Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell–cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.

The concept of nudge theory, from the fields of behavioural science, political theory and behavioural economics, has sparked government initiatives yielding significant public value. A nudge is a method for predictably altering behaviour without restricting consumer choice options or significantly changing incentives. Nudges work by leveraging default human behaviour such as the tendency to take the path of least resistance when exercising choice. Government agencies have run many successful trials with simple textual nudges designed to positively influence behaviours such as tax compliance, voter registration and student attrition. This article develops the concept of the digital nudge in social security administration. The digital nudge leverages predictive analytics technology within a digital government framework to support a social investment policy approach. Based on a literature review of nudges within a digital government context, the article identifies examples of innovation within social security administration where nudges are contributing to better social outcomes. At the same time, concerns regarding ethics and privacy are identified as nudges are applied at the individual rather than the population level. The use of data and personal information to drive the nudge process has to be managed in such a way that individual rights are protected. This requirement has to be reconciled with the broader interests of society in achieving affordable outcomes, the parameters of which are determined through the political process.

Tissue engineering (TE) approaches that involve seeding cells into predetermined tissue scaffolds ignore the complex environment where the material properties are spatially inhomogeneous and evolve over time. We present a new approach for controlling mechanical forces inside bioreactors, which enables spatiotemporal control of flow fields in real time. Our adaptive approach offers the flexibility of dialing-in arbitrary shear stress distributions and adjusting flow field patterns in a scaffold over time in response to cell growth without needing to alter scaffold structure. This is achieved with a multi-inlet bioreactor and a control algorithm with learning capabilities to dynamically solve the inverse problem of computing the inlet pressure distribution required over the multiple inlets to obtain a target flow field. The new method constitutes a new platform for studies of cellular responses to mechanical forces in complex environments and opens potentially transformative possibilities for TE.

We anticipate that such readouts of tissue culture growth will provide valuable feedback for controlled cell growth in bioreactors.

Digital data and the social license governing its use are fundamental to a new wave of digital technology innovations needed to address the looming social policy challenges. To address these modern social policy challenges, social security needs to reinforce the capabilities for digital enabled human decision making. To enable the latter, digital data, once collected in raw form is refined and transformed as it moves through the data lifecycle of research, policy, program design, service delivery and evaluation. Social policy thinking and decision making is informed by these new and innovative data products emerging at each phase of the data life cycle. The human dimension, guided by insight and knowledge from a dynamic evidence base of digital data, is essential for managing the risks (i.e., privacy, security, ethics) while achieving the benefits (i.e., better social outcomes for stronger societies). The performance and integrity of human decision-makers in managing these risks for the public good will determine the direction of public trust and confidence in the social security administration