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Abstract AimsDissecting complex interactions among transcription factors (TFs), microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are central for understanding heart development and function. Although computational approaches and platforms have been described to infer relationships among regulatory factors and genes, current approaches do not adequately account for how highly diverse, interacting regulators that include noncoding RNAs (ncRNAs) control cardiac gene expression dynamics over time. MethodsTo overcome this limitation, we devised an integrated framework, cardiac gene regulatory modeling (CGRM) that integrates LogicTRN and regulatory component analysis bioinformatics modeling platforms to infer complex regulatory mechanisms. We then used CGRM to identify and compare the TF-ncRNA gene regulatory networks that govern early- and late-stage cardiomyocytes (CMs) generated by in vitro differentiation of human pluripotent stem cells (hPSC) and ventricular and atrial CMs isolated during in vivo human cardiac development. ResultsComparisons of in vitro versus in vivo derived CMs revealed conserved regulatory networks among TFs and ncRNAs in early cells that significantly diverged in late staged cells. We report that cardiac genes (“heart targets”) expressed in early-stage hPSC-CMs are primarily regulated by MESP1, miR-1, miR-23, lncRNAs NEAT1 and MALAT1, while GATA6, HAND2, miR-200c, NEAT1 and MALAT1 are critical for late hPSC-CMs. The inferred TF-miRNA-lncRNA networks regulating heart development and contraction were similar among early-stage CMs, among individual hPSC-CM datasets and between in vitro and in vivo samples. However, genes related to apoptosis, cell cycle and proliferation, and transmembrane transport showed a high degree of divergence between in vitro and in vivo derived late-stage CMs. Overall, late-, but not early-stage CMs diverged greatly in the expression of “heart target” transcripts and their regulatory mechanisms. ConclusionsIn conclusion, we find that hPSC-CMs are regulated in a cell autonomous manner during early development that diverges significantly as a function of time when compared to in vivo derived CMs. These findings demonstrate the feasibility of using CGRM to reveal dynamic and complex transcriptional and posttranscriptional regulatory interactions that underlie cell directed versus environment-dependent CM development. These results with in vitro versus in vivo derived CMs thus establish this approach for detailed analyses of heart disease and for the analysis of cell regulatory systems in other biomedical fields. 

Abstract In this paper, we present results from an experiment using EEG to measure brain activity and explore EEG frequency power associated with gender differences of professional industrial designers while performing two prototypical stages of constrained and open design tasks, problem-solving and design sketching. Results indicate no main effect of gender. However, among other main effects, a consistent main effect of hemisphere for the six frequency bands under analysis was found. In the problem-solving stage, male designers show higher alpha and beta bands in channels of the prefrontal cortices and female designers in the right occipitotemporal cortex and secondary visual cortices. In the design sketching stage, male designers show higher alpha and beta bands in the right prefrontal cortex, and female designers in the right temporal cortex and left prefrontal cortex, where higher theta is also found. Prioritising different cognitive functions seem to play a role in each gender's approach to constrained and open design tasks. Results can be useful to design professionals, students and design educators, and for the development of methodological approaches in design research and education. 

Design space is a common abstraction in design research used in the investigation of design cognition. Although its usefulness has been alleged and has contributed to the knowledge about designing, characteristics and properties of design spaces and how they change while designing are underexplored. Creativity has been recognized as an essential skill for changing the design space from constrained to open spaces. We analyzed the brain activity of designers while performing constrained and open design tasks. This study investigates the neurophysiological activations of professional mechanical engineers and industrial designers in two prototypical design tasks, a problem-solving constrained layout task and an open design sketching task. The analysis focused on comparing the neurophysiological activations of the cognitive demand in three stages of categorical similarity of designing in constrained and open design spaces. Results indicate significant differences of frequency bands activations between stages of the design spaces across and between domains. In particular, the stage of reflecting evoked visual imagination and associative reasoning modes and revealed significant differences in beta bands from the problem-solving stage leading to expanded activation in the sketching stage, which translates in higher activation in the open design task with significant differences in upper alpha and beta bands. We propose the neurophysiological activations as a measure of the pliability of design spaces.