Optimizing dosage-specific treatments in a multi-scale model of a tumor growth

The emergence of cell resistance in cancer treatment is a complex phenomenon that emerges from the interplay of processes that occur at different scales. For instance, molecular mechanisms and population-level dynamics such as competition and cell-cell variability have been described as playing a key role in the emergence and evolution of cell resistances. Multi-scale models are a useful tool to study biology at a very different time and spatial scales, as they can integrate different processes that take place at the molecular, cellular and intercellular levels. In the present work, we use an extended hybrid multi-scale model of 3T3 fibroblast spheroid to perform a deep exploration of the parameter space of effective treatment strategies based on TNF pulses. To explore the parameter space of effective treatments in different scenarios and conditions, we have developed an HPC-optimized model exploration workflow based on EMEWS. We first studied the effect of the cells spatial distribution in the values of the treatment parameters by optimizing the supply strategies in 2D monolayers and 3D spheroids of different sizes. We later study the robustness of the effective treatments when heterogeneous populations of cells are considered. We found that our model exploration workflow can find effective treatments in all the studied conditions. Our results show that cells' spatial geometry, as well as, population variability should be considered when optimizing treatment strategies in order to find robust parameter sets.

The Method for Optimum Design of Resin Injection Molding Process Conditions using Multivariate Analysis with Robust Parameter Design

In recent years, the demand for plastic products has increased, and along with the deepening of academics, mass production, weight reduction, and high precision are progressing. In the fields of design development and production technology, there are many issues related to quality assurance such as molding defects and product strength. In particular, in the resin molding process, there is a high degree of freedom in product shape and mold structure, and it is an important issue to create quality functions that apply analysis of complex multidimensional information. In this study, the important factors of the resin molding process related to the optimization of resin strength are extracted by applying the multivariate analysis method and robust parameter design. As a result of verification of the proposed method, it is clarified that uniformization of the resin filling density in the mold is extremely important for stabilizing the resin strength.

Robust Parameter Design of Shielded Metal Arc Welding (SMAW) for Optimum Tensile Strength

Shielded Metal Arc Welding (SMAW), an arc welding process, is widely used in applications. In practice, SMAW is widely applied to the welding process on hollow square pipe. Performance expected from this welding is the tensile strength of weld joint. The tensile strength is influenced by parameters process which have possibility for an optimization process to become ‘robust’. Robust is a design which less sensitive to the effect of uncertain quantities or noise factors. Taguchi method is the most efficient optimization method which accommodates the noise factors effect and requires less experiment. This study is focusing on optimizing the welding process on hollow square pipe. Parameters process such as welding current (I), electrode angle (θ), root gap (d) and electrode type (E) are adopted as parameters design. Taguchi method are chosen as a strategy and L9 fractional orthogonal array are chosen as the design experiment, which only 9 experiment samples needed from 81 experiments that should have been carried out for full factorial design. The objectivity is to maximize the tensile strength of weld joint. Three replications of L9 fractional orthogonal array Taguchi had been performed to generate the tensile strength and estimates the fluctuation of the output caused by noise factors. This study found that the welding current of 100A (I), electrode angle (θ) of 90°, root gap (d) of 2 mm, and electrode type (E) of E7018 produce the optimum results. Tensile strength improved from this robust parameter design is about 98.39 MPa based on initial parameter design.

Robust Parameter Estimation of an Empirical Manoeuvring Model Using Free-Running Model Tests

The work presents the identification and validation of the hydrodynamic coefficients for the surge, sway, and yaw motion. This is performed in two ways: using simulated data and free-running test data. The identification and validation with the simulation data are carried out using a 25° turning test and a 20°−20° zigzag manoeuvring test. For the free-running test data, two zigzag manoeuvres are used: 30°−30° zigzag for identification and 20°−20° zigzag for validation. A nonlinear manoeuvring model is proposed based on the standard Euler equations, and the hydrodynamic coefficients are computed using empirical equations. To obtain robust results, the truncated singular value decomposition is employed to diminish the multicollinearity and the parameter uncertainties due to noise. The validation is carried out by comparing the result of the measured values with the predictions obtained using the manoeuvring models. Finally, a sensitivity analysis for the simulation data is performed to understand the influence of the parameters in the manoeuvres.

Importance of frame rate for the measurement of strain and synchrony in fetuses using speckle tracking echocardiography

Objectives To assess the influence of frame rate settings on longitudinal strain (LS) and mechanical synchrony (SYN) values in Speckle Tracking Echocardiography (STE) of healthy fetuses. Methods In this prospective study, we collected transversal or apical four-chamber-views of 121 healthy fetuses between 20 and 38 weeks of gestation using three different frame rate (FR) settings (≥ 110, 100 ± 10, 60 ± 10 frames per second). We assessed the segmental and the global LS of both ventricles (2C) and of the left ventricle (LV) offline with QLab 10.8 (Philips Medical Systems, Andover, MA, USA). Inter- and intraventricular SYN were calculated as time difference in peak myocardial strain between the mid-segments of left and right ventricle (interventricular, 2C_Syn) and lateral wall and septum of the left ventricle (intraventricular, LV_Syn), respectively. Results In 84.3% STE was feasible at all three FR settings. The LS increased in both views at higher FRs to a statistically noticeable extent. SYN measurements and the absolute differences at patient level between the FR settings showed no statistically noticeable alterations. Conclusions STE is feasible at low and high FR settings. SYN emerges to be a robust parameter for fetal STE as it is less affected by the FR. High FRs enable high temporal resolutions and thus an accurate examination of fetal hearts. Future research for the technical implementation of tailored fetal STE software is necessary for reliable clinical application.

Robust Static Structural System Identification Using Rotations

Deflections are commonly measured in the static structural system identification of structures. Comparatively less attention has been paid to the possibility of measuring rotations for structural system identification purposes, despite the many advantages of using inclinometers, such as a high resolution and being reference free. Although some work using rotations can be found in the literature, this paper, for the very first time, proposes a statistical analysis that justifies the theoretical advantage of measuring rotations. The analytical expressions for the target parameters are obtained via static structural system identification using the constrained observability method first. Combined with the inverse distribution theory, the probability density function of the estimations of the target parameters can be obtained. Comparative studies on a simply supported bridge and a frame structure demonstrate the advantage of measuring rotations regarding the unbiasedness and the extent of variation in the estimations. To achieve robust parameter estimations, four strategies to use redundant rotations are proposed and compared. Numerical verifications on a bridge structure and a high-rise building have shown promising results.

Application of robust parameter design in the development of a quantitative chemical analysis procedures in metallurgy

The paper presents the results of experimental research for the quantitative chemical analysis procedures using the robust parameter design methodology. There is an example of the parameter design in development of the measurement procedure for the mass fraction of chlorine in dusty waste in the ferronickel production. Results of experiment analysis has provided an information about the optimal conditions for sample preparation procedure.