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We present the coupled oscillator: a new mechanism for signal amplification with widespread application in metrology. We introduce the mechanical theory of this framework, and support it by way of simulations. We present a particular implementation of coupled oscillators: a microelectromechanical system (MEMS) that uses one large (~100mm) N52 magnet coupled magnetically to a small (~0.25mm), oscillating N52 magnet, providing a force resolution of 200zN measured over 1s in a noiseless environment. We show that the same system is able to resolve magnetic gradients of 130aT/cm at a single point (within 500um). This technology therefore has the potential to revolutionize force and magnetic gradient sensing, including high-impact areas such cardiac and brain imaging., Comment: 13 pages, 17 figures

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.

We present a method for converting denoising neural networks from spatial into spatio-temporal ones by modifying the network architecture and loss function. We insert Robust Average blocks at arbitrary depths in the network graph. Each block performs latent space interpolation with trainable weights and works on the sequence of image representations from the preceding spatial components of the network. The temporal connections are kept live during training by forcing the network to predict a denoised frame from subsets of the input sequence. Using temporal coherence for denoising improves image quality and reduces temporal flickering independent of scene or image complexity.

The Casimir Force, a quantum mechanical effect, has been observed in several microelectromechanical systems (MEMS) platforms. Due to its extreme sensitivity to the separation of two objects, the Casimir Force has been proposed as an excellent avenue for quantum metrology. Practical application, however, is challenging due to attractive forces leading to stiction and failure of the device, called Casimir pull-in. In this work, we design and simulate a Casimir-driven metrology platform, where a time-delay based parametric amplification technique is developed to achieve a steady state and avoid pull-in. We apply the design to the detection of weak, low frequency, gradient magnetic fields, similar to those emanating from ionic currents in the heart and brain. Simulation parameters are selected from recent experimental platforms developed for Casimir metrology and magnetic gradiometry, both on MEMS platforms. While MEMS offer many advantages to such an application, the detected signal must typically be at the resonant frequency of the device, with diminished sensitivity in the low frequency regime of biomagnetic fields. Using a Casimir-drive parametric amplifier, we report a 10,000 fold improvement in the best-case resolution of MEMS single-point gradiometers, with a maximum sensitivity of 6 Hz/(pT/cm) at 1 Hz. The development of the proposed design has the potential to revolutionize metrology, and specifically may enable unshielded monitoring of biomagnetic fields in ambient conditions.

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

How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies.

Magnetic sensing is present in our everyday interactions with consumer electronics, and also demonstrates potential for measurement of extremely weak biomagnetic fields, such as those of the heart and brain. In this work, we leverage the many benefits of the micro-electromechanical systems (MEMS) devices to fabricate a small, low power, inexpensive sensor whose resolution is in the range of weak biomagnetic fields. The sensor works at room temperature, and is suitable for consumer electronics integration. At present, such biomagnetic fields can only be measured by expensive mechanisms such as optical pumping and superconducting quantum interference devices (SQUIDs). Thus, our sensor suggests the opening of a large phase space for medical and consumer applications. The prototype fabrication is achieved by assembling micro-objects, including a permanent micromagnet, onto a post-release commercial MEMS accelerometer. With this system, we demonstrate a room temperature MEMS magnetometer, whose design is only sensitive to gradient magnetic fields and is generally insensitive to the Earth's uniform field. In air, the sensor's response is linear with a resolution of 1.1 nT cm-1 and spans over 3 decades of dynamic range to 4.6 {\mu}T cm-1. In 1 mTorr vacuum with 20 dB magnetic shielding, the sensor achieved 100 pT cm-1 resolution at resonance. The theoretical floor of this design is 110 fT cm-1 Hz-1/2 with a resolution of 13 fT cm-1, thus these devices hold promise for both magnetocardiography (MCG) and magnetoencephalography (MEG) applications.

We use mesoscale simulations to gain insight into the digestion of biopolymers by studying the break-up dynamics of polymer aggregates (boluses) bound by physical cross-links. We investigate aggregate evolution, establishing that the linking bead fraction and the interaction energy are the main parameters controlling stability with respect to diffusion. We show $\textit{via}$ a simplified model that chemical breakdown of the constituent molecules causes aggregates that would otherwise be stable to disperse. We further investigate breakdown of biopolymer aggregates in the presence of fluid flow. Shear flow in the absence of chemical breakdown induces three different regimes depending on the flow Weissenberg number ($Wi$). i) At $Wi \ll 1$, shear flow has a negligible effect on the aggregates. ii) At $Wi \sim 1$, the aggregates behave approximately as solid bodies and move and rotate with the flow. iii) At $Wi \gg 1$, the energy input due to shear overcomes the attractive cross-linking interactions and the boluses are broken up. Finally, we study bolus evolution under the combined action of shear flow and chemical breakdown, demonstrating a synergistic effect between the two at high reaction rates.

The Casimir Effect is a physical manifestation of quantum fluctuations of the electromagnetic vacuum. When two metal plates are placed closely together, typically much less than a micron, the long wavelength modes between them are frozen out, giving rise to a net attractive force between the plates, scaling as d^-4 (or d^-3 for a spherical-planar geometry) even when they are not electrically charged. In this paper we observe the Casimir Effect in ambient conditions using a modified capacitive MEMS accelerometer. Using a feedback assisted pick-and-place assembly process we are able to attach various micro-structures onto the post-release MEMS, converting it from an inertial force sensor to a direct force measurement platform with pN resolution. With this system we are able to directly measure the Casimir force between a silver-coated microsphere and gold-coated silicon plate. This device is a step towards leveraging the Casimir Effect for cheap, sensitive, room temperature quantum metrology.

Multi-peaked analytically extended function (AEF), previously applied by the authors to modelling of lightning discharge currents, is used in this paper for representation of the electrostatic discharge (ESD) currents. The fitting to data is achieved by interpolation of certain data points. In order to minimize unstable behaviour, the exponents of the AEF are chosen from a certain arithmetic sequence and the interpolated points are chosen according to a D-optimal design. ESD currents' modelling is illustrated through two examples: one corresponding to an approximation of the IEC Standard 61000-4-2 waveshape, and the other to representation of some measured ESD current., Comment: 15 pages, 6 figure

A multi-peaked version of the analytically extended function (AEF) intended for approximation of multi-peaked lightning current wave-forms will be presented along with some of its basic properties. A general framework for estimating the parameters of the AEF using the Marquardt least-squares method (MLSM) for a waveform with an arbitrary (finite) number of peaks as well as a given charge trans-fer and specific energy will also be described. This framework is used to find parameters for some common single-peak wave-forms and some advantages and disadvantages of the approach will be discussed., Comment: 4 pages, 5 figure. arXiv admin note: text overlap with arXiv:1604.05109

A multi-peaked form of the analytically extended function (AEF) is used for approximation of lightning current waveforms in this paper. The AEF function's parameters are estimated using the Marquardt least-squares method (MLSM), and the general procedure for fitting the $p$-peaked AEF function to a waveform with an arbitrary (finite) number of peaks is briefly described. This framework is used for obtaining parameters of 2-peaked waveforms typically present when measuring first negative stroke currents. Advantages, disadvantages and possible improvements of the approach are also discussed., Comment: 11 pages, 6 figures