The discharge of a spinal alpha motoneuron and the resulting contraction of its muscle fibres represents the functional quantum of the motor system. Recent advances in the recording and decomposition of the electromyographic signal allow for the identification of several tens of concurrently active motor units. These detailed population data provide the potential to achieve deep insights into the synaptic organization of motor commands. Yet most of our understanding of the synaptic input to motoneurons is derived from intracellular recordings in animal preparations. Thus, it is necessary to extend the new electrode and decomposition methods to recording of motor unit populations in these same preparations. To achieve this goal, we use high-density electrode arrays and decomposition techniques, analogous to those developed for humans, to record and decompose the activity of tens of concurrently active motor units in a hindlimb muscle in the in vivo cat. Our results showed that the decomposition method in this animal preparation was highly accurate, with conventional two-source validation providing rates of agreement equal to or superior to those found in humans. Multidimensional reconstruction of the motor unit action potential provides the ability to accurately track the same motor unit across multiple contractions. Additionally, correlational analyses demonstrate that the composite spike train provides better estimates of whole muscle force than conventional estimates obtained from the electromyographic signal. Lastly, stark differences are observed between the modes of activation, in particular tendon vibration produced quantal interspike intervals at integer multiples of the vibration period.

The primary purpose of this study was to determine the influence of load compliance on time to failure during sustained isometric contractions performed with the elbow flexor muscles at four submaximal target forces. Subjects pulled against a rigid restraint during the force task and maintained a constant elbow angle, while supporting an equivalent inertial load during the position task. Each task was sustained for as long as possible. Twenty-one healthy adults (23 ± 6 yr; 11 men) participated in the study. The maximal voluntary contraction (MVC) force was similar (P = 0.95) before the subjects performed the force and position tasks at each of the four target forces: 20, 30, 45, and 60% of MVC force. The time to task failure was longer for the force tasks (576 ± 80 and 325 ± 70 s) than for the position tasks (299 ± 77 and 168 ± 35 s) at target forces of 20 and 30% (P < 0.001), but was similar for the force tasks (178 ± 35 and 86 ± 14 s) and the position tasks (132 ± 29 and 87 ± 14 s) at target forces of 45 and 60% (P > 0.19). The briefer times to failure for the position task at the lower forces were accompanied by greater rates of increase in elbow flexor muscle activity, mean arterial pressure, heart rate, and rating of perceived exertion. There was no difference in the estimates of external mechanical work at any target force. The dominant mechanisms limiting time to failure of sustained isometric contractions with the elbow flexor muscles appear to change at target forces between 30 and 45% MVC, with load compliance being a significant factor at lower forces only.

We demonstrate the optimization of the concentration, temperature and cycling of a piranha (H 2 O 2 :H 2 SO 4 ) mixture that produces high yields while quickly etching hollow structures made using a highly crosslinked SU8 polymer sacrificial core. The effects of the piranha mixture on the thickness, refractive index and roughness of common micro-electromechanical systems and microopto-electromechanical systems fabrication materials (SiN, SiO 2 and Si) were determined. The effectiveness of the optimal piranha mixture was demonstrated in the construction of hollow antiresonant reflecting optical waveguides.

New Findings r What is the central question of this study?How long can humans sustain motor unit discharge during a voluntary contraction? r What is the main finding and its importance?Human motor units can discharge action potentials for a longer time during a voluntary contraction than can be achieved by intracellular or extracellular current injection of motor neurons with in vivo and in vitro animal preparations. These recordings comprise a previously unexplored range of durations for human motor unit recordings during a continuously sustained isometric recording.The purpose of the study was to determine how long humans could sustain the discharge of single motor units during a voluntary contraction. The discharge of motor units in first dorsal interosseus of subjects (27.8 ± 8.1 years old) was recorded for as long as possible. The task was terminated when the isolated motor unit stopped discharging action potentials, despite the ability of the individual to sustain the abduction force. Twenty-three single motor units were recorded. Task duration was 21.4 ± 17.8 min. When analysed across discharge duration, mean discharge rate (10.6 ± 1.8 pulses s −1 ) and mean abduction force (5.5 ± 2.8% maximum) did not change significantly (discharge rate, P = 0.119; and abduction force, P = 0.235). In contrast, the coefficient of variation for interspike interval during the initial 30 s of the task was 22.2 ± 6.0% and increased to 31.9 ± 7.0% during the final 30 s (P < 0.001). All motor units were recruited again after 60 s of rest. Although subjects were able to sustain a relatively constant discharge rate, the cessation of discharge was preceded by a gradual increase in discharge variability. The findings also showed that the maximal duration of human motor unit discharge exceeds that previously reported for the discharge elicited in motor neurons by intracellular current injection in vitro.

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We demonstrate the fabrication of micropore and nanopore features in hollow antiresonant reflecting optical waveguides to create an electrical and optical analysis platform that can size select and detect a single nanoparticle. Micropores (4 μm diameter) are reactive-ion etched through the top SiO2 and SiN layers of the waveguides, leaving a thin SiN membrane above the hollow core. Nanopores are formed in the SiN membranes using a focused ion-beam etch process that provides control over the pore size. Openings as small as 20 nm in diameter are created. Optical loss measurements indicate that micropores did not significantly alter the loss along the waveguide.

Pascoe MA, Holmes MR, Enoka RM. Discharge characteristics of biceps brachii motor units at recruitment when older adults sustained an isometric contraction. J Neurophysiol 105: 571-581, 2011. First published December 15, 2010 doi:10.1152/jn.00841.2010. The purpose of this study was to compare the discharge characteristics of motor units recruited during an isometric contraction that was sustained with the elbow flexor muscles by older adults at target forces that were less than the recruitment threshold force of each isolated motor unit. The discharge times of 27 single motor units were recorded from the biceps brachii in 11 old adults (78.8 Ϯ 5.9 yr). The target force was set at either a relatively small (6.6 Ϯ 3.7% maximum) or large (11.4 Ϯ 4.5% maximum) difference below the recruitment threshold force and the contraction was sustained until the motor unit was recruited and discharged action potentials for about 60 s. The time to recruitment was longer for the large target-force difference (P ϭ 0.001). At recruitment, the motor units discharged repetitively for both target-force differences, which contrasts with data from young adults when motor units discharged intermittently at recruitment for the large difference between recruitment threshold force and target force. The coefficient of variation (CV) for the first five interspike intervals (ISIs) increased from the small (18.7 Ϯ 7.9) to large difference (35.0 Ϯ 10.2%, P ϭ 0.008) for the young adults, but did not differ for the two target force differences for the old adults (26.3 Ϯ 14.7 to 24.0 Ϯ 13.1%, P ϭ 0.610). When analyzed across the discharge duration, the average CV for the ISI decreased similarly for the two target-force differences (P ϭ 0.618) in old adults. These findings contrast with those of young adults and indicate that the integration of synaptic input during sustained contractions differs between young and old adults.

Federated multi-partner machine learning can be an appealing and efficient method to increase the effective training data volume and thereby the predictivity of models, particularly when the generation of training data is resource intensive. In the landmark MELLODDY project, each of ten pharmaceutical companies realized aggregated improvements on its own classification and/or regression models through federated learning. To this end, they leveraged a novel implementation extending multi-task learning across partners, on a platform audited for privacy and security. The experiments involved an unprecedented cross-pharma dataset of 2.6+ billion confidential experimental activity data points, documenting 21+ million physical small molecules and 40+ thousand assays in on-target and secondary pharmacodynamics and pharmacokinetics. Appropriate complementary metrics were developed to evaluate predictive performance in the federated setting. In addition to predictive performance increases in labeled space, the results point towards an extended applicability domain in federated learning. Increases in collective training data volume, including by means of auxiliary data resulting from single concentration high-throughput and imaging assays, continued to boost predictive performances, albeit with saturating return. Markedly higher improvements were observed for pharmacokinetics and safety panel assay-based task subsets.