Search PubMed⌕ Search

Biomedical subjects

M Eigen

Publications and source records attributed to M Eigen.

At least 55 records · Page 3Linked to original sources

The AIDS debate.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Statistical geometry in sequence space: a method of quantitative comparative sequence analysis.

A statistical method of comparative sequence analysis that combines horizontal and vertical correlations among aligned sequences is introduced. It is based on the analysis mainly of quartet combinations of sequences considered as geometric configurations in sequence space. Numerical invariants related to relative internal segment lengths are assigned to each such configuration and statistical averages of these invariants are established. They are used for internal calibration of the topology of divergence and for quantitative determination of the noise level. Comparison of computer simulations with experimental data reveals the high sensitivity of assignment of basic topologies even if much randomized. In addition, these procedures are checked by vertical analysis of the aligned sequences to allow the study of divergences with positionally varying substitution probabilities.

Base Sequence↗

Kinetics of RNA replication: competition and selection among self-replicating RNA species.

The process of Darwinian selection in the self-replication of single-stranded RNA by Q beta replicase was investigated by analytical and computer-simulation methods. For this system, the relative population change of the competing species was found to be a useful definition of selection value, calculable from measurable kinetic parameters and concentrations of each species. Critical differences in the criteria for selection were shown to pertain for replicase/RNA ratios greater than or less than 1, for the case that formation of double-stranded RNA occurs and when comparisons are made of closed with open systems. At a large excess of enzyme, RNA species grow exponentially without interfering with each other, and selection depends only on the fecundity of the species, i.e., their overall replication rates. For RNA concentrations greater than the replicase concentration, the selection of species is governed by their abilities to compete for enzyme. Under conditions where formation of double strands occurs, competition leads to a coexistence of the species; the selection values vanish, and the concentration ratios depend only on the template binding and double-strand formation rates. The approach to coexistence is rapid, because when its competitors are in a steady state, a species present in trace amount is amplified exponentially. When formation of hybrid double strands occurs at a substantial rate, coexistence of hybridizing species is essentially limited to cases where the formation rate of heterologous double strands is smaller than the geometric mean of the formation rates of the homologous double strands. At limiting cases, e.g. in the steady states, simple analytical expressions for the main aspects of the selection process were found. Experimental data support the analytical expressions and the simulations.

Computers↗

[Epidemiology of AIDS].

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Pattern analysis of 5S rRNA.

Some 200 different 5S rRNA sequences from eubacteria, chloroplasts, mitochondria, archaebacteria, and eukaryotes were analyzed for evolutionary kinship relationships and associated sequential features. Group-specific occupation schemes for the 149 positions of an overall alignment were established. Eubacterial, archaebacterial, and intermediate occupation schemes all yield a strongly biased base triplet pattern in one of the three possible reading frames strongest for eubacterial, chloroplastic, and archaebacterial, but still detectable for mitochondrial and eukaryotic cytoplasmic sequences. The frequency of triplets decays in the order RNY greater than RNR greater than YNY greater than YNR; R being a purine (guanine or adenine), Y is a pyrimidine (cytosine or uracil), and N is any base. A strong preference for guanine or cytosine was found in all triplet positions. The effects show no exceptions and are clearly above the level of statistical fluctuations.

Archaea↗

Toward Bion's starting point: between catastrophe and faith.

Catastrophe and faith are explored as the most basic terms of Bion's work. In doing so it is shown how Bion gets underneath Kleinian concepts to expand the depth phenomenology of a catastrophic sense of origins. For Bion the self is born, evolves and dissolves with a sense of catastrophe. Whether or not Bion is right in various aspects of his account, catastrophe is an elemental term of our existence. For Bion, Faith is a proper primordial and developed response to catastrophe. This paper discusses aspects of the relationship between faith, knowledge, container-contained and catastrophe.

Defense Mechanisms↗

Kinetics of RNA replication: plus-minus asymmetry and double-strand formation.

The effects of kinetic plus-minus asymmetry and formation of inactive double strands on the self-replication of single-stranded RNA were investigated by analytical and computer simulation methods. It was found that extensions of the analysis developed previously for more restricted models lead to simple formulations that can be used for interpretation of experiments. Relaxation to linear growth or to steady-state conditions for double-strand formation was found to depend upon initial conditions but to be essentially complete for typical laboratory situations. Experimental data confirmed that in the linear growth phase the total nucleotide incorporation rate is about equal in the complementary strands; mostly double strand is formed. However, the enzyme is usually not shared equally, and some steps proceed at different rates in the two strands. The asymmetry is, however, not found to be dramatic for any of the RNA variants studied so far. It appears that the observed prevalence of kinetically rather symmetric self-replication is due to selection of RNA species with similar rate constants during the exponential growth phase.

Computers↗

Kinetics of RNA replication.

The reaction kinetics of single-stranded RNA replication were investigated by means of analytical and computer simulation methods. A model reaction mechanism is proposed that is in accord with the extensive experimental data available for the replication of various templates by the enzyme Q beta replicase. Despite the complexity of this mechanism, conventional concepts of steady-state and dynamic enzyme catalysis and plausible values of the rate and stability constants for the elementary reactions suffice to provide detailed understanding of RNA replication kinetics. The main features can be described with simple formulas that are analogous to traditional descriptions of enzyme kinetics.

Genes, Viral↗