To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared to those from healthy individuals. We performed single-cell RNA-sequencing of a total of 330,569 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 2,235 significant loci across all cell types, 58 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 54 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.

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The use of differential evolution (DE) is investigated for the optimization of a novel rocket based combined cycle (RBCC) engine inlet, over the supersonic flight regime.An RBCC engine is designed to incorporate the advantages of both rocket propulsion and airbreathing engines. This novel design is the result of ongoing research, at Carleton University, to improve the efficiency of future single stage to orbit engine designs. This novel inlet design, referred to as the exchange inlet, is designed to entrain air using a semi-annular rocket-ejector exhaust profile. The purpose of the exchange inlet is to increase the air mass flow and air/fuel mixing over existing rocket ejector/RBCC designs. In addition, by using a single circular rocket throat the exchange inlet is designed to be compatible with existing rockets.