Coarsening of Two Dimensional Foam on a Dome

In this paper we report on bubble growth rates and on the statistics of bubble topology for the coarsening of a dry foam contained in the narrow gap between two hemispheres. By contrast with coarsening in flat space, where six-sided bubbles neither grow nor shrink, we observe that six sided bubbles grow with time at a rate that depends on their size. This result agrees with the modification to von Neumann's law predicted by J.E. Avron and D. Levine. For bubbles with a different number of sides, except possibly seven, there is too much noise in the growth rate data to demonstrate a difference with coarsening in flat space. In terms of the statistics of bubble topology, we find fewer 3, 4, and 5 sided bubbles, and more 6 and greater sided bubbles, in comparison with the stationary distribution for coarsening in flat space. We also find good general agreement with the Aboav-Weaire law for the average number of sides of the neighbors of an n-sided bubble

Periodicity of high-order functions in the CNS Final progress report, year ending 30 Jun. 1971

Analysis of cerebral slow potentials underlying human attentive processes in central nervous syste

Periodicity of high-order neural functions

The results of recent studies on higher order, integrative processes in the central nervous system are reported. Attempts were made to determine whether these processes exhibit any ongoing rhythmicity which might manifest itself in alterations of attention and alertness. Experiments were also designed to determine if a periodicity approximating that of the REM could be detected in various parameters of brain electrical activity

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder

Background: Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attentiondeficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague–Dawley comparator strains. Results: Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague–Dawley strains but not in Wistar Kyoto rats. Conclusions: Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders

Engineered neural tissue made using hydrogels derived from decellularised tissues for the regeneration of peripheral nerves

Engineered neural tissue (EngNT) promotes in vivo axonal regeneration. Decellularised materials (dECM) are complex biologic scaffolds that can improve the cellular environment and also encourage positive tissue remodelling in vivo. We hypothesised that we could incorporate a hydrogel derived from a decellularised tissue (dECMh) into EngNT, thereby providing an alternative to the currently used purified collagen I hydrogel for the first time. Decellularisation was carried out on bone (B-ECM), liver (LIV-ECM), and small intestinal (SIS-ECM) tissues and the resultant dECM was biochemically and mechanically characterised. dECMh differed in mechanical and biochemical properties that likely had an effect on Schwann cell behaviour observed in metabolic activity and contraction profiles. Cellular alignment was observed in tethered moulds within the B-ECM and SIS-ECM derived hydrogels only. No difference was observed in dorsal root ganglia (DRG) neurite extension between the dECMh groups and collagen I groups when applied as a coverslip coating, however, when DRG were seeded atop EngNT constructs, only the B-ECM derived EngNT performed similarly to collagen I derived EngNT. B-ECM EngNT further exhibited similar axonal regeneration to collagen I EngNT in a 10 mm gap rat sciatic nerve injury model after 4 weeks. Our results have shown that various dECMh can be utilised to produce EngNT that can promote neurite extension in vitro and axonal regeneration in vivo

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1

\ua9 2024 The Author(s). AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier

Using low-cost sensor technologies and advanced computational methods to improve dose estimations in health panel studies: results of the AIRLESS project.

BACKGROUND: Air pollution epidemiology has primarily relied on fixed outdoor air quality monitoring networks and static populations. METHODS: Taking advantage of recent advancements in sensor technologies and computational techniques, this paper presents a novel methodological approach that improves dose estimations of multiple air pollutants in large-scale health studies. We show the results of an intensive field campaign that measured personal exposures to gaseous pollutants and particulate matter of a health panel of 251 participants residing in urban and peri-urban Beijing with 60 personal air quality monitors (PAMs). Outdoor air pollution measurements were collected in monitoring stations close to the participants' residential addresses. Based on parameters collected with the PAMs, we developed an advanced computational model that automatically classified time-activity-location patterns of each individual during daily life at high spatial and temporal resolution. RESULTS: Applying this methodological approach in two established cohorts, we found substantial differences between doses estimated from outdoor and personal air quality measurements. The PAM measurements also significantly reduced the correlation between pollutant species often observed in static outdoor measurements, reducing confounding effects. CONCLUSIONS: Future work will utilise these improved dose estimations to investigate the underlying mechanisms of air pollution on cardio-pulmonary health outcomes using detailed medical biomarkers in a way that has not been possible before.This project is funded under the Newton Fund Programme awarded by Natural Environmental Research Council (NERC Grant NE/N007018/1) with support from Medical Research Council (MRC) and by the National Natural Science Foundation of China (NSFC Grant 81571130100). The NSFC funding is mainly used to support the field work in China, and NERC funding is mainly used for coordination and the further analysis

Interictal Spiking Increases with Sleep Depth in Temporal Lobe Epilepsy

Purpose : To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. Methods: At the time of study, subjects were seizure-free for 224 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. Conclusions: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65422/1/j.1528-1157.1998.tb01329.x.pd

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth

Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict crucial regulatory modules required for AML growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD+ AML and that its removal leads to GRN collapse and cell death.</p