Abstract biological systems as sequential machines

It is shown that a rather close relationship exists between the (ℳ,ℛ)-systems, defined previously as prototypes of abstract biological systems, and the sequential machines which have been studied by various authors. The theory of sequential machines is reformulated in a way suitable for its application to the study of the intertransformability of (ℳ,ℛ)-systems as a result of environmental alteration. The important concept of strong connectedness is most useful in this direction, and is used to derive a number of results on intertransformability. Some suggestions are made for further studies along these lines.     

Categories of (ℓ, ℛ)-systems

We show that when we represent (ℓ, ℛ)-systems with fixed genome as automata (sequential machines), we get automata with output-dependent states. This yields a short proof that ((ℓ, ℛ)-systems from a subcategory of automata—and with more homomorphisms than previously exhibited. We show how ((ℓ, ℛ)-systems with variable genetic structure may be represented as automata and use this embedding to set up a larger subcategory of the category of automata. An analogy with dynamical systems is briefly discussed. This paper presents a formal exploration and extension of some of the ideas presented by Rosen (Bull. Math. Biophyss,26, 103–111, 1964;28, 141–148;28 149–151). We refer the reader to these papers, and references cited therein, for a discussion of the relevance of this material to relational biology.     

Abstract biological systems as sequential machines: Behavioral reversibility

Rosen’s identification of abstract biological systems, called (M,R)-systems, with sequential machines is formally characterized. It is then shown that the determination of environmental alterations of (M,R)-systems from a knowledge of the response sequence and the structure of the system, which we call behavioral reversibility, can be interpreted as information-losslessness of sequential machines. Applying this relationship, necessary conditions for behavioral reversibility are derived. It is further shown that, similar to Rosen’s work on structural reversibility, (M,R)-systems are behaviorally reversible only if the number of physically realizable mappings are restricted.     

Some comments on re-estalishability

The present note consists of two separate but related parts. In the first, a new graphtheoretic proof is presented that an (ℳ,R)-system must always contain a nonreestablishable component. The second considers some questions concerning the relation between re-establishability and the time-lag structure in (ℳ,R)-systems. It is supposed that the reader is familiar with the terminology of the author's previous work on (ℳ,R)-systems, particularly R. Rosen,Bull. Math. Biophysics,20, 245–260, 1958.     

Re-establishability in abstract biology

It is shown that any (ℳ ℛ) has some component which cannot be re-established after it has been inhibited. If there is only one such component, it must be central, that is, its inhibition stops the whole system. These results hold even when it is not assumed that ℳ is connected.     

Some algebraic properties of (M,R)-systems

On the basis of Rosen's representation of (M, R)-systems as sequential machines (Rosen,Bull. Math. Biophys.,26, 103–111, 1964), the existence of projective limits in categories of general (M, R)-systems is proved.     

On the reversibility of environmentally induced alterations in abstract biological systems

The environmentally induced alterations in structure of (M, ℜ) which were described previously (R. Rosen,Bull. Math. Biophysics,23, 165–171, 1961) are examined from the standpoint of determining under what circumstances they can be reversed by further environmental interactions. For simplicity we consider only the case of (M, ℜ)-systems possessing one “metabolic” and one “genetic” component. In the case of environmentally induced alteration of the “metabolic” component alone, a necessary and sufficient condition is given for the reversibility of the alteration. In the case of alteration of the “genetic” component, the situation becomes more complex; several partial results are given, but a full analysis is not available at this time. Some possible biological implications of this analysis are discussed. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Contract no. AF-49(638)-917 and Grant no. AF-AFOSR-9-63.     

On the Final Size of Epidemics with Seasonality

We first study an SIR system of differential equations with periodic coefficients describing an epidemic in a seasonal environment. Unlike in a constant environment, the final epidemic size may not be an increasing function of the basic reproduction number ℛ₀ or of the initial fraction of infected people. Moreover, large epidemics can happen even if ℛ₀<1. But like in a constant environment, the final epidemic size tends to 0 when ℛ₀<1 and the initial fraction of infected people tends to 0. When ℛ₀>1, the final epidemic size is bigger than the fraction 1−1/ℛ₀ of the initially nonimmune population. In summary, the basic reproduction number ℛ₀ keeps its classical threshold property but many other properties are no longer true in a seasonal environment. These theoretical results should be kept in mind when analyzing data for emerging vector-borne diseases (West-Nile, dengue, chikungunya) or air-borne diseases (SARS, pandemic influenza); all these diseases being influenced by seasonality.     

A note on replication in (M,R)-systems

The condition which allows the existence of induced replication maps in (M,R)-systems is shown to place strong restrictions on the “richness” of the category from which these systems can be constructed. This condition also admits of a simple biological interpretation, which can be checked empirically, and which may offer insight into the physical and biological realizations of these abstract systems.     

A relational theory of the structural changes induced in biological systems by alterations in environment

It is shown that a wide variety of structural alterations in both the “metabolic” and “genetic” apparatus of ( , ℜ)-systems can result from specific changes in the environment of such systems. A number of specific examples are investigated in order to demonstrate the scope of these alterations. Certain biological applications of this discussion are suggested, including a suggestion for a possible interpretation of the mitotic cycle. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Contract #AF 49 (638)-917.     

Contributions to relational biology

The principle of biotopological mapping (Rashevsky, 1954,Bull. Math. Biophysics,16, 317–48) is given a generalized formulation, as the principle of relational epimorphism in biology. The connection between this principle and Robert Rosen’s representation of organisms by means of categories (1958,Bull. Math. Biophysics,20, 317–41) is studied. Rosen’s theory of (M,R)-systems, (1958,Bull. Math. Biophysics,20, 245–60) is generalized by dropping the assumption that only terminalM _i components are sending inputs into theR _i components. It is shown that, if the primordial organism is an (M,R)-system, then the higher organisms, obtained by a construction well discussed previously (1958,Bull. Math. Biophysics,20, 71–93), are also (M,R)-systems. Several theorems about such derived (M,R)-systems are demonstrated. It is shown that Rosen’s concept of an organism as a set of mappings throws light on phenomena of synesthesia and also leads to the conclusion that Gestalt phenomena must occur not only in the fields of visual and auditory perception but in perceptions of any modality.     

A relational theory of biological systems II

The general Theory of Categories is applied to the study of the (M, R)-systems previously defined. A set of axioms is provided which characterize “abstract (M, R)-systems”, defined in terms of the Theory of Categories. It is shown that the replication of the repair components of these systems may be accounted for in a natural way within this framework, thereby obviating the need for anad hoc postulation of a replication mechanism. A time-lag structure is introduced into these abstract (M, R)-systems. In order to apply this structure to a discussion of the “morphology” of these systems, it is necessary to make certain assumptions which relate the morphology to the time lags. By so doing, a system of abstract biology is in effect constructed. In particular, a formulation of a general Principle of Optimal Design is proposed for these systems. It is shown under what conditions the repair mechanism of the system will be localized into a spherical region, suggestive of the nuclear arrangements in cells. The possibility of placing an abstract (M, R)-system into optimal form in more than one way is then investigated, and a necessary and sufficient condition for this occurrence is obtained. Some further implications of the above assumptions are then discussed.     

Transmission Dynamics of an Influenza Model with Vaccination and Antiviral Treatment

Vaccination and antiviral treatment are two important prevention and control measures for the spread of influenza. However, the benefit of antiviral use can be compromised if drug-resistant strains arise. In this paper, we develop a mathematical model to explore the impact of vaccination and antiviral treatment on the transmission dynamics of influenza. The model includes both drug-sensitive and resistant strains. Analytical results of the model show that the quantities ℛ _SC and ℛ _RC , which represent the control reproduction numbers of the sensitive and resistant strains, respectively, provide threshold conditions that determine the competitive outcomes of the two strains. These threshold conditions can be used to gain important insights into the effect of vaccination and treatment on the prevention and control of influenza. Numerical simulations are also conducted to confirm and extend the analytic results. The findings imply that higher levels of treatment may lead to an increase of epidemic size, and the extent to which this occurs depends on other factors such as the rates of vaccination and resistance development. This suggests that antiviral treatment should be implemented appropriately.     

Mathematical Study of the Role of Gametocytes and an Imperfect Vaccine on Malaria Transmission Dynamics

A mathematical model is developed to assess the role of gametocytes (the infectious sexual stage of the malaria parasite) in malaria transmission dynamics in a community. The model is rigorously analysed to gain insights into its dynamical features. It is shown that, in the absence of disease-induced mortality, the model has a globally-asymptotically stable disease-free equilibrium whenever a certain epidemiological threshold, known as the basic reproduction number (denoted by ℛ₀), is less than unity. Further, it has a unique endemic equilibrium if ℛ₀>1. The model is extended to incorporate an imperfect vaccine with some assumed therapeutic characteristics. Theoretical analyses of the model with vaccination show that an imperfect malaria vaccine could have negative or positive impact (in reducing disease burden) depending on whether or not a certain threshold (denoted by ∇) is less than unity. Numerical simulations of the vaccination model show that such an imperfect anti-malaria vaccine (with a modest efficacy and coverage rate) can lead to effective disease control if the reproduction threshold (denoted by ℛ_vac) of the disease is reasonably small. On the other hand, the disease cannot be effectively controlled using such a vaccine if ℛ_vac is high. Finally, it is shown that the average number of days spent in the class of infectious individuals with higher level of gametocyte is critically important to the malaria burden in the community.     

A note on abstract relational biologies

It is shown that the class of abstract block diagrams of (M, ℜ)-systems which can be constructed out of the objects and mappings of a particular subcategoryG ₀ of the categoryG of all sets depends heavily on the structure ofG ₀, and in particular on the number of sets of mappingsH(A, B) which are empty inG ₀. In the context ofG ₀-systems, there-fore, each particular categoryG ₀ gives rise to a different “abstract biology” in the sense of Rashevsky. A number of theorems illustrating the relation between the structure of a categoryG ₀ and the embeddability of an arbitrary mapping αεG ₀ into an (M, ℜ)-system are proved, and their biological implication is discussed. This research was supported by the United States Air Force through the Air Force Office of Scientific Reserch of the Air Research and Development Command, under Contract No. AF 49(638)-917.     

The rainbow bridge: Hamiltonian limits and resonance in predator-prey dynamics

 In the presence of seasonal forcing, the intricate topology of non-integrable Hamiltonian predator-prey models is shown to exercise profound effects on the dynamics and bifurcation structure of more realistic schemes which do not admit a Hamiltonian formulation. The demonstration of this fact is accomplished by writing the more general models as perturbations of a Hamiltonian limit, ℋ, in which are contained infinite numbers of periodic, quasiperiodic and chaotic motions. From ℋ, there emanates a surface, Γ, of Nejmark-Sacker bifurcations whereby the annual oscillations induced by seasonality are destabilized. Connecting Γ and ℋ is a bridge of resonance horns within which invariant motions of the Hamiltonian case persist. The boundaries of the resonance horns are curves of tangent (saddle-node) bifurcations corresponding to subharmonics of the yearly cycle. Associated with each horn is a rotation number which determines the dominant frequency, or “color”, of attractors within the horn. When viewed through the necessarily coarse filter of ecological data acquisition, and regardless of their detailed topology, these attractors are often indistinguishable from multi-annual cycles. Because the tips of the horns line up monotonically along Γ, it further follows that the distribution of observable periods in systems subject to fluctuating parameter values induced, for example, by year-to-year variations in the climate, will often exhibit a discernible central tendency. In short, the bifurcation structure is consistent with the observation of multi-annual cycles in Nature. Fundamentally, this is a consequence of the fact that the bridge between ℋ and Γ is a rainbow bridge. While the present analysis is principally concerned with the two species case (one predator and one prey), Hamiltonian limits are also observed in other ecological contexts: 2n-species (n predators, n prey) systems and periodically-forced three level food chain models. Hamiltonian limits may thus be common in models involving the destruction of one species by another. Given the oft-commented upon structural instability of Hamiltonian systems and the corresponding lack of regard in which they are held as useful caricatures of ecological interactions, the pivotal role assigned here to Hamiltonian limits constitutes a qualitative break with the conventional wisdom. Received: 2 November 1998     

Abstract mathematical molecular biology: II some relational consequences of the “one gene-one enzyme” hypothesis

Following the program outlined in a previous paper (Bull. Math. Biophysics,23, 237–260, 1961), a further abstract study is made of some simple relational systems which possess some properties of living organisms. It is shown that the “one gene-one enzyme” hypothesis leads to the conclusion that either all genes are built of the same chemical building blocks, or that at least all genes have a number of building blocks in common. A consistent relational application of the “one gene-one enzyme” hypothesis leads moreover to the conclusion that replication is not an inherent property of a gene. Rather there must be a set of enzymes which “copy” the genes. The number of enzymes in this set must be less than the number of genes and therefore the activity of those “copying” enzymes cannot be absolutely specific.     

Natural transformations of organismic structures

The mathematical structures underlying the theories of organismic sets, (M, R)-systems and molecular sets are shown to be transformed naturally within the theory of categories and functors. Their natural transformations allow the comparison of distinct entities, as well as the modelling of dynamics in “organismic” structures.     

Some results in graph theory and their application to abstract relational biology

It has been shown in earlier work that one approach to what Rashevsky has called “abstract biology” is through the study of the class of ( )-systems that can be formed in an arbitrary subcategory of the category of sets. The concept of the ( )-system, however, depends on the availability of mappings that contain other mappings in their range. It is shown that, by introducing an appropriate measure for this property, the problem of characterizing those categories suitable for a rich theory of ( )-systems reduces to a problem familiar from the general theory of graphs. Some new results in these directions are obtained, and it is then shown that any category with mappings that possess properties we might expect to hold in the physical world will also admit a rich theory of ( )-systems. In particular, it is shown that a sufficiently large family of mappings drawn at random from such a category will with overwhelming probability contain an ( )-system. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Grant No. AF-AFOSR-9-63.     

Heterogeneity ratio: a measure of beta-diversity and its use in community classification

Fifteen previously proposed similarity indices are examined for the effects of sample size and/or group size (the number of samples included in a cluster). The three indices ofCλ,NESS, andC′λ are free from effects, but the former two are unsuitable for arithmetic averaging unless all of the sample sizes are equal. Thus clustering usingC′λ is found to be superior to the combination of any other similarity index and the group-average strategy. Unfortunately none of these measures have the desirable property of measuring the difference in component species among samples independent of the alpha-diversity. A new index of similarity (HR) is developed based on the assumption that community from which samples are taken is described by a logseries distribution. This new index measures the beta-diversity among samples without the influence of sample size and group size, and has the advantage that the significance of fusing samples can statistically be tested. An example clustering withHR is shown and compared with those obtained by other clustering strategies.