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Biomedical subjects

M Conrad

Publications and source records attributed to M Conrad.

At least 109 records · Page 6Linked to original sources
PubMed1982

Bootstrapping model of the origin of life.

The origin of life is analyzed in terms of the self-facilitating aspect of evolution. According to the self-facilitation (or bootstrap) principle the structure of biological systems becomes increasingly suited to effective evolutionary search through the process of evolution. The principle may be extended to primitive collections of polymers with catalytic properties. The origin of the code may be based on a form of bootstrapping evolution. Once a primitive code appeared it could become more sophisticated through a multi-coding mechanism together with classical Darwinian mechanisms. The bootstrapping principle is also formulated in terms of the fluctuation-instability framework of Prigogine, Nicolis, and Babloyantz. Primitive collections of polymers accumulate evolution-enhancing redundancies which tend to reduce the extent to which they change when destabilized by fluctuation, but which increase the chances that these changes will lead to new predominant regimes. We show that the bootstrapping of evolutionary amenability is accompanied by the accumulation of a thermodynamic load, that is, a free energy cost which reduces the mechanistic efficiency. The bootstrapping effect suggests that the origin of life is most fruitfully approached as a long process during which the capacity to evolve facilitates itself in a step by step fashion rather than as a series of low probability events.

Genetic Code↗
PubMed1982

Natural selection and the evolution of neutralism.

The efficiency of evolutionary search increases as the density of acceptable proteins in a protein space increases. Populations caught in regions whose density is too low to support evolution can be pulled into high density regions by hitchhiking selection. As they move into such regions, the action of natural selection becomes more effective, yet these populations will satisfy conditions which lead to predictions made by neutral, so-called non-Darwinian models.

Amino Acid Sequence↗
PubMed1982

Microinjection of cyclic nucleotides provides evidence for a diffusional mechanism of intraneuronal control.

Cyclic 3',5'-AMP and cyclic 3',5'-GMP injected into large neurons of the snail Helix lucorum altered neuron activity. The effect of cAMP is usually depolarizing and that of cGMP hyperpolarizing. The results are specific for 3',5'-cyclic nucleotides. The experiments support the hypothesis that reaction-diffusion processes involving cyclic nucleotides form the basis of an intraneuronal system of information processing.

Animals↗
PubMed1981

Algorithmic specification as a technique for computing with informal biological models.

Conceptual biological models can sometimes be usefully expressed in algorithmic form. Models expressed in this way are often capable of capturing more aspects of the complete system than could be captured by other modeling approaches, though in general each aspect is captured in a highly simplified way. Two examples are given. The first involves algorithmic specification of the theory of evolution. The second involves a recently implemented computational model of the brain. Work with such models has, to some extent, the style of experimental work. It often suggests interesting problems or exposes subtle features of the system whose importance has been overlooked.

Biological Evolution↗
PubMed1980

Computational illustration of the bootstrap effect.

A constructive computational model is used to show that even under poor case assumptions genetic systems accumulate features which increase their amenability to evolution. These features decrease the fitness of the individual organism, but hitchhike along with the fitness-increasing traits whose probability of appearance they increase.

Biological Evolution↗
PubMed1979

Bootstrapping on the adaptive landscape.

Different versions of a gene or of a multigenic system may be essentially equivalent so far as the specific function of the structures which they code for or control is concerned, but very different with respect to their amenability to evolution. The structural features which increase evolutionary amenability are a disadvantage to the organism in terms of energy. Nevertheless, they accumulate in the course of evolution as a consequence of hitchhiking along with the desirable traits whose evolution they make possible. This is the bootstrap principle of evolutionary adaptability. In terms of the adaptive landscape bootstrapping corresponds to populations evolving in such a way that they occupy regions of the landscape which are more amenable to evolutionary hill climbing. The bootstrapping idea has implications for structure-function relations in a number of complex biological information processing systems, including biochemical systems, the immune system, and the brain. Bootstrapping is also discussed in connection with the origin of information processing (the origin of life) and in connection with possible designs for macromolecular computing systems.

Adaptation, Biological↗
PubMed1979

Systemic mastocytosis and the mastocytosis syndrome.

A patient with extensive systemic mastocytosis and the mastocytosis syndrome was studied by light and electron microscopy. Mast cell proliferation was found in the bone marrow, the liver, spleen and lymph node. In addition, the patient had telangiectasia macularis eruptiva perstans and elevated histamine levels.

Bone Marrow↗
PubMed1979

Hepatitis B antigen and antibody in heroin users.

Hepatitis B surface antigen (HBsAg) and antibody (anti-HBsAg) were determined on 442 asymptomatic heroin users and 246 controls. Of the drug-taking group, 124 used heroin intravenously and 318 nonintravenously (smoking, sniffing). Twenty-three (5.2%) heroin users were HBsAg positive and 118 (26.7%) anti-HBsAg positive, compared to three (1.2%) HBsAg positive and 28 (11.4%) anti-HBsAg positive controls, both statistically significant. HBsAg was positive in eight (6.5%) intravenous heroin users and statistically identical to 15 (4.7%) HBsAg positive nonintravenous users. Positive anti-HBsAg in 55 (44.4%) intravenous heroin users compared to 63 (19.8%) nonintravenous users, however, is statistically significicant.

Adult↗
PubMed1978

Evaluation of ultrasound in the diagnosis of acute and chronic biliary tract disease.

Oral cholecystography and intravenous cholangiography are the two studies most frequently used to confirm the diagnosis of biliary tract disease. Since it is not always practical to obtain these in acutely ill patients, gray scale sonography was evaluated to determine its accuracy. One hundred eight patients had sonography performed prior to operation. The sonogram was correct in 96 of the 108 patients (89%). There were four false-negatives (3.7%), one false-positive (0.9%), and seven patients (6.4%) in whom the study was nondiagnostic. Stones were seen in 88 patients and confirmed in 87 patients for an accuracy of 98.9% Sonography is a simple, noninvasive procedure by which cholelithiasis can be accurately detected. Because of the high correlation between sonography and operative findings, we suggest that cholecystosonography be used as the initial screening study in patients suspected of having biliary tract disease.

Acute Disease↗
PubMed1977

Evolutionary adaptability of biological macromolecules.

The degree of gradualism with which tertiary structure and function of protein changes with stepwise changes in primary structure (assumed to be influenced by redundancy of weak bonding) is both a precondition for and consequence of evolution. The resulting selection for degree of gradualism has implications for a number of structural and functional properties of modern proteins as well as for the significance of neutral (so-called non-Darwinian) phenomena in relation to selection.

Amino Acids↗
PubMed1976

Molecular information structures in the brain.

This paper presents a theory of memory and memory mediated learning based on the manipulation of macromolecular conformations. The main features of the theory are: 1) the brain contains primary and reference neurons; 2) inputs from the external environment produce particular patterns of primary firing; 3) the firing of a primary neuron sensitizes certain of its dendrites; 4) the sensitized primaries are loaded by the reference neuron active at the time and in such a way that they fire when called by this reference neuron, thus reconstructing the original pattern of primary activity. The reference neurons may also be loaded by primaries, thus making it possible for the reconstruction process to be initiated by some feature of the initial input. Each reference neuron loads and calls at most one primary pattern of activity, thereby preventing superposition of memories. If the primaries are loadable by sequences of impulses, this makes it possible to increase the connectivity among the various types of neurons by using party-line organization. The loading and calling processes themselves are mediated by call molecules. These are allosteric enzymes, located in the dendrites of primary and reference neurons, whose states are set either by an impulse or sequence of impulses and which catalyze events leading to impulse formation whenever this input recurs. The call molecules are capable of duplicating their setting (or conformation) using either intra- or interneuronal potentials, thereby ensuring stability of the memory trace. The theory allows for general powers of memory manipulation (by rememorization), for the construction of time ordered, content ordered, and associative data structures, and for computation with global representations of the environment. It makes a large number of testable predictions, provides a natural interpretation for the structure of the cerebral cortex, and accounts for: resistance to cooling, differential effects of chemical agents on short and long term memory, distributed character of memory, accessibility of memories by stimulation of specific brain loci, and also the details of classical conditioning and instrumental learning.

Association Learning↗
PubMed1976

Complementary molecular models of learning and memory.

The functional capabilities of the brain are formally characterizable interms of a finite system along with a memory space which it can manipulate. Two types of learning are possible: (1) modification-based learning, associated with alternate realizations of the finite system; (2) memory-based learning, associated with the assimilation, manipulation, and retrieval of memories. Constructive models which fulfill these conditions and which at the same time operate on the basis of molecular information processing principles have certain general features. We describe these features in terms of two interfaced submodels, the first for the finite system and the second for the memory space. The finite system may be realized by networks of neurons in which the specificity of enzyme molecules controls the nerve impulse. Such a realization is amenable to modification-based learning mediated by processes analogous to those of natural evolution and selective theories of antibody synthesis. The memory space is realizable by networks of neurons in which the conformation of dendritic receptor molecules controls the nerve impulse. In this case certain neurons firing in response to an external input undergo sensitization at the dendrites and in such a way that they are loadable and later callable by reference neurons, thereby allowing for reconstruction of manipulation of the firing pattern associated with this input. The overall construction makes a large number of biochemical, anatomical, physiological, and psychological predictions which are either testable or in good agreement with fact.

Brain↗