Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness

A GPU-accelerated simulator for the DEM analysis of granular systems composed of clump-shaped elements

We discuss the use of the Discrete Element Method (DEM) to simulate the dynamics of granular systems made up of elements with nontrivial geometries. The DEM simulator is GPU accelerated and can handle elements whose shape is defined as the union with overlap of diverse sets of spheres with user-specified radii. The simulator can also handle complex materials since each sphere in an element can have its own Young's modulus $E$, Poisson ratio $\nu$, friction coefficient $\mu$, and coefficient of restitution CoR. To demonstrate the simulator, we produce a "digital simulant" (DS), a replica of the GRC-1 lunar simulant. The DS follows an element size distribution similar but not identical to that of GRC-1. We validate the predictive attributes of the simulator via several numerical experiments: repose angle, cone penetration, drawbar pull, and rover incline-climbing tests. Subsequently, we carry out a sensitivity analysis to gauge how the slope vs. slip curves change when the element shape, element size, and friction coefficient change. The paper concludes with a VIPER rover simulation that confirms a recently proposed granular scaling law. The simulation involves more than 11 million elements composed of more than 34 million spheres of different radii. The simulator works in the Chrono framework and utilizes two GPUs concurrently. The GPU code for the simulator and all numerical experiments discussed are open-source and available on GitHub for reproducibility studies and unfettered use and distribution.Comment: Main text 28 pages, including 27 figures. Submitted to Engineering with Computer

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics

Evaluation of Decentralized Reactive Swing-Leg Controllers on Powered Robotic Legs

<p>We present work to transfer decentralized neuromuscular control strategies of human locomotion to powered segmented robotic legs. State-of-the-art robotic locomotion control approaches, like centralized planning and tracking in fully robotic systems and predefined motion pattern replay in prosthetic systems, do not enable the dynamism and reactiveness of able-bodied humans. Animals largely realize dexterous segmented leg performance with leg-encoded biomechanics and local feedback controls that bypass central processing. A decentralized neuromuscular controller was recently developed that enables robust locomotion for a simulated multi-segmented planar humanoid. A portion of this controller was used in an active ankle-foot prosthesis to modulate ankle torque during stance, enabling level and inclined ground walking. While these results suggest that the neuromuscular controller is a promising alternative control method for both fully robotic systems and powered prostheses, it is unclear if the controller can be transferred to multi-segmented robotic legs. The goal of this thesis is to investigate the feasibility of controlling a multi-segmented robotic leg with the proposed neuromuscular control approach, which may enable robots and powered prostheses to react to locomotion disturbances dynamically and in a human-like way. Specifically, work in this thesis investigates two hypotheses. Hypothesis one posits that the proposed decentralized swing-leg controllers enable more robust foot placements into ground targets than state-of-the-art impedance controls. Hypothesis two posits that neuromuscular swing-leg control enables more human-like motion than state-of-the-art impedance control. To transfer neuromuscular controls to powered segmented robotic legs, we use a model-based design approach. The initial transfer is focused on neuromuscular swing-leg controls, important for maintaining dynamic stability of both fully robotic systems and powered prostheses in the presence of unexpected locomotion disturbances, such as trips and pushes. We first present the design of RNL, a three segment, cable-driven, antagonistically actuated robotic leg with joint compliance. The robot’s size, weight, and actuation capabilities correspond to dynamically scaled human values. Next, a highfidelity simulation of the robot is created to investigate the feasibility of transferring neuromuscular controls, pre-tune hardware gains via optimization, and serve as a benchmark for hardware experiments. An idealized version of the swing-leg controller with mono-articular actuation, as well as the neuromuscular interpretation of this controller with multi-articular actuation is then transferred to RNL and evaluated with foot placement experiments. The results suggest that the proposed swing-leg controllers can accurately regulate foot placement of robotic legs during undisturbed and disturbed motions. Compared to impedance control, the proposed controls achieve foot placements over a range of ground targets with a single set of gains, which make them attractive candidates for regulating the motion of legged robots and prostheses in the real-world. Furthermore, the ankle trajectory traced out by the robot under neuromuscular control is more human-like than the trajectories traced out under the proposed idealized control and impedance control. In parallel to this control transfer, a synthesis method for creating compact nonlinear springs with user-defined torque-deflection profiles is presented to explore methods for improving RNL’s series elastic actuators. The springs use rubber as their elastic element, which, while enabling a compact spring design, introduce viscoelastic behavior in the spring that needs to be accounted for with additional control. To accurately estimate force developed in the rubber, an empirically characterized constitutive rubber model is developed and integrated into the series elastic actuator controller used by the RNL test platforms. Benchtop experiments show that in conjunction with an observer, the nonlinear spring prototype achieves desired behavior at actuation frequencies up to 2 Hz, after which spring behavior degrades due to rubber hysteresis. These results show that while the presented methodology is capable of realizing compact nonlinear springs, careful rubber selection that mitigates viscoelastic behavior is necessary during the spring design process.</p