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Accurate tyre models are essential for all full vehicle simulation models. Tyre models are usually parameterised based on measurements on new tyres. This article performs a sensitivity analysis, based on experimental data, to determine the effects of age and wear on a 235/55R19 tyre’s stiffness characteristics as well as the effect of wear on the tyre’s longitudinal friction characteristics. A well-researched and documented method was used to artificially age the tyres. Static tests were performed periodically on the tyre to monitor the changes in stiffness characteristics. Tyres were also subjected to accelerated wear by performing repeated side force versus slip angle and longitudinal force versus slip tests on a coarse concrete surface. The results indicate that the vertical and longitudinal force versus displacement characteristics have small but convincing dependencies on the age and wear. While the aging process was a trustworthy method, the wear process created irregular lateral and circumferential wear which impacted results. Overall the effects of age and wear did not exhibit substantial enough influence on the tyre stiffness to merit a full tyre model update. However, the wear did have a significant effect, in the order of 10%, on the longitudinal friction of the tyre.

Migraineurs can show brain hyperexcitability and oxidative stress that may promote headache. Since hyperexcitability can enhance oxidative stress which promotes hyperexcitability, ending this feed-back loop may reduce migraine. Neocortical spreading depression, an anrefeimal model of migraine begins with hyperexcitability and triggers oxidative stress in the neocortical area involved and in the trigeminal system, which is important to pain pathway nociceptive activation in migraine. Additionally, oxidative stress causes increased trigeminal ganglion calcitonin gene-related peptide release and oxidative stress can reduce spreading depression threshold. Insulin-like growth factor-1 significantly protects against spreading depression in vitro by reducing oxidative stress and it is effective against spreading depression after intranasal delivery to animals. Here, we used adult male rats and extend this work to study the trigeminal system where insulin-like growth factor-1 receptors are highly expressed. Recurrent neocortical spreading depression significantly increased surrogate markers of trigeminal activation - immunostaining for trigeminal ganglion oxidative stress, calcitonin gene related peptide levels and c-fos in the trigeminocervical complex versus sham. These effects were significantly reduced by intranasal delivery of insulin-like growth factor-1 a day before recurrent neocortical spreading depression. Furthermore, intranasal treatment with insulin-like growth factor-1 significantly reduced naïve levels of trigeminal ganglion calcitonin gene related peptide versus sham with no impact on blood glucose levels. Intranasal delivery of insulin-like growth factor-1 not only mitigates neocortical spreading depression, a cause of migraine hyperexcitability modeled in animals, but also when neocortical spreading depression is triggered by suprathreshold stimuli, insulin-like growth factor-1 effectively reduces nociceptive activation in the trigeminal system.

Additional file 1. 2016 Blood Brain Interface Workshop Agenda.

With all wheeled vehicles, the tire contact patch is the only connection between the vehicle and the road. All the forces, except for aerodynamic forces, that are acting on the vehicle are generated in the tire contact patch. The size, shape and the pressure distribution of the contact patch are important to the performance, ride qualities and handling characteristics of a vehicle. Tire footprint studies are essential in understanding tire force generation and tire wear mechanisms. It is thus important to accurately determine the tire contact patch size and dimensions. This paper discusses various methods for measuring the static tire contact patch dimensions. A set of tests are conducted on various tires and at different inflation pressures. These tests are used to discuss the suitability of the methods depending on the type, size, load and contact surface of the tire. A list of advantages and disadvantages for each method is generated and discussed. The aim of this paper is not to study the tire footprints but to discuss the various testing methods. Insight into the different methods can help to select the suitable method for future tire contact studies.Copyright © 2016 by ASME

Cold pre-conditioning reduces subsequent brain injury in small animals but the underlying mechanisms remain undefined. As hypothermia triggers systemic macrophage tumor necrosis factor alpha (TNF-α) production and other neural pre-conditioning stimuli depend on this cytokine, we reasoned that microglia and TNF-α would be similarly involved with cold pre-conditioning neuroprotection. Also, as slice cultures closely approximate their in vivo counterpart and include quiescent microglia, we used rat hippocampal slice cultures to confirm this hypothesis. Furthermore, inflammatory cytokine gene screening with subsequent PCR and immunostaining confirmation of targeted mRNA and related protein changes showed that cold pre-conditioning triggered a significant rise in TNF-α that localized to microglia and a significant rise in interleukin (IL)-11 that localized mainly to hippocampal pyramidal neurons and, more rarely, astrocytes. Importantly, co-stimulation with cold and IL-11, an anti-inflammatory cytokine that inhibits TNF-α expression, abrogated the otherwise evident protection. Instead, cold pre-conditioning coupled with blockade of IL-11 signaling further enhanced neuroprotection from that seen with cold pre-conditioning alone. Thus, physiological activation of brain pro-inflammatory cytokine signaling, and its amplification by inhibition of coincident anti-inflammatory cytokine signaling, may be opportune targets for the development of novel therapeutics that can mimic the protection seen in cold pre-conditioning.

Increases in astroglial Cl- conductance accompany changes in cell morphology and disassembly of cytoskeletal actin, but Cl- channels underlying these conductance increases have not been described. We characterize an outwardly rectifying Cl- channel in rodent neocortical cultured astrocytes and describe how cell shape and cytoskeletal actin modulate channel gating. In inside-out patch-clamp recordings from cultured astrocytes, outwardly rectifying Cl- channels either were spontaneously active or inducible in quiescent patches by depolarizing voltage steps. Average single-channel conductance was 36 pS between -60 and -80 mV and was 75 pS between 60 and 80 mV in symmetrical (150 mM NaCl) solutions. The permeability ratio (PNa/PCl) was 0.14 at lower ionic strength but increased at higher salt concentrations. Both ATP and 4, 4-diisothiocyanostilbene-2,2'-disulfonic acid produced a flicker block, whereas Zn2+ produced complete inhibition of channel activity. The frequency of observing both spontaneous and inducible Cl- channel activity was markedly higher in stellate than in flat, polygonally shaped astrocytes. In addition, cytoskeletal actin modulated channel open-state probability (PO) and conductance at negative membrane potentials, controlling the degree of outward rectification. Direct application of phalloidin, which stabilizes actin, preserved low PO and promoted lower conductance levels at negative potentials. Lower PO also was induced by direct application of polymerized actin. The actions of phalloidin and actin were reversed by coapplication of gelsolin and cytochalasin D, respectively. These results provide the first report of an outwardly rectifying Cl- channel in neocortical astrocytes and demonstrate how changes in cell shape and cytoskeletal actin may control Cl- conductance in these cells.