm that the model reproduces historically observed behavior. We use the calibrated model to test effectiveness of certain modiﬁcations that have been proposed for real P2P networks. Simulation results are explained by reviewing the interplay of reinforcing and limiting feedbacks that drive the system. Copyright © 2004 John Wiley & Sons, Ltd.
A preliminary study of stress symptoms and nutritional state in children
Authors: Stefanello Rosina
Published: September 2004

The aim of this work was to examine the occurrence of stressful events in the lives of children, using the ‘Scale of Infantile Social Readjustment’ (SISR), and the ‘Inventory of Symptoms of Infantile Stress’ (ISIS) to identify the presence of stress symptoms. The results of these evaluations were then used to examine the relationship between the levels of stress and the nutritional state of the children, by correlation. Forty 7–10‐year‐old children were included in the evaluation. From the analysed sample 49 per cent of them were eutrophic (weight/height normal to age), 50 per cent were above weight and 1 per cent was undernourished. Whereas 70 per cent of the girls were eutrophic and 30 per cent were above weight, only 35 per cent of the boys were eutrophic, 60 per cent were above weight and 5 per cent were undernourished. The results obtained in this first study indicated that 45 per cent of eutrophic girls demonstrated symptoms of stress, while 20 per cent of them were asymptomatic (with no symptoms of stress). Of the overweight boys, 30 per cent of them showed symptoms of stress and 35 per cent did not. This study indicated a possible relationship between weight and the symptoms of stress. Copyright © 2004 John Wiley & Sons, Ltd.
Health related quality of life of patients with refractory angina before and one year after enrolment onto a refractory angina program
Authors: Moore R.K. , Groves D. , Bateson S. , Barlow P. , Hammond C. , Leach A.A. , Chester M.R.
Published: September 2004

Objective: This study was designed to assess the impact of a refractory angina programme on the health related quality of life for patients with chronic refractory angina (CRA) one year following enrolment.

Design: A one year prospective audit.

Setting: Specialist refractory angina clinic at a tertiary cardiac referral centre.

Patients: 69 consecutive refractory angina patients referred to a regional refractory angina centre from 1/03/2001 to 1/09/2002.

Interventions: Pain treatment algorithm in accordance with the recommendations of the national refractory angina guideline committee.

Main outcome measures: Improvements in quality of life indices were assessed using Seattle angina questionnaire (SAQ), and short form‐12 (SF‐12) with changes in mood determined using the hospital anxiety and depression (HAD) questionnaire.

Results: All dimensions of the SF‐12 and SAQ were superior at one year with significant improvement seen with the mental component of SF‐12 (p = 0.023), and four of the five SAQ domains, angina stability (p = 0.028), angina frequency (p = 0.02), treatment satisfaction (p = 0.001) and quality of life (p < 0.001). All the significant changes within the SAQ domains were large enough to be considered clinically relevant. At one year the anxiety and depression domains were significantly improved from baseline (p = 0.015, 0.018) with clinical anxiety levels falling significantly from 55% to 40%, a relative reduction of 28% (p = 0.008).

Conclusions: Implementation of the national refractory angina guidelines in a prospective study of 69 consecutive CRA patients significantly improved health related quality of life status at one year.
ERR‐10: a new repressor in transcriptional signaling activation of estrogen receptor‐α
Authors: Meng Qinghui , Zhao Zeguo , Yan Ming , Zhou Lixin , Li Jiyou , Kitt Christina , Bin Gao , Fan Saijun
Published: September 2004

Estrogen receptor‐alpha (ER‐α) is a nuclear transcriptional factor that is part of the nuclear receptor superfamily. In this study, we isolated and identified a new LXXLL‐containing protein that interacts with the ER‐α via a yeast two‐hybrid assay. We have termed this protein estrogen receptor repressor‐10 (ERR‐10). The ERR‐10 cDNA is predicted to encode a polypeptide of 94 amino acids, with a molecular mass of about 10 kDa. Although the ERR‐10 mRNA transcript is expressed in a wide range of normal human tissues, higher expression levels are found in endocrinal tissues relative to other tissues. We have demonstrated, through immunoprecipitation, Western blot and GST pull‐down assays, that ERR‐10 associates with ER‐α. Moreover, ERR‐10 decreased 17β‐estrodial‐induced activation of ER‐α transcriptional activity in transient transfection assays of mammalian cells. The ERR‐10 N‐terminus, which resembles two LXXLL motifs, is essential for ER‐α binding and repression activity. Estrogen modulation of estrogen‐responsive gene expression was markedly blocked by ERR‐10. These results suggest that ERR‐10 is a novel mediator in ER transcriptional activation.
Mouse acetylcholinesterase interacts in yeast with the extracellular matrix component laminin‐1β
Authors: Paraoanu Laura E. , Layer Paul G.
Published: September 2004

Acetylcholinesterase (AChE) is likely to have roles other than the hydrolysis of acetylcholine, e.g., related to developmental processes like neurite outgrowth, differentiation and adhesion. Here, we investigated whether AChE can function as a heterophilic cell adhesion molecule and searched for proteins interacting with it. Using the yeast two‐hybrid method and a mouse brain cDNA library, we have identified an interaction between a partial cDNA encoding the globular domain IV of laminin chain β1 and the amino acids 240–503 of mouse AChE. Biochemical co‐immunoprecipitation assays confirmed the genetic results. We suggest that AChE, by interacting with laminin‐1, is able to exert changes in adhesion signaling pathways.
Synergistic activation of insect cAMP‐dependent protein kinase A (type II) by cyclicAMP and cyclicGMP
Authors: Leboulle Gérard , Müller Uli
Published: September 2004

The high cGMP sensitivity of cAMP‐dependent protein kinase A (type II) (PKAII) from invertebrates led to the hypothesis that cGMP directly activates PKAII under physiological conditions. We tested this idea using PKAII holoenzyme purified from the honeybee brain in an assay with short stimulation times. In the presence of very low cAMP concentrations, we found a synergistic increase in PKAII activation by physiological cGMP concentrations. Cloning honeybee regulatory subunit RII and phylogenetic comparison of the two cyclic nucleotide‐binding sites of RII reveal a high relation of domain A of insect RII with cGMP‐binding domains of cGMP‐dependent protein kinases.
Endothelin‐1 is an essential co‐factor for β2‐adrenergic receptor‐induced proliferation of human cardiac fibroblasts
Authors: Turner Neil A. , O'Regan David J. , Ball Stephen G. , Porter Karen E.
Published: September 2004

We previously demonstrated that chronic stimulation of the β2‐adrenergic receptor (β2‐AR) increases proliferation of cultured human cardiac fibroblasts (CF) via an autocrine mechanism. Here, we investigated the role of endothelin‐1 (ET‐1) in this process. ETA‐receptor antagonism or protein kinase C inhibition abolished the β2‐AR‐induced increase in cell proliferation. RT‐PCR and ELISA analysis demonstrated that although CF synthesized and secreted ET‐1, this occurred independently of β2‐AR stimulation. Furthermore, despite activation of the MAP kinase pathway, ET‐1 treatment did not stimulate CF proliferation. Therefore, the role of ET‐1 in this process is that of an essential co‐factor acting independently of β2‐AR stimulation.
Determination and comparison of specific activity of the HIF‐prolyl hydroxylases
Authors: Tuckerman Jason R. , Zhao Yuguang , Hewitson Kirsty S. , Tian Ya-Min , Pugh Christopher W. , Ratcliffe Peter J. , Mole David R.
Published: September 2004

Hypoxia‐inducible factor (HIF) is a transcriptional complex that is regulated by oxygen sensitive hydroxylation of its α subunits by the prolyl hydroxylases PHD1, 2 and 3. To better understand the role of these enzymes in directing cellular responses to hypoxia, we derived an assay to determine their specific activity in both native cell extracts and recombinant sources of enzyme. We show that all three are capable of high rates of catalysis, in the order PHD2=PHD3 >
PHD1, using substrate peptides derived from the C‐terminal degradation domain of HIF‐α subunits, and that each demonstrates similar and remarkable sensitivity to oxygen, commensurate with a common role in signaling hypoxia.
The role of raffinose in the cold acclimation response of Arabidopsis thaliana
Authors: Zuther Ellen , Büchel Kerstin , Hundertmark Michaela , Stitt Mark , Hincha Dirk K. , Heyer Arnd G.
Published: September 2004

In many plants raffinose family oligosaccharides are accumulated during cold acclimation. The contribution of raffinose accumulation to freezing tolerance is not clear. Here, we investigated whether synthesis of raffinose is an essential component for acquiring frost tolerance. We created transgenic lines of Arabidopsis thaliana accessions Columbia‐0 and Cape Verde Islands constitutively overexpressing a galactinol synthase (GS) gene from cucumber. GS overexpressing lines contained up to 20 times as much raffinose as the respective wild‐type under non‐acclimated conditions and up to 2.3 times more after 14 days of cold acclimation at 4 °C. Furthermore, we used a mutant carrying a knockout of the endogenous raffinose synthase (RS) gene. Raffinose was completely absent in this mutant. However, neither the freezing tolerance of non‐acclimated leaves, nor their ability to cold acclimate were influenced in the RS mutant or in the GS overexpressing lines. We conclude that raffinose is not essential for basic freezing tolerance or for cold acclimation of A. thaliana.
Heterologously expressed protein phosphatase calcineurin downregulates plant plasma membrane H+‐ATPase activity at the post‐translational level
Authors: Marı́n-Manzano Mari Carmen , Rodrı́guez-Rosales Maria Pilar , Belver Andrés , Donaire Juan Pedro , Venema Kees
Published: September 2004

To investigate the effects of calcineurin expression on cellular ion homeostasis in plants, we have obtained a transgenic cell culture of tomato, expressing constitutively activated yeast calcineurin. Transgenic cells exhibited reduced growth rates and proton extrusion activity in vivo. We show that reduction of plasma membrane H+‐ATPase activity by expression of calcineurin is the basis for the observed phenotypes. Transgenic calli and cell suspensions displayed also increased salt tolerance and contained slightly higher Ca2+ and K+ levels. This demonstrates that calcineurin can modulate ion homeostasis in plants as it does in yeast by affecting the activity of primary ion transporters.
Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease
Authors: Boutajangout A. , Boom A. , Leroy K. , Brion J.P.
Published: September 2004

In Alzheimer's disease (AD), selective expression of tau isoforms might underlie the susceptibility of different brain areas to develop neurofibrillary tangles and this pattern might change in the disease. In this study, we have analyzed in control subjects and in sporadic AD patients the pattern of expression of tau mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter), moderately affected (occipital striate cortex, thalamus, caudate nucleus, and putamen) or strongly affected by neurofibrillary tangles (temporal and frontal associative cortex). After RT‐PCR amplification, five products corresponding to the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon 10 and without exon 10 were identified. In control subjects, these five PCR products were present in all areas except in white matter, where transcripts with exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of transcripts was observed in different areas, regardless of the presence of neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six tau isoforms were identified in the same areas by immunoblotting, including in the white matter, suggesting that most tau isoforms with exons 2 and 3 are transported along axons. The relative expression of 0N3R isoforms was higher in the temporal cortex than in the cerebellar cortex, both in control and AD subjects. The qualitative pattern of expression was identical in subjects with or without an APOE4 allele. Our results suggest that splicing regulation of the tau gene and the relative expression of tau isoforms are not significantly changed in sporadic cases of the disease, although differential expression of tau isoforms in temporal cortex might underlie this brain area susceptibility to neurofibrillary tangles formation.
Mutations dislocate caspase‐12 from the endoplasmatic reticulum to the cytosol
Authors: Hoppe Viviane , Hoppe Jürgen
Published: September 2004

Mouse AKR‐2B cells express two forms of caspase‐12: the full‐length form coding for a protein of 47.8 kDa and a new splice variant of 40.2 kDa which is devoid of the CARD domain. In addition, three point mutations were disclosed: I/L‐15, E/D‐46 and P/L‐105. A major portion of the two protein variants was found in the cytosol. Immunofluorescence studies showed an even distribution of caspase‐12 within the cell, indicative for a cytoplasmatic localization. Transfection of AKR‐2B cells with wild‐type caspase‐12 showed a colocalization of this protein with the endoplasmic reticulum (ER). Unlike mouse embryonal fibroblasts (MEF) which contain wild‐type caspase‐12, AKR‐2B cells were largely resistant against treatment with the endoplasmatic reticulum stressing reagents brefeldin and tunicamycin. In AKR‐2B cells, cytoplasmatic caspase‐12 is bound to high molecular weight complexes of >1000 kDa [Cell Death Differ. 9 (2001) 125] and serum depletion leads to cleavage and detachment of caspase‐12 from this high molecular weight complex. Cleavage of caspase‐12 and ‐3 occurred almost simultaneously reaching a maximum 3–5 h after serum deprivation at which time also maximum apoptosis is found. Analysis of caspase‐12 cleavage in vitro in comparison with fragmentation in vivo suggests that during death in AKR‐2B cells induced by starvation, cleavage was brought about by caspase‐3 at positions D24 and D94. Thus, mutated caspase‐12 is differently integrated in signaling pathways of cell death and has lost its function as initiator caspase upon ER‐stress. Instead, it is turned into a substrate of effector caspases. The implication of these findings in the pathological phenotype of ARK‐2B mice is discussed.
Medical treatment of missed abortion using misoprostol
Authors: Ngoc N.T.N. , Blum J. , Westheimer E. , Quan T.T.V. , Winikoff B.
Published: September 2004

Objective: To compare the efficacy of two routes of misoprostol administration (oral and vaginal) for treatment of missed abortion. Methods:Two hundred women with confirmed missed abortion received 800 mcg misoprostol either orally or vaginally. All women returned for follow‐up care 2 days later. If the pregnancy was not completely evacuated at this time, women could wait an additional 5 days or undergo immediate surgical completion. Efficacy was defined as the percent of women discharged from the study without need for surgical intervention. Results:Efficacy was high in both groups and not statistically different (oral=89.0%, vaginal=92.9%). While the groups did not differ in terms of the completion rate by day 2 (oral=41.6%, vaginal=52.7%), the mean time to expulsion was longer (21.04 h) in the oral group than the vaginal group (13.47 h), p=0.041. Women in both groups were highly satisfied with the method. Conclusions:Medical management of missed abortion with either oral or vaginal misoprostol is highly effective and highly acceptable.
Ankle eversion torque response to sudden ankle inversion Torque response in unbraced, braced, and pre‐activated situations
Authors: Konradsen Lars , Peura Glenn , Beynnon Bruce , Renström Per
Published: September 2004

In 13 young ankle stable subjects, ankle eversion torque and peroneal EMG were simultaneously recorded in response to sudden ankle inversion. The eversion torque response was bi‐phasic. The initial development of torque, which was responsible for 30% of the maximal eversion torque response, was observed 135ms after the start of platform rotation and correlated well with the onset of the automatic postural peroneal EMG response. The remaining eversion torque response commenced after 305 ms, strongly correlating with the onset of the peroneal long latency voluntary EMG activity.

With the ankle unbraced, 66% of the maximal torque level was reached in 326ms. While braced, the same torque magnitude was reached using 230ms (p < 0.02), and pre‐activation of the peroneal muscles allowed the subjects to reach the same level of torque in 89ms (p < 0.0005).

Prior to the study, a common reaction pattern to sudden inversion was expected in an ankle stable population, but review of the eversion torque and EMG data from the 13 subjects revealed three different voluntary reaction patterns: 10 subjects showed an efficient activation of evertor muscles; two subjects stiffened their ankles with activation of both in‐ and evertor muscles; and one subject showed a marginal voluntary activation of the ankle evertors.

The results of the study indicate that the reaction to sudden ankle inversion is not solely automatic. The main part of the torque response is voluntarily mediated and inter‐individual differences in strategy seem to exist in healthy subjects. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Age‐related changes in electromyographic quadriceps activity during stair descent
Authors: Hinman Rana S. , Cowan Sallie M. , Crossley Kay M. , Bennell Kim L.
Published: September 2004

Purpose: To determine the effects of age on (i) the onset of vastus medialis obliquus (VMO) activity relative to that of vastus lateralis (VL) and (ii) the onset of quadriceps activity in terminal swing relative to heel‐strike, during stair descent.

Methods: Sixty‐six healthy men and women with no known knee pathology were recruited from the community and the University of Melbourne. Thirty‐three older people aged over 50 (mean (SD) 68 (8) years) and 33 younger people aged under 40 (mean (SD) 25 (4) years) participated. Surface electromyography (EMG) was used to record muscle activity during stair descent. Muscle onset was identified from individual EMG traces with a computer algorithm and validated visually.

Results: Both younger and older participants demonstrated a relatively synchronous onset of VMO and VL (i.e. within 10ms of each other) with no differences between the age groups evident (P = 0.262). However older participants activated their quadriceps significantly earlier than the younger group (P < 0.001) even when differences in body mass and speed of stair descent were accounted for.

Conclusion: Age‐related changes in quadriceps activity are apparent. The clinical implications of such changes are unknown, but increases in joint loading are possible. Earlier quadriceps activation may compensate for balance and strength impairments in older people during challenging activities. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
The effect of bone microstructure on the initiation and growth of microcracks
Authors: O'Brien Fergal J. , Taylor David , Lee T. Clive
Published: September 2004

Osteonal bone is often compared to a composite material and to metals as discontinuities within the material may provide sites of stress concentration for crack initiation and serve as barriers to crack growth. However, little experimental data exist to back up these hypotheses. Fluorescent chelating agents were applied at specific intervals to bone specimens fatigue tested in cyclic compression at a stress range of 80 MPa. The failed specimens were sectioned and labelled microcracks identified using UV epifluorescence microscopy. Microcrack lengths were measured and their relationship to cement lines surrounding secondary osteons recorded. Microcrack length at the time of encountering a cement line was also measured. Microcracks of less than 100 μm stopped growing when they encountered a cement line. Microcracks of greater than 100 μm in length continued to grow after encountering a cement line surrounding an osteon. Only microcracks greater than 300 μm in length were capable of penetrating osteons and these microcracks were the only ones which were observed to cause failure in the specimen. These experimental data support the hypothesis that secondary osteons act as barriers to crack propagation in compact bone. However, it shows that this microstructural barrier effect is dependent on the crack length at the time of encountering an osteon. For the vast majority of cracks, osteons act as barriers to growth but for the minority of cracks that are long enough and do break through the cement line, an osteon may actually act as a weakness in the bone and facilitate crack propagation. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Railway interests and the ‘rope of air’, 1840–8
Authors: ATMORE HENRY
Published: September 2004

This paper examines the usefulness of the category ‘interest’ in the history of technology through a case study of the failed attempt to introduce atmospheric railway traction in Britain in the 1840s. It argues for a reflective deployment of the term in question, sensitive to contemporary usages. A schematic typology of railway ‘interests’ shows just how various these were. Financial interests, for example, were not the same as professional ones; or an investor might feel the pull of contrary interests, depending on whether she was checking her dividends or taking a train. The history of atmospheric traction demonstrates the interlocking of railway ‘interests’, and their utility in explaining the success or failure of railway technologies. As might be expected, determinism, whether technological or ‘social’, does not answer the case. ‘Interest’ relations are contingent, and so must be understood the failure of the atmospheric railway.
Did Jenkin's swamping argument invalidate Darwin's theory of natural selection?
Authors: BULMER MICHAEL
Published: September 2004

Fleeming Jenkin's swamping argument (1867) is re-examined in relation to subsequent criticisms of its assumptions. Jenkin's original argument purported to show that, under blending inheritance, natural selection could not operate on ‘sports’ or ‘single variations’. A serious flaw in Jenkin's model was exposed in a forgotten paper in 1871. Darwin accepted Jenkin's ‘flawed’ conclusion, though he did not fully understand the argument. Both Jenkin and Darwin regarded the swamping argument as a barrier to evolution within a single lineage. A completely different interpretation of the phrase ‘swamping argument’, first put forward by Romanes in 1886, identified it with the problem of the role of free intercrossing in preventing speciation. The latter problem also underlies current debate about the possibility of sympatric speciation and is as serious under particulate as under blending inheritance. Jenkin's argument depended on the assumption of blending inheritance; when modified to remove the ‘flaw’ in his model, it ceased to present a barrier to the operation of natural selection within a lineage, provided that the mutation rate was high enough to maintain adequate genetic variability under blending.
Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions
Authors: Geisbert Thomas W. , Hensley Lisa E.
Published: September 2004

Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicised isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection.
Numerical simulation of turbulent, oscillatory flow over sand ripples
Authors: Barr Brian C. , Slinn Donald N. , Pierro Thomas , Winters Kraig B.
Published: September 2004

Turbulent oscillatory flow over sand ripples is examined using three‐dimensional numerical simulations. The model solves the time‐dependent Navier‐Stokes equations on a curvilinear grid in a horizontally periodic domain. The flow transitions to turbulence and the presence of sand ripples increases the rate of dissipation of shoaling wave energy compared to flow over a smooth boundary. The influence of the ripple shape is shown to alter the mean flow field and affect the induced drag and dissipation rates. Shear instabilities near the boundary during phases of flow reversal resulting in vortex shedding from the ripple crest produce a continuously turbulent boundary layer, differing from results obtained in simulations over smooth boundaries.
A three‐dimensional, multinutrient, and size‐structured ecosystem model for the North Atlantic
Authors: Lima Ivan D. , Doney Scott C.
Published: September 2004

We incorporate multinutrient and size‐structured ecosystem dynamics into a three‐dimensional ocean general circulation model for the North Atlantic. The model reproduces the magnitude and general spatial and temporal patterns in nutrients, chlorophyll and primary production seen in in situ (BATS, NABE, and OWSI) and satellite (SeaWiFS) data, showing substantial improvements over prior basin‐scale simulations. Model skill is evaluated quantitatively against SeaWiFS data using a Taylor diagram approach. Model‐data correlation R for the overall surface chlorophyll time‐space distribution is ∼0.6, with comparable model and observed total variability. The agreement relative to satellite‐based primary production is somewhat weaker (0.2 < R < 0.5). The simulations capture observed ecological characteristics, e.g., the dominance of picoplankton and episodic diatom blooms in the subtropics, nutrient‐controlled plankton succession at higher latitudes, and associated seasonal/depth changes in new and regenerated production and particle export. In a sensitivity experiment that mimics behavior of simpler single‐species models, removal of diatom silica limitation leads to major shifts in community structure and export and larger model‐data errors similar to previous model studies. Model results also suggest that episodic diatom blooms at BATS may be related to interannual variations in the southward transport of nutrients, mainly SiO3, and plankton cells.
Observation and model comparisons of the traveling atmospheric disturbances over the Western Pacific region during the 6–7 April 2000 magnetic storm
Authors: Lee Chien‐Chih , Liu Jann‐Yenq , Chen Ming‐Quey , Su Shin‐Yi , Yeh Huey‐Ching , Nozaki Kenro
Published: September 2004

The ionospheric features of traveling atmospheric disturbances (TADs) over the Western Pacific region have been observed by the Wuhan, NCU‐DPS, and Cebu ionosondes and the ROCSAT‐1 satellite during the 6–7 April 2000 magnetic storm. The nighttime observations are further compared with the simulation results of the Thermosphere‐Ionosphere Electrodynamics General Circulation Model (TIEGCM). Both observation and model demonstrate that the TADs propagate equatorward with a phase speed of 610–650 m/s. The observations and corresponding TIEGCM simulations show a negative initial correlation between NmF2 and HmF2 caused by equatorward wind surges at various locations from midlatitudes to the equator. These qualitative agreements reveal that the TIEGCM is capable of simulating the TADs. The TIEGCM simulations of two locations located in the downwind hemisphere further show decreases in NmF2 and HmF2 mainly due to the enhanced transequatorial winds. After lowering the F2 layer at the two locations, the HmF2 is raised for several hours and shows slightly enhanced NmF2 daytime values while the meridional wind is at background magnitude. We propose that this effect is caused by accumulation of plasma transported from northern latitudes. However, we also find that the NmF2, HmF2, and the lifetimes of HmF2 uplift phase and equatorial vertical drift in the model results are quantitatively inconsistent with that in the observed data.
Stick‐slip motion in simulated granular layers
Authors: Aharonov Einat , Sparks David
Published: September 2004

Two‐dimensional numerical simulations of shear in a gravity‐free layer of circular grains were conducted to illuminate the basic mechanics of shear of granular layers (such as layers of fault gouge). Our simulated granular layers exhibit either stable (steady state) or unstable (stick slip) motion. The transition from steady to stick‐slip sliding depends on loading velocity and applied confining stress in a way similar to a simple model of a block on a frictional surface. We investigate the conditions which lead to naturally occurring stick‐slip behavior and study in detail the systems behavior prior to and during slip events. Matching our numerical results to a spring block model, the system of grains was found to have bulk static and dynamic coefficients of friction that differ by about 0.1. This differing static and dynamic friction emerged spontaneously, from the collective behavior of grains, and was not prescribed a priori via a frictional rule between grain contacts. Results show that the micromechanics of contact forces is responsible for stick‐slip behavior: During the “stuck” phase, and in preparation for slip, more and more grain contacts which carry low forces slide, resulting in accelerating internal stress release. When enough of the low‐force contacts frictionally slide, the granular layer weakens and losses rigidity, leading to motion of contacts that carry larger forces and large‐scale slip. Our results may have implications to the understanding of the stability of gouge layers and are thus related to the underlying physics of earthquakes.