Regulatory T Cells: Potential Target in Anticancer Immunotherapy

SummaryThe concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed

A leg exoskeleton simulator for design, sensing and control development

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.Cataloged from PDF version of thesis.Includes bibliographical references (pages 137-143).Leg exoskeletons have been developed in an effort to augment human locomotion for over a century. However, only two portable leg exoskeletal devices have shown a significant decrease in walking metabolism [35, 11], not to mention, no device that has shown effective assistance and biomimetic behavior across different walking speeds and terrains. This thesis aims to build a Leg Exoskeleton Simulator to effectively search the space of potential prosthetic and orthotic design, control, and sensing strategies so as to find the best means to improve human locomotion through wearable electromechanical technology and modern bionics, enabling rapid advancement of the human-machine interface. This thesis presents the MIT Exoskeleton Simulator, which is a modular tethered system that includes cable-drive mechanisms along with off-board power, actuation, control hardware, and wearable end-effector modules. In order to effectively transmit force to a wearable end-effector module, high-performance cable-drive modules with the Rolling Cable Transmission for both unidirectional actuation and bidirectional actuation were developed. A new Adaptive Coupling Joint design principle was proposed for designing a simple mechanical interface that can transmit pure torque from an input actuation source to any biological joint without altering the biological joint motions. The Simulator has been controlled with a bio-inspired control based controller that emulates the behavior of human morphology and neural control for the non-amputee participants. In this thesis, I tried to provide a base of knowledge regarding effective design, control, and sensing strategies for effective human augmentation. In the near future, more criteria can be further established for building effective leg exoskeletons that will improve the ambulatory speed, metabolic economy, and stability of walking humans. The Simulator could potentially enhance the ambulation of able-bodied persons or individuals with movement pathology, as well as providing the treatment or relief of gait dysfunction resulting from movement pathology, or restoration of age-related reduced locomotory function.by Jiun-Yih Kuan.Ph. D

Development of an Integrated System for a Humanoid Robot Arm

本論文主要的目的，在發展不同於傳統工業機器手臂之擬人形機器手臂整合系統。此系統將可安裝於為不同目的而設計的機器人平台上，應用於不同環境中，取代人類或協助人類工作，甚至與人類進行安全的互動行為。 為了研發出一具備上述功能之多自由度擬人形機器手臂整合系統，本論文主要可分為兩大部分。第一部分將著重於擬人形機器手臂之機構與硬體架構建制，平滑軌跡規劃理論與強健控制理論之發展。而有鑑於傳統的致動器，無法同時滿足操作效能與安全互動之需求，本論文的第二部分將討論具安全互動行為機制的致動器與設計準則，提出一可分別滿足安全與效能之驅動方式與致動器設計。此設計將可取代傳統致動器，安裝於任一機器人系統上，提升系統性能。文第一部分，擬人形機械手臂之機構與硬體架構建制，包含擬人形機器手臂與單一自由度夾爪之機構設計與硬體控制架構之整合與實現。平滑軌跡規劃理論，則針對擬人形機器手臂，提出一可避免演算奇異點及具避障效果之平滑軌跡規劃方法。強健控制理論，建立於可變結構控制(sliding mode control or variable structure control)架構之上，提出可消除或減少控制訊號之顫振現象(chattering phenomenon)的強健控制器。 論文第二部分，則提出一可以滿足人機安全互動及提升系統效能的彈性耦合驅動方式(Coupled Elastic Actuation)，並建立具有此特性之系統廣義線性數學模型，更進一步針對此一模型進行分析與控制器設計。最後並實際設計製作一可隨負載外力與控制輸入自行調整輸出特性的適應性彈性耦合致動器(Adaptive Coupled Elastic Actuator)，並解釋其作用原理。 未來期許以本論文所發展的適應性彈性耦合致動器來取代傳統致動器設計，安裝於所設計製作的多自由度擬人形機器手臂上，應用於不同環境中，達到具有高操作效能仍可與人類進行安全的互動行為之最終設計目標。The aim of this thesis is to develop an integrated system of a humanoid robot arm to be assembled into any kind of robot platforms designed for different purposes, say to cooperate, assist, and even interact with humans in different fields and environments. To develop the integrated system of a humanoid robot possessing the aforementioned functions and capacities, this thesis mainly contains two major parts. The first part focuses on developing an integrated system of a rigid humanoid robot arm in which the safety level of human-robot interaction is not carefully considerate. Construction of mechanism and hardware and development of smooth trajectory planning and robust control theorems are emphasized. For the reason that the traditional actuation design causes the robot hardly interact with people and environments under safety constraints and satisfy performance requirements simultaneously, the second part discusses the actuation design promising a proper safety level of human-robot interaction, and what is more, provides new actuation making a compromise between a proper safety level of human-robot interaction and good performance of manipulation. In the first part of the thesis, design of a 7-DOF humanoid robot involving in mechanism design and control hardware construction is presented and discussed; a trajectory planning method of generating a smooth trajectory with joint limit, singularity and obstacle avoidance is proposed; a near chattering-free robust control theorem based on sliding mode control scheme is developed. The second part of the thesis proposes a new actuation approach, Coupled Elastic Actuation, to provide oncoming humanoid robot arms an intrinsic compromise between performance and safety in unstructured environments; moreover, a linear model constructed to present a general Coupled Elastic Actuation system provides useful information to analyze the performance and characteristics of the system, and benefits to design a suitable controller with respect to the corresponding system. In the long run, a prototype of an Adaptive Coupled Elastic Actuator with adjustable characteristics adaptive to the applied output force and input force is invented, providing a favorable solution by a novel TorqueSwitch mechanism.致謝 IIist of Tables Xist of Figures XIhapter 1 Introduction 1.1 Motivation 1.2 Overview of the Thesis 4.3 Contributions of the Thesis 9hapter 2 Building a Humanoid Robot Arm 12.1 Introduction 12.2 Mechanism Design 17.2.1 Estimate Required Rated Torque 18.2.2 Design Outcome 21.3 Control Architecture 24.4 Summary 26hapter 3 Trajectory Planning for Humanoid Robot Arms 27.1 Introduction 27.2 Robust Double-Space Multi-Tension Spline Method (RDSMTS) 31.2.1 Overall scheme of the RDSMTS Method 32.2.2 Robust Weighted Least-Square Solution 34.2.3 Proposed Inverse Kinematics Solution 37.2.4 Modified Tension Spline Formulation (MTS) 38.3 Simulations of the NTU Humanoid Robot Arm 43.4 Experiment and Demo Results 48.5 Summary 50hapter 4 Control of Humanoid Robot Arms 51.1 Introduction 52.2 Dynamic Model of an Individual Joint 56.3 Independent Joint Sliding Mode Control 59.4 Observer-Based Independent Joint Sliding-mode Control with Gravity Compensation 63.5 Independent Joint Adaptive Sliding Mode Control 65.6 A LTR-observer-based Independent Joint Dynamic Sliding-mode Control with Gravity Compensation 69.6.1 Sliding Variable Design in IJDSMC 69.6.2 LTR Observer Design in IJDSMC 71.6.3 Control design in IJDSMC 73.7 Simulations of the NTU Humanoid Robot Arm 76.8 Experiment Results of the NTU Humanoid Robot Arm II 83.9 Summary 85hapter 5 Background and Related Work of Inherently Safe Actuating Mechanisms 87.1 Introduction 88.2 Performance and Safety Constrains 90.2.1 Performance Indices 90.2.2 Safety Criterions 92.3 Pre-existing Compliant and Safety Actuator Design 95.3.1 Cable-and-cylinder Drive Transmissions 96.3.2 Series Elastic Actuators (SEA) 97.3.3 Programmed Impedance Actuators 98.3.4 Variable Stiffness Actuators 99.3.5 Parallel Coupled Micro-Macro Actuators (DM2) 101.3.6 Antagonistic Pneumatic Artificial Muscle 101.3.7 Safe Link Mechanism and Safe Joint Mechanism 102.4 Summary 104hapter 6 Safe Actuation: Coupled Elastic Actuation 107.1 Concept of Coupled Elastic Actuation (CEA) 108.2 Properties of Coupled Elastic Actuation 112.3 Properties of CEA Control Systems 114hapter 7 Modeling, Analysis, Control of a CEA System 117.1 Modeling 117.2 Analysis 119.2.1 General Power Domain Open-Loop Model 119.2.2 Introduction to an Environmental Force Model 124.2.3 General Closed-Loop Model for Force Control 128.3 Control of a CEA System 132.3.1 Force Control Law of a CEA System 133.3.2 Control of CEA Impedance 137.3.3 An Idea of High Level Control of a CEA System 139.4 Summary 141hapter 8 Mechanism Design of a CEA Actuator 142.1 Preliminary CEA Design Concept 142.2 Mechanism Design of an Adaptive CEA Actuator 144.3 Actuation Principle of the Adaptive CEA Actuator 147.4 Summary 151hapter 9 Conclusions and Future Work 152.1 Conclusions 152.2 Future Work 154eferences 15

Mechanism and Control of Continuous-State Coupled Elastic Actuation

Focusing on the physical interaction between people and machines within safety constraints in versatile situations, this paper proposes a new, efficient, coupled elastic actuation (CEA) to provide future human-machine systems with an intrinsically programmable stiffness capacity to shape the output force corresponding to the deviation between human motions and the set positions of the system. As a possible CEA system, a prototype of a two degrees of freedom (2-DOF) continuous-state coupled elastic actuator (CCEA) is designed to provide a compromise between performance and safety. Using a pair of antagonistic four-bar linkages, the inherent stiffness of the system can be adjusted dynamically. In addition, the optimal control in a simple various stiffness model is used to illustrate how to find the optimal stiffness and force trajectories. Using the optimal control results, the shortest distance control is proposed to control the stiffness and force trajectory of the CCEA. Compared to state-of-the-art variable stiffness actuators, the CCEA system is unique in that it can achieve near-zero mechanical stiffness efficiently and the shortest distance control provides an easy way to control various stiffness mechanisms. Finally, a CCEA exoskeleton is built for elbow rehabilitation. Simulations and experiments are conducted to show the desired properties of the proposed CCEA system and the performance of the shortest distance control.National Science Council (China) (grants NSC 100-2221-E-002-127-MY3 and NSC 100-2221-E-002-077- MY3

Development and Evaluation of a Powered Artificial Gastrocnemius for Transtibial Amputee Gait

Existing robotic transtibial prostheses provide only ankle joint actuation and do not restore biarticular function of the gastrocnemius muscle. This paper presents the first powered biarticular transtibial prosthesis, which is a combination of a commercial powered ankle-foot prosthesis and a motorized robotic knee orthosis. The orthosis is controlled to emulate the human gastrocnemius based on neuromuscular models of matched nonamputees. Together with the ankle-foot prosthesis, the devices provide biarticular actuation. We evaluate differences between this biarticular condition and a monoarticular condition with the orthosis behaving as a free-joint. Six participants with transtibial amputation walk with the prosthesis on a treadmill while motion, force, and metabolic data are collected and analyzed for differences between conditions. The biarticular prosthesis reduces affected-side biological knee flexion moment impulse and hip positive work during late-stance knee flexion, compared to the monoarticular condition. The data do not support our hypothesis that metabolism decreases for all participants, but some participants demonstrate large metabolic reductions with the biarticular condition. These preliminary results suggest that a powered artificial gastrocnemius may be capable of providing large metabolic reductions compared to a monoarticular prosthesis, but further study is warranted to determine an appropriate controller for achieving more consistent metabolic benefits.United States. National Aeronautics and Space Administration (Grant NNX12AM16G