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Biomedical subjects

M Conrad

Publications and source records attributed to M Conrad.

At least 37 records · Page 2Linked to original sources
PubMed1989

Towards an artificial brain.

Three components of a brain model operating on neuromolecular computing principles are described. The first component comprises neurons whose input-output behavior is controlled by significant internal dynamics. Models of discrete enzymatic neurons, reaction-diffusion neurons operating on the basis of the cyclic nucleotide cascade, and neurons controlled by cytoskeletal dynamics are described. The second component of the model is an evolutionary learning algorithm which is used to mold the behavior of enzyme-driven neurons or small networks of these neurons for specific function, usually pattern recognition or target seeking tasks. The evolutionary learning algorithm may be interpreted either as representing the mechanism of variation and natural selection acting on a phylogenetic time scale, or as a conceivable ontogenetic adaptation mechanism. The third component of the model is a memory manipulation scheme, called the reference neuron scheme. In principle it is capable of orchestrating a repertoire of enzyme-driven neurons for coherent function. The existing implementations, however, utilize simple neurons without internal dynamics. Spatial navigation and simple game playing (using tic-tac-toe) provide the task environments that have been used to study the properties of the reference neuron model. A memory-based evolutionary learning algorithm has been developed that can assign credit to the individual neurons in a network. It has been run on standard benchmark tasks, and appears to be quite effective both for conventional neural nets and for networks of discrete enzymatic neurons. The models have the character of artificial worlds in that they map the hierarchy of processes in the brain (at the molecular, neuronal, and network levels), provide a task environment, and use this relatively self-contained setup to develop and evaluate learning and adaptation algorithms.

Artificial Intelligence↗
PubMed1989

The artificial worlds approach to emergent evolution.

Artificial worlds models of evolutionary systems are computer models that map the essential logical structure of ecological systems, defined as self-sustaining biological organizations. The artificial world comprises an artificial environment, with mass components, energy input, and physical states. It also comprises artificial organisms, including a genome, a phenome, and a (developmental) map that connects the genome to the phenome. Mass components are cycled and space is limited. The evolution process results, as in nature, from genetic variation combined with natural selection imposed by the finiteness of the environment. The selection criteria (fitness values) are not imposed, but rather emerge from the interactions of the organisms with each other and with the environment. The dynamics at the population level also emerges from these basic interactions. In this paper we describe the comparative properties of the EVOLVE family of artificial worlds models.

Artificial Intelligence↗
PubMed1989

The brain-machine disanalogy.

The comparative study of information processing in brains and machines leads to a picture in which disanalogies are more fundamental than analogies. The major dichotomy is between evolvability and programmability. Brain models, to be tenable, must pass an extended Turing test in which the capacity to self organize through the Darwinian mechanism of variation and selection is a key element. Programmable machines that simulate the type of structure-function relations that allow evolution to occur are, however, too inefficient in their use of resources for problem solving to support cognitive abilities comparable to those of biological organisms. Furthermore, real evolutionary systems are open in that it is always possible for them to tap previously unexploited physical interactions for computing. Nevertheless, computer simulation provides a powerful tool for studying brain function; and non-programmable designs that exploit the high efficiency, high adaptability domain of computing are in principle possible.

Algorithms↗
PubMed1989

Role of maternal depression in perceptions of child maladjustment.

We investigated (a) the relation of maternal depression to perceptions of externalizing and internalizing disorders in children and (b) quality of communication in a mother-child interaction task as a function of maternal depression and perceptions of the child. 64 children of unipolar or bipolar mothers, chronic medically ill or normal mothers were studied; clinical diagnoses, children's reports, and teachers' ratings served as objective criteria of children's maladjustment. Maternal depression defined by current symptomatology on the Beck Depression Inventory and by psychiatric status was not associated with misperceptions of psychopathology. Maternal depression interacted with children's actual behaviors to predict mothers' perceptions: nondepressed mothers were less accurate reporters of problems in children than were depressed mothers. Depressed mothers who perceived maladjustment in their disturbed children made more negative comments in interactions that did nondepressed mothers of disturbed children. The apparent mutual impact of mothers' and children's maladjustment requires fuller exploration in offspring studies.

Adolescent↗
PubMed1989

DNA and spermidine provide a switch mechanism to regulate the activity of restriction enzyme Nae I.

Sequence-specific DNA-protein interactions are basic to DNA function. To better understand these interactions, we studied the effect of position on cleavage of DNA by the type II restriction enzyme (EC 3.1.21.4) Nae I. We discovered two classes of Nae I restriction sites: sites susceptible and sites resistant to cleavage. Kinetic analysis showed that Nae I was activated by DNA containing cleavable Nae I sites to rapidly cleave resistant Nae I sites by a noncompetitive mechanism with a Km for substrate DNA of about 2 nM and a KA for activating DNA of about 6 nM; activation increased catalysis but not substrate binding. Deletion mutagenesis in vitro showed that sequences flanking the Nae I recognition site were responsible for the differences between activating and nonactivating Nae I sites. The polyamine spermidine had a dramatic effect on the interaction of Nae I with DNA; in the presence of 1 mM spermidine, resistant sites were cleaved rapidly and cleavable DNA inhibited cleavage. The direct regulation of enzymatic activity by DNA sequences in trans, and the modulation of this regulation by a polyamine that is sensitive to the cell cycle, provides a regulatory switch mechanism. The implications of this switch for biological control functions are discussed.

Base Sequence↗
PubMed1989

Excision repair of O6-methylguanine synthesized at the rat H-ras N-methyl-N-nitrosourea activation site and introduced into Escherichia coli.

O6-methylguanine (O6-methylG) is believed to be the premutagenic lesion responsible for mutational activation of the H-ras proto-oncogene in rats treated with N-methyl-N-nitrosourea (MNU). Research on the repair of O6-methylG has primarily focused on the methyltransferases. Potentially, other repair proteins may be involved in repair of O6-methylG. We have investigated the effect of Escherichia coli UvrABC excision repair on O6-methylG synthesized at the rat H-ras MNU activation site in a partial rat H-ras sequence constructed in an M13mp vector. An oligonucleotide self-selection technique was used to identify progeny phage containing DNA replicated from the O6-methylG-containing strand. We found that excision repair can help protect against mutation by O6-methylG at the rat H-ras MNU activation site.

Base Sequence↗
PubMed1988

Maturation of the immune response: a computational model.

Experimental studies of the effect on antibody affinity of antigen dose and time after immunization show that average affinity increases progressively with time after immunization, and that this increase is greater at lower doses of antigen. In this paper we describe a polyclonal computer model of the immune system that yields all the essential phenomena of affinity maturation, including dose-dependency. Our main findings are (1) the dose-dependency relationship is not produced when typical assumptions regarding B-cell populations and binding reactions are employed, and (2) it is possible to reproduce this dependency by assuming two classes of lymphocytes: generalists and specialists. Generalists have a low threshold for response and produce antibody of low effectiveness, whereas specialists have a high threshold for response, and produce highly effective antibody. We make an analogy between the generalists and a pioneer species in ecological succession, and suggest how the generalists may contribute to a more effective defense against real infections.

Antibody Affinity↗
PubMed1988

Unexpected dystocia secondary to a fetal sacrococcygeal teratoma: a successful outcome.

Sacrococcygeal teratoma is a rare cause of dystocia. With recent advances in perinatal care, particularly the increasing use of maternal ultrasound, it is unlikely that unexpected dystocia secondary to this tumor will be seen by many physicians. Recent reports of this type of dystocia are rare and infant mortality secondary to it is high. However, if and when encountered, such dystocia need not imply a bad prognosis for either mother or infant. This is a report of successful management of one case as well as a presentation of recently reported cases and recommendations for management.

Adult↗
PubMed1986

Induction of deletion and insertion mutations by 9-aminoacridine. An in vitro model.

The ability of 9-aminoacridine to induce mutagenic lesions during DNA replication in vitro was investigated. The ampicillinase gene of pBR322 was replicated in vitro in the presence of 9-aminoacridine. Transfection of the replicated DNA into Escherichia coli gave Amps mutants. Determination of the base changes in 76 of these mutants indicated that the spectrum of mutations induced by 9-aminoacridine was consistent with its action in vivo. Both large (407-base) and small (1- and 2-base) deletions were induced at repetitive sequences. The frequency of deletion mutations depended on the identity of the base deleted and sequences surrounding the deletions. The characteristics of the frameshift mutations induced were consistent with the interactions of 9-aminoacridine with DNA. These results establish that 9-aminoacridine can induce frameshift mutations during the replication process and provide an in vitro model of frameshift induction for mechanistic studies.

Aminacrine↗
PubMed1986

O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine.

Mutations were induced in the ampicillinase gene of a bacteriophage f1/pBR322 chimera both by incorporation of O6-methyl-dGTP opposite T during DNA replication in vitro and by site-directed mutagenesis using O6-methylguanine-containing oligonucleotides. After passage of the DNA through Escherichia coli, analysis of 151 O6-methyl-dGTP-induced mutations indicated a significantly greater number of unmutated mutation sites than expected, whereas the mutated sites generally fit a Poisson distribution. The unmutated sites are assumed to be caused by the inability of some sequences to tolerate the presence of a tetrahedral methyl group within the confines of a Watson-Crick helix (Toorchen, D., and Topal, M.D. (1983) Carcinogenesis 4, 1591-1597). A consensus of the DNA sequences surrounding unmutated mutation sites was derived. The consensus sequence had significant similarity to the region of the rat Harvey ras oncogene containing the N-methyl-N-nitrosourea activated site for transformation (Zarbl, H., Sukumar, S., Arthur, A. V., Dionisio, M.-Z., and Barbacid, M. (1985) Nature 315, 382-385). We propose that direct alkylation at O6 of a guanine present within the consensus sequence may produce a DNA conformation less subject to repair. Mutation by O6-methylguanine-containing oligonucleotides demonstrated that repair of the O6-methylguanine lesions varied at least 3-4-fold with position of the lesion.

Alkylation↗
PubMed1986

DNA structural variability as a factor in gene expression and evolution.

Redundant DNA can buffer sequence dependent structural deviations from an ideal double helix. Buffering serves a mechanistic function by reducing extraneous conformational effects which could interfere with readout or which would impose energetic constraints on evolution. It also serves an evolutionary function by allowing for gradual variations in conformation-dependent regulation of gene expression. Such gradualism is critical for the rate of evolution. The buffer structure concept provides a new interpretation for repetitive DNA and for exons and introns.

Base Sequence↗