A mechanistic protrusive-based model for 3D cell migration.

Cell migration is essential for a variety of biological processes, such as embryogenesis, wound healing, and the immune response. After more than a century of research-mainly on flat surfaces-, there are still many unknowns about cell motility. In particular, regarding how cells migrate within 3D matrices, which more accurately replicate in vivo conditions. We present a novel in silico model of 3D mesenchymal cell migration regulated by the chemical and mechanical profile of the surrounding environment. This in silico model considers cell's adhesive and nuclear phenotypes, the effects of the steric hindrance of the matrix, and cells ability to degradate the ECM. These factors are crucial when investigating the increasing difficulty that migrating cells find to squeeze their nuclei through dense matrices, which may act as physical barriers. Our results agree with previous in vitro observations where fibroblasts cultured in collagen-based hydrogels did not durotax toward regions with higher collagen concentrations. Instead, they exhibited an adurotactic behavior, following a more random trajectory. Overall, cell's migratory response in 3D domains depends on its phenotype, and the properties of the surrounding environment, that is, 3D cell motion is strongly dependent on the context.

Influence of field of view in visual prostheses design: Analysis with a VR system.

OBJECTIVE: Visual prostheses are designed to restore partial functional vision in patients with total vision loss. Retinal visual prostheses provide limited capabilities as a result of low resolution, limited field of view and poor dynamic range. Understanding the influence of these parameters in the perception results can guide prostheses research and design. APPROACH: In this work, we evaluate the influence of field of view with respect to spatial resolution in visual prostheses, measuring the accuracy and response time in a search and recognition task. Twenty-four normally sighted participants were asked to find and recognize usual objects, such as furniture and home appliance in indoor room scenes. For the experiment, we use a new simulated prosthetic vision system that allows simple and effective experimentation. Our system uses a virtual-reality environment based on panoramic scenes. The simulator employs a head-mounted display which allows users to feel immersed in the scene by perceiving the entire scene all around. Our experiments use public image datasets and a commercial head-mounted display. We have also released the virtual-reality software for replicating and extending the experimentation. MAIN RESULTS: Results show that the accuracy and response time decrease when the field of view is increased. Furthermore, performance appears to be correlated with the angular resolution, but showing a diminishing return even with a resolution of less than 2.3 phosphenes per degree. SIGNIFICANCE: Our results seem to indicate that, for the design of retinal prostheses, it is better to concentrate the phosphenes in a small area, to maximize the angular resolution, even if that implies sacrificing field of view.

Semantic and structural image segmentation for prosthetic vision.

Prosthetic vision is being applied to partially recover the retinal stimulation of visually impaired people. However, the phosphenic images produced by the implants have very limited information bandwidth due to the poor resolution and lack of color or contrast. The ability of object recognition and scene understanding in real environments is severely restricted for prosthetic users. Computer vision can play a key role to overcome the limitations and to optimize the visual information in the prosthetic vision, improving the amount of information that is presented. We present a new approach to build a schematic representation of indoor environments for simulated phosphene images. The proposed method combines a variety of convolutional neural networks for extracting and conveying relevant information about the scene such as structural informative edges of the environment and silhouettes of segmented objects. Experiments were conducted with normal sighted subjects with a Simulated Prosthetic Vision system. The results show good accuracy for object recognition and room identification tasks for indoor scenes using the proposed approach, compared to other image processing methods.

Funneled Bayesian Optimization for Design, Tuning and Control of Autonomous Systems.

In this paper, we tackle several problems that appear in robotics and autonomous systems: algorithm tuning, automatic control, and intelligent design. All those problems share in common that they can be mapped to global optimization problems where evaluations are expensive. Bayesian optimization (BO) has become a fundamental global optimization algorithm in many problems where sample efficiency is of paramount importance. BO uses a probabilistic surrogate model to learn the response function and reduce the number of samples required. Gaussian processes (GPs) have become a standard surrogate model for their flexibility to represent a distribution over functions. In a black-box settings, the common assumption is that the underlying function can be modeled with a stationary GP. In this paper, we present a novel kernel function specially designed for BO, that allows nonstationary behavior of the surrogate model in an adaptive local region. This kernel is able to reconstruct nonstationarity even with the irregular sampling distribution that arises from BO. Furthermore, in our experiments, we found that this new kernel results in an improved local search (exploitation), without penalizing the global search (exploration) in many applications. We provide extensive results in well-known optimization benchmarks, machine learning hyperparameter tuning, reinforcement learning, and control problems, and UAV wing optimization. The results show that the new method is able to outperform the state of the art in BO both in stationary and nonstationary problems.

Integration of in vitro and in silico Models Using Bayesian Optimization With an Application to Stochastic Modeling of Mesenchymal 3D Cell Migration.

Cellular migration plays a crucial role in many aspects of life and development. In this paper, we propose a computational model of 3D migration that is solved by means of the tau-leaping algorithm and whose parameters have been calibrated using Bayesian optimization. Our main focus is two-fold: to optimize the numerical performance of the mechano-chemical model as well as to automate the calibration process of in silico models using Bayesian optimization. The presented mechano-chemical model allows us to simulate the stochastic behavior of our chemically reacting system in combination with mechanical constraints due to the surrounding collagen-based matrix. This numerical model has been used to simulate fibroblast migration. Moreover, we have performed in vitro analysis of migrating fibroblasts embedded in 3D collagen-based fibrous matrices (2 mg/ml). These in vitro experiments have been performed with the main objective of calibrating our model. Nine model parameters have been calibrated testing 300 different parametrizations using a completely automatic approach. Two competing evaluation metrics based on the Bhattacharyya coefficient have been defined in order to fit the model parameters. These metrics evaluate how accurately the in silico model is replicating in vitro measurements regarding the two main variables quantified in the experimental data (number of protrusions and the length of the longest protrusion). The selection of an optimal parametrization is based on the balance between the defined evaluation metrics. Results show how the calibrated model is able to predict the main features observed in the in vitro experiments.