Structural basis for feedforward control in the PINK1/Parkin pathway.

PINK1 and parkin constitute a mitochondrial quality control system mutated in Parkinson's disease. PINK1, a kinase, phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to mitochondria. PINK1 controls both parkin localization and activity through phosphorylation of both ubiquitin and the ubiquitin-like (Ubl) domain of parkin. Here, we observed that phospho-ubiquitin can bind to two distinct sites on parkin, a high-affinity site on RING1 that controls parkin localization and a low-affinity site on RING0 that releases parkin autoinhibition. Surprisingly, ubiquitin vinyl sulfone assays, ITC, and NMR titrations showed that the RING0 site has higher affinity for phospho-ubiquitin than phosphorylated Ubl in trans. We observed parkin activation by micromolar concentrations of tetra-phospho-ubiquitin chains that mimic mitochondria bearing multiple phosphorylated ubiquitins. A chimeric form of parkin with the Ubl domain replaced by ubiquitin was readily activated by PINK1 phosphorylation. In all cases, mutation of the binding site on RING0 abolished parkin activation. The feedforward mechanism of parkin activation confers robustness and rapidity to the PINK1-parkin pathway and likely represents an intermediate step in its evolutionary development.

Battery Powered Portable Thermal Cycler for Continuous-Flow Polymerase Chain Reaction Diagnosis by Single Thermostatic Thermoelectric Cooler and Open-Loop Controller.

Temperature control is the most important and fundamental part of a polymerase chain reaction (PCR). To date, there have been several methods to realize the periodic heating and cooling of the thermal-cycler system for continuous-flow PCR reactions, and three of them were widely used: the thermo-cycled thermoelectric cooler (TEC), the heating block, and the thermostatic heater. In the present study, a new approach called open-loop controlled single thermostatic TEC was introduced to control the thermal cycle during the amplification process. Differing from the former three methods, the size of this microdevice is much smaller, especially when compared to the microdevice used in the heating block method. Furthermore, the rising and cooling speed of this method is much rapider than that in a traditional TEC cycler, and is nearly 20-30% faster than a single thermostatic heater. Thus, a portable PCR system was made without any external heat source, and only a Teflon tube-wrapped TEC chip was used to achieve the continuous-flow PCR reactions. This provides an efficient way to reduce the size of the system and simplify it. In addition, through further experiments, the microdevice is not only found to be capable of amplification of a PCR product from Human papillomavirus type 49 (Genbank ref: X74480.1) and Rubella virus (RUBV), but also enables clinical diagnostics, such as a test for hepatitis B virus.

Model-Based Angular Scan Error Correction of an Electrothermally-Actuated MEMS Mirror.

In this paper, the actuation behavior of a two-axis electrothermal MEMS (Microelectromechanical Systems) mirror typically used in miniature optical scanning probes and optical switches is investigated. The MEMS mirror consists of four thermal bimorph actuators symmetrically located at the four sides of a central mirror plate. Experiments show that an actuation characteristics difference of as much as 4.0% exists among the four actuators due to process variations, which leads to an average angular scan error of 0.03°. A mathematical model between the actuator input voltage and the mirror-plate position has been developed to predict the actuation behavior of the mirror. It is a four-input, four-output model that takes into account the thermal-mechanical coupling and the differences among the four actuators; the vertical positions of the ends of the four actuators are also monitored. Based on this model, an open-loop control method is established to achieve accurate angular scanning. This model-based open loop control has been experimentally verified and is useful for the accurate control of the mirror. With this control method, the precise actuation of the mirror solely depends on the model prediction and does not need the real-time mirror position monitoring and feedback, greatly simplifying the MEMS control system.

Refining Insulin on Board with netIOB for Automated Insulin Delivery.

Automated insulin delivery (AID) systems enhance glucose management by lowering mean glucose level, reducing hyperglycemia, and minimizing hypoglycemia. One feature of most AID systems is that they allow the user to view "insulin on board" (IOB) to help confirm a recent bolus and limit insulin stacking. This metric, along with viewing glucose concentrations from a continuous glucose monitoring system, helps the user understand bolus insulin action and the future "threat" of hypoglycemia. However, the current presentation of IOB in AID systems can be misleading, as it does not reflect true insulin action or automatic, dynamic insulin adjustments. This commentary examines the evolution of IOB from a bolus-specific metric to its contemporary use in AID systems, highlighting its limitations in capturing real-time insulin modulation during varying physiological states.

Fabrication and open-loop control of three-lobed nonspherical Janus microrobots.

In this study, we propose a simple and efficient method to fabricate three-lobed nonspherical Janus microrobots. These microrobots can be actuated by a harmless magnetic field. Utilizing organosilica as the material of choice, we leverage its versatile silane chemistry to enable various surface modifications and functionalities. The fabricated microrobots demonstrate two distinct modes of motion, making them well-suited for cell transportation and drug delivery tasks. Their unique shape and motion characteristics allow for precise and targeted movement. Integrating these microrobots into therapeutic delivery platforms can revolutionize medical treatments, offering enhanced precision, efficiency, and versatility in delivering therapies to specific sites.

An insect-scale robot reveals the effects of different body dynamics regimes during open-loop running in feature-laden terrain.

The transition from the lab to natural environments is an archetypal challenge in robotics. While larger robots can manage complex limb-ground interactions using sensing and control, such strategies are difficult to implement on small platforms where space and power are limited. The Harvard Ambulatory Microrobot (HAMR) is an insect-scale quadruped capable of effective open-loop running on featureless, hard substrates. Inspired by the predominantly feedforward strategy of rapidly-running cockroaches on uneven terrain (Sponberg, 2007), we used HAMR to explore open-loop running on two 3D printed heterogeneous terrains generated using fractional Brownian motion. The 'pocked' terrain had foot-scale features throughout while the 'jagged' terrain features increased in height in the direction of travel. We measured the performance of trot and pronk gaits while varying limb amplitude and stride frequency. The frequencies tested encompassed different dynamics regimes: body resonance (10-25 Hz) and kinematic running (30-40 Hz), with dynamics typical of biological running and walking, respectively, and limb-transmission resonance (45-60 Hz). On the featureless and pocked terrains, low mechanical cost-of-transport (mCoT) kinematic running combinations performed best without systematic differences between trot and pronk; indicating that if terrain features are not too tall, a robot can transition from homo-to heterogeneous environments in open-loop. Pronk bypassed taller features than trot on the jagged terrain, and higher mCoT, lower frequency running was more often effective. While increasing input power to the robot improved performance in general, lower frequency pronking on jagged terrain allowed the robot to bypass taller features compared with the same input power at higher frequencies. This was correlated with the increased variation in center-of-mass orientation occurring at frequencies near body resonance. This study established that appropriate choice of robot dynamics, as mediated by gait, frequency, and limb amplitude, can expand the terrains accessible to microrobots without the addition of sensing or closed-loop control.

Alleviation of Residual Vibrations in Hard-Magnetic Soft Actuators Using a Command-Shaping Scheme.

Hard-magnetic soft materials belong to a class of the highly deformable magneto-active elastomer family of smart materials and provide a promising technology for flexible electronics, soft robots, and functional metamaterials. When hard-magnetic soft actuators are driven by a multiple-step input signal (Heaviside magnetic field signal), the residual oscillations exhibited by the actuator about equilibrium positions may limit their performance and accuracy in practical applications. This work aims at developing a command-shaping scheme for alleviating residual vibrations in a magnetically driven planar hard-magnetic soft actuator. The control scheme is based on the balance of magnetic and elastic forces at a critical point in an oscillation cycle. The equation governing the dynamics of the actuator is devised using the Euler-Lagrange equation. The constitutive behaviour of the hard-magnetic soft material is modeled using the Gent model of hyperelasticity, which accounts for the strain-stiffening effects. The dynamic response of the actuator under a step input signal is obtained by numerically solving the devised dynamic governing equation using MATLAB ODE solver. To demonstrate the applicability of the developed command-shaping scheme, a thorough investigation showing the effect of various parameters such as material damping, the sequence of desired equilibrium positions, and polymer chain extensibility on the performance of the proposed scheme is performed. The designed control scheme is found to be effective in controlling the motion of the hard-magnetic soft actuator at any desired equilibrium position. The present study can find its potential application in the design and development of an open-loop controller for hard-magnetic soft actuators.

Contributions of open-loop and closed-loop control in a continuous tracking task differ depending on attentional demands during practice.

Improving tracking performance requires numerous adjustments in the motor system, including peripheral muscle functions and central motor commands. These commands can rely on sensory feedback processing during tracking, i.e., closed-loop control. In the case of repeated tracking sequences, these commands can rely on an inner representation of the target trajectory to optimize pre-planning, i.e., open-loop control. Implicit learning in a continuous tracking task with repeated sequences proves the availability of an inner target representation, which emerges by learning task regularities, even without explicit knowledge. We hypothesize that the actual use of open-loop or closed-loop control is influenced by the demand for attention. Specifically, we suggest that closed-loop control and its development during practice need attentional resources, whereas open-loop control can work and evolve in a more automatic way without attentional demands. To test this, we investigated motor-control strategies when extensively practicing a continuous compensatory force-tracking task using isometric leg muscle activation, either as a single-motor task or as a motor-cognitive dual task. After training, we found evidence for predominantly closed-loop control in the single-task training group and for open-loop control in the dual-task training group. In particular, we ascertained dual-task motor costs and a weakly developed implicit knowledge of task regularities in the single-task training group. In contrast, in the dual-task training group dual-task motor costs disappeared, while implicit learning was clearly observed. We conclude that motor-cognitive dual-task training may boost implicit motor learning, without necessarily impeding concurrent improvement in the cognitive task. Data repository: reserved doi: https://doi.org/10.5281/zenodo.6759377.

Input Shaping Based on an Experimental Transfer Function for an Electrostatic Microscanner in a Quasistatic Mode.

This paper describes an input shaping method based on an experimental transfer function to effectively obtain a desired scan output for an electrostatic microscanner driven in a quasistatic mode. This method features possible driving extended to a higher frequency, whereas the conventional control needs dynamic modeling and is still ineffective in mitigating harmonics, sub-resonances, and/or higher modes. The performance of the input shaping was experimentally evaluated in terms of the usable scan range (USR), and its application limits were examined with respect to the optical scan angle and frequency. The experimental results showed that the usable scan range is as wide as 96% for a total optical scan angle (total OSA) of up to 9° when the criterion for scan line error is 1.5%. The usable scan ranges were degraded for larger total optical scan angles because of the nonlinear electrostatic torque with respect to the driving voltage. The usable scan range was 90% or higher for most frequencies up to 160 Hz and was drastically decreased for the higher driving frequency because fewer harmonics are included in the input shaping process. Conclusively, the proposed method was experimentally confirmed to show good performance in view of its simplicity and its operable range, quantitatively compared with that of the conventional control.

Foot muscle morphology is related to center of pressure sway and control mechanisms during single-leg standing.

Maintaining balance is vitally important in everyday life. Investigating the effects of individual foot muscle morphology on balance may provide insights into neuromuscular balance control mechanisms. This study aimed to examine the correlation between the morphology of foot muscles and balance performance during single-leg standing. Twenty-eight recreational runners were recruited in this study. An ultrasound device was used to measure the thickness and cross-sectional area of three intrinsic foot muscles (abductor hallucis, flexor digitorum brevis and quadratus plantae) and peroneus muscles. Participants were required to perform 30s of single-leg standing for three trials on a force plate, which was used to record the center of pressure (COP). The standard deviation of the amplitude and ellipse area of the COP were calculated. In addition, stabilogram diffusion analysis (SDA) was performed on COP data. Pearson correlation coefficients were computed to examine the correlation between foot muscle morphology and traditional COP parameters as well as with SDA parameters. Our results showed that larger abductor hallucis correlated to smaller COP sway, while larger peroneus muscles correlated to larger COP sway during single-leg standing. Larger abductor hallucis also benefited open-loop dynamic stability, as well as supported a more efficient transfer from open-loop to closed loop control mechanisms. These results suggest that the morphology of foot muscles plays an important role in balance performance, and that strengthening the intrinsic foot muscles may be an effective way to improve balance.

Technical developments of functional electrical stimulation to correct drop foot: sensing, actuation and control strategies.

This work presents a review on the technological advancements over the last decades of functional electrical stimulation based neuroprostheses to correct drop foot. Functional electrical stimulation is a technique that has been put into practice for several years now, and has been shown to functionally restore and rehabilitate individuals with movement disorders, such as stroke, multiple sclerosis and traumatic brain injury, among others. The purpose of this technical review is to bring together information from a variety of sources and shed light on the field's most important challenges, to help in identifying new research directions. The review covers the main causes of drop foot and its associated gait implications, along with several functional electrical stimulation-based neuroprostheses used to correct it, developed within academia and currently available in the market. These systems are thoroughly analyzed and discussed with particular emphasis on actuation, sensing and control of open- and closed-loop architectures. In the last part of this work, recommendations on future research directions are suggested.