Mutation-absorption model of the enzyme.
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Biomedical subjects
Publications and source records attributed to M Conrad.
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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.
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.
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.
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.
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.
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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.
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.
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