Biomedical subjects
Publications and source records attributed to W Losert.
Fluid-mediated interactions between particles in a vibrating fluid lead to both long range attraction and short range repulsion. The resulting patterns include hexagonally ordered microcrystallites, time-periodic structures, and chaotic fluctuating patterns with complex dynamics. A model based on streaming flow gives a good quantitative account of the attractive part of the interaction.
The frictional response of granular binary mixtures to an applied shear stress is studied experimentally by sliding a rough plate across a granular surface. The static friction force is found to be up to 25% larger than a linear interpolation between the frictional properties of each component. The dynamical friction coefficient can exhibit a maximum, a minimum, or an oscillatory behavior as a function of mixing ratio, depending on the size ratio or shape of the two components. In addition, visualization of the granular flow makes it possible to show that the shear layer thickness and the characteristic shear displacement, over which a steady state dilation is reached, change linearly with the mass concentration.
We analyze the main features of granular shear flow through experimental measurements in a Couette geometry and a comparison to a locally Newtonian, continuum model of granular flow. The model is based on earlier hydrodynamic models, adjusted to take into account the experimentally observed coupling between fluctuations in particle motion and mean-flow properties. Experimentally, the local velocity fluctuations are found to decrease more slowly with distance from the shear surface than the velocity. This can be explained by an effective viscosity that diverges more rapidly as the random-close-packing density is approached than is predicted by Enskog theory for dense hard-sphere systems. Experiment and theory are in good agreement, especially for the following key features of granular flow: The flow is confined to a small shear band, fluctuations decay approximately exponentially away from the sheared wall, and the shear stress is approximately independent of the shear velocity. The functional forms of the velocity and fluctuation profiles predicted by the model agree with the experimental results.
We investigate experimentally the flow of a monolayer of spherical beads through a channel on a smooth incline that is bounded by rough sidewalls. Using high-speed video imaging and particle tracking, we measure the positions and velocities of all particles in the field of view. We find that the flows are accelerating and dilute if the channel exit is open. On the other hand, if the exit is constricted, flows can reach a state in which the local time-averaged velocity is invariant along the stream. In the latter case, we find a continuous transition from an oscillatory two-phase flow (2PF) regime with wide density variations to a uniform dense flow regime, depending on the channel width and the mean flow speed. These two regimes exhibit distinct density variation, time regularity, and transverse profiles. The rough sidewalls are found to be necessary for the 2PF regime. In the dense regions of both flows, particles exhibit temporary arches, long-range correlated velocities, inhomogenuous propagation of disturbances, and hexagonal lattice structures. On the other hand, the dilute regions of the two-phase flow are nearly collisionless. Existing models can neither fully describe the dynamics of both the dense and the dilute regions nor explain the spontaneous switching between them.
We study the dynamics of the front separating a spatiotemporally chaotic region from a stable steady region using a simple model applicable to periodically forced systems. In particular, we investigate both the coarsening of the front induced by the inherent "noise" of the chaotic region, and the long wavelength dynamics causing the front to develop cusps.
The particle dynamics and shear forces of granular matter in a Couette geometry are determined experimentally. The normalized tangential velocity V(y) declines strongly with distance y from the moving wall, independent of the shear rate and of the shear dynamics. Local rms velocity fluctuations deltaV(y) scale with the local velocity gradient to the power 0.4+/-0.05. These results agree with a locally Newtonian, continuum model, where the granular medium is assumed to behave as a liquid with a local temperature [deltaV(y)](2) and density dependent viscosity.
Several mechanisms cause a granular material to strengthen over time at low applied stress. The strength is determined from the maximum frictional force F(max) experienced by a shearing plate in contact with wet or dry granular material after the layer has been at rest for a waiting time tau. The layer strength increases roughly logarithmically with tau only if a shear stress is applied during the waiting time. The mechanisms of strengthening are investigated by sensitive displacement measurements, and by imaging of particle motion in the shear zone. Granular matter can strengthen due to a slow shift in the particle arrangement under shear stress. Humidity also leads to strengthening, but is found not to be its sole cause. In addition to these time dependent effects, the static friction coefficient can also be increased by compaction of the granular material under some circumstances, and by a cycling of the applied shear stress.
A partial monolayer of approximately 20 000 uniform spherical steel beads, vibrated vertically on a flat plate, shows remarkable ordering transitions and cooperative behavior just below 1g maximum acceleration. We study the stability of a quiescent disordered or "amorphous" state formed when the acceleration is switched off in the excited "gaseous" state. The transition from the amorphous state back to the gaseous state upon increasing the plate's acceleration is generally subcritical: An external perturbation applied to one bead initiates a propagating front that produces a rapid transition. We measure the front velocity as a function of the applied acceleration. This phenomenon is explained by a model based on a single vibrated particle with multiple attractors that is perturbed by collisions. A simulation shows that a sufficiently high rate of interparticle collisions can prevent trapping in the attractor corresponding to the nonmoving ground state.
The mechanical response of a wet granular layer to imposed shear is studied experimentally at low applied normal stress. The granular material is immersed in water and the shear is applied by sliding a plate resting on the upper surface of the layer. We monitor simultaneously the horizontal and the vertical displacements of the plate to submicron accuracy with millisecond time resolution. The relations between the plate displacement, the dilation of the layer and the measured frictional force are analyzed in detail. When slip begins, the dilation increases exponentially over a slip distance comparable to the particle radius. We find that the total dilation and the steady state frictional force do not depend on the driving velocity, but do depend linearly on the applied normal stress. The frictional force also depends linearly on the dilation rate (rather than the dilation itself), and reaches a maximum value during the transient acceleration. We find that the layer can temporarily sustain a shear stress that is in excess of the critical value that will eventually lead to slip. We describe an empirical model that describes much of what we observe. This model differs in some respects from those used previously at stresses 10(6) times larger.
The evolution of a dendritic pattern from a planar solid-liquid interface during directional solidification of a binary alloy was investigated experimentally. The model alloy used was the transparent organic crystal succinonitrile doped with the laser dye coumarin 152. The buildup of solute ahead of the initially stable planar interface and the subsequent instability of the planar front were measured in detail and compared with recent theoretical calculations by Warren and Langer [Warren, J. A. & Langer, J. S. (1993) Phys. Rev. E 47, 2702- 2712]. The fluorescence of coumarin 152 was used for direct observations of the evolution of the solute concentration profile ahead of the initially planar solid-liquid interface. UV absorption was used to produce thermal perturbations of the sample that generated spatially periodic modulations of the planar interface. This technique allows for measurement of both positive and negative linear growth coefficients (determined from the growth or decay rate of the modulation after the perturbation is switched off) for a large range of wave vectors. Measurements of the evolution of the concentration profile and the linear growth coefficients, and the occurrence of the initial instability, were in good agreement with the Warren-Langer predictions.
The evolution of the crystal-melt interface was investigated during directional solidification of a dilute binary alloy, starting at the marginal stability time t(i) at which the planar interface first becomes unstable. The time delay between t(i) and the crossover time t(0) at which the interface modulation becomes observable was determined experimentally. The interface morphology was analyzed as the cellular pattern appeared, and it was followed through the coarsening phase to the final steady-state dendritic pattern. The relevance of the initial instability for steady-state pattern selection was verified experimentally, and some aspects of the coarsening dynamics were measured and compared with theoretical predictions of Warren and Langer [Warren, J. A. & Langer, J. S. (1990) Phys. Rev. A 42, 3518-3525; Warren, J. A. & Langer, J. S. (1993) Phys. Rev. E 47, 2702-2712].
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Several steroidal 6,6-ethylene-15,16-methylene 17-spirolactones were synthesized to find new progestogens that exhibit both progestational and antimineralocorticoidal activities. The influence of substituents in the 10- and 13-position of the steroidal framework on both properties was investigated. It was found that only compound 12, carrying methyl groups at the 10- and 13-positions, possesses high progestational and antimineralocorticoidal activity.
Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-methylene derivative 17 exhibited a 2-fold higher aldosterone antagonistic activity compared to either spironolactone or the 15,16-unsubstituted derivative 29 while showing remarkably reduced antiandrogenicity.
Some 15,16-methylene derivatives of the aldosterone antagonist spironolactone were synthesized with the purpose of increasing the antialdosterone potency and reducing the endocrinological effects of this standard compound. By introduction of a 1,2-double bond and a 15 beta,16 beta-methylene ring in the spironolactone molecule both goals were achieved. In animal studies mespirenone exhibited a threefold-greater antialdosterone potency and less than 10% of the antiandrogenic activity of spironolactone.
The ability of a series of 15,16-methylene-spirolactones in comparison to known antimineralocorticoids to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The standard procedure involved continuous i.v. infusion with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 micrograms/(kg X h)] resulting in a long-lasting reduction of renal sodium excretion, increase of renal potassium excretion and hence decrease of the urinary Na/K-ratio. In some experiments sodium input was increased (0.2% NaCl + 4.3% glucose or 0.9% NaCl, respectively). The test drugs either were administered orally 1 h before start of the infusion or were added to the infused solution. With the exception of two steroids which could only be tested at single doses, all compounds were administered at three doses ranging from 2.2 to 40 mg/kg (p.o.) or from 0.83 to 6.7 mg/kg/h (i.v.). Spironolactone or spirorenone (oral administration) and potassium canrenoate (i.v. infusion) served as reference compounds. The antimineralocorticoid activity of the steroids was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used as controls. To obtain preliminary information on potential antiandrogenic and progestogenic (side-)effects, binding of the test-compounds to androgen receptors (rat prostate cytosol) and progestogen receptors (rabbit uterus cytosol) was measured in vitro using 3H-dihydrotestosterone (DHT) and 3H-progesterone (prog.) as tracer and unlabelled DHT and prog. as references. All steroids tested exhibited antimineralocorticoid activity. For compounds tested at three doses levels the potency relative to the standard used was evaluated using regression analysis based on the Na/K-ratio or the log (Na X 100)/K-ratio. The relative potency of the other compounds was estimated by comparing the biological effect of single doses of test drug and standard drug, respectively, using nonparametric statistical tests.(ABSTRACT TRUNCATED AT 400 WORDS)