bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling thermal decay of high-aspect-ratio nanostructures
Authors: Castez Marcos F. , Salvarezza Roberto C.
Published: February 2009

A multiapproach modeling of surface diffusion driven decay of three dimensional high-aspect-ratio nanostructures is presented. Three different strategies are used: a continuous model, kinetic Monte Carlo simulations, and a molecular dynamics approach using an embedded atom model potential. All these models predict that an initially single-valued surface evolves into an intermediate multivalued state, in which features on the surface develop into a nonconvex shape. Moreover, such nanofeatures in the case of discrete models are quite well described in terms of the continuous modeling. Quantitative bounds for the aspect-ratios in which emergence of overhangs starts are estimated.
Focused patterning of nanoparticles by controlling electric field induced particle motion
Authors: Lee Heechul , You Sukbeom , Woo Chang Gyu , Lim Kyunghoon , Jun Kimin , Choi Mansoo
Published: February 2009

We report a general methodology for producing focused arrays of nanoparticles via electrodynamic focusing approach and controlling the inertial effect of charged aerosols. An important effect of particle inertia is identified and verified by performing detailed calculations of electric field induced particle motion and experimenting with electrosprayed nanoparticles. The controllability of focusing is demonstrated by changing the curvature of electric field lines.
Chemical degradation of fluorinated antisticking treatments in UV nanoimprint lithography
Authors: Truffier-Boutry D. , Zelsmann M. , De Girolamo J. , Boussey J. , Lombard C. , Pépin-Donat B.
Published: February 2009

In general, fluorinated antisticking layers (F-ASL) are deposited on the imprint stamps to ease their separation from the imprinted resist in UV nanoimprint lithography. However, these layers are found to degrade with repeated imprint operations. A drastic decrease in fluorinated species is observed on the mold surface. Yet, there is still a debate on the nature of the exact mechanisms involved in this degradation. In this paper, electron spin resonance (ESR) is used to investigate the chemical reaction occurring between the fluorinated molecules and the UV curable resist. Free radicals of the resist, generated under UV illumination, have been observed by ESR. The decrease in their corresponding signal in the presence of fluorinated ASL species shows evidence of the chemical reactivity of the resist toward the F-ASL.
Metal-hydride transformation kinetics in Mg nanoparticles
Authors: Pasquini L. , Callini E. , Piscopiello E. , Montone A. , Antisari M. Vittori , Bonetti E.
Published: February 2009

The hydrogen sorption kinetics of magnesium nanoparticles prepared by inert gas condensation and coated by a magnesium oxide layer were investigated by a volumetric apparatus. The metal-hydride transformation was studied by transmission electron microscopy of the nanoparticles both in the as-prepared state and after hydrogen cycling. In small nanoparticles (≈35 nm) hydride formation proceeds by one-dimensional growth controlled by diffusion through the hydride, while the reverse transformation to metal involves interface-controlled three-dimensional growth of nuclei formed at constant rate. Large nanoparticles (≈450 nm) exhibit very low reactivity attributed to reduced probability of hydrogen dissociation/recombination and nucleation at the particle surface.
Gate-defined quantum-dot devices realized in InGaAs/InP by incorporating a HfO2 layer as gate dielectric
Authors: Sun Jie , Larsson Marcus , Maximov Ivan , Hardtdegen Hilde , Xu H. Q.
Published: February 2009

Gate-defined quantum dots in an InGaAs/InP heterostructure are realized by incorporating a high-κ HfO2 material as a gate dielectric using atomic layer deposition. The fabricated quantum-dot devices show Coulomb blockade effect at low temperature. The Coulomb blockade current peaks are found to shift in pairs with the magnetic field applied perpendicular to the quantum-dot plane, due to the filling of electrons into spin-degenerate orbital states. When the magnetic field is applied parallel to the quantum-dot plane, spin splittings of orbital states are observed and the extracted effective g-factors are found to be different for different orbital states.
Electrocaloric effect of the relaxor ferroelectric poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) terpolymer
Authors: Neese Bret , Lu S. G. , Chu Baojin , Zhang Q. M.
Published: February 2009

We investigate the temperature dependence of the electrocaloric effect in a relaxor ferroelectric poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) terpolymer and show that the isothermal entropy change ΔS is proportional to the square of the electric displacement D (ΔS=−1/2βΔD2) and the coefficient β increases with temperature. This temperature dependent behavior of β is caused by the ferroelectric relaxor nature of the polymer in which the polarization response from the nanopolar regions does not generate much entropy change. Consequently, the electrocaloric effect in the relaxor ferroelectric terpolymer is smaller than that in the normal ferroelectric copolymer.
The role of electric field-induced strain in the degradation mechanism of AlGaN/GaN high-electron-mobility transistors
Authors: Rivera C. , Muñoz E.
Published: February 2009

The effect of strain induced by electric field in AlGaN/GaN high-electron-mobility transistors is investigated by theoretical calculations based on the minimization of the electric enthalpy functional. Results of the proposed model show that the converse piezoelectric effect increases (decreases) the stored elastic energy at positive gate voltage under biaxial tensile (compressive) strain, whereas it decreases (increases) at negative gate voltage. Hence, strain relaxation of piezoelectric origin is only expected in the on-state operation. In contrast, the degradation in the off-state operation could be identified with the effect of the electrostatic force generated by the increase in the stored electrostatic energy.
Digital I/Q demodulation for KSTAR ion cyclotron range of frequency system
Authors: Wang S. J. , Kwak J. G. , Hwang C. K.
Published: February 2009

An ion cyclotron range of frequency system requires rf diagnostics for a rf-plasma coupling or for maintaining a correct operation. A detector based on a digital I/Q demodulation technique collects the rf amplitude and phase at the same time without errors from the I/Q imbalance inherent in an analog counterpart. The theory of such a detector was studied and implemented for the first campaign of the KSTAR tokamak. Experimental results of the rf and other diagnostics are presented and discussed.
Microstructural improvements of InP on GaAs (001) grown by molecular beam epitaxy by in situ hydrogenation and postgrowth annealing
Authors: Morales F. M. , García R. , Molina S. I. , Aouni A. , Postigo P. A. , Fonstad C. G.
Published: February 2009

The characterization of high quality InP on GaAs (001) fabricated by molecular beam epitaxy using a two-step growth method involving hydrogenation during growth is reported. Electron diffraction and high-resolution transmission electron microscopy confirm that ∼2 μm thick InP epilayers on GaAs are heteroepitaxial and strain relaxed. Stacking faults and threading dislocations are mostly confined near the InP/GaAs interface and their densities decrease monotonically toward the InP surface. Additionally, rapid-thermal annealing following growth is found to result in a marked reduction in the number of dislocations and the disappearance of planar defects.
Controlled dielectrophoretic assembly of carbon nanotubes using real-time electrical detection
Authors: Sorgenfrei Sebastian , Meric Inanc , Banerjee Sarbajit , Akey Austin , Rosenblatt Sami , Herman Irving P. , Shepard Kenneth L.
Published: February 2009

We investigate dielectrophoretic deposition of single-walled carbon nanotubes using an in situ detection system. Pairs of electrodes are stimulated with a small-amplitude, low-frequency voltage superimposed on a large-amplitude, high-frequency dielectrophoretic voltage. Measuring the magnitude of the current both at dc (Idc) and at the low frequency (Iac) through a digital lock-in technique allows us to determine when a nanotube has made electrical contact and to halt the dielectrophoretic process. Because Idc is determined by nonlinearities in the device current-voltage characteristic, measurement of the Idc/Iac ratio allows the real-time determination of whether the deposited nanotube is metallic or semiconducting.
Atomistic simulation of a NiZr model metallic glass under hydrostatic pressure
Authors: Guo Yu-zheng , Li Mo
Published: February 2009

Compressive behavior of a model NiZr metallic glass under hydrostatic pressure is simulated using molecular dynamics. The equation of state obtained exhibits two distinct regimes, one at low and the other at high pressure, along with an intermediate region in between. The densification is associated with topological rearrangement of atoms at low pressure and hard-sphere-like compaction dictated by the strong interatomic repulsion at high pressure. Different from many isotropic materials, the atomic rearrangement in the metallic glass during compression is accompanied by strong local topological structure change and chemical short-range (re)ordering. The possibility of a pressure-induced phase transition is briefly discussed.
Thickness-gradient dependent Raman enhancement in silver island films
Authors: Oates T. W. H. , Noda S.
Published: February 2009

We show evidence of a dependence of the enhancement of the Raman scattering cross section on the length of the gradient in graded silver island films. A factor-of-three increase in the Raman signal is observed for gradients with length of the order of 0.5 mm when compared to gradients of the order of 9 mm. Scanning electron microscopy reveals the nanostructure of the two films to be statistically similar. We attribute the observation to differences in plasmon hybridization in the gradients arising from long range structural differences.
Performance and reliability improvement of HfSiON gate dielectrics using chlorine plasma treatment
Authors: Park Hong Bae , Ju Byongsun , Kang Chang Yong , Park Chanro , Park Chang Seo , Lee Byoung Hun , Kim Tea Wan , Kim Beom Seok , Choi Rino
Published: February 2009

The effects of chlorine plasma treatment on HfSiON gate dielectrics were investigated with respect to device performance and reliability characteristics. The chlorine plasma treatment was performed on atomic layer deposited HfSiON films to remove the residual carbon content. The optimal chlorine plasma treatment is shown to lower gate leakage current density without increasing equivalent oxide thickness of the gate stack. Secondary ion mass spectroscopy depth profiling showed that the carbon residue in HfSiON was reduced by the chlorine plasma treatment. It is demonstrated that an optimized chlorine plasma treatment improves the transistor Ion-Ioff characteristics and reduces negative-bias temperature instability.
A thermal lens model including the Soret effect
Authors: Cabrera Humberto , Sira Eloy , Rahn Kareem , García-Sucre Máximo
Published: February 2009

In this letter we generalize the thermal lens model to account for the Soret effect in binary liquid mixtures. This formalism permits the precise determination of the Soret coefficient in a steady-state situation. The theory is experimentally verified using the measured values in the ethanol/water mixtures. The time evolution of the Soret signal has been used to derive mass-diffusion times from which mass-diffusion coefficients were calculated.
Thermal-strain-induced enhancement of electromagnetic properties of SiC–MgB2 composites
Authors: Zeng R. , Dou S. X. , Lu L. , Li W. X. , Kim J. H. , Munroe P. , Zheng R. K. , Ringer S. P.
Published: February 2009

The effect of thermal strain caused by the different thermal expansion coefficients (α) of the MgB2 and SiC phases on the electromagnetic properties was studied for SiC–MgB2 composite, which was made by premixing SiC and B, followed by Mg diffusion and reaction. Thermal strain in the MgB2 phase was demonstrated with x-ray diffraction, Raman spectroscopy, and transmission electron microscopy. In contrast to the common practice of improving the critical current density Jc and the upper critical field Hc2 of MgB2 through chemical substitution, by taking advantage of residual thermal strains, we are able to design a composite showing only a small decrease in the critical temperature and a little increase in resistivity but a significant improvement over the Jc and Hc2 of pure MgB2.
Whispering gallery modes in micron-sized SrS:Eu octahedrons
Authors: Korthout Katleen , Smet Philippe F. , Poelman Dirk
Published: February 2009

Optical whispering gallery modes were observed in micron-sized SrS:Eu2+ octahedrons. Cathodoluminescence in a scanning electron microscope was used to evaluate the emission characteristics of individual octahedrons with various sizes. The resonance modes superposed on the orange Eu2+ broadband emission were explained by a plane wave model, taking the wavelength dispersion of the refractive index into account. The resonance modes occur in the three equatorial planes in the octahedrons, which were approximated by corner-cut square disks.
A non-free-space propagation x-ray phase contrast imaging method sensitive to phase effects in two directions simultaneously
Authors: Olivo A. , Bohndiek S. E. , Griffiths J. A. , Konstantinidis A. , Speller R. D.
Published: February 2009

We present an x-ray phase contrast imaging method based on coded apertures sensitive to phase effects in two directions simultaneously. To date, this is the only non-free-space propagation approach with this capability. Whereas the use of free-space propagation methods is limited to synchrotron radiation or microfocal x-ray sources, which impose severe limits in terms of practical applicability, coded-aperture based methods have been shown to provide synchrotronlike phase contrast enhancements with conventional x-ray sources. A two-directional sensitive method working with conventional sources could create a breakthrough in medical imaging, where two-directional sensitivity is often a mandatory requirement.
Capitalism beyond Harmonious Equilibrium: Mathematics as If Human Agency Mattered
Authors: Bergmann Luke , Sheppard Eric , Plummer Paul S
Published: February 2009

Narrating a world of flux entails moving away from equilibrium-oriented thinking toward considerations of emergence, uncertain futures, and unintended consequences. This is not the exclusive domain of the qualitative theory construction and analysis that has dominated such thinking in sociospatial theory: it is also involved in mathematical theory construction. It requires a relational approach to mathematical theory, however, that moves beyond unidirectional claims of cause and effect, avoids deterministic and teleological thinking, and recognizes the incompleteness and openness of any such theoretical construction. These arguments are explored through an example that employs mathematical techniques often associated with complexity theory to examine unevenly shifting economic landscapes where the best guesses of capitalist entrepreneurs are interrelated with the emergent multiregional economy in which capitalists participate. This highlights the unexpectedly heightened dynamical importance of regions in a globally connected world; how cherished theoretical principles become renegotiated, as relationality leads to emergence; and that there is space for human agency, through modeling praxis appropriate to ‘incomplete systems’. We open modest cracks in the supposed wall between quantitative and qualitative approaches, oriented toward a methodological reinterpretation of what employing mathematical arguments could mean within larger, postpositivist theoretical projects in critical human geography.
The Moss Physcomitrella patens: A Novel Model System for Plant Development and Genomic Studies
Authors: Cove David J. , Perroud Pierre-François , Charron Audra J. , McDaniel Stuart F. , Khandelwal Abha , Quatrano Ralph S.
Published: February 2009

INTRODUCTION

The moss Physcomitrella patens has been used as an experimental organism for more than 80 years. Within the last 15 years, its use as a model to explore plant functions has increased enormously. The ability to use gene targeting and RNA interference methods to study gene function, the availability of many tools for comparative and functional genomics (including a sequenced and assembled genome, physical and genetic maps, and more than 250,000 expressed sequence tags [ESTs]), and a dominant haploid phase that allows direct forward genetic analysis have all led to a surge of new activity. P. patens can be easily cultured and spends the majority of its life cycle in the haploid state, allowing the application of experimental techniques similar to those used in microbes and yeast. Its development is relatively simple, and it generates only a few tissues that contain a limited number of cell types. Although mosses lack vascular tissue, true roots/stems/leaves, and flowers and seeds, many signaling pathways found in angiosperms are intact in moss. For example, the phytohormones auxin, cytokinin, and abscisic acid, as well as the photomorphogenic pigments phytochrome and cryptochrome, are all interwoven into distinct but overlapping pathways and linked to clear developmental phenotypes. In addition, about one-quarter of the moss genome contains genes with no known function based on sequence motifs, raising the likelihood of successful discovery efforts to identify new and novel gene functions.
The Choanoflagellates: Heterotrophic Nanoflagellates and Sister Group of the Metazoa
Authors: King Nicole , Young Susan L. , Abedin Monika , Carr Martin , Leadbeater Barry S.C.
Published: February 2009

INTRODUCTION

Choanoflagellates are the closest living relatives of the metazoa, and the study of their cell biology and genomes promises to provide new insights into metazoan ancestry and origins. These heterotrophic flagellates are a cosmopolitan group of small, colorless protozoa that are present in marine and freshwater environments as well as in hydrated soils. Monosiga brevicollis, a marine species, has emerged as a representative of the group because it is easily grown and manipulated in the laboratory and was the subject of a recently completed genome project. Because of the similarity in morphology and ecology shown across the order Choanoflagellida, the protocols mentioned in this article should be transferable to most choanoflagellate species.
In-Gel Trypsin Digest of Gel-Fractionated Proteins
Authors: Link Andrew J. , LaBaer Joshua
Published: February 2009

INTRODUCTION

This protocol describes a method for in-gel digestion of proteins after fractionation using SDS-PAGE. It is applicable to both one- and two-dimensional polyacrylamide gels of different thicknesses, acrylamide concentrations, and band (spot) sizes. This protocol followed by liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) or matrix-assisted laser desorption/ionization/time of flight/time of flight (MALDI-TOF/TOF) is capable of identifying low femtomole quantities of a protein. High-sensitivity mass spectrometry should be capable of identifying attomole quantities of protein.
Culturing the Moss Physcomitrella patens: Figure 1.
Authors: Cove David J. , Perroud Pierre-François , Charron Audra J. , McDaniel Stuart F. , Khandelwal Abha , Quatrano Ralph S.
Published: February 2009

INTRODUCTION

This article includes a series of methods for culturing the moss Physcomitrella patens at all stages of its life cycle. Gametophytes are axenically cultured on solid agar-based media and in shaken liquid cultures. For long-term storage of gametophytes, cultures are maintained on solid medium at 10°C in a very short day. Cryopreservation may also be used. Finally, sporophytes are generated by self-fertilization and sexual crossing.
Isolation and Regeneration of Protoplasts of the Moss Physcomitrella patens: Figure 1.
Authors: Cove David J. , Perroud Pierre-François , Charron Audra J. , McDaniel Stuart F. , Khandelwal Abha , Quatrano Ralph S.
Published: February 2009

INTRODUCTION

This protocol describes how to isolate individual protoplasts from young gametophyte tissue of the moss Physcomitrella patens and how to regenerate them into plants if desired. Protonemal tissue is grown on cellophane-overlay plates, harvested, and treated with 0.5% Driselase to produce protoplasts. After filtration and washing, the protoplasts are regenerated on solid medium.
Transformation of the Moss Physcomitrella patens Using T-DNA Mutagenesis
Authors: Cove David J. , Perroud Pierre-François , Charron Audra J. , McDaniel Stuart F. , Khandelwal Abha , Quatrano Ralph S.
Published: February 2009

INTRODUCTION

In this protocol, the transformation of moss (Physcomitrella patens) protoplasts is performed via Agrobacterium-mediated transfer of T-DNA. Protoplasts are incubated with Agrobacterium and acetoseringone in regeneration medium. They are then washed and plated on antibiotic-containing medium to select for T-DNA insertion in stable transformants. The transformation rate for this protocol is typically 10−4 (expressed as the frequency of stable transformants among regenerants surviving the transformation procedure).
Starting and Maintaining Monosiga brevicollis Cultures
Authors: King Nicole , Young Susan L. , Abedin Monika , Carr Martin , Leadbeater Barry S.C.
Published: February 2009

INTRODUCTION

Choanoflagellates are heterotrophic nanoflagellates: small, colorless protozoa that are present in marine and freshwater environments as well as in hydrated soils. Because they are the closest living relatives of the metazoa, the study of their cell biology and genomes promises to provide new insights into metazoan ancestry and origins. Most, if not all, choanoflagellates are heterotrophs that prey on bacteria. Thus, all choanoflagellate media provide nutrition for bacteria, which are in turn consumed by the choanoflagellates. If a culture is axenic or has low bacterial content, it can be supplemented with a specific bacterial strain that has been grown separately. On the other hand, if a culture already contains a well-established flora of bacteria, it can be cocultured with the choanoflagellate isolate. In either case, it is common to enrich the medium with an organic extract, such as liver extract, cereal grass infusion, or a mixture of proteose peptone and yeast extract. This protocol describes how to start cultures of the marine choanoflagellate species, Monosiga brevicollis, from frozen stocks. These cultures can then be maintained and expanded in preparation for DNA or RNA isolation or cell biological assays.
Basics of Photoactivation
Authors: Ellis-Davies Graham C.R.
Published: February 2009

INTRODUCTION

Specific molecular interactions control cellular function. The photorelease of caged compounds (nucleotides, neurotransmitters, peptides, second messengers, proteins, etc.) can be used to control these interactions in living cells. Caged compounds are biological effector molecules whose active functionality has been chemically masked with a photoremovable protecting group. Illumination produces a concentration jump from the caged molecule. This article discusses the basic principles underlying photoactivation, the properties of caging chromophores and commercially available caged compounds, and practical considerations for their effective use.
A curved image-plate detector system for high-resolution synchrotron X-ray diffraction
Authors: Sarin P. , Haggerty R. P. , Yoon W. , Knapp M. , Berghaeuser A. , Zschack P. , Karapetrova E. , Yang N. , Kriven W. M.
Published: February 2009

The developed curved image plate (CIP) is a one-dimensional detector which simultaneously records high-resolution X-ray diffraction (XRD) patterns over a 38.7° 2θ range. In addition, an on-site reader enables rapid extraction, transfer and storage of X-ray intensity information in ≤30 s, and further qualifies this detector to study kinetic processes in materials science. The CIP detector can detect and store X-ray intensity information linearly proportional to the incident photon flux over a dynamical range of about five orders of magnitude. The linearity and uniformity of the CIP detector response is not compromised in the unsaturated regions of the image plate, regardless of saturation in another region. The speed of XRD data acquisition together with excellent resolution afforded by the CIP detector is unique and opens up wide possibilities in materials research accessible through X-ray diffraction. This article presents details of the basic features, operation and performance of the CIP detector along with some examples of applications, including high-temperature XRD.
Effects of ketoconazole and carbamazepine on lapatinib pharmacokinetics in healthy subjects
Authors: Smith Deborah A. , Koch Kevin M. , Arya Nikita , Bowen Carolyn J. , Herendeen Jill M , Beelen Andrew
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Lapatinib is an orally administered tyrosine kinase inhibitor indicated for use in combination with capecitabine to treat advanced or metastatic breast cancers that overexpress ErbB2 in patients previously treated with anthracyclines, taxanes and trastuzumab.

• In vitro studies have suggested that lapatinib is metabolized primarily by CYP3A4, that it is a substrate of the efflux transporter ABCB1, and that it is a modest inhibitor of both CYP3A4 and ABCB1.

• However, no data regarding thein vivometabolism of lapatinib have as of yet been reported.

WHAT THIS STUDY ADDS

• Thein vivopharmacokinetics of lapatinib in healthy subjects was determined in the presence of a potent inhibitor (ketoconazole) or inducer (carbamazepine) of CYP3A4.

• The results indicated that systemic exposure to lapatinib was significantly altered by inhibition or induction of CYP3A4.

• Thus, dose adjustments may be required when lapatinib is administered orally concomitantly with drugs that potently alter CYP3A4 activity.

AIMSTo characterize the impact of potent CYP3A4 inhibition and induction on lapatinib pharmacokinetics.

METHODSTwo studies were conducted in healthy subjects. One study examined the effect of ketoconazole 200 mg b.i.d. for 7 days on a single 100‐mg dose of lapatinib in 22 healthy subjects. The other study examined the effect of carbamazepine titrated up to 200 mg b.i.d. over 20 days on a single 250‐mg dose of lapatinib in 24 healthy subjects.

RESULTSKetoconazole altered lapatinib AUC,Cmaxand half‐life, with geometric mean [95% confidence interval (CI)] increases of 3.57‐fold (3.07, 4.15), 2.14‐fold (1.74, 2.64) and 1.66‐fold (1.50, 1.84), respectively, but had no effect on absorption rate. Carbamazepine altered lapatinib AUC,Cmaxand absorption rate, with geometric mean (95% CI) decreases of 72% (68, 77), 59% (49, 66) and 28% (4, 46), respectively, but had no effect on half‐life.

CONCLUSIONSSystemic exposure to lapatinib was significantly altered by potent inhibition and induction of CYP3A4. Dose adjustments may be required when lapatinib is administered with orally administered drugs that potently alter the activity of this enzyme.
Large increase of the use of psycho‐stimulants among youth in the Netherlands between 1996 and 2006
Authors: Trip Anne‐Marie , Visser Sipke T. , Kalverdijk Luuk J. , De Jong‐van den Berg Lolkje T. W.
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?

• In the USA psycho‐stimulant use has increased rapidly in the 1990s and stabilized around 2000.

• This study describes the prevalence of psycho‐stimulant use between1996 and 2006 in the Netherlands.

WHAT THIS STUDY ADDS

• The prevalence of psycho‐stimulant use among youth in the Netherlands has increased more than eightfold in the period 1996–2006, but in 2006 it is still below the prevalence in the USA.

AIM To describe the use of psycho‐stimulants in the Netherlands between 1996 and 2006 in children and adolescents, and in relation to age and sex.

METHODS With the pharmacy prescription database the IADB.nl, yearly prevalences of psycho‐stimulants per 1000 children were calculated, as was the length of psycho‐stimulant use with Kaplan–Meier method in SPSS 12.0.

RESULTS Psycho‐stimulant use increased in boys (0–19) from 4.5‰ in 1996 to 31.1‰ in 2006 and for girls from 0.7 to 8.1‰, respectively. The largest increase was among boys aged 10–19 years. There is a trend towards prescribing the sustained release preparation of methylphenidate (Concerta).

CONCLUSIONS In the Netherlands a large increase in psycho‐stimulants use is observed. However, in the Netherlands the prevalence ratio male/female declined from 6.4 in 1996 to 3.8 in 2006.
Time‐dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate
Authors: Oliver James J. , Kerr Debra M. , Webb David J.
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Co‐administration of inhibitors of phosphodiesterase type 5 with organic nitrates can cause profound hypotension.

• For this reason, it is recommended that sildenafil and organic nitrates are not administered within 24 h of one another.

• However, the time course of the interaction between sildenafil and sublingual glyceryl trinitrate (GTN) has not previously been investigated.

WHAT THIS STUDY ADDS

• In men with angina there is an interaction between oral sildenafil and sublingual GTN for ≥8 h, but from 6 h this interaction is not more than additive.

• These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h.

AIM To investigate the time course of the hypotensive interaction between sildenafil and glyceryl trinitrate (GTN).

METHODS Two double‐blind, placebo‐controlled, randomized, crossover studies were performed. Subjects were challenged with sublingual GTN 400 µg at different times after oral sildenafil 100 mg. After each GTN challenge frequent measures of blood pressure (BP) were made. In the first study GTN was given 1–48 h after sildenafil/placebo to 33 healthy men. In the second study GTN was given 1–8 h after sildenafil/placebo to 20 men with stable angina.

RESULTS In healthy men there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN only at 1 h. In angina patients, there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN for up to 8 h. The mean (95% confidence interval) differences in maximum systolic BP reduction (mmHg) at 1, 4, 6 and 8 h were −16 (−12, −21), −12 (−4, −20), −6 (1, −12) and −9 (−3, −15), all P < 0.05 except at 6 h (NS). At 6 and 8 h the interaction was not more than additive, and hypotensive symptoms did not occur.

CONCLUSIONS In men with angina there is an interaction on BP reduction between sildenafil and GTN for ≥ 8 h after sildenafil administration, but this is no more than additive from 6 h. These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h.
Electrocardiogram changes and arrhythmias in venlafaxine overdose
Authors: Isbister Geoffrey K.
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The major clinical effects of venlafaxine overdose are seizures and serotonin toxicity.

• There is controversy over the risk of cardiac toxicity in venlafaxine overdose.

WHAT THIS STUDY ADDS

• Venlafaxine overdose is unlikely to cause clinically significant cardiac toxicity, including QT prolongation or malignant arrhythmias, and the commonest cardiovascular effects are tachycardia and mild hypertension.

• Massive ingestions >8 g may result in cardiac toxicity and patients should be observed carefully.

AIMS To investigate serial electrocardiogram (ECG) parameters, haemodynamic changes and arrhythmias following venlafaxine overdose.

METHODS The study included 369 venlafaxine overdoses in 273 patients presenting to a toxicology unit where an ECG was available. Demographic information, details of ingestion, haemodynamic effects [heart rate and blood pressure (BP)] and complications (arrhythmias and conduction defects) were obtained. ECG parameters (QT, QRS) were measured manually and analysed by visual inspection, including plotting QT–HR pairs on a QT nomogram.

RESULTS The median ingested dose was 1500 mg [interquartile range (IQR) 600–3000 mg; range 75–13 500 mg). Tachycardia occurred in 54% and mild hypertension (systolic BP >140 mmHg) in 40%. Severe hypertension (systolic BP >180 mmHg) and hypotension (systolic BP <90 mmHg) occurred in 3% and 5%, respectively. No arrhythmias occurred based on continuous telemetry, and conduction defects were found in only seven of 369 admissions; five of these conduction defects were pre‐existing abnormalities. In 22 admissions [6%, 95% confidence interval (CI) 4–10] there was an abnormal QT–HR pair, with larger doses being more likely to be associated with an abnormal QT. The median maximum QRS width was 85 ms (IQR 80–90 ms; range 70–145 ms) and the QRS was greater than 120 ms in only 24 admissions (7%, 95% CI 4–10).

CONCLUSIONS Venlafaxine overdose causes only minor abnormalities in the QT and QRS intervals, unlikely to be associated with major arrhythmias, except possibly with large doses.
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients
Authors: Yip W K , Abdullah M A , Yusoff S M , Seow H F
Published: February 2009

The pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a double-enzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 non-malignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3ζ and CD3ε was also determined. The prevalence of CD4+FoxP3+ cells in CD4+ T cells and the ratio of FoxP3+/CD8+ were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3+/CD25+FoxP3− in NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25+FoxP3− cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3+/CD25+FoxP3− was found in non-keratinizing and undifferentiated carcinomas. Increased CD4+FoxP3+/CD4+ proportion and FoxP3+/CD8+ ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3ζ in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.
T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease
Authors: Lambers C , Hacker S , Posch M , Hoetzenecker K , Pollreisz A , Lichtenauer M , Klepetko W , Jan Ankersmit H
Published: February 2009

Pathogenetic mechanisms leading to chronic obstructive pulmonary disease (COPD) remain poorly understood. Because clonogenic T cells (CD4+CD28null) were shown to be increased in autoimmune diseases we hypothesized that CD4+CD28null T cells play a role in COPD. Here we describe that enhanced presence of CD4+CD28null cells is associated with impaired lung function. Sixty-four patients and controls were included. T cell phenotype was analysed using flow cytometry. Enzyme-linked immunosorbent assays were utilized to determine cytokines. Statistical evaluations were performed using non-parametric group comparisons and correlations. A logistic regression model was used to determine predictive values of CD4+CD28null in the diagnosis of COPD. Populations of CD4+ T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4+CD28null cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages. Receiver operating characteristic curve plotting revealed that presence of CD4+CD28null T cells has a diagnostic value. These CD4+CD28null T cells show increased expression of NK-like T cell receptors (CD94, 158) and intracellular perforin and granzyme B. Furthermore, triggering of PBMCs obtained from patients with mild COPD led to increased interferon-γ and tumour necrosis factor-α production in vitro compared with controls. Our finding of increased CD4+CD28null T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients.
Consensus protocol for the use of recombinant activated factor VII [eptacog alfa (activated); NovoSeven®] in elective orthopaedic surgery in haemophilic patients with inhibitors
Authors: GIANGRANDE P. L. F. , WILDE J. T. , MADAN B. , LUDLAM C. A. , TUDDENHAM E. G. D. , GODDARD N. J. , DOLAN G. , INGERSLEV J.
Published: February 2009

Summary.  Patients with haemophilia complicated by inhibitors have a significant burden of joint disease, which is associated with a negative impact on their quality of life. Successful elective orthopaedic surgery can result in decreased bleed frequency into a new joint, less time spent in hospital, increased mobility and improved well being. This paper describes a new protocol for use of recombinant activated factor VII (rFVIIa) in elective orthopaedic surgery, based on a review of published data as well as the personal experience of a group of expert physicians. The protocol offers guidance on the planning of the surgery and preoperative testing as well as the bolus schedule for rFVIIa and advice on the concomitant use of antifibrinolytic agents and fibrin sealants. A total of 10 operations involving 13 procedures in eight patients in five comprehensive care centres have been undertaken until now using the protocol, which employs an initial bolus dose of rFVIIa in the range of 120–180 μg kg−1 to cover surgery. The clinical experience reported here encompasses all cases of elective orthopaedic surgery using rFVIIa as initial treatment carried out in the UK and Republic of Ireland over the last 2 years. In all cases, there was good control of haemostasis during surgery and the final outcome was rated as ‘excellent’ or ‘extremely satisfactory’ by the reporting clinicians. Although the initial cost of product to cover surgery such as arthroplasty is high, it needs to be borne in mind that this may be offset in subsequent years by savings resulting from avoidance of bleeding episodes in the affected joint.
Forum on: the role of recombinant factor VIII in children with severe haemophilia A
Authors: FRANCHINI M. , COPPOLA A. , MOLINARI A. C. , SANTORO C. , SCHINCO P. , SPECIALE V. , TAGLIAFERRI A.
Published: February 2009

Summary.  The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood‐borne virus transmission in the 1970–1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first‐choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on‐demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti‐FVIII alloantibodies, whereas other treatment‐related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti‐FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first‐choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long‐lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report.
Ca2+ Affects Physicochemical and Conformational Changes of Threadfin Bream Myosin and Actin in a Setting Model
Authors: Hemung Bung‐Orn , Yongsawatdigul Jirawat
Published: February 2009

The effect of Ca2+ on physicochemical and conformational changes of threadfin bream (TB) myosin and actin during setting at 25 and 40°C was investigated. Ca2+ ion at 10 to 100 mM induced the unfolding of myosin and actin as evident by an increase of surface hydrophobicity (So ANS) at 40 °C. Total SH groups also decreased with an increased Ca2+ concentration, suggesting that Ca2+ promoted the formation of disulfide bonds during setting at 40 °C. Both hydrophobic interactions and disulfide linkages were involved in formation of myosin aggregates at 40 °C and were enhanced by addition of 10 to 100 mM Ca2+. Myosin Ca‐ATPase activity decreased when Ca2+ was greater than 50 mM, indicating conformational changes of myosin head. Circular dichroism spectra demonstrated that Ca2+ reduced the α‐helical content of myosin and actin incubated at either 25 or 40 °C. Ca2+ induced conformational changes of TB myosin and actin incubated at 40 °C to a greater extent than at 25 °C.
Validation of a High‐performance Liquid Chromatography‐Ultraviolet Method to Quantify Soy Sapogenols A and B in Soy Germs from Different Cultivars and in Soy Isoflavone‐Enriched Supplements
Authors: Hubert Jane , Berger Monique , Daydé Jean
Published: February 2009

An increasing number of studies investigating the health effects of soy phytochemicals has led to the commercialization of many soy‐based products. Due to its particularly high concentration in many secondary metabolites, the use of soy germ as raw material is emerging for the processing of soy dietary supplements. However, the soybean seeds and germs do not exhibit the same major phytochemical profiles. This is particularly the case for soy saponins. Due to their structural diversity, the analysis of each individual soy saponin remains difficult. In this study, the total amount of these health‐protective phytochemicals was determined through the quantification of their aglucon precursors, soy sapogenols A and B. A simple and rapid analytical method was developed using high‐performance liquid chromatography coupled with an ultraviolet detection. The within‐day and between‐day variabilities of total soy sapogenol concentration were 7.3% and 10.9% in the whole seed and 3.3% and 4.7% in the germ, respectively. The total soy sapogenol contents investigated among the germs from 43 cultivars ranged from 32.8 μmol/g to 63.1 μmol/g. High amounts of soy saponins were also observed in several soy‐based dietary supplements, from 5.5 μmol/g to 107.8 μmol/g, with an A/B ratio varying from 0.3 to 8.6, showing large differences between the raw materials and concentration process used. These results indicate that these compounds have to be clearly determined when discussing the biological activity of dietary supplements issued from soy.
Lipid Oxidation in Microsomal Fraction of Squid Muscle (Loligo peali)
Authors: Thanonkaew Amonrat , Benjakul Soottawat , Visessanguan Wonnop , Decker Eric A.
Published: February 2009

Frozen squid is susceptible to both lipid oxidation and yellow/brown discoloration during frozen storage. The involvement of lipid oxidation in the microsomal fraction of squid muscle on oxidative rancidity and discoloration was investigated using iron and either enzymatic or non‐enzymatic redox cycling pathways. Lipid oxidation was measured by thiobarbituric acid‐reactive substances (TBARS), and color changes were measured spectrophotometrically using an integrating sphere. The lipid oxidation was not observed in the squid microsomes in the presence of Fe3+ and β‐nicotinamide adenine dinucleotide disodium salt (NADH) or β‐nicotinamide adenine dinucleotide phosphate, reduced (NADPH), suggesting that the enzymatic redox cycling pathway was not active. Iron‐promoted TBARS formation was observed in the non‐enzymatic pathway when ascorbic acid was used as a reducing compound. Non‐enzymatic lipid oxidation increased with increasing temperature (4 °C to 37 °C), iron (0 to 100 μM), and ascorbic acid (0 to 200 μM) concentrations. As lipid oxidation in the microsomes or isolated microsomal lipids increased, color changes were observed as could be seen by an increase in b* values (yellowness) and a decrease in a* (redness) values. The ability of iron and ascorbate to promote both lipid oxidation and pigment formation in the microsomal fraction suggests that this pathway could be responsible for quality deterioration of squid muscle during storage.