bluuebunny/crossref_metadata_2025 huggingface dataset:
A new update procedure for internal variables in an ALE‐description of rolling contact
Authors: Ziefle M. , Nackenhorst U.
Published: November 2005

In FEM analysis of rolling contact problems Arbitrary Lagrangian‐Eulerian (ALE) methods are the state of the art. These methods allow mesh refinements concentrated to the contact region and offer a time independent formulation of stationary elastic rolling. The relative‐kinematic description of rolling leads to a relative motion between the finite element mesh and the material points. Thus in the case of inelastic material behavior history dependent constitutive equations contain convective terms. The handling of these convective terms is performed by a so called fractional step method. A material step is followed by a convection step. In the first step the nonlinear solid contact problem is resolved by neglecting the convective terms. In the following step the internal variables are transported on the streamlines of the material particles by solving the advection equation via a time‐discontinuous Galerkin method. This update procedure is demonstrated on a typical FEM‐tire model. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cosserat continuum modelling of grain size effects in metal polycrystals
Authors: Zeghadi Asmahana , Forest Samuel , Gourgues Anne‐Françoise , Bouaziz Olivier
Published: November 2005

The global response of polycrystalline aggregates is investigated, in order to simulate grain size effects in IF ferritic steels. The mechanics of generalized continua is used to describe the studied phenomena. The polycrystal is regarded as a heterogeneous Cosserat medium, and the overall properties are estimated using a specific homogenization technique. To illustrate the capabilities of the model, some simple bidimensionnal computations are presented for different grain sizes. Afterwards tridimensionnal computations are shown in order to extract the global effect on the mechanical behaviour for grain sizes ranging from 5 µm to 120 µm. The finite element response is harder for the smallest grain size, but the model still underestimate the grain size effect on the tensile response. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Synergy Between N and O Atom Action and Substrate Surface Temperature in a Sterilization Process Using a Flowing N2‐O2 Microwave Post Discharge
Authors: Villeger Sandrine , Sarrette Jean Philippe , Ricard André
Published: November 2005

Summary: It is demonstrated here that the sterilization process using a flowing N2‐O2 post discharge reactor involves a specific heating of the bacteria metal holder produced by heterogeneous O and N atoms recombination. Such heating increases with N and O‐atom concentrations, which can be varied with the microwave discharge power. It also depends on the metallic material of the holder: a brass support can reach a maximum surface temperature of 120 °C while the surface temperature of the stainless steel holder increases to 60–70 °C after 40 min of exposure to a N2‐5% O2 post discharge at 0.6 kPa (5 Torr), 1 Ln · min−1 and 100 W. It is demonstrated that the E. coli destruction efficiency increases with N and O atom density at a constant temperature (60 °C) of the stainless steel support and with the support temperature (up to 60 °C) at constant N and O atom densities. A cumulative effect was also found with increasing N and O atom density and of the support temperature.

Bacteria survivor number versus the exposure time to a N2‐5% O2 post discharge.

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Bacteria survivor number versus the exposure time to a N2‐5% O2 post discharge.
Physical, chemical and environmental properties of selected chemical alternatives for the pre‐plant use of methyl bromide as soil fumigant
Authors: Ruzo Luis O
Published: November 2005

Production and use of methyl bromide, a soil fumigant, are being restricted because of this chemical's deleterious effects on stratospheric ozone concentrations. Several products, some of which are currently used as soil fumigants, are being considered as possible replacements for methyl bromide, alone and in various combinations. Among these, 1,3‐dichloropropene, methyl isothiocyanate generators such as metam‐sodium, and chloropicrin are currently registered, while others such as methyl iodide and sodium azide are at different stages of the registration process. This review examines physicochemical properties, environmental fate, and metabolism of the various potential methyl bromide replacement products. Copyright © 2005 Society of Chemical Industry
Selectivity of pesticides used on cotton (Gossypium hirsutum) to Trichogramma pretiosum reared on two laboratory‐reared hosts
Authors: Bastos Cristina S , de Almeida Raul P , Suinaga Fábio A
Published: November 2005

The side‐effects of pesticides (insecticides, fungicides, herbicides and plant growth regulators) used on cotton were tested on adults and pupae of Trichogramma pretiosum Riley reared in the laboratory on two different hosts, the Angoumois grain moth (Sitotroga cerealella Olivier) and the Mediterranean flour moth (Ephestia kuehniella (Zeller)). The eggs of the host enclosing the parasitoid pupae received direct pesticide sprays, while the adults of the parasitoid were exposed to the pesticides through contact with residues on sprayed eggs offered to parasitism. Alpha‐cypermethrin, carbosulfan, deltamethrin, endosulfan, profenofos and zeta‐cypermethrin were highly noxious to the parasitoid, significantly reducing the percentage of emergence and parasitism of T. pretiosum developing in E. kuehniella or S. cerealella eggs. However, the pupal stage of the parasitoid developing in S. cerealella eggs was less susceptible to alpha‐cypermethrin and deltamethrin. Lufenuron and metamidophos greatly reduced the percentage of adult emergence from eggs of both hosts, while novaluron only interfered on this variable when the wasps were developing in E. kuehniella eggs. However, lufenuron and monocrotophos had no effect on the parasitoid pupae of T. pretiosum developing in E. kuehniella eggs. Chlorfluazuron, diafenthiuron, diflubenzuron, fentin hydroxide, mepiquat chloride, novaluron, thiacloprid and triflumuron did not affect T. pretiosum emergence when eggs of S. cerealella enclosing pupae of the wasps were surface treated. The pesticides azoxystrobin, carbendazin + thiram, mepiquat chloride and novaluron had no effect on the ability of the wasps to parasitise E. kuehniella eggs. However, only mepiquat chloride did not affect the percentage of F1 wasps emerging from E. kuehniella eggs. The remaining pesticides moderately reduced the percentage of emergence and parasitism of the wasps when they had contact with the chemicals during their pupal or adult stage. Thus there were differences in pesticide toxicity according to the host used for parasitoid development. These differences were hypothesised to occur because of differences in egg morphology and parasitoid performance. Copyright © 2005 Society of Chemical Industry
Long‐term persistence and efficacy of spinosad against Rhyzopertha dominica (Coleoptera: Bostrychidae) in wheat
Authors: Daglish Gregory J , Nayak Manoj K
Published: November 2005

A laboratory study was undertaken to determine the persistence and efficacy of spinosad against Rhyzopertha dominica (F.) in wheat stored for 9 months at 30 °C and 55 and 70% relative humidity. The aim was to investigate the potential of spinosad for protecting wheat from R. dominica during long‐term storage in warm climates. Wheat was treated with spinosad at 0.1, 0.5 and 1 mg kg−1 grain and sampled after 0, 1.5, 3, 4.5, 6, 7.5 and 9 months of storage for bioassays and residue analyses. Residues were estimated to have declined by 30% during 9 months of storage at 30 °C and there was no effect of relative humidity. Spinosad applied at 0.5 or 1 mg kg−1 was completely effective for 9 months, with 100% adult mortality after 14 days of exposure and no live F1 adults produced. Adult mortality was <100% in some samples of wheat treated with 0.1 mg kg−1 of spinosad, and live progeny were produced in all samples treated at this level. The results show that spinosad is likely to be an effective grain protectant against R. dominica in wheat stored in warm climates. Copyright © 2005 Society of Chemical Industry
Space, time and the vulnerable witness: exploring the tensions between policy and personal perspectives on witness intimidation
Authors: Fyfe Nicholas R.
Published: November 2005

Focusing on a specific vulnerable group (witnesses to crimes who have experienced or fear intimidation from offenders and their associates), this paper examines attempts by policy‐makers to address their anxieties and fears, and the impact of experiencing intimidation on the witnesses themselves. The first section traces the ‘discovery’ by policy‐makers of vulnerable witnesses in Britain in the mid‐1990s and how this led to the introduction of a range of spatial tactics and strategies aimed at reducing the vulnerability of witnesses to intimidation. This policy response has, however, been founded on a particular reading of the geography of witness vulnerability, narrowly focused around the courtroom during the trial period. Using interviews with witnesses who have experienced intimidation, the second section examines how the spatial and temporal coordinates of witnesses' fears are more complex than current policy measures allow for. The third section of the paper then juxtaposes policy and personal discourses around intimidation, focusing on the different understandings of the social, spatial and temporal contexts of intimidation and the differences between situational and social approaches to addressing witnesses' concerns. Many of the issues raised in this section concerning the dangers of relocating risk as a result of adopting situational approaches to witness vulnerability, and the tendency to address symptoms rather than causes, intersect with wider concerns that geographers have in relation to vulnerability research; these are discussed in the conclusion. Copyright © 2005 John Wiley & Sons, Ltd.
Towards an interdisciplinary conceptualisation of vulnerability
Authors: Hogan Daniel Joseph , Marandola Eduardo
Published: November 2005

Each discipline uses uncertainty in different ways. This paper reviews the range of definitions and methodologies used by researchers to approach vulnerability in the search for an interdisciplinary conceptualisation. Two themes (poverty, exclusion and marginalisation on the one hand, and society–environment interactions on the other) are used to explore the authors' conceptualisation of vulnerability. The paper points towards possible convergences of these approaches. Copyright © 2005 John Wiley & Sons, Ltd.
Quantum fluctuations of ultracold atom–molecule mixtures
Authors: Domański T.
Published: November 2005

We investigate the evolution of quantum coherence in an ultracold mixture of fermionic atoms and bosonic dimer molecules. Interactions are experimentally controlled via tuning the external magnetic field. Consequently, the fermionic atoms and their bosonic counterparts can be driven to a behavior resembling the usual BCS to BEC crossover. We analyze in some detail how this quantum coherence evolves with respect to time upon a smooth and abrupt sweep across the Feshbach resonance inducing the atom–molecule quantum fluctuations. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Two dimensional model for correlated eg electrons in doped nickelates
Authors: Rościszewski Krzysztof , Oleś Andrzej M.
Published: November 2005

We investigate the magnetic, orbital and charge instabilities in eg band for the average filling by n = 2 – x electrons per site, as in La2–x Srx NiO4. The calculations were performed on 8 × 8 clusters, with electron correlations included within the local ansatz method. The C ‐type antiferromagnetic phase was found in a broad range of doping, but distinct stripe phases could not be identified. The nonuniform orbital order is present for some dopings and couples to charge and spin order. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin fluctuations in coupled two‐dimensional magnetic trilayers
Authors: Wende H. , Sorg C. , Bernien M. , Scherz A. , Jensen P. J. , Ponpandian N. , Baberschke K.
Published: November 2005

Magnetic trilayer systems consisting of two ultrathin ferromagnetic films of Co and Ni separated by a non‐magnetic spacer of Cu are investigated in order to analyze the effect of spin fluctuations in the ultrathin film limit (2D). The element specificity of the X‐ray magnetic circular dichroism technique is applied to study the temperature dependence of the Co and Ni magnetization separately. The effect of (i) the interlayer exchange coupling and (ii) the enhanced 2D spin fluctuations on the shift of the critical temperature of the Ni films is determined by varying both the Cu and the Ni thicknesses. For a detailed understanding of these effects the experimental results are compared to a microscopic many‐body Green's function theory. Both experiment and theory provide clear indications that for nanostructured magnets a static mean field description is insufficient. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin transport in disordered single‐wall carbon nanotubes contacted to ferromagnetic leads
Authors: Krompiewski S. , Nemec N. , Cuniberti G.
Published: November 2005

Recent conductance measurements on multi‐wall carbon nanotubes (CNTs) reveal an effective behavior similar to disordered single‐wall CNTs. This is due to the fact that electric current flows essentially through the outermost shell and is strongly influenced by inhomogeneous electrostatic potential coming from the inner tubes. Here, we present theoretical studies of spin‐dependent transport through disorder‐free double‐wall CNTs as well as single‐wall CNTs with Anderson‐type disorder. The CNTs are end‐contacted to ferromagnetic electrodes modelled as fcc (111) surfaces. Our results shed additional light on the giant magnetoresistance effect in CNTs. Some reported results concern realistically long CNTs, up to several hundred nanometers. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin accumulation, spin currents, and torque, in the problem of motion of a sharp domain wall in magnetic nanowires
Authors: Vieira V. R. , Dugaev V. K. , Sacramento P. D. , Barnaś J. , Araújo M. A. N. , Berakdar J.
Published: November 2005

We consider the motion of a sharp domain wall in magnetic nanowires with electric current. The width of the domain wall is much smaller than the electron wavelength, which is typical for magnetic semiconductors. We calculate the distributions of the spin density and the spin current related to different modes of the scattering states. The accumulated transverse components of the spin density and the spin current oscillate in the vicinity of the wall and they essentially affect its dynamics, whereas the longitudinal part of the spin current is responsible for another component of the spin torque creating a force for the current‐induced motion of the domain wall along the nanowire. We also analyze the dynamics of the sharp domain wall using the standard Landau–Lifshits–Gilbert formalism and the two‐component spin torque calculated for this model. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Orbital Kondo effect and spin polarized transport through quantum dots
Authors: Lipiński S. , Krychowski D.
Published: November 2005

The coherent spin dependent transport through a set of two capacitively coupled quantum dots placed in a magnetic field is considered within the equation of motion method. The magnetic field breaks the spin degeneracy. For special choices of gate voltages the dot levels are tuned to resonance and the orbital Kondo effect results. For different Zeemann splittings at the dots the Kondo resonance can be formed for only one spin channel. In this case the system operates as an efficient spin filter. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Correlation between growth and magnetic properties of Fe/Ti multilayers
Authors: Smardz K. , Smardz L.
Published: November 2005

Fe/Ti multilayers (MLs) were prepared onto glass substrates at 295 K using UHV RF/DC magnetron sputtering. Planar growth of the Fe and Ti sublayers was confirmed in‐situ by X‐ray photoelectron spectroscopy (XPS). We have observed exponential variation of the XPS Fe‐2p and Ti‐2p integral intensities with increasing sublayer thicknesses. Systematic structural and magnetic studies showed, that iron sublayers grow on Ti in the soft magnetic nanocrystalline phase up to a critical thickness d crit ∼ 2.3 nm. For a thickness greater than d crit, the Fe sublayers undergo a structural transition to the polycrystalline phase with much higher coercivity. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Changes in magnetic and magnetoresistive characteristics of Ni–Fe/Au/Co/Au multilayers induced by annealing
Authors: Szymański B. , Stobiecki F. , Urbaniak M.
Published: November 2005

In this contribution the influence of annealing on magnetization reversal and on the giant magnetoresistance effect of [Ni80Fe20/Au(t Au)/Co(t Co)/Au(t Au)]10 multilayers with t Co = 0.6, 0.8 nm and t Au = 1.5, 2.2 nm was studied. Measurements performed for as‐deposited samples and after subsequent annealing at T a (423 K < T a < 523 K) show that the GMR effect is stable under annealing below 475 K. It even slightly increases, for T a above 450 K, opening a path for a GMR value control and therefore is important for applications. The most pronounced changes were observed in the saturation field H CoS‖ which is a measure of perpendicular anisotropy. The significant variations were also noticed in the central part of the M (H ) and R (H ) curves. They are characterized by the nucleation field H N and the saturation field H S⊥ which are related to the appearance and disappearance of stripe domains in Co layers, respectively. The influence of T a on values of H CoS‖, H S⊥ and H N will be discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Role of inter‐dot Coulomb repulsion and exchange interactions on transport in double quantum dot
Authors: Michałek Grzegorz , Bułka Bogdan R.
Published: November 2005

Effects of inter‐dot many‐body electronic correlations on the coherent transport through double quantum dots (DQD) connected in series are studied. Conductance as well as another physical quantities are calculated by means of Green's functions. The many‐body electronic correlations are treated in the slave‐boson (SB) mean‐field approach, developed by Kotliar and Ruckenstein. The conductance in the model is characterized by competition between the dot–dot tunnelling coupling and the level broadening (dot–lead coupling). In the case, when the inter‐dot coupling is weaker than the dot–lead coupling each dot accommodates one electron and forms the Kondo resonant state with conducting electrons in a lead. In the opposite limits, when the inter‐dot coupling exceeds level broadening, the conductance vanishes for sufficiently low gate voltages, which means the Kondo effect disappeared. The resonance region is broadened with increasing inter‐dot Coulomb repulsion as well as with decreasing exchange interactions. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin and orbital magnetism of Au3Co: Density functional calculations
Authors: Sargolzaei Mahdi , Opahle Ingo , Richter Manuel
Published: November 2005

The metastable L12 compound Au3Co has been considered as a model for high Co impurity concentration in gold. The spin and orbital moments of this compound have been calculated in the framework of local spin density approximation (LSDA) with and without orbital polarization corrections, using the relativistic version of the full‐potential local orbital minimum basis code. We also calculated the magnetocrystalline anisotropy energy. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnetic properties of Cu‐flux‐grown UCu2Si2 single crystals
Authors: Troć R. , Bukowski Z.
Published: November 2005

In order to solve a serious problem of understanding the magnetic properties of UCu2Si2, we have grown single crystals of this compound from Cu‐flux. Here we focus primarily on the magnetic behavior of this compound. In contrast to some previous polycrystalline and single‐crystalline reports on UCu2Si2 no signs of the transition into antiferromagnetic behavior have been observed below T C = 104(1) K. The magnetic properties of this compound are highly anisotropic, with an easy axis of magnetization along the [001] direction. The saturation moment has been determined at 4.2 K to be 1.55μ B. In the paramagnetic region the effective moments for the easy and hard directions are both about 3.0μ B. An extensive discussion of the obtained data, compared to those recently published by Fisk et al. and Matsuda et al., also based on single crystalline materials, has been presented. No an antiferromagnetic phase above T C has been detected. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermal properties of U3Al2Si3 single crystal
Authors: Mihalik Marián , Flachbart Karol , Gabáni Slavomír , Maťaš Slavomír , Mihalik Matúš , Rogl Peter , Troć Robert
Published: November 2005

Heat capacity data of U3Al2Si3 single crystal exhibit a maximum at 38 K connected with a transition to a magnetically ordered state. For a full description of the electron part we used γ 0 = 145 mJ/mol K2 and for the phonon part of the specific heat we used the harmonic approximation of the phonon spectrum including both the Debye model with T D = 296 K and the Einstein model with T E = 136, 249 and 438 K. The heat capacity data below the magnetic transition down to 2 K fit very well within the model introducing the energy gap Δ = 39 K in the dispersion relation of magnons. An upturn of the C /T (T ) curve, found below T = 2 K, can not be fully attributed to the nuclear Schottky contribution. The electronic heat capacity coefficient (γ ≈ 230 mJ/mol K2 is enhanced and varies between 0.15 K and 12 K as the square root of T . (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electronic structure studies of DyNi4Cu
Authors: Pugaczowa‐Michalska M. , Chełkowska G. , Toliński T. , Kowalczyk A.
Published: November 2005

Electronic structure of the DyNi4Cu compound, crystallising in the hexagonal CaCu5‐type of structure has been studied using the XPS method as well as the self‐consistent spin‐polarised TB‐LMTO (tigh‐binding linear muffin‐tin orbital) method. Our calculations show that DyNi4Cu is ferromagnetically ordered at 0 K. The analysis of the valence band shape in vicinity of the Fermi level shows that this part of the spectrum comes mainly from 3d electrons of Ni and Cu atoms. The features of the experimental XPS valence band spectra near the Fermi level are reproduced in our calculations. Peaks below –7.5 eV are connected with the contribution of the f ‐electrons of Dy. The obtained peak positions in the valence band are in good agreement with the binding energies of metallic dysprosium, copper and nickel. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Andreev reflection at ferromagnetic metal‐triplet superconductor junction
Authors: Kowalewski L. , Wojciechowski R. J. , Wojtuś P.
Published: November 2005

Properties of tunneling conductance spectra of a ferromagnetic‐insulator‐anisotropic spin triplet superconductor junction are theoretically investigated. The Andreev reflection and transmission of quasiparticles at the interfaces, parallel to the c ‐axis of the superconductor Sr2RuO4, for unitary p ‐wave and non‐unitary states are discussed. Asymmetry of the Andreev reflection amplitude with respect to the boundary normal is analyzed. Discussion of the resonance peak in this reflection is also performed. The essential influence of the magnitude and direction of the exchange field on the conduction spectrum is investigated. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Orbital‐selective Mott transitions in the 2‐band Jz‐model: a high‐precision quantum Monte Carlo study
Authors: van Dongen P. G. J. , Knecht C. , Blümer N.
Published: November 2005

Using high‐precision quantum Monte Carlo (QMC) simulations within the framework of dynamical mean field theory (DMFT), we show that the anisotropic degenerate two‐orbital Hubbard model contains two consecutive orbital‐selective Mott transitions (OSMTs) even in the absence of spin‐flip terms and pair‐hopping processes. In order to reveal the second transition we carefully analyze the low‐frequency part of the self‐energy and the local spectral functions. This paper extends our previous work to lower temperatures. We discuss the nature – in particular the order – of both Mott transitions and list various possible extensions. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamic response of magnetic ions in the colossal magnetoresistance manganites La1–xCaxMnO3
Authors: Deac I. G. , Tetean R. V. , Miron M. , Burzo E.
Published: November 2005

We present a detailed study of the nonlinear dynamic susceptibility of the polycrystalline perovskite manganites La1–x Cax MnO3 (0.30 ≤ x ≤ 0.66), below and above the transition temperature as functions of frequency and temperature. Near to x = 0.5 the system changes from ferromagnetic and conducting to antiferromagnetic and insulating with a large hysteretic behavior in M (T ) and ρ (T ). The Curie temperatures determined from dynamic susceptibility analysis were compared to the data obtained previously by electrical and static magnetic measurements, and a new phase diagram was drawn. The data suggest the presence of correlated magnetic clusters near to the magnetic transition. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Non‐collinear magnetic states in Ni–Fe/Au/Co/Au multilayers investigated by magnetoresistance measurements
Authors: Stobiecki F. , Urbaniak M. , Szymański B. , Schmidt M. , Luciński T.
Published: November 2005

Sputtered Ni80Fe20/Au/Co/Au multilayers (MLs) exhibit perpendicular anisotropy of Co layers and easy‐plane anisotropy of Permalloy layers. In these samples the changes of relative orientation of magnetization between Co and NiFe layers, with magnetic field, can be determined by magnetoresistance measurements. The magnetic structure is discussed for two types of Ni80Fe20/Au/Co/Au MLs characterized by a weak coupling between ferromagnetic layers: (i) MLs with rectangular hysteresis loops and small coercive field, (ii) MLs with dense stripe domain structure in Co layers. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sample size of 12 per group rule of thumb for a pilot study
Authors: Julious Steven A.
Published: November 2005

When designing a clinical trial an appropriate justification for the sample size should be provided in the protocol. However, there are a number of settings when undertaking a pilot trial when there is no prior information to base a sample size on. For such pilot studies the recommendation is a sample size of 12 per group. The justifications for this sample size are based on rationale about feasibility; precision about the mean and variance; and regulatory considerations. The context of the justifications are that future studies will use the information from the pilot in their design. Copyright © 2005 John Wiley & Sons, Ltd.
Cost‐efficient higher‐order crossover designs for two‐treatment clinical trials
Authors: Yuan Ying , Zhou Jihao
Published: November 2005

Higher‐order crossover designs have drawn considerable attention in clinical trials, because of their ability to test direct treatment effects in the presence of carry‐over effects. The important question, when applying higher‐order crossover designs in practice, is how to choose a design with both statistical and cost efficiencies from various alternatives. In this paper, we propose a general cost function and compare five statistically optimal or near‐optimal designs with this cost function for a two‐treatment study under different carry‐over models. Based on our study, to achieve both statistical and cost efficiencies, a four‐period, four‐sequence crossover design is generally recommended under the simple carry‐over or no carry‐over models, and a three‐period, two‐sequence crossover design is generally recommended under the steady‐state carry‐over models. Copyright © 2005 John Wiley & Sons, Ltd.
Multiple imputation compared with restricted pseudo‐likelihood and generalized estimating equations for analysis of binary repeated measures in clinical studies
Authors: Lipkovich Ilya , Duan Yuyan , Ahmed Saeeduddin
Published: November 2005

Non‐likelihood‐based methods for repeated measures analysis of binary data in clinical trials can result in biased estimates of treatment effects and associated standard errors when the dropout process is not completely at random. We tested the utility of a multiple imputation approach in reducing these biases. Simulations were used to compare performance of multiple imputation with generalized estimating equations and restricted pseudo‐likelihood in five representative clinical trial profiles for estimating (a) overall treatment effects and (b) treatment differences at the last scheduled visit. In clinical trials with moderate to high (40–60%) dropout rates with dropouts missing at random, multiple imputation led to less biased and more precise estimates of treatment differences for binary outcomes based on underlying continuous scores. Copyright © 2005 John Wiley & Sons, Ltd.
The formation of neutral CCCO2H and HCCCO2 molecules from anionic precursors in the gas phase: a joint experimental and theoretical study
Authors: Fitzgerald Mark , Bowie John H. , Schröder Detlef , Schwarz Helmut
Published: November 2005

Calculations at the CCSD(T)/aug‐cc‐pVDZ//B3LYP/6‐31G(d) level of theory indicate that the anions −CCCO2H and HCCCO are stable species in their singlet states. Upon collision‐induced, vertical one‐electron oxidation under neutralisation‐reionisation (−NR+) conditions, they produce the neutral molecules CCCO2H and HCCCO2, respectively. Some of the CCCO2H neutrals should be stable for the duration of the neutralisation‐reionisation experiment (10−6 s), while others will dissociate to CCCO and OH (requires 125 kJ mol−1). In contrast, neutral HCCCO2 is expected to be much less stable, and dissociate to HCC and CO2 (37 kJ mol−1). Neither CCCO2H nor HCCCO2 is expected to interconvert, or to rearrange to other isomers. The anions −CCCO2H and HCCCO have been formed in the ion source of the mass spectrometer by the reactions between (CH3)3SiCCCO2H and F− and HCCCO2Si(CH3)3 and F−, respectively. The −NR+ spectrum of −CCCO2H shows a recovery signal and also indicates that the lowest energy dissociation pathway of neutral CCCO2H corresponds to the loss of OH. The −NR+ spectrum of HCCCO2 displays little or no recovery signal, and the spectrum is dominated by the [CO2]+ ion. The experimental observations are in agreement with the predictions of the extensive theoretical studies. Copyright © 2005 John Wiley & Sons, Ltd.
High precision measurements of 17O/16O and 18O/16O ratios in H2O
Authors: Barkan Eugeni , Luz Boaz
Published: November 2005

We have optimized the method of water fluorination using the solid reagent CoF3 to produce O2. This allows isotope ratio measurements by dual‐inlet mass spectrometry with very high precision of 0.01 to 0.03‰ for both δ17O and δ18O. Using this method, δ17O and δ18O of atmospheric O2 were determined as 12.08 and 23.88‰ vs. VSMOW, respectively. Likewise, δ17O and δ18O of GISP were −13.12 and −24.73‰, and for SLAP they were −29.48 and −55.11‰ vs. VSMOW, respectively. Analysis of these data in a ln(δ17O + 1) vs. ln(δ18O + 1) plot yields a line with a regression coefficient (λ) of 0.5279 ± 0.0001 (R2 = 0.999999). We also determined the fractionation factors 17α and 18α in liquid‐vapor equilibrium, and found that the ratio ln17α/ln18α is constant (0.529 ± 0.001) over the temperature range 11.4 to 41.5°C. Copyright © 2005 John Wiley & Sons, Ltd.
Study of fragmentation pattern and adsorption of 9‐O‐(triphenylsilyl)‐10,11‐dihydrocinchonidine on platinum by hydrogen/deuterium exchange using electrospray ionization ion‐trap tandem mass spectrometry
Authors: Szöllősi György , Bucsi Imre , Cserényi Szabolcs , Bartók Mihály
Published: November 2005

We have studied the adsorption on a platinum (Pt) catalyst of two compounds utilizable as a chiral basic catalyst and a chiral modifier, dihydrocinchonidine (DHCD), and a new cinchona alkaloid derivative containing a bulky group, the Ph3SiO‐DHCD molecule. The method of choice was the detection by electrospray ionization (ESI) ion‐trap tandem mass spectrometry (MS/MS) of hydrogen/deuterium (H/D) exchange at room temperature, in tetrahydrofuran, at a D2 pressure of 1 bar. Based on the ESI‐MS/MS spectrum of the new compound, we propose a mechanism for the formation of the silatropylium cation containing a SiO bond. From the fragmentation pattern of Ph3SiO‐DHCD it was confirmed that ESI‐ion‐trap MS/MS can be used to study the adsorption processes of complicated carbon compounds by investigating their H/D exchange reactions. In the case of Ph3SiO‐DHCD, the results demonstrate that H/D exchange takes place mainly on the quinoline skeleton. However, the strong π‐bonded adsorption of the quinoline skeleton parallel with the imaginary plane of Pt is not preferred because the bulky Ph3Si group inhibits the multiple π‐bonded adsorption of the Ph3SiO‐DHCD. Because of this hindrance the molecule was adsorbed tilted via the nonbonding electron pair of the N atom and C2′ atom of the quinoline skeleton; consequently, mainly alkaloid‐d1 and alkaloid‐d2 are formed. Copyright © 2005 John Wiley & Sons, Ltd.
Detection limits of matrix‐assisted laser desorption/ionisation mass spectrometry coupled to chromatography – a new application of solvent‐free sample preparation
Authors: Falkenhagen Jana , Weidner Steffen M.
Published: November 2005

The detection limits of matrix‐assisted laser desorption/ionisation mass spectrometry (MALDI‐MS) by semi‐online coupling with chromatography were investigated using various mixtures of polyethylene oxides (PEOs) with different end groups. In contrast to the common ‘dried‐droplet’ sample preparation technique, which results in an inhomogeneous sample‐to‐matrix ratio within the MALDI spot, the used coupling technique offers a very high reproducibility combined with surpassing sensitivity of a few femtograms over a broad range of sample‐to‐matrix ratios. These results are in correlation with the results of the recently established solvent‐free MALDI‐TOFMS method utilising the grinding approach and are also of assistance towards the more theoretical aspect of MALDI that suggests that there is no necessity for an analyte incorporation into a matrix crystal for excellent matrix‐assistance. Copyright © 2005 John Wiley & Sons, Ltd.
Identification of a trace colored impurity in drug substance by preparative liquid chromatography and mass spectrometry
Authors: Wang Peng , Shi Y.‐J. , Helmy Roy , Reamer Robert , Vailaya Anant
Published: November 2005

6‐(Nitrooxy)hexyl‐(2z)‐4‐(acetyloxy)‐3‐[4‐(methylsulfonyl)phenyl]‐2‐phenylbut‐2‐enoate (enoate 1) was investigated as a novel therapy for pain relief. In a recent manufacturing run at the pilot plant scale, the enoate drug substance was found to have a yellowish color not observed previously. An unknown impurity at trace level was detected by high‐performance liquid chromatographic (HPLC) analysis and found to be the primary cause for the color of the drug substance. The colored impurity was enriched by preparative HPLC and structurally elucidated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). It was found that the colored impurity was derived from the product of oxidative dimerization of rofecoxib, an impurity present in the enoic acid intermediate. It was further revealed by the photodiode array and LC/MS/MS data that the colored impurity exists in the drug substance as a pair of double‐bond isomers with one isomer at majority. These findings were also confirmed by synthesizing the colored impurity through the proposed pathway. Copyright © 2005 John Wiley & Sons, Ltd.
Improved 2‐nitrobenzenesulfenyl method: optimization of the protocol and improved enrichment for labeled peptides
Authors: Matsuo Ei‐ichi , Toda Chikako , Watanabe Makoto , Iida Tetsuo , Masuda Taro , Minohata Toshikazu , Ando Eiji , Tsunasawa Susumu , Nishimura Osamu
Published: November 2005

We have developed the NBS (2‐nitrobenzenesulfenyl) method, a quantitative proteome analysis method utilizing stable isotope labeling followed by mass spectrometry. The potential of this method was reported previously, and the procedure has now been further optimized. Here, we describe a procedure utilizing urea or guanidine hydrochloride as a protein denaturant, in conjunction with an improved chromatographic enrichment method for the NBS‐labeled peptides using a phenyl resin column. By using this new protocol, both sample loss throughout the protocol and the elution of unwanted unlabeled peptides can be minimized, improving the efficiency of the analysis significantly. Copyright © 2005 John Wiley & Sons, Ltd.
Direct infusion electrospray ionization mass spectra of crude cell extracts for microbial characterizations: influence of solvent conditions on the detection of proteins
Authors: Vaidyanathan Seetharaman , O'Hagan Steve , Goodacre Royston
Published: November 2005

Direct infusion electrospray ionization mass spectrometry (DIES‐MS) of crude bacterial extracts is a rapid method that can be used to characterize microbial cells. Phospholipids, metabolites, and proteins can be detected rapidly with minimal sample preparation. However, several factors influence the detection of signals in such high‐throughput analyses. We studied the influence of solvent conditions, including the organic content and pH of the solvent, on the extraction and subsequent detection of signals in DIES‐MS, with a view to improving the detection of protein signals. Unfractionated cell extracts from three strains of the Gram‐negative Escherichia coli (including one encoding a recombinant green fluorescence protein), and the Gram‐positive Bacillus sphaericus and B. subtilis were investigated. Both pH and the organic content of the solvent were found to influence the spectral information as observed from principal component analysis of the spectral data. A polar solvent with higher organic content resulted in the extraction of phospholipids that overtly dominate the spectral information. Decreasing the organic content of the extraction solvent resulted in the improved detection of protein peaks. Altering the pH of the extraction solvent resulted in different protein profiles from the same bacterium, as observed after spectral deconvolution. In addition, the protein profiles were also different when using different organic solvents. Spectral deconvolution showed several protein peaks that had mass‐based homology with those in protein databases for the (sequenced) organisms studied. These results suggest that a combination of solvent conditions can be used to generate protein profiles rapidly that when combined can provide additional valuable proteomic information. Copyright © 2005 John Wiley & Sons, Ltd.
Rapid and direct measurement of free concentrations of highly protein‐bound fluoxetine and its metabolite norfluoxetine in plasma
Authors: Guo Bin , Li Chuan , Wang Guangji , Chen Laishun
Published: November 2005

Fluoxetine (F) and its active N‐demethylated metabolite, norfluoxetine (NF), are selective serotonin re‐uptake inhibitors that bind extensively to plasma proteins. Development and validation of a novel method for measuring free concentrations of F and NF in plasma are reported here. The plasma filtrate was prepared by a high‐speed short‐duration ultrafiltration (UF) and then submitted directly to a short‐column liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay. There was no significant matrix effect on the analysis, and non‐specific binding of the analytes to the UF devices was negligible. For validation of the method, the recovery of the free analytes was compared to that from an optimized equilibrium dialysis method, and analyte stability was examined under conditions mimicking the sample storage, handling, and analysis procedures. The linearity range was 0.37–12 ng/mL for F and NF; the within‐run and between‐run relative standard deviations were less than 11.9%, and accuracies across the assay range were 100 ± 10.3%. This new method was then further validated in a pharmacokinetic (PK) study in beagle dogs receiving a single oral dose of fluoxetine hydrochloride. The integrity of the resulting PK data of free F and NF was absolute. The PK data indicate that the novel method is accurate and reliable. To our knowledge this is the first report describing a rapid and reliable method for direct measurement of free concentrations of F and NF in plasma, which will be useful for clinical pharmacokinetic/pharmacodynamic studies of F. Furthermore, the strategies described herein may be applied to the development and validation of methods for measuring the free concentrations of other drugs in plasma. Copyright © 2005 John Wiley & Sons, Ltd.
Top‐down characterization of proteins and drug‐protein complexes using nanoelectrospray tandem mass spectrometry
Authors: Mandal Rupasri , Li Xing‐Fang
Published: November 2005

We report a ‘top‐down’ approach for characterization of proteins, and identification of binding sites in protein‐drug complexes using nanoelectrospray ionization hybrid quadrupole time‐of‐flight tandem mass spectrometry (nanoESI‐MS/MS). The efficiency of direct fragmentation of intact protein ions and the feasibility of this method were initially demonstrated using several well‐characterized proteins with different molecular weights including metallothionein (6126 Da), cytochrome c (horse, 12360 Da), myoglobin (horse, 16592 Da), and hemoglobin (human, 64453 Da). Simply varying collision energy without enzyme digestion and gel or LC separation generated a range of peptide fragments of these proteins. Over 80% of these peptide ions matched those in the SWISS‐PROT database with mass accuracy of 8 to 32 ppm with external calibration. This technique was further applied to fragment a cisplatin‐metallothionein complex to identify the binding sites, demonstrating a potential application in the study of drug‐protein binding. Copyright © 2005 John Wiley & Sons, Ltd.
Characterization of boldione and its metabolites in human urine by liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometry
Authors: Kim Yunje , Jun Myungyoon , Lee Won
Published: November 2005

Boldione (1,4‐androstadiene‐3,17‐dione) is a direct precursor (prohormone) to the anabolic steroid boldenone (1,4‐androstadiene‐17β‐ol‐3‐one). It is advertised as a highly anabolic/androgenic compound promoting muscularity, enhancing strength and overall physical performance, and is available on the Internet and in health stores. This work was undertaken to determine and characterize boldione and its metabolites in human urine, using both liquid chromatography with electrospray ionization mass spectrometry and gas chromatography with mass spectrometry and derivatization. Boldione and its three metabolites were detected in dosed human urine after dosing a healthy volunteer with 100 mg boldione. The excretion studies showed that boldione and its metabolites were detectable in urine for 48 h after oral administration, with maximum excretion rates after 1.8 and 3.6 h (boldenone case). The amounts of boldione and boldenone excreted in urine from this 100 mg dose were 34.45 and 15.95 mg, respectively. Copyright © 2005 John Wiley & Sons, Ltd.
Myocardial regulatory proteins and heart failure
Authors: Adamcová Michaela , Štěrba Martin , Šimůnek Tomáš , Potáčová Anna , Popelová Olga , Geršl Vladimír
Published: November 2005

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are considered to be the most specific and sensitive biochemical markers of myocardial damage. Troponins have been studied in a wide range of clinical settings, including heart failure; however, there are few data on the role of regulatory proteins in the pathogenesis of heart failure, although a few interesting hypotheses have been proposed. A considerable body of evidence favours the view that alteration of the myocardial thin filament is the primary event leading to defective contractility of the failing myocardium, while the changes in Ca2+ handling are a compensatory response. A better understanding of the role of regulatory proteins under different physiological and pathological conditions could lead to new therapeutic approaches in heart failure. Recently, calcium sensitisation has been proposed as a novel method by which cardiac performance may be enhanced via an increase in the affinity of troponin C for calcium but without affecting intracellular calcium concentration. To date, the only calcium sensitizer used in clinical practice is levosimendan.
Influence of ACE‐inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices
Authors: Milting Hendrik , Kassner Astrid , Arusoglu Latif , Meyer Helmut E. , Morshuis Michel , Brendel Ramona , Klauke Bärbel , El Banayosy Aly , Körfer Reiner
Published: November 2005

Background:

Whether adverse structural changes in the myocardium due to remodelling can be reversed by ventricular assist device (VAD) support in patients with end‐stage heart failure is controversial.

Aims:

To investigate the effect of VAD support on the extra‐cellular matrix.

Methods:

We analysed the collagen content in terminal failing ventricles of VAD‐patients and donor hearts using 4‐hydroxyproline for total collagen and real time RT‐PCR for fibronectin (FN), collagen I alpha 1 (Col1A1), III alpha 1 (Col3A1) and TGF beta 1 analysis.

Results:

Compared to donor hearts we found similar increases in Col1A1 and TGF beta1 but not Col3A1 and FN mRNAs, which were similar in the myocardium from patients receiving a VAD or heart transplant. However, patients receiving ACE‐I during VAD‐support had lower Col1A1 mRNA content at transplantation. The total collagen content was not influenced by mechanical unloading or by ACE‐I medication.

Conclusion:

Mechanical unloading by VAD does not reduce the collagen content of the terminal failing ventricle possibly due to increased TGF beta1 levels. However, Col1A1 production may be reduced by ACE‐I medication during VAD support.
Decreased survival in diabetic patients with heart failure due to systolic dysfunction☆
Authors: Kamalesh Masoor , Subramanian Usha , Sawada Stephen , Eckert George , Temkit M'Hamed , Tierney William
Published: November 2005

Background:

Prognosis of patients with heart failure (HF) has improved in recent years due to advances in therapy. Whether this is also true for diabetic subjects with HF in clinical practice has not been studied in a prospective manner.

Methods:

All patients with HF and left ventricular systolic dysfunction attending the outpatient clinic at our Veteran's Hospital between October 1999 and November 2000 were enrolled in our study and followed prospectively. Electronic medical records were accessed for data on comorbid conditions, medications, echocardiogram results and mortality information. Mean follow‐up was 2.7 years.

Results:

Of 495 patients with HF due to systolic dysfunction enrolled in the study, 293 (59%) had diabetes. Prevalence of hypertension, diuretic use and angiotensin converting enzyme inhibitor use was higher among diabetics. Beta‐blocker usage was equal and high in both groups (60%). On follow‐up, 109/273 (37%) patients in the diabetic group died, compared with 49/202 (24%) in the non‐diabetic group. Independent predictors of death were diabetes (p<0.005, OR=1.73), age at enrollment (p<0.0001, OR=1.06), serum creatinine (p<0.01, OR=1.44) and diuretic use (p=0.038, OR=1.85). Beta‐blocker use was associated with a decreased risk of death on univariate analysis only.

Conclusions:

Our results show that diabetic patients with HF continue to have higher mortality than non‐diabetic patients with HF despite advances in therapy.