Morphological Evolution of Physical Robots through Model-Free Phenotype Development

Artificial evolution of physical systems is a stochastic optimization method in which physical machines are iteratively adapted to a target function. The key for a meaningful design optimization is the capability to build variations of physical machines through the course of the evolutionary process. The optimization in turn no longer relies on complex physics models that are prone to the reality gap, a mismatch between simulated and real-world behavior. We report model-free development and evaluation of phenotypes in the artificial evolution of physical systems, in which a mother robot autonomously designs and assembles locomotion agents. The locomotion agents are automatically placed in the testing environment and their locomotion behavior is analyzed in the real world. This feedback is used for the design of the next iteration. Through experiments with a total of 500 autonomously built locomotion agents, this article shows diversification of morphology and behavior of physical robots for the improvement of functionality with limited resources.     

Engineering entrainment and adaptation in limit cycle systems

Periodic behavior is key to life and is observed in multiple instances and at multiple time scales in our metabolism, our natural environment, and our engineered environment. A natural way of modeling or generating periodic behavior is done by using oscillators, i.e., dynamical systems that exhibit limit cycle behavior. While there is extensive literature on methods to analyze such dynamical systems, much less work has been done on methods to synthesize an oscillator to exhibit some specific desired characteristics. The goal of this article is twofold: (1) to provide a framework for characterizing and designing oscillators and (2) to review how classes of well-known oscillators can be understood and related to this framework. The basis of the framework is to characterize oscillators in terms of their fundamental temporal and spatial behavior and in terms of properties that these two behaviors can be designed to exhibit. This focus on fundamental properties is important because it allows us to systematically compare a large variety of oscillators that might at first sight appear very different from each other. We identify several specifications that are useful for design, such as frequency-locking behavior, phase-locking behavior, and specific output signal shape. We also identify two classes of design methods by which these specifications can be met, namely offline methods and online methods. By relating these specifications to our framework and by presenting several examples of how oscillators have been designed in the literature, this article provides a useful methodology and toolbox for designing oscillators for a wide range of purposes. In particular, the focus on synthesis of limit cycle dynamical systems should be useful both for engineering and for computational modeling of physical or biological phenomena.     

Biophysics; fifty years after Schrödinger

E. Schrödinger described his mechanistic view on life in his book “What is Life?” published in 1944. H. Yukawa stated that life is like a building of bricks. Is life understandable in this manner?In 1950–1960 the generation of structure and function in living cells was shown to be analyzable, step by step, within the theoretical framework of physics. In the 1970's the concept of a molecular machine or unit machine in living cells was clearly presented and the effort to experimentally define unit machines was promoted. Recently, new techniques to directly observe their behaviors have been developed. The machines are not always rigid. In sliding machines, the influx-efflux coupling has been found to be loose. For loose coupling, intramachine flexibility seems to be useful.Living cells can be regarded as an organized system composed of many unit machines, some of which exhibit deterministic behaviors while others exhibit probabilistic behaviors. The cells do not always show a definite response to a given input. We need new statistical mechanics for the study of unit machines and their systems which have complex spatial and temporal structures. They may have a mechanism beyond a simple building of bricks.     

The cell biological basis of ciliary disease

Defects in cilia cause a broad spectrum of human diseases known collectively as the ciliopathies. Although all ciliopathies arise from defective cilia, the range of symptoms can vary significantly, and only a small subset of the possible ciliary disease symptoms may be present in any given syndrome. This complexity is puzzling until one realizes that the cilia are themselves exceedingly complex machines that perform multiple functions simultaneously, such that breaking one piece of the machine can leave some functions intact while destroying others. The clinical complexity of the ciliopathies can therefore only be understood in light of the basic cell biology of the cilia themselves, which I will discuss from the viewpoint of cell biological studies in model organisms.     

Steps in the Bacterial Flagellar Motor

The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps. Here we propose a simple physical model, based on the storage of energy in protein springs, that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. We also predict a sublinear speed versus torque relationship for fixed load at low torque, and a peak in rotor diffusion as a function of torque. Our model provides a comprehensive framework for understanding and analyzing stepping behavior in the bacterial flagellar motor and proposes novel, testable predictions. More broadly, the storage of energy in protein springs by the flagellar motor may provide useful general insights into the design of highly efficient molecular machines.     

Personal reflections on the nature of intelligence in humans and machines

Computers, the human mind, and social systems have common problems of inadequate memory and insufficient data manipulation speed. In each of these domains, information compression techniques have evolved to reduce storage and processing needs. Among the techniques for information compression, coding of information in procedures stands out as exceptionally powerful. Procedural information coding also gives rise to behavior that may be defined as intelligent. It is found in the human mind, in machines and in social systems. Its use in human thought is aided by language development which promotes regular review of abstract procedures. A practical consequence of better understanding of procedural information coding is the possibility of training people to exhibit greater mental capacity, a controversial possibility. This paper explores the impact of data processing resource limitations, data compression and procedural thinking in men and machines.     

Weak Intra-Ring Allosteric Communications of the Archaeal Chaperonin Thermosome Revealed by Normal Mode Analysis

Chaperonins are molecular machines that use ATP-driven cycles to assist misfolded substrate proteins to reach the native state. During the functional cycle, these machines adopt distinct nucleotide-dependent conformational states, which reflect large-scale allosteric changes in individual subunits. Distinct allosteric kinetics has been described for the two chaperonin classes. Bacterial (group I) chaperonins, such as GroEL, undergo concerted subunit motions within each ring, whereas archaeal and eukaryotic chaperonins (group II) undergo sequential subunit motions. We study these distinct mechanisms through a comparative normal mode analysis of monomer and double-ring structures of the archaeal chaperonin thermosome and GroEL. We find that thermosome monomers of each type exhibit common low-frequency behavior of normal modes. The observed distinct higher-frequency modes are attributed to functional specialization of these subunit types. The thermosome double-ring structure has larger contribution from higher-frequency modes, as it is found in the GroEL case. We find that long-range intersubunit correlation of amino-acid pairs is weaker in the thermosome ring than in GroEL. Overall, our results indicate that distinct allosteric behavior of the two chaperonin classes originates from different wiring of individual subunits as well as of the intersubunit communications.     

Linear viscoelastic properties of the vertex model for epithelial tissues

Epithelial tissues act as barriers and, therefore, must repair themselves, respond to environmental changes and grow without compromising their integrity. Consequently, they exhibit complex viscoelastic rheological behavior where constituent cells actively tune their mechanical properties to change the overall response of the tissue, e.g., from solid-like to fluid-like. Mesoscopic mechanical properties of epithelia are commonly modeled with the vertex model. While previous studies have predominantly focused on the rheological properties of the vertex model at long time scales, we systematically studied the full dynamic range by applying small oscillatory shear and bulk deformations in both solid-like and fluid-like phases for regular hexagonal and disordered cell configurations. We found that the shear and bulk responses in the fluid and solid phases can be described by standard spring-dashpot viscoelastic models. Furthermore, the solid-fluid transition can be tuned by applying pre-deformation to the system. Our study provides insights into the mechanisms by which epithelia can regulate their rich rheological behavior.     

HORIZONTAL GENE TRANSFER AND THE EVOLUTION OF BACTERIAL COOPERATION

Bacteria frequently exhibit cooperative behaviors but cooperative strains are vulnerable to invasion by cheater strains that reap the benefits of cooperation but do not perform the cooperative behavior themselves. Bacterial genomes often contain mobile genetic elements such as plasmids. When a gene for cooperative behavior exists on a plasmid, cheaters can be forced to cooperate by infection with this plasmid, rescuing cooperation in a population in which mutation or migration has allowed cheaters to arise. Here we introduce a second plasmid that does not code for cooperation and show that the social dilemma repeats itself at the plasmid level in both within‐patch and metapopulation scenarios, and under various scenarios of plasmid incompatibility. Our results suggest that although plasmid carriage of cooperative genes can provide a transient defense against defection in structured environments, plasmid and chromosomal defection remain the only stable strategies in an unstructured environment. We discuss our results in the light of recent bioinformatic evidence that cooperative genes are overrepresented on mobile elements.     

Theory of molecular machines. I. Channel capacity of molecular machines

Like macroscopic machines, molecular-sized machines are limited by their material components, their design, and their use of power. One of these limits is the maximum number of states that a machine can choose from. The logarithm to the base 2 of the number of states is defined to be the number of bits of information that the machine could "gain" during its operation. The maximum possible information gain is a function of the energy that a molecular machine dissipates into the surrounding medium (Py), the thermal noise energy which disturbs the machine (Ny) and the number of independently moving parts involved in the operation (dspace): Cy = dspace log2 [( Py + Ny)/Ny] bits per operation. This "machine capacity" is closely related to Shannon's channel capacity for communications systems. An important theorem that Shannon proved for communication channels also applies to molecular machines. With regard to molecular machines, the theorem states that if the amount of information which a machine gains is less than or equal to Cy, then the error rate (frequency of failure) can be made arbitrarily small by using a sufficiently complex coding of the molecular machine's operation. Thus, the capacity of a molecular machine is sharply limited by the dissipation and the thermal noise, but the machine failure rate can be reduced to whatever low level may be required for the organism to survive.     

Synchrony and Asynchrony in a Fully Stochastic Neural Network

We describe and analyze a model for a stochastic pulse-coupled neural network, in which the randomness in the model corresponds to synaptic failure and random external input. We show that the network can exhibit both synchronous and asynchronous behavior, and surprisingly, that there exists a range of parameters for which the network switches spontaneously between synchrony and asynchrony. We analyze the associated mean-field model and show that the switching parameter regime corresponds to a bistability in the mean field, and that the switches themselves correspond to rare events in the stochastic system.     

Mechanics,Structure and Function of Biopolymer Condensates

The spontaneous nature of biopolymer phase separation in cells entails that the resulting condensates can be thermodynamic machines, which, in the process of condensing, can take on distinct forms themselves and deform neighboring cellular structures. We introduce here general notions of material and mechanical properties of protein condensates with an emphasis on how molecular arrangements and intermolecular interaction within condensates determine their ability to do work on their surroundings. We further propose functional implications of these concepts to cellular and subcellular morphology and biogenesis.     

In defence of the high energy phosphate bond

The concept of the “high energy phosphate bond” has recently been strongly criticised by Banks &; Vernon. The criticisms were: (i) energy cannot be stored in molecules; let alone in bonds; (ii) a muscle is an open system, so that the free energy of hydrolysis of ATP is irrelevant; (iii) biological reactions cannot be at equilibrium, therefore they must be inefficient. It is argued that all of these criticisms arise because the timescale appropriate to molecular events has been left out; in particular “stored energy” needs to be defined relative to the machine which uses that energy. The criticisms may be answered using a conceptual framework which overcomes this deficiency and which was developed previously to extend classical thermodynamics to the molecular level. Criticism (i) is refuted by discussing in detail the chemiluminescent reaction of rubrene oxide, which can only be described as liberating internal energy stored in a single molecule; while it is true that entropy cannot be retained in a single molecule for long enough to do useful work with it, there is nothing which forbids internal energy from being so stored. Criticism (ii) would be true if, and only if, a muscle uses the same kind of mechanism as do the ordinary chemical machines with which we are familiar (batteries, etc). But this assumption is shown to be false; a muscle cannot use this type of mechanism. Criticism (iii) is answered by finding the conditions under which a biological machine could in fact approach 100% efficiency. These conditions are: (i) in metabolism ΔF = 0; the steps are in thermal equilibrium; (ii) in the molecular machines themselves ΔS = 0, so that ΔF = ΔH; the machines are mechanical. It is also shown that not only are these conditions perfectly conceivable, but also that there is good evidence that, over the course of evolution, they have actually been attained.     

Decreased locomotor activity in mice expressing tTA under control of the CaMKII alpha promoter

Transgenic mice in which the tetracycline transactivator (tTA) is driven by the forebrain-specific calcium–calmodulin-dependent kinase IIα promoter (CaMKIIα-tTA mice) are used to study the molecular genetics of many behaviors. These mice can be crossed with other transgenic mice carrying a transgene of interest coupled to the tetracycline-responsive promoter element to produce mice with forebrain-specific expression of the transgene under investigation. The value of using CaMKIIα-tTA mice to study behavior, however, is dependent on the CaMKIIα-tTA mice themselves lacking a behavioral phenotype with respect to the behaviors being studied. Here we present data that suggest CaMKIIα-tTA mice have a behavioral phenotype distinct from that of their wild-type (WT) littermates. Most strikingly, we find that CaMKIIα-tTA mice, both those with a C57BL/6NTac genetic background (B6-tTA) and those with a 129S6B6F1/Tac hybrid genetic background (F1-tTA), exhibit decreased locomotor activity compared with WT littermates that could be misinterpreted as altered anxiety-like behavior. Despite this impairment, neither B6-tTA nor F1-tTA mice perform differently than their WT littermates in two commonly used learning and memory paradigms – Pavlovian fear conditioning and Morris water maze. Additionally, we find data regarding motor coordination and balance to be mixed: B6-tTA mice, but not F1-tTA mice, exhibit impaired performance on the accelerating rotarod and both perform as well as their WT littermates on the balance beam.     

Self-awareness and the emergence of mind in primates

To date humans, chimpanzees, and orangutans are the only species which have been shown capable of recognizing themselves in mirrors. Several species of macaques have now been provided with years of continuous exposure to mirrors, but they still persist in reacting to their reflection as if they were seeing other monkeys. Even gibbons (apes) and gorillas (great apes) seem incapable of learning that their behavior is the source of the behavior depicted in the image. Most primates, therefore, appear to lack a cognitive category for processing mirrored information about themselves. The implications of these data for traditional views of consciousness are considered briefly, and a recent attempt to develop an operant analog to self-recognition is critically evaluated. Finally, an attempt is made to show that self-awareness, consciousness, and mind are not mutually exclusive cognitive categories and that the emergence of self-awareness may be equivalent to the emergence of mind. Several indices of “mind” which can be applied to nonhuman species are discussed in the context of an attempt to develop a comparative psychology of mind.     

Inhibiting influence of testosterone on stress responsiveness during adolescence

The maturation of the hypothalamo-pituitary-adrenal (HPA) axis is a key-component of the changes that occur during adolescence. In guinea pigs, HPA responsiveness during late adolescence depends strongly on the quantity and quality of social interactions: Males that lived in a large mixed-sex colony over the course of adolescence exhibit a lower stress response than males that were kept in pairs (one male/one female). Since colony-housed males have higher testosterone (T) levels than pair-housed males, and inhibiting effects of T on HPA function are well known, we tested the hypothesis that the decrease in stress responsiveness found in colony-housed males is due to their high T concentrations. We manipulated T levels in two experiments: 1) gonadectomy/sham-gonadectomy of colony-housed males (which usually have high T levels), 2) application of T undecanoate/vehicle to pair-housed males (which usually have low T levels). As expected, gonadectomized males showed a significantly increased stress response in comparison with sham-gonadectomized males, and T-injected males had a significantly lower stress response than vehicle-injected males. Both experiments thus confirm an inhibiting effect of T on HPA responsiveness during adolescence, which can mediate the influence of social interactions. The reduction in stress responsiveness is hypothesized to have a biologically adaptive value: A sudden increase in glucocorticoid concentrations can enhance aggressive behavior. Thus, pair-housed males might be adapted to aggressively defend their female (‘resource defense strategy’), whereas colony-housed males display little aggressive behavior and are capable of integrating themselves into a colony (‘queuing strategy’).     

Neural mechanisms of persistent aggression

While aggression is often conceptualized as a highly stereotyped, innate behavior, individuals within a species exhibit a surprising amount of variability in the frequency, intensity, and targets of their aggression. While differences in genetics are a source of some of this variation across individuals (estimates place the heritability of behavior at around 25–30%), a critical driver of variability is previous life experience. A wide variety of social experiences, including sexual, parental, and housing experiences can facilitate “persistent” aggressive states, suggesting that these experiences engage a common set of synaptic and molecular mechanisms that act on dedicated neural circuits for aggression. It has long been known that sex steroid hormones are powerful modulators of behavior, and also, that levels of these hormones are themselves modulated by experience. Several recent studies have started to unravel how experience-dependent hormonal changes during adulthood can create a cascade of molecular, synaptic, and circuit changes that enable behavioral persistence through circuit level remodeling. Here, we propose that sex steroid hormones facilitate persistent aggressive states by changing the relationship between neural activity and an aggression “threshold”.     

A logarithmic ratio amplifier and range expander for use with dual-beam colorimeters

Many early-model Technicon amino acid analyzers and Autoanalyzers are still in use. They lack, however, the sensitivity of current-model machines. the colorimeter design used in these machines employs a single light source which provides dual beams, a reference beam and a sample beam which pass to identical photovoltaic cells. The ratio of sample to the reference voltage is measured continously in a null balance system by the recorder. The design provides an extremely stable output which as such is amenable to range expansion. Nevertheless, a range expander and linear absorbance output unit is not readily available commercially.The present communication presents details of the design and performance of a logarithmic ratio amplifier and range expander for use with dual-beam colorimeters, as examplified by the Technicon system. The unit is simple and may be constructed by a nonspecialist in 2–3 days. The design chosen allows the use of low-cost components, thus keeping materials cost less than $75.     

Clonal heterogeneity in physiological properties of melanized cells induced from goldfish erythrophoroma cell lines

Abstract. Cells of the uncloned goldfish erythrophoroma lines, GEM-81 and GEM-218, have been induced to melanize by cultivation in autologous serum. The melanized cells continue to proliferate and exhibit clonal heterogeneity in terms of morphology, growth rates, contact behavior and pigment content, and distribution and translocation in response to hormones. Based on these characteristics and those of their normal counterparts, the melanized tumor cells have been categorized as type-I and type-I1 melanocytomas, and melanophoromas. The melanophoroma cells are capable of pigment translocation in response to epinephrine, melatonin, and/or MSH, whereas melanocytoma cells are not. The distinguishing characteristics of each type are apparent at the first appearance of melanized cells and appear to be stable except in some type-II melanocytoma clones which contain cells capable of differentiating into melanophoroma cells in long-term cultures. It appears that the parent erythrophoroma lines contain stem cells, melanoblastomas, which are capable of melanogenesis. These stem cells may themselves be a heterogeneous population with respect to the characteristics of the melanized cells to which they give rise.