The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The generated CMs expressed CM-specific genes and were highly concordant in their total expressed transcriptome across the 12 samples (correlation coefficient at 95% CI =0.92 ± 0.02). The functional annotation and enrichment analysis of the 2116 genes that were significantly upregulated in CMs suggest that generated CMs have a transcriptomic and functional profile of immature atrial-like CMs; however, the CMs-upregulated transcriptome also showed high overlap and significant enrichment in primary cardiomyocyte (p-value = 4.36 × 10−9), primary heart tissue (p-value = 1.37 × 10−41) and cardiomyopathy (p-value = 1.13 × 10−21) associated gene sets. Modeling the effect of MACE in the generated CMs-upregulated transcriptome identified gene expression phenotypes consistent with the predisposition of the MACE-affected sibship to arrhythmia, prothrombotic, and atherosclerosis risk.

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Six Sigma is a business strategy that helps organizations to improve its organizational efficiency and Customer satisfaction; it decreases operating cost and increases profits. Six Sigma is a widely used method to improve processes from various industrial sectors. The target failure rate for Six Sigma projects is 3.4 parts per million Numerous practitioner studies claim that Six Sigma improves organizational performance. However, its implementation to design process is limited. So, in this study we have implemented the six-sigma philosophy in piping design process. Piping isometric drawings, which feature their intrinsically topological relation rather than just geometrical shape, are important industrial art works in the field of Computer-Aided Design (CAD). This study suggests that the link between Six Sigma and piping design process performance can be explained and developed by integrating organizational knowledge creation processes. We have quantified the performance of a design process in terms of sigma level and tried to find the possible ways to improve it. The method used in this study is based on five main steps summarized in the acronym (DMAIC): Define Measure, Analyse, Improve and Control. Application of the method on the design process during the five phases of the method will help to reduce costs and losses of man-hours to strive for optimum results in terms of profit and quality.

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