Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13 resulted in adult deficits in spatial learning in the Morris water maze and decreased social exploration for all drugs tested. Phenobarbital exposure led to deficits in cued fear conditioning, risk assessment in the elevated plus maze, and sensorimotor gating as measured by prepulse inhibition, but it did not affect motor coordination on the rotorod task. In contrast, phenytoin and lamotrigine exposure led to impaired rotorod performance, but no deficits in sensorimotor gating. Phenytoin, but not lamotrigine or phenobarbital, increased exploration in the open field. Phenytoin and phenobarbital, but not lamotrigine, disrupted cued fear conditioning. These results indicate that AED administration during a limited sensitive postnatal period is sufficient to cause a range of behavioral deficits later in life, and the specific profile of behavioral deficits varies across drugs. The differences in the long-term outcomes associated with the three AEDs examined are not predicted by either the mechanism of AED action or the proapoptotic effect of the drugs. Our findings suggest that a history of AED therapy during development must be considered as a variable when assessing later-life cognitive and psychiatric outcomes.

We report on a series of experiments in which a grain-sized intruder is pulled by a spring through a 2D granular material comprised of photoelastic disks in a Couette geometry. We study the intruder dynamics as a function of packing fraction for two types of supporting substrates: a frictional glass plate and a layer of water for which basal friction forces are negligible. We observe two dynamical regimes: intermittent flow, in which the intruder moves freely most of the time but occasionally gets stuck, and stick-slip dynamics, in which the intruder advances via a sequence of distinct, rapid events. When basal friction is present, we observe a smooth crossover between the two regimes as a function of packing fraction, and we find that reducing the interparticle friction coefficient causes the stick-slip regime to shift to higher packing fractions. When basal friction is eliminated, we observe intermittent flow at all accessible packing fractions. For all cases, we present results for the statistics of stick events, the intruder velocity, and the force exerted on the intruder by the grains. Our results indicate the qualitative importance of basal friction at high packing fractions and suggest a possible connection between intruder dynamics in a static material and clogging dynamics in granular flows.

We discuss the results of simulations of an intruder pulled through a two-dimensional granular system by a spring, using a model designed to lend insight into the experimental findings described by Kozlowski et al. [Phys. Rev. E 100, 032905 (2019)]. In that previous study the presence of basal friction between the grains and the base was observed to change the intruder dynamics from clogging to stick-slip. Here we first show that our simulation results are in excellent agreement with the experimental data for a variety of experimentally accessible friction coefficients governing interactions of particles with each other and with boundaries. Then, we use simulations to explore a broader range of parameter space, focusing on the friction between the particles and the base. We consider a range of both static and dynamic basal friction coefficients, which are difficult to vary smoothly in experiments. The simulations show that dynamic friction strongly affects the stick-slip behaviour when the coefficient is decreased below 0.1, while static friction plays only a marginal role in the intruder dynamics.

Taken together, our data indicate that OxyR regulates the secretion of potent cytotoxic factors by P. aeruginosa.

Experiments, simulations, and theoretical treatments of granular materials typically feature circular or elliptical grains. However, grains found in natural systems often have flat faces that introduce local rotational constraints; these rotational constraints have been shown to affect, for example, the jamming transition, discontinuous shear thickening, and ordered states in colloids and thermalized grains. In this work, we experimentally investigate the effects of grain angularity on stick-slip dynamics. A weighted slider is pulled by a spring over a gravity-packed granular bed composed of polygonal grains with varying angularity. We find that packings of triangular or square grains have higher shear strengths than packings of pentagons, hexagons, heptagons, or disks. Additionally, as the number of sides increases, sticking periods, during which the slider remains motionless while the spring force on it increases, become shorter on average, with the material yielding at smaller applied stresses. Lastly, we find that dilation of the medium during sticking periods tends to be larger for grains with higher angularity, in part because of the presence of stilt-like columnar structures that prop the slider up. We report on measurements of the pulling force on the slider, particle dynamics during slip events, and properties of force-bearing contact networks identified via photoelasticity. Our findings indicate that high angularity of grains (pentagons, squares, triangles) leads to differences in grain-scale flow and macroscopic stick-slip dynamics of bulk granular materials. Our experiments also indicate a continuous change in dynamics with decreasing angularity as the circular grain limit is approached.