bluuebunny/crossref_metadata_2025 huggingface dataset:
An efficient approach for eigenmode analysis of transient distributive mixing by the mapping method
Authors: Gorodetskyi O. , Speetjens M. F. M. , Anderson P. D.
Published: May 2012

The mapping method is an efficient tool to investigate distributive mixing induced by periodic flows. Computed only once, the mapping matrix can be applied a number of times to determine the distribution of concentration inside the flow domain. Spectral analysis of the mapping matrix reveals detailed properties of the distributive mixing as all relevant information is stored in its eigenmodes. Any vector that describes a distribution of concentration can be expanded in the complete system of linearly independent eigenvectors of the mapping matrix. The rapid decay of the contribution of each mode in the eigenmode decomposition allows for a truncation of the eigenmode expansion from the whole spectrum to only the dominant eigenmodes (characterized by a decay rate significantly lower than the duration of the mixing process). This truncated decomposition adequately represents the distribution of concentration inside the flow domain already after a low number of periods, because contributions of all non-dominant eigenmodes rapidly become insignificant. The truncation is determined independently of the initial distribution of concentration and based on the decay rates of the eigenmodes, which are inversely proportional to the corresponding eigenvalues. Only modes with eigenvalues above a certain threshold are retained. The key advantage of the proposed compact eigenmode representation of the mapping method is that it includes practically relevant transient states and not just the asymptotic one. As such the method enables an eigenmode analysis of realistic problems yet with a substantial reduction in computational effort compared to the conventional approach.
Grand canonical-like molecular dynamics simulations: Application to anisotropic mass diffusion in a nanoporous medium
Authors: Hoang Hai , Galliero Guillaume
Published: May 2012

In this work, we describe two grand canonical-like molecular dynamics approaches to investigate mass diffusion phenomenon of a simple Lennard-Jones fluid confined between solid surfaces and in direct contact with reservoirs. In the first method, the density is used as the control variable in the reservoir whereas it is the pressure in the second method. Both methods provide consistent results, however, the constant density approach is the most efficient with respect to the computational time and implementation. Then, employing the constant density approach, we have studied the transient behavior of the diffusion process associated with the migration of one fluid into another one confined between parallel solid walls. Results have shown that the evolution of molar fraction of the invading fluid follows roughly a 1D diffusion model when the solid phase is weakly or moderately adsorbent with a characteristic time increasing when the pore width decreases. However, when the adsorption is high and the pore width small (i.e., below ten molecular sizes), the apparent mass diffusion in the adsorbed layer is reduced compared to that in the center of the slit pore. Hence, this mass diffusion process becomes a two-dimension phenomenon that must take into account an effective mass diffusion coefficient varying locally.
Residual charge density distribution measurement of surface leader with feedback electrostatic probe
Authors: Deng Junbo , Kumada Akiko , Hidaka Kunihiko , Zhang Guanjun , Mu Haibao
Published: May 2012

A charge density distribution scanning system is fabricated using an electrostatic probe, which utilizes DC voltage feedback principle to nullify the electric field between the probe and charged insulator surface. A two-layer structure pipe is designed to lower the surface potential after discharge. In this way, the surface potential distribution caused by the residual charge of leader discharge under the impulse application voltage up to 40 kV can be measured. In this Letter, the residual surface charge density distribution under 23.5 kV application voltage is given, and the numerical characteristics of residual charge in the leader channel and streamer channel are analyzed.
Oxygen transport and GeO2 stability during thermal oxidation of Ge
Authors: da Silva S. R. M. , Rolim G. K. , Soares G. V. , Baumvol I. J. R. , Krug C. , Miotti L. , Freire F. L. , da Costa M. E. H. M. , Radtke C.
Published: May 2012

Oxygen transport during thermal oxidation of Ge and desorption of the formed Ge oxide are investigated. Higher oxidation temperatures and lower oxygen pressures promote GeO desorption. An appreciable fraction of oxidized Ge desorbs during the growth of a GeO2 layer. The interplay between oxygen desorption and incorporation results in the exchange of O originally present in GeO2 by O from the gas phase throughout the oxide layer. This process is mediated by O vacancies generated at the GeO2/Ge interface. The formation of a substoichiometric oxide is shown to have direct relation with the GeO desorption.
Electric field control of domain wall propagation in Pt/Co/GdOx films
Authors: Bauer Uwe , Emori Satoru , Beach Geoffrey S. D.
Published: May 2012

The influence of a gate voltage on domain wall (DW) propagation is investigated in ultrathin Pt/Co/gadolinium oxide (GdOx) films with perpendicular magnetic anisotropy. The DW propagation field can be enhanced or retarded by an electric field at the Co/GdOx interface and scales linearly with gate voltage up to moderate bias levels. Higher gate voltage levels, corresponding to electric fields >0.2 V/nm, produce a large irreversible change to the magnetic anisotropy that can enable nonvolatile switching of the coercivity.
Thermal stability of wetting layer in quantum dot self-assembly
Authors: Cao Y. Y. , Yang G. W.
Published: May 2012

A quantitative thermodynamic theory was established to address the thermal stability of the wetting layer (WL) in quantum dot (QD) self-assembly by introducing a thermal effect based on statistical mechanics. It was found that the thickness of the WL is related to the growth temperature, and the critical temperature deduced by the QD potential energy can be the QD thermal stability dividing line. The agreement between theoretical results and experiments implies that the established approach is expected to contribute to the understanding and design of QD self-assembly.
Microstructure and dielectric properties of piezoelectric magnetron sputtered w-ScxAl1−xN thin films
Authors: Zukauskaite Agne , Wingqvist Gunilla , Palisaitis Justinas , Jensen Jens , Persson Per O. Å. , Matloub Ramin , Muralt Paul , Kim Yunseok , Birch Jens , Hultman Lars
Published: May 2012

Piezoelectric wurtzite ScxAl1−xN (x = 0, 0.1, 0.2, 0.3) thin films were epitaxially grown by reactive magnetron co-sputtering from elemental Sc and Al targets. Al2O3(0001) wafers with TiN(111) seed and electrode layers were used as substrates. X-ray diffraction shows that an increase in the Sc content results in the degradation of the crystalline quality. Samples grown at 400 °C possess true dielectric behavior with quite low dielectric losses and the leakage current is negligible. For ScAlN samples grown at 800 °C, the crystal structure is poor and leakage current is high. Transmission electron microscopy with energy dispersive x-ray spectroscopy mapping shows a mass separation into ScN-rich and AlN-rich domains for x ≥ 0.2 when substrate temperature is increased from 400 to 800 °C. The piezoelectric response of epitaxial ScxAl1−xN films measured by piezoresponse force microscopy and double beam interferometry shows up to 180% increase by the addition of Sc up to x = 0.2 independent of substrate temperature, in good agreement with previous theoretical predictions based on density-functional theory.
Surface acoustic wave in yttrium iron garnet as tunable magnonic crystals for sensors and signal processing applications
Authors: Kryshtal R. G. , Medved A. V.
Published: May 2012

Experimental results on investigation of magnonic crystals arising at surface acoustic wave (SAW) propagation in yttrium iron garnet as an artificial structure for surface magnetostatic waves propagation are presented. Tuning of magnonic gap frequency and gap depth were obtained by changing frequency and intensity of SAW that was explained in the frame of inelastic scattering of magnetostatic waves by SAW. Such tuning was shown can compensate drift of parameters due to possible change of temperature when using magnonic crystals as very sensitive magnetic field sensors. Suggested magnonic crystals are promising also for signal processing in GHz range.
Communication: Electronic band gaps of semiconducting zig-zag carbon nanotubes from many-body perturbation theory calculations
Authors: Umari P. , Petrenko O. , Taioli S. , De Souza M. M.
Published: May 2012

Electronic band gaps for optically allowed transitions are calculated for a series of semiconducting single-walled zig-zag carbon nanotubes of increasing diameter within the many-body perturbation theory GW method. The dependence of the evaluated gaps with respect to tube diameters is then compared with those found from previous experimental data for optical gaps combined with theoretical estimations of exciton binding energies. We find that our GW gaps confirm the behavior inferred from experiment. The relationship between the electronic gap and the diameter extrapolated from the GW values is also in excellent agreement with a direct measurement recently performed through scanning tunneling spectroscopy.
Genetic parameter estimates for growth traits of Gansu Alpine Finewool sheep
Authors: Li Wenhui , Purvis Ian W.
Published: May 2012

Estimation of genetic parameters for growth traits of Gansu Alpine Finewool sheep that separately identify maternal effects has not been previously conducted. (Co)variance components and corresponding genetic parameters for lamb growth traits were estimated from Gansu Alpine Finewool sheep maintained at Gansu Sheep Breeding Technology Extension Station in north-western China. Records of 17 703 lambs at birth, born over 9 years (2000–2008) and sired by 315 rams, were used in the study. Birth type, sex, dam age, record age and birth year were fitted as fixed effects. Analyses were carried out using a restricted maximum likelihood procedure (ASReml). Six different animal models were fitted for all traits and the most appropriate model was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the growth traits. In addition to the direct genetic effect, and maternal genetic effects, significant negative correlations between direct genetic and maternal genetic effects were found for all the growth traits. The maternal permanent environmental effects were only significant for birthweight, weaning weight and pre-weaning growth rate. The estimates of direct heritability for birthweight, weaning weight, pre-weaning average daily gain, post-weaning average daily gain and yearling weight were 0.22, 0.16, 0.15, 0.27 and 0.19 respectively. The maternal heritability estimates were relatively high and ranged from 0.17 to 0.27. The study provides the breed and its associated finewool sheep industry with a more encompassing basis for designing more effective breeding programs for improvement of growth traits of Gansu Alpine Finewool sheep.
The yield of peptides and amino acids following acid hydrolysis of haemoglobin from porcine blood
Authors: Alvarez Carlos , Rendueles Manuel , Diaz Mario
Published: May 2012

Animal blood is the most important waste product from the meat industry due to the huge volumes produced and its pollutant power. Different methods are currently employed to process this by-product, such as drying, incineration or enzymatic hydrolysis. All these techniques are expensive, do not result in revalorisation or are not applicable at an industrial scale. In this paper, chemical hydrolysis is presented as an alternative to recover and increase the value of purified haemoglobin, the most abundant protein in blood. Non-enzymatic hydrolysis of haemoglobin is a good method for obtaining peptides due to its low cost, ease of control and the large amount of peptides produced, as well as being suitable for industrial applications. This paper presents a study of the use of two acids (sulfuric and hydrochloric) for this purpose under different experimental conditions. From the analysis of the kinetics of the hydrolysis process, four fractions can be defined: unbroken haemoglobin, soluble peptides, non-soluble peptides and free amino acids. A kinetic model was developed to simulate the hydrolysis mechanisms, providing a good fit to the experimental results. Both sulfuric and hydrochloric acid at concentrations of 6 M can hydrolyse the haemoglobin completely, but the average peptide size is lower for sulfuric than for hydrochloric acid.
Folding helical proteins in explicit solvent using dihedral-biased tempering
Authors: Zhang Cheng , Ma Jianpeng
Published: May 2012

Using a single-trajectory-based tempering method with a high-temperature dihedral bias, we repeatedly folded four helical proteins [
α
3
D (PDB ID: 2A3D, 73 residues),
α
3
W (1LQ7, 67 residues), Fap1-NR

α

(2KUB, 81 residues) and S-836 (2JUA, 102 residues)] and some of the mutants in explicit solvent within several microseconds. The lowest root-mean-square deviations of backbone atoms from the experimentally determined structures were 1.9, 1.4, 1.0, and 2.1 Å, respectively. Cluster analyses of folding trajectories showed the native conformation usually occupied the most populated cluster. The simulation protocol can be applied to large-scale simulations of other helical proteins on commonly accessible computing platforms.
Melanocortin-3 receptor regulates the normal fasting response
Authors: Renquist Benjamin J. , Murphy Jonathan G. , Larson Emily A. , Olsen Dawn , Klein Robert F. , Ellacott Kate L. J. , Cone Roger D.
Published: May 2012

The melanocortin-3 receptor–deficient (MC3-R
−/−
) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R
−/−
mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R
−/−
mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model.
Control of bone resorption in mice by Schnurri-3
Authors: Wein Marc N. , Jones Dallas C. , Shim Jae-Hyuck , Aliprantis Antonios O. , Sulyanto Rosalyn , Lazarevic Vanja , Poliachik Sandra L. , Gross Ted S. , Glimcher Laurie H.
Published: May 2012

Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.
Engineering of exchange bias by A-site disorder in Pr1−xEuxMnO3
Authors: Karmakar A , Majumdar S , Giri S
Published: May 2012

We report tuning of exchange bias (EB) by manipulating A-site disorder in Pr1−x
Eu
x
MnO3 (x = 0, 0.25, 0.5, 0.75 and 1.0). The EB field is enhanced up to ∼7.5 times from 0.23 kOe to 1.7 kOe for Eu doping corresponding to x = 0 to 0.75, respectively. This substantial increase is uncorrelated with the magnitude of Pr3+-moment, rather it is correlated with the strong orthorhombic and Jahn–Teller distortions. The EB confirms an uncommon scenario of low-temperature magnetic phase separation with stable interface between a highly anisotropic component involving rare-earth ordering and an antiferromagnetic component arising from Mn ordering.
Modelling a nanowire grid for light-sensing applications
Authors: Marasovic I , Garma T , Betti T
Published: May 2012

Nanostructures hold promise as building blocks for a new generation of sensing devices because they could enhance detection and conversion of nonelectrical phenomena into electrical signals. In this paper, we discuss the possible use of a semiconductor (GaAs) nanowire grid as a light sensor. Based on the previously measured electrical properties of a single GaAs nanowire, we propose a model to determine the resistance of a structure consisting of many nanowires forming a grid with metallic contacts. Due to the fact that the proposed geometry is partially disordered, the total resistance of the structure is determined implementing the random resistor network (RRN) methodology in our simulation model. In order to reduce the error caused by condition number and the machine epsilon, the RRN model is improved by introducing additional conditions for solving the transfer matrix formulation precisely. The proposed complex nanowire geometry is analysed for different grid sizes varying the number of nanowires and contacts. According to the nanowire doping profile, we have defined the fraction of active segments (FoS) that is light-sensitive. Simulation results have shown that light sensitivity of a nanowire grid is enhanced with increasing number of active segments while a relative change in the active segment resistance has only a minor influence on the resistance of the complete structure. Finally, we have optimized nanowire grid dimensions with respect to the simulation results and practical limitations.
Analysis and enhancement of the bandwidth of ultrathin absorbers based on high-impedance surfaces
Authors: Pang Yongqiang , Cheng Haifeng , Zhou Yongjiang , Wang Jun
Published: May 2012

A design for ultrathin absorbers with wideband absorption is presented. The absorber is composed of a high-impedance surface comprising a lossy patch array over an electrically thin grounded dielectric substrate. This class of absorbers is usually considered as a narrowband structure. Here, we show that the performance of this absorber can be considered as the low-frequency case of a λ/4-thick absorber and wideband absorption can be actually achieved by the use of multi-resonance arrays. Arrays with different resonant geometries are proposed to design dual-band and triple-band ultrathin absorbers. By tuning these absorption bands closer to each other, we obtain a wideband absorber without increasing the thickness, and the experimental verification is also presented.
Effect of O2, Ar/H2 and CF4 plasma treatments on the structural and dielectric properties of parylene-C thin films
Authors: Kahouli A , Sylvestre A , Laithier J-F , Pairis S , Garden J-L , André E , Jomni F , Yangui B
Published: May 2012

Plasma treatment of parylene-C surfaces not only causes structural modification of the surface during the plasma exposure, but also leaves active sites on the surfaces, which decreases the dielectric properties. In this work, the effects of oxygen, argon/hydrogen and fluorine plasma treatment on the surface and dielectric properties of parylene-C thin films were investigated using Fourier transform-IR spectroscopy, energy dispersive x-ray analysis and dielectric spectroscopy measurement. The results showed that the plasma treatment successfully introduced fluorine functional groups and decreased the oxygen content on the parylene-C surfaces. It appears that the replacement of oxygen and hydrogen by fluorine atoms led to a decrease in the local orientational polarizability of parylene-C. Consequently, it was found that the atmospheric fluorine plasma-treated parylene-C possessed lower dielectric characteristics, 16% lower than the untreated parylene-C at industrial frequencies (10–104 Hz). The Ar/H2 plasma treatment is also an experimental means to reduce the dielectric properties and to decrease the oxygen content in parylene-C. In contrast, the oxygen plasma increases the dielectric constant and can cause deterioration of the leakage current associated with carbon depletion showing C–O and C=O formation. CF4 and Ar/H2 plasma treatment does not significantly affect the long molecular motion (α-relaxation). Additional extrinsic oxygen content due to O2 plasma treatment in the parylene-C structure reproduces the increase in the time constant of both the short (β-relaxation) and long molecular motion.
Fission yeast Cyk3p is a transglutaminase-like protein that participates in cytokinesis and cell morphogenesis
Authors: Pollard Luther W. , Onishi Masayuki , Pringle John R. , Lord Matthew
Published: May 2012

Cell morphogenesis is a complex process that relies on a diverse array of proteins and pathways. We have identified a transglutaminase-like protein (Cyk3p) that functions in fission yeast morphogenesis. The phenotype of a cyk3 knockout strain indicates a primary role for Cyk3p in cytokinesis. Correspondingly, Cyk3p localizes both to the actomyosin contractile ring and the division septum, promoting ring constriction, septation, and subsequent cell separation following ring disassembly. In addition, Cyk3p localizes to polarized growth sites and plays a role in cell shape determination, and it also appears to contribute to cell integrity during stationary phase, given its accumulation as dynamic puncta at the cortex of such cells. Our results and the conservation of Cyk3p across fungi point to a role in cell wall synthesis and remodeling. Cyk3p possesses a transglutaminase domain that is essential for function, even though it lacks the catalytic active site. In a wider sense, our work illustrates the physiological importance of inactive members of the transglutaminase family, which are found throughout eukaryotes. We suggest that the proposed evolution of animal transglutaminase cross-linking activity from ancestral bacterial thiol proteases was accompanied by the emergence of a subclass whose function does not depend on enzymatic activity.
A role for myosin IXb, a motor–RhoGAP chimera, in epithelial wound healing and tight junction regulation
Authors: Chandhoke Surjit K. , Mooseker Mark S.
Published: May 2012

Polymorphisms in the gene encoding the heavy chain of myosin IXb (Myo9b) have been linked to several forms of inflammatory bowel disease (IBD). Given that Myo9b contains a RhoGTPase-activating protein domain within its tail, it may play key roles in Rho-mediated actin cytoskeletal modifications critical to intestinal barrier function. In wounded monolayers of the intestinal epithelial cell line Caco2BBe(BBe), Myo9b localizes to the extreme leading edge of lamellipodia of migrating cells. BBe cells exhibiting loss of Myo9b expression with RNA interference or Myo9b C-terminal dominant-negative (DN) tail-tip expression lack lamellipodia, fail to migrate into the wound, and form stress fiber–like arrays of actin at the free edges of cells facing the wound. These cells also exhibit disruption of tight junction (TJ) protein localization, including ZO-1, occludin, and claudin-1. Torsional motility and junctional permeability to dextran are greatly increased in cells expressing DN-tail-tip. Of interest, this effect is propagated to neighboring cells. Consistent with a role for Myo9b in regulating levels of active Rho, localization of both RhoGTP and myosin light chain phosphorylation corresponds to Myo9b-knockdown regions of BBe monolayers. These data reveal critical roles for Myo9b during epithelial wound healing and maintenance of TJ integrity—key functions that may be altered in patients with Myo9b-linked IBD.
Mitotic exit kinase Dbf2 directly phosphorylates chitin synthase Chs2 to regulate cytokinesis in budding yeast
Authors: Oh Younghoon , Chang Kuang-Jung , Orlean Peter , Wloka Carsten , Deshaies Raymond , Bi Erfei
Published: May 2012

How cell cycle machinery regulates extracellular matrix (ECM) remodeling during cytokinesis remains poorly understood. In the budding yeast Saccharomyces cerevisiae, the primary septum (PS), a functional equivalent of animal ECM, is synthesized during cytokinesis by the chitin synthase Chs2. Here, we report that Dbf2, a conserved mitotic exit kinase, localizes to the division site after Chs2 and directly phosphorylates Chs2 on several residues, including Ser-217. Both phosphodeficient (chs2‑S217A) and phosphomimic (chs2‑S217D) mutations cause defects in cytokinesis, suggesting that dynamic phosphorylation–dephosphorylation of Ser-217 is critical for Chs2 function. It is striking that Chs2‑S217A constricts asymmetrically with the actomyosin ring (AMR), whereas Chs2-S217D displays little or no constriction and remains highly mobile at the division site. These data suggest that Chs2 phosphorylation by Dbf2 triggers its dissociation from the AMR during the late stage of cytokinesis. Of interest, both chs2‑S217A and chs2‑S217D mutants are robustly suppressed by increased dosage of Cyk3, a cytokinesis protein that displays Dbf2‑dependent localization and also stimulates Chs2‑mediated chitin synthesis. Thus Dbf2 regulates PS formation through at least two independent pathways: direct phosphorylation and Cyk3‑mediated activation of Chs2. Our study establishes a mechanism for direct cell cycle control of ECM remodeling during cytokinesis.
GBF1 bears a novel phosphatidylinositol-phosphate binding module, BP3K, to link PI3Kγ activity with Arf1 activation involved in GPCR-mediated neutrophil chemotaxis and superoxide production
Authors: Mazaki Yuichi , Nishimura Yasuharu , Sabe Hisataka
Published: May 2012

Most chemoattractants for neutrophils bind to the Gαifamily of heterotrimeric G protein–coupled receptors (GPCRs) and release Gβγ subunits to activate chemotaxis and superoxide production. GIT2, a GTPase-activating protein for Arf1, forms a complex with Gβγ and is integral for directional sensing and suppression of superoxide production. Here we show that GBF1, a guanine nucleotide exchanging factor for Arf-GTPases, is primarily responsible for Arf1 activation upon GPCR stimulation and is important for neutrophil chemotaxis and superoxide production. We find that GBF1 bears a novel module, namely binding to products of phosphatidyl inositol 3-kinase (PI3K), which binds to products of PI3Kγ. Through this binding, GBF1 is translocated from the Golgi to the leading edge upon GPCR stimulation to activate Arf1 and recruit p22phox and GIT2 to the leading edge. Moreover, GBF1-mediated Arf1 activation is necessary to unify cell polarity during chemotaxis. Our results identify a novel mechanism that links PI3Kγ activity with chemotaxis and superoxide production in GPCR signaling.
Rationale and design of ARTS: a randomized, double‐blind study of BAY 94‐8862 in patients with chronic heart failure and mild or moderate chronic kidney disease
Authors: Pitt Bertram , Filippatos Gerasimos , Gheorghiade Mihai , Kober Lars , Krum Henry , Ponikowski Piotr , Nowack Christina , Kolkhof Peter , Kim So‐Young , Zannad Faiez
Published: May 2012

Aims

BAY 94‐8862 is a novel, non‐steroidal, mineralocorticoid receptor antagonist with greater selectivity than spironolactone and stronger mineralocorticoid receptor binding affinity than eplerenone. The aims of the MinerAlocorticoid Receptor Antagonist Tolerability Study (ARTS; NCT01345656) are to evaluate the safety and tolerability of BAY 94‐8862 in patients with heart failure associated with a reduced left ventricular ejection fraction (HFREF) and chronic kidney disease (CKD), and to examine the effects on biomarkers of cardiac and renal function.

Methods

ARTS is a multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group study divided into two parts. In part A, oral BAY 94‐8862 [2.5, 5, or 10 mg once daily (o.d.)] is compared with placebo in ~60 patients with HFREF and mild CKD. Outcome measures include serum potassium concentration, biomarkers of renal injury, estimated glomerular filtration rate (eGFR), and albuminuria. Part B compares BAY 94‐8862 (2.5, 5, or 10 mg o.d., or 5 mg twice daily), placebo, and open‐label spironolactone (25–50 mg o.d.) in ~360 patients with HFREF and moderate CKD. Outcome measures include the change in serum potassium concentration with BAY 94‐8862 vs. placebo (primary endpoint) and vs. spironolactone, safety and tolerability, biomarkers of cardiac and renal function or injury, eGFR, and albuminuria. BAY 94‐8862 pharmacokinetics are also assessed.

Perspectives

ARTS is the first phase II clinical trial of BAY 94‐8862 and is expected to provide a wealth of information on BAY 94‐8862 in patients with HFREF and CKD, including the optimal dose range for further studies.
Genetic characterization of the endangered and endemic anchialine squat lobster Munidopsis polymorpha from Lanzarote (Canary Islands): management implications
Authors: Cabezas Patricia , Alda Fernando , Macpherson Enrique , Machordom Annie
Published: May 2012

Cabezas, P., Alda, F., Macpherson, E., and Machordom, A. 2012. Genetic characterization of the endangered and endemic anchialine squat lobster Munidopsis polymorpha from Lanzarote (Canary Islands): management implications. – ICES Journal of Marine Science, 69: 1030–1037. Anchialine species show restricted geographic ranges, high habitat specificity, and small population sizes. These factors make them particularly vulnerable to human activities, yet little is known about their ecology and evolutionary history. Munidopsis polymorpha is a decapod endemic to an anchialine cave system of the Corona lava tube in Lanzarote (Canary Islands). The present study, the first genetic survey conducted on this largely unknown species, was designed to characterize its genetic diversity, population structure and recent demographic history, using sequence data for the cytochrome oxidase I gene and eight microsatellites. A single haplotype was identified in the mitochondrial dataset. Nuclear genetic diversity was also low (average = 4.375 ± 1.685). No significant genetic structure was detected between sampling sites and years, either by analysis of molecular variance (FST = 0.006, p = 0.110) or Bayesian clustering analysis (K = 1), indicating this species should be treated as a single management unit. Neither did we find evidence for a recent bottleneck event, and estimates of effective population size were extremely low (∼50). The lack of population structure, low genetic diversity and extremely low effective population size reinforce the high degree of isolation and endemicity of this species, and, consequently, the need to implement appropriate management actions.
The World in Your Consulting Room
Authors: Hutt Patrick
Published: May 2012

GPs working in the UK need travel no further than their consulting room to see the world. This article aims to highlight some of the rewards and challenges of working in a multicultural society, with a view to helping facilitate high standards of patient care. This article shall first consider population trends and representations of immigration in the UK. It will then discuss some practical aspects of arrival, departure and the use of interpreters within the National Health Service (NHS). Case studies will be used to highlight key learning throughout. It is hoped that consultations in general practice, when looked at with an international gaze, will provide a glimpse into a much wider world than the four walls within which they occur.
Interactive Effects of Fungicide, Application Timing, and Spray Volume on Peanut Diseases and Yield
Authors: Augusto Joao , Brenneman Timothy B.
Published: May 2012

Fungicide penetration of the peanut (Arachis hypogaea) canopy to target soilborne pathogens is difficult due to the dense foliage present when mid- to late-season applications are made. To assess the effect of application timing and volume on leaf spot and stem rot control as well as peanut yield, pyraclostrobin (0.21 kg a.i./ha) or chlorothalonil (1.26 kg a.i./ha), a systemic and a contact fungicide, respectively, were applied four times on cv. Georgia Green during the day (on unfolded leaves) or at night (on folded leaves) at 187, 243, or 355 liters/ha. Night application of pyraclostrobin, across spray volumes, gave the best stem rot control and pod yield increase. Pyraclostrobin applied during the day at higher spray volumes also slightly increased control of stem rot, apparently by improving canopy penetration. Neither application timing nor spray volume affected leaf spot control with pyraclostrobin. Higher spray volumes for the chlorothalonil applications tended to improve control of early and late leaf spot, possibly by increasing coverage of foliage and stems.

Accepted for publication 10 January 2012. Published 20 April 2012.
Evaluation of Anterior Vertebral Interbody Fusion Using Osteogenic Mesenchymal Stem Cells Transplanted in Collagen Sponge
Authors: Yang Wencheng , Dong Youhai , Hong Yang , Guang Qian , Chen Xujun
Published: May 2012

Study Design:

The study used a rabbit model to achieve anterior vertebral interbody fusion using osteogenic mesenchymal stem cells (OMSCs) transplanted in collagen sponge.

Objective:

We investigated the effectiveness of graft material for anterior vertebral interbody fusion using a rabbit model by examining the OMSCs transplanted in collagen sponge.

Summary of Background Data:

Anterior vertebral interbody fusion is commonly performed. Although autogenous bone graft remains the gold-standard fusion material, it requires a separate surgical procedure and is associated with significant short-term and long-term morbidity. Recently, mesenchymal stem cells from bone marrow have been studied in various fields, including posterolateral spinal fusion. Thus, we hypothesized that cultured OMSCs transplanted in porous collagen sponge could be used successfully even in anterior vertebral interbody fusion.

Methods:

Forty mature male White Zealand rabbits (weight, 3.5–4.5 kg) were randomly allocated to receive one of the following graft materials: porous collagen sponge plus cultured OMSCs (group I); porous collagen sponge alone (group II); autogenous bone graft (group III); and nothing (group IV). All animals underwent anterior vertebral interbody fusion at the L4/L5 level. The lumbar spine was harvested en bloc, and the new bone formation and spinal fusion was evaluated using radiographic analysis, microcomputed tomography, manual palpation test, and histologic examination at 8 and 12 weeks after surgery.

Results:

New bone formation and bony fusion was evident as early as 8 weeks in groups I and III. And there was no statistically significant difference between 8 and 12 weeks. At both time points, by microcomputed tomography and histologic analysis, new bone formation was observed in both groups I and III, fibrous tissue was observed and there was no new bone in both groups II and IV; by manual palpation test, bony fusion was observed in 40% (4/10) of rabbits in group I, 70% (7/10) of rabbits in group III, and 0% (0/10) of rabbits in both groups II and IV.

Conclusions:

These findings suggest that mesenchymal stem cells that have been cultured with osteogenic differentiation medium and loaded with collagen sponge could induce bone formation and anterior vertebral interbody fusion. And the rabbit model we developed will be useful in evaluating the effects of graft materials for anterior vertebral interbody fusion. Further study is needed to determine the most appropriate carrier for OMSCs and the feasibility in the clinical setting.
Minimally Invasive Surgical Implantation of the Percutaneous Left Atrial Appendage Transcatheter Occlusion Device Initial Experience in a Canine Model
Authors: Hill Arthur C. , Guy T. Sloane
Published: May 2012

Objective

Atrial fibrillation (AF) is a significant cause of thromboembolism and stroke. Left atrial appendage (LAA) occlusion is associated with a decreased risk of stroke in patients with AF. Percutaneous implantation of the percutaneous LAA transcatheter occlusion (PLAATO) device has shown reduction in stroke risk and decreased need for anticoagulation. A surgical method of PLAATO implantation is proposed for its utility and efficacy in cardiac surgical procedures, where LAA occlusion is indicated as a primary procedure or as an adjunct. We describe a surgical method for PLAATO deployment in an experimental model that simulates various operative scenarios including right minithoracotomy, right video-assisted thoracoscopic, or median sternotomy.

Methods

The PLAATO LAA occlusion device was deployed into the LAA in six dogs using a right minithoracotomy incision and catheter deployment via direct left atrial access. Intracardiac echocardiography and left atrial angiography were used to size, position, and verify proper deployment of the device.

Results

Successful PLAATO deployment was achieved in six of the six dogs. One dog required replacement of an undersized device. One dog required replacement of an oversized device. Four dogs required minor repositioning for optimal positioning. Complete flush occlusion of the LAA was achieved in three dogs; the other three dogs had trace leak by LAA angiography.

Conclusions

Experimental surgical implantation of the PLAATO device produces stable and complete occlusion of the LAA. Potential surgical indications for PLAATO implantation include patients with AF where a percutaneous approach to LAA occlusion is contraindicated or in patients with AF who require concurrent cardiac surgery.
Case Series of Bail-Out Procedures with a Balloon-Expandable Sheath after Unsuccessful Introduction of the NovaFlex Device
Authors: Fusari Melissa , Bona Veronica , Biglioli Paolo
Published: May 2012

Objective

Vascular complications remain the main problem of transcatheter aortic valve replacement, despite downsizing of delivery catheter diameter and judicious patient selection. In case of diffusely calcified and/or very tortuous access vessels, the SoloPath Balloon Expandable TransFemoral Introducer (Onset Medical Corporation, Irvine, CA USA), providing the smallest insertion profile of any sheath in its class, may enable exceptional trackability and offer the largest working diameter, thus helping to prevent feared vascular complications. We report the successful use of SoloPath sheath to face six cases of NovaFlex (Edwards Lifesciences Inc, Irvine, CA USA) sheath failed insertion due to vessel tortuosity and calcifications.

Methods

In six patients enrolled for transfemoral transcatheter Edwards SAPIEN XT replacement, resistance to NovaFlex sheath pushing was encountered, subsequent to the bending of the distal portion of the sheath due to vessel tortuosity and calcifications. Damaged Edwards sheaths were exchanged for a SoloPath sheath with a 21-French inner diameter. SoloPath Controlled Deployment Technology design provides the introducer, once expanded, with great radial and pillar resistance.

Results

The unexpanded SoloPath sheath-dilator combination tracked without resistance or kinking over a stiff guide wire through the iliofemoral axis and then was expanded. All transcatheter prostheses were successfully deployed within the native annulus, showing good hemodynamic function.

Conclusions

We report six successful bail-out procedures with the SoloPath Balloon Expandable TransFemoral sheath after unsuccessful introduction of the NovaFlex device. If similar results are confirmed, use of the SoloPath during transcatheter aortic valve replacement may help prevent vascular complications and eliminate the need for other preoperative steps (eg, vascular stenting), therefore reducing procedural mortality, surgical expense, and patient recovery time.
Robotic Totally Endoscopic Multivessel Coronary Artery Bypass Grafting Procedure Development, Challenges, Results
Authors: Bonatti Johannes , Lee Jeffrey D. , Bonaros Nikolaos , Schachner Thomas , Lehr Eric J.
Published: May 2012

Closed-chest totally endoscopic coronary artery bypass grafting (TECAB) is feasible using robotic technology. During the early phases, TECAB was restricted to single bypass grafts to the left anterior descending artery system. Because most patients referred for coronary artery bypass surgery have multivessel disease, development of endoscopic multiple bypass grafting is mandatory. Experimental work on multivessel TECAB was carried out in the early 2000s, and first clinical cases were already performed. With further technological development of operating robots, double, triple, and quadruple TECAB has become feasible both on the arrested heart and on the beating heart. To date, 161 cases of multivessel TECAB using the da Vinci telemanipulation systems are published in the literature. The main advances enabling multivessel TECAB were the availability of a robotic endostabilizer for beating heart procedures and increased surgeon skills using remote access heart-lung machine perfusion and endo-cardioplegia. Both internal mammary arteries can be harvested and both radial artery and vein graft can be used in multivessel TECAB. Y-grafting and sequential grafting are feasible. Multivessel endoscopic surgical revascularization can be combined with percutaneous coronary interventions in advanced hybrid coronary revascularization. Time requirements for multivessel TECAB are significant, and conversion rates to larger thoracic incisions are higher than those observed for single-vessel TECAB. Clinical short- and long-term outcomes, however, seem to meet the standards of open coronary bypass surgery through sternotomy. The main advantages of multivessel TECAB are a completely preserved sternum, use of double internal mammary artery even in risk groups, and a remarkably short recovery time.
Hybrid Minimally Invasive Extraction of Atrial Clot Avoids Redo Sternotomy in Jehovah's Witness
Authors: Pillai Jain Bhaskara , DeLaney Edward R. , Patel Nirav C. , Subramanian Valavanur A.
Published: May 2012

We report the novel use of the AngioVac device in a percutaneous hybrid approach to remove a large right atrial clot as an effective and potentially lifesaving alternative to a very high-risk redo-sternotomy in a Jehovah's Witness patient.
Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models
Authors: Andrews T. D. , Whittle B. , Field M. A. , Balakishnan B. , Zhang Y. , Shao Y. , Cho V. , Kirk M. , Singh M. , Xia Y. , Hager J. , Winslade S. , Sjollema G. , Beutler B. , Enders A. , Goodnow C. C.
Published: May 2012

Accurate identification of sparse heterozygous single-nucleotide variants (SNVs) is a critical challenge for identifying the causative mutations in mouse genetic screens, human genetic diseases and cancer. When seeking to identify causal DNA variants that occur at such low rates, they are overwhelmed by false-positive calls that arise from a range of technical and biological sources. We describe a strategy using whole-exome capture, massively parallel DNA sequencing and computational analysis, which identifies with a low false-positive rate the majority of heterozygous and homozygous SNVs arising de novo with a frequency of one nucleotide substitution per megabase in progeny of
N
-ethyl-
N
-nitrosourea (ENU)-mutated C57BL/6j mice. We found that by applying a strategy of filtering raw SNV calls against known and platform-specific variants we could call true SNVs with a false-positive rate of 19.4 per cent and an estimated false-negative rate of 21.3 per cent. These error rates are small enough to enable calling a causative mutation from both homozygous and heterozygous candidate mutation lists with little or no further experimental validation. The efficacy of this approach is demonstrated by identifying the causative mutation in the
Ptprc
gene in a lymphocyte-deficient strain and in 11 other strains with immune disorders or obesity, without the need for meiotic mapping. Exome sequencing of first-generation mutant mice revealed hundreds of unphenotyped protein-changing mutations, 52 per cent of which are predicted to be deleterious, which now become available for breeding and experimental analysis. We show that exome sequencing data alone are sufficient to identify induced mutations. This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease.
The evolution of pebble size and shape in space and time
Authors: Domokos G. , Gibbons G. W.
Published: May 2012

We propose a mathematical model which suggests that the two main geological observations about shingle beaches, i.e. the emergence of predominant pebble size ratios and strong segregation by size, are interrelated. Our model is based on a system of ordinary differential equations (ODEs) called the
box equations
that describe the evolution of pebble ratios. We derive these ODEs as a heuristic approximation of Bloore's partial differential equation (PDE) describing collisional abrasion and verify them by simple experiments and by direct simulation of the PDE. Although representing a radical simplification of the latter, our system admits the inclusion of additional terms related to frictional abrasion. We show that non-trivial attractors (corresponding to predominant pebble size ratios) only exist in the presence of friction. By interpreting our equations as a Markov process, we illustrate by direct simulation that these attractors may only be stabilized by the ongoing segregation process.
Boundary heating of poro-elastic and poro-elasto-plastic spheres
Authors: Selvadurai A. P. S. , Suvorov A. P.
Published: May 2012

This paper examines the coupled hydro-thermo-mechanical behaviour of a fluid-saturated porous sphere with a skeletal fabric that can exhibit either elastic or elasto-plastic mechanical behaviour. Analytical results for the thermo-poro-elastic response of the sphere subjected to transient heat transfer are complemented by computational results for the analogous thermo-poro-elasto-plastic problem. The results presented in the paper examine the influence of the permeability, thermal expansion properties of the pore fluid and the skeleton, and the elasto-plasticity effects of the porous skeleton on the time-dependent pore fluid pressure, displacement and stress within the sphere.