Muscle demand and kinematic similarities between pediatric-modified motor-assisted elliptical training at fast speed and fast overground walking: Real-world implications for pediatric gait rehabilitation

The purpose of this research was to compare children’s lower extremity muscle activity and kinematics while walking at fast pace and training at fast speeds with and without motor-assistance on a pediatric-modified motor-assisted elliptical. Twenty-one children without disabilities were recruited and fifteen completed all three training conditions at self-selected fast pace. Repeated-measures ANOVAs identified muscle demand (peak, mean, duration) differences across device conditions and fast walking. Root mean square error compared overall kinematic profiles and statistical parametric mapping identified kinematic differences between conditions. Motor-assisted training reduced lower extremity muscle demands compared to training without the motor’s assistance (16 of 21 comparisons) and to fast walking (all but one comparison). Training without the motor’s assistance required less muscle effort than fast walking (16 of 21 comparisons). Kinematic differences between device conditions and fast walking were greater distally (thigh, knee, ankle) than proximally (trunk, pelvis, hip). In summary, transitioning from training with to without the motor’s assistance promoted progressively greater activity across the lower extremity muscles studied, with sagittal plane kinematic changes most apparent at the distal joints. Our findings highlight how motor-assistance can be manipulated to customize physiologic challenges to lower extremity muscles prior to fast overground walking.     

Real-time inverse kinematics and inverse dynamics for lower limb applications using OpenSim

Real-time estimation of joint angles and moments can be used for rapid evaluation in clinical, sport, and rehabilitation contexts. However, real-time calculation of kinematics and kinetics is currently based on approximate solutions or generic anatomical models. We present a real-time system based on OpenSim solving inverse kinematics and dynamics without simplifications at 2000 frame per seconds with less than 31.5 ms of delay. We describe the software architecture, sensitivity analyses to minimise delays and errors, and compare offline and real-time results. This system has the potential to strongly impact current rehabilitation practices enabling the use of personalised musculoskeletal models in real-time.     

An improved inverse dynamics formulation for estimation of external and internal loads during human sagittal plane movements

Planar musculoskeletal models are common in the inverse dynamics analysis of human movements such as walking, running and jumping. The continued interest in such models is justified by their simplicity and computational efficiency. Related to a human planar model, a unified formulation for both the flying and support phases of the sagittal plane movements is developed. The actuation involves muscle forces in the lower limbs and the resultant muscle torques in the other body joints. The dynamic equations, introduced in absolute coordinates of the segments, are converted into useful compact forms using the projective technique. The solution to a determinate inverse dynamics problem allows for the explicit determination of the external reactions (presumed to vanish during the flying phases) and the resultant muscle torques in all the model joints. The indeterminate inverse dynamics problem is then focused on the assessment of muscle forces and joint reaction forces selectively in the supporting lower limb. Numerical results of the inverse dynamics simulation of sample sagittal plane movements are reported to illustrate the validity and effectiveness of the improved formulation.     

A two-dimension otolith growth inverse model

An inverse growth model was developed to describe fish otolith ontogenetic growth to find the most parsimonious growth field that drives the actual shape of an internal incremental structure to the actual external shape of the otolith. This approach is based in a pure physic model, and the single implicit assumption was that the otolith accretion occurred perpendicular to its external surface. The model could be used to define a general hypothesis situation, in the sense that it predicts the most plausible shape of the otolith at any time, assuming that no additional external forces have acted. Therefore, severe departures between the observed growth structure and the closest prediction to it could be used to identify anatomical constraints and physiological factors that modulate the pure physical expectations.     

Molecular dynamics studies of alanine racemase: a structural model for drug design

Alanine racemase (AlaR) is a bacterial enzyme that catalyzes the interconversion of L- and D-alanine, which is an essential constituent of the peptidoglycan layer of the bacterial cell wall and requires pyridoxal 5'-phosphate (PLP) as a cofactor. The enzyme is universal to bacteria, including mycobacteria, making it an attractive target for drug design. To investigate the effects of flexibility on the binding modes of the substrate and an inhibitor and to analyze how the active site is affected by the presence of the substrate versus inhibitor, a molecular dynamics simulation on the full AlaR dimer from Bacillus stearothermophilus (pdb code: 1SFT) with a D-alanine molecule in one active site and the noncovalent inhibitor, propionate, in the second site has been carried out. Within the time scale of the simulation, we show that the active site becomes more stabilized in the presence of substrate versus inhibitor. The results of this simulation are in agreement with the proposed mechanism of alanine racemase reaction in which the substrate carboxyl group directly participates in the catalysis by acting cooperatively with Tyr 265' and Lys 39. A structural water molecule in contact with both substrate and inhibitor (i.e., in both active sites) and bridging residues in both active sites was identified. It shows a remarkably low mobility and does not exchange with bulk water. This water molecule can be taken into account for the design of specific AlaR inhibitors by either utilizing it as a bridging group or displacing it with an inhibitor atom. The results presented here provide insights into the dynamics of the alanine racemase in the presence of substrate/inhibitor, which will be used for the rational design of novel inhibitors.     

A bipedal compliant walking model generates periodic gait cycles with realistic swing dynamics

A simple spring mechanics model can capture the dynamics of the center of mass (CoM) during human walking, which is coordinated by multiple joints. This simple spring model, however, only describes the CoM during the stance phase, and the mechanics involved in the bipedality of the human gait are limited. In this study, a bipedal spring walking model was proposed to demonstrate the dynamics of bipedal walking, including swing dynamics followed by the step-to-step transition. The model consists of two springs with different stiffnesses and rest lengths representing the stance leg and swing leg. One end of each spring has a foot mass, and the other end is attached to the body mass. To induce a forward swing that matches the gait phase, a torsional hip joint spring was introduced at each leg. To reflect the active knee flexion for foot clearance, the rest length of the swing leg was set shorter than that of the stance leg, generating a discrete elastic restoring force. The number of model parameters was reduced by introducing dependencies among stiffness parameters. The proposed model generates periodic gaits with dynamics-driven step-to-step transitions and realistic swing dynamics. While preserving the mimicry of the CoM and ground reaction force (GRF) data at various gait speeds, the proposed model emulated the kinematics of the swing leg. This result implies that the dynamics of human walking generated by the actuations of multiple body segments is describable by a simple spring mechanics.     

基于系统动力学的辽宁省水环境承载力模拟与预测

应用系统动力学方法建立了水环境承载力模型,并结合层次分析法和向量模法,模拟了辽宁省水环境系统的动态变化,预测了2000-2050年辽宁省水环境在不同发展方案下的承载能力.结果表明：若保持现行发展方案不变,2000-2050年,辽宁省水环境承载力将呈逐年下降趋势;仅增加水资源供给、不进行科学合理的水环境保护与治理,将无法提高该区域水环境承载能力;只有将开源、节流、治污、减排等多种手段相结合,才能有效提高辽宁省水环境承载能力,促进该地区经济、社会和环境的协调发展.     

A statistical light scattering approach to separating fast and slow dynamics

Light scattering is a powerful technique to study the structural and dynamical properties of biomolecular systems or other soft materials such as polymeric solutions and blends or gels. An important application of this technique is the study of the kinetics of formation of supramolecular structures. However, in such cases, the system under study is rapidly changing, and consequently the integration time for each measurement is limited. In order to overcome this difficulty, a statistical approach has been developed based on the analysis of the scattered light intensity distribution (Manno et al. 2006, 2004). Indeed the intensity distribution depends upon the ratio between the integration time of each measurement and the coherence time of scattered radiation. This method has been applied to protein aggregation (Manno et al. 2006) and to sol-gel transition (Manno et al. 2004), to obtain information on the heterogeneity of morphological and dynamical features during such processes. In the present work, we accurately test the validity of this approach by analyzing the statistical properties of the light scattered by a model system: a solution of polystyrene spherical macromolecules of different sizes. Each molecular size is related to a given diffusion coefficient and to a given coherence time of the scattered intensity. The effect of changing the experimental integration time is systematically investigated. A mixture of particles of two different sizes is also analyzed to test the validity and robustness of the model based on the convolution of a gaussian with an exponential distribution. Proceedings of the XVIII Congress of the Italian Society of Pure and Applied Biophysics (SIBPA), Palermo, Sicily, September 2006.     

A procedure to estimate normal and friction contact parameters in the stance phase of the human gait

A new approach to estimate normal and tangential contact parameters in the foot-ground contact during human gait was proposed. A correct estimation of the contact parameters would be very important in the resolution of predictive forward dynamic problems. The normal contact forces have been well estimated in the literature. But accurate estimation of tangential forces has not been reached yet. This work proposed a new procedure to accurately estimate friction forces. The approach has been based on the consideration of the modulus of the tangential force instead of its components. This modulus was introduced together with the modulus of the normal contact force and its two associated moments in an optimization algorithm to fit the contact forces provided by the model to the experimental data obtained with a force plate. An inverse dynamics problem was solved as a step previous to the optimization algorithm. The results showed that both the normal and tangential forces and the moments in the horizontal plane were in agreement with the experimental measurements. This work also analyzed the influence on the results of the friction law. The results obtained with the general friction law, which considered dry (static and dynamic) and viscous friction, were compared with results provided by simpler laws. The analysis of the components of the friction forces pointed out the importance of the Stribeck component in the resultant force instead of the viscous friction which played a minimal role. But for modelling the stick-slip transition, the implementation of a general friction law is necessary.     

A novel protocol of energy optimisation for predicted protein structures built by homology modelling

Homology modelling was applied to predict the three-dimensional (3D) structures of six sets of lipase proteins. Sequence identities between the target and template were 34.6, 44.9, 57.4, 69.9, 79.0 and 86.2%, respectively. Then, eight different protocols including three optimising factors [periodically bounded cell (PBC) water, molecular dynamics (MD) simulation, ‘grade-unpacking’ strategy or ‘combinatorial’ strategy] were used to refine the initial model of each system. By comparing the energy-optimised models with the true 3D structure of the target protein in terms of all backbone atoms' root mean square deviation, we determined a novel but all-purpose protocol for model refinement. The protocol refined a homology model by adopting the ‘grade-unpacking’ strategy for energy minimisation while the model was solvated in PBC water. Furthermore, by comparing the influence of each single optimising factor on the accuracy of the refined structure, we found that introducing the MD simulation into the model refinement method would decrease the accuracy of the final protein structure while methods with either PBC water or the ‘grade-unpacking’ strategy would increase the accuracy of the final model.     

A fast generalizable solution method for glucose control algorithms

In critical care tight control of blood glucose levels has been shown to lead to better clinical outcomes. The need to develop new protocols for tight glucose control, as well as the opportunity to optimize a variety of other drug therapies, has led to resurgence in model-based medical decision support in this area. One still valid hindrance to developing new model-based protocols using so-called virtual patients, retrospective clinical data, and Monte Carlo methods is the large amount of computational time and resources needed.This paper develops fast analytical-based methods for insulin-glucose system model that are generalizable to other similar systems. Exploiting the structure and partial solutions in a subset of the model is the key in finding accurate fast solutions to the full model. This approach successfully reduced computing time by factors of 5600-144 000 depending on the numerical error management method, for large (50-164 patients) virtual trials and Monte Carlo analysis. It thus allows new model-based or model-derived protocols to be rapidly developed via extensive simulation. The new method is rigorously compared to existing standard numerical solutions and is found to be highly accurate to within 0.2%.     

Molecular dynamics studies of the conformation of sorbitol

Molecular dynamics simulations of a 3 molal aqueous solution of d-sorbitol (also called d-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data support a more bent structure.     

Conformations of a model cyclic hexapeptide,CYIQNC: 1H-NMR and molecular dynamics studies

Solution conformation of the cyclic hexapeptide sequence, [cyclo-S-Cys-Tyr-Ile-Gln-Asn-Cys-S] (CYIQNC) – a disulfide-linked fragment of a neurohypophyseal peptide hormone oxytocin (OT) – has been investigated by high-field one-dimensional (1D) and two-dimensional (2D) NMR spectroscopic methods and compared with the results obtained from computer simulation studies. ¹H-NMR results based on temperature dependence of amide proton chemical shifts and nuclear Overhauser effect indicate that peptide in solution populates different conformations, characterized by two fused β-turns. The segment Ile³-Gln⁴-Asn⁵-Cys⁶ yields a preferred type-III β-turn at residues 4, 5 (HB, 3HN → 6CO), while the segment Cys⁶, Cys¹-Tyr²-Ile³ exhibits inherently weaker, flexible β-turn either of type I/II’/III/half-turn at residues 1, 2 (HB, 6HN → 3CO). The computer simulation studies using a mixed protocol of distance geometry-simulated annealing followed by constrained minimization, restrained molecular dynamics, and energy minimization showed the possibility of existence of additional conformations with the hydrogen bonds, (a) 5HN → 3CO and (b) 2HN → 6CO. These results, therefore, indicate that the additional conformations obtained from both NMR and simulation studies can also be possible to the peptide. These additional conformations might have very small population in the solution and did not show their signatures in these conditions. These findings will be helpful in designing more analogs with modifications in the cyclic moiety of OT.     

A fast algorithm for Bayesian multi-locus model in genome-wide association studies

Genome-wide association studies (GWAS) have identified a large amount of single-nucleotide polymorphisms (SNPs) associated with complex traits. A recently developed linear mixed model for estimating heritability by simultaneously fitting all SNPs suggests that common variants can explain a substantial fraction of heritability, which hints at the low power of single variant analysis typically used in GWAS. Consequently, many multi-locus shrinkage models have been proposed under a Bayesian framework. However, most use Markov Chain Monte Carlo (MCMC) algorithm, which are time-consuming and challenging to apply to GWAS data. Here, we propose a fast algorithm of Bayesian adaptive lasso using variational inference (BAL-VI). Extensive simulations and real data analysis indicate that our model outperforms the well-known Bayesian lasso and Bayesian adaptive lasso models in accuracy and speed. BAL-VI can complete a simultaneous analysis of a lung cancer GWAS data with ~3400 subjects and ~570,000 SNPs in about half a day.     

A dynamic global vegetation model for use with climate models: concepts and description of simulated vegetation dynamics

Changes in vegetation structure and biogeography due to climate change feedback to alter climate by changing fluxes of energy, moisture, and momentum between land and atmosphere. While the current class of land process models used with climate models parameterizes these fluxes in detail, these models prescribe surface vegetation and leaf area from data sets. In this paper, we describe an approach in which ecological concepts from a global vegetation dynamics model are added to the land component of a climate model to grow plants interactively. The vegetation dynamics model is the Lund–Potsdam–Jena (LPJ) dynamic global vegetation model. The land model is the National Center for Atmospheric Research (NCAR) Land Surface Model (LSM). Vegetation is defined in terms of plant functional types. Each plant functional type is represented by an individual plant with the average biomass, crown area, height, and stem diameter (trees only) of its population, by the number of individuals in the population, and by the fractional cover in the grid cell. Three time‐scales (minutes, days, and years) govern the processes. Energy fluxes, the hydrologic cycle, and carbon assimilation, core processes in LSM, occur at a 20 min time step. Instantaneous net assimilated carbon is accumulated annually to update vegetation once a year. This is carried out with the addition of establishment, resource competition, growth, mortality, and fire parameterizations from LPJ. The leaf area index is updated daily based on prevailing environmental conditions, but the maximum value depends on the annual vegetation dynamics. The coupling approach is successful. The model simulates global biogeography, net primary production, and dynamics of tundra, boreal forest, northern hardwood forest, tropical rainforest, and savanna ecosystems, which are consistent with observations. This suggests that the model can be used with a climate model to study biogeophysical feedbacks in the climate system related to vegetation dynamics.     

INSTAR,a discrete event model for simulating zooplankton population dynamics

In this paper we discuss the basic principles of discrete event, individual oriented, data based modelling in ecology, and we present an application of this modelling strategy. The strategy is contrasted with some more conventional modelling strategies with respect to its purpose, its basic units and its heuristic properties.INSTAR applies this modelling strategy to the simulation of the fluctuations of the population structure and density of microcrustaceans through the year. The model encompasses one microcrustacean species at a time, and its interface with the rest of the ecosystem; it has been applied to several Cladocera and Copepoda species in a shallow eutrophic lake in the Netherlands (Vijverberg & Richter 1982a, b). Possibilities for extending the model are discussed.