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  1. Free, publicly-accessible full text available January 1, 2023
  2. Patients suffering from medical conditions resulting in hand impairment experience difficulty in performing simple daily tasks, like getting dressed or using a pencil, resulting in a poorer quality of life. Rehabilitation attempts to help such individuals regain a sense of control and normalcy. In this context, recent advances in robotics have manifested in multiple designs of hand exoskeletons and exosuit gloves for assistance and rehabilitation. These designs are typically actuated using pneumatic, shape memory alloys and motor-tendon actuators. The proposed Motor Tendon Actuated Exosuit Glove (MTAEG) with an open palm is a soft material glove capable of both flexion andmore »extension of all four fingers of the human hand. Its minimally invasive design maintains an open palm to facilitate haptic and tactile interaction with the environment. The MTAEG achieves flexion-extension motion with joint angles of 45° at the metacarpal joint which is 57% of the desired motion; 90° at the proximal interphalangeal joint which is 100% of the desired motion; and 50° at the distal interphalangeal joint which is 96% of the desired motion. The paper discusses the challenges in achieving the desired motion without the ability to directly model human tendons, and the inability to actuate joints individually.« less
  3. The human voltage-gated proton channel Hv1 is a drug target for cancer, ischemic stroke, and neuroinflammation. It resides on the plasma membrane and endocytic compartments of a variety of cell types, where it mediates outward proton movement and regulates the activity of NOX enzymes. Its voltage-sensing domain (VSD) contains a gated and proton-selective conduction pathway, which can be blocked by aromatic guanidine derivatives such as 2-guanidinobenzimidazole (2GBI). Mutation of Hv1 residue F150 to alanine (F150A) was previously found to increase 2GBI apparent binding affinity more than two orders of magnitude. Here, we explore the contribution of aromatic interactions between themore »inhibitor and the channel in the presence and absence of the F150A mutation, using a combination of electrophysiological recordings, classic mutagenesis, and site-specific incorporation of fluorinated phenylalanines via nonsense suppression methodology. Our data suggest that the increase in apparent binding affinity is due to a rearrangement of the binding site allowed by the smaller residue at position 150. We used this information to design new arginine mimics with improved affinity for the nonrearranged binding site of the wild-type channel. The new compounds, named “Hv1 Inhibitor Flexibles” (HIFs), consist of two “prongs,” an aminoimidazole ring, and an aromatic group connected by extended flexible linkers. Some HIF compounds display inhibitory properties that are superior to those of 2GBI, thus providing a promising scaffold for further development of high-affinity Hv1 inhibitors.

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