Differential regulation of bladder pain and voiding function by sensory afferent populations revealed by selective optogenetic activation

Bladder-innervating primary sensory neurons mediate reflex-driven bladder function under normal conditions, and contribute to debilitating bladder pain and/or overactivity in pathological states. The goal of this study was to examine the respective roles of defined subtypes of afferent neurons in bladder sensation and function in vivo via direct optogenetic activation. To accomplish this goal, we generated transgenic lines that express a Channelrhodopsin-2-eYFP fusion protein (ChR2-eYFP) in two distinct populations of sensory neurons: TRPV1-lineage neurons (Trpv1Cre;Ai32, the majority of nociceptors) and Nav1.8+ neurons (Scn10aCre;Ai32, nociceptors and some mechanosensitive fibers). In spinal cord, eYFP+ fibers in Trpv1Cre;Ai32 mice were observed predominantly in dorsal horn (DH) laminae I-II, while in Scn10aCre;Ai32 mice they extended throughout the DH, including a dense projection to lamina X. Fiber density correlated with number of retrogradely-labeled eYFP+ dorsal root ganglion neurons (82.2% Scn10aCre;Ai32 vs. 62% Trpv1Cre;Ai32) and degree of DH excitatory synaptic transmission. Photostimulation of peripheral afferent terminals significantly increased visceromotor responses to noxious bladder distension (30–50 mmHg) in both transgenic lines, and to non-noxious distension (20 mmHg) in Scn10aCre;Ai32 mice. Depolarization of ChR2+ afferents in Scn10aCre;Ai32 mice produced low- and high-amplitude bladder contractions respectively in 53% and 27% of stimulation trials, and frequency of high-amplitude contractions increased to 60% after engagement of low threshold (LT) mechanoreceptors by bladder filling. In Trpv1Cre;Ai32 mice, low-amplitude contractions occurred in 27% of trials before bladder filling, which was pre-requisite for light-evoked high-amplitude contractions (observed in 53.3% of trials). Potential explanations for these observations include physiological differences in the thresholds of stimulated fibers and their connectivity to spinal circuits

Optimisation of patch distribution strategies for AMR applications

As core counts increase in the world's most powerful supercomputers, applications are becoming limited not only by computational power, but also by data availability. In the race to exascale, efficient and effective communication policies are key to achieving optimal application performance. Applications using adaptive mesh refinement (AMR) trade off communication for computational load balancing, to enable the focused computation of specific areas of interest. This class of application is particularly susceptible to the communication performance of the underlying architectures, and are inherently difficult to scale efficiently. In this paper we present a study of the effect of patch distribution strategies on the scalability of an AMR code. We demonstrate the significance of patch placement on communication overheads, and by balancing the computation and communication costs of patches, we develop a scheme to optimise performance of a specific, industry-strength, benchmark application

A Simulation Study of Path and Speed Through Double-Lane Roundabouts

This study assessed the effects of geometric curvature and lane demarcation on drivers’ selection of path and speed in double-lane roundabouts. By means of a PC-based simulator, path and speed data were collected as subjects drove twice through six roundabouts. The six roundabouts varied in terms of pavement markings and geometric curvature on the entry and exit. Seventy-five participants were tested using a fixed-base driving simulator. The results showed that drivers maintained lane position better when the roundabouts had lane demarcation than when the roundabouts had no lane demarcation. Furthermore, lane-tracking behavior for participants exposed to roundabouts with pavement markings was similar to lane-tracking behavior observed in a recent field study. Observations of speed indicated that drivers drove faster though roundabouts with a large central island radius as opposed to a roundabout with a smaller central island radiu

A Simulation Study of Path and Speed Through Double-Lane Roundabouts

This study assessed the effects of geometric curvature and lane demarcation on drivers’ selection of path and speed in double-lane roundabouts. By means of a PC-based simulator, path and speed data were collected as subjects drove twice through six roundabouts. The six roundabouts varied in terms of pavement markings and geometric curvature on the entry and exit. Seventy-five participants were tested using a fixed-base driving simulator. The results showed that drivers maintained lane position better when the roundabouts had lane demarcation than when the roundabouts had no lane demarcation. Furthermore, lane-tracking behavior for participants exposed to roundabouts with pavement markings was similar to lane-tracking behavior observed in a recent field study. Observations of speed indicated that drivers drove faster though roundabouts with a large central island radius as opposed to a roundabout with a smaller central island radiu

Teachers Beliefs and Predictors of Response to Verbal, Physical and Relational Bullying Behavior in Preschool Classrooms

Relatively few research studies exist on bullying in preschool classrooms despite research indicating bullying roles can be formed at the preschool level. The purpose of this study was to examine preschoolers’ teachers’ beliefs about the existence of bullying in classrooms, and the factors likely to predict teachers’ response towards bullying behavior. Results revealed that teachers’ empathy, perception of seriousness, and response significantly predicted preschoolers’ verbal, physical, and relational bullying behaviors. The findings of the study highlight the need for advocacy and interventions in preschool classrooms

Experiments and Modeling of the Autoignition of Methyl-Cyclohexane at High Pressure

The autoignition delays of mixtures of methyl-cyclohexane (MCH), oxygen, nitrogen, and argon have been studied in a heated rapid compression machine under the conditions $P_C$ = 50 bar, $T_C$ = 690 - 910K. Three different mixture compositions were studied, with equivalence ratios ranging from $\phi$ = 0.5 - 1.5. The trends of the ignition delay measured at 50 bar were similar to the trends measured in earlier experiments at $P_C$ = 15.1 and 25.5 bar. The experimentally measured ignition delays were compared to a newly updated chemical kinetic model for the combustion of MCH. The model has been updated to include newly calculated reaction rates for much of the low-temperature chemistry. The agreement between the experiments and the model was substantially improved compared to a previous version of the model. Nevertheless, despite the encouraging improvements, work continues on further advances, e.g. in improving predictions of the first stage ignition delays.Comment: 8 pages, 8 figures, 1 table, presented at the 8th US National Combustion Meetin