The operational approach to the problem of tetrapodization

The problem of tetrapodization is considered as a part of the general problem of the formation of large higher taxa on the basis of morphophysiological and morphogenetic organization of ancestors. It is shown that the formation of tetrapod-like characters in Paleozoic crossopterygians followed the patterns of preadaptation, parallel and mosaic development. The main task of the operational approach to the problem is the reconstruction of the sequence and rates of the formation of tetrapod-like characters in crossopterygians, the loss of fish characters at the tetrapod level, and the mechanisms of these processes.     

An integrated approach to the characterization of cell movement.

BACKGROUND: Most phenomena in developmental biology involve or depend upon cell migration. This article describes a comprehensive framework for the characterization and analysis of trajectories defined by cell movement. The following two perspectives are considered: (a) the behavior of each individual cell and (b) interactions between neighboring pairs of cells. METHODS: The measurements considered for individual trajectories include the velocity magnitude and orientation, maximum spatial dispersion, displacement effectiveness, and displacement entropies. Interactions between two trajectories are characterized by comparing the respective velocities. RESULTS: The potential of the overall framework is illustrated using data of moving cells in different biological environments. The work shows that it is possible to use the new algorithm presented here to characterize cell motility. CONCLUSIONS: The features of the algorithm were successful in determining the motility changes under different experimental conditions.     

An evolutionary approach to the traveling salesman problem

Evolutionary optimization has been proposed as a method to generate machine learning through automated discovery. A simulation of natural evolution is conducted using the traveling salesman problem as an artificial environment. For an exact solution of a traveling salesman problem, the only known algorithms require the number of steps to grow at least exponentially with the number of elements in the problem. Three adaptive techniques are described and analyzed. Evolutionary adaptation is demonstrated to be worthwhile in a variety of contexts. Local stagnation is prevented by allowing for the probabilistic survival of the simulated organisms. In complex problems, the final routing is estimated to be better than 99.99999999999% of all possible tours, even though only a small fraction (8.58 × 10^–151) of the total number of tours are examined.     

Cerebral palsy; an approach to the problem

A program for the cerebral palsied child has been developed in California which has been made possible through the cooperation of the state and local departments of education, the state and local departments of health, the Children's Hospital and Orthopedic Hospital at Los Angeles and the University of California School of Medicine in San Francisco. An attempt is being made to deal with not only the medical and educational needs of the cerebral palsied but also the social and emotional aspects.     

Outline of a mathematical approach to the cancer problem

The fact that the growth of every organism, as it develops through cell multiplication from the ovum, eventually ceases, makes plausible the hypothesis that each cell of an organism exerts some kind of inhibitory influence upon the growth and multiplication of every other cell through the medium of some factorj. Each cell, however, is considered to possess an amount of a “growth factor”g, the activity of which is inhibited byj. In the course of development, most cells differentiate. A number of them remains relatively undifferentiated, and those are used for repairs of natural tear and wear as well as for healing of wounds. With age either the number of those cells or their “potency” decreases, which accounts for a general decrease in the speed of wound healing. Due to statistical fluctuations, the amount of theg is not uniformly distributed amongst the cells. Some of them have accidentally a greater amount than others. As the number or potency of the undifferentiated cells decreases with age, so does their inhibitory influence upon other cells. Therefore, those cells which do have an accidental dental excess ofg-factor will begin to grow and multiply, producing neoplasms. Putting the above assumptions into mathematical form, it is possible to derive a relation which gives theprobability of cancer incidence as a function of age. The theoretical relation is compared to the rather inadequate empirical data and found in agreement with them. A relation for the speed of wound healing as a function of age is also derived, and also found in general agreement with the rather scant data. Several other conclusions are discussed and possibilities of their practical applications pointed out.     

Differential regulation of dynein-driven melanosome movement

Cytoplasmic dyneins are multisubunit minus-end-directed microtubule motors. Different isoforms of dynein are thought to provide a means for independent movement of different organelles. We investigated the differential regulation of dynein-driven transport of pigment organelles (melanosomes) in Xenopus melanophores. Aggregation of melanosomes to the cell center does not change the localization of mitochondria, nor does dispersion of melanosomes cause a change in the perinuclear localization of the Golgi complex, indicating that melanosomes bear a dedicated form of dynein. We examined the subcellular fractionation behavior of dynein light intermediate chains (LIC) and identified at least three forms immunologically, only one of which fractionated with melanosomes. Melanosome aggregation was specifically blocked after injection of an antibody recognizing this LIC. Our data indicate that melanosome-associated dynein is regulated independently of bulk cytoplasmic dynein and involves a subfraction of dynein with a distinct subunit composition.     

A note on the probabilistic approach to the cancer problem

Assuming that the initiation of cancer growth is due to a purely accidental fluctuation of some physicochemical condition, it is possible to derive the equation for the cancer incidence as a function of age. The final result depends on whether it is assumed that a single accidental fluctuation in a cell is sufficient to produce cancer, or that a finite number,k, of repetitions of the accidental fluctuation must occur in the same cell. In principle it is possible to determine from observed incidence curves the numberk. Actually, however, this cannot be done at present, because the difference of the theoretical curves for differentk's is rather small, and the available cancer statistics are not accurate enough to show such differences.     

On the measurement of movement difficulty in the standard approach to Fitts' law

Fitts' law is an empirical rule of thumb which predicts the time it takes people, under time pressure, to reach with some pointer a target of width W located at a distance D. It has been traditionally assumed that the predictor of movement time must be some mathematical transform of the quotient of D/W, called the index of difficulty (ID) of the movement task. We ask about the scale of measurement involved in this independent variable. We show that because there is no such thing as a zero-difficulty movement, the IDs of the literature run on non-ratio scales of measurement. One notable consequence is that, contrary to a widespread belief, the value of the y-intercept of Fitts' law is uninterpretable. To improve the traditional Fitts paradigm, we suggest grounding difficulty on relative target tolerance W/D, which has a physical zero, unlike relative target distance D/W. If no one can explain what is meant by a zero-difficulty movement task, everyone can understand what is meant by a target layout whose relative tolerance W/D is zero, and hence whose relative intolerance 1-W/D is 1 or 100%. We use the data of Fitts' famous tapping experiment to illustrate these points. Beyond the scale of measurement issue, there is reason to doubt that task difficulty is the right object to try to measure in basic research on Fitts' law, target layout manipulations having never provided users of the traditional Fitts paradigm with satisfactory control over the variations of the speed and accuracy of movements. We advocate the trade-off paradigm, a recently proposed alternative, which is immune to this criticism.     

A genetic approach to the species problem in wild potato

Wild potatoes are native to the Americas, where they present very wide geographical and ecological distribution. Most are diploid, obligate out-crossers due to a multiallelic gametophytic self-incompatibility (S) locus that prevents self-fertilisation and crossing between individuals carrying identical S-alleles. They have two alternative modes of reproduction: sexual (by seeds) and asexual (by stolons and tubers), which provide, respectively, for genetic flexibility in changing environments and high fitness of adapted genotypes under stable conditions. Since the early twentieth century, their taxonomic classification has been mostly based on morphological phenotypes (Taxonomic Species Concept). More recently, attempts have been made to establish phylogenetic relationships, applying molecular tools in samples of populations (accessions) with a previously assigned specific category. However, neither the reproductive biology and breeding relations among spontaneous populations nor the morphological and genetic variability expected in obligate allogamous populations are considered when the taxonomic species concept is applied. In nature, wild potato populations are isolated through external and internal hybridisation barriers; the latter, which are genetically determined, can be either pre-zygotic (pollen-pistil incompatibility) or post-zygotic (abortion of embryo, endosperm or both tissues, sterility, and hybrid weakness and breakdown in segregating generations). The internal barriers, however, can be incomplete, providing opportunities for hybridisation and introgression within and between populations and ploidy levels in areas of overlap. The widespread occurrence of spontaneous hybrids in nature was recognised in the mid-twentieth century. Using genetic approaches, results have been obtained that provide strong support to the assertion that populations are at different stages of genetic divergence and are not at the end of the evolutionary process, as presupposed by the Taxonomic Species Concept. Furthermore, since wild potatoes have uniparental and biparental overlapping generations, the Biological Species Concept - developed for sexually reproducing biparental organisms - cannot be applied to them. In this paper, morphological, genetic, molecular and taxonomic studies in wild potato are reviewed, considering the genetic consequences of their reproductive biology, in an attempt to shed light on the species problem, because of its relevance in germplasm conservation and breeding.     

An approach to the problem of the structuro-functional organization of natural peptides

Theory and computational scheme of three-dimensional structure and dynamic conformational properties of naturally occurring peptides are proposed basing on a known amino acid sequence. The diverse biological activity of a low-molecular peptide is shown to arise from a restricted number of preferable spatial structures which may occur under physiological conditions. Each particular function of an oligopeptide is connected to a definite spatial structure, belonging to the set of low-energy conformations from one biological activity of a peptide shift of the conformational equilibrium caused by a change of environmental conditions. This shift is provided for by specific intramolecular interactions, alternative in their nature, which stabilize a particular structure. An approach is suggested which enables to construct a synthetic analog with the predetermined physiologically active conformation, prior to all chemical and biological tests.     

Topology fingerprint approach to the inverse protein folding problem.

We describe the most general solution to date of the problem of matching globular protein sequences to the appropriate three-dimensional structures. The screening template, against which sequences are tested, is provided by a protein "structural fingerprint" library based on the contact map and the buried/exposed pattern of residues. Then, a lattice Monte Carlo algorithm validates or dismisses the stability of the proposed fold. Examples of known structural similarities between proteins having weakly or unrelated sequences such as the globins and phycocyanins, the eight-member alpha/beta fold of triose phosphate isomerase and even a close structural equivalence between azurin and immunoglobulins are found.     

A developmental approach to the problem of variation in evolutionary rates

Certain general features are widely recognized in evolution, one of which is the variability in the rate at which morphological characters evolve and taxa are replaced by others. Although some rate-variability in evolution no doubt arises because of different rates of ecological change, it is proposed that some of the variability also arises from developmental, rather than ecological, sources. A theory is outlined whereby early-acting genes influencing the course of development evolve more slowly, but have individually larger effects, than genes affecting development at a later stage in the life-cycle. The erratic course of morphological evolution that results is illustrated by computer simulation. It is suggested that the applicability of the theory is restricted to long-term evolution and that variability in the rate of evolution over shorter periods may be of an entirely different nature.