Trajectory tracking control of a hydraulic-tendon actuator with an application to the exoskeleton

This paper presents a hydraulic actuator and tendon drive system that was specifically designed for a lower-limb exoskeleton to provide high power and low inertia. The dynamics of the actuator-tendon system were analyzed based on the exoskeleton system and an adaptive sliding-mode trajectory tracking controller was designed for the drive system. The stability proof indicates that the controller is globally stable. The experimental results demonstrated that the controller provides high tracking accuracy and is robust to external disturbances and unmodeled nonlinearities. Moreover, the controller has less errors than the conventional PID controller. Further tests that included the joints of the exoskeleton were conducted to verify the performance of the controller

Kinematics analysis and optimization of the exoskeleton’s knee joint

Two major defects of the exoskeleton’s single-axis knee joint were exposed in human-machine coordination experiments, which are chattering of hip and knee joints and pull-feeling at ankle joint. In order to analyze and solve these issues, human gait experiments were conducted to obtain the human gait data, and a kinematic model of the exoskeleton was established. Kinematics analysis of the exoskeleton based on the human’s hip and knee joint angles indicated the obvious human-machine ankle joint movement error; inverse kinematics analysis of the exoskeleton according to the human ankle joint trajectory reflected the abrupt angle changes of exoskeleton’s hip and knee joints. According to these analysis results, kinematics differences between the exoskeleton’s single-axis knee joint and human’s trochlea knee joint were regarded as the primary cause of the defects observed in human-machine coordination experiments. The exoskeleton’s knee joint was optimized in four-bar linkage type to imitate the kinematics characteristics of human’s knee joint. Kinematics simulation results of the optimized exoskeleton showed that human-machine ankle joint movement error and abrupt angle changes of the exoskeleton’s hip and knee joints have been both significantly reduced, thus the effectiveness of the exoskeleton’s knee joint optimization for improving the human-machine coordination could be confirmed

Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers

AbstractBackgroundFew pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China.Purpose1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions.MethodsThis open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests.ResultsTotally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94±6.59 and 9.47±5.47h, Cmax 435.74±348.10 and 346.54±155.66ng·mL−1, AUC0-t 8600.52±5264.77 and 9315.10±6820.03ng·mL−1·h, AUC0–∞ 8845.38±5838.18 and 9669.24±7326.53ng·mL−1·h, t1/2 10.06±8.83 and 9.87±10.35h; single dosing under fasting conditions, Tmax 7.29±4.87 and 6.57±1.85h, Cmax 247.85±110.05 and 244.64±132.43ng·mL−1, AUC0-t 3385.41±1418.92 and 3496.24±1767.29ng·mL−1·h, AUC0–∞ 3781.53±1556.96 and 3829.56±1981.25ng·mL−1·h, t1/2 13.07±17.24 and 10.26±7.78h; single dosing under fed conditions, Tmax 17.72±9.42 and 19.50±9.84h, Cmax 183.90±74.52 and 168.14±60.67ng·mL−1, AUC0-t 3181.71±1368.24 and 3575.11±1416.39ng·mL−1·h, AUC0–∞3442.39±2002.53 and 3624.44±1418.12ng·mL−1·h, t1/2 8.76±12.28 and 6.67±4.84h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC0–t and AUC0–∞ were located within 80%–125%, 90% CI for Cmax was within 70%–143%.ConclusionsSimilar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence.Chictr.org identifier: ChiCTR-TTRCC-14004853

Deletion of heat shock protein 60 in adult mouse cardiomyocytes perturbs mitochondrial protein homeostasis and causes heart failure.

To maintain healthy mitochondrial enzyme content and function, mitochondria possess a complex protein quality control system, which is composed of different endogenous sets of chaperones and proteases. Heat shock protein 60 (HSP60) is one of these mitochondrial molecular chaperones and has been proposed to play a pivotal role in the regulation of protein folding and the prevention of protein aggregation. However, the physiological function of HSP60 in mammalian tissues is not fully understood. Here we generated an inducible cardiac-specific HSP60 knockout mouse model, and demonstrated that HSP60 deletion in adult mouse hearts altered mitochondrial complex activity, mitochondrial membrane potential, and ROS production, and eventually led to dilated cardiomyopathy, heart failure, and lethality. Proteomic analysis was performed in purified control and mutant mitochondria before mutant hearts developed obvious cardiac abnormalities, and revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria. We also utilized an in vitro system to assess the effects of HSP60 deletion on mitochondrial protein import and protein stability after import, and found that both HSP60-dependent and HSP60-independent mitochondrial proteins could be normally imported in mutant mitochondria. However, the former underwent degradation in mutant mitochondria after import, suggesting that the protein exhibited low stability in mutant mitochondria. Interestingly, the degradation could be almost fully rescued by a non-specific LONP1 and proteasome inhibitor, MG132, in mutant mitochondria. Therefore, our results demonstrated that HSP60 plays an essential role in maintaining normal cardiac morphology and function by regulating mitochondrial protein homeostasis and mitochondrial function