Engineering topics
Publications and source records attributed to Tran, Phu N..
Deep learning-based optical flow (DLOF) extracts features in video frames with deep convolutional neural networks to estimate the inter-frame motions of objects. DLOF computes velocity fields more accurately than PIV for densely labeled systems.
A machine learning model for reliable director fields calculation from raw experimental images of active nematics. The model is accurate, robust to noise and generalizable, enhancing analysis such as the detection and tracking of topological defects.
Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QT C prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QT C prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QT C prolongation and TdP are most commonly caused by acute inhibition of hERG current (I hERG ) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na + (I NaL ) and/or L-type Ca 2+ (I CaL ) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca 2+ , and Na + ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QT C prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, Ca V 1.2, and Na V 1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on I hERG , I CaL , I NaL , and peak Na + current (I NaP ) at clinically relevant concentrations. In contrast, methadone inhibited I hERG , I CaL , and I NaL . Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QT C prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QT C prolongation not mediated by acute hERG channel block warrants further study.
The International Council on Harmonization (ICH) S7B and E14 regulatory guidelines are sensitive but not specific for predicting which drugs are pro‐arrhythmic. In response, the Comprehensive In Vitro Proarrhythmia Assay (Ci PA ) was proposed that integrates multi‐ion channel pharmacology data in vitro into a human cardiomyocyte model in silico for proarrhythmia risk assessment. Previously, we reported the model optimization and proarrhythmia metric selection based on Ci PA training drugs. In this study, we report the application of the prespecified model and metric to independent Ci PA validation drugs. Over two validation datasets, the Ci PA model performance meets all pre‐specified measures for ranking and classifying validation drugs, and outperforms alternatives, despite some in vitro data differences between the two datasets due to different experimental conditions and quality control procedures. This suggests that the current Ci PA model/metric may be fit for regulatory use, and standardization of experimental protocols and quality control criteria could increase the model prediction accuracy even further.