Musculoskeletal Model of the Upper Limb Based on the Visible Human Male Dataset

A mathematical model of Ihe human upper limb was developed based on high-resolution medical images of the muscles and bones obtained from the Visible Human Male ( HM) project. Three-dimensional surfaces of the muscles and bones were reconstructed from Computed Tomography (CT) images and Color Cryosection images obtained from the VHM cadaver. Thirteen degrees of freedom were used to describe the orientations of seven bones in the model: clavicle, scapula, humerus, radius, ulna, carpal bones, and hand. All of the major articulations from the shoulder girdle down to the wrist were included in the model. The model was actuated by 42 muscle bundles, which represented the actions of 26 muscle groups in the upper limb. The paths of the muscles were modeled using a new approach called the Obstacle-set Method (33) The calculated paths of the muscles were verified by comparing the muscle moment arms computed in the model with the results of anatomical studies reported in the literature, In-vivo measurements of maximum isometric muscle torques developed at the shoulder, elbow, and wrist were also used to estimate the architectural properties of each musculotendon actuator in the model. The entire musculoskeletal model can be reconstructed using the data given in this paper, along with information presented in a companion paper which defines the kinematic structure of the model (26)     

A Case Study on Human Upper Limb Modelling for Dynamic Simulation

Modelling consists of developing a representation of the properties of an object or a phenomenon with respect to the goals of its analysis. In this paper, the procedure presented is that followed in the CHARM project for human upper limb modelling with respect to the project constraints on the model implementation and simulation. The objective is to develop a Comprehensive Human Animation Resource Model allowing the simulation of human motion, including the finite element simulation of soft tissue deformation and muscular contraction. Generally, models are presented based on assumptions left for a fortiori validation. The a priori considerations which lead to these assumptions are rarely detailed. Here, the aim is to form a basis for the choices and assumptions which are to be made prior to the validation. The analysis is based on the general approach for the modelling of multi-body deformable systems as well as on previous studies on the human upper limb.     

A Brain Motor Control Assessment (BMCA) Protocol for Upper Limb Function

The Brain Motor Control Assessment (BMCA) protocol is a surface electromyography (sEMG)-based measure of motor output from central nervous system during a variety of reflex and voluntary motor tasks performed under strictly controlled conditions. The aim of this study was to evaluate the BMCA protocol for upper limb with the addition of shoulder voluntary tasks. The voluntary response index (VRI) was calculated from quantitative analysis of sEMG data during defined voluntary movement in neurologically intact people for comparison with that of patients after neurological injuries. The BMCA protocol included one bilateral and 4 unilateral voluntary tasks at different joints of both arms. The VRI, measured from 19 neurologically intact participants, comprises the total muscle activity recorded for the voluntary motor task (magnitude). The calculated similarity index (SI) for each phase of each task show the similarity of “the distribution of activity across the recorded muscles” for that task in this group off participants. Results: The VRI magnitude values from right and left sides for different tasks showed no significant difference (ANOVA: F_Side: 0.09, P = 0.77). Therefore these values were pooled before calculating SI. SI values were higher for tasks against gravity: elbow flexion (0.99±0.03), wrist flexion with palm up (0.98±0.03) and wrist extension with palm down (0.97±0.07). On the other hand, the SI values were the lowest for bilateral shoulder abduction (0.84±0.08) and shoulder adduction (0.84±0.08). Conclusion: To validate this index for clinical use, serial studies on patients with neurological impairments should be performed. Tasks involving movement against gravity may be more suitable in future BMCAs.     

A Brief Review on the Human Encyclopedia of DNA Elements (ENCODE) Project

The ENCyclopedia Of DNA Elements (ENCODE) project is an international research consortium that aims to identify all functional elements in the human genome sequence. The second phase of the project comprised 1640 datasets from 147 different cell types, yielding a set of 30 publications across several journals. These data revealed that 80.4% of the human genome displays some functionality in at least one cell type. Many of these regulatory elements are physically associated with one another and further form a network or three-dimensional conformation to affect gene expression. These elements are also related to sequence variants associated with diseases or traits. All these findings provide us new insights into the organization and regulation of genes and genome, and serve as an expansive resource for understanding human health and disease.     

Investigation of the Peculiarities of Two-joint Muscles Using a 3 DOF Model of the Human Upper Limb in the Sagittal Plane: an Optimization Approach

Abstract

The purpose of this paper is an investigation of the peculiarities of biarticular muscles by means of modelling and analytical solution of the indeterminate problem. The basic model includes 10 muscle elements performing flexio/extensio in the shoulder, elbow and wrist. Four of them are biarticular muscles. Two modifications of the model with only monoarticular muscles are developed. The indeterminate problem is solved analytically using the objective criterion σc_iF_i ² where F( is the module of the i-th muscle force and Cj is a weight coefficient. The predicted muscle forces, joint reactions and moments are compared in-between the basic model and its two modifications for different joint angles, external loading and weight coefficients. The main conclusions are: it is impossible to formulate strict advantages of the biarticular muscles under quasistatical conditions, their peculiarities depend on limb position, external loading and neural control; in general, monoarticular muscles are more powerful than biarticular ones; the biarticular muscles fine tune muscle coordination, their control is more precise and graceful; the presence of biarticular muscles leads to an increase of the joint reactions and moments, thus stabilizing the limb.     

Prediction of Individual Muscle Forces Using Lagrange Multipliers Method - A Model of the Upper Human Limb in the Sagittal Plane: II. Numerical Experiments and Sensitivity Analysis

Using the method of Lagrange multipliers an analytical solution of the optimization problem formulated for a two-dimensional, 3DOF model of the human upper limb has been described in Part I of this investigation. The objective criterion used is the following: [formula: see text], where F(i) -s are the muscle forces modelled and c(i) -s are unknown weight factors. This study is devoted to the numerical experiments performed in order to investigate which sets of the weight factors may predict physiologically reasonable muscle forces and joint reactions. A sensitivity analysis is also presented. The influence of: the gravity forces, different external loads applied to the hand, changes of the weight factors and of joint angle on the optimal solution is studied. A general conclusion may be drawn: using the above mentioned objective criterion, practically all motor tasks performed by the human upper limb may be described if the c(i) -s are properly chosen. These weight factors generally depend on the joint moments and must be different (their magnitudes as well as their signs) for agonistic muscles and for their antagonists.     

Proteogenomics in the context of the Human Proteome Project (HPP)

Introduction: The technological and scientific progress performed in the Human Proteome Project (HPP) has provided to the scientific community a new set of experimental and bioinformatic methods in the challenging field of shotgun and SRM/MRM-based Proteomics. The requirements for a protein to be considered experimentally validated are now well-established, and the information about the human proteome is available in the neXtProt database, while targeted proteomic assays are stored in SRMAtlas. However, the study of the missing proteins continues being an outstanding issue.

Areas covered: This review is focused on the implementation of proteogenomic methods designed to improve the detection and validation of the missing proteins. The evolution of the methodological strategies based on the combination of different omic technologies and the use of huge publicly available datasets is shown taking the Chromosome 16 Consortium as reference.

Expert commentary: Proteogenomics and other strategies of data analysis implemented within the C-HPP initiative could be used as guidance to complete in a near future the catalog of the human proteins. Besides, in the next years, we will probably witness their use in the B/D-HPP initiative to go a step forward on the implications of the proteins in the human biology and disease.     

A 3D Model for the Human Hepatic Asialoglycoprotein Receptor (ASGP-R)

Abstract

The human hepatic Asialoglycoprotein Receptor (ASGP-R) consists of two different types of liver specific membrane glycoproteins that bind to terminal galactose and acetylgalactosamine residues of serum glycoproteins. The two different polypeptide chains are referred to as two receptor subunits, HH1 and HH2, which are both involved in the activity of the functional receptor. This receptor has served as a model for understanding receptor-mediated endocytosis and carbohydrate mediated recognition phenomena.

Here models for the C-terminal extracellular region of both HH1 and HH2 subunit are presented. The standard homology building procedure was modified in order to make it suitable for the modeling problem at hand. The models for the extracellular regions of HH1 and HH2 were initially constructed by exploiting several fragments, belonging to proteins of known 3D structure, and showing high local sequence similarity with respect to the glycoproteins of interest. Putative binding sites were first hypothesized on the basis of the comparison with other complexes of lectins, the crystal structure of which was available in the Protein Data Bank. A model for the complex involving the HH2 subunit and the typical high affinity ligand N-acetylgalactosamine (NacGal) was refined as the first by a suitable combination of MD simulations and Energy Minimization calculations, since it seemed to quickly converge to a plausible structure. An intermediate model for HH1 was then rebuilt on the basis of the refined model for HH2. It was then submitted to a sequence of molecular dynamics simulations with templates which took into account the secondary structure prediction for a final refinement. The structures of small regions of the models, located around the binding sites, were compared with more recent crystallographic data regarding a complex involving the mutant of Mannose Binding Protein QPDWGH (1BCH entry in the Protein Data Bank) and NacGal. This mutant shows high local sequence similarity with HH1 and HH2 at the binding sites. On the basis of the above comparison, different locations of the binding sites were also considered. In addition to other expected interactions, two hydrophobic interactions were observed in the models with Trp residues (positions 243 in HH1 and 181 or 267 in HH2 respectively) and His residues (positions 256 in HH1 and 184 in HH2 respectively). The quality of the models was evaluated by the Procheck program and they seemed plausible. This observation together with analogies found between binding sites of the models and 1BCH supported the validity of the models. A further validation element arose by comparison between experimental binding data available in the literature about the homologous rat receptor subunits and theoretical interaction energies evaluated, by means of the DOCK 3.5 program, in models for the rat subunits obtained from the corresponding human ones. The new modeling procedure used here appears to be a well-suited method for structural analysis of small regions, located around the ligands, in proteins of unknown 3D structure.     

A型肉毒毒素联合肌电生物反馈治疗脑卒中后上肢肌痉挛的临床疗效分析

目的:分析A型肉毒毒素与肌电生物反馈联合用于治疗脑卒中后上肢肌痉挛的临床疗效。方法:选择2014年10月至2016年12月辽宁本溪市中心医院和北京博爱医院收治的84例脑卒中后上肢肌痉挛患者,并将其随机分为观察组和对照组,每组42例。两组患者均首先接受常规康复训练,随后对照组加用肌电生物反馈治疗,观察组患者在对照组的基础之上注射A型肉毒毒素。采用改良Ashworth痉挛量表(MAS)比较两组治疗前后的上肢肌痉挛改善情况,采用Fugl-Meyer评定量表评价患者上肢运动功能,采用量角器测量治疗前后患者的腕关节主动活动范围,采用改良的Barthel指数评价患者治疗前后的日常生活能力。结果:治疗后,观察组的上肢痉挛改善总有效率显著高于对照组(P0.05);治疗2周和4周时,两组的Fugl-Meyer评分、腕关节主动活动范围、改良的Barthel指数(MBI)均较治疗前显著升高(P0.05),且观察组治疗后2周和4周的Fugl-Meyer评分、腕关节主动活动范围、改良的Barthel指数(MBI)均显著高于对照组(P0.05)。结论:A型肉毒毒素与肌电生物反馈联合用于治疗脑卒中后上肢肌痉挛的临床疗效显著,可有效降低患者上肢痉挛状态,改善上肢和腕部运动能力,提高患者的日常生活能力。     

A Homology Based Model and Virtual Screening of Inhibitors for Human Geranylgeranyl Transferase 1 (GGTase1)

Protein prenylation is a post translational modification that is indispensable for Ras–Rho mediated tumorigenesis. In mammals, three enzymes namely protein farnesyltransferase (FTase), geranylgeranyl transferase1 (GGTase1), and geranylgeranyl transferase2 (GGTase2) were found to be involved in this process. Usually proteins of Ras family will be farnesylated by FTase, Rho family will be geranylgeranylated by GGTase1. GGTase2 is exclusive for geranylgeranylating Rab protein family. FTase inhibitors such as FTI- 277 are potent anti-cancer agents in vitro. In vivo, mutated Ras proteins can either improve their affinity for FTase active site or undergo geranylgeranylation which confers resistance and no activity of FTase inhibitors. This led to the development of GGTase1 inhibitors. A well-defined 3-D structure of human GGTase1 protein is lacking which impairs its in silico and rational designing of inhibitors. A 3-D structure of human GGTase1 was constructed based on primary sequence available and homology modeling to which pubchem molecules library was virtually screened through AutoDock Vina. Our studies show that natural compounds Camptothecin (-8.2 Kcal/mol), Curcumin (-7.3 Kcal/mol) have higher binding affinities to GGTase-1 than that of established peptidomimetic GGTase-1 inhibitors such as GGTI-297 (-7.5 Kcal/mol), GGTI-298 (-7.5 Kcal/mol), CHEMBL525185 (-7.2 Kcal/mol).     

基于可视中国人高分辨人体结构数据集的辐射剂量模拟研究进展

中国数字化辐射虚拟人研究是以中国数字人高分辨三维结构数据集为基础,构建可用于蒙特卡洛辐射模拟的三维计算模型,并实现X射线、中子、质子等多粒子多能级的仿真计算。论著中讨论了基于高分辨人体结构数据集的辐射模型构建过程和特点,以及蒙特卡洛模拟软件,并将剂量测定结果与现有的国外人体模型模拟数据进行了比较。中国数字化辐射虚拟人模型是具备中国人体特征的辐射模型。计算结果很大程度上补充或校正了现有放射学计量数据集,为临床放疗规划、核医药、核辐射防护设计提供精确量化参考。     

A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation (VCA) Research

Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma and devastating tissue loss. Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. Therefore, research in this novel field needs to focus on translational studies related to unique immunologic features of VCA and to develop novel immunomodulatory strategies for immunomodulation and tolerance induction following VCA without the need for long term immunosuppression.This article describes a reliable and reproducible translational large animal model of VCA that is comprised of an osteomyocutaneous flap in a MHC-defined swine heterotopic hind limb allotransplantation. Briefly, a well-vascularized skin paddle is identified in the anteromedial thigh region using near infrared laser angiography. The underlying muscles, knee joint, distal femur, and proximal tibia are harvested on a femoral vascular pedicle. This allograft can be considered both a VCA and a vascularized bone marrow transplant with its unique immune privileged features. The graft is transplanted to a subcutaneous abdominal pocket in the recipient animal with a skin component exteriorized to the dorsolateral region for immune monitoring.Three surgical teams work simultaneously in a well-coordinated manner to reduce anesthesia and ischemia times, thereby improving efficiency of this model and reducing potential confounders in experimental protocols. This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA.     

Limb bone histology and growth in Placerias hesternus (Therapsida: Anomodontia) from the Upper Triassic of North America

Abstract: Patterns of bone deposition are reported and deduced from mid‐shaft sections of 21 limb bones of the dicynodont Placerias hesternus from the Placerias Quarry (Upper Triassic), Arizona, USA. All sampled elements of P. hesternus have a large medullary cavity completely filled with bony trabeculae surrounded by dense cortical bone. Dense Haversian bone extends from the perimedullary region to at least the mid‐cortex in all sampled bones. Primary bone in the outer cortex of limb elements of P. hesternus is generally zonal fibrolamellar with a peripheral layer of parallel‐fibred bone. These data suggest periodic rapid osteogenesis followed by slower growth. Among dicynodonts, this strategy is most similar to growth previously reported in other Triassic (Lystrosaurus, Wadiasaurus) and some Permian taxa (Oudenodon, Tropidostoma). An external fundamental system (EFS), suggesting complete or near complete cessation of appositional growth, is present in the largest tibia. This is the first report of EFS in dicynodonts and may represent the attainment of maximum size in P. hesternus. Slow‐growing peripheral bone was observed in elements of varying size in our sample and may support a differential growth pattern between P. hesternus individuals from this locality. A complete growth series of P. hesternus, analysis of Placerias specimens from other localities, and further sampling of other Upper Triassic dicynodonts are needed to better understand a more complete picture of the growth and remodelling patterns that we have initially investigated.     

一种新的基于蒙特卡罗模拟和光子传输模型的图像分割算法

本文以蒙特卡罗模拟方法为基础,结合组织光学的光子传输模型,提出了一种新的图像分割算法,该算法将复杂的图像分割问题简化为大量简单的光子传输随机实验,通过分析传输规律来获取目标区域.在随后的实验中,结合细胞核提取这一问题建立了一个简单的光学传输模型,并依据此模型分别对人造图和实际图进行了分割.人造图的分割结果表明了该算法的可行性,说明了该算法的一些优点;而实际图的分割结果则反映了该算法的不足之处,文章针对其中存在的问题和算法待改进之处进行了分析.