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In cardiac cells, structural organization is an important indicator of cell maturity and healthy function. Healthy cardiomyocytes exhibit well-aligned morphology with densely packed and organized sarcomeres. Immature or diseased cardiomyocytes typically lack this organized structure. Critically, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a valuable model for studying human cardiac cells in a controlled environment. However, these cells often exhibit a disorganized structure. In this work, we extend the SarcGraph computational framework -- designed to assess the structural and functional behavior of hiPSC-CMs -- to better accommodate the structural features of immature cells. There are two key enhancements: (1) incorporating a deep learning-based z-disc classifier, and (2) introducing a novel ensemble graph-scoring approach. These modification significantly reduced false positive sarcomere detections in immature cells, and resulted in the detection of longer myofibrils in mature samples. With this enhanced framework, we analyze an open-source dataset published by the Allen Institute for Cell Science, where, for the first time, we are able to extract key structural features from these data using information from each individually detected sarcomere. Not only are we able to use these structural features to predict expert scores, but we are also able to use these structural features to identify bias in expert scoring and offer an alternative unsupervised learning approach based on explainable clustering. These results demonstrate the efficacy of our modified SarcGraph in extracting biologically meaningful features, enabling a deeper understanding of hiPSC-CM structural integrity. By making our code and tools open-source, we aim to empower the broader cardiac research community and foster further development of computational tools for cardiac tissue analysis.

Random fiber networks form the structural foundation of numerous biological tissues and engineered materials, from living tissue in the human body to everyday materials like fabric and paper. From a mechanics perspective, understanding the structure-function relationships of random fiber networks is particularly interesting because when external force is applied to these networks, only a small subset of fibers will actually carry the majority of the load. Specifically, these load-bearing fibers propagate through the network to form load paths, also called force chains. However, the relationship between fiber network geometric structure, force chains, and the overall mechanical behavior of random fiber network structures remains poorly understood. To this end, we implement a finite element model of random fiber networks with geometrically exact beam elements, and use this model to explore random fiber network mechanical behavior. Our focus is twofold. First, we explore the mechanical behavior of single fiber chains and random fiber networks. Second, we propose and validate an interpretable analytical approach to predicting fiber network mechanics from structural information alone. Key findings include insight into the critical strain-stiffening transition point for single fiber chains and fiber networks, and a connection between force chains and the distance-weighted graph shortest paths that arise by treating fiber networks as spatial graph structures. This work marks an important step towards mapping the structure-function relationships of random fiber networks undergoing large deformations. Additionally, with our code distributed under open-source licenses, we hope that future researchers can directly build on our work to address related problems beyond the scope defined here., Comment: 37 pages, 19 figures

Estimating out-of-sample risk for models trained on large high-dimensional datasets is an expensive but essential part of the machine learning process, enabling practitioners to optimally tune hyperparameters. Cross-validation (CV) serves as the de facto standard for risk estimation but poorly trades off high bias ($K$-fold CV) for computational cost (leave-one-out CV). We propose a randomized approximate leave-one-out (RandALO) risk estimator that is not only a consistent estimator of risk in high dimensions but also less computationally expensive than $K$-fold CV. We support our claims with extensive simulations on synthetic and real data and provide a user-friendly Python package implementing RandALO available on PyPI as randalo and at https://github.com/cvxgrp/randalo., Comment: 25 pages, 9 figures

The most important characteristic of a Quantum Key Distribution (QKD) protocol is its security against third-party attacks, and the potential countermeasures available. While new types of attacks are regularly developed in the literature, they rarely involve the use of weak continuous measurement. Here, we design a new attack scheme called $\textit{Deep-learning-based continuous attack}$ (DLCA) that exploits continuous measurement together with the powerful pattern recognition capacities of deep recurrent neural networks. We show that, when applied to the BB84 protocol, our attack can be difficult to notice while still allowing the spy to extract significant information about the states of the qubits sent in the quantum communication channel. Finally, we study how the spy can exploit quantum feedback to further cover their tracks. Our attack scheme, while still at the early stages of a toy model, constitutes a potential threat which is worthwhile to be investigated, also as it could be applied to different QKD protocols and generalized in many different ways., Comment: 13 pages, 10 figures

The recent pandemic emphasized the need to consider the role of human behavior in shaping epidemic dynamics. In particular, it is necessary to extend beyond the classical epidemiological structures to fully capture the interplay between the spread of disease and how people respond. Here, we focus on the challenge of incorporating change in human behavior in the form of "risk response" into compartmental epidemiological models, where humans adapt their actions in response to their perceived risk of becoming infected. The review examines 37 papers containing over 40 compartmental models, categorizing them into two fundamentally distinct classes: exogenous and endogenous approaches to modeling risk response. While in exogenous approaches, human behavior is often included using different fixed parameter values for certain time periods, endogenous approaches seek for a mechanism internal to the model to explain changes in human behavior as a function of the state of disease. We further discuss two different formulations within endogenous models as implicit versus explicit representation of information diffusion. This analysis provides insights for modelers in selecting an appropriate framework for epidemic modeling., Comment: 28 pages, 7 figures

The energy landscape of multiply connected superconducting structures is ruled by fluxoid quantization due to the implied single-valuedness of the complex wave function. The transitions and interaction between these energy states, each defined by a specific phase winding number, are governed by classical and/or quantum phase slips. Understanding these events requires the ability to probe, non-invasively, the state of the ring. Here, we employ a niobium resonator to examine the superconducting properties of an aluminum loop. By applying a magnetic field, adjusting temperature, and altering the loop's dimensions via focused ion beam milling, we correlate resonance frequency shifts with changes in the loop's kinetic inductance. This parameter is a unique indicator of the superconducting condensate's state, facilitating the detection of phase slips in nanodevices and providing insights into their dynamics. Our method presents a proof-of-principle spectroscopic technique with promising potential for investigating the Cooper pair density in inductively coupled superconducting nanostructures.

Movies of human induced pluripotent stem cell (hiPSC)-derived engineered cardiac tissue (microbundles) contain abundant information about structural and functional maturity. However, extracting these data in a reproducible and high-throughput manner remains a major challenge. Furthermore, it is not straightforward to make direct quantitative comparisons across the multiple in vitro experimental platforms employed to fabricate these tissues. Here, we present "MicroBundlePillarTrack," an open-source optical flow-based package developed in Python to track the deflection of pillars in cardiac microbundles grown on experimental platforms with two different pillar designs ("Type 1" and "Type 2" design). Our software is able to automatically segment the pillars, track their displacements, and output time-dependent metrics for contractility analysis, including beating amplitude and rate, contractile force, and tissue stress. Because this software is fully automated, it will allow for both faster and more reproducible analyses of larger datasets and it will enable more reliable cross-platform comparisons as compared to existing approaches that require manual steps and are tailored to a specific experimental platform. To complement this open-source software, we share a dataset of 1,540 brightfield example movies on which we have tested our software. Through sharing this data and software, our goal is to directly enable quantitative comparisons across labs, and facilitate future collective progress via the biomedical engineering open-source data and software ecosystem., Comment: 8 main pages, 1 main figure, Supplementary Information included. microPublication Biology (2024)

While effective in practice, iterative methods for solving large systems of linear equations can be significantly affected by problem-dependent condition number quantities. This makes characterizing their time complexity challenging, particularly when we wish to make comparisons between deterministic and stochastic methods, that may or may not rely on preconditioning and/or fast matrix multiplication. In this work, we consider a fine-grained notion of complexity for iterative linear solvers which we call the spectral tail condition number, $\kappa_\ell$, defined as the ratio between the $\ell$th largest and the smallest singular value of the matrix representing the system. Concretely, we prove the following main algorithmic result: Given an $n\times n$ matrix $A$ and a vector $b$, we can find $\tilde{x}$ such that $\|A\tilde{x}-b\|\leq\epsilon\|b\|$ in time $\tilde{O}(\kappa_\ell\cdot n^2\log 1/\epsilon)$ for any $\ell = O(n^{\frac1{\omega-1}})=O(n^{0.729})$, where $\omega \approx 2.372$ is the current fast matrix multiplication exponent. This guarantee is achieved by Sketch-and-Project with Nesterov's acceleration. Some of the implications of our result, and of the use of $\kappa_\ell$, include direct improvement over a fine-grained analysis of the Conjugate Gradient method, suggesting a stronger separation between deterministic and stochastic iterative solvers; and relating the complexity of iterative solvers to the ongoing algorithmic advances in fast matrix multiplication, since the bound on $\ell$ improves with $\omega$. Our main technical contributions are new sharp characterizations for the first and second moments of the random projection matrix that commonly arises in sketching algorithms, building on a combination of techniques from combinatorial sampling via determinantal point processes and Gaussian universality results from random matrix theory., Comment: 32 pages

Transformation optics applied to low frequency magnetic systems has been recently implemented to design magnetic field concentrators and cloaks with superior performance. Although this achievement has been amply demonstrated theoretically and experimentally in bulk 3D macrostructures, the performance of these devices at low dimensions remains an open question. In this work, we numerically investigate the non-monotonic evolution of the gain of a magnetic metamaterial field concentrator as the axial dimension is progressively shrunk. In particular, we show that in planar structures the role played by the diamagnetic components becomes negligible, whereas the paramagnetic elements increase their magnetic field channeling efficiency. This is further demonstrated experimentally by tracking the gain of superconductor-ferromagnet concentrators through the superconducting transition. Interestingly, for thicknesses where the diamagnetic petals play an important role for the concentration gain, they also help to reduce the stray field of the concentrator, thus limiting the perturbation of the external field (invisibility). Our findings establish a roadmap and set clear geometrical limits for designing low dimensional magnetic field concentrators.

There has been significant recent interest in the mechanics community to design structures that can either violate reciprocity, or exhibit elastic asymmetry or odd elasticity. While these properties are highly desirable to enable mechanical metamaterials to exhibit novel wave propagation phenomena, it remains an open question as to how to design passive structures that exhibit both significant non-reciprocity and elastic asymmetry. In this paper, we first define several design spaces for chiral metamaterials leveraging specific design parameters, including the ligament contact angles, the ligament shape, and circle radius. Having defined the design spaces, we then leverage machine learning approaches, and specifically Bayesian optimization, to determine optimally performing designs within each design space satisfying maximal non-reciprocity or stiffness asymmetry. Finally, we perform multi-objective optimization by determining the Pareto optimum and find chiral metamaterials that simultaneously exhibit high non-reciprocity and stiffness asymmetry. Our analysis of the underlying mechanisms reveals that chiral metamaterials that can display multiple different contact states under loading in different directions are able to simultaneously exhibit both high non-reciprocity and stiffness asymmetry. Overall, this work demonstrates the effectiveness of employing ML to bring insights to a novel domain with limited prior information, and more generally will pave the way for metamaterials with unique properties and functionality in directing and guiding mechanical wave energy.

The Finite Element Method (FEM) is a well-established procedure for computing approximate solutions to deterministic engineering problems described by partial differential equations. FEM produces discrete approximations of the solution with a discretisation error that can be an be quantified with \emph{a posteriori} error estimates. The practical relevance of error estimates for biomechanics problems, especially for soft tissue where the response is governed by large strains, is rarely addressed. In this contribution, we propose an implementation of \emph{a posteriori} error estimates targeting a user-defined quantity of interest, using the Dual Weighted Residual (DWR) technique tailored to biomechanics. The proposed method considers a general setting that encompasses three-dimensional geometries and model non-linearities, which appear in hyperelastic soft tissues. We take advantage of the automatic differentiation capabilities embedded in modern finite element software, which allows the error estimates to be computed generically for a large class of models and constitutive laws. First we validate our methodology using experimental measurements from silicone samples, and then illustrate its applicability for patient-specific computations of pressure ulcers on a human heel.

For parameterized mixed-binary optimization problems, we construct local decision rules that prescribe near-optimal courses of action across a set of parameter values. The decision rules stem from solving risk-adaptive training problems over classes of continuous, possibly nonlinear mappings. In asymptotic and nonasymptotic analysis, we establish that the decision rules prescribe near-optimal decisions locally for the actual problems, without relying on linearity, convexity, or smoothness. The development also accounts for practically important aspects such as inexact function evaluations, solution tolerances in training problems, regularization, and reformulations to solver-friendly models. The decision rules also furnish a means to carry out sensitivity and stability analysis for broad classes of parameterized optimization problems. We develop a decomposition algorithm for solving the resulting training problems and demonstrate its ability to generate quality decision rules on a nonlinear binary optimization model from search theory.

We employ random matrix theory to establish consistency of generalized cross validation (GCV) for estimating prediction risks of sketched ridge regression ensembles, enabling efficient and consistent tuning of regularization and sketching parameters. Our results hold for a broad class of asymptotically free sketches under very mild data assumptions. For squared prediction risk, we provide a decomposition into an unsketched equivalent implicit ridge bias and a sketching-based variance, and prove that the risk can be globally optimized by only tuning sketch size in infinite ensembles. For general subquadratic prediction risk functionals, we extend GCV to construct consistent risk estimators, and thereby obtain distributional convergence of the GCV-corrected predictions in Wasserstein-2 metric. This in particular allows construction of prediction intervals with asymptotically correct coverage conditional on the training data. We also propose an "ensemble trick" whereby the risk for unsketched ridge regression can be efficiently estimated via GCV using small sketched ridge ensembles. We empirically validate our theoretical results using both synthetic and real large-scale datasets with practical sketches including CountSketch and subsampled randomized discrete cosine transforms., Comment: 45 pages, 7 figures; this version fixes some typos and updates some references

In multi-agent search planning for a randomly moving and camouflaging target, we examine heterogeneous searchers that differ in terms of their endurance level, travel speed, and detection ability. This leads to a convex mixed-integer nonlinear program, which we reformulate using three linearization techniques. We develop preprocessing steps, outer approximations via lazy constraints, and bundle-based cutting plane methods to address large-scale instances. Further specializations emerge when the target moves according to a Markov chain. We carry out an extensive numerical study to show the computational efficiency of our methods and to derive insights regarding which approach should be favored for which type of problem instance.

From biological organs to soft robotics, highly deformable materials are essential components of natural and engineered systems. These highly deformable materials can have heterogeneous material properties, and can experience heterogeneous deformations with or without underlying material heterogeneity. Many recent works have established that computational modeling approaches are well suited for understanding and predicting the consequences of material heterogeneity and for interpreting observed heterogeneous strain fields. In particular, there has been significant work towards developing inverse analysis approaches that can convert observed kinematic quantities (e.g., displacement, strain) to material properties and mechanical state. Despite the success of these approaches, they are not necessarily generalizable and often rely on tight control and knowledge of boundary conditions. Here, we will build on the recent advances (and ubiquity) of machine learning approaches to explore alternative approaches to detect patterns in heterogeneous material properties and mechanical behavior. Specifically, we will explore unsupervised learning approaches to clustering and ensemble clutering to identify heterogeneous regions. Overall, we find that these approaches are effective, yet limited in their abilities. Through this initial exploration (where all data and code is published alongside this manuscript), we set the stage for future studies that more specifically adapt these methods to mechanical data., Comment: 26 pages, 10 figures

In order to better understand feature learning in neural networks, we propose a framework for understanding linear models in tangent feature space where the features are allowed to be transformed during training. We consider linear transformations of features, resulting in a joint optimization over parameters and transformations with a bilinear interpolation constraint. We show that this optimization problem has an equivalent linearly constrained optimization with structured regularization that encourages approximately low rank solutions. Specializing to neural network structure, we gain insights into how the features and thus the kernel function change, providing additional nuance to the phenomenon of kernel alignment when the target function is poorly represented using tangent features. We verify our theoretical observations in the kernel alignment of real neural networks., Comment: 14 pages, 3 figures. Appeared at the First Conference on Parsimony and Learning (CPAL 2024)

Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present "MicroBundleCompute," a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, requires little to no parameter tuning, and runs quickly on a personal computer. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate "MicroBundleCompute" as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community., Comment: 16 main pages, 7 main figures, Supplementary Information included as appendices

Seismic advances in generative AI algorithms for imagery, text, and other data types has led to the temptation to use synthetic data to train next-generation models. Repeating this process creates an autophagous (self-consuming) loop whose properties are poorly understood. We conduct a thorough analytical and empirical analysis using state-of-the-art generative image models of three families of autophagous loops that differ in how fixed or fresh real training data is available through the generations of training and in whether the samples from previous generation models have been biased to trade off data quality versus diversity. Our primary conclusion across all scenarios is that without enough fresh real data in each generation of an autophagous loop, future generative models are doomed to have their quality (precision) or diversity (recall) progressively decrease. We term this condition Model Autophagy Disorder (MAD), making analogy to mad cow disease., Comment: 31 pages, 31 figures, pre-print