Philip E. Seiden

A computer model of cellular interactions in the immune system.

The power of modern computers allows the modeling and simulation of complex biological systems. The last decade has seen the emergence of a growing number of simulations of the immune system. In this article, Franco Celada and Philip Seiden present a model that, they suggest, is rich enough to allow computer experiments to be used as practical adjuncts to the usual biological experiments, at a saving of cost and time.

A model for simulating cognate recognition and response in the immune system.

We have constructed a model of the immune system that focuses on the clonotypic cell types and their interactions with other cells, and with antigens and antibodies. We carry out simulations of the humoral immune system based on a generalized cellular automaton implementation of the model. We propose using computer simulation as a tool for doing experiments in machine, in the computer, as an adjunct to the usual in vivo and in vitro techniques. These experiments would not be intended to replace the usual biological experiments since, in the foreseeable future, a complete enough computer model capable of reliably simulating the whole immune would not be possible. However a model simulating areas of interest could be used for extensively testing ideas to help in the design of the critical biological experiments. Our present model concentrates on the cellular interactions and is quite adept at testing the importance and effects of cellular interactions with other cells, antigens and antibodies. The implementation is quite general and unrestricted allowing most other immune system components to be added with relative ease when desired.

Spiral arm amplitude variations and pattern speeds in the grand design galaxies M51, M81, and M100

In the modal theory of galactic spiral structure, the amplitude of a prominent two-arm spiral pattern should oscillate slightly with galactocentric distance because of an interference between the outward and inward propagating waves. In the stellar dynamical theory, the spiral arm amplitudes should oscillate because of differential crowding near and between wave-orbit resonances. Two and three cycles of such oscillations have been found in computer-enhanced images at B and I passbands of the grand design galaxies M81 and M100, respectively, and what is probably one cycle of such an amplitude variation in M51. These three galaxies are the most symmetric and global of the two-arm spirals in the near-IR survey of Elmegreen (1981), so the occurrence of such spiral amplitude oscillations could be common among galaxies of this type. The positions of the features discussed are used to suggest possible arm pattern speeds. 23 refs.

A systematic approach to vaccine complexity using an automaton model of the cellular and humoral immune system I. Viral characteristics and polarized responses

A modern approach to vaccination faces the compound complexity of microorganism behavior and immune response triggering and regulation. Since computational modeling can yield useful guidelines for biological experimentation, we have used IMMSIM(3), a cellular automaton model for simulating humoral- and cell-mediated responses, to explore a wide range of virus-host relations. Sixty-four virtual viruses were generated by an assortment of speed of growth, infectivity level and lethal load. The outcome of the infections, as influenced by the immune response and the bolstering of cures, obtained by vaccine presensitization are illustrated in this first article. The results of the in machina experiments allow us to relate the success rate of responses to certain combinations of viral parameters and by freezing one or the other branch, and to determine that some viruses are more susceptible to humoral, and others to cellular responses, depending either on single parameters or combinations thereof. This finding allows prediction of which infection may be susceptible to polarized ((Th)(1)>Th(2) and Th(1)<Th(2)) responses and will eventually help designing vaccines whose action relies on antagonizing both the specificity and the behavior of the invader. A second, not lesser, result of this study is the finding that humoral and cellular responses, while cooperating, towards the cure of the infected body, also show significant patterns of competition and mutual thwarting.

Percolation and Galaxies

A theory is presented in which much of the structure of spiral galaxies arises from a percolation phase transition that underlies the phenomenon of propagating star formation. According to this view, the appearance of spiral arms is a consequence of the differential rotation of the galaxy and the characteristic divergence of correlation lengths for continuous phase transitions. Other structural properties of spiral galaxies, such as the distribution of the gaseous components and the luminosity, arise directly from a feedback mechanism that pins the star formation rate close to the critical point of the phase transition. The approach taken in this article differs from traditional dynamical views. The argument is presented that, at least for some galaxies, morphological and other features are already fixed by general properties of phase transitions, irrespective of detailed dynamic or other considerations.

IMMSIM, a flexible model for in machina experiments on immune system responses

This paper describes the basic structure and the developments of IMMSIM, a modified cellular automaton to simulate chance encounters and discrete effects of cell-cell and cell-molecule interactions in the lymphoid system. Thanks to its flexibility, this model has proven a useful tool in theoretical immunology, experimental research and educational applications. Of the various versions available, we show here the most advanced one (IMMSIM3), that incorporates both humoral and cellular responses. We describe the results obtained by simulating the responses to viral infection, the impact of viral behavior on the quality of response needed to reach a cure, the cooperation/competition relation between cellular and humoral branches and the effect of vaccination.

Percolation model of galactic structure

Abstract Galactic structure is generally studied from the point of view of Newtonian dynamics. The goal of this paper is to show that modern statistical physics also has an important contribution to make in understanding the structure of galaxies. In particular, we show how the process of star formation can be modelled as a percolation process, and how the phase transition associated with this percolation process plays a critical role in the stabilization and control of star formation. For galaxies well described by our model, the dominant morphological feature, the presence of spiral arms, is a consequence of the proximity to the second-order phase transition associated with the percolation threshold. We present an introduction to the astrophysical problem we are investigating and an analysis of the directed percolation problem, called stochastic self-propagating star formation, that controls star formation. We also describe a simulation of the galactic evolution problem in terms of a cellular automaton ...

The transition between immune and disease states in a cellular automaton model of clonal immune response

In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infections virus and killer T cells (cellular response). The model represents molecules and cells with bitstrings. The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the hosts ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connected to spatial extension is lost, as is the oscillating feature. Thus the mean field approximation introduced with coupled maps destroys oscillations.

Solar active regions as a percolation phenomenon

The appearance of solar active regions is modeled using percolation theory. Our motivation: magnetic fields of active regions presumably are released and rise from some deep site of the solar dynamo. We attempt to bundle all the very complicated magnetic phenomena into two dimensionless parameters. The main parameter is the probability that the release and rise of one flux tube stimulates the subsequent release and rise of a neighboring flux tube. A second parameter measures the lifetime of flux once it has arrived at the surface

Galactic disk is not a true exponential

Stochastic self-propagating star formation predicts that the distribution of atomic hydrogen in a galactic disk should be relatively independent of radius. The molecular hydrogen density should therefore vary as the total gas density minus a constant. The most likely distribution for the total gas density is approximately 1/r the same as the distribution of column density in a halo that produces a flat rotation curve. Thus the molecular column density, the star formation rate per unit area, and the total stellar surface brightness should all vary as r/sup -1/-constant. This function resembles an exponential over a wide range of galactic radii. We propose that the approximately exponential surface brightness distribution observed in disk galaxies results from the intrinsic r/sup -1/-constant distribution produced by propagating star formation. The exponential fit has no intrinsic physical meaning. In fact, the exponential scale lengths derived for all galaxies are approximately the same when scaled to the galaxy size, and they are equal to the relative scale length predicted from the theory. The observed constancy of the extrapolated central surface brightness of disk galaxies is also obtained from the theory.