Inverse Dynamics Simulation Research Articles

Human Target Proteins for Benzo(a)pyrene and Acetaminophen (And Its Metabolites): Insights from Inverse Molecular Docking and Molecular Dynamics Simulations

Acetaminophen (APAP) is a widely used analgesic and antipyretic, whereas benzo(a)pyrene (B[a]P) is a carcinogen with significant global health risks due to environmental exposure. While APAP is generally safe at therapeutic doses, co-exposure to B[a]P can exacerbate its toxicity. This study aimed to identify potential human target proteins for B[a]P and APAP through inverse molecular docking and molecular dynamics simulations. We performed inverse docking with B[a]P, APAP, and three APAP metabolites against 689 human proteins involved in various biological processes. Five proteins were selected based on high docking affinity and their involvement in multiple pathways. Molecular dynamics simulations revealed that B[a]P primarily interacted via hydrophobic and π-stacking interactions with proteins like LXR-β, HSP90α, HSP90β, and AKT1, while AM404 formed hydrogen bonds and hydrophobic interactions. The simulations confirmed that the complexes had high conformational stability, except for protein AKT1. These results provide insights into the potential impacts of B[a]P and AM404 on protein functions and their implications for understanding the toxic effects of combined exposure.

Research into how carvacrol and metformin affect several human proteins in a hyperglycemic condition: A comparative study in silico and in vitro

Carvacrol (CV) is an organic compound found in the essential oils of many aromatic herbs. It is nearly unfeasible to analyze all the current human proteins for a query ligand using in vitro and in vivo methods. This study aimed to clarify whether CV possesses an anti-diabetic feature via Docking-based inverse docking and molecular dynamic (MD) simulation and in vitro characterization against a set of novel human protein targets. Herein, the best poses of CV docking simulations according to binding energy ranged from −7.9 to −3.5 (kcal/mol). After pathway analysis of the protein list through GeneMANIA and WebGestalt, eight interacting proteins (DPP4, FBP1, GCK, HSD11β1, INSR, PYGL, PPARA, and PPARG) with CV were determined, and these proteins exhibited stable structures during the MD process with CV. In vitro application, statistically significant results were achieved only in combined doses with CV or metformin. Considering all these findings, PPARG and INSR, among these target proteins of CV, are FDA-approved targets for treating diabetes. Therefore, CV may be on its way to becoming a promising therapeutic compound for treating Diabetes Mellitus (DM). Our outcomes expose formerly unexplored potential target human proteins, whose association with diabetic disorders might guide new potential treatments for DM.

Antiplasmodial potential of phytochemicals from Citrus aurantifolia peels: a comprehensive in vitro and in silico study

Phytochemical investigation of Key lime (Citrus aurantifolia L., F. Rutaceae) peels afforded six metabolites, known as methyl isolimonate acetate (1), limonin (2), luteolin (3), 3ˋ-hydroxygenkwanin (4), myricetin (5), and europetin (6). The structures of the isolated compounds were assigned by 1D NMR. In the case of limonin (2), further 1- and 2D NMR experiments were done to further confirm the structure of this most active metabolite. The antiplasmodial properties of the obtained compounds against the pathogenic NF54 strain of Plasmodium falciparum were assessed in vitro. According to antiplasmodial screening, only limonin (2), luteolin (3), and myricetin (5) were effective (IC50 values of 0.2, 3.4, and 5.9 µM, respectively). We explored the antiplasmodial potential of phytochemicals from C. aurantifolia peels using a stepwise in silico-based analysis. We first identified the unique proteins of P. falciparum that have no homolog in the human proteome, and then performed inverse docking, ΔGBinding calculation, and molecular dynamics simulation to predict the binding affinity and stability of the isolated compounds with these proteins. We found that limonin (2), luteolin (3), and myricetin (5) could interact with 20S a proteasome, choline kinase, and phosphocholine cytidylyltransferase, respectively, which are important enzymes for the survival and growth of the parasite. According to our findings, phytochemicals from C. aurantifolia peels can be considered as potential leads for the development of new safe and effective antiplasmodial agents.

Customized design and biomechanical property analysis of 3D-printed tantalum intervertebral cages.

Intervertebral cages used in clinical applications were often general products with standard specifications, which were challenging to match with the cervical vertebra and prone to cause stress shielding and subsidence. To design and fabricate customized tantalum (Ta) intervertebral fusion cages that meets the biomechanical requirements of the cervical segment. The lattice intervertebral cages were customized designed and fabricated by the selective laser melting. The joint and muscle forces of the cervical segment under different movements were analyzed using reverse dynamics method. The stress characteristics of cage, plate, screws and vertebral endplate were analyzed by finite element analysis. The fluid flow behaviors and permeability of three lattice structures were simulated by computational fluid dynamics. Compression tests were executed to investigate the biomechanical properties of the cages. Compared with the solid cages, the lattice-filled structures significantly reduced the stress of cages and anterior fixation system. In comparison to the octahedroid and quaddiametral lattice-filled cages, the bitriangle lattice-filled cage had a lower stress shielding rate, higher permeability, and superior subsidence resistance ability. The inverse dynamics simulation combined with finite element analysis is an effective method to investigate the biomechanical properties of the cervical vertebra during movements.

Extraction of actuator forces and displacements involved in human walking and running and estimation of time-series neural signals by inverse dynamics simulation

Extraction of actuator forces and displacements involved in human walking and running and estimation of time-series neural signals by inverse dynamics simulation

The gait1415+2 OpenSim musculoskeletal model of transfemoral amputees with a generic bone-anchored prosthesis

This short communication presents the gait1415+2 musculoskeletal model, that has been developed in OpenSim to describe the lower-extremity of a human subject with transfemoral amputation wearing a generic lower-limb bone-anchored prosthesis. The model has fourteen degrees of freedom, governed by fifteen musculotendon units (placed at the contralateral and residual limbs) and two generic actuators (one placed at the knee joint and one at the ankle joint of the prosthetic leg). Even though the model is a simplified abstraction, it is capable of generating a human-like walking gait and, specifically, it is capable of reproducing both the kinematics and the dynamics of a person with transfemoral amputation wearing a bone-anchored prosthesis during normal level-ground walking. The model is released as support material to this short communication with the final goal of providing the scientific community with a tool for performing forward and inverse dynamics simulations, and for developing computationally-demanding control schemes based on artificial intelligence methods for lower-limb prostheses.

Investigating the biomechanics of the biceps brachii muscle during dumbbell curl exercise: A comprehensive approach

Investigation of the mechanical behavior of the biceps brachii (BB) muscle at different dynamic forces is essential to improve training techniques, prevent sports injuries and optimize rehabilitation results. In previous studies, researchers studied mechanical changes during muscle contraction using various mathematical methods and simulation models. The models adopted by the majority of these studies assumed a constant value for muscle force. However, variable muscle force has different effects on muscle mechanics. In this study, an inverse dynamic simulation model was initially utilized to determine the dynamic muscle forces generated in the BB while performing the dumbbell curl exercise with 5 kg and 10 kg weights. Subsequently, the finite element method (FEM) was used to calculate the stress and strain changes experienced by BB as a consequence of the applied forces. Moreover, simultaneous analysis through electromyography (EMG) was carried out to investigate muscle contraction during the dumbbell curl exercise. Consequently, it was concluded that the average BB force during the dumbbell curl exercise with 5 kg and 10 kg weights was 433.9 N and 695.0 N, respectively. The maximum stresses in the BB during exercise were calculated to be 960.5 Pa and 1484.9 Pa, respectively. Additionally, the maximum displacements were determined to be 102.30 μm and 158.28 μm, respectively. According to the findings of muscle force 100% increase in dumbbell weight increases the maximum muscle force by 83.13% and the average muscle force by 60.17%. Therefore, it is understood that there was no linear correlation between weight gain and muscle force.

Effect of subscapularis repair on joint contact forces based on degree of posterior-superior rotator cuff tear severity in reverse shoulder arthroplasty.

Massive irreparable rotator cuff tears (RCTs) affect the clinical outcomes of reverse shoulder arthroplasty (RSA). However, the effects of subscapularis repair on the outcomes of RSA, based on the degree of posterior-superior RCTs, are unclear. This study aimed to examine the effect of subscapularis repair on three-dimensional joint contact forces (JCFs) based on the degree of posterior-superior RCT severity in RSA. Ten human in vivo experimental data were used as input to the musculoskeletal model. A six-degrees-of-freedom (DOF) anatomical shoulder model was developed and validated against three-dimensional JCFs. The 6-DOF musculoskeletal shoulder model of RSA was then developed by importing the reverse shoulder implant into the validated anatomical shoulder model. Based on the various types of posterior-superior RCT severity, inverse dynamic simulations of subscapularis-torn and subscapularis-repaired models of RSA were performed: from isolated supraspinatus tears to partial or massive tears of the infraspinatus and teres minor. The intact rotator cuff model of RSA was also simulated for comparison with the different types of models. Our results showed that the more posterior-superior RCTs progressed in RSA, the more superior JCFs were observed at 90°, 105°, and 120° abduction in the subscapularis-torn model. However, subscapularis repair decreased the superior JCF at those angles sufficiently. In addition, the teres minor muscle-tendon force increased as infraspinatus bundle tears progressed in both the subscapularis-torn and -repaired models, in order to compensate for the reduced force during abduction. However, the teres minor muscle-tendon force was not as high as that of the infraspinatus muscle-tendon, which could result in muscle force imbalance between repaired subscapularis and teres minor. Therefore, our results suggest that repairing the subscapularis and the repairable infraspinatus during RSA can improve glenohumeral joint stability in the superior-inferior direction by restoring muscle force balance between the anterior cuff (i.e., subscapularis) and posterior cuff (i.e., infraspinatus and teres minor). The findings of this study can help clinician decide whether to repair the rotator cuff during RSA to enhance joint stability.

Increase in lateral contact force in the tibiotalar joint during walking in flatfoot patients with reduced stiffness of the spring ligament

Foot deformities in patients with flexible flatfeet, such as the flattened medial arch and hindfoot valgus, affect the force distribution around the tibiotalar joint during walking and increase the risk of secondary injuries. In this study, we developed a multi-segment foot model that could calculate the dynamics around the tibiotalar joint and investigated the difference in the kinetics between normal feet and feet with flatfoot. Ten participants with normal feet and ten with flexible flatfoot were enrolled in the study. The body kinematics, ground reaction force, and foot pressure of the participants were recorded during walking. A five-segment foot model was developed to calculate contact forces in the tibiotalar joint. A flatfoot model was developed by modifying the stiffness of the spring ligaments of a normal foot model. Ground reaction force was applied to the plantar surface of the foot models. The foot models were attached to a full-body musculoskeletal model to conduct inverse dynamic simulations of walking. Participants with flatfoot had significantly greater lateral contact force (1.19 BW vs. 0.80 BW) and more posteriorly located center of pressure (33.7 % vs. 46.6 %) in the tibiotalar joint than those with normal feet (p < 0.05). The average and peak posterior tibialis muscle forces were significantly larger in participants with flatfoot than in those with normal feet (3.06 BW vs. 2.22 BW; 4.52 BW vs. 3.33 BW). The altered mechanics may influence the risk of arthritis.

Energy-Efficient Actuator Design Principles for Robotic Leg Prostheses and Exoskeletons: A Review of Series Elasticity and Backdrivability

AbstractRobotic leg prostheses and exoskeletons have traditionally been designed using highly-geared motor-transmission systems that minimally exploit the passive dynamics of human locomotion, resulting in inefficient actuators that require significant energy consumption and thus provide limited battery-powered operation or require large onboard batteries. Here we review two of the leading energy-efficient actuator design principles for legged and wearable robotic systems: series elasticity and backdrivability. As shown by inverse dynamic simulations of walking, there are periods of negative joint mechanical work that can be used to increase efficiency by recycling some of the otherwise dissipated energy using series elastic actuators and/or backdriveable actuators with energy regeneration. Series elastic actuators can improve shock tolerance during foot-ground impacts and reduce the peak power and energy consumption of the electric motor via mechanical energy storage and return. However, actuators with series elasticity tend to have lower output torque, increased mass and architecture complexity due to the added physical spring, and limited force and torque control bandwidth. High torque density motors with low-ratio transmissions, known as quasi-direct drives, can likewise achieve low output impedance and high backdrivability, allowing for safe and compliant human-robot physical interactions, in addition to energy regeneration. However, torque-dense motors tend to have higher Joule heating losses, greater motor mass and inertia, and require specialized motor drivers for real-time control. While each actuator design has advantages and drawbacks, designers should consider the energy-efficiency of robotic leg prostheses and exoskeletons during daily locomotor activities besides continuous level-ground walking.

Identification of source location in a single-sided building with natural ventilation: Case of interunit pollutant dispersion

A sudden outbreak of COVID-19 occurred in December 2019 and its rapid spread over the last two years caused a global pandemic. A special airborne transmission via aerosols called interunit dispersion is risky in a high-density urban environment, which needs more attention. In order to identify the source location of pollutants or viruses under the interunit transmission condition with natural ventilation, this study adopted the inverse Computational Fluid Dynamics (CFD) simulation with the adjoint probability method. The detailed process of the inverse modeling was presented. Also, the possible interunit transmission routes of the pollutants or viruses were analyzed. A three-story building model with single-sided openings was built. Six different combinations of fixed sensor locations were tested, and it was determined that setting sensors in the four corner regions of the building was the optimist strategy. A total of 25 cases with five different wind directions (0°, 45°, 90°, 135°, and 180°) were tested to verify the accuracy of the source location with inverse modeling. The results showed that 67%–78% of the rooms in the building can be identified with a limited number of pollutant sensors and all rooms can be identified with one additional sensor in the downstream room of the building under different wind direction. This research revealed that the inverse modeling method could be used to identify the pollutant source in the coupled indoor and outdoor environment. Further, this work can provide guidance for the pollutant monitor positions in the applications.

Evaluation of a machine-learning-driven active-passive upper-limb exoskeleton robot: Experimental human-in-the-loop study.

Evaluating exoskeleton actuation methods and designing an effective controller for these exoskeletons are both challenging and time-consuming tasks. This is largely due to the complicated human-robot interactions, the selection of sensors and actuators, electrical/command connection issues, and communication delays. In this research, a test framework for evaluating a new active-passive shoulder exoskeleton was developed, and a surface electromyography (sEMG)-based human-robot cooperative control method was created to execute the wearer's movement intentions. The hierarchical control used sEMG-based intention estimation, mid-level strength regulation, and low-level actuator control. It was then applied to shoulder joint elevation experiments to verify the exoskeleton controller's effectiveness. The active-passive assistance was compared with fully passive and fully active exoskeleton control using the following criteria: (1) post-test survey, (2) load tolerance duration, and (3) computed human torque, power, and metabolic energy expenditure using sEMG signals and inverse dynamic simulation. The experimental outcomes showed that active-passive exoskeletons required less muscular activation torque (50%) from the user and reduced fatigue duration indicators by a factor of 3, compared to fully passive ones.

A facile inverse dynamics method to study the impacts of fatigue on the lower limb biomechanics

ABSTRACT Fatigue can significantly affect the biomechanics of the anterior cruciate ligament (ACL) during single-legged jumping, and these changes are closely related to ACL injuries. Unfortunately, there is no convenient way to accurately and quickly track these changes. This present study aimed to develop such a method based on video capture and inverse dynamics simulation.Are our method’s results accurate and reliable? Fifteen participants performed sing-legged jumping before and after the fatigue protocol, and their actions were videotaped. The videos were processed and converted to marked motion data, used to drive the mannequin model in AnyBody Modelling System (AMS) for the inverse dynamics simulations. The ACL segment was also constructed based on one participant’s MRI data and added the mannequin model.Our results were similar to the findings from previous studies. Neuromuscular fatigue decreased the peak flexion angles and increased the low-the-limb muscle strength and activation. These alterations might contribute to ACL tears and ruptures. In addition, the simulation showed that the ACL force significantly (p < 0.05) increased as a result of fatigue during single-legged jumping. Our study provides a facile and reliable method to study the effects of neuromuscular fatigue on lower-the-limb biomechanics. Such a method can be applied to investigate other risk factors on ACL injuries and assist in developing workable plans for athlete training in the future.

Design of a Non-Back-Drivable Screw Jack Mechanism for the Hitch Lifting Arms of Electric-Powered Tractors

The agricultural sector is constantly evolving. The rise in the world’s population generates an increasingly growing demand for food, resulting in the need for the agroindustry to meet this demand. Tractors are the vehicles that have made a real difference in agriculture’s development throughout history, lowering costs in soil tillage and facilitating activities and operations for workers. This study aims to successfully design and build an autonomous, electric agricultural tractor that can autonomously perform recurring tasks in open-field and greenhouse applications. This project is fully part of the new industrial and agronomic revolution, known as Factory 4.0 and Agriculture 4.0. The predetermined functional requirements for the vehicle are its lightweight, accessible price, the easy availability of its spare parts, and its simple, ordinary maintenance. In this first study, the preliminary phases of sizing and conceptual design of the rover are reported before subsequently proceeding to the dynamical analysis. To optimize the design of the various versions of the automated vehicle, it is decided that a standard chassis would be built based on a robot operating inside a greenhouse on soft and flat terrains. The SimScape multi-body environment is used to model the kinematics of the non-back-drivable screw jack mechanism for the hitch-lifting arms. The control unit for the force exerted is designed and analyzed by means of an inverse dynamics simulation to evaluate the force and electric power consumed by the actuators. The results obtained from the analysis are essential for the final design of the autonomous electric tractor.

Computational modeling and simulation of closed chain arm-robot multibody dynamic systems in OpenSim

Rehabilitation robot efficacy for restoring upper extremity function post-stroke could potentially be improved if robot control algorithms accounted for patient-specific neural control deficiencies. As a first step toward the development of such control algorithms using model-based methods, this study provides general guidelines for creating and simulating closed chain arm-robot models in the OpenSim environment, along with a specific example involving a three-dimensional arm moving within a two degree-of-freedom upper extremity rehabilitation robot. The closed chain arm-robot model developed in OpenSim was evaluated using experimental robot motion and torque data collected from a single healthy subject under four conditions: 1) active robot alone, 2) active robot with passive arm, 3) passive robot with active arm, and 4) active robot with active arm. Computational verification of the combined model was performed for all four conditions, whereas experimental validation was performed for only the first two conditions since torque measurements were not available for the arm. For the four verification problems, forward dynamic simulations reproduced experimentally measured robot joint angles with average root-mean-square (RMS) errors of less than 0.3 degrees and correlation coefficients of 1.00. For the two validation problems, inverse dynamic simulations reproduced experimentally measured robot motor torques with average RMS errors less than or equal to 0.5 Nm and correlation coefficients between 0.92 and 0.99. If patient-specific muscle–tendon and neural control models can be successfully added in the future, the coupled arm-robot OpenSim model may provide a useful testbed for designing patient-specific robot control algorithms that facilitate recovery of upper extremity function post-stroke.

Prediction of 3D natural convection heat transfer characteristics in a shallow enclosure with experimental data

This study presents an inverse computational fluid dynamics (CFD) simulation combined with the least-squares method and overdetermined experimental temperature data to predict the unknown heat transfer rate Qh and three-dimensional (3D) natural convection heat transfer characteristics in a closed shallow enclosure. This novel study belongs to the inverse convection-conduction conjugate heat transfer problem. The results show that the zero-equation turbulence model is more suitable for this study compared to other flow models. Thus, the zero-equation model is chosen as the suitable flow model because its estimates are the closest to the experimental data and existing correlation. An important finding is that, for H/L = 1/15 and Ra = 1820, Bénard convection cells and eight vortices appear in 3D and two-dimensional (2D) temperature contours, respectively. This Ra value is close to the existing critical Rayleigh number of 1708. The arrangement of these cells and vortices can be merged with each other and reorganized as H/L increases. The obtained 2D velocity patterns and air temperature contours agree with existing patterns and isotherms. The obtained h‾hi values also agree well with the existing correlation. Thus, the present results have good accuracy. A review of the literature indicates that a few studies have been conducted on using the inverse method along with overdetermined experimental temperature data to study the present problem.

Kinematics and Dynamics Simulation of a Stewart Platform

Position and orientation adjustment of the secondary mirror is one of the effective ways to improve the image quality of space camera. In order to optimize the structural design of a 6-DOF Stewart platform for secondary mirror, simulation method of kinematics and dynamics of parallel manipulator based on virtual prototyping technology was studied. Firstly, the ADAMS parametric model and inverse mathematical model are built. Secondly, theory analysis of inverse kinematics of Stewart platform was performed, and the analytical results of inverse kinematics were obtained by mathematical modeling. Thirdly, simulation of inverse kinematics run in ADAMS after the virtual prototype of parallel manipulator was established. The simulation results in ADAMS and analysis results are consistent, which proved the correctness of the virtual prototype model. Lastly, the kinematics and inverse dynamics simulation were realized by driving each strut using result of inverse kinematics. The analysis method of kinematics and dynamics of parallel manipulator provided a theoretical basis for optimizing design of a Stewart platform.

Fractional-Order PIλDμ Controller Using Adaptive Neural Fuzzy Model for Course Control of Underactuated Ships

For the uncertainty caused by the time-varying modeling parameters with the sailing speed in the course control of underactuated ships, a novel identification method based on an adaptive neural fuzzy model (ANFM) is proposed to approximate the inverse dynamic characteristics of the ship in this paper. This model adjusts both its own structure and parameters as it learns, and is able to automatically partition the input space, determine the number of membership functions and the number of fuzzy rules. The trained ANFM is used as an inverse controller, in parallel with a fractional-order PIλDμ controller for the course control of underactuated ships. Meanwhile, the sine wave curve and the sawtooth wave curve are considered as the input learning samples of ANFM, respectively, and the inverse dynamics simulation experiments of the ship are carried out. Two different ANFM structures are obtained, which are connected in parallel with the fractional-order PIλDμ controller respectively to control the course of ship. The simulation results show that the proposed method can effectively overcome the influence of uncertainty of ship modeling parameters, track the desired course quickly and effectively, and has a good control effect. Finally, comparative experiments of four different controllers are carried out, and the results show that the FO PIλDμ controller using ANFM has the advantages of small overshoot, short adjustment time, and precise control.

Dynamic Parameter Identification of a Human-Exoskeleton System With the Motor Torque Data

The objective of this paper is to identify dynamic parameters of the human-exoskeleton system (HES) with the motor torque data considering modeling the passive elastic joint torque of the user. Based on a lower limb exoskeleton prototype we recently developed, the dynamics of the joint actuators and two degrees of freedom link-based swing leg are firstly modeled. The passive elasticity of the human joint is modeled by double-exponential equations. Systematic experiments are then conducted, during which the motor current is measured to compute the motor torque for identification. Finally, the dynamic parameters of the joint actuators, the exoskeleton leg and the human-exoskeleton leg are successively identified. The identification is implemented through the off-line inverse dynamic model simulation with the measured motor torque data. A consistent tendency is found between the simulated motor torque after identification and the measured one. This demonstrates the validity of the identification method proposed. This paper provides a systemic method of identifying the HES with the motor torque data and enriches the experimental proof that the double-exponential model is feasible to describe the passive elastic joint torque.

Dynamic Modeling and Solution of 6-DOF Parallel Mechanism

When a parallel robot used in a scene that requires force control, rapid attitude adjustment, or precise positioning, we need to know the dynamic characteristics of the moving platform and the motion branch, so it is necessary to do the dynamic analysis of the parallel robot. In this study, for the six-degree-of-freedom parallel mechanism, the Newton-Eulerian method is used to model the dynamics, and then the inverse dynamics simulation is performed through the ADAMS simulation software to verify the correctness of the established dynamic equations. Finally, the Euler integration method is used to solve the dynamic equations numerically. When establishing dynamic equations, it is more convenient to use spiral coordinates to express the angular motion of the motion platform of the parallel mechanism. However, it is difficult to solve the equation numerically. When solving the equations in this study, Euler angles are used to express angular motion. The Euler angle is used as an iterative variable representing the angular motion in the solving process. Then the Euler angle is converted into a rotation matrix, and the parameters of the spiral coordinates are obtained through the rotation matrix, and the dynamic equation is finally solved. The simulation and calculation results show that the established dynamic equation is correct, and the solution to the dynamic equation is also correct.