Robust numerical analysis of fibrous composites from X-ray computed tomography image data enabling low resolutions

X-ray computed tomography scans can provide detailed information about the state of the material after manufacture and in service. X-ray computed tomography aided engineering (XAE) was recently introduced as an automated process to transfer 3D image data to finite element models. The implementation of a structure tensor code for material orientation analysis in combination with a newly developed integration point-wise fibre orientation mapping allows an easy applicable, computationally cheap, fast, and accurate model set-up. The robustness of the proposed approach is demonstrated on a non-crimp fabric glass fibre reinforced composite for a low resolution case with a voxel size of 64 μm corresponding to more than three times the fibre diameter. Even though 99.8% of the original image data is removed, the simulated elastic modulus of the considered non-crimp fabric composite is only underestimated by 4.7% compared to the simulation result based on the original high resolution scan

Suppressed plastic deformation at blunt crack tips due to strain gradient effects

AbstractLarge deformation gradients occur near a crack-tip and strain gradient dependent crack-tip deformation and stress fields are expected. Nevertheless, for material length scales much smaller than the scale of the deformation gradients, a conventional elastic–plastic solution is obtained. On the other hand, for significant large material length scales, a conventional elastic solution is obtained. This transition in behaviour is investigated based on a finite strain version of the Fleck–Hutchinson strain gradient plasticity model from 2001. The predictions show that for a wide range of material parameters, the transition from the conventional elastic–plastic to the elastic solution occurs for length scales ranging from 0.001 times the size of the plastic zone to a length scale of the same order of magnitude as the plastic zone

Functional interaction between Lypd6 and nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain‐containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross‐linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane‐bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine‐induced hippocampal inward currents in rat brain slices and decreases nicotine‐induced extracellular signal‐regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR‐mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post‐natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. [Image: see text] Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine‐induced ERK phosphorylation and attenuates nicotine‐induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain

A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency

The established causal genes in Alzheimer’s disease (AD), APP, PSEN1, and PSEN2, are functionally characterized using biomarkers, capturing an in vivo profile reflecting the disease’s initial preclinical phase. Mutations in SORL1, encoding the endosome recycling receptor SORLA, are found in 2%–3% of individuals with early-onset AD, and SORL1 haploinsufficiency appears to be causal for AD. To test whether SORL1 can function as an AD causal gene, we use CRISPR-Cas9-based gene editing to develop a model of SORL1 haploinsufficiency in Göttingen minipigs, taking advantage of porcine models for biomarker investigations. SORL1 haploinsufficiency in young adult minipigs is found to phenocopy the preclinical in vivo profile of AD observed with APP, PSEN1, and PSEN2, resulting in elevated levels of β-amyloid (Aβ) and tau preceding amyloid plaque formation and neurodegeneration, as observed in humans. Our study provides functional support for the theory that SORL1 haploinsufficiency leads to endosome cytopathology with biofluid hallmarks of autosomal dominant AD