Individuation and the organization in complex living ecosystem: recursive integration and self-assertion by holon-lymphocytes

International audienceIndividuation and organization in complex living multi-level ecosystem occurs as dynamical processes from early ontogeny. The notion of living “holon” displaying dynamic self-assertion and integration is used here to explain the ecosystems dynamic processes. The update of the living holon state according to the continuous change of the dynamic system allows for its viability. This is interpreted as adaptation, selection and organization by the human that observes the system at posteriori from its level. Our model concerns the complex dynamics of the adaptive immune system, integrating holon-lymphocytes that collectively preserve the identity and integrity of the organism. Each lymphocyte individualizes as a dynamic holon-lymphocyte, with somatic gene individuation leading to an individual, singular antigen immunoreceptor type, promoting the self-assertion. In turn, the “Immunoception” allows for perception of the environmental antigenic context, thus integration of the holon in its environment. The self-assertion/integration of holon-lymphocyte starts from fetal stages and is influenced by mother Lamarckian acquired historicity transmissions, a requisite for the integrity of the holobiont-organism. We propose a dynamic model of the perception by holon-lymphocyte, and at the supra-clonal level of the immune system functions that sustain the identity and integrity of the holon-holobiont organism

In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation.

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease

Signaling Pathways Activated by Interleukin-2 and Interluekin-4 Receptors Mediate T Lymphocyte Clonal Expansion

Cells sense and respond to chemical and physical stimuli through signal transduction pathways, which mediate cell proliferation, differentiation, migration, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the adaptive immune system, particularly influencing the clonal expansion and differentiation of T cells. At least in culture, both synergistic and antagonistic effects of IL-2 and IL-4 co-stimulation have been reported; the antagonism, when observed, is thought to arise from the utilization of a common subunit shared by IL-2 and IL-4 receptors. We have sought to characterize IL-2 and IL-4 signaling at the level of intracellular pathways activated by these receptors. IL-2 receptors are known to activate the Ras/extracellular signal-regulated kinase (Erk) and phosphoinositide (PI) 3-kinase/Akt pathways as well as the STAT5 transcription factor. IL-4 is unique among cytokines in that it does not activate Ras/Erk; it does activate PI 3-kinase/Akt as well as a distinct STAT, STAT6. The HT-2 mouse T cell line responds to both IL-2 and IL-4. We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation in a dose-dependent manner. Additionally, transient signaling through the PI3K/Akt and Ras/Erk pathways are required for optimal T cell proliferation. IL-4 stimulates cell adhesion in static cultures, again in a dose-dependent fashion, and it partially inhibits IL-2-stimulated activation of Akt, Erk and STAT5, consistent with a competition effect. IL-2/IL-4 co-stimulation provokes transient activation of Akt, Erk and STAT5 coupled with prolonged activation of STAT6. This signaling profile and the cell adhesion response suggest potential mechanisms by which IL-4 influences the proliferation of helper T cells

통합형 무인 수상선-케이블-수중선 시스템의 다물체동역학 거동 및 제어

Underwater exploration is becoming more and more important, since a vast range of unknown resources in the deep ocean remain undeveloped. This dissertation thus presents a modeling of the coupled dynamics of an Unmanned Surface Vehicle (USV) system with an Underwater Vehicles (UV) connected by an underwater cable (UC). The complexity of this multi-body dynamics system and ocean environments is very difficult to model. First, for modeling this, dynamics analysis was performed on each subsystem and further total coupled system dynamics were studied. The UV which is towed by a UC is modeled with 6-DOF equations of motion that reflects its hydrodynamic characteristic was studied. The 4th-order Runge–Kutta numerical method was used to analyze the motion of the USV with its hydrodynamic coefficients which were obtained through experiments and from the literature. To analyze the effect of the UC, the complicated nonlinear and coupled UC dynamics under currents forces, the governing equations of the UC dynamics are established based on the catenary equation method, then it is solved by applying the shooting method. The new formulation and solution of the UC dynamics yields the three dimensional position and forces of the UC end point under the current forces. Also, the advantage of the proposed method is that the catenary equations using shooting method can be solved in real time such that the calculated position and forces of UC according to time can be directly utilized to calculate the UV motion. The proposed method offers advantages of simple formulation, convenient use, and fast calculation time with exact result. Some simple numerical simulations were conducted to observe the dynamic behaviors of AUV with cable effects. The simulations results clearly reveal that the UC can greatly influence the motions of the vehicles, especially on the UV motions. Based on both the numerical model and simulation results developed in the dissertation, we may offer some valuable information for the operation of the UV and USV. Secondly, for the design controller, a PD controller and its application to automatic berthing control of USV are also studied. For this, a nonlinear mathematical model for the maneuvering of USV in the presence of environmental forces was firstly established. Then, in order to control rudder and propeller during automatic berthing process, a PD control algorithm is applied. The algorithm consists of two parts, the forward velocity control and heading angle control. The control algorithm was designed based on the longitudinal and yaw dynamic models of USV. The desired heading angle was obtained by the so-called “Line of Sight” method. To support the validity of the proposed method, the computer simulations of automatic USV berthing are carried out. The results of simulation showed good performance of the developed berthing control system. Also, a hovering-type AUV equipped with multiple thrusters should maintain the specified position and orientation in order to perform given tasks by applying a dynamic positioning (DP) system. Besides, the control allocation algorithm based on a scaling factor is presented for distributing the forces required by the control law onto the available set of actuators in the most effective and energy efficient way. Thus, it is necessary for the robust control algorithm to conduct successfully given missions in spite of a model uncertainty and a disturbance. In this dissertation, the robust DP control algorithm based on a sliding mode theory is also addressed to guarantee the stability and better performance despite the model uncertainty and disturbance of current and cable effects. Finally, a series of simulations are conducted to verify the availability of the generated trajectories and performance of the designed robust controller. Thirdly, for the navigation of UV, a method for designing the path tracking controller using a Rapidly-exploring Random Trees (RRT) algorithm is proposed. The RRT algorithm is firstly used for the generation of collision free waypoints. Next, the unnecessary waypoints are removed by a simple path pruning algorithm generating a piecewise linear path. After that, a path smoothing algorithm utilizing cubic Bezier spiral curves to generate a continuous curvature path that satisfies the minimum radius of curvature constraint of underwater is implemented. The angle between two waypoints is the only information required for the generation of the continuous curvature path. In order to underwater vehicle follow the reference path, the path tracking controller using the global Sliding Mode Control (SMC) approach is designed. To verify the performance of the proposed algorithm, some simulation results are performed. Simulation results showed that the RRT algorithm could be applied to generate an optimal path in a complex ocean environment with multiple obstacles.Acknowledgement .................................................................................................. vi Abstract……. ....................................................................................... ………….viii Nomenclature ....................................................................................................... xvi List of Abbreviations ........................................................................................... xxi List of Tables ...................................................................................................... xxiii List of Figures ..................................................................................................... xxiv Chapter 1: Introduction ......................................................................................... 1 1.1 Background .................................................................................................. 1 1.1.1 Unmanned Surface Vehicles (USVs) ...................................................... 1 1.1.2 Umbilical Cable ....................................................................................... 4 1.1.3 Unmanned Underwater Vehicles (UUVs) ............................................... 5 1.1.4 Literature on Modeling of Marine Vehicles ............................................ 9 1.1.5 Literature on Control and Guidance of Marine Vehicles ...................... 11 1.2 Our System Architecture ........................................................................... 12 1.3 Motivation ................................................................................................. 13 1.4 Contribution ............................................................................................... 16 1.5 Publications Associated to the Dissertation .............................................. 17 1.6 Structure of the Dissertation ...................................................................... 18 Chapter 2: Mathematical Model of Unmanned Surface Vehicle (USV) ......... 20 2.1 Basic Assumptions .................................................................................... 20 2.2 Three Coordinate Systems ......................................................................... 20 2.3 Variable Notation ...................................................................................... 22 2.4 Kinematics ................................................................................................. 23 2.5 Kinetics ...................................................................................................... 26 2.5.1 Rigid Body Equations of Motion ........................................................... 26 2.5.2 Hydrodynamic Forces and Moments ..................................................... 28 2.5.3 Restoring Forces and Moments ............................................................. 31 2.5.4 Environmental Disturbances .................................................................. 32 2.5.5 Propulsion Forces and Moments ........................................................... 35 2.6 Nonlinear 6DOF Dynamics ....................................................................... 35 2.7 Mathematical Model of USV in 3 DOF .................................................... 36 2.7.1 Planar Kinematics .................................................................................. 36 2.7.2 Planar Nonlinear 3 DOF Dynamics ....................................................... 38 2.8 Configuration of Thrusters ........................................................................ 40 2.9 General Structure and Model Parameters .................................................. 41 2.9.1 Structure of USV ................................................................................... 41 2.9.2 Control System of USV ......................................................................... 42 2.9.3 Winch Control System ........................................................................... 43 Chapter 3: Mathematical Model of the Umbilical Cable (UC) ........................ 45 3.1 Basic Assumptions for UC ........................................................................ 45 3.2 Analysis on Forces of UV ......................................................................... 47 3.3 Relation for UC Equilibrium ..................................................................... 50 3.4 Catenary Equation in the Space Case ........................................................ 51 3.5 Shooting Method ....................................................................................... 55 3.6 Boundary Conditions ................................................................................. 57 3.7 Cable Effects ............................................................................................. 58 3.8 Model Parameters and Simulation ............................................................. 59 Chapter 4: Mathematical Model of Underwater Vehicle (UV) ........................ 63 4.1 Background ................................................................................................ 63 4.1.1 Basic Assumptions................................................................................. 63 4.1.2 Reference Frames .................................................................................. 64 4.1.3 Notations ................................................................................................ 65 4.2 Kinematics Equations ................................................................................ 66 4.3 Kinetic Equations ...................................................................................... 67 4.3.1 Rigid-Body Kinetics .............................................................................. 67 4.3.2 Hydrostatic Terms ................................................................................. 69 4.3.3 Hydrodynamic Terms ............................................................................ 70 4.3.4 Actuator Modeling ................................................................................. 75 4.3.5 Umbilical Cable Forces ......................................................................... 75 4.4 Nonlinear Equations of Motion (6DOF) ................................................... 76 4.5 Simplification of UV Dynamic Model ...................................................... 77 4.5.1 Simplifying the Mass and Inertia Matrix ............................................... 78 4.5.2 Simplifying the Hydrodynamic Damping Matrix.................................. 79 4.5.3 Simplifying the Gravitational and Buoyancy Vector ............................ 80 4.6 Thruster Modeling ..................................................................................... 80 4.7 Current Modeling ...................................................................................... 83 4.8 Dynamic Model Including Ocean Currents ............................................... 84 4.9 Complete Motion Equations of AUV (6DOF) .......................................... 89 4.10 Dynamics Model Parameter Identification ................................................ 91 4.11 Numerical Solution for Equations of Motion ............................................ 93 4.12 General Structure and Model Parameters .................................................. 94 4.12.1 Structure of AUV ............................................................................... 94 4.12.2 Control System of AUV ..................................................................... 96 Chapter 5: Guidance Theory ............................................................................... 97 5.1 Configuration of GNC System .................................................................. 97 5.1.1 Guidance ................................................................................................ 98 5.1.2 Navigation .............................................................................................. 98 5.1.3 Control ................................................................................................... 98 5.2 Maneuvering Problem Statement .............................................................. 99 5.3 Guidance Objectives ................................................................................ 100 5.3.1 Target Tracking ................................................................................... 100 5.3.2 Trajectory Tracking ............................................................................. 100 5.4 Waypoint Representation ........................................................................ 101 5.5 Path Following ......................................................................................... 102 5.6 Line of Sight (LOS) Waypoint Guidance ................................................ 102 5.6.1 Enclosure-Based Steering .................................................................... 104 5.6.2 Look-ahead Based Steering ................................................................. 105 5.6.3 LOS Control......................................................................................... 106 5.7 Cubic Polynomial for Path-Following ..................................................... 107 Chapter 6: Control Algorithm Design and Analysis ....................................... 110 6.1 Proportional Integral Differential (PID) Controller ................................ 110 6.1.1 General Theory .................................................................................... 110 6.1.2 Stability of General PID Controller ..................................................... 112 6.1.3 PID Tuning .......................................................................................... 114 6.1.4 Nonlinear PID for Marine Vehicles ..................................................... 116 6.1.5 Nonlinear PD for Marine Vehicles ...................................................... 117 6.1.6 Stability of Designed PD Controller .................................................... 117 6.2 Sliding Mode Controller .......................................................................... 118 6.2.1 Tracking Error and Sliding Surface ..................................................... 119 6.2.2 Chattering Situation ............................................................................. 120 6.2.3 Control Law and Stability .................................................................... 121 6.3 Allocation Control ................................................................................... 124 6.3.1 Linear Quadratic Unconstrained Control Allocation Using Lagrange Multipliers ................................................................................................ 125 6.3.2 Thruster Allocation with a Constrained Linear Model ........................ 127 6.4 Simulation Results and Discussion ......................................................... 131 6.4.1 Berthing (parking) Control of USV ..................................................... 133 6.4.2 Motion Control of UV ......................................................................... 136 Chapter 7: Obstacle Avoidance and Path Planning for Vehicle Using Rapidly-Exploring Random Trees Algorithm.................................................................. 168 7.1 Path Planning and Guidance: Two Interrelated Problems ....................... 168 7.2 RRT Algorithm for Exploration .............................................................. 171 7.2.1 Random Node Selection ...................................................................... 172 7.2.2 Nearest Neighbor Node Selection ....................................................... 173 7.2.3 RRT Exploration with Obstacles ......................................................... 174 7.3 RRT Algorithm for Navigation of AUV ................................................. 176 7.3.1 Basic RRT Algorithm .......................................................................... 176 7.3.2 Biased-Greedy RRT Algorithm ........................................................... 178 7.3.3 Synchronized Biased-Greedy RRT Algorithm .................................... 179 7.4 Path Pruning ............................................................................................ 182 7.4.1 Path Pruning Using LOS ..................................................................... 182 7.4.2 Global Path Pruning ............................................................................. 183 7.5 Summarize the Proposed RRT Algorithm ............................................... 185 7.6 Simulation for Path Following of AUV .................................................. 187 Chapter 8: Simulation of Complete USV-UC-UV Systems ............................ 196 8.1 Simulation Procedure .............................................................................. 196 8.2 Simulation Results and Discussion ......................................................... 201 8.2.1 Dynamic Behaviors of Complete USV (Stable)-Cable- AUV (Turning Motion) ..................................................................................................... 201 8.2.2 Dynamic Behaviors of Complete USV (Forward motion)-Cable- AUV (Turning Motion) ...................................................................................... 207 8.2.3 Applied Controller to Complete USV -Cable- AUV ........................... 215 Chapter 9: Conclusions and Future Works ..................................................... 238 9.1 Modeling of Complete USV-Cable-AUV System .................................. 238 9.2 Motion Control ........................................................................................ 239 9.3 Cable Force and Moment at the Tow Points ........................................... 239 9.4 Path Planning ........................................................................................... 239 9.5 Future Works ........................................................................................... 240Docto