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Computer simulators are widely used for the study of complex systems. In many applications, there are multiple simulators available with different scientific interpretations of the underlying mechanism, and the goal is to identify an optimal simulator based on the observed physical experiments. To achieve the goal, we propose a selection criterion based on leave-one-out cross-validation. This criterion consists of a goodness-of-fit measure and a generalized degrees of freedom penalizing the simulator sensitivity to perturbations in the physical observations. Asymptotic properties of the selected optimal simulator are discussed. It is shown that the proposed procedure includes a conventional calibration method as a special case. The finite sample performance of the proposed procedure is demonstrated through numerical examples. In the application of cell biology, an optimal simulator is selected, which can shed light on the T cell recognition mechanism in the human immune system. for this article are available online. [ABSTRACT FROM AUTHOR]

Sequential administration of immunotherapy following radiotherapy (immunoRT) has attracted much attention in cancer research. Due to its unique feature that radiotherapy upregulates the expression of a predictive biomarker for immunotherapy, novel clinical trial designs are needed for immunoRT to identify patient subgroups and the optimal dose for each subgroup. In this article, we propose a Bayesian phase I/II design for immunotherapy administered after standard‐dose radiotherapy for this purpose. We construct a latent subgroup membership variable and model it as a function of the baseline and pre‐post radiotherapy change in the predictive biomarker measurements. Conditional on the latent subgroup membership of each patient, we jointly model the continuous immune response and the binary efficacy outcome using plateau models, and model toxicity using the equivalent toxicity score approach to account for toxicity grades. During the trial, based on accumulating data, we continuously update model estimates and adaptively randomize patients to admissible doses. Simulation studies and an illustrative trial application show that our design has good operating characteristics in terms of identifying both patient subgroups and the optimal dose for each subgroup. [ABSTRACT FROM AUTHOR]

Motivated by an analysis of single molecular experiments in the study of T‐cell signaling, a new model called varying coefficient frailty model with local linear estimation is proposed. Frailty models have been extensively studied, but extensions to nonconstant coefficients are limited to spline‐based methods that tend to produce estimation bias near the boundary. To address this problem, we introduce a local polynomial kernel smoothing technique with a modified expectation‐maximization algorithm to estimate the unknown parameters. Theoretical properties of the estimators, including their unbiased property near the boundary, are derived along with discussions on the asymptotic bias‐variance trade‐off. The finite sample performance is examined by simulation studies, and comparisons with existing spline‐based approaches are conducted to show the potential advantages of the proposed approach. The proposed method is implemented for the analysis of T‐cell signaling. The fitted varying coefficient model provides a rigorous quantification of an early and rapid impact on T‐cell signaling from the accumulation of bond lifetime, which can shed new light on the fundamental understanding of how T cells initiate immune responses. [ABSTRACT FROM AUTHOR]

Heat generation in integrated circuits (ICs) has become a severe issue, which limits the utilization of miniaturized semiconductor devices in high-density 3-D IC technologies. Herein, Al2O3 was doped in ZrO2 thin films by plasma-enhanced atomic layer deposition (PEALD) to enhance their antiferroelectric (AFE) characteristics for highly reliable electrocaloric (EC) cooling applications. The cycling endurance in AFE behaviors of the Al:ZrO2 thin films under a high electric field of 5 MV/cm was significantly improved because of the enlargement of the energy bandgap with high resistance in trap-induced leakage current. Hence, the reliability of the EC effect of the 1% Al:ZrO2 thin film was examined with a negligible change in adiabatic temperature change ($\Delta {T}$) of 2.6% after a cycling endurance test of $10^{{6}}$ cycles. With the competitive cycling reliabilities in AFE and EC behaviors, devices with optimized Al2O3-incorporated ZrO2 thin films show significant potential for future nanoscale cooling systems in chip-level ICs. [ABSTRACT FROM AUTHOR]

We discuss the problem of approximating a deterministic function using Gaussian processes (GPs). The role of transformation in GP modeling is not well understood. We argue that transformation of the response can be used for making the deterministic function approximately additive, which can then be easily estimated using an additive GP. We call such a GP a transformed additive Gaussian (TAG) process. To capture possible interactions which are unaccounted for in an additive model, we propose an extension of the TAG process called transformed approximately additive Gaussian (TAAG) process. We develop efficient techniques for fitting a TAAG process. In fact, we show that it can be fitted to high-dimensional data much more efficiently than a standard GP. Furthermore, we show that the use of the TAAG process leads to better estimation, interpretation, visualization, and prediction. The proposed methods are implemented in the R package TAG. [ABSTRACT FROM AUTHOR]

The objective of this study was to use surface functionalization to evaluate the antiadhesion property and thermal injury effects on the liver when using a novel electrosurgical unit with nanostructured-doped diamond-like carbon (DLC-Cu) thin films for tumor ablations. The physical and chemical properties of DLC-Cu thin films were characterized by contact angle goniometer, scanning electron microscope, and transmission electron microscope. Three-dimensional (3D) hepatic models were reconstructed using magnetic resonance imaging to simulate a clinical electrosurgical operation. The results indicated a significant increase of the contact angle on the nanostructured DLC-Cu thin films, and the antiadhesion properties were also observed in an animal model. Furthermore, the surgical temperature in the DLC-Cu electrosurgical unit was found to be significantly lower than the untreated unit when analyzed using 3D models and thermal images. In addition, DLC-Cu electrodes caused a relatively small injury area and lateral thermal effect. The results indicated that the nanostructured DLC-Cu thin film coating reduced excessive thermal injury and tissue adherence effect in the liver. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 96-105, 2016. [ABSTRACT FROM AUTHOR]