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Prototyping is a core element of engineering and technology activity, giving form to design concepts and facilitating iteration and testing. With the rise of the "maker movement," higher fidelity forms of prototyping have often been privileged, without deep investigation into prototyping activities that support materially-focused exploration across difTerent levels of fidelity. In this paper, we describe how students in an interdisciplinary undergraduate audio engineering course adapted to a loss of fabrication equipment and the COVID-19 pandemic, relying more heavily on cardboard prototypes as they "iterated overnight" at home to realize the design of their loudspeaker. We analyzed a range ofiterative prototypes using a prototyping framework we operationalized from Lim. Tenenberg, and Stolterman, describing the filtering and manifestation dimensions across a range of student projects. We reflect upon the trajectories of prototyping, considering strengths and weaknesses of different types of materials in supporting student exploration and the pedagogical supports that may be needed to encourage this exploration. [ABSTRACT FROM AUTHOR]

The activating transcription factor 3 (ATF3) gene is induced by a variety of signals, including many of those encountered by cancer cells. We present evidence that ATF3 is induced by TGFβ in the MCF10CA1a breast cancer cells and plays an integral role for TGFβ to upregulate its target genes snail, slug and twist, and to enhance cell motility. Furthermore, ATF3 upregulates the expression of the TGFb gene itself, forming a positive-feedback loop for TGFβ signaling. Functionally, ectopic expression of ATF3 leads to morphological changes and alterations of markers consistent with epithelial-to-mesenchymal transition (EMT). It also leads to features associated with breast-cancer-initiating cells: increased CD24low-CD44high population of cells, mammosphere formation and tumorigenesis. Conversely, knockdown of ATF3 reduces EMT, CD24low-CD44high cells and mammosphere formation. Importantly, knocking down twist, a downstream target, reduces the ability of ATF3 to enhance mammosphere formation, indicating the functional significance of twist in ATF3 action. To our knowledge, this is the first report demonstrating the ability of ATF3 to enhance breast cancer-initiating cell features and to feedback on TGFβ. Because ATF3 is an adaptive-response gene and is induced by various stromal signals, these findings have significant implications for how the tumor microenvironment might affect cancer development. [ABSTRACT FROM AUTHOR]

Objective: beta-Cell failure is an essential component of all types of diabetes, and the insulin receptor substrate 2 (IRS2) branch of signaling plays a key role in beta-cell survival and function. We tested the hypothesis that activating transcription factor 3 (ATF3), a stress-inducible proapoptotic gene, downregulates the expression of IRS2 in beta-cells.Research Design and Methods: We used both the gain- and loss-of-function approaches to test the effects of ATF3 on IRS2 gene expression. We also analyzed the binding of ATF3 to the IRS2 promoter by chromatin immunoprecipitation assay and the transcription of the IRS2 gene by polymerase II occupancy assay. Furthermore, we tested the ability of IRS2 to alleviate the proapoptotic effects of ATF3 in cultured beta-cells and in transgenic mice using the rat insulin promoter to drive the transgenes.Results: Expression of ATF3 is sufficient to reduce IRS2 gene expression; in contrast, knockdown or knockout of ATF3 reduces the ability of stress signals to downregulate IRS2 expression. ATF3 binds to the IRS2 promoter in vivo, and the binding of ATF3 correlates with decreased IRS2 gene transcription. Functionally, expression of IRS2 protects beta-cells from ATF3-induced apoptosis.Conclusions: IRS2 is a target gene of ATF3, and its repression by ATF3 contributes, at least partly, to the apoptosis induced by ATF3. Because ATF3 is a stress-inducible gene, our work provides a direct link to explain how environmental stress factors can modulate IRS2 gene transcription. [ABSTRACT FROM AUTHOR]