Learning feedforward commands to muscles using time-shifted sensory feedback

In adapting to changing forces in the mechanical environment, humans change the force being applied by the limb by reciprocal changes in the activation of antagonistic muscles. However, they also cocontract these muscles when interaction with the environment is mechanically unstable to increase the mechanical impedance of the limb. We have postulated that appropriate patterns of muscle activation could be learned using a simple scheme in which the naturally occurring stretch reflex is used as a template to adjust feedforward commands to muscles. Feedforward commands are modified iteratively by shifting a scaled version of the reflex response forward in time and adding it to the previous feedforward command. We show that such an algorithm can account for the principal features of changes in muscle activation observed when human subjects adapt to instabilities in the mechanical environment. © 2006.

Lentivirus介导神经营养因子- 3促进脊髓损伤大鼠功能恢复

　目的　探讨Lentivirus介导分泌神经营养因子- 3 (NT - 3)直接体内转基因治疗大鼠脊髓损伤作用和机制。　方法　将28只Wistar大鼠在T10水平制成半横断损伤模型,随机分为体内转基因治疗组和损伤对照组,每组14只;用携带NT - 3和绿色荧光蛋白(GFP)的Lentivirus对大鼠行直接体内转基因治疗;荧光显微镜观察体内转基因表达,后肢运动功能评分法(BBB评分) 检测大鼠后肢功能恢复情况。　结果　用荧光显微镜检测到损伤脊髓内有较多的持续表达转基因的细胞; BBB评分结果显示,从伤后第4周开始,实验组大鼠后肢功能较对照组明显恢复( P < 0. 01) ,至第10周时,实验组和对照组BBB分差增大,达3. 3分。　结论　Lentivirus是一种有效的转基因载体,由Lentivirus介导分泌NT - 3的直接体内转基因治疗能够明显促进损伤脊髓的功能恢复。

Task-dependent coordination of rapid bimanual motor responses.

Optimal feedback control postulates that feedback responses depend on the task relevance of any perturbations. We test this prediction in a bimanual task, conceptually similar to balancing a laden tray, in which each hand could be perturbed up or down. Single-limb mechanical perturbations produced long-latency reflex responses ("rapid motor responses") in the contralateral limb of appropriate direction and magnitude to maintain the tray horizontal. During bimanual perturbations, rapid motor responses modulated appropriately depending on the extent to which perturbations affected tray orientation. Specifically, despite receiving the same mechanical perturbation causing muscle stretch, the strongest responses were produced when the contralateral arm was perturbed in the opposite direction (large tray tilt) rather than in the same direction or not perturbed at all. Rapid responses from shortening extensors depended on a nonlinear summation of the sensory information from the arms, with the response to a bimanual same-direction perturbation (orientation maintained) being less than the sum of the component unimanual perturbations (task relevant). We conclude that task-dependent tuning of reflexes can be modulated online within a single trial based on a complex interaction across the arms.

Impedance control is selectively tuned to multiple directions of movement

Humans are able to learn tool-handling tasks, such as carving, demonstrating their competency to make movements in unstable environments with varied directions. When faced with a single direction of instability, humans learn to selectively co-contract their arm muscles tuning the mechanical stiffness of the limb end point to stabilize movements. This study examines, for the first time, subjects simultaneously adapting to two distinct directions of instability, a situation that may typically occur when using tools. Subjects learned to perform reaching movements in two directions, each of which had lateral instability requiring control of impedance. The subjects were able to adapt to these unstable interactions and switch between movements in the two directions; they did so by learning to selectively control the end-point stiffness counteracting the environmental instability without superfluous stiffness in other directions. This finding demonstrates that the central nervous system can simultaneously tune the mechanical impedance of the limbs to multiple movements by learning movement-specific solutions. Furthermore, it suggests that the impedance controller learns as a function of the state of the arm rather than a general strategy. © 2011 the American Physiological Society.

MULTIVARIATE COMPARISON OF THE FORELIMB BETWEEN STUMP-TAILED AND RHESUS MACAQUES

Rhesus macaques and stump-tailed macaques are sympatric in western Yunnan (China), coexisting or occupying habitats that show little difference. This paper tests hypotheses based on theoretical expectation from the differing biomechanical demands of terrestrial and arboreal quadrupedalism in stump-tailed macaques and rhesus macaques, respectively. Individuals of these two macaque taxa were markedly separated by the first two principal components and discriminant analyses based on 18 variables of the upper limb. The rhesus macaques appear to be more adapted for arboreal quadruped habits because of elongation of the clavicle and forearm, a larger humeral head and greater midshaft sagittal diameters of the radius and ulna.

CLASSIFICATION AND EVOLUTION OF ASIAN COLOBINES

In order to study the differentiation of Asian colobines, 14 variables measured on 123 skulls, including Rhinopithecus, Presbytis, Presbytiscus (Rhinopithecus avunculus), Pygathrix and Nasalis were analyzed by one-way, cluster and discriminant function analyses. Information on paleoenvironmental changes in China and southeast Asia since the late Tertiary was used to examine the influences of migratory routes and range of distribution in Asian colobines. A cladogram for 6 genera of Asian colobines was constructed from the results of various analyses. Some new points or revisions were suggested: (1) Following one of two migratory routes, ancient species of Asian colobines perhaps passed through Xizang (Tibet) along the northern bank of the Tethys sea and through the Heng Duan Shan regions of Yunnan into Vietnam. An ancient landmass linking Yunnan and Xizang was already present on the east bank of the Tethys sea. Accordingly, Asian colobines would have two centers of evolutionary origin: Sundaland and the Heng Duan Shan regions of China. (2) Pygathrix shares more cranial features with Presbytiscus than with Rhinopithecus. This differs somewhat from the conclusion reached by Groves. (3) Nasalis (karyotype: 2n = 48) may be the most primitive genus among Asian colobines. Certain features shared with Rhinopithecus, e.g. large body size, terrestrial activity and limb proportions, can be interpreted as symple-siomorphic characters. (4) Rhinopithecus, with respect to craniofacial features, is a special case among Asian colobines. It combines a high degree of evolutionary specialization with retention of some primitive features thought to have been present in the ancestral Asian colobine.

Robotics and neuroscience: A rhythmic interaction

At the crossing between motor control neuroscience and robotics system theory, the paper presents a rhythmic experiment that is amenable both to handy laboratory implementation and simple mathematical modeling. The experiment is based on an impact juggling task, requiring the coordination of two upper-limb effectors and some phase-locking with the trajectories of one or several juggled objects. We describe the experiment, its implementation and the mathematical model used for the analysis. Our underlying research focuses on the role of sensory feedback in rhythmic tasks. In a robotic implementation of our experiment, we study the minimum feedback that is required to achieve robust control. A limited source of feedback, measuring only the impact times, is shown to give promising results. A second field of investigation concerns the human behavior in the same impact juggling task. We study how a variation of the tempo induces a transition between two distinct control strategies with different sensory feedback requirements. Analogies and differences between the robotic and human behaviors are obviously of high relevance in such a flexible setup. © 2008 Elsevier Ltd. All rights reserved.

Twitching in sensorimotor development from sleeping rats to robots.

It is still not known how the 'rudimentary' movements of fetuses and infants are transformed into the coordinated, flexible and adaptive movements of adults. In addressing this important issue, we consider a behavior that has been perennially viewed as a functionless by-product of a dreaming brain: the jerky limb movements called myoclonic twitches. Recent work has identified the neural mechanisms that produce twitching as well as those that convey sensory feedback from twitching limbs to the spinal cord and brain. In turn, these mechanistic insights have helped inspire new ideas about the functional roles that twitching might play in the self-organization of spinal and supraspinal sensorimotor circuits. Striking support for these ideas is coming from the field of developmental robotics: when twitches are mimicked in robot models of the musculoskeletal system, the basic neural circuitry undergoes self-organization. Mutually inspired biological and synthetic approaches promise not only to produce better robots, but also to solve fundamental problems concerning the developmental origins of sensorimotor maps in the spinal cord and brain.

Self-organization of spinal reflexes involving homonymous, antagonist and synergistic interactions

Recent results in spinal research are challenging the historical view that the spinal reflexes are mostly hardwired and fixed behaviours. In previous work we have shown that three of the simplest spinal reflexes could be self-organised in an agonist-antagonist pair of muscles. The simplicity of these reflexes is given from the fact that they entail at most one interneuron mediating the connectivity between afferent inputs and efferent outputs. These reflexes are: the Myotatic, the Reciprocal Inibition and the Reverse Myotatic reflexes. In this paper we apply our framework to a simulated 2D leg model actuated by six muscles (mono- and bi-articular). Our results show that the framework is successful in learning most of the spinal reflex circuitry as well as the corresponding behaviour in the more complicated muscle arrangement. © 2012 Springer-Verlag.

Enlarging regions of stable running with segmented legs

In human and animal running spring-like leg behavior is found, and similar concepts have been demonstrated by various robotic systems in the past. In general, a spring-mass model provides self-stabilizing characteristics against external perturbations originated in leg-ground interactions and motor control. Although most of these systems made use of linear spring-like legs. The question addressed in this paper is the influence of leg segmentation (i.e. the use of rotational joint and two limb-segments) to the self-stability of running, as it appears to be a common design principle in nature. This paper shows that, with the leg segmentation, the system is able to perform self-stable running behavior in significantly broader ranges of running speed and control parameters (e.g. control of angle of attack at touchdown, and adjustment of spring stiffness) by exploiting a nonlinear relationship between leg force and leg compression. The concept is investigated by using a two-segment leg model and a robotic platform, which demonstrate the plausibility in the real world. ©2008 IEEE.

东亚人群 LMBR1 基因 Intron 5的遗传多样性研究

人LMBR1(Limb region 1 homolog (mouse)) 基因位于染色体7q36区域，全长约210.2 kb，含17个外显子，编码一个由490个氨基酸构成的跨膜蛋白。研究表明，LMBR1 基因的表达活性与脊椎动物四肢的手指或脚趾数目变化有关；另外，发生在其重要元件——intron 5 内的许多变异与多种表型的轴前多指症((PPD, Preaxial polydactyly)存在相关性，这主要是因为LMBR1 intron 5 内含有一个与骨骼系统发育有关的基因（SHH(Sonic hedgehog)基因）的远程顺式调控元件。本研究旨在探究LMBR1基因 intron 5 内的遗传多样性，进而评估HapMap计划的样本选择策略，并检测该区域是否受自然选择的作用。 国际人类基因组单体型图计划(HapMap Project，The International Haplotype Map Project) 于2002年10月正式启动，该计划旨在构建人类基因组中常见变异的遗传图式。自其数据发布以来，广泛应用于生物医学、群体遗传学等领域，在复杂疾病的遗传机理研究、自然选择的检测等方面做出了前所未有的贡献；但是HapMap计划中样本的代表性有待评估。 本研究中，我们综合考虑地理来源信息及线粒体单倍型类群 (Haplogroup)信息选择了41个东亚人作为样本（以保证样本的代表性），测定位于LMBR1 基因intron 5 内的目的片段中存在的单核苷酸多态性(SNP, Singe nucleotide polymorphism)位点，通过所得数据与HapMap数据的比较，发现二者之间差异显著且HapMap数据不能覆盖所有我们得到的常见变异，因而我们认为：HapMap计划中国部分的样本选择策略有待进一步完善。 关于自然选择的研究不仅可以使我们了解生物的进化机制，同时还对复杂疾病的遗传机理研究具有重要的提示作用，因而，对于自然选择的检测，一直以来都是生物学研究的重点。平衡选择是一种维持遗传多态性的自然选择方式，现已发现很多与特定疾病或性状相关的基因或调控序列受平衡选择的作用，如 G6PD 基因、PTC 基因、FMO3 基因、FSHB 基因及 CCR5 基因5’端顺式调控区等我们对41个东亚样本中LMBR1 intron 5 内一段长为9256 bp (Chr7: 156280954-156271699 (Build36))的序列进行以 Tajima’s D 检验为主的群体遗传学分析，发现该区域在进化历程中受到平衡选择的作用。LMBR1 intron 5 内的多态位点与多种表型的多指症存在相关性，受其调控的 SHH 基因在骨骼系统发育中具有重要作用，人类骨骼系统的适应性进化等三方面的因素为该区域受平衡选择的作用提供了进一步的佐证。 总之，本研究对HapMap计划的样本选择策略和数据应用提供了一定的参考；同时还发现一个与骨骼系统发育有关的基因调控元件受平衡选择的作用。

东营凹陷辛镇复杂断块油藏形成机制和剩余油分布规律研究

In this paper, the complex faulted-block oil reservoir of Xinzhen area in Dongying depression is systematically studied from basic conditions forming faulted-block oil and gas reservoir integrating geology, seismic, logging and reservoir engineering information and computer; guided by petroleum geology, geomechanics, structural geology and geophysics and other theories. Based on analysis of background condition such as regional strata, structure and petroleum geology, structural research on geometry, kinemaitcs and dynamics, oil-controlling fault research on the seal features, sealing mechanism and sealing pattern, and research on enrichment rules and controlling factors of complex faulted-block oil reservoir are carried out to give out the formation mechanics of oil reservoir of Xinzhen complex faulted-block oil reservoir. As a result, the reservoir formation pattern is established. At the same time, through dissecting the characteristics and hydrocarbon enrichment law of complex faulted-block oil reservoir, and studying its distribution law of remaining oil after entering extra high water-cut period, a set of technologies are formed to predict complex faulted-block oil reservoir and its remaining oil distribution and to enhance oil recovery (EOR). Based on the time relationship between migration of hydrocarbon and trap formation, accumulating period of Xinzhen oil reservoir is determined. The formation of Xinzhen anticlinal trap was prior to the primary migration. This is favorable to formation of Xinzhen anticlinal hydrocarbon reservoir. Meanwhile, because anticline top caving isn't at the sane time as that of moving or faulted-trap forming inner anticline, oil and gas migrated many times and Xinzhen complex faulted-block oil reservoir formed from ES_3~(upper) to EG. Accumulating law and controlling factors of complex faulted-block reservoir are analyzed from many aspects such as regional structure background controlling hydrocarbon accumulating, plastic arch-open structure controlling oil-bearing series and reservoir types, sealing-opening of fault controlling hydrocarbon distribution and structure pattern controlling enriched trap types. Also, we established the structure pattern in Xinzhen a'ea: the arch-open of underlying strata cause expanding fracture. The main block groups developed here are shovel-like normal fault block group in the north area of Xinzhen and its associated graben block group. Block groups dominate the formation and distribution of reservoirs. We studied qualitatively and quantitatively the sealing characteristics, sealing history and sealing mechanism of faults, too. And, the sealing characteristics are evaluated and the distribution pattern of hydrocarbon controlled by faults is researched. Due to movement intensity of big faults, deep falling of downthrown block, high degree of repture and development of fracture, shallow layers close to the downthrown block of secondary faults are unfavorable to hydrocarbon accumulation. This is confirmed by the exploration practice in Xinzhen anticline. In terms of the downthrown blocks of sencondary contemporaneous faults lied in the south and north area of Xinzhen, hydrocarbon is poor close to fracture belt, while it is relatively abundant in tertiary companion faults. Because of long-term movement of faults that control hydrocarbon, fi'om ES3 to EG, six set of oil-bearing series formed. And their opening causes the inhomogeneity in hydrocarbon abundance among each block--in two flanks of anticline reservoirs are abundant while in the axial area, oil and gas are sporadic. There the sealing characteristics control oil-bearing area of oil/gas accumulation and the height of oil reservoir. Longitudinally, oil and gas are enriched in dip-flat areas in mid-plane of faults. It is established that there are four types of accumulating patterns in complex faulted-block oil reservoirs in Xinzhen. The first is accumulating pattern of lithologic oil reservoirs in E~S_3~(mid-lowwer), that is, self-generating-self-reserving-self-covering lithologic trap pattern. The second is drag-anticline accumulating pattern in Xinzhen. The structure traps are drag anticlines formed by the contemporaneous faults of the second basement in the north of Xinzhen, and the multiple source rocks involve Ek_2, Es_4, Es_3 and Es_1 members. The reservoirs are fluvial-delta sandstones of the upper member of Shahejie formation and Guantao formation, covered by regional thick mudstone of the upper member of Guantao formation and MingHuazhen formation. The third is the accumulating pattern of reverse listric fault, the third-degree fault of Xinzhen anticline limb and the reservoirs form reservoir screened by reverse listric faults. The forth is accumulating pattern of crossing faults which form closing or semi-closing faulted-blocks that accumulate hydrocarbon. The technologies of predicting remaining oil in complex faulted-block reservoir during the mid and late development stage is formed. Remaining oil in simple large faulted-blocks enriches in structural high, structural middle, structural low of thick bottom water reservoirs, points near bent edge-fault oftertiary faults and part the fourth ones with big falling displacement, microstructure high place of oil-sandbodies and areas where local well pattern isn't perfect. While that in small complex faulted-blocks enriches near small nose, small high point, angle of small faults, small oil-bearing faulted-blocks without well and areas with non-perfect well pattern. The technologies of enhancing recovery factor in complex faulted-block reservoir during the mid and late development stage is formed as follows: fine reservoir description, drilling adjust wells, designing directional wells, sub-dividing layer series of development, improving flooding pattern, changing water-injection direction and enhancing swept volume, cyclic waterflooding and gas-injection, etc. Here, directional wells include directional deflecting wells, lateral-drilling wells, lateral-drilling horizontal wells and horizontal wells. The results of this paper have been used in exploration and development of Shengli oilfield, and have achieved great social and economic profit, especially in predicting distribution of complex faulted-block reservoir, remaining oil distribution during middle and late stage of development, and in EOR. Applying the achievement of fault-closure research, new hydrocarbon-bearing blocks are discovered in flanks of Dongying central uplift and in complex blocks with proved reserves 15 million tons. With the study of remaining oil distribution law in complex faulted-block reservoirs, recovery factors are increased greatly in Dongxin, Xianhe and Linpan complex faulted-block reservoirs and accumulated oil production increment is 3 million tons.

Motor Control and Learning by the State Space Model

A model is presented that deals with problems of motor control, motor learning, and sensorimotor integration. The equations of motion for a limb are parameterized and used in conjunction with a quantized, multi-dimensional memory organized by state variables. Descriptions of desired trajectories are translated into motor commands which will replicate the specified motions. The initial specification of a movement is free of information regarding the mechanics of the effector system. Learning occurs without the use of error correction when practice data are collected and analyzed.

C-Kit(+) Cells Isolated from Developing Kidneys Are a Novel Population of Stem Cells with Regenerative Potential

The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit(+) cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit(+) cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex vivo expanded c-kit(+) cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together, these findings document a novel neonatal rat kidney c-kit(+) stem cell population that can be isolated, expanded, cloned, differentiated, and used for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. STEM Cells 2013;31:1644-1656

Development of process control methodology for tracking the quality and safety of pain, agitation and sedation management in critical care units

Objective: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. Design: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. Setting: Eight Scottish ICUs over a 12-month period. Patients: Mechanically ventilated patients. Interventions: None. Measurements and Main Results: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman [rho] = 0.75) and were reliable in clinician-clinician (weighted kappa; [kappa] = 0.66) and clinician-researcher ([kappa] = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale ([rho] = 0.24) and was reliable in clinician-clinician ([kappa] = 0.58) and clinician-researcher ([kappa] = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale ([rho] = 0.54), and reliability in clinician-clinician ([kappa] = 0.29) and clinician-researcher ([kappa] = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. Conclusions: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time