Biology subjects

Chiu, V. L.

Publications and source records attributed to Chiu, V. L..

3 recordsLinked to original sources

bioRxiv2026

Optimizing histatin 5: Effects of K13 and K17 substitutions on proteolytic stability and antifungal activity

Candida albicans is an opportunistic human fungal pathogen found in the oral cavity. Human saliva contains a 24-amino acid peptide called histatin 5 (Hst5) that has activity against C. albicans, but degradation of Hst5 by secreted aspartyl proteases (Saps) produced by C. albicans and by salivary proteases can reduce its antifungal efficacy. Building on our previous work that identified K13 and K17 as important residues for stability and activity of Hst5, we systematically investigated amino acid modification at these sites. Modifications explored the influence of hydrophobicity, charge, polarity, size, and aromaticity on Hst5s interaction with Saps and saliva. The K13R variant retained proteolytic stability and antifungal activity after incubation with Sap1, Sap2, Sap3, and Sap9, while other K13 variants generally had reduced stability and activity, emphasizing the importance of a positive charge at this position. At K17, substitutions generally enhanced proteolytic stability and improved antifungal activity after incubation with Saps. We introduced the normalized intact peptide (NIP) parameter as a tool for identifying Hst5 variants with improved stability in the presence of multiple Saps, and NIP revealed K17W as the most proteolytically stable variant overall. Additionally, we observed modest differences in peptide stability in saliva, and the K17W variant was the only variant that retained more activity than Hst5 following incubation with saliva. We further assessed the K17W variants ability to prevent biofilm formation and found it to be more effective than the parent peptide Hst5. Our findings highlight the interactions between the Hst5 K13 and K17 residues with Saps and saliva and provide a strong foundation for future Hst5 engineering efforts to improve proteolytic stability and antifungal efficacy in diverse proteolytic environments.

microbiology↗

bioRxiv2020

Shortcomings of human-in-the-loop optimization for an ankle-foot prosthesis: a case series

Human-in-the-loop optimization allows for individualized device control based on measured human performance. This technique has been used to produce large reductions in energy expenditure during walking with exoskeletons but has not yet been applied to prosthetic devices. In this series of case studies, we applied human-in-the-loop optimization to the control of an active ankle-foot prosthesis used by participants with unilateral transtibial amputation. We optimized the parameters of five control architectures that captured aspects of successful exoskeletons and commercial prostheses, but none resulted in significantly lower metabolic rate than generic control. In one control architecture, we increased the exposure time per condition by a factor of five, but the optimized controller still resulted in higher metabolic rate. Finally, we optimized for self-reported comfort instead of metabolic rate, but the resulting controller was not preferred. There are several reasons why human-in-the-loop optimization may have failed for people with amputation. Control architecture is an unlikely cause given the variety of controllers tested. The lack of effect likely relates to adaptation protocol or differences in the learning mechanisms or objectives of people with amputation. Future work should investigate these causes to determine whether human-in-the-loop optimization for prostheses could be successful.

bioengineering↗

bioRxiv2020

Teleoperation of an ankle-foot prosthesis with a wrist exoskeleton

ObjectiveWe aimed to develop a system for people with amputation that non-invasively restores missing control and sensory information for an ankle-foot prosthesis. MethodsIn our approach, a wrist exoskeleton allows people with amputation to control and receive feedback from their prosthetic ankle via teleoperation. We implemented two control schemes: position control with haptic feedback of ankle torque at the wrist; and torque control that allows the user to modify a baseline torque profile by moving their wrist against a virtual spring. We measured tracking error and frequency response for the ankle-foot prosthesis and the wrist exoskeleton. To demonstrate feasibility and evaluate system performance, we conducted an experiment in which one participant with a transtibial amputation tracked desired wrist trajectories during walking, while we measured wrist and ankle response. ResultsBenchtop testing demonstrated that for relevant walking frequencies, system error was below human perceptual error. During the walking experiment, the participant was able to voluntarily follow different wrist trajectories with an average RMS error of 1.55{degrees} after training. The ankle was also able to track desired trajectories below human perceptual error for both position control (RMSE = 0.8{degrees}) and torque control (RMSE = 8.4%). ConclusionWe present a system that allows a user with amputation to control an ankle-foot prosthesis and receive feedback about its state using a wrist exoskeleton, with accuracy comparable to biological neuromotor control. SignificanceThis bilateral teleoperation system enables novel prosthesis control and feedback strategies that could improve prosthesis control and aid motor learning.

bioengineering↗