Dynamical splayed ferromagnetic ground state in the quantum spin ice Yb(2)Sn(2)O(7).

From magnetic, specific heat, (170)Yb Mössbauer effect, neutron diffraction, and muon spin relaxation measurements on polycrystalline Yb(2)Sn(2)O(7), we show that below the first order transition at 0.15 K all of the Yb(3+) ions are long-range magnetically ordered and each has a moment of 1.1 µ(B) which lies at ≃ 10° to a common fourfold cubic axis. The four sublattice moments have four different directions away from this axis and are therefore noncoplanar. We term this arrangement splayed ferromagnetism. This ground state has a dynamical component with a fluctuation rate in the megahertz range. The net ferromagnetic exchange interaction has an anisotropy that favors the local threefold axis. We discuss our results in terms of the phase diagram proposed by Savary and Balents [Phys. Rev. Lett. 108, 037202 (2012)] for a pyrochlore lattice of Kramers 1/2 effective spins.

Chain formation of spheres in oscillatory fluid flows.

A collection of spherical particles subjected to horizontal oscillatory fluid flow is known to form chains perpendicular to the direction of the oscillation. We have developed computer simulations to model such a system and have validated them against experiments carried out in a small fluid-filled cell. In both experiment and simulation we find that the particles go through the same stages of evolution from a dispersed initial configuration to an ordered chain structure. We then use our computer simulations to investigate in detail the interactions responsible for chain formation and the interaction between fully formed chains.

Partition instability in water-immersed granular systems.

It is well known that a system of grains, vibrated vertically in a cell divided into linked columns, may spontaneously move into just one of the columns due to the inelastic nature of their collisions. Here we study the behavior of a water-immersed system of spherical barium titanate particles in a rectangular cell which is divided into two columns, linked by two connecting holes, one at the top and one at the bottom of the cell. Under vibration the grains spontaneously move into just one of the columns via a gradual transfer of grains through the connecting hole at the base of the cell. We have developed numerical simulations that are able to reproduce this behavior and provide detailed information on the instability mechanism. We use this knowledge to propose a simple analytical model for this fluid-driven partition instability based on two coupled granular beds vibrated within an incompressible fluid.

The donor nature of muonium in undoped, heavily n-type and p-type InAs.

The charge state of muonium has been investigated in p-type doped, nominally undoped (low n-type) and heavily n-type doped InAs. The donor Mu(+) state is shown to be the dominant defect in all cases. Consequently, muonium does not simply counteract the prevailing conductivity in this material. This is consistent with the charge neutrality level lying above the conduction band minimum in InAs.

Poly(triazolyl methacrylate) glycopolymers as potential targeted unimolecular nanocarriers.

Synthetic glycopolymers are increasingly investigated as multivalent ligands for a range of biological and biomedical applications. This study indicates that glycopolymers with a fine-tuned balance between hydrophilic sugar pendant units and relatively hydrophobic polymer backbones can act as single-chain targeted nanocarriers for low molecular weight hydrophobic molecules. Non-covalent complexes formed from poly(triazolyl methacrylate) glycopolymers and low molecular weight hydrophobic guest molecules were characterised through a range of analytical techniques - DLS, SLS, TDA, fluorescence spectroscopy, surface tension analysis - and molecular dynamics (MD) modelling simulations provided further information on the macromolecular characteristics of these single chain complexes. Finally, we show that these nanocarriers can be utilised to deliver a hydrophobic guest molecule, Nile red, to both soluble and surface-immobilised concanavalin A (Con A) and peanut agglutinin (PNA) model lectins with high specificity, showing the potential of non-covalent complexation with specific glycopolymers in targeted guest-molecule delivery.

The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface.

CONTEXT: There are at least 24 missense, nonconservative mutations found in the ACTH receptor [melanocortin 2 receptor (MC2R)] that have been associated with the autosomal recessive disease familial glucocorticoid deficiency (FGD) type 1. The characterization of these mutations has been hindered by difficulties in establishing a functional heterologous cell transfection system for MC2R. Recently, the melanocortin 2 receptor accessory protein (MRAP) was identified as essential for the trafficking of MC2R to the cell surface; therefore, a functional characterization of MC2R mutations is now possible. OBJECTIVE: Our objective was to elucidate the molecular mechanisms responsible for defective MC2R function in FGD. METHODS: Stable cell lines expressing human MRAPalpha were established and transiently transfected with wild-type or mutant MC2R. Functional characterization of mutant MC2R was performed using a cell surface expression assay, a cAMP reporter assay, confocal microscopy, and coimmunoprecipitation of MRAPalpha. RESULTS: Two thirds of all MC2R mutations had a significant reduction in cell surface trafficking, even though MRAPalpha interacted with all mutants. Analysis of those mutant receptors that reached the cell surface indicated that four of six failed to signal, after stimulation with ACTH. CONCLUSION: The majority of MC2R mutations found in FGD fail to function because they fail to traffic to the cell surface.

Influence of magnetic cohesion on the stability of granular slopes.

We use a molecular dynamics model to simulate the formation and evolution of a granular pile in two dimensions in order to gain a better understanding of the role of magnetic interactions in avalanche dynamics. We find that the angle of repose increases only slowly with magnetic field; the increase in angle is small even for intergrain cohesive forces many times stronger than gravity. The magnetic forces within the bulk of the pile partially cancel as a result of the anisotropic nature of the dipole-dipole interaction between grains. However, we show that this cancellation effect is not sufficiently strong to explain the discrepancy between the angle of repose in wet systems and magnetically cohesive systems. In our simulations we observe shearing deep within the pile, and we argue that it is this motion that prevents the angle of repose from increasing dramatically. We also investigate different implementations of friction with the front and back walls of the container, and conclude that the nature of the friction dramatically affects the influence of magnetic cohesion on the angle of repose.

Migration of an asymmetric dimer in oscillatory fluid flow.

We describe the motion of an asymmetric dimer across a horizontal surface when exposed to an oscillatory fluid flow. The dimer consists of two spheres of distinct sizes, rigidly attached to each other. The dimer is found to move in a direction perpendicular to the fluid flow, with the smaller sphere foremost. We have determined how the speed depends upon the vibratory conditions, on the fluid viscosity, and on the dimer size and aspect ratio. Computer simulations are used to give an insight into the mechanism responsible for the motion. We use a scaling argument based on the asymmetry of the streaming flow to predict the approximate dependence of the migration speed on the system parameters.

Interaction between intruders in vibrated granular beds.

Two neutrally buoyant intruder particles in a granular bed fluidized by vertical, sinusoidal vibration are known to interact with each other over a range of about five intruder diameters. Using molecular dynamics simulations, we investigate in detail the spatial and temporal nature of this interaction. We show that the force of attraction between intruders can be calculated from the local density and kinetic energy using a simple equation of state. Moreover, the interaction can be changed from attractive to repulsive by reducing the coefficient of restitution between the intruders and host particles, one of the key results of this work.

Velocity statistics in dissipative, dense granular media.

We use a two-dimensional random-force model to investigate the velocity distributions in driven granular media. In general, the shape of the distribution is found to depend on the degree of dissipation and the packing fraction but, in highly dissipative systems, the velocity distributions have tails close to exponential. We show that these arise from the dynamics of single particles traveling in dilute regions and influenced predominantly by the random force. A self-consistent kinetic theory is developed to describe this behavior.

Interaction of spheres in oscillatory fluid flows.

Rigid spherical particles in oscillating fluid flows form interesting structures as a result of fluid mediated interactions. Here we show that spheres under horizontal vibration align themselves at right angles to the oscillation and sit with a gap between them. The details of this behavior have been investigated through experiments and simulations. We have carried out experiments in which a pair of stainless steel spheres is shaken horizontally in a cell filled with glycerol-water fluid mixtures of three different viscosities, at various frequencies and amplitudes of oscillation. There is an equilibrium gap between the particles resulting from a long-range attraction and a short-range repulsion. The size of the gap was found to depend on the fluid viscosity and the vibratory parameters, and we have identified two distinct scaling regimes for the dependence of the gap on the system parameters. Using a Navier-Stokes solver the same system was simulated. The interaction force between the spheres was measured and the streaming flows induced by the motion were determined.

Intruder clustering in three-dimensional granular beds.

We present results of computer simulations for neutrally buoyant intruders in a vertically vibrated three-dimensional granular bed of smaller host particles. Under sinusoidal excitation, pairs of intruders interact over a distance of several intruder diameters; a group of intruders forms a cluster. The strength of the interaction grows as the number of intruders is increased. We show that the tendency to cluster may be manipulated through the use of nonsinusoidal excitation, which allows partial mixing. Finally, we investigate the effects of walls on the clustering of intruders.

Stochastic dynamics of a rod bouncing upon a vibrating surface.

We describe the behavior of a rod bouncing upon a horizontal surface which is undergoing sinusoidal vertical vibration. The predictions of computer simulations are compared with experiments in which a stainless-steel rod bounces upon a metal-coated glass surface. We find that, as the dimensionless acceleration parameter Gamma is increased appreciably above unity, the motion of a long rod passes from periodic or near-periodic motion into stochastic dynamics. Within this stochastic regime the statistics of the times between impacts follow distributions with tails of approximately Gaussian form while the probability distributions of the angles at impact have tails that are close to exponential. We determine the dependence of each distribution upon the length of the rod, upon frequency, and on Gamma. The statistics of the total energy and of the translational and rotational components each approximately follow a Boltzmann distribution in their tails, the translational and rotational energy components being strongly correlated. The time-averaged mean vertical translational energy is significantly larger than the mean rotational energy, and both are considerably larger than the energy associated with horizontal motion.

Mutants of Arabidopsis thaliana hypersensitive to DNA-damaging treatments.

A simple screening method was developed for the isolation of Arabidopsis thaliana mutants hypersensitive to X-ray irradiation. The root meristem was used as the target for irradiation with sublethal doses of X rays, while protection of the shoot meristem by a lead cover allowed the rescue of hypersensitive individuals. We isolated nine independent X-ray-hypersensitive mutants from 7000 M2 seedlings. Analysis of three chosen mutants (xrs4, xrs9 and xrs11) showed that alterations in single recessive alleles are responsible for their phenotypes. The mutations are not allelic but linked and map to chromosome 4, suggesting mutations in novel genes as compared to previously mapped mutant alleles. Importantly, hypersensitivity to X rays was found to correlate with hypersensitivity to the DNA-alkylating agent mitomycin C, which provokes interstrand crosslinks, and/or to methyl methanesulfonate, which is known as a radiomimetic chemical. These novel phenotypes suggest that the mutants described here are altered in the repair of DNA damage, most probably by recombinational repair.

Traveling waves in a water-immersed binary granular system vibrated within an annular cell.

It has been known since the time of Faraday that vertically vibrated fine grains may spontaneously form piles through their interaction with a fluid. More recently, it has been observed that a fine binary mixture may separate under vertical vibration through the differential influence of the fluid on the two granular components. Here, we report a detailed study of a system of water-immersed bronze and glass grains held between two coaxial cylinders. Under vertical vibration, the bronze separates to form a layer above the glass, which itself breaks symmetry to form a pile. Symmetry is broken a second time by the bronze forming layers of different thicknesses upon the two slopes of the glass pile. The pile then travels as a wave with the thicker bronze layer upon its leading surface. We examine the conditions for these traveling waves and determine how their speed varies with particle size, frequency, and amplitude of vibration. A model is developed which provides a semiquantitative account of the wave motion.

Separation of binary granular mixtures under vibration and differential magnetic levitation force.

The application of both a strong magnetic field and a magnetic field gradient to a diamagnetic or paramagnetic material can produce a vertical force that acts in concert with the force of gravity. We consider a binary granular mixture in which the two components have different magnetic susceptibilities and therefore experience different effective forces of gravity when subjected to an inhomogeneous magnetic field. Under vertical vibration, such a mixture may rapidly separate into regions almost pure in the two components. We investigate the conditions for this behavior, studying the speed and completeness of separation as a function of differential effective gravity and the frequency and amplitude of vibration. The influence of the cohesive magnetic dipole-dipole interactions on the separation process is also investigated. In our studies insight is gained through the use of a molecular dynamics simulation model.

Faraday tilting of water-immersed granular beds.

Under low-frequency vertical vibration, a system of fine grains within a fluid is observed to tilt or to form piles, an effect studied by Faraday for grains in air. Here, we investigate the physical mechanisms behind Faraday tilting in a bed of vertically vibrated bronze spheres fully immersed in water. Experimental observations of surface tilting and bulk convection are compared with the results of molecular dynamics simulations in which the water is treated as an incompressible fluid. Our simulations reproduce the main features observed experimentally. Most tilt construction is shown to be due to horizontal fluid flow within the bed, principally occurring when the gap between the bed and the supporting platform is close to a maximum. Tilt destruction occurs by granular surface flow and in the bulk of the bed at times during each vibratory cycle close to and just later than bed impact. Destruction becomes more important for higher values of frequency and vibration amplitude, leading to lower tilt angles, partial tilting, or the symmetric domed geometry of Muchowski flow.

Evoked potentials in motor system diseases.

We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis.

Cervical magnetic stimulation.

We stimulated the cervical region with a 9-cm-diameter magnetic coil on centered on the spinous processes in 21 normal subjects. We obtained maximal amplitudes with clockwise coil current in right-sided upper extremity muscles and counterclockwise coil current in left-sided upper extremity muscles. Optimal stimulation sites for biceps, triceps, and abductor digiti minimi were C-3 or C-4, C-4 or C-5, and C-4, C-5, or C-6, respectively. The latencies of the muscle responses varied little in the same subject in spite of marked amplitude changes due to suboptimal position of the coil or submaximal stimulator output. In abductor digiti minimi, the amplitude of the muscle response on cervical magnetic stimulation was 9 to 100% of the supramaximal amplitude on wrist electrical stimulation. We established normal values for latency, amplitude, and interside differences for the above 3 upper extremity muscles. The findings were reproducible, and the latencies obtained with large coils from different manufacturers in the same subjects were comparable. We found no advantage in bipolar recording over tendon-belly montage. Comparison of magnetic and electrical needle root stimulation in the same subjects showed that the magnetic stimulus was more proximal in biceps and triceps, and that the site of excitation was approximately the same in abductor digiti minimi. Indirect assessment of the longitudinal site of excitation based on F-wave minimal latency indicated that excitation occurred within millimeters of the emergence of axon of the peripheral motor neuron.

Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.

The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 microM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 microM. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.