Computer models and automata theory in biology and medicine

The applications of computers to biological and biomedical problem solving go back to the very beginnings of computer science, automata theory [1], and mathematical biology [2]. With the advent of more versatile and powerful computers, biological and biomedical applications of computers have proliferated so rapidly that it would be virtually impossible to compile a comprehensive review of all developments in this field. Limitations of computer simulations in biology have also come under close scrutiny, and claims have been made that biological systems have limited information processing power [3]. Such general conjectures do not, however, deter biologists and biomedical researchers from developing new computer applications in biology and medicine. Microprocessors are being widely employed in biological laboratories both for automatic data acquisition/processing and modeling; one particular area, which is of great biomedical interest, involves fast digital image processing and is already established for routine clinical examinations in radiological and nuclear medicine centers, Powerful techniques for biological research are routinely employing dedicated, on-line microprocessors or array processors; among such techniques are: Fourier-transform nuclear magnetic resonance (NMR), NMR imaging (or tomography), x-ray tomography, x-ray diffraction, high performance liquid chromatography, differential scanning calorimetry and mass spectrometry. Networking of laboratory microprocessors linked to a central, large memory computer is the next logical step in laboratory automation. Previously unapproachable problems, such as molecular dynamics of solutions, many-body interaction calculations and statistical mechanics of biological processes are all likely to benefit from the increasing access to the new generation of "supercomputers". In view of the large number, diversity and complexity of computer applications in biology and medicine, we could not review in any degree of detail all computer applications in these fields; instead, we shall be selective and focus our discussion on suggestive computer models of biological systems and those fundamental aspects of computer applications that are likely to continue to make an impact on biological and biomedical research. Thus, we shall consider unifying trends in mathematics, mathematical logics and computer science that are relevant to computer modeling of biological and biomedical systems. The latter are pitched at a more formal, abstract level than the applications and, therefore, encompass a number of concepts drawn from the abstract theory of sets and relations, network theory, automata theory, Boolean and n-valued logics, abstract algebra, topology and category theory. The present analysis of relational theories in biology and computer simulation has also inspired a number of new results which are presented here as "Conjectures" since their proofs are too lengthy and too technical to be included in this review. In order to maintain a self-contained presentation-the definitions of the main concepts are given, with the exception of a minimum of simple mathematical concepts. The purpose of these theoretical sections is to provide the basis for approaching a number of basic biological questions: (1) What are the essential characteristics of a biological organism as opposed to an automaton? (2) Are biological systems recursively computable? (3) What is the structure of the simplest (primordial) organism? (4) What are the basic structures of neural and genetic networks? (5) What are the common properties of classes of biological organisms? (6) Which system representations are adequate for biodynamics? (7) What is the optimal strategy for modifying an organism through genetic engineering? (8) What is the optimal simulation of a biological system with a digital or analog computer? (9) What is life?

[1]  M. Witten Some generalized conjugacy theorems and the concepts of fitness and survival in logistic growth models. , 1980, Bulletin of mathematical biology.

[2]  J. B. Shukla,et al.  Effects of stenosis on non-Newtonian flow of the blood in an artery. , 1980, Bulletin of mathematical biology.

[3]  R. Carnap Logical Syntax of Language , 1937 .

[4]  S. Levin Lectu re Notes in Biomathematics , 1983 .

[5]  Economy in the brain. , 1973, Lancet.

[6]  F. Rawlins Design for a Brain—2nd Edition , 1960 .

[7]  I Băianu,et al.  Organismic supercategories. I. Proposals for a general unitary theory of systems. , 1968, The Bulletin of mathematical biophysics.

[8]  W. Pitts,et al.  A Statistical Consequence of the Logical Calculus of Nervous Nets , 1943 .

[9]  Britton Chance,et al.  Biological and biochemical oscillators , 1973 .

[10]  Alwyn C. Scott,et al.  The electrophysics of a nerve fiber , 1975 .

[11]  R. Borchert,et al.  Bifurcation Ratios and the Adaptive Geometry of Trees , 1981, Botanical Gazette.

[12]  F. W. Lawvere,et al.  The Category of Categories as a Foundation for Mathematics , 1966 .

[13]  R. Hodges,et al.  Co-operativity and calcium/magnesium binding to troponin C and muscle calcium binding parvalbumin: an hypothesis. , 1980, Journal of theoretical biology.

[14]  Nicolas Bourbaki,et al.  Eléments de Mathématique , 1964 .

[15]  J Grasman The mathematical modeling of entrained biological oscillators. , 1984, Bulletin of mathematical biology.

[16]  R. Plant,et al.  The effects of calcium++ on bursting neurons. A modeling study. , 1978, Biophysical journal.

[17]  S. Sarna,et al.  Simulation of slow-wave electrical activity of small intestine. , 1971, The American journal of physiology.

[18]  Werner Horsthemke,et al.  The Influence of External Real and White Noise on the LOTKA‐VOLTERRA Model , 1979 .

[19]  Michael Conrad,et al.  Limits on the computing power of biological systems , 1981 .

[20]  K. Gausing,et al.  Post-transcriptional control of coordinated ribosomal protein synthesis in Escherichia coli , 1980, Nature.

[21]  S. Kauffman Gene regulation networks: a theory for their global structure and behaviors. , 1971, Current topics in developmental biology.

[22]  J. Kiefer A model of feedback-controlled cell populations. , 1968, Journal of Theoretical Biology.

[23]  A. Holden Stochastic processes in neurophysiology: transformation from point to continuous processes. , 1983, Bulletin of mathematical biology.

[24]  B. V. van Gelder,et al.  Large signal, low frequency characteristics of the systemic arterial system. , 1982, Bulletin of mathematical biology.

[25]  Willi Jäger,et al.  Biological Growth and Spread , 1980 .

[26]  A. Lindenmayer,et al.  Developmental algorithms for multicellular organisms: a survey of L-systems. , 1975, Journal of theoretical biology.

[27]  R R Kampfner,et al.  Computational modeling of evolutionary learning processes in the brain. , 1983, Bulletin of mathematical biology.

[28]  O. E. Rössler Chaos and Strange Attractors in Chemical Kinetics , 1979 .

[29]  J. S. Frame Explicit solutions in two species Volterra systems. , 1974, Journal of theoretical biology.

[30]  J. B. Shukla,et al.  Effects of peripheral layer viscosity on blood flow through the artery with mild stenosis , 1980 .

[31]  M. Kim,et al.  Mathematical description of a bursting pacemaker neuron by a modification of the Hodgkin-Huxley equations. , 1976, Biophysical journal.

[32]  Giles R Cokelet,et al.  The rheology of human blood , 1963 .

[33]  J. Varley,et al.  Satellite DNA is transcribed on lampbrush chromosomes , 1980, Nature.

[34]  S. Kauffman Metabolic stability and epigenesis in randomly constructed genetic nets. , 1969, Journal of theoretical biology.

[35]  M. W. Warner Representations of (M, R)-systems by categories of automata , 1982 .

[36]  D A Linkens,et al.  A conversational program for analytical modelling of action potentials in nerve and muscle. , 1975, Computer programs in biomedicine.

[37]  R. Baserga,et al.  THE RELATIONSHIP OF THE CELL CYCLE TO TUMOR GROWTH AND CONTROL OF CELL DIVISION: A REVIEW. , 1965, Cancer research.

[38]  Aldo Rescigno,et al.  Chapter 4 – THE DETERMINISTIC THEORY OF POPULATION DYNAMICS† , 1973 .

[39]  R. Keskinen,et al.  On the effect of the concentration profile of red cells on blood flow in the artery with stenosis , 1983 .

[40]  Concept of energy in biological systems. , 1975, Bulletin of mathematical biology.

[41]  W. Rittgen Positive Recurrence of Multi-Dimensional Population-Dependent Branching Processes , 1980 .

[42]  Elliott W. Montroll,et al.  Nonlinear Population Dynamics. (Book Reviews: On the Volterra and Other Nonlinear Models of Interacting Populations) , 1971 .

[43]  M. Iosifescu,et al.  Stochastic processes and applications in biology and medicine , 1975 .

[44]  F. Fogelman-Soulié,et al.  Random Boolean Networks , 1981 .

[45]  M. Gola,et al.  Qualitative study of a dynamical system for metrazol-induced paroxysmal depolarization shifts , 1984, Bulletin of mathematical biology.

[46]  K. Horsfield Morphology of the bronchial tree in the dog. , 1976, Respiration physiology.

[47]  M Lieberman A stochastic model based upon computer simulation using pre-emption to predict size distribution and species equitability. , 1977, Bulletin of mathematical biology.

[48]  Wolfgang Kliemann,et al.  Qualitative Theory of Stochastic Systems , 1983 .

[49]  L. M.-T. Grundzüge der theoretischen Logik , 1929, Nature.

[50]  H. Kössel,et al.  The primary structure of 16S rDNA from Zea mays chloroplast is homologous to E. coli 16S rRNA , 1980, Nature.

[51]  T. Vincent,et al.  Optimal control analysis in the chemotherapy of IgG multiple myeloma. , 1977, Bulletin of mathematical biology.

[52]  I. Bäianu Organismic supercategories and qualitative dynamics of systems. , 1971, The Bulletin of mathematical biophysics.

[53]  A. Gill SWITCHING AND AUTOMATA THEORY. , 1970 .

[54]  Local stability in metabolic networks with conserved moieties and steady state subnetworks. , 1975 .

[55]  D. A. Linkens,et al.  The stability of entrainment conditions forRLC coupled van der pol oscillators used as a model for intestinal electrical rhythms , 1977 .

[56]  J. C. Barrett A mathematical model of the mitotic cycle and its application to the interpretation of percentage labeled mitoses data. , 1966, Journal of the National Cancer Institute.

[57]  E. Attinger,et al.  Pressure‐Flow Relations in Dog Arteries , 1966, Circulation research.

[58]  G M Saidel,et al.  System dynamics of metastatic process from an implanted tumor. , 1976, Journal of theoretical biology.

[59]  D. Bergel,et al.  The dynamic elastic properties of the arterial wall , 1961, The Journal of physiology.

[60]  G. Drummond,et al.  Cyclic Nucleotides in the Nervous System , 1984 .

[61]  A. Bartholomay Molecular set theory. 3. The wide sense kinetics of molecular sets. , 1971, The Bulletin of mathematical biophysics.

[62]  Michael Conrad,et al.  Example of a system which is computation universal but not effectively programmable , 1982 .

[63]  Derek A. Linkens,et al.  Mathematical Modeling of the Colorectal Myoelectrical Activity in Humans , 1976, IEEE Transactions on Biomedical Engineering.

[64]  J. D. Cowan,et al.  Statistical Mechanics of Nervous Nets , 1968 .

[65]  C K Kang,et al.  The effect of microstructure on the rheological properties of blood. , 1976, Bulletin of mathematical biology.

[66]  H. Honda Description of the form of trees by the parameters of the tree-like body: effects of the branching angle and the branch length on the sample of the tree-like body. , 1971, Journal of theoretical biology.

[67]  M. Sanders Handbook of Sensory Physiology , 1975 .

[68]  Yukio Ogura,et al.  Recurrence properties of Lotka-Volterra models with random fluctuations , 1981 .

[69]  C. L. Stephens,et al.  Cyclic variation of potassium conductance in a burst‐generating neurone in Aplysia , 1973, The Journal of physiology.

[70]  Stubbs D.F Perceptual-learning machines and the brain , 1975 .

[71]  A F Bartholomay,et al.  Some mathematical aspects of the medical diagnostic process. I. A general mathematical model. , 1971, The Bulletin of mathematical biophysics.

[72]  M. W. Warner Lattices and lattice-valued relations in biology. , 1983, Bulletin of mathematical biology.

[73]  Charles Ehresmann Trends toward unity in mathematics , 1966 .

[74]  R. Rosen,et al.  Abstract biological systems as sequential machines. 3. Some algebraic aspects. , 1966, The Bulletin of mathematical biophysics.

[75]  L. Glass,et al.  Phase locking, period-doubling bifurcations, and irregular dynamics in periodically stimulated cardiac cells. , 1981, Science.

[76]  J. Folkman,et al.  ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESIS , 1971, The Journal of experimental medicine.

[77]  I. Băianu Some algebraic properties of (M, R)-systems , 1973 .

[78]  A. Turing On Computable Numbers, with an Application to the Entscheidungsproblem. , 1937 .

[79]  P. Waltman THE EQUATIONS OF GROWTH. , 1964, The Bulletin of mathematical biophysics.

[80]  S. A. Newman A source of stability in metabolic networks. , 1972, Journal of theoretical biology.

[81]  R. Rosen THE REPRESENTATION OF BIOLOGICAL SYSTEMS FROM THE STANDPOINT OF THE THEORY OF CATEGORIES , 1958 .

[82]  R Rosen,et al.  Some realizations of (M,R)-systems and their interpretation. , 1971, The Bulletin of mathematical biophysics.

[83]  F. H. Lopes da Silva,et al.  Models of neuronal populations: the basic mechanisms of rhythmicity. , 1976, Progress in brain research.

[84]  Kenneth L. Artis Design for a Brain , 1961 .

[85]  M. Kim,et al.  Mathematical description and analysis of cell cycle kinetics and the application to Ehrlich ascites tumor. , 1975, Journal of theoretical biology.

[86]  E. Doubek Least energy regulation of the arterial system , 1978 .

[87]  Françoise Fogelman-Soulié,et al.  Specific roles of the different Boolean mappings in random networks , 1982 .

[88]  F. Roberge,et al.  Characteristics of pacemaker oscillations in Aplysia neurons. , 1971, Canadian journal of physiology and pharmacology.

[89]  T. Kenner Models of the Arterial System , 1978 .

[90]  Bifurcation analysis of reaction-diffusion equations—III. Chemical oscillations , 1976 .

[91]  J. Higgins The Theory of Oscillating Reactions - Kinetics Symposium , 1967 .

[92]  A. J. Hermans,et al.  A model of the spatial-temporal characteristics of the alpha rhythm , 1982 .

[93]  K. Horsfield,et al.  Some mathematical properties of branching trees with application to the respiratory system. , 1976, Bulletin of mathematical biology.

[94]  Paul Greengard,et al.  Cyclic Nucleotides, Phosphorylated Proteins, And Neuronal Function , 1978 .

[95]  D. Quemada,et al.  Rheology of concentrated disperse systems and minimum energy dissipation principle , 1977 .

[96]  G M Saidel,et al.  Diffusion model of tumor vascularization and growth , 1977, Bulletin of mathematical biology.

[97]  J. Rhodes,et al.  Algebraic theory of machines. I. Prime decomposition theorem for finite semigroups and machines , 1965 .

[98]  Shun-ichi Amari,et al.  A Mathematical Approach to Neural Systems , 1977 .

[99]  H D Landahl,et al.  Some conditions for sustained oscillations in biochemical chains with feedback inhibition. , 1969, The Bulletin of mathematical biophysics.

[100]  G. A. Petrillo,et al.  Phase locking of the respiratory rhythm in cats to a mechanical ventilator. , 1983, Canadian journal of physiology and pharmacology.

[101]  Ensemble entrainment of self-sustaining oscillators: a possible application to neural signals , 1970 .

[102]  B. Hassard Bifurcation of periodic solutions of Hodgkin-Huxley model for the squid giant axon. , 1978, Journal of theoretical biology.

[103]  Beyond the binary case in random nets , 1984 .

[104]  D. Linkens,et al.  Stability of entrainment conditions for a particular form of mutually coupled Van der Pol oscillators , 1976 .

[105]  R. A. Sherlock Analysis of the behaviour of Kauffman binary networks—I. State space description and the distribution of limit cycle lengths , 1979 .

[106]  Theodosios Pavlidis,et al.  Biological Oscillators: Their Mathematical Analysis , 1973 .

[107]  J. Cowan Spontaneous symmetry breaking in large scale nervous activity , 1982 .

[108]  A. Rapoport Cycle distributions in random nets. , 1948, The Bulletin of mathematical biophysics.

[109]  C. Nicolini,et al.  Mathematical approaches to optimization of cancer chemotherapy , 1979 .

[110]  Virendra. Singh Analytical theory of the control equations for protein synthesis in the Goodwin model , 1977 .

[111]  P. Schuster,et al.  Dynamical machinery of a biochemical clock , 1984 .

[112]  T. Soong,et al.  Mathematical analysis of cancer chemotherapy: the effects of chemotherapeutic agents on the cell cycle traverse. , 1978, Bulletin of mathematical biology.

[113]  M. D. Di Berardino,et al.  Origin of chromosomal abnormalities in nuclear transplants--a reevaluation of nuclear differentiation and nuclear equivalence in amphibians. , 1970, Developmental biology.

[114]  J. Legay Contribution a l’etude de la forme des plantes: discussion d’un modele de ramification , 1971 .

[115]  Michael Abib Categories of (ℓ, ℛ)-systems , 1966 .

[116]  W. Kliemann Qualitative theory of stochastic dynamical systems—Applications to life sciences , 1983 .

[117]  K. Horsfield,et al.  Morphometry of the Small Pulmonary Arteries in Man , 1978, Circulation research.

[118]  R. Bhattacharya Criteria for Recurrence and Existence of Invariant Measures for Multidimensional Diffusions , 1978 .

[119]  D. Moisescu Interfilament forces in striated muscle. , 1973, Bulletin of mathematical biology.

[120]  M Zamir,et al.  Local geometry of arterial branching. , 1982, Bulletin of mathematical biology.

[121]  H. Honda,et al.  Two Geometrical Models of Branching of Botanical Trees , 1982 .

[122]  E. Davison,et al.  Computer simulation of intestinal slow-wave frequency gradient. , 1970, The American journal of physiology.

[123]  W. Dchting Krebs, ein instabiler Regelkreis: Versuch einer Systemanalyse , 1968 .

[124]  I Băianu,et al.  Organismic supercategories. II. On multistable systems. , 1970, The Bulletin of mathematical biophysics.

[125]  A SHIMBEL,et al.  An analysis of theoretical systems of differentiating nervous tissue. , 1948, The Bulletin of mathematical biophysics.

[126]  J. Hammersley,et al.  Diffusion Processes and Related Topics in Biology , 1977 .

[127]  N. Goel,et al.  Diffusion models for firing of a neuron with varying threshold. , 1973, Journal of theoretical biology.

[128]  W Düchting Simulation of disturbed cell renewal systems by means of a microprocessor system. , 1979, International journal of bio-medical computing.

[129]  B. Goodwin Temporal organization in cells , 1963 .

[130]  J. Changeux,et al.  Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks , 1976, Nature.

[131]  L. B. Leopold,et al.  Trees and streams: the efficiency of branching patterns. , 1971, Journal of theoretical biology.

[132]  Lars Löfgren,et al.  An axiomatic explanation of complete self-reproduction , 1968 .

[133]  S. Maclane,et al.  General theory of natural equivalences , 1945 .

[134]  Jacques Monod,et al.  On the Regulation of Gene Activity , 1961 .

[135]  R. Rosen,et al.  Some comments on activation and inhibition. , 1979, Bulletin of mathematical biology.

[136]  G. B. M. Principia Mathematica , 1911, Nature.

[137]  N. Rashevsky Topology and life: In search of general mathematical principles in biology and sociology , 1954 .

[138]  Alan E. Gelfand A behavioral summary for completely random nets , 1982 .

[139]  Pressure-flow relationships in a model for the arterial system. , 1978, Bulletin of mathematical biology.

[140]  A. Scott Nerve Pulse Interactions , 1982 .

[141]  A. G. Hawkes,et al.  Stochastic Models for Spike Trains of Single Neurons , 1977 .

[142]  S P Gupta,et al.  Biorheological aspects of blood flow through artery with mild stenosis : effects of peripheral layer. , 1980, Biorheology.

[143]  J. Cowan,et al.  Excitatory and inhibitory interactions in localized populations of model neurons. , 1972, Biophysical journal.

[144]  R. Rosen,et al.  On the dynamical realization of (M,R)-systems. , 1973, Bulletin of mathematical biology.

[145]  W Rittgen,et al.  Controlled branching processes and their applications to normal and malignant haematopoiesis. , 1983, Bulletin of mathematical biology.

[146]  K. Horsfield,et al.  Morphology of the bronchial tree in man. , 1968, Journal of applied physiology.

[147]  A. Rapoport,et al.  Connectivity of random nets , 1951 .

[148]  The methods of harmonic balance applied to coupled asymmetrical van der Pol oscillators for intestinal modelling. , 1979, Bulletin of mathematical biology.

[149]  Igor Aleksander Random logic nets: Stability and adaptation , 1973 .

[150]  W. Pitts The linear theory of neuron networks: The dynamic problem , 1942 .

[151]  L. Glass,et al.  A simple model for phase locking of biological oscillators , 1979, Journal of mathematical biology.

[152]  K G Kirby,et al.  The enzymatic neuron as a reaction-diffusion network of cyclic nucleotides , 1984, Bulletin of mathematical biology.

[153]  Tracy Allen,et al.  On the arithmetic of phase locking: Coupled neurons as a lattice on R2 , 1983 .

[154]  Robert Rosen,et al.  Pattern Generation in Networks , 1981 .

[155]  M. W. Warner,et al.  The dynamics of symmetric nets. , 1983, Bulletin of mathematical biology.

[156]  Patrick Doreian,et al.  On the connectivity of social networks , 1974 .

[157]  R. Meech,et al.  Intracellular calcium injection causes increased potassium conductance in Aplysia nerve cells. , 1972, Comparative biochemistry and physiology. A, Comparative physiology.

[158]  M. Woldenberg,et al.  Finding the optimal lengths for three branches at a junction. , 1983, Journal of theoretical biology.

[159]  J. Gollub,et al.  Periodicity and Chaos in Coupled Nonlinear Oscillators , 1978, Science.

[160]  H. Honda,et al.  COMPUTER SIMULATION OF BRANCH INTERACTION AND REGULATION BY UNEQUAL FLOW RATES IN BOTANICAL TREES , 1981 .

[161]  George Georgescu,et al.  On the characterization of centered Lukasiewicz algebras , 1970 .

[162]  Ion C. Baianu NATURAL TRANSFORMATION MODELS IN MOLECULAR BIOLOGY , 1983 .

[163]  H. Uylings,et al.  Optimization of diameters and bifurcation angles in lung and vascular tree structures. , 1977, Bulletin of mathematical biology.

[164]  F. W. Lawvere,et al.  FUNCTORIAL SEMANTICS OF ALGEBRAIC THEORIES. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[165]  A. J. Lotka,et al.  Elements of Physical Biology. , 1925, Nature.

[166]  R. Khasminskii Stochastic Stability of Differential Equations , 1980 .

[167]  R. Rosen,et al.  ABSTRACT BIOLOGICAL SYSTEMS AS SEQUENTIAL MACHINES. , 1964, The Bulletin of mathematical biophysics.

[168]  S G Waxman,et al.  Regional differentiation of the axon: a review with special reference to the concept of the multiplex neuron. , 1972, Brain research.

[169]  MARK R. GARDNER,et al.  Connectance of Large Dynamic (Cybernetic) Systems: Critical Values for Stability , 1970, Nature.

[170]  Vito Volterra,et al.  Leçons sur la théorie mathématique de la lutte pour la vie , 1931 .

[171]  Michael A. Arbib,et al.  Theories of abstract automata , 1969, Prentice-Hall series in automatic computation.

[172]  C. W. Gear,et al.  The automatic integration of ordinary differential equations , 1971, Commun. ACM.

[173]  S. Kauffman Homeostasis and Differentiation in Random Genetic Control Networks , 1969, Nature.

[174]  S. Salmon,et al.  Kinetics of tumor growth and regression in IgG multiple myeloma. , 1972, The Journal of clinical investigation.

[175]  P. Good,et al.  Connectivity in random networks , 1976 .

[176]  G. Hahn State vector description of the proliferation of mammalian cells in tissue culture. I. Exponential growth. , 1966, Biophysical journal.

[177]  K. Horsfield,et al.  Computer simulation of the geometry of the human bronchial tree. , 1984, Bulletin of mathematical biology.

[178]  J. Griffith On the stability of brain-like structures. , 1963, Biophysical journal.

[179]  H. Landahl Some conditions for sustained oscillations in chain processes with feedback inhibition and saturable removal. , 1977, Bulletin of mathematical biology.

[180]  G Cumming,et al.  Angles of branching and diameters of branches in the human bronchial tree. , 1967, The Bulletin of mathematical biophysics.

[181]  Tetsuro Endo,et al.  Mode analysis of a multimode ladder oscillator , 1976 .

[182]  Zeev Schuss,et al.  Theory and Applications of Stochastic Differential Equations , 1980 .

[183]  D. Linkens,et al.  Frequency Entrainment of Coupled Hodgkin-Huxley-Type Oscillators for Modeling Gastro-Intestinal Electrical Activity , 1977, IEEE Transactions on Biomedical Engineering.

[184]  René Thomas,et al.  Kinetic logic : a Boolean approach to the analysis of complex regulatory systems : proceedings of the EMBO course "Formal analysis of genetic regulation," held in Brussels, September 6-16, 1977 , 1979 .

[185]  R. Pérez,et al.  Fine Structure of Phase Locking , 1982 .

[186]  Abraham Ginzburg,et al.  Algebraic theory of automata , 1968 .

[187]  R. McMurtrie,et al.  Determinants of stability of large randomly connected systems. , 1975, Journal of theoretical biology.

[188]  Michael A. Arbib,et al.  Automata theory and development: Part I , 1967 .

[189]  C. Ince,et al.  Mutual entrainment of two pacemaker cells. A study with an electronic parallel conductance model. , 1980, Journal of theoretical biology.

[190]  J. Rinzel On repetitive activity in nerve. , 1978, Federation proceedings.

[191]  D. Sattinger Group representation theory, bifurcation theory and pattern formation , 1978 .

[192]  Michael A. Arbib,et al.  Simple Self-Reproducing Universal Automata , 1966, Inf. Control..

[193]  K. Horsfield,et al.  Relation between diameter and flow in branches of the bronchial tree. , 1981, Bulletin of mathematical biology.

[194]  R. Somorjai,et al.  Relationship between Stability and Connectedness of Non-linear Systems , 1972, Nature.

[195]  A ROSENBLUETH,et al.  The mathematical formulation of the problem of conduction of impulses in a network of connected excitable elements, specifically in cardiac muscle. , 1946, Archivos del Instituto de Cardiologia de Mexico.

[196]  Jesse B. Wright,et al.  Automata in General Algebras , 1967, Inf. Control..

[197]  I. Băianu,et al.  Abstract representations of biological systems in supercategories. , 1969, The Bulletin of mathematical biophysics.

[198]  G. Ermentrout n:m Phase-locking of weakly coupled oscillators , 1981 .

[199]  D E Olson,et al.  Models of the human bronchial tree. , 1971, Journal of applied physiology.

[200]  J. Cowan,et al.  Secondary Bifurcation in Neuronal Nets , 1980 .

[201]  V. Allfrey,et al.  Different nucleosome structures on transcribing and nontranscribing ribosomal gene sequences. , 1979, Science.

[202]  Robert Rosen,et al.  On analogous systems , 1968 .

[203]  Robin J. Wilson Introduction to Graph Theory , 1974 .

[204]  E W Kruyt,et al.  Phase resetting properties of cardiac pacemaker cells , 1984, The Journal of general physiology.

[205]  S E Fienberg,et al.  Stochastic models for single neuron firing trains: a survey. , 1974, Biometrics.

[206]  Johan Grasman,et al.  Mutually synchronized relaxation oscillators as prototypes of oscillating systems in biology , 1979 .

[207]  D. Linkens Analytical solution of large numbers of mutually coupled nearly sinusoidal oscillators , 1974 .

[208]  A. Scheibel,et al.  Dendrite bundles as sites for central programs: an hypothesis. , 1973, The International journal of neuroscience.

[209]  H. Landau On some problems of random nets , 1952 .

[210]  Robert Rosen,et al.  A relational theory of biological systems II , 1958 .

[211]  E M Harth,et al.  Brain functions and neural dynamics. , 1970, Journal of theoretical biology.

[212]  H. K. Hartline,et al.  Inhibitory Interaction in the Retina of Limulus , 1972 .

[213]  Robert Ransom A Computer Model of Cell Clone Growth , 1977 .

[214]  M. Arbib,et al.  Conceptual models of neural organization. , 1974, Neurosciences Research Program bulletin.

[215]  P. Holland THE MAINTENANCE OF STRUCTURE AND SHAPE IN THREE MALLEE EUCALYPTS , 1969 .

[216]  Alvy Ray Smith,et al.  Simple Computation-Universal Cellular Spaces and Self-Reproduction , 1968, SWAT.

[217]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[218]  M Takahashi,et al.  Theoretical basis for cell cycle analysis: II. Further studies on labelled mitosis wave method. , 1968, Journal of theoretical biology.