The influence of frontal alignment in the advanced reciprocating gait orthosis on energy cost and crutch force requirements during paraplegic gait

Reduction of energy cost and upper body load during paraplegic walking is considered to be an important criterion in future developments of walking systems. A high energy cost limits the maximum walking distance in the current devices, whereas wrist and shoulder pathology can deteriorate because of the high upper body load. A change in alignment of the mechanical brace in the frontal plane, i.e. abduction, can contribute to a more efficient gait pattern with sufficient foot clearance with less pelvic lateral sway. A decrease in pelvic lateral sway after aligning in abduction results in a shift of the centre of mass to the swing leg crutch which may result in a decrease in required crutch force on stance side to maintain foot clearance. Five paraplegic subjects were provided with a standard Advanced Reciprocating Gait Orthosis (ARGO) and an ARGO aligned in 4 different degrees of abduction (0°, 3°, 6° and 9°). After determining an optimal abduction angle for each of the subjects, a cross over design was used to compare the ARGO with the individually optimised abducted orthosis. An abduction angle between 0° and 3° was chosen as optimal abduction angle. Subjects were not able to walk satisfactory with abduction angles 6° and 9°. A significant reduction in crutch peak force on stance side was found (approx. 12% , p < 0.01) in the abducted orthosis. Reduction in crutch force time integral (15%) as well as crutch peak force on swing side (5%) was not significant. No differences in oxygen uptake as well as oxygen cost was found. We concluded that an abduction angle between 0° and 3° is beneficial with respect to upper boHy load, whereas energy requirements did not change

HD Physiology Project-Japanese efforts to promote multilevel integrative systems biology and physiome research.

The HD Physiology Project is a Japanese research consortium that aimed to develop methods and a computational platform in which physiological and pathological information can be described in high-level definitions across multiple scales of time and size. During the 5 years of this project, an appropriate software platform for multilevel functional simulation was developed and a whole-heart model including pharmacokinetics for the assessment of the proarrhythmic risk of drugs was developed. In this article, we outline the description and scientific strategy of this project and present the achievements and influence on multilevel integrative systems biology and physiome research

Passive phloem loading and long-distance transport in a synthetic tree-on-a-chip

Vascular plants rely on differences of osmotic pressure to export sugars from regions of synthesis (mature leaves) to sugar sinks (roots, fruits). In this process, known as M\"unch pressure flow, the loading of sugars from photosynthetic cells to the export conduit (the phloem) is crucial, as it sets the pressure head necessary to power long-distance transport. Whereas most herbaceous plants use active mechanisms to increase phloem concentration above that of the photosynthetic cells, in most tree species, for which transport distances are largest, loading seems to occur via passive symplastic diffusion from the mesophyll to the phloem. Here, we use a synthetic microfluidic model of a passive loader to explore the nonlinear dynamics that arise during export and determine the ability of passive loading to drive long-distance transport. We first demonstrate that in our device, phloem concentration is set by the balance between the resistances to diffusive loading from the source and convective export through the phloem. Convection-limited export corresponds to classical models of M\"unch transport, where phloem concentration is close to that of the source; in contrast, diffusion-limited export leads to small phloem concentrations and weak scaling of flow rates with the hydraulic resistance. We then show that the effective regime of convection-limited export is predominant in plants with large transport resistances and low xylem pressures. Moreover, hydrostatic pressures developed in our synthetic passive loader can reach botanically relevant values as high as 10 bars. We conclude that passive loading is sufficient to drive long-distance transport in large plants, and that trees are well suited to take full advantage of passive phloem loading strategies

Design of an Elastic Actuation System for a Gait-Assistive Active Orthosis for Incomplete Spinal Cord Injured Subjects

A spinal cord injury severely reduces the quality of life of affected people. Following the injury, limitations of the ability to move may occur due to the disruption of the motor and sensory functions of the nervous system depending on the severity of the lesion. An active stance-control knee-ankle-foot orthosis was developed and tested in earlier works to aid incomplete SCI subjects by increasing their mobility and independence. This thesis aims at the incorporation of elastic actuation into the active orthosis to utilise advantages of the compliant system regarding efficiency and human-robot interaction as well as the reproduction of the phyisological compliance of the human joints. Therefore, a model-based procedure is adapted to the design of an elastic actuation system for a gait-assisitve active orthosis. A determination of the optimal structure and parameters is undertaken via optimisation of models representing compliant actuators with increasing level of detail. The minimisation of the energy calculated from the positive amount of power or from the absolute power of the actuator generating one human-like gait cycle yields an optimal series stiffness, which is similar to the physiological stiffness of the human knee during the stance phase. Including efficiency factors for components, especially the consideration of the electric model of an electric motor yields additional information. A human-like gait cycle contains high torque and low velocities in the stance phase and lower torque combined with high velocities during the swing. Hence, the efficiency of an electric motor with a gear unit is only high in one of the phases. This yields a conceptual design of a series elastic actuator with locking of the actuator position during the stance phase. The locked position combined with the series compliance allows a reproduction of the characteristics of the human gait cycle during the stance phase. Unlocking the actuator position for the swing phase enables the selection of an optimal gear ratio to maximise the recuperable energy. To evaluate the developed concept, a laboratory specimen based on an electric motor, a harmonic drive gearbox, a torsional series spring and an electromagnetic brake is designed and appropriate components are selected. A control strategy, based on impedance control, is investigated and extended with a finite state machine to activate the locking mechanism. The control scheme and the laboratory specimen are implemented at a test bench, modelling the foot and shank as a pendulum articulated at the knee. An identification of parameters yields high and nonlinear friction as a problem of the system, which reduces the energy efficiency of the system and requires appropriate compensation. A comparison between direct and elastic actuation shows similar results for both systems at the test bench, showing that the increased complexity due to the second degree of freedom and the elastic behaviour of the actuator is treated properly. The final proof of concept requires the implementation at the active orthosis to emulate uncertainties and variations occurring during the human gait

Increased gravitational force reveals the mechanical, resonant nature of physiological tremor

Human physiological hand tremor has a resonant component. Proof of this is that its frequency can be modified by adding mass. However, adding mass also increases the load which must be supported. The necessary force requires muscular contraction which will change motor output and is likely to increase limb stiffness. The increased stiffness will partly offset the effect of the increased mass and this can lead to the erroneous conclusion that factors other than resonance are involved in determining tremor frequency. Using a human centrifuge to increase head-to-foot gravitational field strength, we were able to control for the increased effort by increasing force without changing mass. This revealed that the peak frequency of human hand tremor is 99% predictable on the basis of a resonant mechanism. We ask what, if anything, the peak frequency of physiological tremor can reveal about the operation of the nervous system.This work was funded by a BBSRC Industry Interchange Award to J.P.R.S. and R.F.R. C.J.O. was funded by BBSRC grant BB/I00579X/1. C.A.V. was funded by A∗Midex (Aix-Marseille Initiative of Excellence

A metabolite-sensitive, thermodynamically-constrained model of\ud cardiac cross-bridge cycling: Implications for force development during ischemia

We present a metabolically regulated model of cardiac active force generation with which we investigate the effects of ischemia on maximum forceproduction. Our model, based on the Rice et al. (2008) model of cross-bridge kinetics, reproduces many of the observed effects of MgATP, MgADP, Pi and H+ on force development while still retaining the force/length/Ca2+ properties of the original model. We introduce three new parameters to account for the competitive binding of H+ to the Ca2+ binding site on troponin C and the binding of MgADP within the cross-bridge cycle. These parameters along with the Pi and H+ regulatory steps within the cross-bridge cycle were constrained using data from the literature and validated using a range of metabolic and sinusoidal length perturbation protocols. The placement of the MgADP binding step between two strongly-bound and force-generating states leads to the emergence of an unexpected effect on the force-MgADP curve, where the trend of the relationship (positive or negative) depends on the concentrations of the other metabolites and [H+]. The model is used to investigate the sensitivity of maximum force production to changes in metabolite concentrations during the development of ischemia

Rates of Performance Loss and Neuromuscular Activity in Men and Women During Cycling: Evidence for A Common Metabolic Basis of Muscle Fatigue

The durations that muscular force and power outputs can be sustained until failure fall predictably on an exponential decline between an individual’s 3-s burst maximum to the maximum performance they can sustain aerobically. The exponential time constants describing these rates of performance loss are similar across individuals, suggesting that a common metabolically based mechanism governs muscle fatigue; however, these conclusions come from studies mainly on men. To test whether the same physiological understanding can be applied to women, we compared the performance-duration relationships and neuromuscular activity between seven men [23.3 ± 1.9 (SD) yr] and seven women (21.7 ± 1.8 yr) from multiple exhaustive bouts of cycle ergometry. Each subject performed trials to obtain the peak 3-s power output (Pmax), the mechanical power at the aerobic maximum (Paer), and 11–14 constant-load bouts eliciting failure between 3 and 300 s. Collectively, men and women performed 180 exhaustive bouts spanning an ~6-fold range of power outputs (118–1116 W) and an ~35-fold range of trial durations (8–283 s). Men generated 66% greater Pmax (956 ± 109 W vs. 632 ± 74 W) and 68% greater Paer (310 ± 47 W vs. 212 ± 15 W) than women. However, the metabolically based time constants describing the time course of performance loss were similar between men (0.020 ± 0.003/s) and women (0.021 ± 0.003/s). Additionally, the fatigue-induced increases in neuromuscular activity did not differ between the sexes when compared relative to the pedal forces at Paer. These data suggest that muscle fatigue during short-duration dynamic exercise has a common metabolically based mechanism determined by the extent that ATP is resynthesized by anaerobic metabolism

Dislocation-mediated growth of bacterial cell walls

Recent experiments have illuminated a remarkable growth mechanism of rod-shaped bacteria: proteins associated with cell wall extension move at constant velocity in circles oriented approximately along the cell circumference (Garner et al., Science (2011), Dominguez-Escobar et al. Science (2011), van Teeffelen et al. PNAS (2011). We view these as dislocations in the partially ordered peptidoglycan structure, activated by glycan strand extension machinery, and study theoretically the dynamics of these interacting defects on the surface of a cylinder. Generation and motion of these interacting defects lead to surprising effects arising from the cylindrical geometry, with important implications for growth. We also discuss how long range elastic interactions and turgor pressure affect the dynamics of the fraction of actively moving dislocations in the bacterial cell wall.Comment: to appear in PNA