ALBERT

Notes: Abstract We present a new symmetric model of the idiotypic immune network. The model specifies clones of B-lymphocytes and incorporates: (1) influx and decay of cells; (2) symmetric stimulatory and inhibitory idiotypic interactions; (3) an explicit affinity parameter (matrix); (4) external (i.e. non-idiotypic) antigens. Suppression is the dominant interaction, i.e. strong idiotypic interactions are always suppressive. This precludes reciprocal stimulation of large clones and thus infinite proliferation. Idiotypic interactions first evoke proliferation, this enlarges the clones, and may in turn evoke suppression. We investigate the effect of idiotypic interactions on normal proliferative immune responses to antigens (e.g. viruses). A 2-D, i.e. two clone, network has a maximum of three stable equilibria: the virgin state and two asymmetric immune states. The immune states only exist if the affinity of the idiotypic interaction is high enough. Stimulation with antigen leads to a switch from the virgin state to the corresponding immune state. The network therefore remembers antigens, i.e. it accounts for immunity/memory by switching beteen multiple stable states. 3-D systems have, depending on the affinities, 9 qualitatively different states. Most of these also account for memory by state switching. Our idiotypic network however fails to account for the control of proliferation, e.g. suppression of excessive proliferation. In symmetric networks, the proliferating clones suppress their anti-idiotypic suppressors long before the latter can suppress the former. The absence of proliferation control violates the general assumption that idiotypic interactions play an important role in immune regulation. We therefore test the robustness of these results by abandoning our assumption that proliferation occurs before suppression. We thus define an “escape from suppression” model, i.e. in the “virgin” state idiotypic interactions are now suppressive. This system erratically accounts for memory and never for suppression. We conclude that our “absence of suppression from idiotypic interactions” does not hinge upon our “proliferation before suppression” assumption.

Notes: Abstract Analytical bounding functions for diffusion problems with Michaelis-Menten kinetics were recently presented by Anderson and Arthurs, 1985 (Bull. math. Biol. 47, 145–153). Their methods, successful to some extent for a small range of parameters, has the disadvantage of providing a weak upper bound. The optimal approach for the use of one-line bounding kinetics is presented. The use of two-line bounding kinetics is also shown, in order to give, sufficient accuracy in those cases where the one-line approach does not provide satisfactory results. The bounding functions provide excellent upper and lower bounds on the true solution for the entire range of kinetic and transport parameters.

Notes: Abstract Thresholds for survival and extinction are important for assessing the risk of mortality in systems exposed to exogeneous stress. For generic, rudimentary population models and the classical resource-consumer models of Leslie and Gallopin, we demonstrate the existence of a survival threshold for situations where demographic parameters are fluctuating, generally, in a nonperiodic manner. The fluctuations are assumed, to be generated by exogenous, anthropogenic stresses such as toxic chemical exposures. In general, the survival threshold is determined by a relationship between mean stress measure in organisms to the ratio of the population intrinsic growth rate and stress response rate.

Notes: Abstract A stochastic analog to a deterministic model describing subpopulation emergence in heterogeneous tumors is developed. The resulting system is described by the Fokker-Planck or forward Kolmogorov equation. A finite element approach for the numerical solution to this equation is described. Four biological and clinical scenarios are simulated (emergence of heterogeneity, exclusion of a subpopulation, and induction of drug resistance in both pure and heterogeneous tumors). The results of the simulations show that the stochastic model describes the same basic dynamics as its deterministic counterpart via a convective component, but that for each simulation a distribution of tumor sizes and mixes can also be derived from a diffusive component in the model. These distributions yield estimates for subpopulation extinction probabilities. The biological and clinical relevance of these results are discussed.

Notes: Abstract Two algorithms for the efficient identification of segment neighborhoods are presented. A segment neighborhood is a set of contiguous residues that share common features. Two procedures are developed to efficiently find estimates for the parameters of the model that describe these features and for the residues that define the boundaries of each segment neighborhood. The algorithms can accept nearly any model of segment neighborhood, and can be applied with a broad class of best fit functions including least squares and maximum likelihood. The algorithms successively identify the most important features of the sequence. The application of one of these methods to the haemagglutinin protein of influenza virus reveals a possible mechanism for conformational change through the finding of a break in a strong heptad repeat structure.

Notes: Abstract Given a sequenceA and regular expressionR, theapproximate regular expression matching problem is to find a sequence matchingR whose optimal alignment withA is the highest scoring of all such sequences. This paper develops an algorithm to solve the problem in timeO(MN), whereM andN are the lengths ofA andR. Thus, the time requirement is asymptotically no worse than for the simpler problem of aligning two fixed sequences. Our method is superior to an earlier algorithm by Wagner and Seiferas in several ways. First, it treats real-valued costs, in addition to integer costs, with no loss of asymptotic efficiency. Second, it requires onlyO(N) space to deliver just the score of the best alignment. Finally, its structure permits implementation techniques that make it extremely fast in practice. We extend the method to accommodate gap penalties, as required for typical applications in molecular biology, and further refine it to search for substrings ofA that strongly align with a sequence inR, as required for typical data base searches. We also show how to deliver an optimal alignment betweenA andR in onlyO(N+logM) space usingO(MN logM) time. Finally, anO(MN(M+N)+N 2logN) time algorithm is presented for alignment scoring schemes where the cost of a gap is an arbitrary increasing function of its length.

Notes: Abstract The stochastic complexity of a data base of 365 protein-coding regions is analysed. When the primary sequence is modeled as a spatially homogeneous Markov source, the fit to observed codon preference is very poor. The situation improves substantially when a non-homogeneous model is used. Some implications for the estimation of species phylogeny and substitution rates are discussed.

Notes: Abstract We present, in an easy to use form, the large deviation theory of the binomial distribution: how to approximate the probability ofk or more successes inn independent trials, each with success probabilityp, when the specified fraction of successes,a≡k/n, satisfies 0〈p〈a〈1.

Notes: Abstract A linear segment in which a number of pairs of intervals of equal length are identified as potential stems is the subject of a folding problem analogous to inference of RNA secondary structure. A quantity of free energy (or equivalently, energy per unit length) is associated with each stem, and the various types of loops are assigned energy costs as a function of their lengths. Inference of stable structures can then be carried out in the same way as in RNA folding. More important, perturbation of stem lengths and energy densities (modelling various mutational processes affecting nucleotide sequences) allows the delineation of domains of stability of various foldings, through the explicit calculation of their boundaries, in a low-dimensional parameter space.

Notes: Abstract In sensory physiology, various System Identification methods are implemented to formalized stimulus-response relationships. We applied the Volterra approach for characterizing input-output relationships of cells in the medial geniculate body (MGB) of an awake squirrel monkey. Intraspecific communication calls comprised the inputs and the corresponding cellular evoked responses—the outputs. A set of vocalization was used to calculate the kernels of the transformation, and these kernels subserved to predict the responses of the cell to a different set of vocalizations. It was found that it is possible to predict the response (PSTH) of MGB cells to natural vocalizations, based on envelopes of the spectral components of the vocalization. Some of the responses could be predicted by assuming a linear transformation function, whereas other responses could be predicted by non-linear (second order) kernels. These two modes of transformation, which are also reflected by a distinct spatial distribution of the linearvis-à-vis non-linear responding cells, apparently representa new revelation of parallel processing of auditory information.

Notes: Abstract The time-dependent surface coverage of antigen-antibody complexes for a sensor in which antigens are bound to surface immobilized antibodies is determined analytically. Assuming a reversible first order reaction between the antigens and antibodies, a model is derived describing the dynamical response of the sensor. The surface coverage is related explicitly to the antigen concentration which is of special interest in experimental situations. The stationary state and short time behaviour are determined explicitly. Several illustrations of the full solution are provided.

Notes: Abstract Simple reaction time is the minimum time required to respond to a signal such as a steady light or tone. Such a reaction time is taken to be the time required for transmission of a fixed quantity of information, ΔH, from stimulus to subject. That is, information summation replaces energy summation. This information is calculated from consideration of the quantum nature of the stimulus. The theoretically derived equation for reaction time is fitted to experimental data. Piéron's empirical law for reaction time is obtained as an approximation from a proposed informational equation. The exponent in Piéron's law is found to be the same as the exponent in the power law of sensation. Threshold appears to be the smallest stimulus capable of transmitting the quantity of information ΔH.

Notes: Abstract The performance of a symmetric nonrecursive filter can be improved by multiple use of the same filter. The method is based on an Amplitude Change Function (ACF). An approach to the design of nonrecursive filters using an ACF is discussed in this paper. The prototype filter chosen is a Recursive Running Sum (RRS) filter which does not require any multipliers for its implementation. The required filter specifications are met by multiple use of the RRS filters. The overall filter requires a much smaller number of multiplications and adders than the one designed using the conventional method. It is shown that this method provides reduced noise due to coefficient quantization and product quantization compared with the conventional design technique.

Notes: Abstract This paper establishes the large-sample accuracy properties of two nonlinear least-squares estimators (NLSE) of sine-wave parameters: the basic NLSE, which ignores the possible correlation of the noise, and the optimal NLSE, which, besides the sine-wave parameters, also estimates the noise correlation (appropriately parametrized). It is shown that these two NLS estimators have thesame accuracy in large samples. This result provides complete justification for preferring the computationally less expensive basic NLSE over the “optimal” NLSE. Both estimators are shown to achieve the Cramér-Rao Bound (CRB) as the sample size increases. A simple explicit expression for the CRB matrix is provided, which should be useful in studying the performance of sine-wave parameter estimators designed to work in the colored-noise case.

Notes: Abstract Multidimensional lossless networks are of special interest for use as reference structures for multidimensional wave digital filters [l]–[3]. The starting point of the presented synthesis procedure for two-dimensional representatives of the networks mentioned is a scattering matrix description of the desired multiport. This given matrix is assumed to have those properties which have turned out to be necessary [9], [10] for any scattering matrix of a multidimensional lossless network. The method presented for the synthesis of 2-D reactancem-ports is based mainly on known properties of block-companion matrices and the factorization of a univariable rational matrix which is discrete para-Hermitian and nonnegative definite on the unit circle. The resulting network always contains only a minimal number of frequency-dependent building elements. No restrictions are made concerning the coefficients of the rational entries of the scattering matrix; they may be either real or complex, so as to include even complex networks which are of special interest for multi-dimensional wave digital filters [3].

Notes: Abstract Examples are given concerning the range of applicability of recent representation results that provide a means of studying the input-output properties of nonlinear systems in terms of the familiar impulse-response concept, and which extend the concept of integral transformation to nonlinear maps. We show that such representations, which we call “g-” and “h-representations,” exist for important classes of systems governed by nonlinear integral equations. In particular, it is proved that a large class of maps that have Volterra series representations also have these representations.

Notes: Abstract This article extends the use of dynamic programming algorithms in molecular sequence comparison to the alignment of the α-carbon (Cα-) coordinates of two protein structures in three dimensions. The algorithm is described in detail and is applied to the comparison of α-lactalbumin with both hen egg white lysozyme and T4 lysozyme. In the first case, the structures are similar, while the second comparison is between two distantly related molecules. References are made to the usual sequence alignments. A variety of complementary methods are introduced to display the results.

Notes: Abstract The composition of naturally occurring DNA sequences is often strikingly heterogeneous. In this paper, the DNA sequence is viewed as a stochastic process with local compositional properties determined by the states of a hidden Markov chain. The model used is a discrete-state, discreteoutcome version of a general model for non-stationary time series proposed by Kitagawa (1987). A smoothing algorithm is described which can be used to reconstruct the hidden process and produce graphic displays of the compositional structure of a sequence. The problem of parameter estimation is approached using likelihood methods and an EM algorithm for approximating the maximum likelihood estimate is derived. The methods are applied to sequences from yeast mitochondrial DNA, human and mouse mitochondrial DNAs, a human X chromosomal fragment and the complete genome of bacteriophage lambda.

Notes: Abstract A new and apparently rather useful and natural concept in cluster analysis is studied: given a similarity measure on a set of objects, a sub-set is regarded as a cluster if any two objectsa, b inside this sub-set have greater similarity than any third object outside has to at least one ofa, b. These clusters then form a closure system which can be described as a hypergraph without triangles. Conversely, given such a system, one may attach some weight to each cluster and then compose a similarity measure additively, by letting the similarity of a pair be the sum of weights of the clusters containing that particular pair. The original clusters can be reconstructed from the obtained similarity measure. This clustering model is thus located between the general additive clustering model of Shepard and Arabie (1979) and the standard hierarchical model. Potential applications include fitting dendrograms with few additional nonnested clusters and simultaneous representation of some families of multiple dendrograms (in particular, two-dendrogram solutions), as well as assisting the search for phylogenetic relationships by proposing a somewhat larger system of possibly relevant “family groups”, from which an appropriate choice (based on additional insight or individual preferences) remains to be made.

Notes: Abstract An important component of computer programs for determining the solution conformation of proteins and other flexible molecules from nuclear magnetic resonance data are the so-called “bound smoothing algorithms”, which compute lower and upper limits on the values of all the interatomic distances from the relatively sparse set which can usually be measured experimentally. To date, the only methods efficient enough for use in large problems take account of only the triangle inequality, but an appreciable improvement in the precision of the limits is possible if the algebraic relations between the distances among each quadruple of atoms are also considered. The goal of this paper is to use a recently improved algorithm for computing these “tetrangle inequality limits” to determine just how much improvement really is possible, given the types of experimental data that are usually available.

Notes: Abstract We apply the concept of marginal stability hypothesis, which has been proposed for solving the problem of dendritic crystal growth, to the pattern selection problem in the Gierer-Meinhardt models. In the case of a large system, the system selects a definite wavelength of the ultimate spatial pattern when the unstable homogeneous steady state is locally disturbed. The numerical results are analyzed theoretically by means of the marginal stability hypothesis, and they are in good agreement with it. Biologically, these results imply why for large systems the Gierer-Meinhardt model (and presumably other reaction-diffusion schemes) have the ability to explain the observation that pattern-generating mechanisms are remarkably insensitive to a wide range of environmental and experimental conditions.

Notes: Abstract Small networks of threshold automata are used to model complex interactions between populations of regulatory cells (helpers and suppressors, antigen specific and anti-idiotypic) which participate in the immune response. The models, being discrete and semiquantitative, are well adapted to the situation of incomplete information often encounteredin vivo. However, the dynamics of many different network structures usually end up in the same attractor set. Thus, many different theories are equivalent in their explicative power for the same facts. This property, known as underdetermination of the theories by the facts, is given a quantitative estimate. It appears that such an underdetermination, as a kind of irreductible complexity, can be expected in manyin vivo biological processes, even when the number of interacting and functionally coupled elements is relatively small.

Notes: Abstract The “paradox of enrichment” predicts that increasing the growth rate of the resource in a resource-consumer dynamic system, by nutrient enrichment, for example, can lead to local instability of the system—that is, to a Hopf bifurcation. The approach to the Hopf bifurcation is accompanied by a decrease in resilience (rate of return to equilibrium). On the other hand, studies of nutrient cycling in food webs indicate that an increase in the nutrient input rate usually results in increased resilience. Here these two apparently conflicting theoretical results are reconciled with a model of a nutrient-limited resource-consumer system in which the tightly recycled limiting nutrient is explicitly modelled. It is shown that increasing nutrient input may at first lead to increased resilience and that resilience decreases sharply only immediately before the Hopf bifurcation is reached.

Notes: Abstract Statistical properties of topological binary trees are studied on the basis of the distribution of segments in relation to centrifugal order. Special attention is paid to the mean of this distribution in a tree as it will be used as a measure of tree topology. It will be shown how the expectation of the mean centrifugal order depends both on the size of the tree and on the mode of growth in the context of modelling the growth of tree structures. Observed trees can be characterized by their mean orders and procedures are described to find the growth mode that optimally corresponds to these data. The variance structure of the mean-order measure appears to be a crucial factor in these fitting procedures. Examples indicate that mean-order analysis is an accurate alternative to partition analysis that is based on the partitioning of segments over sub-tree pairs at branching points.

Notes: Abstract We propose certain general conditions that we believe are reasonable for any pattern recognition algorithm. We find that these conditions give rise to paradoxical identification. The algorithms are incapable of distinguishing composite patterns and must be able to distinguish patterns at an atomistic level.

Notes: Abstract A stratigraphically oriented series of the Miocene foraminiferal speciesBrizalina mandoroveensis from Ikang, Cameroon, was analyzed both by conventional multivariate morphometric procedures and by the tensor biometric method of Bookstein (1986;Statist. Sci. 1, 181–142), a method which analyzes sets of landmark points rather than specific variables of shape or size. The conventional analysis used five size-measures upon 170 specimens from five stratigraphic levels; the tensor analysis encompassed six landmarks (12 coordinates) upon 50 specimens. Whereas certain features appeared in both analyses, such as the separation between levels one and five, the techniques did not always agree with respect to the interpretation of those findings or about most details in the sequence of mean phenotypes. The canonical variate analysis bases its ordination upon a general size factor (the meaning of which is obscured by the foreshortening of within-group variation which is built into the technique). The tensor analysis locates a similar ordination using mainly features of shape.

Notes: Abstract In a separate paper, we developed a mathematical model describing HIV infection and used it to suggest experiments for quantifying characteristic viral parameters. In this paper we generalize the model to any well-mixed assay system. We also present complete and rigorous derivations of fundamental results needed for the design and analysis of HIV infectivity assays. The model is applicable to infectious agents with multiple receptors for their target cell (e.g. HIV, Epstein-Barr virus and Plasmodium), and to blockers (both reversible and irreversible), as long as blocker and target cells are the same diffusion compartment.

Notes: Abstract A general version of a model of Ebenman for the dynamics of a population consisting of competing juveniles and adults is analyzed using methods of bifurcation theory. A very general existence results is obtained for non-trivial equilibria and non-negative synchronous two-cycles that bifurcate simultaneously at the critical valuer=1 of the inherent net reproductive rater. Stability is studied in this general setting near the bifurcation point and conditions are derived that determine which of these two bifurcating branches is the stable branch. These general results are supplemented by numerical studies of the asymptotic dynamics over wider parameter ranges where various other bifurcations and stable attractors are found. The implications of these results are discussed with respect to the effects on stability that age class competition within a population can have and whether such competition is stabilizing or destabilizing.

Notes: Abstract Phototransduction is a process which links the absorption of photons by a rod or cone to the modulation of voltage across the cell membrane. An important feature of many vertebrate photoreceptors is a mechanism that adjusts the sensitivity and dynamics of the response to light according to the level of illumination. We construct a system of ordinary differential equations that models what are currently thought to be the important molecule mechanisms involved in phototransduction: this includes consideration of both intracellular enzyme kinetics and the properties of light-insensitive and light-sensitive conductances in the cone membrane. The system contains negative feedback whose functional form is determined by constraining the steady-state behaviour of the system. Despite the highly nonlinear nature of the system of ordinary differential equations, our methods permit us to derive an analytic expression for the first-order frequency response parametric in the steady-state value of only one dynamic variable, the light input. Various unknown kinetic parameters are found by fitting the model to experimental data on the first-order frequency response of cones measured at several mean light levels spanning a range of four log units. Good fits are obtained to the data, and the computed shape of the feedback function agrees qualitatively with recent experiment. Moreover, the model accounts for the dramatic speeding up of the response kinetics and the decrease in response gain with increasing light level.

Notes: Abstract We first analyse a simple symmetric model of the idiotypic network. In the model idiotypic interactions regulate B cell proliferation. Three non-idiotypic processes are incorporated: (1) influx of newborn cells; (2) turnover of cells: (3) antigen. Antigen also regulates proliferation. A model of 2 B cell populations has 3 stable equilibria: one virgin, two immune. The twodimensional system thus remembers antigens, i.e. accounts for immunity. By contrast, if an idiotypic clone proliferates (in response to antigen), its anti-idiotypic partner is unable to control this. Symmetric idiotypic networks thus fail to account for proliferation regulation. In high-D networks we run into two problems. Firstly, if the network accounts for memory, idiotypic activation always propagates very deeply into the network. This is very unrealistic, but is an implication of the “realistic” assumption that it should be easier to activate all cells of a small virgin clone than to maintain the activation of all cells of a large (immune) clone. Secondly, graph theory teaches us that if the (random) network connectance exceeds a threshold level of one interaction per clone, most clones are interconnected. We show that this theory is also applicable to immune networks based on complementary matching idiotypes. The combination of the first “percolation” result with the “interconnectancr” result means that the first stimulation of the network with antigen should eventually affect most of the clones. We think this is unreasonable. Another threshold property of the network connectivity is the existence of a virgin state. A gradual increase in network connectance eliminates the virgin state and thus causes an abrupt change in network behaviour. In contrast to weakly connected systems, highly connected networks display autonomous activity and are unresponsive to external antigens. Similar differences between neonatal and adult networks have been described by experimentalists. The robustness of these results is tested with a network in which idiotypic inactivation of a clone occurs more generally than activation. Such “long-range inhibition” is known to promote pattern formation. However, in our model it fails to reduce the percolation, and additionally, generates semi-chaotic behaviour. In our network, the inhibition of a clone that is inhibiting can alter this clone into a clone that is activating. Hence “long-range inhibition” implies “long-range activation”, and idiotypic activation fails to remain localized. We next complicate this model by incorporating antibody production. Although this “antibody” model statically accounts for the same set of equilibrium points, it dynamically fails to account for state switching (i.e. memory). The switching behaviour is disturbed by the autonomous slow decay of the (long-lived) antibodies. After antigenic triggering the system now performs complex cyclic behaviour. Finally, it is suggested that (idiotypic) formation of antibody complexes can play only a secondary role in the network. In conclusion, our results cast doubt on the functional role of a profound idiotypic network. The network fails to account for proliferation regulation, and if it accounts for memory phenomena, it “explodes” upon the first encounter with antigen due to extensive percolation.

Notes: Abstract A new biomathematical description is given for the shape of the birch leaf roller's (Deporaus betulae) incisions. These incisions are investigated for different leaves. The theoretical patterns agree well with the real ones, and the presented mathematical expressions describe well the shape of the real incisions.

Notes: Abstract Nucleotide sequences carry genetic information of many different kinds, not just instructions for protein synthesis (triplet code). Several codes of nucleotide sequences are discussed including: (1) the translation framing code, responsible for correct triplet counting by the ribosome during protein synthesis; (2) the chromatin code, which provides instructions on appropriate placement of nucleosomes along the DNA molecules and their spatial arrangement; (3) a putative loop code for single-stranded RNA-protein interactions. The codes are degenerate and corresponding messages are not only interspersed but actually overlap, so that some nucleotides belong to several messages simultaneously. Tandemly repeated sequences frequently considered as functionless “junk” are found to be grouped into certain classes of repeat unit lengths. This indicates some functional involvement of these sequences. A hypothesis is formulated according to which the tandem repeats are given the role of weak enhancer-silencers that modulate, in a copy number-dependent way, the expression of proximal genes. Fast amplification and elimination of the repeats provides an attractive mechanism of species adaptation to a rapidly changing environment.

Notes: Abstract The kinematics of an area-conserving tank-treading disk-shaped red blood cell membrane is studied using the stream function method suggested by Secomb and Skalak (Q. Jl Mech. appl. Math. 35, Pt 2, 233–247, 1982). Two simple area-conserving velocity fields are superimposed to satisfy the continuity condition at the curved edges of the disk. A differential equation for the trajectory of any material point of the membrane is derived. The requirement of synchrony of the cycle for all membrane points leads to an integral equation which determines a magnitude function. An approximate solution is made possible by assuming small trajectory deflections.

Notes: Abstract The probability of becoming infected with HIV is formulated in terms of the total number of sexual contacts (N), the probability that a sexual act is infectious (r) and the prevalence (p). Using the appropriate equations we studied the effect of reducing each of the risk factors on lowering the probability of infection. We show that for many realistic situations the probability of becoming infected by multiple partners is equal to the probability of becoming infected by one partner in a monogamous relationship given that the prevalence is the same in both cases; however if the multiple partners are chosen over time from a pool of a growing prevalence, then one is better off in a monogamous relationship where that partner is chosen early in the epidemic.

Notes: Abstract In this article the question of reconstructing a phylogeny from additive distance data is addressed. Previous algorithms used the complete distance matrix of then OTUs (Operational Taxonomic Unit), that corresponds to the tips of the tree. This usedO(n 2) computing time. It is shown that this is wasteful for biologically reasonable trees. If the tree has internal nodes with degrees that are bounded onO(n*log(n)) algorithm is possible. It is also shown if the nodes can have unbounded degrees the problem hasn 2 as lower bound.

Notes: Abstract In this paper we analyse time series data as the growth of organisms using markers such as treerings and otolith deposits (fish). The series studied belong to two tree species (Pinus uncinata, Fagus sylvatica) and one fish species (Dicentrarchus labrax). Spectral analyses of the time series growth show that the main frequencies of fluctuation may be due to variations of the energy input. However, any causal explanation must consider the internal continuous readjustment in the system as reported by the corresponding chaotic properties of the asymptotic decay of the spectra time structure. Since the output of noisy and chaotic systems tend to show similar spectral densities, an attempt to differentiate them has been carried out. The chaotic behaviour has been characterized by the study of the attractors. The dimmensions of these multiple topologies were 3.2 and 3.4 for the tree species and 2.3 for the fish species. Therefore, we are dealing with fractal attractors and the minimum number of variables that can be used to describe the systems are 4 and 3 respectively. It is suggested that some of the variables that most influence growth are those obtained by the response functions in the case of trees.

Notes: Abstract In this article we present a method that allows conditioning of the response of a linear distributed memory to a variable context. This method requires a system of two neural networks. The first net constructs the Kronecker product between the vector input and the vector context, and the second net supports a linear associative memory. This system is easily adaptable for different goals. We analyse here its capacity for the conditional extraction of features from a complex perceptual input, its capacity to perform quasi-logical operations (for instance, of the kind of “exclusive-or”), and its capacity to structurate a memory for temporal sequences which access is conditioned by the context. Finally, we evaluate the potential importance of the capacity to establish arbitrary contexts, for the evolution of biological cognitive systems.

Notes: Abstract Hoffmann (1982) analysed a very simple model of suppressive idiotypic immune networks and showed that idiotypic interactions are stabilizing. He concluded that immune networks provide a counterexample to the general analysis of large dynamic systems (Gardner and Ashby, 1970; May, 1972). The latter is often verbalized as: an increase in size and/or connectivity decreases the system stability. We here analyse this apparent contradiction by extending the Hoffmann model (with a decay term), and comparing it to an ecological model that was used as a paradigm in the general analysis. Our analysis confirms that the neighbourhood stability of such idiotypic networks increases with connectivity and/or size. However, the contradiction is one of interpretation, and is not due to exceptional properties of immune networks. The contradiction is caused by the awkward normalization used in the general analysis.

Notes: Abstract In the commonly used model (Sokoloff) for the transport and metabolism of glucose and 2-deoxyglucose in brain tissue a novel choice of constant parameters is proposed. In particular, the maximal transport capacity for glucose is assumed proportional to the rate of glucose consumption. The proportionality factor, the “transport factor”, may be calculated from the lumped constant and is more likely than the latter to remain constant under varying conditions. Calculations founded on these considerations should yield results similar to the Sokoloff procedure in many situations, but differences appear when the arterial glucose concentration changes. The model is flexible and allows changes.

Notes: Abstract We briefly review the results of other authors concerning the analysis of systems with time hierarchy, especially the Tikhonov theorem. A theorem, recently proved by the authors, making possible rigorous analysis of systems with complex fast dynamics is stated and discussed. A model example of a simple enzymatic reaction with product activation and slow (genetically driven) enzyme turnover is rigorously studied. It is shown that even in such a simple model there exist certain regions of parameters for which fast variables oscillate. Thus the classical Tikhonov theorem is not applicable here and we are forced to use another method-for example the author's presented theorem—or a purely numerical solution. These two methods are compared.

Notes: Abstract The linear isobole that is commonly used as a reference for the study of interaction is derived from the interaction of an agent with itself. It is shown that the general use of the linear isobole in the study of the combined effects of mixtures of agents implies interaction between the agents whether the dose-effect curves of the agents are the same or not. It is difficult to generalize the interaction between two doses of the same agent to the interaction between two doses of different agents with different action mechanisms without the use of a mechanistic model. Predictions using non-interaction defined as independent action are generally different from those using linear isobole. A simple mechanistic framework based on the concept of common intermediate lesions is introduced in this paper to relate these two methods used for the analysis of synergism and antagonism. In this framework of lesion development, two agents that have no common intermediate lesion in their action will be non-interactive (referred to as independent action). When the two agents share a common intermediate, it is shown that the combined effect will follow the linear isobole (referred to as common action). This simple framework of analysis is applicable to the general study of interaction between two agents with different types of dose-effect curves.

Notes: Abstract Pseudorandom (or maximal length) sequences and arrays have been known for a long time, and have been reported by several authors. Pseudorandom volumes have also been mentioned. This paper presents a different type of sequence of arrays in which the arrays share many properties with the pseudorandom arrays of the literature, and the sequence (or group) of arrays has many properties in common with the pseudorandom sequences. It is proposed that this set of arrays be called a “pseudorandom sequence of arrays,” or PRSAs. Some interesting properties of the PRSA as well as its practical (hardware) implementation have been mentioned. It has also been shown that our result is a special case of the generalN(3)/D(3) case.

Notes: Abstract For linear time-invariant discrete-time systems, an exponentially convergent recursive parameter identification scheme is derived requiring only that the regression vector be sufficiently exciting, that is the sum of the outer products of the regression vector is eventually positive definite. The algorithm produces a parameter estimate that converges to the batch-form (nonrecursive) least-squares estimate without requiring a persistent excitation. The rate of convergence can be selected as a design parameter. If the regression vector is persistently exciting, it is shown that a forgetting factor can be added to the formulation in such a way that the magnitude of the forgetting factor and the rate of exponential convergence can be set separately.

Notes: Abstract The semistate theory of circuits and systems is reviewed with regard to its applications. Among these latter discussed are electronic circuit design and analysis, hysteresis, knot generation, neural networks, and constrained robot characterizations.

Notes: Abstract Four notions of controllability for general (i.e., possibly nonregular) implicit linear discrete-time systems are considered. Relationships between them are studied. A Hautus-type characterization of all of these notions is also given.

Notes: Abstract A new concept of system equivalence which allows the establishment of a formal relation between singular and regular systems has been introduced. By applying this concept, an open-loop strategy for finite-time control of a given solvable singular system, which is simple for both computation and implementation, is developed. A strategy for finite-time output feedback control is considered for a continuous singular system. It is shown that provided the system is observable, a desired polynomial command for finite-time control can be determined from a finite sequence of output measurements sampled at discrete instants of time.

Notes: Abstract In this paper we study the system-theoretic properties of two related classes of shift-invariant two-point boundary-value descriptor systems (TPBVDSs), namelydisplacement systems for which Green's function is shift-invariant, andstationary systems for which the input-output map is stationary. For such systems it is possible to obtain detailed characterizations of the properties of weak reachability and observability introduced in [16] and of minimality as well. An important difference, that has also been noted before in a different context [9], is that there is a certain level of nonuniqueness in minimal realizations. Another property that is studied in this paper is that of extendibility, i.e., the concept of considering a TPBVDS as being defined on a sequence of intervals of increasing length. Necessary and sufficient conditions for extendibility are given.

Notes: Abstract Scaling of filter variables is central to fixed-point implementation of digital filters. A simple method of scaling based on scaling constants of individual sections of a cascade digital filter is presented. The proposed method saves much computational labor in the implementation of higher-order digital filters. Maximal amplitude expressions of second-order filter transfer functions are also presented.

Notes: Abstract This paper is concerned with the stability analysis of second-order direct-form digital filters with two magnitude truncation quantizers. Zero-input stability is proved for the parameter regions where no conclusion can be drawn using the methods previously suggested in the literature. The areas of the parameter plane in which only limit cycles of period 1 or 2 exist, are determined and related to the cycle amplitudes. Finally, a transition graph is suggested to study the convergence patterns of the filter output.

Notes: Abstract The work of digital PLL is analysed. For this analysis a Markov model is used.

Notes: Abstract The formulation of one-multiplier lattice structures of the Gray-Markel type forinfinite impulse response filters is reviewed. Several special cases of this formulation — including the well-known Gray-Markel normalized lattice—are presented as scaled polynomial versions of the two-multiplier lattice. A new adaptive algorithm is presented for updating the parameters of one-multiplier lattice structured recursive filters. The LMS-based algorithm requires fewer computations than earlier reported algorithms [1]–[4].

Notes: Abstract In this paper we consider the problem of obtaining minimal-order representations of generalized state-space systems described by equations of the formE x(t)=A x(t)+B u(t),y(t)=C x(t)+D u(t) withE singular and det(sE−A)≠0. The underlying principle is that of removal of impulsive and exponential uncontrollable and unobservable modes. When this is followed by the removal of the remaining impulsive modes, we get a minimal-order generalized or standard state-space representation. Simple reduction procedures and numerical algorithms based on these principles are developed and illustrated by means of two numerical examples.

Notes: Abstract In this paper we consider models for noncausal processes consisting of discrete-time descriptor dynamics and boundary conditions on the values of the process at the two ends of the interval on which the process is defined. We discuss the general solution and well-posedness of systems of this type and then apply the method of complementary processes to obtain a specification of the optimal smoother in terms of a boundary-value descriptor Hamiltonian system. We then study the implementation of the optimal smoother. Motivated by the Hamiltonian diagonalization results for nondescriptor systems, we show how the descriptor Hamiltonian dynamics can be transformed to two lower-order systems by the use of transformation matrices involving the solution of two generalized Riccati equations. We present several examples illustrating our results and the nature of the smoothing solution and also present equations for covariance analysis of boundary-value descriptor processes including the smoothing error.

Notes: Abstract The structure inherent to the centrosymmetric matrices is exploited to obtain factorization results leading to significant computational savings in many engineering applications. Several interesting properties of the matrices are discussed with a view toward algorithm computational complexity. It is shown that the multiplicative complexity involved in the process of principal component (eigen-value/eigenvector) extraction, and in the evaluation of the determinant and inverse of such matrices, can be reduced by nearly 75% by employing the results presented here. The theory presented hereunifies andgeneralizes previous computationally efficient results onseveral specialized generalized centrosymmetric matrices; for example, the class of symmetric centrosymmetric (or doubly symmetric) matrices is shown to be a special case of the class of centrosymmetric matrices, and since the results obtained here are applicable over the field of complex numbers, the factorization results available for centrosymmetric matrices are readilyextended to the complex field. The centrosymmetric matrices play an important role in a number of areas such as pattern recognition, antenna theory, mechanical and electrical systems, and quantum physics. Specific examples of pattern recognition feature selection, a uniform linear antenna array, vibration in structures, and the quantummechanical oscillator are discussed to demonstrate that the theory developed here has a wide range of applications. In addition, certain specialized cases of the centrosymmetric matrices have, in the past, proved their indisputable usefulness in the areas of communication theory, digital filters, linear systems, linear prediction, and speech analysis.

Notes: Abstract The well-known Jury and Blanchard's stability test for discrete systems is with an array of (2n−3) rows of elements. Raible simplified Jury and Blanchard's array to (n+1) rows by introducing an additional element at the end of each row. Chen and Chan recently derived a Liapunov function through Schwarz' transform to prove the criterion directly and to produce a very compact form. The purpose of this paper is to explore the various singular cases by using the newly established Chen-Chan criterion. Some existing methods for studying singular cases are re-examined under the light shed by Chen and Chan. A by-product is to define and to determine the relative stability of discrete systems.

Notes: Abstract A new negative resistance oscillator model was proposed by Walker and Connelly. We investigate the mathematical properties of the associated nonlinear differential equation for a single-mode LCR network oscillator. In particular, we prove that under suitable conditions, small-amplitude stable limit-cycle oscillations can occur. The method of harmonic balance is used to calculate an analytic approximation to the limit-cycle parameters. Also, the general properties of trajectories in phase-space are presented. These predictions are compared with the results obtained by numerical integration of the differential equation.

Notes: Abstract A general structure is presented for the block realization of two-dimensional infinite impulse response digital filters, which is based on the two-dimensional matrix convolution equations and the decomposition of their associated transfer function matrices. The proposed decomposition may be considered as an extension of the scalar decomposition technique, which has already been used for the realization of two-dimensional digital filters associated with two-variable polynomials. The decomposition structure is considered in two different forms, which correspond to the direct forms I and II. It is shown that if a given two-dimensional single-input, single-output filter is realizable, then realizable block decomposition structures may be always selected. The proposed approach is general and applies without any restriction for the block implementation of any two-dimensional filter. The resulting structures are characterized by high inherent parallelism, modularity, regularity, reconfigurability, local interconnections, and very high sampling and throughput rates. Thus they are well suited for VLSI implementation and implementation via multiprocessor systems and array processors, such as systolic and wavefront arrays.

Notes: Abstract It has been observed that the backward differentiation approximation to the solutions ofEx′+Fx =f can fail to converge even pointwise in an initial boundary layer. This paper shows that the approximations converge in a distributional sense even if the exact solution is also distributional.

Notes: Abstract This paper deals with a refined qualitative analysis of motions of a broad class of continuous time-varying nonlinear singular differential systems. These systems consist of a finite number of first-order differential equations that cannot be set into the normal form. Some novel qualitative concepts, convenient for the description of solutions of singular systems, are introduced and analyzed. These concepts involve some inherent properties of singular systems. General sufficient conditions for these concepts are derived in terms of the existence of a suitable Lyapunov function. Also, for the subclass of singular systems considered, the construction of a Lyapunov function candidate that can be effectively applied in the analysis is proposed. The results obtained generalize some known results in stability theory.

Notes: Abstract The objective of this paper is to make clear the fundamental importance of thefundamental matrix ϕ k in the analysis of linear discrete-time singular systems. We relateϕ k to the coefficientsR k of the adjoint matrix (zE-A)−1, find an autoregressive recursion for theϕ k , and give the solution of the singular semistate equation in terms ofϕ k . Also discussed are thesemistatetransition matrix and the singular systemTschirnhausen polynomials. We close by giving a stable numerical technique for the computation of the sequenceϕ k that is based on first taking the pencilzE-A to triangular form.

Notes: Abstract Impulsive solutions of linear homogeneous matrix differential equations are re-examined in the light of the theory of Jordan chains that correspond to infinite elementary divisors of the associated polynomial matrix. Infinite elementary divisors of general polynomial matrices are defined and their relation to the pole-zero structure of polynomial matrices at infinity is examined. It is shown that impulsive solutions are due to Jordan chains of a “dual” polynomial matrix that correspond to infinite elementary divisors that are associated with the orders of “zeros at infinity” of the original matrix.

Notes: Abstract Generalized linear systems are classified according to their algebraic structure and their regularizability and normalizability properties under generalized state feedback are investigated. New feedback invariants are introduced in terms of the input-space restriction pencil and the Plücker matrix of the system. It is shown that the classification of subspaces of the state space of generalized linear systems is reduced to an equivalent problem of classifying the subspacesV of the domain of an ordered pair (F, G), F, Gεℝm×n. The set of strict equivalence invariants of the restriction pencil (F, G)/V provides a complete, basis-free algebraic characterization and leads to the definition of notions of geometric invariance. The key geometric notions that emerge are those of (F, G)-, (G, F)-, complete-(F, G)-, partitioned(F, G)-, cyclic-, and semicyclic-invariant subspaces. A complete set of geometric algorithms leading to the computation of the above families is also given. The above families of invariant subspaces are characterized in terms of the invariants of (F, G)/V, and this provides the links with their dynamic characterization. These results provide an “open-loop” or “feedback-free” unifying treatment of spaces of generalized systems, which for the case of proper systems is reduced to the standard geometric theory results.

Notes: Abstract This paper develops a set of fast prime factor decomposition algorithms (PFDAs) for a family of discrete trigonometric transforms of sizeN, whereN is a product of two relatively prime integers. Relevant equations for the PFDAs are derived. Computational procedures are presented followed by a specific example forN= 12. The input and output index mappings necessary for the algorithm are obtained and the computational complexity is briefly outlined.

Notes: Abstract In the studies of singular systems regularity is often presumed although it may not be satisfied in some real cases. Therefore, natural questions are: What is the difference between regularity and irregularity? How far can we go from regularity to irregularity in the studies of singular systems? This paper partially answers these questions. The results show that the concepts of reachability, controllability, and observability for regular systems can be easily extended to irregular cases. There is minor difference between regular and irregular singular systems. Thus the assumption of regularity is reasonable.

Notes: Abstract An optimization method is proposed for the design of high-order all-pass delay equalizers for a prescribed group-delay characteristic by using the cascade form realization of digital filters. Unlike other methods, in the proposed method stability is guaranteed by imposing certain mild constraints on the filter coefficients so that the unconstrained optimization technique of Fletcher and Powell is used. To reduce the function minimization time, design values of the parameters of the delay equalizers, obtained by Bernhardt's simplified method, are used as the initial vector in the optimization technique of the proposed method. It is shown that the proposed method for the design of optimal delay equalizers results in all classes of equalizers with real and complex poles and approximates the prescribed group delay more accurately.

Notes: Abstract Given the Volterra series representation of a single input, single output nonlinear system, we examine conditions on the Volterra kernels that determine if the system is in some sense equivalent to a linear system. The systems considered herein are known as “feedback linearizable” systems. Feedback linearizable systems are usually discussed in terms of their state-space representations. A key result relates the Volterra series description of a feedback linearizable system to its state-space description.

Notes: Abstract The comparison of entire genomes in evolutionary studies gives rise to alignments characterized by many intersections, or inversions in the order of two fragments in different genomes. To model this, we suggest a random migration process for fragments, and discuss its equilibrium distribution in the case of linear and circular genomes. Simulations are carried out to explore “cut-off” behavior as the process approaches equilibrium. We define a new process to take into account the indistinguishability of two fragments which are adjacent in both genomes being compared. Questions of applicability of these models are discussed.

Notes: Abstract There is still controversy as to which characteristics of the pressure-volume relation should be used to define myocardial contractility. In the present study a mathematical model for the left ventricle as a two-dimensional cylinder contracting radially and symmetrically was used to establish a relation between a calculated intramyocardial pressure (Dh) and theP-V relation (PVR) at end-systole. Four new indices are introduced that allow a better assessment of change in inotropic state of the myocardium, namely the calculated intramyocardial pressure (Dh), the calculated resultant pressure across the inner surface of the myocardium (Dh-P) (P=cavity pressure), the workW t related to the pressure (Dh) and the workW d related to the pressure (Dh-P). A relation betweenW t andW d and different parts of the area under the PVR is established. Indices derived in this manner from the PVR to study changes in myocardial contractility appear to have a clear physical meaning.

Notes: Abstract A mathematical model for cell sorting and migration in the slug stage of cellular slime moldsDictyostelium discoideum is proposed. Assuming that a slug is a “mixed fluid” of prespore and prestalk cells, a set of equations which describe the dynamics of cell distribution, internal pressure and velocity of hte slug are derived from the balance formula of individual cell movement. These equations are analyzed to obtain the spatial patterns of the two types of cells at dynamical equilibrium and the relationship between the migration velocity and the slug size. The body shape of the elongated slug at the migrating stage is also investigated, taking account of the law of surface tension. The stable shapes of slugs with different volumes are explicity obtaained and the existence of critical size of a slug is suggested.

Notes: Abstract The mesodermal tissue of some amphibian gastrula develops into a dorsal-to-ventral sequence of notochord, somite, pronephros, and lateral plate cell types. The cellular proportions regulate with respect to embryo size. The dorsal blastoporal lip appears to function as an organizer for the embryo. The transplantation of a donor lip to the ventral side of a host causes a second, opposed embryo to form and the system commits similar total proportions of cells as do normally developing embryos. Transplantation of donor somite to the ventral side of a host causes a reduction in the proportion of host somite developed. A modified reaction-diffusion system governing embryo development is proposed. Developmental simulations consistent with experimental observations are presented and analyzed. The results suggest that the degree of somite inhibition is positively correlated with the size of the somite transplant. Further predictions are that sufficiently large somite transplants would induce ectopic, ventral pronephros to form and ventral pronephros transplants would inhibit host pronephros development.

Notes: Abstract Neurophysiological and anatomical observations are used to derive a non-linear delay-differential equation for the pupil light reflex with negative feedback. As the gain or the time delay in the reflex is increased, a supercritical Hopf bifurcation occurs from a stable fixed point to a stable limit cycle oscillation in pupil area. A Hopf bifurcation analysis is used to determine the conditions for instability and the period and amplitude of these oscillations. The more complex waveforms typical of the occurrence of higher order bifurcations were not seen in numerical simulations of the model. This model provides a general framework to study the different types of dynamical behaviors which can be produced by the pupil light reflex, e.g. edge-light pupil cycling.

Notes: Abstract Amiodarone concentrationsy(t) have been measured from 1 min to more than 50 days following 10 min of infusion, with about 40 observations on each of six normal subjects (Tuckeret al., 1984,Eur. J. clin. Pharmacol. 26, 655–656). The form of the log-log plots—ln(y) vs ln(t)—is investigated. These appear to show three phases. First there is a rapid decrease ofy(t). then a straight line corresponding to a small negative power oft, ca −0.3, and this line changes continuously but quickly at about 0.5 day into a steeper line that is almost straight. For the curve fitting a simple “spline-type” device was successful. Two continuity conditions were imposed at the time of changeover, which was one of the unknown parameters. The results are compared in detail with those from a set of 15 radiocalcium curves obtained during 2 weeks or more from a single injection of47Ca (Neeret al., 1967,J. clin. Invest. 46, 1364–1379). Again two power functions of time can be seen. The changeover is much more gradual than with amiodarone, and the fits are still better. Both sets of curves are fitted with fewer adjustable parameters than with the usual multiexponentials that are interpreted in terms of homogeneous compartments. Theoretical and practical implications are mentioned. There is much indirect evidence that hundreds of other clearance curves may consist largely of one or two of such power functions of time.

Notes: Abstract We propose the use of a stationary probability distribution for the analysis of data on population size. Predicting this long term population property from short term individual events is accomplished by the use of the asymptotic theory of stochastic processes. A WKB approximation to the stationary density is obtained and then applied to observations on the flour beetleTribolium.

Notes: Summary Sterilization of bioreactor media, to destroy viability of the indigenous microbial population, is normally accomplished by autoclaving, or heating with pressurized steam. However, simultaneous chemical changes in media can also be expected to result from the high temperatures. A kinetic procedure involving on-line computer calculation of heat input, designated asF 0 values, was previously developed to estimate sterility achievement. A similar kinetic procedure, based on a general purpose Arrhenius ‘pseudo’ rate equation and designated asR 0 values, has now been designed to evaluate, and control the effects of temperature and heating time on chemical reactions occurring in the media. Data are presented indicating thatR 0 may be a useful parameter for reducing variability in culture metabolism and ‘scale-up’ when these variations result from different nutrient concentrations produced by non-standard heating during media sterilization in stirred bioreactors.

Notes: Summary Eight species of bacteria were incubated in culture media containing 10 μg/ml aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), or aflatoxin G2 (AFG2). Their culture density at 20°C was determined at four and eight days (d) after inoculation. In all species of bacteria studied (Bacillus cereus, Proteus mirabilis, Erysipylothrix rusiopathie (insidiosa), Streptococcus fecalis, Staphylococcus epidermis, Klebsiella pneumoniae, Micrococcus spp., andEscherichia coli), AFB1, AFB2 and AFG2 substantially decreased culture sizes at 4 d, but not at 8 d. InB. cereus andP. mirabilis, culture sizes were increased by AFB1, AFB2, and AFG2 at 8 d post inoculation. These results indicate that AFB1, AFB2, and AFG2 suppressed initial growth of these species in vitro, while later growth in some species was either unaltered or enhanced.

Notes: Summary The toxicity of germanium dioxide (GeO2) to 21 bacterial and 13 yeast strains was investigated in liquid broth medium to obtain information on strains tolerant to high (1 to 2 mg/ml) GeO2 concentrations.Arthrobacter sp. NRC 32005,enterobacter aerogenes NRC 2926,Klebsiella aerogenes NCTC 418 andPseudomonas putida NRC 5019 were tolerant to 1 mg/ml GeO2.Bacillus sp. RC607 was able to grow in the presence of 2 mg/ml GeO2 at pH 10 in broth culture. The yeastsCandida guilliermondii, Candida shehatae andPachysolen tannophilus were the most sensitive to GeO2 as evidenced by their diminished growth rates at a GeO2 concentration as low as 0.1 mg/ml. None of the yeast strains tested exhibited growth in the presence of 1 mg/ml GeO2. The high pH of the medium containing germanium may be partially responsible for the growth inhibition of the yeast cultures. Select bacterial cultures previously exposed to 1 mg/ml GeO2 could tolerate and grow better at 2 mg/ml GeO2, suggesting the existence of very efficient adaptive mechanisms. The pH of the medium could modulate GeO2 tolerance and this effect was found to be strain-dependent.

Notes: Summary Protocols for protoplast formation, L-colony cultivation, and regeneration ofClostridium beijerinckii NRRL B-592, B-593 andC. acetobutylicum ATCC 10132 were developed. Two osmotically reinforced media were formulated. Protoplasts of B-592, B-593, and ATCC 10132 grew as cell wall-deficient forms (L-colonies) when plated on the first medium (BLM) and continued to do so through at least 3 passages on this medium. The second (BRM) permitted the L-colonies to regenerate cell walls after transfer to this medium. TransferredC. beijerinckii B-592 L-colonies reverted to bacillary colonies at a frequency of 25%. Likewise, L-colonies of B-593 andC. acetobutylicum ATCC 10132 could be regenerated at frequencies of 7.0 and 8.6%, respectively. Thus, these procedures are suitable for genetic engineering of these industrial microorganisms using protoplast manipulation techniques.