Search

The sensitivity of heterogeneous energetic (HE) materials (propellants, explosives, and pyrotechnics) is critically dependent on their microstructure. Initiation of chemical reactions occurs at hot spots due to energy localization at sites of porosities and other defects. Emerging multi-scale predictive models of HE response to loads account for the physics at the meso-scale, i.e. at the scale of statistically representative clusters of particles and other features in the microstructure. Meso-scale physics is infused in machine-learned closure models informed by resolved meso-scale simulations. Since microstructures are stochastic, ensembles of meso-scale simulations are required to quantify hot spot ignition and growth and to develop models for microstructure-dependent energy deposition rates. We propose utilizing generative adversarial networks (GAN) to spawn ensembles of synthetic heterogeneous energetic material microstructures. The method generates qualitatively and quantitatively realistic microstructures by learning from images of HE microstructures. We show that the proposed GAN method also permits the generation of new morphologies, where the porosity distribution can be controlled and spatially manipulated. Such control paves the way for the design of novel microstructures to engineer HE materials for targeted performance in a materials-by-design framework.

Post-translational modifications (PTMs) are key modulators of protein function. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene. A spectrum of PTMs have been shown to modify the normal functions of HTT, including proteolysis, phosphorylation and lipidation, but the full contribution of these PTMs to the molecular pathogenesis of HD remains unclear. In this study, we examine all commonly occurring missense mutations in HTT to identify potential human modifiers of HTT PTMs relevant to HD biology. We reveal a SNP that modifies post-translational myristoylation of HTT, resulting in downstream alterations to toxic HTT proteolysis in human cells. This is the first SNP shown to functionally modify a PTM in HD and the first validated genetic modifier of post-translational myristoylation. This SNP is a high-priority candidate modifier of HD phenotypes and may illuminate HD biology in human studies.

Changes in lung function after exercise in healthy primary school children have mostly been described in field studies. More complete description and insight into relevant mechanisms may be provided in lung function laboratory. The aim was to describe airway caliber and response to deep inhalation (DI) after exercise in healthy primary school children. Respiratory resistance (Rrs) by the forced oscillation technique and spirometry were measured before and after exercise in 50 healthy primary school children. The Rrs response to DI was assessed in 31 subjects, assuming a significantly larger decrease in Rrs after exercise would attest relief of exercise-induced airway smooth muscle contraction. Measurements were taken before, 5 min (E5) and 15 min (E15) after exercise. Significantly larger Rrs and lower forced expiratory volume in 0.5 s were observed at E5 versus baseline or E15 (p < 0.05). DI induced significant decrease in Rrs (p = 0.01) that was not different between E5 and baseline. Healthy primary school children exhibit changes in Rrs and spirometry after exercise indicating small but significant airway narrowing. The response to DI similar at baseline and E5 suggests airway narrowing from hyperemia in the bronchial wall rather than airway smooth muscle constriction.

The upper airway wall motion may be responsible for significant error when measuring respiratory resistance (Rrs) with the forced oscillation technique (FOT), particularly in young children with airway obstruction. Assessing the response to methacholine from the change in respiratory admittance (Ars, the reciprocal of respiratory impedance, Zrs) avoids the artifact. The aim of the study was to explore the possibility of assessing the response to a bronchodilator from the change in Ars. FOT measurements were performed at 12 Hz in 36 young children before and after salbutamol. Transrespiratory pressure was varied in two ways: directly at the mouth (standard generator, SG) and around the head (head generator, HG), a variant nearly free of upper airway artifact. Salbutamol induced significantly lower Rrs and Zrs change with SG than HG (respectively, p = 0.0003 and 0.05). The relative change in Ars was not significantly different with SG and HG. Both estimates were significantly correlated (p < 0.0001). The change in Ars may thus be useful to avoid the upper airway artefact when assessing the response to salbutamol using the FOT in young children.