Design mining interacting wind turbines

© 2016 by the Massachusetts Institute of Technology. An initial study has recently been presented of surrogate-assisted evolutionary algorithms used to design vertical-axis wind turbines wherein candidate prototypes are evaluated under fan-generated wind conditions after being physically instantiated by a 3D printer. Unlike other approaches, such as computational fluid dynamics simulations, no mathematical formulations were used and no model assumptions weremade. This paper extends that work by exploring alternative surrogate modelling and evolutionary techniques. The accuracy of various modelling algorithms used to estimate the fitness of evaluated individuals from the initial experiments is compared. The effect of temporally windowing surrogate model training samples is explored. A surrogateassisted approach based on an enhanced local search is introduced; and alternative coevolution collaboration schemes are examined

Control of Transonic Cavity Flow Instability by Streamwise Air Injection

A time-dependent numerical model of a turbulent Mach 1.5 flow over a rectangular cavity has been developed, to investigate suppression strategies for its natural self-sustained instability. This instability adversely affects the cavity form drag, it produces large-amplitude pressure oscillations in the enclosure and it is a source of far-field acoustic radiation. To suppress the natural flow instability, the leading edge of the two-dimensional cavity model is fitted with a simulated air jet that discharges in the downstream direction. The jet mass flow rate and nozzle depth are adjusted to attenuate the instability while minimising the control mass flow rate. The numerical predictions indicate that, at the selected inflow conditions, the configurations with the deepest nozzle (0.75 of the cavity depth) give the most attenuation of the modelled instability, which is dominated by the cavity second mode. The jet affects both the unsteady pressure field and the vorticity distribution inside the enclosure, which are, together, key determinants of the cavity leading instability mode amplitude. The unsteadiness of the pressure field is reduced by the lifting of the cavity shear layer at the rear end above the trailing edge. This disrupts the formation of upstream travelling feed-back pressure waves and the generation of far-field noise. The deep nozzle also promotes a downstream bulk flow in the enclosure, running from the upstream vertical wall to the downstream one. This flow attenuates the large-scale clockwise recirculation that is present in the unsuppressed cavity flow. The same flow alters the top shear layer vorticity thickness and probably affects the convective growth of the shear layer cavity second mode

POD Analysis of Cavity Flow Instability

A Mach 1.5 turbulent cavity flow develops large-amplitude oscillations, pressure drag and noise. This type of flow instability affects practical engineering applications, such as aircraft store bays. A simple model of the flow instability is sought towards developing a real-time model-based active control system for simple geometries, representative of open aircraft store bays. An explicit time marching second-order accurate finite-volume scheme has been used to generate time-dependent benchmark cavity flow data. Then, a simpler and leaner numerical predictor for the unsteady cavity pressure was developed, based on a Proper Orthogonal Decomposition of the benchmark data. The low order predictor gives pressure oscillations in good agreement with the benchmark CFD method. This result highlights the importance of large-scale phase-coherent structures in the Mach 1.5 turbulent cavity flow. At the selected test conditions, the significant pressure ‘energy’ content of these structures enabled an effective reduced order model of the cavity dynamic system. Directions and methods to further streamline and simplify the unsteady pressure predictor have been highlighted

In vitro safety “clinical trial” of the cardiac liability of drug polytherapy

Abstract Only a handful of US Food and Drug Administration (FDA) Emergency Use Authorizations exist for drug and biologic therapeutics that treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Potential therapeutics include repurposed drugs, some with cardiac liabilities. We report on a chronic preclinical drug screening platform, a cardiac microphysiological system (MPS), to assess cardiotoxicity associated with repurposed hydroxychloroquine (HCQ) and azithromycin (AZM) polytherapy in a mock phase I safety clinical trial. The MPS contained human heart muscle derived from induced pluripotent stem cells. The effect of drug response was measured using outputs that correlate with clinical measurements, such as QT interval (action potential duration) and drug‐biomarker pairing. Chronic exposure (10 days) of heart muscle to HCQ alone elicited early afterdepolarizations and increased QT interval past 5 days. AZM alone elicited an increase in QT interval from day 7 onward, and arrhythmias were observed at days 8 and 10. Monotherapy results mimicked clinical trial outcomes. Upon chronic exposure to HCQ and AZM polytherapy, we observed an increase in QT interval on days 4–8. Interestingly, a decrease in arrhythmias and instabilities was observed in polytherapy relative to monotherapy, in concordance with published clinical trials. Biomarkers, most of them measurable in patients’ serum, were identified for negative effects of monotherapy or polytherapy on tissue contractile function, morphology, and antioxidant protection. The cardiac MPS correctly predicted clinical arrhythmias associated with QT prolongation and rhythm instabilities. This high content system can help clinicians design their trials, rapidly project cardiac outcomes, and define new monitoring biomarkers to accelerate access of patients to safe coronavirus disease 2019 (COVID‐19) therapeutics

Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.

Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS-both created with the same hiPSC line-to study drug-drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS. These results establish integration of hiPSC-based liver and cardiac MPSs to facilitate screening for DDI, and thus drug efficacy and toxicity, isogenic in the same genetic background