Sarcoglycans in muscular dystrophy

Muscular dystrophy is a heterogeneous genetic disease that affects skeletal and cardiac muscle. The genetic defects associated with muscular dystrophy include mutations in dystrophin and its associated glycoproteins, the sarcoglycans. Furthermore, defects in dystrophin have been shown to cause a disruption of the normal expression and localization of the sarcoglycan complex. Thus, abnormalities of sarcoglycan are a common molecular feature in a number of dystrophies. By combining biochemistry, molecular cell biology, and human and mouse genetics, a growing understanding of the sarcoglycan complex is emerging. Sarcoglycan appears to be an important, independent mediator of dystrophic pathology in both skeletal muscle and heart. The absence of sarcoglycan leads to alterations of membrane permeability and apoptosis, two shared features of a number of dystrophies. beta-sarcoglycan and delta-sarcoglycan may form the core of the sarcoglycan subcomplex with alpha- and gamma-sarcoglycan less tightly associated to this core. The relationship of epsilon-sarcoglycan to the dystrophin-glycoprotein complex remains unclear. Animals lacking alpha-, gamma- and delta-sarcoglycan have been described and provide excellent opportunities for further investigation of the function of sarcoglycan. Dystrophin with dystroglycan and laminin may be a mechanical link between the actin cytoskeleton and the extracellular matrix. By positioning itself in close proximity to dystrophin and dystroglycan, sarcoglycan may function to couple mechanical and chemical signals in striated muscle. Sarcoglycan may be an independent signaling or regulatory module whose position in the membrane is determined by dystrophin but whose function is carried out independent of the dystrophin-dystroglycan-laminin axis.     

Merosin and congenital muscular dystrophy

Merosin (also called as Laminin-2) is an isoform of laminin comprised of the alpha2, beta1 and gamma1 chains. In European populations, half of the patients with classical congenital muscular dystrophy have mutations of the LAMA2 gene (6q22-23) and present reduced or absence of laminin alpha2 chain. This form is generally referred to as merosin-deficient CMD. Merosin-deficient CMD is characterized by involvement of not only skeletal muscle but also central and peripheral nervous systems: Extensive brain white matter abnormalities are found by magnetic resonance imaging (MRI). However, most patients show no mental retardation. Recent case studies reported that some patients have several structural abnormalities such as abnormal cerebral cortical gyration, hypoplasia of cerebellum and pons, and dilation of ventricles. At present, functions of merosin related to muscle degeneration have not been fully elucidated. In addition, the mechanisms responsible for pathogenesis of diffuse brain white matter abnormalities remain to be determined. As mouse models for merosin-deficient CMD, three spontaneous mutants(dy, dy(2J), dy(PAS1)) and two mutants named dy(W) and dy(3K) by targeted gene disruption have been reported. These mice will help to elucidate the pathogenesis of merosin-deficient CMD and serve to develop therapy.     

Immunocytochemical analysis of human muscular dystrophy

Immunocytochemistry is an essential tool for the assessment of muscle biopsies from patients with muscular dystrophy, especially the recessive forms. Antibodies can detect primary defects when there is an alteration in expression, in particular in Xp21 muscular dystrophies, Emery-Dreifuss muscular dystrophy, the limb-girdle dystrophies caused by abnormal expression of the sarcoglycans, and in the form of congenital muscular dystrophy linked to the gene for laminin alpha2. Absence of a protein is easily observed and reduction in expression can be assessed provided adequate controls and baselines are established. Assessment of secondary defects can also be of diagnostic value; they widen the understanding of pathology changes, and are helping in the development of therapeutic strategies.     

Developments in gene therapy for muscular dystrophy

Gene therapy for muscular dystrophy (MD) presents significant challenges, including the large amount of muscle tissue in the body, the large size of many genes defective in different muscular dystrophies, and the possibility of a host immune response against the therapeutic gene. Overcoming these challenges requires the development and delivery of suitable gene transfer vectors. Encouraging progress has been made in modifying adenovirus (Ad) vectors to reduce immune response and increase capacity. Recently developed gutted Ad vectors can deliver full-length dystrophin cDNA expression vectors to muscle tissue. Using muscle-specific promoters to drive dystrophin expression, a strong immune response has not been observed in mdx mice. Adeno-associated virus (AAV) vectors can deliver small genes to muscle without provocation of a significant immune response, which should allow long-term expression of several MD genes. AAV vectors have also been used to deliver sarcoglycan genes to entire muscle groups. These advances and others reviewed here suggest that barriers to gene therapy for MD are surmountable.     

Towards the control of a powered orthosis for people with muscular dystrophy.

The paper describes the development of a passive/active orthosis for people with limited anti-gravity strength in their arms. This is symptomatic of conditions such as muscular dystrophy and spinal muscular atrophy. A passive orthosis was designed and developed using linear elastic elements. The system is being tested with children with disabilities and preliminary results are encouraging. An RT200 robot was also used as a test-bed for an active orthosis. The robot was instrumented with a six-axis force/torque sensor at the end-effector. The force acted as the input to the robot. The robot kinematics and dynamics were modelled. A number of control schemes were implemented on the test-bed including force proportional to velocity and acceleration; these schemes were evaluated with two subjects.     

Variations in several acoustic emission parameters during testing of low-carbon steel specimens

The acoustic emissions that are formed during tension of specimens made from low-carbon steels is investigated. Interpretation of the experimental data is made from the point of view of real tests of engineering objects made from low-carbon steels in order to analyze the correlation of informative parameters with the deflected mode of a metal.     

Morphological and ultrastructural evaluation of the golden retriever muscular dystrophy trachea,lungs, and diaphragm muscle

Duchenne muscular dystrophy (DMD) is a genetic disease, characterized by atrophy and muscle weakness. The respiratory failure is a common cause of early death in patients with DMD. Golden retriever muscular dystrophy (GRMD) is a canine model which has been extensively used for many advances in therapeutics applications. As the patients with DMD, the GRMD frequently died from cardiac and respiratory failure. Observing the respiratory failure in DMD is one of the major causes of mortality we aimed to describe the morphological and ultrastructural data of trachea, lungs (conductive and respiratory portion of the system), and diaphragm muscle using histological and ultrastructural analysis. The diaphragm muscle showed discontinuous fibers architecture, with different diameter; a robust perimysium inflammatory infiltrate and some muscle cells displayed central nuclei. GRMD trachea and lungs presented collagen fibers and in addition, the GRMD lungs showed higher of levels collagen fibers that could limit the alveolar ducts and alveoli distension. Therefore, the most features observed were the collagen areas and fibrosis. We suggested in this study that the collagen remodeling in the trachea, lungs, and diaphragm muscle may increase fibrosis and affect the trachea, lungs, and diaphragm muscle function that can be a major cause of respiratory failure that occur in patients with DMD. Microsc. Res. Tech. 77:857–861, 2014. © 2014 Wiley Periodicals, Inc.     

Torque Variations in Instrument Ball Bearings

Disturbances in the torques and motions in angular contact instrument ball bearing pairs are described and analyzed. Among others, a motion of the ball retainer, analogous to dry friction whirl, is attributed to frictional coupling between balls and retainer, and an interaction between bearings, resulting in several low frequency perturbations, is explained in terms of ball errors. Experimental confirmation is obtained.     

四足机器人运动学分析及步态研究

在对典型哺乳动物机体结构分析基础上,提出一种液压驱动四足机器人的简化结构,完成机器人腿部结构的设计,并对腿部机构进行正逆运动学求解,研究不同负载因子下的直行起步调整到稳定行走步态并计算稳定裕度。结果表明:两种步态均能实现稳定的起步和周期行走,其中非连续调整步态的平均稳定裕度较大。     

下肢步态矫形器轨迹控制设计

为了模拟正常人的行走步态,设计了具有外骨骼结构的动力步态矫形器。采用LabVIEW软件和多功能数据采集卡以及交流伺服平台,完成了下肢步态矫形器步态轨迹的半闭环控制,同时介绍了步态生成方法以及软件的设计。研究结果表明,步态矫形器能够较好地复原正常人的行走步态,并已应用到下肢康复机器人的控制系统中。     

Modelling of ergonomics and muscular comfort

Commercially available software packages permit to position human models of various geometries in practical scenarios while respecting the anatomical constraints of the skeletal joints and of the bulk of the bodies. Beyond such features, the PAM-Comfort^TM software has been conceived to provide direct access to the muscular forces needed by humans to perform physical actions where muscle force is required. The PAM-Comfort^TM human models are made of multi-body linked anatomical skeletons, equipped with finite elements of the relevant skeletal muscles. The hyper-static problem of determination of muscle forces is solved by optimisation techniques. Voluntary stiffening of muscles can be added to the basic contraction levels needed to perform a specific task. The calculated muscle forces obey Hill's model. The model and software have been applied in several interesting scenarios of various fields of application, such as car industry, handling of equipment and sports activities.     

Automatic diagnosis of neuro-degenerative diseases using gait dynamics

Here an approach for the diagnosis of neuro-degenerative diseases based on gait dynamics is proposed. The proposed method uses information from a time series of stride intervals, swing intervals, stance intervals and double support intervals of stride-to-stride measures of footfall contact times using force-sensitive resistors. Different features were extracted from these time series and the best of them were selected for the diagnosis. The support vector machines using different kernels were examined for the diagnosis. The radial basis function kernel obtained the best performance for this aim. The results show that features derived from double support intervals are common effective features for the diagnosis of neuro-degenerative diseases using the gait dynamics.     

Modeling and simulation of normal and hemiparetic gait

Gait is the collective term for the two types of bipedal locomotion, walking and running. This paper is focused on walking. The analysis of human gait is of interest to many different disciplines, including biomechanics, human-movement science, rehabilitation and medicine in general. Here we present a new model that is capable of reproducing the properties of walking, normal and pathological. The aim of this paper is to establish the biomechanical principles that underlie human walking by using Lagrange method. The constraint forces of Rayleigh dissipation function, through which to consider the effect on the tissues in the gait, are included. Depending on the value of the factor present in the Rayleigh dissipation function, both normal and pathological gait can be simulated. First of all, we apply it in the normal gait and then in the permanent hemiparetic gait. Anthropometric data of adult person are used by simulation, and it is possible to use anthropometric data for children but is necessary to consider existing table of anthropometric data. Validation of these models includes simulations of passive dynamic gait that walk on level ground. The dynamic walking approach provides a new perspective of gait analysis, focusing on the kinematics and kinetics of gait. There have been studies and simulations to show normal human gait, but few of them have focused on abnormal, especially hemiparetic gait. Quantitative comparisons of the model predictions with gait measurements show that the model can reproduce the significant characteristics of normal gait.     

Variations in wear particle concentration in lubricating oil

Methods and the resulting general mathematical model of concentration variation rates of particles in lubricating oil during the life of a mechanism such as a gear box are presented. Calculations for the pre-failure period not considered earlier by Kjer are reported.     

人体步态周期中骨盆自由度的分析

下肢康复训练过程中,需要控制患者骨盆与下肢各关节的协调运动,以及重心与步态的协调运动,实现行走过程中的平衡控制,从而达到较好的训练效果.通过正常人的运动特性分析,并针对步态周期中摆动期和支撑期的不同支撑状态,分别分析确定了骨盆所具有的自由度.同时又研究了特殊位姿(立正时)情况下骨盆的运动能力,并分析了下肢各个关节的耦合现象.利用Adams软件对在不同情况下人体骨盆自由度进行了验证,依据骨盆运动规律,提出一种绳牵引并联机构,实现了对骨盆运动的控制.     

Tripod gait-based turning gait of a six-legged walking robot

The turning gait planning and improvement methods of a six-legged walking robot on the basis of tripod gait are presented in this study. A projection method that considers an unstructured environment is proposed for the turning gait planning of the six-legged walking robot. The body and foot motion trajectories of the swing legs are planned with polynomial curves to keep the robot steady while walking. Two basic turning gaits, namely, circling and spinning gaits, are successfully designed with the planning method. An optimized method is proposed to improve the turning angle, which is subjected to stability, kinematics, and relief amplitude constraints in the unstructured environment. The turning ability of the turning gait is improved with the optimized turning angle. The circling and spinning gaits are implemented in simulations and experiments. Results demonstrate that the planning and improvement methods for the turning gait are valid and correct.

     

一种用于多足步行机器人步态控制的CPG模型

基于对生物节律性周期运动的CPG控制的概念,采用Lakshmanan和Murali的双变量简化Hodgkin-Huxley振荡神经元模型作为CPG的振子。对该模型进行了不动点及稳定性分析和分岔分析,指出了其二次Hopf分岔特性和振荡条件。在此基础上,建立了一种用于八足步行机器人步态控制的CPG模型。通过分阶段遗传算法,分别针对几种步态进行了参数优化,通过仿真验证了所提出的CPG模型的可行性。     

基于步态参数的助行器设计方法

以人机(助行器)适配为设计目标,提出了基于人体步态参数分析的动力式助行器设计方法.利用Vicon三维运动分析系统开展了人体步态实验研究,以获取的步态参数为动力式助行器运动控制依据.基于杆状模型,将ADAMS仿真结果与计算结果对比,得到了动力设计要求.在运动控制及动力需求的基础上,提出了一款基于直线角位移机构驱动的动力式助行器设计方案.     

步行康复训练机器人协调控制的研究

为了实现步行康复训练机器人的协调控制,对外骨骼助行腿与跑步机的协调控制以及减重支撑系统与外骨骼助行腿的协调控制,提出了协调控制方法。最后用假人代替真实患者通过实验验证了外骨骼助行腿、跑步机和减重支撑系统之间的协调控制效果。实验结果表明,步行康复训练机器人能够很好的对假人进行减重步行康复训练,外骨骼助行腿、跑步机和减重支撑系统很好地实现了协调控制,同时为进一步对真实患者进行实验研究奠定了很好的基础。