Biomedical subjects

T Kazic

Publications and source records attributed to T Kazic.

6 recordsLinked to original sources

PubMed2000

Semiotes: a semantics for sharing.

MOTIVATION: Reliable, automated communication of biological information requires methods to declare the information's semantics. In this paper I describe an approach to semantic declaration intended to permit independent, distributed databases, algorithms, and servers to exchange and process requests for information and computations without requiring coordination or agreement among them on universe of discourse, data model, schema, or implementation. RESULTS: This approach uses Glossa, a formal language defining the semantics of biological ideas, information, and algorithms, to executably define the semantics of complex ideas and computations by constructs of semiotes, terms which axiomatically define very simple notions. A database or algorithm wishing to exchange information or computations maintains a set of mappings between its particular notions and semiotes, and a parser to translate between its indigenous ideas and implementation and the semiotes. Requests from other databases or algorithms are issued as semiotic messages, locally interpreted and processed, and the results returned as semiotes to the requesting entity. Thus, semiotes serve as a shared, abstract layer of definitions which can be computably combined by each database or algorithm according to its own needs and ideas. By combining the explicit declaration of semantics with the computation of the semantics of complex ideas, Glossa and its semiotes permit independent computational entities to lightly federate their capabilities as desired while maintaining their unique perspectives on both scientific and technical questions.

Algorithms↗

PubMed1999

Elements of a more comprehensive theory of computing.

Problems implementing DNA computers stem from the physical nature of molecules and their reactions. The present theory of computation requires assumptions that, at best, are extremely crude approximations of the physical chemistry. Here, I consider the hypothesis that discarding those assumptions in favor of more physically realistic descriptions would produce a more comprehensive theory of computing, yielding both theoretical insights and help in designing better molecular computers. I describe the discordances between the theories of physical biochemistry and computation, indicate some elements of a more comprehensive theory, and discuss some of the challenges the construction of a unified theory faces.

Animals↗

PubMed1990

Context effects in the formation of deletions in Escherichia coli.

We have examined the frequency with which identical deletions are formed in different chromosomal contexts. A panel of six mutant bla genes containing palindrome/direct repeat structures were moved from pBR322 to three locations: at lambda att, at chromosomal lac, and at F'lac. Deletion of the palindromes and one of the direct repeats results in reversion to Ampr. The frequency of deletion for all alleles declines beyond the reduction in copy number when they are moved from the multicopy plasmid environment to a single-copy chromosome. The magnitude of the declines varies in an allele-specific and location-specific manner. Our data support the hypothesis that context can influence the frequency of mutation independent of the immediate DNA sequence.

Alleles↗

PubMed1989

Formation of supercoiling domains in plasmid pBR322.

Twin domains of positive and negative supercoiling are thought to form in DNA molecules whenever free rotation of a transcription complex around the DNA helix is impeded. Evidence for these domains has come from findings with Escherichia coli strains that are deficient in DNA topoisomerase I (top mutants) or that have been treated with DNA gyrase inhibitors. Plasmid pBR322 is highly supercoiled in these strains, whereas some of its deletion derivatives are not. The studies of pBR322 derivatives presented here show that high negative supercoiling in top strains requires translation as well as transcription of the first 98 codons of the tet gene and does not require the divergently transcribed amp gene. The N-terminal region of the TetA protein is thought to insert into the inner membrane. Our results favor models in which supercoiling domains are created when DNA segments are anchored to a large cellular structure via coupled transcription, translation, and membrane insertion of a nascent protein.

DNA Mutational Analysis↗

PubMed1979

Late replication and recombination in the vegetative pool of T4.

The rates and extents of replication are the same for all members of the vegetative pool, whether already residing (progeny) or newly entered (superinfecting). Thus, no member of the pool is sequestered in a replicative complex. Amber N82 infections of nonpermissive host result in extensive breakdown of phage DNA. The extent of fragmentation observed depends on the multiplicity of infection and whether phage ligase is present. Hence, parental DNA suffers single-strand nicks which can be repaired by ligase only if recombination does not interfere. The physiological role of ligase in compensating for such nicks is reemphasized. Superinfecting genomes recombine very rapidly with progeny molecules whose combined lengths are approximately six times that of the superinfecting genomic fragment. The superinfecting phage does not replicate before recombining. Therefore, the lack of replication poses no barrier to efficient recombination.

DNA Ligases↗

PubMed1976

Reduction in brain tyrosine hydroxylase activity following acetylcholinesterase blockade in rats.

Activation of cholinergic neurons in the brain is produced by administration of the acetylcholinesterase inhibitors physostigmine and diisopropylfluorophosphate (DFP). This activation has a biphasic effect on tyrosine hydroxylase (EC 4.14.3-) activity. The acute effect of DFP, 1 mg/kg, intraperitoneally, or physostigmine, 0.2 mg/kg, intravenously, or 10 mug, intraventricularly, was a rapid reduction in tyrosine hydroxylase activity in the hypothalamus. The activities of DOPA decarboxylase (EC 4.1.1.28) and dopamine-beta-hydroxylase (EC 1.14.17.1) were not changed. In contrast to the acute effect, chronic administration of physostigmine, 0.2 mg/kg, intravenously, twice daily for 7 days produced an increase in tyrosine hydroxylase activity in the hypothalamus. The rapid acute effects may be due to an allosteric inactivation of tyrosine hydroxylase, while the chronic effects may reflect enzyme induction.

Animals↗