II. An electrochemical model of the brain: Collective behaviour,irreversibility and information

Here the theory developed in a previous paper is applied to a many-neuron model representing the brain. It is shown that this model may exhibit quiet states in which it functions as a system of coupled harmonic oscillators. The problems arising in the specification of the synaptic and environmental coupling parameters, and a set of compatible initial conditions are resolved, and by an analysis of the normal modes it is shown that in quiet states even a small model consisting of twelve neurons will reflect in magnitude and distribution the basic waves observed in electroencephalograms. The model also possesses a closely spaced spectrum of high frequencies characteristic of active states, which are excited by environmental interactions. When the potential in any neuron exceeds the characteristic threshold value, a firing sequence similar to that found in the isolated neuron is initiated. Such sequences are shown to be modified by and react on neighbouring neurons, and some of the simpler cooperative effects are investigated. In the final section, an information theoretic analysis is made of the model. It is shown how to establish a quantitative measure of the information available to the brain, how to relate such information to the stimuli which the brain experiences in the course of its development, and how such information influences the firing patterns which manifest themselves in the external behaviour of the animal. A tentative relation between quantal effects and decision-making processes is discussed.     

On the computation of the tertiary structure of globular proteins. III. Inter-residue distances and computed structures

An analysis of geometrical models for computing the tertiary structure of globular proteins from the primary structure is presented. The roles of initial configuration, input information on inter-residue distances and the errors in this information are delineated. It is shown that for local information like that on secondary structure, the calculated structure is very sensitive to errors and to the initial configuration. Thus, such information is far from adequate for predicting the tertiary structure. On the other hand, global information on all the inter-residue distances is quite insensitive to errors. A semi-empirical method is presented to estimate these distances and the calculated structures are given for two proteins—pancreatic trypsin inhibitor and parvalbumin. These structures have good resemblances to those determined by X-ray diffraction. A strategy for further refinement of the method is indicated.     

Neurophysiological mechanisms underlying face processing within and beyond the temporal cortical visual areas.

The ways in which information about faces is represented and stored in the temporal lobe visual areas of primates, as shown by recordings from single neurons in macaques, are considered. Some neurons that respond primarily to faces are found in the cortex in the anterior part of the superior temporal sulcus (in which neurons are especially likely to be tuned to facial expression and to face movement involved in gesture), and in the TE areas more ventrally forming the inferior temporal gyrus (in which neurons are more likely to have responses related to the identity of faces). Quantitative studies of the responses of the neurons that respond differently to the faces of different individuals show that information about the identity of the individual is represented by the responses of a population of neurons, that is, ensemble encoding rather than 'grandmother cell' encoding is used. It is argued that this type of tuning is a delicate compromise between very fine tuning, which has the advantage of low interference in neuronal network operations but the disadvantage of losing the useful properties (such as generalization, completion and graceful degradation) of storage in neuronal networks, and broad tuning, which has the advantage of allowing these properties of neuronal networks to be realized but the disadvantage of leading to interference between the different memories stored in an associative network. There is evidence that the responses of some of these neurons are altered by experience so that new stimuli become incorporated in the network. It is shown that the representation that is built in temporal cortical areas shows considerable invariance for size, contrast, spatial frequency and translation. Thus the representation is in a form which is particularly useful for storage and as an output from the visual system. It is also shown that one of the representations that is built is object based, which is suitable for recognition and as an input to associative memory, and that another is viewer centred, which is appropriate for conveying information about gesture. Ways are considered in which such cortical representations might be built by competitive self-organization aided by back projections in the multi-stage cortical processing hierarchy which has convergence from stage to stage.     

Generation of valuable information and the problem of goal self-setting in living systems

The problem of origination of capacity for goal self-setting is discussed. It was shown that the definition "goal" in living systems differs from the definition "target function" in physical problems concerned with nonliving systems. It was also shown that the main goal of the elements of a system is the storage of information. In biology, this goal is the extension of the principle of struggle for existence. Conditions were determined that the dynamic system describing the goal self-setting process must satisfy. It was shown that living systems meet these conditions. In inorganic nature, such systems may also arise but only as a result of long-term evolution, after which they become living.     

Diversity in the practice of district ethics committees.

A survey of ethics committees in district health authorities was carried out to find out the size and make up of committees and what information and guidance they offered to scientists who apply to do research. A sample (n = 28) of committees in England (n = 190), half from teaching districts and half from non-teaching districts, was contacted by post requesting this information. A high degree of diversity was found, not only in the methods that committees used but also in the ethical criteria each considered to be pertinent for research. It was also shown that published guidelines have made little impact. It is suggested that issuing more guidelines will be of limited use. Rather, the following are needed: information about why guidelines have been widely ignored, better communication between committees, some form of education for committee members, and a formal register of committees compiled.     

On the interpretation of biochemical data by molecular dynamics computer simulation.

The application of computer simulation to molecular systems of biochemical interest is reviewed. It is shown that computer simulation is a tool complementary to experimental methods, which can be used to access atomic details inaccessible to experimental probes. Examples are given in which computer simulation augments the experimental information by providing an atomic picture of high resolution with respect to space, energy or time. The usefulness of a computer simulation largely depends on its quality. The most important factors that limit the accuracy of simulated results are discussed. The accuracy of different simulation studies can differ by orders of magnitude. The accuracy will depend on the type of biomolecular system and process studied. It will also depend on the choice of force field, the simulation set-up and the protocol that is used. A list of quality-determining factors is given, which may be useful when interpreting simulation studies appearing in the literature.     

Error catastrophe in and the evolution of the protein synthesizing machinery

The theory of the propagation of errors in the system of enzymes translating genetic information proposed earlier is developed further. It is shown that if initially for some of these enzymes the normal molecules are more than, for some less than, and for some equal to the erroneous ones, the evolution of the system can lead to many asymptotic conditions including error catastrophe and complete recovery from errors.     

Species-specific differences in the corticohypothalamic connections of lizards.

In lizards, information from the various senses is relayed to the hypothalamus via the cortico-septo-hypothalamic pathway. It appears that the anatomical organization of the incoming fibres in the medial cortex differs considerably between the various lizard species. In the present account it is shown that it is the location of the termination of the incoming fibres in the medial cortex that determines what kind of sensory information will reach the hypothalamic centres that are responsible for sexual and feeding behaviour.     

Equilibrium muscle cross-bridge behavior. Theoretical considerations.

We have developed a model for the equilibrium attachment and detachment of myosin cross-bridges to actin that takes into account the possibility that a given cross-bridge can bind to one of a number of actin monomers, as seems likely, rather than to a site on only a single actin monomer, as is often assumed. The behavior of this multiple site model in response to constant velocity, as well as instantaneous stretches, was studied and the influence of system parameters on the force response explored. It was found that in the multiple site model the detachment rate constant has considerably greater influence on the mechanical response than the attachment rate constant. It is shown that one can obtain information about the detachment rate constants either by examining the relationship between the apparent stiffness and duration of stretch for constant velocity stretches or by examining the force-decay rate constants following an instantaneous stretch. The main effect of the attachment rate constant is to scale the mechanical response by influencing the number of attached cross-bridges. The significance of the modeling for the interpretation of experimental results is discussed.     

Firing pattern and synchronization property analysis in a network model of the olfactory bulb

In the olfactory system, both the temporal spike structure and spatial distribution of neuronal activity are important for processing odor information. In this paper, a biophysically-detailed, spiking neuronal model is used to simulate the activity of olfactory bulb. It is shown that by varying some key parameters such as maximal conductances of Ks and Nap the spike train of single neuron can exhibit various firing patterns. Synchronization in coupled neurons is also investigated as the coupling strength varying in the situation of two neurons and network. It is illustrated that the coupled neurons can exhibit different types of pattern when the coupling strength varies. These results may be instructive to understand information transmission in olfactory system.     

The study of the mixing layer by the point image method

The properties of the mixing layer in dynamic systems were studied by the example of a mathematical model of the cubic image type. Its role in the generation of information and the evolution of its significance was shown. At the moment of generation, information is of zero significance, and this significance then increases. A criterion of efficiency was proposed, and the optimum moment of making a decision in creative work was determined. It was shown that the increase in the variability of the parameters of a living system upon entry into the mixing layer and its decrease upon exit can serve as objective indicators of the transition of the system from one dynamic regime (attractor) to another.     

Analysis of the code relating sequence to conformation in globular proteins. Theory and application of expected information

1. An information theory analysis of the folding of a globular protein is proposed. 2. The folding is seen as a transfer of information between two messages, the primary sequence and the biologically active conformation. 3. It is shown how the information transferred was estimated by inspection of proteins of known primary sequence and conformation. 4. In this estimation, concerted use of subjective (Bayesian) probabilities leads to a more robust approach which can be employed whether the number of proteins of known sequence and conformation is large or small. 5. Further, it is demonstrated that the problem then becomes a very simple algebraic formulation for information estimates. 6. Finally, it is shown how this process of information theory analysis can be reversed to predict the conformation of a protein by using its primary sequence and the above information estimates obtained from other proteins. 7. The present paper provides the theoretical basis for the derivation and application of a stereochemical alphabet (Robson & Pain, 1974a,c), and for an investigation of the effects of residues on the conformations of their neighbours (Robson & Pain, 1974b).     

Group selection of early replicators and the origin of life

A major problem of the origin of life has been that of information integration. As Eigen (1971) has shown, a mutant distribution of RNAs replicating without the aid of a replicase cannot integrate sufficient information for the functioning of a higher-level unit utilizing several types of encoded enzymes. He proposed the hypercycle model to bridge this gap in prebiology. It can be shown by a nonlinear game model, incorporating mutation of a hypercycle, that the selection properties of hypercycles make them inefficient information integrators as they cannot compete favourably with all kinds of less efficient information carriers or mutationally coupled hypercycles. The stochastic corrector model is presented as an alternative resolution of Eigen's paradox. It assumes that replicative templates are competing within replicative compartments, whose selective values depend on the internal template composition via a catalytic acid in replication and "metabolism". The dynamics of template replication are analyzed by numerical simulation of master equations. Due to the stochasticity in replication and compartment fission the best compartment types recur. An Eigen equation at the compartment level is set up and calculated. Even selfish template mutants cannot destroy the system though they make it less efficient. The genetic information of templates is evaluated at both levels, and the higher (compartment) level successfully constrains the lower (template) one. Compartmentation together with stochastic effects is sufficient to integrate information dispersed in competitive replicators. Compartment selection is considered to be group selection of replicators. Implications for the origin of life are discussed.     

Information in the Neuronal Representation of Individual Stimuli in the Primate Temporal Visual Cortex

To analyze the information provided about individual visual stimuliin the responses of single neurons in the primate temporal lobevisual cortex, neuronal responses to a set of 65 visual stimuli wererecorded in macaques performing a visual fixation task and analyzedusing information theoretical measures. The population of neuronsanalyzed responded primarily to faces. The stimuli included 23 facesand 42 nonface images of real-world scenes, so that the function ofthis brain region could be analyzed when it was processing relativelynatural scenes.It was found that for the majority of the neurons significantamounts of information were reflected about which of several of the23 faces had been seen. Thus the representation was not local, forin a local representation almost all the information available canbe obtained when the single stimulus to which the neuron respondsbest is shown. It is shown that the information available about anyone stimulus depended on how different (for example, how manystandard deviations) the response to that stimulus was from theaverage response to all stimuli. This was the case for responsesbelow the average response as well as above.It is shown that the fraction of information carried by the lowfiring rates of a cell was large—much larger than that carried bythe high firing rates. Part of the reason for this is that theprobability distribution of different firing rates is biased towardlow values (though with fewer very low values than would bepredicted by an exponential distribution). Another factor is thatthe variability of the response is large at intermediate and highfiring rates.Another finding is that at short sampling intervals (such as 20 ms)the neurons code information efficiently, by effectively acting asbinary variables and behaving less noisily than would be expectedof a Poisson process.     

Aspects of the Clausius-Shannon Identity: Emphasis on the components of transitive information in linear,branched and composite physical systems

In this paper I consider how information is required to specify various systems. It is shown that the transitive information of any physical system, is distributed among three distinct components. One of these, the selective component, is required to specify the elemental parts of the system. Another, the connective component, is required to specify the macrostructure of the system; that is the way the parts are put together. And a third, the conformative component, is required to specify the intrinsic complexion or microstructure of the system. An interesting method for analyzing branched systems which takes account of connective ambiguity is described in some detail. The relationship between information and entropy, known as the Clausius-Shannon Identity, is then discussed with reference to selected thermodynamic models: and that aspect of information which is often overlooked, namely the distinction, between transitive and intransitive information is highlighted. The applications (or perhaps more correctly, the limitations of applying this treatment) to problems of biological interest are also indicated.     

A sequence analysis system encompassing rules for DNA helical distortion.

Recently, it has been shown by Calladine (1982) and Dickerson (1983) that DNA distortions due to steric clashes between opposing purines and pyrimidines can be quantitated based upon four sum functions. The distortions involve helical twist, roll, torsion angle variations and propeller twist. It is the contention of the authors that these perturbations in structure act as information carriers for various external DNA interactions. This paper describes a system that incorporates these four rules and various other functions that permit the systematic interactive exploration for significant patterns as a consequence of these steric clashes.     

Evolution of the dominance of rec-loci. A mathematical model

The possibility of evolutionary explanation of dominance relations for alleles in selective-neutral rec-loci was explored by means of numerical experiments. It was shown that selection for two-loci fitness system causing the secondary (induced) selection for the rec-system, results in changing the allele frequency of the second-level modificator gene controlling the dominance relations in the rec-locus. The dominance of rec-allele, providing the favourable for the given conditions level of crossing-over between selected fitness loci, is established, due to these changes. It was found that the neutral dominance modificator can influence the dynamics of the whole system.     

Replication of the deoxyribonucleic acid of multiple-drug-resistance factor in Escherichia coli.

1. It was shown that a system previously described for labelling R-factor DNA during transfer to an irradiated recipient strain of Escherichia coli did not allow high selectivity in the incorporation of thymine into R-factor DNA. 2. Lack of selectivity was shown to be due to cross-feeding from recipient to donor strain. 3. An improved system using a nalidixic acid-resistant recipient strain is described in which incorporation of thymine into the DNA of donor cells is minimized by addition of nalidixic acid after completion of transfer of the plasmid during conjugation.     

The Movement of Tracers along the Petiole of Nymphoides peltatum: I. A. PRELIMINARY STUDY WITH 137Cs

It is shown that the general postulate of a mass flow with lateralescape of tracer accounts fairly satisfactorily for the well-establishedexponential fall-off in tracer activity down the axis. The shapeof the curves relating the logarithm of the activity to distanceis concave upwards, and it is suggested on the assumption ofa mass-flow model that this is evidence either of an acceleratingvelocity down the petiole, or of a falling rate of lateral leakageout of the sieve tubes. It has also been shown that no satisfactoryestimate of the linear velocity of movement can be got fromthe usual type of tracer study without further information ofa kind not usually provided, and no estimate has proved possiblein the present case.     

A model for optimal processing of multisensory information in the system for maintaining body orientation in the human

Considered is the optimal processing of multisensory information to maintain body orientation in the human. It is supposed that the orientation is performed by a system of angular stabilization with only small deviations from the equilibrium believed to be coincided with the local vertical. The linear transformation is determined which minimizes the square loss function for the stabilization error. This transformation comprises two successive steps. One of them is the averaging procedure on the the sensory inputs and the other is the optimal Kalman filtering in time domain. It is shown that the presence of two interacting channels for angular position and angular velocity in the structure of the optimal filter ensures sufficient accuracy of stabilization in both channels for the stabilization system as a whole in spite of the substantial unreliability in transmission in the channel of the angular position.