Spatiotemporal Modeling of Stem Cell Differentiation: Partial Differentiation Equation Analysis in R covers topics surrounding how stem cells evolve into specialized cells during tissue formation and in diseased tissue regeneration. As the process of stem cell differentiation occurs in space and time, the mathematical modeling of spatiotemporal development is expressed in this book as systems of partial differential equations (PDEs). In addition, the book explores important feature of six PDE model which can represent, for example, the development of tissue in organs. In addition, the book covers the computer-based implementation of example models through routines coded (programmed) in R. The routines described in the book are available from a download link so that example models can be executed without having to first study numerical methods and computer coding. The routines can then be applied to variations and extensions of the stem differentiation models, such as changes in the PDE parameters (constants) and the form of the model equations.

PDE Modeling of Tissue Engineering and Regenerative Medicine: Computer Analysis in R presents the formulation and computer implementation of mathematical models for the forefront research areas of tissue engineering and regenerative medicine. The mathematical model discussed in this book consists of a system of eight partial differential equations (PDEs) with dependent variables. The computer-based example models are presented through routines coded in R-a quality, open-source scientific computing system that is readily available from the Internet. Formal mathematics is minimized, e.g., no theorems and proofs. Includes detailed examples that the reader can execute on modest computers.

ODE/PDE Analysis of Antibiotic/Antimicrobial Resistance: Programming in R presents mathematical models for antibiotic/antimicrobial resistance based on ordinary and partial differential equations (ODE/PDEs). Sections cover the basic ODE model, the detailed PDE model that gives the spatiotemporal distribution of four dependent variable components, including susceptible bacteria population density, resistant bacteria population density, plasmid number, and antibiotic concentration. The computer-based implementation of the example models is presented through routines coded (programmed) in R, a quality, open-source scientific computing system that is readily available from the Internet. As such, formal mathematics is minimized and no theorems and proofs are required. The PDE analysis is based on the method of lines (MOL), an established general algorithm for PDEs that is implemented with finite differences. Routines are available from a download link so that the example models can be executed without having to first study numerical methods and computer coding. Routines can then be applied to variations and extensions of the antibiotic/antimicrobial models, such as changes in the ODE/PDE parameters (constants) and the form of the model equations.

Modeling of Post-Myocardial Infarction: ODE/PDE Analysis with R presents mathematical models for the dynamics of a post-myocardial (post-MI), aka, a heart attack. The mathematical models discussed consist of six ordinary differential equations (ODEs) with dependent variables Mun; M1; M2; IL10; Ta; IL1. The system variables are explained as follows: dependent variable Mun = cell density of unactivated macrophage; dependent variable M1 = cell density of M1 macrophage; dependent variable M2 = cell density of M2 macrophage; dependent variable IL10 = concentration of IL10, (interleuken-10); dependent variable Ta = concentration of TNF-a (tumor necrosis factor-a); dependent variable IL1 = concentration of IL1 (interleuken-1). The system of six ODEs does not include a spatial aspect of an MI in the cardiac tissue. Therefore, the ODE model is extended to include a spatial effect by the addition of diffusion terms. The resulting system of six diffusion PDEs, with x (space) and t (time) as independent variables, is integrated (solved) by the numerical method of lines (MOL), a general numerical algorithm for PDEs.

ODE/PDE Alpha-Synuclein Models for Parkinson's Disease discusses a mechanism for the evolution of Parkinson's Disease (PD) based on the dynamics of the protein a-synuclein, a monomer that has been implicated in this disease. Specifically, a-synuclein morphs and aggregates into a polymer that can interfere with functioning neurons and lead to neurodegenerative pathology. This book first demonstrates computer-based implementation of a prototype ODE/PDE model for the dynamics of the a-synuclein monomer and polymer, and then details the methodology for the numerical integration of ODE/PDE systems which can be applied to computer-based analyses of alternative models based on the reader's interest. This book facilitates immediate computer use for research without the necessity to first learn the basic concepts of numerical analysis for ODE/PDEs and programming algorithms

Although the Partial Differential Equations (PDE) models that are now studied are usually beyond traditional mathematical analysis, the numerical methods that are being developed and used require testing and validation. This is often done with PDEs that have known, exact, analytical solutions. The development of analytical solutions is also an active area of research, with many advances being reported recently, particularly traveling wave solutions for nonlinear evolutionary PDEs. Thus, the current development of analytical solutions directly supports the development of numerical methods by providing a spectrum of test problems that can be used to evaluate numerical methods.

This book surveys some of these new developments in analytical and numerical methods, and relates the two through a series of PDE examples. The PDEs that have been selected are largely "named'' since they carry the names of their original contributors. These names usually signify that the PDEs are widely recognized and used in many application areas. The authors intention is to provide a set of numerical and analytical methods based on the concept of a traveling wave, with a central feature of conversion of the PDEs to ODEs.

The Matlab and Maple software will be available for download from this website shortly.

www.pdecomp.net
Includes a spectrum of applications in science, engineering, applied mathematicsPresents a combination of numerical and analytical methodsProvides transportable computer codes in Matlab and Maple"

Numerical PDE Analysis of Retinal Neovascularization Mathematical Model Computer Implementation in R provides a methodology for the analysis of neovascularization (formation of blood capillaries) in the retina. It describes the starting point-a system of three partial differential equations (PDEs)-that define the evolution of (1) capillary tip density, (2) blood capillary density and (3) concentration of vascular endothelial growth factor (VEGF) in the retina as a function of space (distance along the retina), x, and time, t, the three PDE dependent variables for (1), (2) and (3), and designated as u1(x, t), u2(x, t), u3(x, t), amongst other topics.

Two models for the spread and control of a virus are detailed in this book: The Lung/Respiratory System Model (LSM) and the SVIR (Susceptible-Vaccinated-Infected-Recovered) Model.The LSM gives the spatiotemporal distribution of four viral-related proteins: virus population density along the lung air passage, host cell primary infection protein (viral genetic material (VGM)) concentration, host cell secondary infection protein (VGM) concentration, and air stream virion population density.The model is executed for a single inhalation, and a series of inhalation/exhalation cycles. For the latter, the progression of the viral infection into the lung is a principal result.The SVIR is first formulated as a system of ordinary differential equations (ODEs) in time, then extended to a system of PDEs to account for spatial effects (spatiotemporal modeling).Principal outputs from the ODE/PDE models are the levels of vaccinations and infections. For the latter, the efficacy of the vaccine is a parameter that can be varied in a computer-based analysis of a vaccine therapy.The coding of the models is in R, a quality, open-source scientific computing system, and can be executed on modest computers. The R routines are available from a download link so that the example models can be executed without having to first study numerical methods and computer coding. The routines can then be applied to variations and extensions of the ODE/PDE models, such as changes in the parameters and the form of the model equations.

Partial differential equations (PDEs) are one of the most used widely forms of mathematics in science and engineering. PDEs can have partial derivatives with respect to (1) an initial value variable, typically time, and (2) boundary value variables, typically spatial variables. Therefore, two fractional PDEs can be considered, (1) fractional in time (TFPDEs), and (2) fractional in space (SFPDEs). The two volumes are directed to the development and use of SFPDEs, with the discussion divided as: Vol 1: Introduction to Algorithms and Computer Coding in R Vol 2: Applications from Classical Integer PDEs. Various definitions of space fractional derivatives have been proposed. We focus on the Caputo derivative, with occasional reference to the Riemann-Liouville derivative. The Caputo derivative is defined as a convolution integral. Thus, rather than being local (with a value at a particular point in space), the Caputo derivative is non-local (it is based on an integration in space), which is one of the reasons that it has properties not shared by integer derivatives. A principal objective of the two volumes is to provide the reader with a set of documented R routines that are discussed in detail, and can be downloaded and executed without having to first study the details of the relevant numerical analysis and then code a set of routines. In the first volume, the emphasis is on basic concepts of SFPDEs and the associated numerical algorithms. The presentation is not as formal mathematics, e.g., theorems and proofs. Rather, the presentation is by examples of SFPDEs, including a detailed discussion of the algorithms for computing numerical solutions to SFPDEs and a detailed explanation of the associated source code.

Aimed at graduates and researchers, and requiring only a basic knowledge of multi-variable calculus, this introduction to computer-based partial differential equation (PDE) modeling provides readers with the practical methods necessary to develop and use PDE mathematical models in biomedical engineering. Taking an applied approach, rather than using abstract mathematics, the reader is instructed through six biomedical example applications, each example characterized by step-by-step discussions of established numerical methods and implemented in reliable computer routines. Adopting this technique, the reader will understand how PDE models are formulated, implemented and tested. Supported by a set of rigorously tested general purpose PDE routines online, and with enhanced understanding through animations, this book will be ideal for anyone faced with interpreting large experimental data sets that need to be analyzed with PDE models in biomedical engineering.

The reproduction and spread of a virus during an epidemic proceeds when the virus attaches to a host cell and viral genetic material (VGM) (protein, DNA, RNA) enters the cell, then replicates, and perhaps mutates, in the cell. The movement of the VGM across the host cell outer membrane and within the host cell is a spatiotemporal dynamic process that is modeled in this book as a system of ordinary and partial differential equations (ODE/PDEs). The movement of the virus proteins through the cell membrane is modeled as a diffusion process expressed by the diffusion PDE (Fick's second law). Within the cell, the time variation of the VGM is modeled as ODEs. The evolution of the dependent variables is computed by the numerical integration of the ODE/PDEs starting from zero initial conditions (ICs). The departure of the dependent variables from zero is in response to the virus protein concentration at the outer membrane surface (the point at which the virus binds to the host cell). The numerical integration of the ODE/PDEs is performed with routines coded (programmed) in R, a quality, open-source scientific computing system that is readily available from the Internet. Formal mathematics is minimized, e.g., no theorems and proofs. Rather, the presentation is through detailed examples that the reader/researcher/analyst can execute on modest computers. The ODE/PDE dependent variables are displayed graphically with basic R plotting utilities. The R routines are available from a download link so that the example models can be executed without having to first study numerical methods and computer coding. The routines can then be applied to variations and extensions of the ODE/PDE model, such as changes in the parameters and the form of the model equations.

The reproduction and spread of a virus during an epidemic proceeds when the virus attaches to a host cell and viral genetic material (VGM) (protein, DNA, RNA) enters the cell, then replicates, and perhaps mutates, in the cell. The movement of the VGM across the host cell outer membrane and within the host cell is a spatiotemporal dynamic process that is modeled in this book as a system of ordinary and partial differential equations (ODE/PDEs). The movement of the virus proteins through the cell membrane is modeled as a diffusion process expressed by the diffusion PDE (Fick's second law). Within the cell, the time variation of the VGM is modeled as ODEs. The evolution of the dependent variables is computed by the numerical integration of the ODE/PDEs starting from zero initial conditions (ICs). The departure of the dependent variables from zero is in response to the virus protein concentration at the outer membrane surface (the point at which the virus binds to the host cell). The numerical integration of the ODE/PDEs is performed with routines coded (programmed) in R, a quality, open-source scientific computing system that is readily available from the Internet. Formal mathematics is minimized, e.g., no theorems and proofs. Rather, the presentation is through detailed examples that the reader/researcher/analyst can execute on modest computers. The ODE/PDE dependent variables are displayed graphically with basic R plotting utilities. The R routines are available from a download link so that the example models can be executed without having to first study numerical methods and computer coding. The routines can then be applied to variations and extensions of the ODE/PDE model, such as changes in the parameters and the form of the model equations.

The focus of this book is a detailed discussion of a dual cancer vaccine (CV)-immune checkpoint inhibitor (ICI) mathematical model formulated as a system of partial differential equations (PDEs) defining the spatiotemporal distribution of cells and biochemicals during tumor growth. A computer implementation of the model is discussed in detail for the quantitative evaluation of CV-ICI therapy. The coding (programming) consists of a series of routines in R, a quality, open-source scientific computing system that is readily available from the internet. The routines are based on the method of lines (MOL), a general PDE algorithm that can be executed on modest computers within the basic R system. The reader can download and use the routines to confirm the model solutions reported in the book, then experiment with the model by varying the parameters and modifying/extending the equations, and even studying alternative models with the PDE methodology demonstrated by the CV-ICI model. Spatiotemporal Modeling of Cancer Immunotherapy: Partial Differential Equation Analysis in R facilitates the use of the model, and more generally, computer- based analysis of cancer immunotherapy mathematical models, as a step toward the development and quantitative evaluation of the immunotherapy approach to the treatment of cancer. To download the R routines, please visit: http://www.lehigh.edu/~wes1/ci_download

The book is intended for readers who are interested in learning about the use of computer-based modelling of the COVID-19 disease. It provides a basic introduction to a five-ordinary differential equation (ODE) model by providing a complete statement of the model, including a detailed discussion of the ODEs, initial conditions and parameters, followed by a line-by-line explanation of a set of R routines (R is a quality, scientific programming system readily available from the Internet). The reader can access and execute these routines without having to first study numerical algorithms and computer coding (programming) and can perform numerical experimentation with the model on modest computers.

This book has a two-fold purpose: (1) An introduction to the computer-based modeling of influenza, a continuing major worldwide communicable disease. (2) The use of (1) as an illustration of a methodology for the computer-based modeling of communicable diseases. For the purposes of (1) and (2), a basic influenza model is formulated as a system of partial differential equations (PDEs) that define the spatiotemporal evolution of four populations: susceptibles, untreated and treated infecteds, and recovereds. The requirements of a well-posed PDE model are considered, including the initial and boundary conditions. The terms of the PDEs are explained. The computer implementation of the model is illustrated with a detailed line-by-line explanation of a system of routines in R (a quality, open-source scientific computing system that is readily available from the Internet). The R routines demonstrate the straightforward numerical solution of a system of nonlinear PDEs by the method of lines (MOL), an established general algorithm for PDEs. The presentation of the PDE modeling methodology is introductory with a minumum of formal mathematics (no theorems and proofs), and with emphasis on example applications. The intent of the book is to assist in the initial understanding and use of PDE mathematical modeling of communicable diseases, and the explanation and interpretation of the computed model solutions, as illustrated with the influenza model.

The remarkable functionality of the brain is made possible by the metabolism (chemical reaction) of oxygen (O2) and nutrients in the brain. These metabolism components are supplied to the brain by an intricate blood circulatory system (vasculature). The blood brain barrier (BBB), which is the central topic of this book, determines the rate of transfer from the blood to the brain tissue.In particular, mathematical models are developed for mass transfer across the BBB based on partial differential equations (PDEs) applied to the blood capillaries, the endothelial membrane, and the brain tissue. The PDEs derived from mass balances and computer routines in R are presented for the numerical (computer-based) solution of the PDEs. The computed concentration profiles of the transferred components are functions of time and space within the BBB system, i.e., spatiotemporal solutions.The R routines and the associated numerical algorithms for computing the numerical solutions are discussed in detail. The discussion is introductory, without formal mathematics, e.g., theorems and proofs. The general methodology (algorithm) for numerical PDE solutions is the method of lines (MOL).The models are used to study the transfer of oxygen and nutrients, harmful substances that should not enter the brain such as chemicals and pathogens (viruses, bacteria), and therapeutic drugs. The intent of the book is to provide a quantitative approach to the study of BBB dynamics using a computer-based methodology programmed in R, a quality open-source scientific programming system that is easily downloaded from the Internet for execution on modest computers.

The intent of this book is to provide a methodology for the analysis of infectious diseases by computer-based mathematical models. The approach is based on ordinary differential equations (ODEs) that provide time variation of the model dependent variables and partial differential equations (PDEs) that provide time and spatial (spatiotemporal) variations of the model dependent variables.The starting point is a basic ODE SIR (Susceptible Infected Recovered) model that defines the S,I,R populations as a function of time. The ODE SIR model is then extended to PDEs that demonstrate the spatiotemporal evolution of the S,I,R populations. A unique feature of the PDE model is the use of cross diffusion between populations, a nonlinear effect that is readily accommodated numerically. A second feature is the use of radial coordinates to represent the geographical distribution of the model populations.The numerical methods for the computer implementation of ODE/PDE models for infectious diseases are illustrated with documented R routines for particular applications, including models for malaria and the Zika virus. The R routines are available from a download so that the reader can reproduce the reported solutions, then extend the applications through computer experimentation, including the addition of postulated effects and associated equations, and the implementation of alternative models of interest.The ODE/PDE methodology is open ended and facilitates the development of computer-based models which hopefully can elucidate the causes/conditions of infectious disease evolution and suggest methods of control.

This book is directed toward the numerical integration (solution) of a system of partial differential equations (PDEs) that describes a combination of chemical reaction and diffusion, that is, reaction-diffusion PDEs. The particular form of the PDEs corresponds to a system discussed by Alan Turing and is therefore termed a Turing model.Specifically, Turing considered how a reaction-diffusion system can be formulated that does not have the usual smoothing properties of a diffusion (dispersion) system, and can, in fact, develop a spatial variation that might be interpreted as a form of morphogenesis, so he termed the chemicals as morphogens.Turing alluded to the important impact computers would have in the study of a morphogenic PDE system, but at the time (1952), computers were still not readily available. Therefore, his paper is based on analytical methods. Although computers have since been applied to Turing models, computer-based analysis is still not facilitated by a discussion of numerical algorithms and a readily available system of computer routines.The intent of this book is to provide a basic discussion of numerical methods and associated computer routines for reaction-diffusion systems of varying form. The presentation has a minimum of formal mathematics. Rather, the presentation is in terms of detailed examples, presented at an introductory level. This format should assist readers who are interested in developing computer-based analysis for reaction-diffusion PDE systems without having to first study numerical methods and computer programming (coding).The numerical examples are discussed in terms of: (1) numerical integration of the PDEs to demonstrate the spatiotemporal features of the solutions and (2) a numerical eigenvalue analysis that corroborates the observed temporal variation of the solutions. The resulting temporal variation of the 2D and 3D plots demonstrates how the solutions evolve dynamically, including oscillatory long-term behavior.In all of the examples, routines in R are presented and discussed in detail. The routines are available through this link so that the reader can execute the PDE models to reproduce the reported solutions, then experiment with the models, including extensions and application to alternative models.

The mathematical model presented in this book, based on partial differential equations (PDEs) describing attractant-repellent chemotaxis, is offered for a quantitative analysis of neurodegenerative disease (ND), e.g., Alzheimer's disease (AD). The model is a representation of basic phenomena (mechanisms) for diffusive transport and biochemical kinetics that provides the spatiotemporal distribution of components which could explain the evolution of ND, and is offered with the intended purpose of providing a small step toward the understanding, and possible treatment of ND.The format and emphasis of the presentation is based on the following elements:In other words, a methodology for numerical PDE modeling is presented that is flexible, open ended and readily implemented on modest computers. If the reader is interested in an alternate model, it might possibly be implemented by: (1) modifying and/or extending the current model (for example, by adding terms to the PDEs or adding additional PDEs), or (2) using the reported routines as a prototype for the model of interest.These suggestions illustrate an important feature of computer-based modeling, that is, the readily available procedure of numerically experimenting with a model. The current model is offered as only a first step toward the resolution of this urgent medical problem.

The mathematical model presented in this book, based on partial differential equations (PDEs) describing attractant-repellent chemotaxis, is offered for a quantitative analysis of neurodegenerative disease (ND), e.g., Alzheimer's disease (AD). The model is a representation of basic phenomena (mechanisms) for diffusive transport and biochemical kinetics that provides the spatiotemporal distribution of components which could explain the evolution of ND, and is offered with the intended purpose of providing a small step toward the understanding, and possible treatment of ND.The format and emphasis of the presentation is based on the following elements:In other words, a methodology for numerical PDE modeling is presented that is flexible, open ended and readily implemented on modest computers. If the reader is interested in an alternate model, it might possibly be implemented by: (1) modifying and/or extending the current model (for example, by adding terms to the PDEs or adding additional PDEs), or (2) using the reported routines as a prototype for the model of interest.These suggestions illustrate an important feature of computer-based modeling, that is, the readily available procedure of numerically experimenting with a model. The current model is offered as only a first step toward the resolution of this urgent medical problem.

This book presents a methodology for the development and computer implementation of dynamic models for transport process systems. Rather than developing the general equations of transport phenomena, it develops the equations required specifically for each new example application. These equations are generally of two types: ordinary differential equations (ODEs) and partial differential equations (PDEs) for which time is an independent variable. The computer-based methodology presented is general purpose and can be applied to most applications requiring the numerical integration of initial-value ODEs/PDEs. A set of approximately two hundred applications of ODEs and PDEs developed by the authors are listed in Appendix 8.

Mathematical modelling of physical and chemical systems is used extensively throughout science, engineering, and applied mathematics. To use mathematical models, one needs solutions to the model equations; this generally requires numerical methods. This book presents numerical methods and associated computer code in Matlab for the solution of a spectrum of models expressed as partial differential equations (PDEs). The authors focus on the method of lines (MOL), a well-established procedure for all major classes of PDEs, where the boundary value partial derivatives are approximated algebraically by finite differences. This reduces the PDEs to ordinary differential equations (ODEs) and makes the computer code easy to understand, implement, and modify. Also, the ODEs (via MOL) can be combined with any other ODEs that are part of the model (so that MOL naturally accommodates ODE/PDE models). This book uniquely includes a detailed line-by-line discussion of computer code related to the associated PDE model.

The focus of this book is a detailed discussion of a dual cancer vaccine (CV)-immune checkpoint inhibitor (ICI) mathematical model formulated as a system of partial differential equations (PDEs) defining the spatiotemporal distribution of cells and biochemicals during tumor growth. A computer implementation of the model is discussed in detail for the quantitative evaluation of CV-ICI therapy. The coding (programming) consists of a series of routines in R, a quality, open-source scientific computing system that is readily available from the internet. The routines are based on the method of lines (MOL), a general PDE algorithm that can be executed on modest computers within the basic R system. The reader can download and use the routines to confirm the model solutions reported in the book, then experiment with the model by varying the parameters and modifying/extending the equations, and even studying alternative models with the PDE methodology demonstrated by the CV-ICI model. Spatiotemporal Modeling of Cancer Immunotherapy: Partial Differential Equation Analysis in R facilitates the use of the model, and more generally, computer- based analysis of cancer immunotherapy mathematical models, as a step toward the development and quantitative evaluation of the immunotherapy approach to the treatment of cancer. To download the R routines, please visit: http://www.lehigh.edu/~wes1/ci_download