Fibre alignment and mechanical performance of carbon fibre Sheet Moulding Compounds under different preform compaction

This work investigates the effect of preform compaction on the mechanical performance and flow-induced fibre alignment of carbon fibre reinforced Sheet Moulding Compounds (SMCs). Two groups of panels have been compression moulded from reclaimed carbon fibre tows in vinyl-ester resin with low (0.5 MPa) and high (10 MPa) preform compaction pressure Additionally, a low-cost fibre orientation analysis method has been further improved in terms of reliability, and a novel flow assessment method has been developed for carbon fibre SMCs. This approach revealed greater fibre alignment with the flow direction in the lower faces of panels as a result of greater contact time with the heated mould and a lower charge viscosity at the time of pressing. As expected, greater fibre alignment in the flow direction was observed outside the initial charge coverage area in both types of panels, where the flow was greatest. Due to additional fibre flow during the high-pressure compaction stage, the mean degree of flow alignment in the high compaction panel was 47% higher than that of the low compaction panel. Improvements in the tensile stiffness (8%) and strength (32%) were also observed as a result of the high-pressure compaction stage and associated flow alignment.

PGC1α Regulates the Endothelial Response to Fluid Shear Stress via Telomerase Reverse Transcriptase Control of Heme Oxygenase-1

Objective: Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow, which is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood. In this study, we determine the role of PGC1α (peroxisome proliferator gamma coactivator-1α)-TERT (telomerase reverse transcriptase)-HMOX1 (heme oxygenase-1) during shear stress in vitro and in vivo. Approach and Results: Here, we have identified PGC1α as a flow-responsive gene required for endothelial flow alignment in vitro and in vivo. Compared with oscillatory FSS (disturbed flow) or static conditions, laminar FSS (undisturbed flow) showed increased PGC1α expression and its transcriptional coactivation. PGC1α was required for laminar FSS-induced expression of TERT in vitro and in vivo via its association with ERRα(estrogen-related receptor alpha) and KLF (Kruppel-like factor)-4 on the TERT promoter. We found that TERT inhibition attenuated endothelial flow alignment, elongation, and nuclear polarization in response to laminar FSS in vitro and in vivo. Among the flow-responsive genes sensitive to TERT status, HMOX1 was required for endothelial alignment to laminar FSS. Conclusions: These data suggest an important role for a PGC1α-TERT-HMOX1 axis in the endothelial stabilization response to laminar FSS.

PGC1α Regulates the Endothelial Response to Fluid Shear Stress via Telomerase Reverse Transcriptase Control of Heme Oxygenase-1

Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow that is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood. Here we have identified peroxisome proliferator gamma coactivator-1α (PGC-1α) as a flow-responsive gene required for endothelial flow alignment in vitro and in vivo. Compared to oscillatory FSS (disturbed flow) or static conditions, laminar FSS (undisturbed flow) increased PGC-1α expression and its transcriptional co-activation. PGC-1α was required for laminar FSS-induced expression of telomerase reverse transcriptase (TERT) in vitro and in vivo via its association with ERRα and KLF4 on the TERT promoter. We found that TERT inhibition attenuated endothelial flow alignment, elongation, and nuclear polarization in response to laminar FSS in vitro and in vivo. Among the flow-responsive genes sensitive to TERT status was heme oxygenase-1 (HMOX1), a gene required for endothelial alignment to laminar FSS. Thus, these data suggest an important role for a PGC-1α-TERT-HMOX1 axis in the endothelial stabilization response to laminar FSS.

Reference flow: reducing reference bias using multiple population genomes

Most sequencing data analyses start by aligning sequencing reads to a linear reference genome, but failure to account for genetic variation leads to reference bias and confounding of results downstream. Other approaches replace the linear reference with structures like graphs that can include genetic variation, incurring major computational overhead. We propose the reference flow alignment method that uses multiple population reference genomes to improve alignment accuracy and reduce reference bias. Compared to the graph aligner vg, reference flow achieves a similar level of accuracy and bias avoidance but with 14% of the memory footprint and 5.5 times the speed.

SMAD6 Integrates Endothelial Cell Homeostatic Flow Responses Downstream of Notch

ABSTRACTLaminar shear stress regulates blood vessel morphogenesis and subsequent quiescence, leading to vascular homeostasis. Although important for vessel function, how vascular homeostasis is set up and maintained is poorly understood. SMAD6, a scaffold for several signaling pathways, is expressed in developing arteries and its expression is flow-regulated. We found that SMAD6 is essential for endothelial cell flow-mediated responses downstream of the mechanosensor Notch1. Endothelial cells with reduced SMAD6 levels failed to align under homeostatic laminar shear flow, while forced SMAD6 expression rescued misalignment induced by reduced Notch1 signaling. SMAD6-dependent homeostatic laminar flow responses required the Notch ligand Dll4 and Notch transcriptional activity. Mechanistically, neither the N-terminal nor the C-terminal domain of SMAD6 alone rescued flow alignment upon loss of Notch signaling. Endothelial cells with reduced Smad6 levels had compromised barrier function, and RNA profiling revealed upregulation of proliferation-associated genes and down regulation of junction-associated genes. Among junction-related genes affected by SMAD6 levels, the proto-cadherin PCDH12 was upregulated by homeostatic flow and required for proper flow-mediated endothelial cell alignment. Thus, SMAD6 is a critical integrator of flow-mediated signaling inputs downstream of Notch1, as vessels transition from an angiogenic to a homeostatic phenotype.

Reducing reference bias using multiple population reference genomes

Most sequencing data analyses start by aligning sequencing reads to a linear reference genome. But failure to account for genetic variation causes reference bias and confounding of results downstream. Other approaches replace the linear reference with structures like graphs that can include genetic variation, incurring major computational overhead. We propose the “reference flow” alignment method that uses multiple population reference genomes to improve alignment accuracy and reduce reference bias. Compared to the graph aligner vg, reference flow achieves a similar level of accuracy and bias avoidance, but with 14% of the memory footprint and 5.5 times the speed.

Highly conductive and transparent coatings from flow-aligned silver nanowires with large electrical and optical anisotropy

A robust flow alignment technique generates conductive and transparent silver nanowire coatings with tunable alignment and anisotropy.