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  1. Abstract

    Cell shape is linked to cell function. The significance of cell morphodynamics, namely the temporal fluctuation of cell shape, is much less understood. Here we study the morphodynamics of MDA-MB-231 cells in type I collagen extracellular matrix (ECM). We systematically vary ECM physical properties by tuning collagen concentrations, alignment, and gelation temperatures. We find that morphodynamics of 3D migrating cells are externally controlled by ECM mechanics and internally modulated by Rho/ROCK-signaling. We employ machine learning to classify cell shape into four different morphological phenotypes, each corresponding to a distinct migration mode. As a result, we map cell morphodynamics at mesoscale into the temporal evolution of morphological phenotypes. We characterize the mesoscale dynamics including occurrence probability, dwell time and transition matrix at varying ECM conditions, which demonstrate the complex phenotype landscape and optimal pathways for phenotype transitions. In light of the mesoscale dynamics, we show that 3D cancer cell motility is a hidden Markov process whereby the step size distributions of cell migration are coupled with simultaneous cell morphodynamics. Morphological phenotype transitions also facilitate cancer cells to navigate non-uniform ECM such as traversing the interface between matrices of two distinct microstructures. In conclusion, we demonstrate that 3D migrating cancer cellsmore »exhibit rich morphodynamics that is controlled by ECM mechanics, Rho/ROCK-signaling, and regulate cell motility. Our results pave the way to the functional understanding and mechanical programming of cell morphodynamics as a route to predict and control 3D cell motility.

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  2. Ranzato, M. ; Beygelzimer, A. ; Dauphin, Y ; Liang, P. S. ; Vaughan, J. W. (Ed.)
    Attention maps are popular tools for explaining the decisions of convolutional neural networks (CNNs) for image classification. Typically, for each image of interest, a single attention map is produced, which assigns weights to pixels based on their importance to the classification. We argue that a single attention map provides an incomplete understanding since there are often many other maps that explain a classification equally well. In this paper, we propose to utilize a beam search algorithm to systematically search for multiple explanations for each image. Results show that there are indeed multiple relatively localized explanations for many images. However, naively showing multiple explanations to users can be overwhelming and does not reveal their common and distinct structures. We introduce structured attention graphs (SAGs), which compactly represent sets of attention maps for an image by visualizing how different combinations of image regions impact the confidence of a classifier. An approach to computing a compact and representative SAG for visualization is proposed via diverse sampling. We conduct a user study comparing the use of SAGs to traditional attention maps for answering comparative counterfactual questions about image classifications. Our results show that the users are significantly more accurate when presented with SAGs comparedmore »to standard attention map baselines.« less
  3. Instance segmentation, which seeks to obtain both class and instance labels for each pixel in the input image, is a challenging task in computer vision. State-ofthe-art algorithms often employ a search-based strategy, which first divides the output image with a regular grid and generate proposals at each grid cell, then the proposals are classified and boundaries refined. In this paper, we propose a novel algorithm that directly utilizes a fully convolutional network (FCN) to predict instance labels. Specifically, we propose a variational relaxation of instance segmentation as minimizing an optimization functional for a piecewise-constant segmentation problem, which can be used to train an FCN end-to-end. It extends the classical Mumford-Shah variational segmentation algorithm to be able to handle the permutation-invariant ground truth in instance segmentation. Experiments on PASCAL VOC 2012 and the MSCOCO 2017 dataset show that the proposed approach efficiently tackles the instance segmentation task. The source code and trained models are released at
  4. Deep networks are often not scale-invariant hence their performance can vary wildly if recognizable objects are at an unseen scale occurring only at testing time. In this paper, we propose ScaleNet, which recursively predicts object scale in a deep learning framework. With an explicit objective to predict the scale of objects in images, ScaleNet enables pretrained deep learning models to identify objects in the scales that are not present in their training sets. By recursively calling ScaleNet, one can generalize to very large scale changes unseen in the training set. To demonstrate the robustness of our proposed framework, we conduct experiments with pretrained as well as fine-tuned classification and detection frameworks on MNIST, CIFAR-10, and MS COCO datasets and results reveal that our proposed framework significantly boosts the performances of deep networks.
  5. Segmentation algorithms are prone to make topological errors on fine-scale structures, e.g., broken connections. We propose a novel method that learns to segment with correct topology. In particular, we design a continuous-valued loss function that enforces a segmentation to have the same topology as the ground truth, i.e., having the same Betti number. The proposed topology-preserving loss function is differentiable and we incorporate it into end-to-end training of a deep neural network. Our method achieves much better performance on the Betti number error, which directly accounts for the topological correctness. It also performs superiorly on other topology-relevant metrics, e.g., the Adjusted Rand Index and the Variation of Information. We illustrate the effectiveness of the proposed method on a broad spectrum of natural and biomedical datasets.