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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)

Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, and designing therapies. Here we use a method not commonly applied to biological materials, small angle X-ray scattering, to characterize the structural development of human-induced pluripotent stem-cell-derived cardiomyocytes within 3D engineered tissues during their preliminary stages of maturation. An X-ray scattering experimental method enables the reliable characterization of the cardiomyocyte myofilament spacing with maturation time. The myofilament lattice spacing monotonically decreases as the tissue matures from its initial post-seeding state over the span of ten days. Visualization of the spacing at a grid of positions in the tissue provides an approach to characterizing the maturation and organization of cardiomyocyte myofilaments and has the potential to help elucidate mechanisms of pathophysiology, and disease progression, thereby stimulating new biological hypotheses in stem cell engineering.

Multi-objective optimization is a ubiquitous problem that arises naturally in many scientific and industrial areas. Network routing optimization with multi-objective performance demands falls into this problem class, and finding good quality solutions at large scales is generally challenging. In this work, we develop a scheme with which near-term quantum computers can be applied to solve multi-objective combinatorial optimization problems. We study the application of this scheme to the network routing problem in detail, by first mapping it to the multi-objective shortest path problem. Focusing on an implementation based on the quantum approximate optimization algorithm (QAOA) -- the go-to approach for tackling optimization problems on near-term quantum computers -- we examine the Pareto plot that results from the scheme, and qualitatively analyze its ability to produce Pareto-optimal solutions. We further provide theoretical and numerical scaling analyses of the resource requirements and performance of QAOA, and identify key challenges associated with this approach. Finally, through Amazon Braket we execute small-scale implementations of our scheme on the IonQ Harmony 11-qubit quantum computer.

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

The dissipation of magnetized turbulence is fundamental to understanding energy transfer and heating in astrophysical systems. Collisionless interactions, such as resonant wave-particle process, are known to play a role in shaping turbulent astrophysical environments. Here, we present evidence for the mediation of turbulent dissipation in the solar wind by ion-cyclotron waves. Our results show that ion-cyclotron waves interact strongly with magnetized turbulence, indicating that they serve as a major pathway for the dissipation of large-scale electromagnetic fluctuations. We further show that the presence of cyclotron waves significantly weakens observed signatures of intermittency in sub-ion-kinetic turbulence, which are known to be another pathway for dissipation. These observations results suggest that in the absence of cyclotron resonant waves, non-Gaussian, coherent structures are able to form at sub-ion-kinetic scales, and are likely responsible for turbulent heating. We further find that the cross helicity, i.e. the level of Alfv\'enicity of the fluctuations, correlates strongly with the presence of ion-scale waves, demonstrating that dissipation of collisionless plasma turbulence is not a universal process, but that the pathways to heating and dissipation at small scales are controlled by the properties of the large-scale turbulent fluctuations. We argue that these observations support the existence of a helicity barrier, in which highly Alfv\'enic, imbalanced, turbulence is prevented from cascading to sub-ion scales thus resulting in significant ion-cyclotron resonant heating. Our results may serve as a significant step in constraining the nature of turbulent heating in a wide variety of astrophysical systems.

We study the nonlinear evolution of very oblique small-scale Alfv\'en waves with $k_\perp d_i\gtrsim 1$. At these scales, the waves become significantly compressive, unlike in MHD, due to the Hall term in the equations. We demonstrate that when frequencies are small compared to the ion gyrofrequency and amplitudes small compared to unity, no new nonlinear interaction appears due to the Hall term alone at the lowest non-trivial order, even when $k_\perp d_i \sim 1$. However, at the second non-trivial order, we discover that the Hall physics leads to a slow but resonant nonlinear interaction between co-propagating Alfv\'en waves, an inherently 3D effect. Including the effects of finite temperature, finite frequency, and electron inertia, the two-fluid Alfv\'en wave also becomes dispersive once one or more of $k_\perp \rho_s$, $k_\perp d_e$, or $k_\parallel d_i$ becomes significant: for oblique waves at low $\beta$ as studied here, this can be at a much smaller scale than $d_i$. We show that the timescale for one-dimensional steepening of two-fluid Alfven waves is only significant at these smaller dispersive scales, and also derive an expression for the amplitude of driven harmonics of a primary wave. Importantly, both new effects are absent in gyrokinetics and other commonly used reduced two-fluid models. Our calculations have relevance for the interpretation of laboratory Alfv\'en wave experiments, as well as shedding light on the physics of turbulence in the solar corona and inner solar wind, where the dominant nonlinear interaction between counter-propagating waves is suppressed, allowing these new effects to become important., Comment: 17 pages; submitted to Physics of Plasmas

At kinetic scales in the solar wind, instabilities transfer energy from particles to fluctuations in the electromagnetic fields while restoring plasma conditions towards thermodynamic equilibrium. We investigate the interplay between background turbulent fluctuations at the small-scale end of the inertial range and kinetic instabilities acting to reduce proton temperature anisotropy. We analyse in-situ solar wind observations from the Solar Orbiter mission to develop a measure for variability in the magnetic field direction. We find that non-equilibrium conditions sufficient to cause micro-instabilities in the plasma coincide with elevated levels of variability. We show that our measure for the fluctuations in the magnetic field is non-ergodic in regions unstable to the growth of temperature anisotropy-driven instabilities. We conclude that the competition between the action of the turbulence and the instabilities plays a significant role in the regulation of the proton-scale energetics of the solar wind. This competition depends not only on the variability of the magnetic field but also on the spatial persistence of the plasma in non-equilibrium conditions., Comment: To be published in Astronomy & Astrophysics

Carrier and phonon dynamics in a multilayer WSe2 film are captured by extreme ultraviolet (XUV) transient absorption (TA) spectroscopy at the W N6,7, W O2,3, and Se M4,5 edges (30-60 eV). After the broadband optical pump pulse, the XUV probe directly reports on occupations of optically excited holes and phonon-induced band renormalizations. By comparing with density functional theory calculations, XUV transient absorption due to holes are identified below the W O3 edge whereas signals at the Se M4,5 edges are dominated by phonon dynamics. Therein, 0.4 ps hole relaxation time, 1.5 ps carrier recombination time, and 1.7 ps phonon heating time are extracted. The acquisition of hole and phonon-induced signals in a single experiment can facilitate the investigation of the correlations between electron and phonon dynamics. Furthermore, the simultaneous observation of signals from different elements can be further extended to explore photochemical processes in multilayers and alloys, thereby providing key information for their applications in electronics, photocatalysts, and spintronics., Comment: 26 pages, 7 figures

Using high-resolution data from Solar Orbiter, we investigate the plasma conditions necessary for the proton temperature anisotropy driven mirror-mode and oblique firehose instabilities to occur in the solar wind. We find that the unstable plasma exhibits dependencies on the angle between the direction of the magnetic field and the bulk solar wind velocity which cannot be explained by the double-adiabatic expansion of the solar wind alone. The angle dependencies suggest that perpendicular heating in Alfv\'enic wind may be responsible. We quantify the occurrence rate of the two instabilities as a function of the length of unstable intervals as they are convected over the spacecraft. This analysis indicates that mirror-mode and oblique firehose instabilities require a spatial interval of length greater than 2 to 3 unstable wavelengths in order to relax the plasma into a marginally stable state and thus closer to thermodynamic equilibrium in the solar wind. Our analysis suggests that the conditions for these instabilities to act effectively vary locally on scales much shorter than the correlation length of solar wind turbulence., Comment: 16 pages, 8 figures. Accepted for publication in ApJ

Sub-terahertz (sub-THz) antenna array architectures significantly impact power usage and communications capacity in multi-user multiple-input multiple-output (MU-MIMO) systems. In this work, we compare the energy efficiency and spectral efficiency of three MU-MIMO capable array architectures for base station receivers. We provide a sub-THz circuits power analysis, based on our review of state-of-the-art D-band and G-band components, and compare communications capabilities through wideband simulations. Our analysis reveals that digital arrays can provide the highest spectral efficiency and energy efficiency, due to the high power consumption of sub-THz active phase shifters or when SNR and system spectral efficiency requirements are high., Comment: Accepted to the 55th IEEE International Symposium on Circuits and Systems (ISCAS 2022), 4 pages + references (without copyright notice), 6 figures

We have designed and fabricated a microfluidic-based platform for sensing mechanical forces generated by cardiac microtissues in a highly-controlled microenvironment. Our fabrication approach combines Direct Laser Writing (DLW) lithography with soft lithography. At the center of our platform is a cylindrical volume, divided into two chambers by a cylindrical polydimethylsiloxane (PDMS) shell. Cells are seeded into the inner chamber from a top opening, and the microtissue assembles onto tailor-made attachment sites on the inner walls of the cylindrical shell. The outer chamber is electrically and fluidically isolated from the inner one by the cylindrical shell and is designed for actuation and sensing purposes. Externally applied pressure waves to the outer chamber deform parts of the cylindrical shell and thus allow us to exert time-dependent forces on the microtissue. Oscillatory forces generated by the microtissue similarly deform the cylindrical shell and change the volume of the outer chamber, resulting in measurable electrical conductance changes. We have used this platform to study the response of cardiac microtissues derived from human induced pluripotent stem cells (hiPSC) under prescribed mechanical loading and pacing., Comment: Main article 15 pages, 6 figures, 1 tables; supplementary 11 pages, 7 figures, 1 table, 6 movies

We investigate the validity of Taylor's Hypothesis (TH) in the analysis of Alfv\'enic fluctuations of velocity and magnetic fields in solar wind streams measured by Parker Solar Probe (PSP)~during the first four encounters. We use PSP velocity and magnetic field measurements from 24 h intervals selected from each of the first four encounters. The applicability of TH is investigated by measuring the parameter $\epsilon=\delta u_0/\sqrt{2}V_\perp$, which quantifies the ratio between the typical speed of large-scale fluctuations, $\delta u_0$, and the local perpendicular PSP speed in the solar wind frame, $V_\perp$. TH is expected to be applicable for $\epsilon\lesssim0.5$ when PSP is moving nearly perpendicular to the local magnetic field in the plasma frame, irrespective of the Alfv\'en Mach number $M_{\rm A}=V_{\rm SW}/V_{\rm A}$, where $V_{\rm SW}$ and $V_{\rm A}$ are the local solar wind and Alfv\'en speed, respectively. For the four selected solar wind intervals we find that between 10% to 60% of the time the parameter $\epsilon$ is below 0.2 when the sampling angle (between the spacecraft velocity in the plasma frame and the local magnetic field) is greater than $30^\circ$. For angles above $30^\circ$, the sampling direction is sufficiently oblique to allow one to reconstruct the reduced energy spectrum $E(k_\perp)$ of magnetic fluctuations from its measured frequency spectra. The spectral indices determined from power-law fits of the measured frequency spectrum accurately represent the spectral indices associated with the underlying spatial spectrum of turbulent fluctuations in the plasma frame. Aside from a frequency broadening due to large-scale sweeping that requires careful consideration, the spatial spectrum can be recovered to obtain the distribution of fluctuation's energy among scales in the plasma frame., Comment: 8 pages, 4 figures, submitted to Astronomy and Astrophysics

Few-femtosecond extreme ultraviolet (XUV) transient absorption spectroscopy, performed with optical 500-1000 nm supercontinuum and broadband XUV pulses (30-50 eV), simultaneously probes dynamics of photoexcited carriers in WS$_{2}$ at the W O$_3$ edge (37-45 eV) and carrier-induced modifications of core-exciton absorption at the W N$_{6,7}$ edge (32-37 eV). Access to continuous core-to-conduction band absorption features and discrete core-exciton transitions in the same XUV spectral region in a semiconductor provides a novel means to investigate the effect of carrier excitation on core-exciton dynamics. The core-level transient absorption spectra, measured with either pulse arriving first to explore both core-level and valence carrier dynamics, reveal that core-exciton transitions are strongly influenced by the photoexcited carriers. A $1.2\pm0.3$ ps hole-phonon relaxation time and a $3.1\pm0.4$ ps carrier recombination time are extracted from the XUV transient absorption spectra from the core-to-conduction band transitions at the W O$_{3}$ edge. Global fitting of the transient absorption signal at the W N$_{6,7}$ edge yields $\sim 10$ fs coherence lifetimes of core-exciton states and reveals that the photoexcited carriers, which alter the electronic screening and band filling, are the dominant contributor to the spectral modifications of core-excitons and direct field-induced changes play a minor role. This work provides a first look at the modulations of core-exciton states by photoexcited carriers and advances our understanding of carrier dynamics in metal dichalcogenides., Comment: 18 pages, 13 figures

Parker Solar Probe (PSP) routinely observes magnetic field deflections in the solar wind at distances less than 0.3 au from the Sun. These deflections are related to structures commonly called 'switchbacks' (SBs), whose origins and characteristic properties are currently debated. Here, we use a database of visually selected SB intervals - and regions of solar wind plasma measured just before and after each SB - to examine plasma parameters, turbulent spectra from inertial to dissipation scales, and intermittency effects in these intervals. We find that many features, such as perpendicular stochastic heating rates and turbulence spectral slopes are fairly similar inside and outside of SBs. However, important kinetic properties, such as the characteristic break scale between the inertial to dissipation ranges differ inside and outside these intervals, as does the level of intermittency, which is notably enhanced inside SBs and in their close proximity, most likely due to magnetic field and velocity shears observed at the edges. We conclude that the plasma inside and outside of a SB, in most of the observed cases, belongs to the same stream, and that the evolution of these structures is most likely regulated by kinetic processes, which dominate small scale structures at the SB edges.

The anisotropy of solar wind turbulence is a critical issue in understanding the physics of energy transfer between scales and energy conversion between fields and particles in the heliosphere. Using the measurement of \emph{Parker Solar Probe} (\emph{PSP}), we present an observation of the anisotropy at kinetic scales in the slow, Alfv\'enic, solar wind in the inner heliosphere. \textbf{The magnetic compressibility behaves as expected for kinetic Alfv\'enic turbulence below the ion scale.} A steepened transition range is found between the inertial and kinetic ranges in all directions with respect to the local background magnetic field direction. The anisotropy of $k_\perp \gg k_\parallel$ is found evident in both transition and kinetic ranges, with the power anisotropy $P_\perp/P_\parallel > 10$ in the kinetic range leading over that in the transition range and being stronger than that at 1 au. The spectral index varies from $\alpha_{t\parallel}=-5.7\pm 1.0$ to $\alpha_{t\perp}=-3.7\pm 0.3$ in the transition range and $\alpha_{k\parallel}=-3.12\pm 0.22$ to $\alpha_{k\perp}=-2.57\pm 0.09$ in the kinetic range. The corresponding wavevector anisotropy has the scaling of $k_\parallel \sim k_\perp^{0.71\pm 0.17}$ in the transition range, and changes to $k_\parallel \sim k_\perp^{0.38\pm 0.09}$ in the kinetic range, consistent with the kinetic Alfv\'enic turbulence at sub-ion scales., Comment: 4 figures; submitted to apjl

A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of the hiPSC-CM research pipeline. Here we introduce "Sarc-Graph," a computational framework to segment, track, and analyze sarcomeres in fluorescently tagged hiPSC-CMs. Our framework includes functions to segment z-discs and sarcomeres, track z-discs and sarcomeres in beating cells, and perform automated spatiotemporal analysis and data visualization. In addition to reporting good performance for sarcomere segmentation and tracking with little to no parameter tuning and a short runtime, we introduce two novel analysis approaches. First, we construct spatial graphs where z-discs correspond to nodes and sarcomeres correspond to edges. This makes measuring the network distance between each sarcomere (i.e., the number of connecting sarcomeres separating each sarcomere pair) straightforward. Second, we treat tracked and segmented components as fiducial markers and use them to compute the approximate deformation gradient of the entire tracked population. This represents a new quantitative descriptor of hiPSC-CM function. We showcase and validate our approach with both synthetic and experimental movies of beating hiPSC-CMs. By publishing Sarc-Graph, we aim to make automated quantitative analysis of hiPSC-CM behavior more accessible to the broader research community., Comment: Link to SI: https://github.com/elejeune11/Sarc-Graph/tree/main/Supplementary_Information

The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for application to pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved functional maturation of hiPSC-CMs, but probing cardiac contractile properties remains challenging in a 3D environment, especially at depth and in live tissues. Using small angle X-ray scattering (SAXS) images, we show that hiPSC-CMs, matured and examined in a 3D environment, exhibit periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. Contractile force is found to correlate with both scattering intensity (R2=0.44) and lattice spacing (R2=0.46). Scattering intensity also correlates with lattice spacing (R2=0.81), suggestive of lower noise in our structural measurement relative to the functional measurement. Notably, we observe decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs., Comment: 12 pages, 6 figures, supplementary material available upon request to the lead author

We use \emph{Parker Solar Probe} (\emph{PSP}) in-situ measurements to analyze the characteristics of solar wind turbulence during the first solar encounter covering radial distances between $35.7R_\odot$ and $41.7R_\odot$. In our analysis we isolate so-called switchback (SB) intervals (folded magnetic field lines) from non-switchback (NSB) intervals, which mainly follow the Parker spiral field. Using a technique based on conditioned correlation functions, we estimate the power spectra of Elsasser, magnetic and bulk velocity fields separately in the SB and NSB intervals. In comparing the turbulent energy spectra of the two types of intervals, we find the following characteristics: 1) The decorrelation length of the backward-propagating Elsasser field $z^-$ is larger in the NSB intervals than the one in the SB intervals; 2) the magnetic power spectrum in SB intervals is steeper, with spectral index close to -5/3, than in NSB intervals, which have a spectral index close to -3/2; 3) both SB and NSB turbulence are imbalanced with NSB having the largest cross-helicity, 4) the residual energy is larger in the SB intervals than in NSB, and 5) the analyzed fluctuations are dominated by Alfv\'enic fluctuations that are propagating in the \emph{sunward} (\emph{anti-sunward}) direction for the SB (NSB) turbulence. These observed features provide further evidence that the switchbacks observed by \emph{PSP} are associated with folded magnetic field lines giving insight into their turbulence nature., Comment: Submitted to The Astrophysical Journal Letters