bluuebunny/crossref_metadata_2025 huggingface dataset:
H2O2 induces abnormal tail flexure in Xenopus embryos: similarities with Paraquat teratogenic effects
Authors: Vismara Claudio , Bacchetta Renato , Di Muzio Andrea , Mantecca Paride , Tarca Silvia , Vailati Giovanni , Colombo Roberto
Published: June 2006

BACKGROUND: As previously shown, Paraquat (PQ) treatments of Xenopus developing embryos mainly induce a characteristic developmental alteration we named “abnormal tail flexure.” PQ oxidative activity has been indicated as the cause of this malformation. Since PQ evokes reactive oxygen species (ROS), among which hydroxyl radicals (OH•), and H2O2 can be converted to (OH•) via Fenton reaction, we compared here the lethal and teratogenic potentials of both oxidants by using the Frog Embryo Teratogenesis Assay‐Xenopus (FETAX), in order to grasp eventual similarities in their teratogenic activity. METHODS: Xenopus embryos were exposed, from stage 8 to stage 47, at 368, 491, 612, and 735 µM H2O2 and 0.388 µM PQ. The probit analysis of H2O2 mortality and malformed larva percents gave a 598.82 µM Lethal Concentration 50% (LC50) and 536.04 µM Teratogenic Concentration 50% (TC50) from which a 1.11 Teratogenic Index (T.I.) has been calculated. This T.I. value should allow the classification of H2O2 as a non‐teratogenic compound. RESULTS: A comparison of H2O2 mortality and malformed larva percents with those obtained from PQ exposure showed the higher embryotoxicity of PQ, but, markedly, both compounds mainly induced the “abnormal tail flexure.” Histological analysis of both H2O2 and PQ malformed embryo tails showed a similar distorted morphology of both somites and myocytes. Some of muscle cells were necrotic and affected by an apical enlargement as well as a detachment from the connective tissue of intersomitic boundaries. CONCLUSIONS: In our opinion, both of the tested chemicals likely weaken the mechanical bridge connecting the myocyte contractile apparatus to the extracellular matrix, therefore causing the detachment of some of tail myocytes from their connectival septum as well as their apical enlargement. This could lead to the unbalance of tail tensional forces and, in turn, to the appearance of the “abnormal tail flexure.” Birth Defects Research (Part B) 77:238–243, 2006. © 2006 Wiley‐Liss, Inc.
Second virial coefficient determination of a therapeutic peptide by self‐interaction chromatography
Authors: Payne Robert W. , Nayar Rajiv , Tarantino Ralph , Terzo Sam Del , Moschera John , Di Jie , Heilman David , Bray Brian , Manning Mark Cornell , Henry Charles S.
Published: June 2006

Self‐interaction of macromolecules has been shown to play an important role in a number of physical processes, including crystallization, solubility, viscosity, and aggregation. Peptide self‐interaction is not as well studied as for larger proteins, but should play an equally important role. The osmotic second virial coefficient, B, can be used to quantify peptide and protein self‐interaction. B values are typically measured using static light scattering (SLS). Peptides, however, do not scatter enough light to allow such measurements. This study describes the first use of self‐interaction chromatography (SIC) for the measurement of peptide B values because SIC does not have the molecular size limitations of SLS. In the present work, SIC was used to measure B for enfuvirtide, a 36‐amino acid therapeutic peptide, as a function of salt concentration, salt type, and pH. B was found to correlate strongly with solubility and apparent molecular weight. In general, the solubility of enfuvirtide increases with pH from 6 to 10 and decreases as the salt concentration increases from 0 to 0.5M for three different salts. The effect of peptide concentration on B was also investigated and shown to have a significant effect, but only at high concentrations (>80 mg/mL). © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 527–533, 2006
Impact of natural reforestation on floodplain sedimentation in the Dragonja basin, SW Slovenia
Authors: Keesstra S. D.
Published: June 2006

Changes in floodplain sediment dynamics have profound effects on riverine habitats and riparian biodiversity. Depopulation due to socio‐economic changes in the Dragonja catchment (91 km2) in southwestern Slovenia resulted in the abandonment of agricultural fields, followed by natural reforestation since 1945. This profoundly changed the water and sediment supply to the streams, as well as floodplain sediment deposition.

This paper presents a reconstruction of the development of the Dragonja floodplain due to these land use changes during the last 60 years. The reconstruction is based on dating of floodplain sediments using 137Cs profiles, measurement of actual sedimentation rates using artificial grass sedimentation mats, and linking this information to the present‐day hydrological behaviour of the river. The sedimentation mats showed that floodplain sedimentation was restricted to peak flows of considerable magnitude. Due to the reforestation, the return period of such high flows increased from 0·31 year in the period 1960–1985 to 0·81 year between 1986 and 2003, with commensurate changes in sedimentation rates. At the 1·5 m river terrace (formed about 60 years ago), 137Cs‐based sedimentation rates (1960–1986) were roughly twice the rates inferred from the artificial grass mats (2001–2003). This finding matches the increase in the return period for larger peak events during the 1986–2003 period, which caused fewer major inundations at this level. Conversely, sedimentation rates determined for the lowest terrace at 0·5 m were similar for both techniques (and periods) because the return periods of the peak events responsible for sediment deposition at this lower level did not change much over the period 1986–2003. Copyright © 2006 John Wiley & Sons, Ltd.
Strategies for fault classification in transmission lines, using learning vector quantization neural networks
Authors: Mazón A. J. , Zamora I. , Sagastabeitia K. J. , Valverde V.
Published: June 2006

This paper analyses different approaches to fault classification, in two‐terminal overhead transmission lines, using learning vector quantization (LVQ) neural networks, just verifying its efficiency. The objective is to classify the fault using the fundamental components of 50/60 Hz of fault and pre‐fault voltage and current magnitudes. These magnitudes are measured in each phase at the reference end. The accuracy of these methods has been checked using properly validated fault simulation software developed with MATLAB. This software allows simulating faults in any location of the line, to obtain the fault and prefault voltage and current values. With these values, the fault can be classified. Copyright © 2006 John Wiley & Sons, Ltd.
Brain maturation in adolescence: Concurrent changes in neuroanatomy and neurophysiology
Authors: Whitford Thomas J. , Rennie Christopher J. , Grieve Stuart M. , Clark C. Richard , Gordon Evian , Williams Leanne M.
Published: June 2006

Adolescence to early adulthood is a period of dramatic transformation in the healthy human brain. However, the relationship between the concurrent structural and functional changes remains unclear. We investigated the impact of age on both neuroanatomy and neurophysiology in the same healthy subjects (n = 138) aged 10 to 30 years using magnetic resonance imaging (MRI) and resting electroencephalography (EEG) recordings. MRI data were segmented into gray and white matter images and parcellated into large‐scale regions of interest. Absolute EEG power was quantified for each lobe for the slow‐wave, alpha and beta frequency bands. Gray matter volume was found to decrease across the age bracket in the frontal and parietal cortices, with the greatest change occurring in adolescence. EEG activity, particularly in the slow‐wave band, showed a similar curvilinear decline to gray matter volume in corresponding cortical regions. An inverse pattern of curvilinearly increasing white matter volume was observed in the parietal lobe. We suggest that the reduction in gray matter primarily reflects a reduction of neuropil, and that the corresponding elimination of active synapses is responsible for the observed reduction in EEG power. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Preparation and magnetic resonance imaging effect of polyvinylpyrrolidone‐coated iron oxide nanoparticles
Authors: Lee Ha Young , Lim Nak Hyun , Seo Jin A. , Yuk Soon Hong , Kwak Byung Kook , Khang Gilson , Lee Hai Bang , Cho Sun Hang
Published: June 2006

Polyvinylpyrrolidone (PVP)‐coated iron oxide nanoparticles were prepared by the thermal decomposition of Fe(CO)5 (iron pentacarbonyl) in one step. X‐ray diffraction (XRD), transmission electron microscopy (TEM), electrophoretic light scattering (ELS), infrared spectroscopy (FTIR) and X‐ray photoelectron spectroscopy (XPS) together with the variation of the molar ratio of PVP/Fe(CO)5, solvent, and molecular weight of PVP, were used to characterize the PVP‐coated iron oxide nanoparticles. Fifty to hundred nanometer‐sized iron oxide nanoclusters with a spherical shape were formed in dimethylformamide (DMF), used as a solvent, and exhibited an enhanced stability in the aqueous media. Their magnetic properties were investigated by superconducting quantum interface device (SQUID). The in vitro cytotoxicity test revealed that the PVP‐coated iron oxide nanoparticles exhibited excellent biocompatibility by MTT assay. Magnetic resonance imaging (MRI) effect was observed with the administration of PVP‐coated iron oxide nanoparticles through the marginal vein of rabbit, resulting in improved detection of the liver lesions. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Effect of sterilization on the physicochemical properties of molded poly(L‐lactic acid)
Authors: Peniston Shawn J. , Choi Sun J.
Published: June 2006

In this study, the process of manufacturing and sterilizing an orthopedic implant constructed from poly(L‐lactic acid) (PLLA) was closely simulated. The hydrogen peroxide gas plasma (HPGP) sterilization process was comparatively investigated against ethylene oxide (EtO). Characterization of the physical, thermal, mechanical, morphological, and chemical properties was monitored. The results indicate that the HPGP sterilization process did not have a significant influence on Mn or Mw initially or through 12 weeks of in vitro conditioning when compared with EtO. Only indications of physical aging were evident in the analysis of the thermal and mechanical properties by differential scanning calorimeter and tensile testing for each sterilization processes. Using wide angle X‐ray diffraction to determine morphology characteristics, it was determined that no changes were observed between the as molded, HPGP, and EtO specimens initially or through the 12 week in vitro conditioning period. Contact angle measurements revealed a significant reduction in the surface energy following treatment by the HPGP process, suggesting the formation of polar groups. However, surface chemistry analysis by ATR‐FTIR indicated no significant chemical modification from either sterilization method. PLLA showed intermediate levels of residual hydrogen peroxide absorption following processing by HPGP. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Effect of cyclic loading and environmental aging on the fracture toughness of dental resin composite
Authors: Ravindranath Viswanath , Gosz Michael , De Santiago Eduardo , Drummond James L. , Mostovoy Sheldon
Published: June 2006

Objective

The main purpose of this study was (1) to investigate the effects of cyclic loading and environmental aging on three dental resin composites with different filler compositions: a fiber filler, a hybrid filler, and a microfill; and (2) to predict fracture in dental resin composite under mixed‐mode loading conditions.

Methods

Diametral disk specimens 25 mm in diameter and 2 mm in thickness were used in this study. Two methods were used for generating initial cracks in the specimen. The first method involved machining a 3‐mm notch in the center of the disk specimens, and then the notch tips were sharpened with a 0.2‐mm‐diameter jeweler's saw blade. In the second method for obtaining sharper crack tips, a three‐way wedge was forced into a 3.175‐mm hole drilled in the center of the specimen, resulting in sharp cracks emanating from the notch tips.

Cyclic Tests

The specimens were aged for 4 months in air, water, artificial saliva, and a 50/50 (by volume) mixture of ethanol and water at room temperature in sealed polyethylene containers. Both unaged and aged specimens (5 specimens for each variable) were subjected to cyclic loading at a frequency of 5 Hz with sinusoidal loads cycling for 1, 1000, and 100,000 cycles at a load level ∼60% of the fracture load for noncycled specimens. Following load cycling, the specimens were tested in compression in a displacement‐controlled loading mode at a loading rate of 1.27 mm/min.

Results

Test results show that aging in a 50/50 alcohol–water mixture lowered the fracture toughness of dental resin composite, which was further reduced by cyclic loading.

Mixed‐mode tests

The maximum tensile stress (MTS) criterion was used to predict fracture in dental resin composite under mixed‐mode loading conditions. The loads at failure were used as input into a finite element model. After obtaining the stress field in the specimens by the finite element method, the mixed‐mode stress intensity factors were calculated using an interaction energy integral method.

Results

Good agreement was obtained between the fracture envelope predicted by the MTS criterion and the experimental fracture toughness data. Hence, it can be concluded that it is only necessary to characterize the mode I fracture toughness to fully characterize the mixed‐mode behavior of the dental resin composites that were considered in the present study. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Application of crosslinkers to dentin collagen enhances the ultimate tensile strength
Authors: Bedran‐Russo Ana Karina B. , Pereira Patricia N. R. , Duarte Wagner R. , Drummond James L. , Yamauchi Mitsuo
Published: June 2006

The stabilization of dentin collagen with biocompatible crosslinking agents may be of clinical importance to improve dentin bond strength. The present study aimed to evaluate the effect of three collagen crosslinking agents on the ultimate tensile strength (UTS) of undemineralized and demineralized dentin. Ten freshly extracted sound molars were sectioned into 0.5 × 0.5 mm2 thick beams. The beams were either demineralized or kept undemineralized. Then, specimens were subdivided into four groups according to treatments—PBS solution (control), 5% glutaraldehyde (GD), 0.5% proanthocyanidin PBS solution (PA), and 0.625% genipin PBS solution (GE). Specimens were kept in their respective solutions for either 4 or 40 h. To assess UTS, specimens were subjected to tensile forces at a crosshead speed of 1 mm/min. Statistical analysis was performed using two‐way ANOVA and Fisher's PLSD test (p < 0.05). Statistically significant increases in UTS were observed for demineralized dentin after PA and GE dentin treatment, when compared with those of the control group. Dentin treated with GD showed no statistically significant differences in UTS when compared with that the control. Undemineralized dentin revealed no significant differences as compared to that of the control, regardless of the collagen crosslinkers. The application of two naturally occurring crosslinkers, i.e., PA and GE, to dentin collagen significantly improves UTS, indicating its potential value in restorative dentistry. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Application of chitosan gel in the treatment of chronic periodontitis
Authors: Akıncıbay Hakan , Şenel Sevda , Yetkin Ay Z.
Published: June 2006

Local administration of antibiotics in periodontal therapy can be provided with an appropriate delivery system. The purpose of this study was to evaluate the clinical effectiveness of chitosan, both as a carrier in gel form and as an active agent in the treatment of chronic periodontitis (CP). The chitosan gel (1% w/w) incorporated with or without 15% metronidazole was prepared and applied adjunctive to scaling and root planing (SRP) in comparison to SRP alone (control group‐C), in CP patients. The clinical parameters such as probing depth (PD), clinical attachment level, the amount of gingival recession, plaque index, gingival index, and gingival bleeding time index were recorded at baseline and at weeks 6, 12, and 24. In all groups, significant improvements were observed in clinical parameters between baseline and week 24 (p < 0.05). The reductions in PD values were 1.21 mm for Ch, 1.48 mm for Ch + M, and 0.94 mm for C groups. No complications related to the chitosan were observed in patients throughout the study period. It is suggested that chitosan itself is effective as well as its combination with metronidazole in CP treatment due to its antimicrobial properties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Achieving plane‐wise uniform B1 amplitude in a 3D volume for high‐field MRI: A computer simulation study
Authors: Wang Zhiyue J. , Chu Zili
Published: June 2006

Purpose

To demonstrate the possibility of achieving plane‐wise uniform B1 field amplitude for human head imaging with an array coil configuration by using computer simulations.

Materials and Methods

We considered the use of an excitation array coil that employed composite excitation elements. Each composite excitation element consisted of three small current loops centered close to each other with axes along the x, y, and z directions, respectively. The excitation elements were distributed to surround a model human head. The vector B1 field from each current loop was calculated using the FDTD numerical method at 170 MHz. Analytical target RF field patterns with plane‐wise uniform B1 field amplitude were derived and approximately constructed from the fields of individual current loops through a least‐squares procedure.

Results

The RF field patterns generated by the computer simulations closely followed the target field patterns. Highly uniform B1 field amplitude was obtained within parallel sagittal planes or parallel axial‐to‐coronal oblique planes in the brain with the expected plane‐to‐plane variations.

Conclusion

In principle, patterns of B1 amplitude distribution with a high degree of plane‐wise homogeneity can be achieved simultaneously in multiple parallel planes in a 3D volume. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
The role of junctional adhesion molecule C (JAM‐C) in acute pancreatitis
Authors: Vonlaufen A , Aurrand‐Lions M , Pastor CM , Lamagna C , Hadengue A , Imhof BA , Frossard J‐L
Published: June 2006

The recruitment of inflammatory cells contributes significantly to tissue injury in acute pancreatitis. This process implies several molecular interactions between circulating and endothelial cells. The adhesion molecule junctional adhesion molecule C (JAM‐C) is involved in leukocyte transendothelial migration and it can form homophilic (JAM‐C/JAM‐C) and heterophilic interactions with the leukocyte integrin αMβ2. In this study, the effect of early administration of monoclonal antibodies directed against JAM‐C in cerulein‐induced acute pancreatitis was assessed. This reagent significantly blocked influx of leukocytes, release of serum amylase, secretion of inflammatory cytokines, and acinar cell necrosis. These effects were rapid and protected against tissue injury throughout the duration of the model. Conversely, cerulein‐induced acute pancreatitis was more severe in transgenic mice overexpressing JAM‐C on endothelial cells under the control of the Tie2 promoter. It is proposed that JAM‐C expressed by endothelial cells contributes to the pathophysiology of acute pancreatitis and could be considered a target for clinical applications. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Protection against chemotherapy induced mucositis by TGF‐β2 in childhood cancer patients: Results from a randomized cross‐over study
Authors: de Koning Barbara A.E. , Philipsen‐Geerling Bertine , Hoijer Maarten , Hählen Karel , Büller Hans A. , Pieters Rob
Published: June 2006

Background

Mucositis is one of the most frequent and severe side‐effect of chemotherapy in childhood‐cancer patients for which there is no prophylaxis available. The efficacy and feasibility of a TGF‐β2‐enriched feeding for preventing oral and gastro‐intestinal‐mucositis in childhood‐cancer patients were studied.

Procedure

The study was designed as a two‐period cross‐over, randomized, double‐blinded, placebo, controlled trial. Patients who had a high risk for developing mucositis and who would receive two comparable cycles of chemotherapy were eligible for the study. During one cycle of chemotherapy, TGF‐β2‐enriched feeding was administered; during the other, a “placebo” (not enriched) feeding was used. WHO toxicity scales of diarrhea, oral mucositis, fever, anal lesions and nausea/vomiting were scored daily. In addition, the incidence of occurrence of blood cultures, antibiotic therapy, and interventions or diagnostics related to mucositis were measured.

Results

The feasibility of the study was good: 83% of the patients completed two cycles and 86% of the study‐feeding was effectively consumed. Administration of TGF‐β2 was safe as serum TGF‐β2 did not increase, and renal and liver function were not affected during TGF‐β2 consumption compared to normal feeding. Differences in toxicity, scored during the whole observation period and the number of days with WHO 3/4 toxicity, were not significantly different between cycles with TGF‐β2 enriched and normal feeding.

Conclusions

TGF‐β2 administration via feeding is well tolerated and safe. Although this study might have had limitations to show potential benefit of TGF‐β2, it does not provide evidence that TGF‐β2 decreases the incidence or degree of mucositis induced by combination chemotherapy in childhood‐cancer patients. Pediatr Blood Cancer 2007;48:532–539. © 2006 Wiley‐Liss, Inc.
First‐ and second‐trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study
Authors: Lambert‐Messerlian G. , Dugoff L. , Vidaver J. , Canick J. A. , Malone F. D. , Ball R. H. , Comstock C. H. , Nyberg D. A. , Saade G. , Eddleman K. , Klugman S. , Craigo S. D. , Timor‐Tritsch I. E. , Carr S. R. , Wolfe H. M. , D'Alton M. E.
Published: June 2006

Objective

To determine whether first‐ and second‐trimester Down syndrome screening markers and screen‐positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs).

Methods

ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF‐OI), IVF with OI and egg donation (IVF‐OI‐ED), IVF with ED (IVF‐ED), and intrauterine insemination with OI (IUI‐OI) or without OI (IUI). Each group was compared to non‐ART controls using Mann–Whitney U analysis.

Results

First‐trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP‐A levels in the IUI‐OI group. In contrast, second‐trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha‐fetoprotein (AFP) was increased in ED pregnancies. Second‐trimester screen‐positive rates were significantly higher than expected for ART pregnancies, except when ED was used.

Conclusions

These data show that ART significantly impacts second‐, but not first‐, trimester markers and screen‐positive rates. The type of adjustment needed in second‐trimester screening depends on the particular type of ART used. Copyright © 2006 John Wiley & Sons, Ltd.
Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopic analysis of telechelic polythiourethanes obtained by the cationic ring‐opening polymerization of six‐membered cyclic thiourethane
Authors: Nagai Daisuke , Sato Masato , Ochiai Bungo , Endo Takeshi
Published: June 2006

A matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectroscopy analysis of polythiourethanes obtained by the cationic ring‐opening polymerization of a six‐membered cyclic thiourethane [3‐benzyltetrahydro‐1,3‐oxazine‐2‐thione (BTOT)] is described. A MALDI‐TOF mass spectrum of a polymer obtained by the polymerization of BTOT with boron trifluoride etherate (BF3OEt2) as the initiator in nitrobenzene at 50 °C for 24 h followed by an end‐capping reaction with diethyldithiocarbamic acid diethylammonium salt showed a series of well‐resolved signals that were assignable to polythiourethanes possessing an amino group at the initiating end and a diethyldithiocarbamate group at the terminating end. In comparison with the MALDI‐TOF mass spectra of polymers obtained by polymerization with trifluoromethanesulfonic acid or methyl trifluoromethanesulfonate, the plausible initiating species in the polymerization with BF3OEt2 was estimated to be a proton, which successively eliminated carbonyl sulfide to produce a secondary amine group at the initiating end. The secondary amine group in the obtained telechelic polymer was converted to a tertiary amine group by a reaction with benzyl bromide in the presence of triethylamine, and this was confirmed by MALDI‐TOF mass spectroscopy. Furthermore, a telechelic polymer with a pyrrole end group was successfully synthesized by the end‐capping reaction of the growing species in the polymerization of BTOT with sodium 1‐pyrrolecarbodithioate. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4281–4289, 2006
Charge density effects in salt‐free polyelectrolyte solution rheology
Authors: Dou Shichen , Colby Ralph H.
Published: June 2006

Solution rheology of 2‐vinyl pyridine andN‐methyl‐2‐vinyl pyridinium chloride random copolymers in ethylene glycol was studied over wide ranges of concentration and effective charge. The fraction of quaternized monomers α and the fraction of monomers bearing an effective chargefof these copolymers were measured using counterion titration and dielectric spectroscopy, respectively. Ethylene glycol is a good solvent for neutral poly(2‐vinyl pyridine), with very few ionic impurities. The viscosity η and relaxation time τ of dilute and semidilute unentangled solutions exhibit the scaling with concentration and effective charge expected by the Dobrynin model. Reduced viscosity data are independent of concentration in dilute solution, giving an intrinsic viscosity that depends on effective charge, and the experimental data obey the Fuoss law in the semidilute unentangled regime. Scaling concentration with the overlap concentration (c/c*) reduces these data to common curves, andc*∼f−12/7as predicted by the Dobrynin model, wherefis the fraction of monomers bearing an effective charge. While the overlap concentration depends strongly on effective charge until counterion condensation occurs, the entanglement concentrationceis surprisingly insensitive to effective charge, indicating that entanglement effects are not understood using the Dobrynin model. The terminal modulusG= η/τ depends only on the number density of chainsG=ckT/Nforc* <cceindependent of the effective charge. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2001–2013, 2006
Atomic structure and relative stability of gallium and nitrogen interstitials in GaN [0001] grain boundaries
Authors: Béré A. , Belabbas I. , Petit S. , Nouet G. , Ruterana P. , Chen J. , Koulidiati J.
Published: June 2006

The atomic and electronic structures of gallium and nitrogen interstitial created at the 8‐interface of the (2$\bar 5$30) Σ = 19 (θ = 13.2°) tilt grain boundary in GaN were investigated by density‐functional based tight‐binding calculations. We found that the structure of lowest energy of the Ga‐ or N‐interstitial boundary is formed by a mixture of 6‐ and 5/7‐atom rings (Gai‐ or Ni‐interface) which is comparable to that of the 5/7‐interface. The calculations show that the non stoichiometric Gai‐interface is energetically more stable than the stoichiometric 5/7‐interface, suggesting that both configurations may exist. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of enhanced temperature and pressure on structural transformations in pre‐annealed Cz‐Si
Authors: Ciosek Jerzy , Misiuk Andrzej , Surma Barbara , Shchennikov Vladimir V.
Published: June 2006

Oxygen‐related defects in oxygen‐containing Czochralski silicon (Cz‐Si) subjected to one or 4‐steps pre‐annealing at 720–1000 K under 105 Pa and next treated at 1170–1400 K (HT) under high hydrostatic pressure (HP, up to 1.2 GPa) were investigated by photoluminescence (PL) and microhardness measurements as well as by spectroscopic reflectrometry. Microstructure of HT‐HP treated Cz‐Si is dependent on nucleation centres for oxygen precipitation created by pre‐annealing and on applied pressure. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Behaviour of the AlN cap during GaN implantation of rare earths and annealing
Authors: Gloux Florence , Wójtowicz Tomasz , Ruterana Pierre , Lorenz K. , Alves E.
Published: June 2006

The structural evolution of 10 nm AlN caps grown on GaN layers has been investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) after growth, and implantation by rare earths ions and annealing at high temperature. The AlN cap relaxation is shown to take place by pinholes formation. During annealing at 1300 °C, pinhole‐free areas of the AlN cap protect the GaN layer and allow efficient optical activation of the rare earths dopants. Through pinholes, an explosive dissociation of the GaN layer occurs. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Feasibility of different mass spectrometric techniques and programs for automated metabolite profiling of tramadol in human urine
Authors: Hakala Kati S. , Kostiainen Risto , Ketola Raimo A.
Published: June 2006

The purpose of the study was to determine the advantages of different mass spectrometric instruments and commercially available metabolite identification programs for metabolite profiling. Metabolism of tramadol hydrochloride and the excretion of it and its metabolites into human urine were used as a test case because the metabolism of tramadol is extensive and well known. Accurate mass measurements were carried out with a quadrupole time‐of‐flight mass spectrometer (Q‐TOF) equipped with a LockSpray dual‐electrospray ionization source. A triple quadrupole mass spectrometer (QqQ) was applied for full scan, product ion scan, precursor ion scan and neutral loss scan measurements and an ion trap instrument for full scan and product ion measurements. The performance of two metabolite identification programs was tested. The results showed that metabolite programs are time‐saving tools but not yet capable of fully automated metabolite profiling. Detection of non‐expected metabolites, especially at low concentrations in a complex matrix, is still almost impossible. With low‐resolution instruments urine samples proved to be challenging even in a search for expected metabolites. Many false‐positive hits were obtained with the automated searching and manual evaluation of the resulting data was required. False positives were avoided by using the higher mass accuracy Q‐TOF. Automated programs were useful for constructing product ion methods, but the time‐consuming interpretation of mass spectra was done manually. High‐quality MS/MS spectra acquired on the QqQ instrument were used for confirmation of the tramadol metabolites. Although the ion trap instrument is of undisputable benefit in MSn, the low mass cutoff of the ion trap made the identification of tramadol metabolites difficult. Some previously unreported metabolites of tramadol were found in the tramadol urine sample, and their identification was based solely on LC/MS and LC/MS/MS measurements. Copyright © 2006 John Wiley & Sons, Ltd.
Therapy through chaperones: Sense or antisense? Cystic fibrosis as a model disease
Authors: Amaral Margarida D.
Published: June 2006

Massive production and accumulation of a single abnormal protein may constitute a major toxic burden for the cell and even compromise the organism's long‐term viability. Consequently, adaptation and survival have forced evolution to create ‘quality control’ mechanisms that detect, monitor, and often degrade such abnormally folded gene products, in which molecular chaperones are key players. Notwithstanding this, there are numerous examples of misfolded proteins which, in spite of being recognized as aberrant and efficiently discarded by cellular quality control, still retain some of the functional properties of their wild‐type counterparts, so that their maintenance in the cell would be beneficial for the organism. Herein are described the cellular roles of molecular chaperones and some new insights on the mechanisms by which they influence the development of human diseases caused by mutations that lead to protein misfolding. A special emphasis is given to cystic fibrosis, a classical genetic disorder resulting from the retention and degradation of a mutant, albeit functional, protein by the endoplasmic reticulum quality control. This particular system has been a good example to describe the mechanisms that are likely to be shared by a number of protein substrates, to define the common characteristics of the mutants, as well as to identify the mechanistic intervenients in their retention and degradation. Finally, new approaches aimed at correcting protein folding defects are discussed, including the potential of molecular chaperones (e.g., through RNA interference) as novel therapeutic targets, and the usage of chemical or pharmacological chaperones as new therapeutic agents.
Hepatocyte transplantation: Studies in preclinical models
Authors: Weber Anne , Mahieu‐Caputo Dominique , Hadchouel Michelle , Franco Dominique
Published: June 2006

Transplantation of allogeneic or genetically modified autologous hepatocytes may be an alternative to whole‐liver transplantation for the treatment of hereditary metabolic liver diseases. Human hepatocytes have already been transplanted in patients, demonstrating the safety and feasibility of both approaches. Although a few cases of allogeneic transplantation have resulted in long‐term engraftment and function, only a partial and transient correction of the disease was achieved. This may partly result from a lack of proliferation of transplanted cells. In rodents, transplanted hepatocytes do not proliferate in adult quiescent livers and repopulate recipient livers only when they display a proliferative advantage over resident hepatocytes. Most of these models are not transposable to humans, however. Our aim is to develop preclinical approaches to hepatocyte transplantation in nonhuman primates. We have defined a strategy that increases the engraftment efficiency of transplanted hepatocytes by inducing their proliferation together with that of resident hepatocytes. We have also immortalized simian fetal hepatic progenitor cells and shown that these cells do not proliferate in situ after transplantation into the livers of immunodeficient mice. By contrast early human hepatoblasts repopulate mouse livers more efficiently. However, if we consider the number of cells to be transplanted (one to several billion), the means of expanding and differentiating stem or progenitor cells other than hepatocytes will have to be determined prior to envisaging treating patients.
Substrate reduction therapy of glycosphingolipid storage disorders
Authors: Aerts Johannes M. F. G. , Hollak Carla E. M. , Boot Rolf G. , Groener Johanna E. M. , Maas Mario
Published: June 2006

In the last 15 years enormous progress has been made regarding therapy of type I Gaucher disease, a severely disabling disorder characterized by intralysosomal storage of glucosylceramide in tissue macrophages. Effective enzyme replacement therapy of type I Gaucher disease, based on chronic intravenous administration of mannose‐terminated recombinant human glucocerebrosidase, has been available since 1990 and has been applied in several thousand patients without serious adverse effects. An alternative therapeutic approach, so‐called substrate reduction therapy, is based on partial reduction of the synthesis of glucosylceramide and hence of subsequent metabolites. Oral administration of an inhibitor of glucosylceramide synthesis (N‐butyldeoxynojirimycin, registered in Europe since 2002 as miglustat (Zavesca)), is effective in reversing clinical symptoms in type I Gaucher patients with mild to moderate disease manifestations. The growing long‐term experience with substrate reduction therapy indicates that this treatment is also without major adverse effects. Substrate reduction therapy, in conjunction with enzyme replacement therapy, may play an important role in the future clinical management of patients suffering from type I Gaucher disease. Clinical trials are under way that should reveal the value of substrate reduction for maintenance therapy of type I Gaucher disease and for treatment of neuronopathic variants of Gaucher disease, Niemann–Pick disease type C, late‐onset Tay–Sachs disease and Sandhoff disease.
β‐Galactosidase deficiency: An approach to chaperone therapy
Authors: Suzuki Yoshiyuki
Published: June 2006

We propose a new molecular therapeutic approach to lysosomal diseases with severe neurological manifestations. Some low‐molecular‐weight compounds, acting as competitive inhibitors of a lysosomal enzyme in vitro, were found to stabilize and restore catalytic activities of the enzyme molecule as a molecular chaperone. We started this trial first in Fabry disease (generalized vasculopathy) using galactose and 1‐deoxygalactonojirimycin, and then in β‐galactosidase deficiency disorders (β‐galactosidosis) with generalized neurosomatic and/or systemic skeletal manifestations (GM1‐gangliosidosis and Morquio B disease), using a newly developed chemical compound N‐octyl‐4‐epi‐β‐valienamine (NOEV). Administration of this chaperone compound resulted in elevation of intracellular enzyme activity in cultured fibroblasts from patients and genetically engineered model mice. In addition, substrate storage was improved after NOEV had been transported into the brain tissue via the blood–brain barrier. We hope this new approach (chemical chaperone therapy) will be useful for certain patients with β‐galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
Anaplerotic diet therapy in inherited metabolic disease: Therapeutic potential
Authors: Roe Charles R. , Mochel Fanny
Published: June 2006

Beginning with phenylketonuria, dietary therapy for inborn errors has focused primarily on the restriction of the precursor to an affected catabolic pathway in an attempt to limit the production of potential toxins. Anaplerotic therapy is based on the concept that there may exist an energy deficit in these diseases that might be improved by providing alternative substrate for both the citric acid cycle (CAC) and the electron transport chain for enhanced ATP production. This article focuses on this basic problem, as it may relate to most catabolic disorders, and provides our current experience involving inherited diseases of mitochondrial fat oxidation, glycogen storage, and pyruvate metabolism using the anaplerotic compound triheptanoin. The observations have led to a realization that ‘inter‐organ’ signalling and ‘nutrient sensors’ such as adenylate monophosphate mediated‐protein kinase (AMPK) and mTOR (mammalian target of rapamycin) appear to play a significant role in the intermediary metabolism of these diseases. Activated AMPK turns on catabolic pathways to augment ATP production while turning off synthetic pathways that consume ATP. Information is provided regarding the inter‐organ requirements for more normal metabolic function during crisis and how anaplerotic therapy using triheptanoin, as a direct source of substrate to the CAC for energy production, appears to be a more successful approach to an improved quality of life for these patients.
Newborn screening for medium‐chain acyl‐CoA dehydrogenase deficiency: A global perspective
Authors: Rhead William J.
Published: June 2006

As judged by tandem mass spectrometry blood spot screening, the incidence of medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency is 1:14 600 (CI 95%: 1:13 500–1:15 900) in almost 8.2 million newborns worldwide and is 2‐ to‐3 fold higher than that identified in the same populations after clinical presentation. In mass‐screened newborn populations, the 985A>G (K329E) mutation accounts for 54–90% of disease alleles, with homozygotes representing about 47–80% of MCAD deficiency cases. Worldwide, octanoylcarnitine levels are an effective primary screen for MCAD deficiency in newborns. Newborns homozygous for the 985A < G mutation have higher octanoylcarnitine levels than do those compound heterozygous for 985A < G and those with other genotypes. Time of sampling after birth also significantly affects octanoylcarnitine levels in MCAD‐deficient newborns. Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, reduces morbidity and mortality, and merits expansion to other populations worldwide.
Impact of diets and nutrients/drugs on early epigenetic programming
Authors: Junien Claudine
Published: June 2006

Specific, often unbalanced diets are used to circumvent the metabolic defects of patients with monogenic inborn errors of metabolism. Human epidemiological studies and appropriately designed dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances, during critical time windows of developmental programming, may have a persistent effect on the health of the child and later in adulthood. Thus patients with monogenic inborn errors of metabolism may also suffer additional types of alterations due to the lack or excess of key nutrients. Interactions of nutrients with the epigenetic machinery lead to epigenetic changes associated with chromatin remodelling and regulation of gene expression that underlie the developmental programming of pathological consequences in adulthood. Today, with the explosion of new technologies, we can explore on a large scale the effects of nutrients on the level of expression of thousands of expressed genes (nutritional genomics and epigenomics), the corresponding protein products and their posttranslationally modified derivatives (proteomics), and the host of metabolites (metabolomics) generated from endogenous metabolic processes or exogenous dietary nutrients and can establish the relationship between these biological entities and diet, health or disease. The combination of these various lines of research on epigenetic programming processes should highlight new strategies for the prevention and treatment of inborn errors of metabolism.
Protein misfolding disorders: Pathogenesis and intervention
Authors: Gregersen N.
Published: June 2006

Newly synthesized proteins in the living cell must go through a folding process to attain their functional structure. To achieve this in an efficient fashion, all organisms, including humans, have evolved a large set of molecular chaperones that assist the folding as well as the maintenance of the functional structure of cellular proteins. Aberrant proteins, the result of production errors, inherited or acquired amino acid substitutions or damage, especially oxidative modifications, can in many cases not fold correctly and will be trapped in misfolded conformations. To rid the cell of misfolded proteins, the living cell contains a large number of intracellular proteases, e.g. the proteasome, which together with the chaperones comprise the cellular protein quality control systems. Many inherited disorders due to amino acid substitutions exhibit loss‐of‐function pathogenesis because the aberrant protein is eliminated by one of the protein quality control systems. Examples are cystic fibrosis and phenylketonuria. However, not all aberrant proteins can be eliminated and the misfolded protein may accumulate and form toxic oligomeric and/or aggregated inclusions. In this case the loss of function may be accompanied by a gain‐of‐function pathogenesis, which in many cases determines the pathological and clinical features. Examples are Parkinson and Huntington diseases. Although a number of strategies have been tried to decrease the amounts of accumulated and aggregated proteins, a likely future strategy seems to be the use of chemical or pharmacological chaperones with specific effects on the misfolded protein in question. Positive examples are enzyme enhancement in a number of lysosomal disorders.
Principles of therapeutic liver repopulation
Authors: Grompe Markus
Published: June 2006

Liver repopulation by transplanted hepatocytes is a promising approach for many inborn errors of metabolism. In this review, examples of liver repopulation in animals and the implications of these models for clinical cell transplantation will be discussed.
Breast feeding in IMD
Authors: MacDonald A. , Depondt E. , Evans S. , Daly A. , Hendriksz C. , Chakrapani A A. , Saudubray J.‐M.
Published: June 2006

Breast feeding has proven benefits for many infants with inherited metabolic disorders (IMDs) but, with the exception of phenylketonuria, there are few reports in other conditions. A questionnaire, completed by dietitians and clinicians from 27 IMD centres from 15 countries (caring for a total of over 8000 patients with IMDs on diet) identified breast feeding experience in IMD. Successful, demand breast feeding (in combination with an infant amino acid formula free of precursor amino acids) was reported in 17 infants with MSUD, 14 with tyrosinaemia type I, and 5 with homocystinuria. Eighty‐nine per cent were still breast fed at 16 weeks. Fewer infants with organic acidaemias were demand breast fed (7 with propionic acidaemia; 6 with methylmalonic acidaemia and 13 with isovaleric acidaemia) (usually preceded by complementary feeds of a protein‐free infant formula or infant amino acid formula free of precursor amino acids). Only 12 infants with urea cycle disorders were given demand breast feeds, but this was unsuccessful beyond 8 days in CPS deficiency. Further work is needed in developing guidelines for feeding and for clinical and biochemical monitoring for breast‐fed infants with IMDs.
Sufficient Conditions for Uniqueness in Candecomp/Parafac and Indscal with Random Component Matrices
Authors: Stegeman Alwin , ten Berge Jos M. F. , De Lathauwer Lieven
Published: June 2006

A key feature of the analysis of three-way arrays by Candecomp/Parafac is the essential uniqueness of the trilinear decomposition. We examine the uniqueness of the Candecomp/Parafac and Indscal decompositions. In the latter, the array to be decomposed has symmetric slices. We consider the case where two component matrices are randomly sampled from a continuous distribution, and the third component matrix has full column rank. In this context, we obtain almost sure sufficient uniqueness conditions for the Candecomp/Parafac and Indscal models separately, involving only the order of the three-way array and the number of components in the decomposition. Both uniqueness conditions are closer to necessity than the classical uniqueness condition by Kruskal.