Part I Applied Methodology
1 Introduction to Quantitative Physiology
1.1 Understanding Physiology
1.2 Towards Quantitative Science
1.3 From Genome to Physiome
1.4 Dealing with Complexity
1.5 Why It Is Timely to Study Quantitative Physiology
1.5.1 Multi-Omic Revolution in Biology
1.5.2 Big Data and Personalised Medicine
1.5.3 Genetic Editing and Synthetic Biology
1.6 Questions
References
2 Systems and Modelling
2.1 Modelling Process
2.2 Physiological Organ Systems
2.3 Equation Models
2.4 Using ODEs in Modelling Physiology
2.4.1 Modelling Oscillations
2.4.2 Linear Stability Analysis
2.4.3 Solving ODEs with the g-Function
2.5 Conservation Laws in Physiology
2.5.1 Conservation of Momentum and Energy
2.5.2 Boxing With and Without Gloves
2.5.3 Rotational Movement
2.6 Questions
References
3 Introduction to Basic Modelling
3.1 Building a Simple Mathematical Model
3.1.1 Model of Falling Flea
3.1.2 Scaling Arguments
3.1.3 Example: How High Can an Animal Jump
3.1.4 Example: How Fast Can we Walk before Breaking into a Run
3.2 Models that Involve Metabolic Rate
3.2.1 Modelling Metabolic Rate
3.2.2 Example: Why do Large Birds find it Harder to Fly
3.2.3 Ludwig von Bertalanffy"s Growth Model
3.3 Questions
Reference
4 Modelling Resources
4.1 Open Courses
4.2 Modelling Software
4.3 Model Repositories
4.4 Questions
References
Part H Basic Case Studies
5 Modelling Gene Expression
5.1 Modelling Transcriptional Regulation and Simple Networks
5.1.1 Basic Notions and Equations
5.1.2 Equations for Transcriptional Regulation
5.1.3 Examples of Some Common Genetic Networks
5.2 Simultaneous Regulation by Inhibition and Activation
5.3 Autorepressor with Delay
5.4 Bistable Genetic Switch
5.5 Questions
References
6 Metabolic Network
6.1 Metabolism and Network
6.2 Constructing Metabolic Network
6.3 Flux Balance Analysis
6.4 Myocardial Metabolic Network
6.5 Questions
References
7 Calcium Signalling
7.1 Functions of Calcium
7.2 Calcium Oscillations
7.3 Calcium Waves
7.4 Questions
References
8 Modelling Neural Activity
8.1 Introduction to Brain Research
8.2 The Hodgkin-Huxley Model of Neuron Firing
8.3 The FitzHugh-Nagumo Model: A Model of the HH Model
8.3.1 Analysis of Phase Plane with Case Ia
8.3.2 Case Ia > 0 and Conditions to Observe a Limit Cycle
8.4 Questions
References
9 Blood Dynamics
9.1 Blood Hydrodynamics
9.1.1 Basic Equations
9.1.2 Poiseuille"s Law
9.2 Properties of Blood and ESR
9.3 Elasticity of Blood Vessels
9.4 The Pulse Wave
9.5 Bernoulli"s Equation and What Happened to Arturo Toscanini in 1954
9.6 The Korotkoff Sounds
9.7 Questions
Reference
10 Bone and Body Mechanics
10.1 Elastic Deformations and the Hooke"s Law
10.2 Why Long Bones are Hollow or Bending of Bones
10.3 Viscoelasticity of Bones
10.4 Questions
Reference
Part IH Complex Applications
11 Constructive Effects of Noise
11.1 Influence of Stochasticity
11.2 Review of Noise-Induced Effects
11.3 New Mechanisms of Noise-Induced Effects
11.4 Noise-Induced Effects
11.4.1 Stochastic Resonance in Bone Remodelling as a Tool to Prevent
Bone Loss in Osteopenic Conditions
11.4.2 Transitions in the Presence of Additive Noise and On-Off
Intermittency
11.4.3 Phase Transitions Induced by Additive Noise
11.4.4 Noise-Induced Excitability
11.5 Doubly Stochastic Effects
11.5.1 Doubly Stochastic Resonance
11.5.2 A Simple Electronic Circuit Model for Doubly Stochastic
Resonance
11.5.3 Doubly Stochastic Coherence: Periodicity via Noise-Induced
Symmetry in Bistable Neural Models
11.6 New Effects in Noise-Induced Propagation
11.6.1 Noise-Induced Propagation in Monostable Media
11.6.2 Noise-Induced Propagation and Frequency Selection of
Bichromatic Signals in Bistable Media
11.7 Noise-Induced Resonant Effects and Resonant Effects in the Presence of
Noise
11.7.1 Vibrational Resonance in a Noise-Induced Structure
11.7.2 System Size Resonance in Coupled Noisy Systems
11.7.3 Coherence Resonance and Polymodality in Inhibitory Coupled
Excitable Oscillators
11.8 Applications and Open Questions
11.9 Questions
References
12 Complex and Surprising Dynamics in Gene Regulatory Networks
12.1 Nonlinear Dynamics in Synthetic Biology
12.2 Clustering and Oscillation Death in Genetic Networks
12.2.1 The Repressilator with Quorum Sensing Coupling
12.2.2 The Dynamical Regimes for a Minimal System of Repressilators
Coupled via Phase-Repulsive Quorum Sensing
12.3 Systems Size Effects in Coupled Genetic Networks
12.3.1 Clustering and Enhanced Complexity of the Inhomogeneous
Regimes
12.3.2 Clustering Due to Regular Oscillations in Cell Colonies
12.3.3 Parameter Heterogeneity on the Regular-Attractor Regime
12.3.4 Irregular and Chaotic Self-Oscillations in Colonies of Identical
Cells
12.4 The Constructive Role of Noise in Genetic Networks
12.4.1 Noise-Induced Oscillations in Circadian Gene Networks
12.4.2 Noise-Induced Synchronisation and Rhythms
12.5 Speed Dependent Cellular Decision Making (SdCDM) in Noisy Genetic
Networks
12.5.1 Speed Dependent Cellular Decision Making in a Small Genetic
Switch
12.5.2 Speed Dependent Cellular Decision Making in Large Genetic
Networks
12.6 What is a Genetic Intelligence
12.6.1 Supervised Learning
12.6.2 Associative Learning
12.6.3 Classification of Complex Inputs
12.6.4 Applications and Implications of Bio-Artificial Intelligence
12.7 Effect of Noise in Intelligent Cellular Decision Making
12.7.1 Stochastic Resonance in an Intracellular Associative Genetic
Perceptron
12.7.2 Stochastic Resonance in Classifying Genetic Perceptron
12.8 Questions
References
13 Modelling Complex Phenomena in Physiology
13.1 Cortical Spreading Depression (CSD)
13.1.1 Whatis CSD
13.1.2 Models of CSD
13.1.3 Applications of CSD Models
13.1.4 Questions
13.2 Heart Physiome
13.2.1 Cardiovascular System
13.2.2 Heart Physiorne
13.2.3 Multi-Level Modelling
13.2.4 Questions
13.3 Modelling of Kidney Autoregulation
13.3.1 Renal Physiology
13.3.2 Experimental Observations
13.3.3 Model of Nephron Autoregulation
13.3.4 Questions
13.4 Brain Project
13.4.1 Mystery of Brain
13.4.2 Brain Projects
13.4.3 Brain Simulation
13.4.4 Mammalian Brain as a Network of Networks
13.4.5 Calculation of Integrated Information
13.4.6 Astrocytes and Integrated Information Theory of Consciousness
13.4.7 Questions
References
