The Validity and Reliability of Two Commercially Available Load Sensors for Clinical Strength Assessment.

OBJECTIVE: Handheld dynamometers are common tools for assessing/monitoring muscular strength and endurance. Health/fitness Bluetooth load sensors may provide a cost-effective alternative; however, research is needed to evaluate the validity and reliability of such devices. This study assessed the validity and reliability of two commercially available Bluetooth load sensors (Activ5 by Activbody and Progressor by Tindeq). METHODS: Four tests were conducted on each device: stepped loading, stress relaxation, simulated exercise, and hysteresis. Each test type was repeated three times using the Instron ElectroPuls mechanical testing device (a gold-standard system). Test-retest reliability was assessed through intraclass correlations. Agreement with the gold standard was assessed with Pearson's correlation, interclass correlation, and Lin's concordance correlation. RESULTS: The Activ5 and Progressor had excellent test-retest reliability across all four tests (ICC(3,1) ≥ 0.999, all p ≤ 0.001). Agreement with the gold standard was excellent for both the Activ5 (ρ ≥ 0.998, ICC(3,1) ≥ 0.971, ρc ≥ 0.971, all p's ≤ 0.001) and Progressor (ρ ≥ 0.999, ICC(3,1) ≥ 0.999, ρc ≥ 0.999, all p's ≤ 0.001). Measurement error increased for both devices as applied load increased. CONCLUSION: Excellent test-retest reliability was found, suggesting that both devices can be used in a clinical setting to measure patient progress over time; however, the Activ5 consistently had poorer agreement with the gold standard (particularly at higher loads).

Estimating Vertical Ground Reaction Force during Walking Using a Single Inertial Sensor.

The vertical ground reaction force (vGRF) and its passive and active peaks are important gait parameters and of great relevance for musculoskeletal injury analysis and prevention, the detection of gait abnormities, and the evaluation of lower-extremity prostheses. Most currently available methods to estimate the vGRF require a force plate. However, in real-world scenarios, gait monitoring would not be limited to a laboratory setting. This paper reports a novel solution using machine learning algorithms to estimate the vGRF and the timing and magnitude of its peaks from data collected by a single inertial measurement unit (IMU) on one of the lower limb locations. Nine volunteers participated in this study, walking on a force plate-instrumented treadmill at various speeds. Four IMUs were worn on the foot, shank, distal thigh, and proximal thigh, respectively. A random forest model was employed to estimate the vGRF from data collected by each of the IMUs. We evaluated the performance of the models against the gold standard measurement of the vGRF generated by the treadmill. The developed model achieved a high accuracy with a correlation coefficient, root mean square error, and normalized root mean square error of 1.00, 0.02 body weight (BW), and 1.7% in intra-participant testing, and 0.97, 0.10 BW, and 7.15% in inter-participant testing, respectively, for the shank location. The difference between the reference and estimated passive force peak values was 0.02 BW and 0.14 BW with a delay of -0.14% and 0.57% of stance duration for the intra- and inter-participant testing, respectively; the difference between the reference and estimated active force peak values was 0.02 BW and 0.08 BW with a delay of 0.45% and 1.66% of stance duration for the intra- and inter-participant evaluation, respectively. We concluded that vertical ground reaction force can be estimated using only a single IMU via machine learning algorithms. This research sheds light on the development of a portable wearable gait monitoring system reporting the real-time vGRF in real-life scenarios.

Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation.

RATIONALE: Ventilator-induced diaphragm dysfunction is a significant contributor to weaning difficulty in ventilated critically ill patients. It has been hypothesized that electrically pacing the diaphragm during mechanical ventilation could reduce diaphragm dysfunction. OBJECTIVES: We tested a novel, central line catheter-based, transvenous phrenic nerve pacing therapy for protecting the diaphragm in sedated and ventilated pigs. METHODS: Eighteen Yorkshire pigs were studied. Six pigs were sedated and mechanically ventilated for 2.5 days with pacing on alternate breaths at intensities that reduced the ventilator pressure-time product by 20-30%. Six matched subjects were similarly sedated and ventilated but were not paced. Six pigs served as never-ventilated, never-paced control animals. MEASUREMENTS AND MAIN RESULTS: Cumulative duration of pacing therapy ranged from 19.7 to 35.7 hours. Diaphragm thickness assessed by ultrasound and normalized to initial value showed a significant decline in ventilated-not paced but not in ventilated-paced subjects (0.84 [interquartile range (IQR), 0.78-0.89] vs. 1.10 [IQR, 1.02-1.24]; P = 0.001). Compared with control animals (24.6 µm2/kg; IQR, 21.6-26.0), median myofiber cross-sectional areas normalized to weight and sarcomere length were significantly smaller in the ventilated-not paced (17.9 µm2/kg; IQR, 15.3-23.7; P = 0.005) but not in the ventilated-paced group (24.9 µm2/kg; IQR, 16.6-27.3; P = 0.351). After 60 hours of mechanical ventilation all six ventilated-paced subjects tolerated 8 minutes of intense phrenic stimulation, whereas three of six ventilated-not paced subjects did not (P = 0.055). There was a nonsignificant decrease in diaphragm tetanic force production over the experiment in the ventilated-paced and ventilated-not paced groups. CONCLUSIONS: These results suggest that early transvenous phrenic nerve pacing may mitigate ventilator-induced diaphragm dysfunction.

A real-time all-atom structural search engine for proteins.

Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new "designability"-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at http://www.degradolab.org/suns/ and the source code is hosted at https://github.com/godotgildor/Suns (PyMOL plugin, BSD license), https://github.com/Gabriel439/suns-cmd (command line client, BSD license), and https://github.com/Gabriel439/suns-search (search engine server, GPLv2 license).

Distributed sensing along fibers for smart clothing.

Textile sensors transform our everyday clothing into a means to track movement and biosignals in a completely unobtrusive way. One major hindrance to the adoption of "smart" clothing is the difficulty encountered with connections and space when scaling up the number of sensors. There is a lack of research addressing a key limitation in wearable electronics: Connections between rigid and textile elements are often unreliable, and they require interfacing sensors in a way incompatible with textile mass production methods. We introduce a prototype garment, compact readout circuit, and algorithm to measure localized strain along multiple regions of a fiber. We use a helical auxetic yarn sensor with tunable sensitivity along its length to selectively respond to strain signals. We demonstrate distributed sensing in clothing, monitoring arm joint angles from a single continuous fiber. Compared to optical motion capture, we achieve around five degrees error in reconstructing shoulder, elbow, and wrist joint angles.

HACS: Helical Auxetic Yarn Capacitive Strain Sensors with Sensitivity Beyond the Theoretical Limit.

The development of flexible strain sensors over the past decade has focused on accessing high strain percentages and high sensitivity (i.e., gauge factors). Strain sensors that employ capacitance as the electrical signal to correlate to strain are typically restricted in sensitivity because of the Poisson effect. By employing auxetic structures, the limits of sensitivity for capacitive sensors have been exceeded, which has improved the competitiveness of this modality of sensing. In this work, the first employment of helical auxetic yarns as capacitive sensors is presented. It is found that the response of the helical auxetic yarn capacitive sensors (termed as HACS) is dependent on the two main fabrication variables-the ratio of diameters and the helical wrapping length. Depending on these variables, sensors that respond to strain with increasing or decreasing capacitance values can be obtained. A greater auxetic character results in larger sensitivities accessible at smaller strains-a characteristic that is not commonly found when accessing high gauge factors. In addition, the highest sensitivity for auxetic capacitive sensors reported thus far is obtained. A mechanism of sensor response that explains both the variable capacitance response and the high gauge factors obtained experimentally is proposed.

Passive and Wireless All-Textile Wearable Sensor System.

Mobile health technology and activity tracking with wearable sensors enable continuous unobtrusive monitoring of movement and biophysical parameters. Advancements in clothing-based wearable devices have employed textiles as transmission lines, communication hubs, and various sensing modalities; this area of research is moving towards complete integration of circuitry into textile components. A current limitation for motion tracking is the need for communication protocols demanding physical connection of textile with rigid devices, or vector network analyzers (VNA) with limited portability and lower sampling rates. Inductor-capacitor (LC) circuits are ideal candidates as textile sensors can be easily implemented with textile components and allow wireless communication. In this paper, the authors report a smart garment that can sense movement and wirelessly transmit data in real time. The garment features a passive LC sensor circuit constructed of electrified textile elements that sense strain and communicate through inductive coupling. A portable, lightweight reader (fReader) is developed for achieving a faster sampling rate than a downsized VNA to track body movement, and for wirelessly reading sensor information suitable for deployment with a smartphone. The smart garment-fReader system monitors human movement in real-time and exemplifies the potential of textile-based electronics moving forward.

Structural informatics, modeling, and design with an open-source Molecular Software Library (MSL).

We present the Molecular Software Library (MSL), a C++ library for molecular modeling. MSL is a set of tools that supports a large variety of algorithms for the design, modeling, and analysis of macromolecules. Among the main features supported by the library are methods for applying geometric transformations and alignments, the implementation of a rich set of energy functions, side chain optimization, backbone manipulation, calculation of solvent accessible surface area, and other tools. MSL has a number of unique features, such as the ability of storing alternative atomic coordinates (for modeling) and multiple amino acid identities at the same backbone position (for design). It has a straightforward mechanism for extending its energy functions and can work with any type of molecules. Although the code base is large, MSL was created with ease of developing in mind. It allows the rapid implementation of simple tasks while fully supporting the creation of complex applications. Some of the potentialities of the software are demonstrated here with examples that show how to program complex and essential modeling tasks with few lines of code. MSL is an ongoing and evolving project, with new features and improvements being introduced regularly, but it is mature and suitable for production and has been used in numerous protein modeling and design projects. MSL is open-source software, freely downloadable at http://msl-libraries.org. We propose it as a common platform for the development of new molecular algorithms and to promote the distribution, sharing, and reutilization of computational methods.

The Effect of Footwear, Running Speed, and Location on the Validity of Two Commercially Available Inertial Measurement Units During Running.

Introduction: Most running-related injuries are believed to be caused by abrupt changes in training load, compounded by biomechanical movement patterns. Wearable technology has made it possible for runners to quantify biomechanical loads (e.g., peak positive acceleration; PPA) using commercially available inertial measurement units (IMUs). However, few devices have established criterion validity. The aim of this study was to assess the validity of two commercially available IMUs during running. Secondary aims were to determine the effect of footwear, running speed, and IMU location on PPA. Materials and Methods: Healthy runners underwent a biomechanical running analysis on an instrumented treadmill. Participants ran at their preferred speed in three footwear conditions (neutral, minimalist, and maximalist), and at three speeds (preferred, +10%, -10%) in the neutral running shoes. Four IMUs were affixed at the distal tibia (IMeasureU-Tibia), shoelaces (RunScribe and IMeasureU-Shoe), and insole (Plantiga) of the right shoe. Pearson correlations were calculated for average vertical loading rate (AVLR) and PPA at each IMU location. Results: The AVLR had a high positive association with PPA (IMeasureU-Tibia) in the neutral and maximalist (r = 0.70-0.72; p ≤ 0.001) shoes and in all running speed conditions (r = 0.71-0.83; p ≤ 0.001), but low positive association in the minimalist (r = 0.47; p < 0.05) footwear condition. Conversely, the relationship between AVLR and PPA (Plantiga) was high in the minimalist (r = 0.75; p ≤ 0.001) condition and moderate in the neutral (r = 0.50; p < 0.05) and maximalist (r = 0.57; p < 0.01) footwear. The RunScribe metrics demonstrated low to moderate positive associations (r = 0.40-0.62; p < 0.05) with AVLR across most footwear and speed conditions. Discussion: Our findings indicate that the commercially available Plantiga IMU is comparable to a tibia-mounted IMU when acting as a surrogate for AVLR. However, these results vary between different levels of footwear and running speeds. The shoe-mounted RunScribe IMU exhibited slightly lower positive associations with AVLR. In general, the relationship with AVLR improved for the RunScribe sensor at slower speeds and improved for the Plantiga and tibia-mounted IMeasureU sensors at faster speeds.

Effect of sequence depth and length in long-read assembly of the maize inbred NC358.

Improvements in long-read data and scaffolding technologies have enabled rapid generation of reference-quality assemblies for complex genomes. Still, an assessment of critical sequence depth and read length is important for allocating limited resources. To this end, we have generated eight assemblies for the complex genome of the maize inbred line NC358 using PacBio datasets ranging from 20 to 75 × genomic depth and with N50 subread lengths of 11-21 kb. Assemblies with ≤30 × depth and N50 subread length of 11 kb are highly fragmented, with even low-copy genic regions showing degradation at 20 × depth. Distinct sequence-quality thresholds are observed for complete assembly of genes, transposable elements, and highly repetitive genomic features such as telomeres, heterochromatic knobs, and centromeres. In addition, we show high-quality optical maps can dramatically improve contiguity in even our most fragmented base assembly. This study provides a useful resource allocation reference to the community as long-read technologies continue to mature.

Nature-inspired design of motif-specific antibody scaffolds.

Aberrant changes in post-translational modifications (PTMs) such as phosphate groups underlie a majority of human diseases. However, detection and quantification of PTMs for diagnostic or biomarker applications often require PTM-specific monoclonal antibodies (mAbs), which are challenging to generate using traditional antibody-selection methods. Here we outline a general strategy for producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot' into an antibody scaffold. Inspired by a natural phosphate-binding motif, we designed and selected mAb scaffolds with hot spots specific for phosphoserine, phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest that each hot spot functions independently of the surrounding scaffold, as phage display antibody libraries using these scaffolds yielded >50 phospho- and target-specific mAbs against 70% of target peptides. Our motif-specific scaffold strategy may provide a general solution for rapid, robust development of anti-PTM mAbs for signaling, diagnostic and therapeutic applications.

Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions.

The complex hydrophobic and hydrophilic milieus of membrane-associated proteins pose experimental and theoretical challenges to their understanding. Here, we produce a nonredundant database to compute knowledge-based asymmetric cross-membrane potentials from the per-residue distributions of C(ß), C(γ) and functional group atoms. We predict transmembrane and peripherally associated regions from genomic sequence and position peptides and protein structures relative to the bilayer (available at http://www.degradolab.org/ez). The pseudo-energy topological landscapes underscore positional stability and functional mechanisms demonstrated here for antimicrobial peptides, transmembrane proteins, and viral fusion proteins. Moreover, experimental effects of point mutations on the relative ratio changes of dual-topology proteins are quantitatively reproduced. The functional group potential and the membrane-exposed residues display the largest energetic changes enabling to detect native-like structures from decoys. Hence, focusing on the uniqueness of membrane-associated proteins and peptides, we quantitatively parameterize their cross-membrane propensity, thus facilitating structural refinement, characterization, prediction, and design.

A photon-free approach to transmembrane protein structure determination.

The structures of membrane proteins are generally solved using samples dissolved in micelles, bicelles, or occasionally phospholipid bilayers using X-ray diffraction or magnetic resonance. Because these are less than perfect mimics of true biological membranes, the structures are often confirmed by evaluating the effects of mutations on the properties of the protein in their native cellular environments. Low-resolution structures are also sometimes generated from the results of site-directed mutagenesis when other structural data are incomplete or not available. Here, we describe a rapid and automated approach to determine structures from data on site-directed mutants for the special case of homo-oligomeric helical bundles. The method uses as input an experimental profile of the effects of mutations on some property of the protein. This profile is then interpreted by assuming that positions that have large effects on structure/function when mutated project toward the center of the oligomeric bundle. Model bundles are generated, and correlation analysis is used to score which structures have inter-subunit C(ß) distances between adjoining monomers that best correlate with the experimental profile. These structures are then clustered and refined using energy-based minimization methods. For a set of 10 homo-oligomeric TM protein structures ranging from dimers to pentamers, we show that our method predicts structures to within 1-2 Å backbone RMSD relative to X-ray and NMR structures. This level of agreement approaches the precision of NMR structures solved in different membrane mimetics.