bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric coalescence of reactively wetting droplets
Authors: Zheng C. X. , Tang W. X. , Jesson D. E.
Published: February 2012

Coalescence of droplets during reactive wetting is investigated for the liquid Ga/GaAs(001) system. In situ mirror electron microscopy reveals that coalescence predominantly involves the motion of one reactive droplet relative to the other. This behaviour differs significantly from coalescence in non-reactive systems and is associated with contact line pinning at a ridge/etch pit edge which is identified using atomic force microscopy and selective etching. A simple geometrical model is presented to describe the pinning.
Functionality in single-molecule devices: Model calculations and applications of the inelastic electron tunneling signal in molecular junctions
Authors: Dash L. K. , Ness H. , Verstraete M. J. , Godby R. W.
Published: February 2012

We analyze how functionality could be obtained within single-molecule devices by using a combination of non-equilibrium Green's functions and ab initio calculations to study the inelastic transport properties of single-molecule junctions. First, we apply a full non-equilibrium Green's function technique to a model system with electron-vibration coupling. We show that the features in the inelastic electron tunneling spectra (IETS) of the molecular junctions are virtually independent of the nature of the molecule-lead contacts. Since the contacts are not easily reproducible from one device to another, this is a very useful property. The IETS signal is much more robust versus modifications at the contacts and hence can be used to build functional nanodevices. Second, we consider a realistic model of a organic conjugated molecule. We use ab initio calculations to study how the vibronic properties of the molecule can be controlled by an external electric field which acts as a gate voltage. The control, through the gate voltage, of the vibron frequencies and (more importantly) of the electron-vibron coupling enables the construction of functionality: nonlinear amplification and/or switching is obtained from the IETS signal within a single-molecule device.
Symmetry groups and fundamental solutions for systems of parabolic equations
Authors: Kang Jing , Qu Changzheng
Published: February 2012

In this paper, the relationship between Lie point symmetry and fundamental solution for systems of parabolic equations is explored. It is shown that the fundamental solutions of the systems of parabolic equations admitting certain symmetries can be obtained by inverting the Laplace transformation of the corresponding group-invariant solutions. Several examples are presented to illustrate the approach. Furthermore, the relationship between fundamental solutions for two systems of parabolic equations related by an equivalence transformation is identified.
Anisotropic bimodal distribution of blocking temperature with multiferroic BiFeO3 epitaxial thin films
Authors: Safeer C. K. , Chamfrault M. , Allibe J. , Carretero C. , Deranlot C. , Jacquet E. , Jacquot J.-F. , Bibes M. , Barthélémy A. , Dieny B. , Béa H. , Baltz V.
Published: February 2012

Controlling BiFeO3 (BFO)/ferromagnet (FM) interfacial coupling appears crucial for electrical control of spintronic devices using this multiferroic. Here, we analyse the magnetic behaviour of exchange-biased epitaxial-BiFeO3/FM bilayers with in-plane or out-of-plane magnetic anisotropies. We report bimodal distributions of blocking temperatures similar to those of polycrystalline-antiferromagnet (AF)/FM bilayers. The high-temperature contribution depends on the FM anisotropy direction and is likely related to thermally activated depinning of domain walls in the BiFeO3 single crystal film as opposed to thermally activated reversal of spins in AF grains for polycrystalline AF. In contrast, the low-temperature contribution weakly depends on the anisotropy direction, consistent with a spin-glass origin.
Shear-band arrest and stress overshoots during inhomogeneous flow in a metallic glass
Authors: Maaß R. , Klaumünzer D. , Villard G. , Derlet P. M. , Löffler J. F.
Published: February 2012

At the transition from a static to a dynamic deformation regime of a shear band in bulk metallic glasses, stress transients in terms of overshoots are observed. We interpret this phenomenon with a repeated shear-melting transition and are able to access a characteristic time for a liquidlike to solidlike transition in the shear band as a function of temperature, enabling us to understand why shear bands arrest during inhomogenous serrated flow in bulk metallic glasses.
High efficiency planar Si/organic heterojunction hybrid solar cells
Authors: He Lining , Jiang Changyun , Wang Hao , Lai Donny , Rusli
Published: February 2012

We present an efficient hybrid solar cell based on poly (3,4-ethylene-dioxythiophene):polystyrenesulfonate and planar Si with (100) and (111) orientations. The effect of Si surface native oxide on cell performance is studied. Compared to cell with hydrogen-terminated Si surface, the cell with oxygen-terminated Si surface reveals a 530-fold increase in power conversion efficiency (PCE) from 0.02% to 10.6%. The formation of SiOx-Si bonds poses a net positive surface dipole which leads to a favorable band alignment for charge separation. However, thicker oxide degrades cell performance due to higher series resistance. This study demonstrates the highest PCE reported to-date in this field.
Sign change in the organic magnetoresistance of tris(8-hydroxyquinolinato)aluminum upon annealing
Authors: Kang Hoju , Lee Ik-Jae , Sup Yoon Choon
Published: February 2012

We report the sign change in the magnetoresistance of a tris(8-hydroxyquinolinato)aluminum film with the morphological change from amorphous to crystalline state upon annealing. The negative component of the magnetoresistance followed power law behavior, whereas the positive one showed non-Lorentzian function behavior. The decreasing absolute values of the negative component with increased annealing temperature may be understood by both intersystem-crossing-based mechanism and quenching of triplet excitons. The increasing values of the positive component with increased annealing temperature may be explained by the increase in the hopping probability of charge carriers with increased crystallinity of the film.
Top-gated germanium nanowire quantum dots in a few-electron regime
Authors: Shin Sung-Kwon , Huang Shaoyun , Fukata Naoki , Ishibashi Koji
Published: February 2012

Top gated quantum dots (QDs) have been fabricated from n-type chemically synthesized germanium nanowires (GeNWs) by constricting its length with metal electrode contacts. With an intermediate HfO2 thin film, the constricted GeNW was fully covered by an Omega-shaped top-gate. The QD was probed and characterized by single-electron transport measurements at liquid helium temperature and has been found to reach a few-electron regime, in which the number of confined electrons was tunable from zero. The absolute zero-electron was confirmed with a charge stability diagram, and it was revealed that the extremely small QD arose from potential fluctuations due to phosphorus donors.
Low operation voltage and high thermal stability of a WSi2 nanocrystal memory device using an Al2O3/HfO2/Al2O3 tunnel layer
Authors: Uk Lee Dong , Jun Lee Hyo , Kyu Kim Eun , You Hee-Wook , Cho Won-Ju
Published: February 2012

A WSi2 nanocrystal nonvolatile memory device was fabricated with an Al2O3/HfO2/Al2O3 (AHA) tunnel layer and its electrical characteristics were evaluated at 25, 50, 70, 100, and 125 °C. The program/erase (P/E) speed at 125 °C was approximately 500 μs under threshold voltage shifts of 1 V during voltage sweeping of 8 V/−8 V. When the applied pulse voltage was ±9 V for 1 s for the P/E conditions, the memory window at 125 °C was approximately 1.25 V after 105 s. The activation energies for the charge losses of 5%, 10%, 15%, 20%, 25%, 30%, and 35% were approximately 0.05, 0.11, 0.17, 0.21, 0.23, 0.23, and 0.23 eV, respectively. The charge loss mechanisms were direct tunneling and Pool-Frenkel emission between the WSi2 nanocrystals and the AHA barrier engineered tunneling layer. The WSi2 nanocrystal memory device with multi-stacked high-K tunnel layers showed strong potential for applications in nonvolatile memory devices.
A study of single-crystal silicon diodes integrated on flexible substrates using conductive adhesives
Authors: Doran C. , Chen W. , Alford T. L. , Lau S. S.
Published: February 2012

In this study, we investigated the possibility of fabricating flexible single-crystal Si-Pd diodes on polymer substrates using silver-filled conductive tape or epoxy. This simple technique mitigates the complexity of process-intensive metal-bonding schemes to achieve backside electrical contacts on semiconductor devices. The performance of such devices is evaluated while bent to a 1.2 cm radius of curvature. The longer-term stability of the devices fabricated is also briefly discussed.
ON-OFF switching mechanism of resistive–random–access–memories based on the formation and disruption of oxygen vacancy conducting channels
Authors: Kamiya Katsumasa , Young Yang Moon , Park Seong-Geon , Magyari-Köpe Blanka , Nishi Yoshio , Niwa Masaaki , Shiraishi Kenji
Published: February 2012

We study the ON-OFF switching mechanism of oxide-based resistive–random–access–memories using theoretical calculations. Electron deficient vacancies (VO) up to 1+ charge states would stabilize a cohesive filament, while further electron removal will stabilize the disrupted VO configurations with 2+ charges. The VO cohesion-isolation transition upon carrier injection and removal is shown to be a strong driving force in the ON-OFF switching process. We also propose that bipolar or unipolar behavior is determined by how the carriers are injected into VO. The control of the carrier injection by the electrode material selection is essential for desired bipolar switching.
Note: Laser-induced acoustic desorption/synchrotron vacuum ultraviolet photoionization mass spectrometry for analysis of fragile compounds and heavy oils
Authors: Jia Liangyuan , Weng Junjie , Zhou Zhongyue , Qi Fei , Guo Wenyue , Zhao Lianming , Chen Juan
Published: February 2012

In this work, we coupled synchrotron vacuum ultraviolet photoionization (SVUV PI) method with the laser-induced acoustic desorption (LIAD) technique for mass spectrometric analysis. The LIAD technique is a “soft” desorption method, which could avoid the degradation of analytes during desorption process. Meanwhile, SVUV PI is an efficient “soft” ionization source. The new combination of the “soft” desorption technique and “soft” photoionization method is well suitable to reduce the difficulty for interpreting the mass spectra of the fragile compounds and heavy oils.
Strain relaxation analysis of LaAlO3/SrTiO3 heterostructure using reciprocal lattice mapping
Authors: Wei Wei , Sehirlioglu Alp
Published: February 2012

Strain-relaxation in LaAlO3/SrTiO3 heterostructures was systematically investigated with LaAlO3 film thickness in the range 4.9-84 nm. Heterostructures were characterized using reciprocal lattice mapping (RLM), high resolution rocking curve, and x-ray reflectivity. RLM enables the measurement of lattice constant with accuracy of 10−6 nm. Lattice constant, mismatch, and strain are independently determined in both out-of-plane and in-plane directions. Heterostructures are tetragonally distorted over the entire range of film thickness, even in the film with thickness of 84 nm, in which plastic deformation occurred. This strain-relaxation analysis of LaAlO3/SrTiO3 heterostructure contributes, on the experimental basis, to the knowledge of the strained heterostructure interfaces from thin film growth point of view.
Commensurate-incommensurate transition of 4He adsorbed on a single C60 molecule
Authors: Shin Hyeondeok , Kwon Yongkyung
Published: February 2012

Path-integral Monte Carlo calculations have been performed to study 4He adsorption on a single C60 molecule. Helium corrugations on the fullerene molecular surface are incorporated with the 4He-C60 interaction described by the sum of all 4He-C interatomic pair potentials. Radial density distributions show a layer-by-layer growth of 4He with the first adlayer being located at a distance of ∼6.3 Å from the center of the C60 molecule. The monolayer shows different quantum states as the number of 4He adatoms N varies. For N = 32, we find a commensurate solid, with each of the 32 adsorption sites on the molecular surface being occupied by a single 4He atom. Various domain-wall structures are observed as more 4He atoms are added and the first layer crystallizes into an incommensurate solid when it is completely filled. This commensurate-incommensurate transition of the helium monolayer is found to be accompanied by re-entrant superfluid response at a low temperature of 0.31 K with the superfluidity being totally quenched at N = 32, 44, and 48. Finally, the different quantum states observed in the helium monolayer around C60 are compared with phase diagrams proposed for the corresponding layer on a graphite surface.
Real-time synchrotoron radiation X-ray diffraction and abnormal temperature dependence of photoluminescence from erbium silicates on SiO2/Si substrates
Authors: Omi H. , Tawara T. , Tateishi M.
Published: February 2012

The erbium silicate formation processes during annealing in Ar gas were monitored by synchrotron radiation grazing incidence X-ray diffraction (GIXD) in real time and the optical properties of the silicates were investigated by photoluminescence measurements in spectral and time-resolved domains. The GIXD measurements show that erbium silicates and erbium oxide are formed by interface reactions between silicon oxide and erbium oxides deposited on silicon oxide by reactive sputtering in Ar gas and O2/Ar mixture gas ambiences. The erbium silicates are formed above 1060 °C in Ar gas ambience and above 1010 °C in O2/Ar gas ambience, and erbium silicides are dominantly formed above 1250 °C. The I15/2-I13/2 Er3+ photoluminescence from the erbium oxide and erbium silicate exhibits abnormal temperature dependence, which can be explained by the phonon-assisted resonant absorption of the 532-nm excitation photons into the 2H11/2 levels of Er3+ ions of the erbium compounds.
Arsenosugar phospholipids and arsenic hydrocarbons in two species of brown macroalgae
Authors: García-Salgado Sara , Raber Georg , Raml Reingard , Magnes Christoph , Francesconi Kevin A.
Published: February 2012

Environmental contextAlthough organoarsenic compounds occur in marine organisms at high concentrations, the origin and role of these compounds is unknown. Arsenic-containing lipids (arsenolipids) are newly discovered compounds in fish. We identify a range of arsenolipids in algae and propose that algae are the origin of these unusual arsenic compounds in marine ecosystems.
AbstractFourteen arsenolipids, including 11 new compounds, were identified and quantified in two species of brown algae, Wakame (Undaria pinnatifida) and Hijiki (Hizikia fusiformis), by high resolution mass spectrometry, high performance liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. Both algal species contained arsenosugar-phospholipids as the major type of arsenolipid, and arsenic-hydrocarbons were also significant components, particularly in Hijiki. The origin of the various arsenolipids, and the possible significance of their relative quantities, is briefly discussed.
Nitrogen loss by surface runoff from different cropping systems
Authors: Jiao P. , Xu D. , Wang S. , Wang Y. , Liu K. , Tang G.
Published: February 2012

Reducing nitrogen (N) loss from agricultural soils as surface runoff is essential to prevent surface water contamination. The objective of 3-year study, 2007–09, was to evaluate surface runoff and N loss from different cropping systems. There were four treatments, including one single-crop cropping system with winter wheat (Triticum aestivum L.) followed by summer fallow (wheat/fallow), and three double-cropping systems: winter wheat/corn (Zea mays L.), wheat/cotton (Gossypium hirsutum L.), and wheat/soybean (Glycine max L. Merrill). The wheat/fallow received no fertiliser in the summer fallow period. The four cropping systems were randomly assigned to 12 plots of 5 m by 2 m on a silty clay soil. Lower runoff was found in the three double-cropping systems than the wheat/fallow, with the lowest runoff from the wheat/soybean. The three double-cropping systems also substantially reduced losses of ammonium-N (NH4+-N), nitrate-N (NO3–-N), dissolved N (DN), and total N (TN) compared with the wheat/fallow. Among the three double-cropping systems, the highest losses of NO3–-N, DN, and TN were from the wheat/cotton, and the lowest losses were from the wheat/soybean. However, the wheat/soybean increased NO3–-N and DN concentrations compared with wheat/fallow. The losses in peak events accounted for >64% for NH4+-N, 58% for NO3–-N, and 41% for DN of the total losses occurring during the 3-year experimental period, suggesting that peak N-loss events should be focussed on for the control of N loss as surface runoff from agricultural fields.
Levels of dispersal and tail loss in an Australian gecko (Gehyra variegata) are associated with differences in forest structure
Authors: Duckett Paul E. , Stow Adam J.
Published: February 2012

Corridors of natural habitat are often sought to maintain dispersal and gene flow among habitat patches. However, structural changes in natural habitat over space and time may influence connectivity. Here we investigate whether differences in forest structure and the frequency of potential retreat sites is associated with the genetic structure of a tree-dwelling Australian gecko (Gehyra variegata). We sampled 113 adult geckos from multiple state forest and adjacent reserve locations within the Pilliga forest, New South Wales, Australia. Individuals were genotyped at 14 microsatellite loci and levels of dispersal were inferred by the degree of genetic structuring observed in state forest and reserve. A greater proportion of dead trees and tree debris (features that are used as retreat sites by G. variegata) were present within the state forests than in the reserve locations (P < 0.05). This reduction in frequency of retreat sites in reserves was associated with significantly less genetic structuring of G. variegata, implying higher levels of dispersal. Tail loss was also significantly higher in G. variegata sampled in reserves than in the state forests. We conclude that dispersal characteristics in G. variegata are associated with structural changes to natural habitat and that this may influence rates of predation.
Development and application of an agent-based model to evaluate methods for estimating relative abundance indices for shoaling fish such as Pacific rockfish (Sebastes spp.)
Authors: Thorson James T. , Stewart Ian J. , Punt André E.
Published: February 2012

Thorson, J. T., Stewart, I. J., and Punt, A. E. 2012. Development and application of an agent-based model to evaluate methods for estimating relative abundance indices for shoaling fish such as Pacific rockfish (Sebastes spp.). – ICES Journal of Marine Science, 69: 635–647. Many marine fish, including Pacific rockfish (Sebastes spp.), exhibit habitat-selective and shoaling behaviours, which can lead to imprecision when using survey data to estimate an annual index of stock abundance. We develop a spatial agent-based model (ABM) for Pacific rockfish, which generates data similar to those observed in existing bottom-trawl surveys and can represent various spatial and shoaling behaviours. We use the ABM to evaluate the performance of a model that uses mixture distribution methods to account for fish shoals and delta-methods to account for range expansion or contraction. This delta-mixture model is compared with conventional delta-generalized linear models (delta-GLMs) and a quantile regression delta-model. The delta-mixture increases precision by 15% relative to delta-GLMs in estimated abundance indices when shoaling behaviours are present, whereas precision is similar between delta-GLM and delta-mixture models when shoals are absent. The delta-quantile method has similar improvements over conventional delta-GLM methods, and the improved precision from delta-mixture and delta-quantile methods is decreased but not eliminated by decreased sampling intensities. These simulations represent the first evaluation of delta-mixture models for index standardization and show a substantial improvement over conventional delta-GLMs for shoaling species such as Pacific rockfish.
Historical variations in the year-class strength of beaked redfish (Sebastes mentella) in the Barents Sea
Authors: Planque B. , Johannesen E. , Drevetnyak K. V. , Nedreaas K. H.
Published: February 2012

Planque, B., Johannesen, E., Drevetnyak, K. V., and Nedreaas, K. H. 2012. Historical variations in the year-class strength of beaked redfish (Sebastes mentella) in the Barents Sea. – ICES Journal of Marine Science, 69: 547–552. The present work provides the first quantitative estimate of the historical fluctuations in the year-class strength of beaked redfish in the Barents Sea. The year-class strength index is based on scientific survey data collected by Norway and Russia during the past three decades. It is defined as the effective number of 0-group fish that will eventually enter the fishery. Uncertainties in the year-class strength indices are estimated using a statistical modelling approach, which accounts for observation errors. The reconstructed series indicate clear periods of high recruitment (late 1980s–early 1990s) and 8 years of near complete recruitment failure (1996–2003). The apparent recovery in recent years is highly uncertain and needs to be confirmed by future observations. The modelling approach developed here can be applied to other fish stocks for which catch-at-age data are available from several surveys.
Using cross-correlations to assess the relationship between time-lagged pressure and state indicators: an exemplary analysis of North Sea fish population indicators
Authors: Probst Wolfgang Nikolaus , Stelzenmüller Vanessa , Fock Heino Ove
Published: February 2012

Probst, W. N., Stelzenmüller, V., and Fock, H. 2012. Using cross-correlations to assess the relationship between time-lagged pressure and state indicators: an exemplary analysis of North Sea fish population indicators. – ICES Journal of Marine Science, 69: 670–681. A sustainable ecosystem-based management, as postulated by the European Union-Marine Strategy Framework Directive (MSFD), requires a sound understanding of the cause–effect relationships between human pressures and ecosystem states. In this study, cross-correlations are used to introduce a protocol for the analysis of time-lagged relationships between pressure and state indicators. To perform meaningful cross-correlations, the time-series of the pressure and the state indicator should be prewhitened by fitting autoregressive integrated moving average models to the pressure indicator time-series. This study provides some theoretical examples on the implications of non-prewhitened and prewhitened cross-correlations and exemplifies the use of prewhitened cross-correlations to compare the pressure–state relationship of a well-established indicator suite vs. the relationship of a new indicator proposed under the MSFD. The established indicator suite is fishing mortality (F) vs. spawning-stock biomass (SSB), the new indicator suite is F vs. the 95% percentile of the length frequency distribution (L95). The L95 aims to characterize the proportion of large individuals within a population. The prewhitened cross-correlations for F and SSB are significant for all four analysed species (cod, haddock, saithe, and plaice), the L95 is correlated with F for cod, haddock, and saithe. However, the L95 was also influenced by the annual survey catch and recruitment.
A comparison of the acid‐inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism
Authors: Hunfeld N. G. , Touw D. J. , Mathot R. A. , van Schaik R. H. , Kuipers E. J.
Published: February 2012

Background

Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25–30% an intermediate and 2–5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences.

Aim

To compare the acid‐inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics.

Methods

Eighteen healthy Helicobacter pylori‐negative Caucasian subjects with CYP2C19*2‐*6 and *17 genotype were included in a randomised investigator‐blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24‐h pH‐monitoring was performed on days 0, 1 and 5 of oral dosing.

Results

Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs.

Conclusions

Once‐daily dosing with esomeprazole 40 mg provides a more effective and faster acid‐inhibitory effect than rabeprazole 20 mg. The acid‐inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP2C19 polymorphism.
Anaesthetists’ risk assessment of placebo nerve block studies using the SHAM (Serious Harm and Morbidity) scale
Authors: Jarman J. , Marks N. , Fahy C.J. , Costi D. , Cyna A. M.
Published: February 2012

The SHAM (Serious Harm and Morbidity) scale was developed to categorise the severity of potential complications of placebo control interventions in the context of local anaesthesia research. A convenience sample of 43 anaesthetists used the SHAM scale to grade ten published randomised controlled trials investigating local anaesthesia nerve blocks. The Fleiss κ statistic assessed agreement between these anaesthetists and probability of random agreement (Pr(e)) when using the SHAM scale; a κ > 0 shows concordance between assessors above random agreement. Overall κ was 0.50 (95% CI 0.49–0.51, p < 0.001), Pr(e) = 0.21. There was moderate agreement between assessors in determining whether studies were low‐risk (SHAM score 0–2) or high‐risk (SHAM score 3–4) (κ 0.60 (95% CI 0.58–0.62), Pr(e) = 0.51). Compared with anaesthetists given clinical examples of interventions when applying the SHAM score, anaesthetists who were not given examples showed significantly less inter‐individual agreement (κ 0.76 (95% CI 0.72–0.81), Pr(e) = 0.5 vs 0.45 (95% CI 0.41–0.49), Pr(e) = 0.52, p < 0.0001). These results suggest that the SHAM score can be successfully used to grade the severity of potential complications of placebo‐controlled interventions in local anaesthesia research and represent a first step towards the score’s validation.
Population pharmacokinetics of mycophenolic acid and dose optimization with limited sampling strategy in liver transplant children
Authors: Barau Caroline , Furlan Valérie , Debray Dominique , Taburet Anne‐Marie , Barrail‐Tran Aurélie
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Population pharmacokinetic data for mycophenolic acid (MPA) have been reported in adult and paediatric kidney transplant recipients but not in paediatric liver transplant recipients.

• MPA AUC during a dosage interval (AUC(0,12 h) is routinely used to optimize mycophenolate mofetil (MMF) dosages in solid organ transplant recipients.

WHAT THIS STUDY ADDS

• This study describes MPA population pharmacokinetics in paediatric liver transplant recipients for the first time.

• The age of the children and the time elapsed since the transplantation were found to affect MPA pharmacokinetics significantly, mainly the apparent volume of distribution.

• The limited sampling strategy chosen to estimate individual MPA AUC(0,12 h) with concentrations measured 0, 1 and 4 h after MMF administration may be useful to optimize child care during the post transplantation period.

AIMS The aims were to estimate the mycophenolic acid (MPA) population pharmacokinetic parameters in paediatric liver transplant recipients, to identify the factors affecting MPA pharmacokinetics and to develop a limited sampling strategy to estimate individual MPA AUC(0,12 h).

METHODS Twenty‐eight children, 1.1 to 18.0 years old, received oral mycophenolate mofetil (MMF) therapy combined with either tacrolimus (n= 23) or ciclosporin (n= 5). The population parameters were estimated from a model‐building set of 16 intensive pharmacokinetic datasets obtained from 16 children. The data were analyzed by nonlinear mixed effect modelling, using a one compartment model with first order absorption and first order elimination and random effects on the absorption rate (ka), the apparent volume of distribution (V/F) and apparent clearance (CL/F).

RESULTS Two covariates, time since transplantation (≤ and >6 months) and age affected MPA pharmacokinetics. ka, estimated at 1.7 h−1 at age 8.7 years, exhibited large interindividual variability (308%). V/F, estimated at 64.7 l, increased about 2.3 times in children during the immediate post transplantation period. This increase was due to the increase in the unbound MPA fraction caused by the low albumin concentration. CL/F was estimated at 12.7 l h−1. To estimate individual AUC(0,12 h), the pharmacokinetic parameters obtained with the final model, including covariates, were coded in Adapt II® software, using the Bayesian approach. The AUC(0,12 h) estimated from concentrations measured 0, 1 and 4 h after administration of MMF did not differ from reference values.

CONCLUSIONS This study allowed the estimation of the population pharmacokinetic MPA parameters. A simple sampling procedure is suggested to help to optimize pediatric patient care.
A novel function for the haemopoietic supportive murine bone marrow MS‐5 mesenchymal stromal cell line in promoting human vasculogenesis and angiogenesis
Authors: Zhou Bob , Tsaknakis Grigorios , Coldwell Kate E. , Khoo Cheen P. , Roubelakis Maria G. , Chang Chao‐Hui , Pepperell Emma , Watt Suzanne M.
Published: February 2012

The bone marrow contains specific microenvironmental stem cell niches that maintain haemopoiesis. CXCL12‐expressing mesenchymal stromal cells are closely associated with the bone marrow sinusoidal endothelia, forming key elements of the haemopoietic stem cell niche, yet their ability to regulate endothelial function is not clearly defined. Given that the murine nestin+ cell line, MS‐5, provides a clonal surrogate bone marrow stromal niche capable of regulating both murine and human primitive haemopoietic stem/progenitor cell (HSC/HPC) fate in vitro, we hypothesized that MS‐5 cells might also support new blood vessel formation and function. Here, for the first time, we demonstrate that this is indeed the case. Using proteome arrays, we identified HSC/HPC active angiogenic factors that are preferentially secreted by haemopoietic supportive nestin+MS‐5 cells, including CXCL12 (SDF‐1), NOV (CCN3), HGF, Angiopoietin‐1 and CCL2 (MCP‐1). Concentrating on CXCL12, we confirmed its presence in MS‐5 conditioned media and demonstrated that its antagonist in receptor binding, AMD‐3100, which mobilizes HSC/HPCs and endothelial progenitors from bone marrow, could significantly reduce MS‐5 mediated human vasculogenesis in vitro, principally by regulating human endothelial cell migration. Thus, the clonal nestin+MS‐5 murine bone marrow stromal cell line not only promotes human haemopoiesis but also induces human vasculogenesis, with CXCL12 playing important roles in both processes.
Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells
Authors: Wei X. , Peng G. , Zheng S. , Wu X.
Published: February 2012

Objectives

Human umbilical cord can be obtained easily and it represents a non‐controversial source of mesenchymal stem cells (MSCs) and umbilical cord Wharton's jelly‐derived MSCs (UC‐MSCs) have low immunogenicity. In this study, UC‐MSCs were induced to become steroidogenic cells and compared to bone marrow‐derived MSCs (BM‐MSCs).

Material and methods

UC‐MSCs and BM‐MSCs were induced to differentiate into steroidogenic cells by infection with adenovirus containing SF‐1. Expression of steroidogenic mRNA was analysed by real‐time RT‐PCR and steroid secretion was detected by ELISA testing. Viability of differentiated cells was examined using cell counting kit‐8 assay.

Results

Both UC‐MSCs and BM‐MSCs expressed typical MSC markers and could differentiate into adipocytes, osteocytes and chondrocytes and both cell types had the potential to differentiate into steroidogenic cells after being infected with adenovirus containing SF‐1 cDNA. However, UC‐MSCs had significantly higher proliferative potential than BM‐MSCs and differentiated UC‐MSCs had significantly higher expression of all steroidogenic mRNAs tested over those of differentiated BM‐MSCs; this included P450 side‐chain cleavage enzyme, 3β‐HSD, 17β‐HSD type 3, LH‐R, ACTH‐R, P450c21 and CYP17. In addition, differentiated UC‐MSCs secreted significantly more steroidogenic hormones than differentiated BM‐MSCs, including testosterone and cortisol. Furthermore, differentiated UC‐MSCs had significantly higher cell viability than differentiated BM‐MSCs.

Conclusions

UC‐MSCs had significantly higher potential of steroidogenic differentiation than BM‐MSCs; thus, UC‐MSCs could be favourable cells of choice for cell‐based therapy for steroidogenic insufficiency compared to BM‐MSCs.
Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules
Authors: Yang S. , Bo J. , Hu H. , Guo X. , Tian R. , Sun C. , Zhu Y. , Li P. , Liu P. , Zou S. , Huang Y. , Li Z.
Published: February 2012

Objectives

Previous studies have demonstrated that mouse‐ and human‐induced pluripotent stem (iPS) cells can differentiate into primordial germ cells in vitro. However, up to now it is not known whether iPS cells would be able to differentiate into male germ cells in vivo. The aim of this study was to explore differentiation potential of iPS cells to male germ cells in vitro and in vivo.

Materials and methods

In this study, approaches using in vitro retinoic acid induction and in vivo ectopic transplantation were combined to induce iPS cells to become male germ cells.

Results

RT‐PCR showed that expression of pre‐meiotic and meiotic germ cell‐specific genes was enhanced in iPS cell‐derived embryoid bodies (EBs) compared to mRNA transcripts of iPS cells. Immunofluorescence analysis revealed that iPS cell‐derived EBs positively expressed germ‐cell markers VASA, c‐Kit and SCP3. Furthermore, iPS cell‐derived cells dissociated from EBs were injected with testicular cells into dorsal skin of mice. Histological examination showed that iPS cell‐derived cells could reconstitute seminiferous tubules, and meanwhile, iPS cell‐derived germ cells could settle at basement membranes of reconstituted tubules.

Conclusion

Our results suggest that iPS cells are able to differentiate into male germ cells in vitro and that reconstituted seminiferous tubules may provide a functional niche for exogenous iPS cell‐derived male germ cells. Derivation of male germ cells from iPS cells has potential application for treating male infertility and provides an ideal platform for elucidating molecular mechanisms of male germ‐cell development.
Comparison of ontogenetic trophic shift in two hake species, Merluccius capensis and Merluccius paradoxus, from the Northern Benguela Current ecosystem (Namibia) using stable isotope analysis
Authors: IITEMBU JOHANNES A. , MILLER TODD W. , OHMORI KOJI , KANIME ABRAHAM , WELLS SEAN
Published: February 2012

Two species of hake, Merluccius capensis (MC) and Merluccius paradoxus (MP), together account for most of Namibia’s fisheries catch and they are collectively the most important secondary consumers in the Benguela Current ecosystem. To better resolve their feeding behavior in the northern Benguela Current ecosystem, we examined the size‐specific ontogenetic shift in MC and MP using stable isotopes of δ13C and δ15N as measures of relative source production and trophic level. We also compared hake isotope values to those of their major zooplankton (four species) and nekton (12 species/groups) prey. Results from δ15N showed a significant positive relationship with size in both MC and MP; however, the slopes of the two species were significantly different, with MP displaying a steeper trophic shift. A significant increase in δ13C with size was observed in MC but not MP. In all size classes (except ≤20–29 cm) MC expressed significantly higher δ13C values, generally matching their respective shelf‐slope adult distributions. Relative to zooplankton and nekton prey, smaller hake of both species (20–39 cm) were trophically indistinguishable at a trophic level (TL) of 3.3, indicating predominant zooplanktivory. The largest MC of 60–70 cm had TLs of approximately 3.5–3.6, whereas MP of the same size were slightly higher, at 3.7–3.8 TL, indicating greater piscivory. This is the first spatially and ontogenetically extensive stable isotope analysis of MC and MP in the Benguela Current. Further extension of this analysis throughout the hake range would provide considerable insight into the trophic dynamics of this commercially and ecologically important group.
An interplay between Centrin2 and Centrin4 on the bi‐lobed structure in Trypanosoma brucei
Authors: Wang Min , Gheiratmand Ladan , He Cynthia Y.
Published: February 2012

Centrins are conserved calcium‐binding proteins important for various regulatory functions. In procyclic Trypanosoma brucei, TbCentrin2 and TbCentrin4 have distinct effects on cell division but both localize to the basal bodies that seed the flagellum, and a bi‐lobed structure important for organelle duplication and cell division. Here we show that TbCentrin2 and TbCentrin4 both bind to the basal bodies and bi‐lobed structure through the conserved C‐terminal domain. Molecular genetic manipulation of TbCentrin4 levels greatly affects TbCentrin2 association with the bi‐lobed structure. Using established synchronization methods, TbCentrin2 expression level is shown to be relatively constant throughout the cell cycle while TbCentrin4 level fluctuates, decreasing most during early S‐phase when the bi‐lobe undergoes duplication. These results thus suggest a co‐ordinated action between these two centrin proteins, where the cell cycle‐dependent TbCentrin4 expression could regulate the abundance of TbCentrin2 on the bi‐lobed structure.
The exported Plasmodium berghei protein IBIS1 delineates membranous structures in infected red blood cells
Authors: Ingmundson Alyssa , Nahar Carolin , Brinkmann Volker , Lehmann Maik J. , Matuschewski Kai
Published: February 2012

The importance of pathogen‐induced host cell remodelling has been well established for red blood cell infection by the human malaria parasite Plasmodium falciparum. Exported parasite‐encoded proteins, which often possess a signature motif, termed Plasmodium export element (PEXEL) or host‐targeting (HT) signal, are critical for the extensive red blood cell modifications. To what extent remodelling of erythrocyte membranes also occurs in non‐primate hosts and whether it is in fact a hallmark of all mammalian Plasmodium parasites remains elusive. Here we characterize a novel Plasmodium berghei PEXEL/HT‐containing protein, which we term IBIS1. Temporal expression and spatial localization determined by fluorescent tagging revealed the presence of IBIS1 at the parasite/host interface during both liver and blood stages of infection. Targeted deletion of the IBIS1 protein revealed a mild impairment of intra‐erythrocytic growth indicating a role for these structures in the rapid expansion of the parasite population in the blood in vivo. In red blood cells, the protein localizes to dynamic, punctate structures external to the parasite. Biochemical and microscopic data revealed that these intra‐erythrocytic P. berghei‐induced structures (IBIS) are membranous indicating that P. berghei, like P. falciparum, creates an intracellular membranous network in infected red blood cells.
Location of and landing on a source of human body odour by female Culex quinquefasciatus in still and moving air
Authors: LACEY EMERSON S. , CARDÉ RING T.
Published: February 2012

The orientation to and landing on a source of human odour by female Culex quinquefasciatus Say (Diptera: Culicidae) is observed in a wind tunnel without an airflow or with a laminar airflow of 0.2 m s−1. Odours from human feet are collected by ‘wearing’ clean glass beads inside a stocking and presenting beads in a Petri dish in a wind tunnel. Mosquitoes are activated by brief exposure to a 1 L min−1 jet of 4% CO2 positioned 10 cm from the release cage. In moving air at 0.2 m s−1, a mean ± SE of 3.45 ± 0.49 landings are observed in 10‐min trials (five mosquitoes per trial), whereas 6.50 ± 0.96 landings are recorded in still air. Furthermore, 1.45 ± 0.31 mosquitoes are recorded on beads at any one time in moving air (a measure of individuals landing versus one landing multiple times) compared with 3.10 ± 0.31 in still air. Upwind flight to beads in moving air is demonstrated by angular headings of flight immediately before landing, whereas approaches to beads in still air are oriented randomly. The mean ± SE latency until first landing is 226.7 ± 17.98 s in moving air compared with 122.5 ± 24.18 in still air. Strategies used to locate a prospective host at close range in still air are considered.
A leaf gas exchange model that accounts for intra‐canopy variability by considering leaf nitrogen content and local acclimation to radiation in grapevine (Vitis vinifera L.)
Authors: PRIETO JORGE A. , LOUARN GAËTAN , PEREZ PEÑA JORGE , OJEDA HERNÁN , SIMONNEAU THIERRY , LEBON ERIC
Published: February 2012

Understanding the distribution of gas exchange within a plant is a prerequisite for scaling up from leaves to canopies. We evaluated whether leaf traits were reliable predictors of the effects of leaf ageing and leaf irradiance on leaf photosynthetic capacity (Vcmax, Jmax) in field‐grown vines (Vitis vinifera L). Simultaneously, we measured gas exchange, leaf mass per area (LMA) and nitrogen content (Nm) of leaves at different positions within the canopy and at different phenological stages. Daily mean leaf irradiance cumulated over 10 d (PPFD10) was obtained by 3D modelling of the canopy structure. Nm decreased over the season in parallel to leaf ageing while LMA was mainly affected by leaf position. PPFD10 explained 66, 28 and 73% of the variation of LMA, Nm and nitrogen content per area (Na), respectively. Nitrogen content per unit area (Na = LMA × Nm) was the best predictor of the intra‐canopy variability of leaf photosynthetic capacity. Finally, we developed a classical photosynthesis‐stomatal conductance submodel and by introducing Na as an input, the model accurately simulated the daily pattern of gas exchange for leaves at different positions in the canopy and at different phenological stages during the season.
Treatment of demodicosis in dogs: 2011 clinical practice guidelines
Authors: Mueller Ralf S. , Bensignor Emmanuel , Ferrer Lluís , Holm Birgit , Lemarie Stephen , Paradis Manon , Shipstone Michael A.
Published: February 2012

Background and Objectives – These guidelines were written by an international group of specialists with the aim to provide veterinarians with current recommendations for the diagnosis and treatment of canine demodicosis.

Methods – Published studies of the various treatment options were reviewed and summarized. Where evidence in form of published studies was not available, expert consensus formed the base of the recommendations.

Results – Demodicosis can usually be diagnosed by deep skin scrapings or trichograms; in rare cases a skin biopsy may be needed for diagnosis.

Immune suppression due to endoparasitism or malnutrition in young dogs and endocrine diseases, neoplasia and chemotherapy in older dogs are considered predisposing factors and should be diagnosed and treated to optimize the therapeutic outcome. Dogs with disease severity requiring parasiticidal therapy should not be bred.

Secondary bacterial skin infections frequently complicate the disease and require topical and/or systemic antimicrobial therapy.

There is good evidence for the efficacy of weekly amitraz rinses and daily oral macrocyclic lactones such as milbemycin oxime, ivermectin and moxidectin for the treatment of canine demodicosis. Weekly application of topical moxidectin can be useful in dogs with milder forms of the disease. There is some evidence for the efficacy of weekly or twice weekly subcutaneous or oral doramectin. Systemic macrocyclic lactones may cause neurological adverse effects in sensitive dogs, thus a gradual increase to the final therapeutic dose may be prudent (particularly in herding breeds).

Treatment should be monitored with monthly skin scrapings and extended beyond clinical and microscopic cure to minimize recurrences.

Editor’s Note – A brief review article by R. Mueller has been published: Evidence‐based treatment of canine demodicosis, Tierarztl Prax Ausg K Kleintiere Heimtiere 2011; 39: 419–24. This is not considered to constitute duplication of the article published here inVeterinary Dermatology.
Analysis of major histocompatibility complex class I folding: novel insights into intermediate forms
Authors: Simone L. C. , Tuli A. , Simone P. D. , Wang X. , Solheim J. C.
Published: February 2012

Folding around a peptide ligand is integral to the antigen presentation function of major histocompatibility complex (MHC) class I molecules. Several lines of evidence indicate that the broadly cross‐reactive 34‐1‐2 antibody is sensitive to folding of the MHC class I peptide‐binding groove. Here, we show that peptide‐loading complex proteins associated with the murine MHC class I molecule Kd are found primarily in association with the 34‐1‐2+ form. This led us to hypothesize that the 34‐1‐2 antibody may recognize intermediately, as well as fully, folded MHC class I molecules. To further characterize the form(s) of MHC class I molecules recognized by 34‐1‐2, we took advantage of its cross‐reactivity with Ld. Recognition of the open and folded forms of Ld by the 64‐3‐7 and 30‐5‐7 antibodies, respectively, has been extensively characterized, providing us with parameters against which to compare 34‐1‐2 reactivity. We found that the 34‐1‐2+Ld molecules displayed characteristics indicative of incomplete folding, including increased tapasin association, endoplasmic reticulum retention, and instability at the cell surface. Moreover, we show that an Ld‐specific peptide induced folding of the 34‐1‐2+Ld intermediate. Altogether, these results yield novel insights into the nature of MHC class I molecules recognized by the 34‐1‐2 antibody.