Coronary computed tomography--present status and future directions.

The use of coronary computed tomography angiography (cCTA) is growing rapidly, in large part because of fast-paced technical innovations that have increased diagnostic accuracy while providing new opportunities for radiation dose reduction. cCTA using recent generation CT scanners has been repeatedly shown to have excellent negative predictive value for ruling out significant coronary stenosis in comparison with invasive coronary angiography (ICA) and is now accepted for this use in selected populations. Current work is increasingly focused on evaluating and optimising radiation dose reduction techniques, the cost-effectiveness of cCTA implementation, and the impact of cCTA on patient management and outcomes. In addition, the potential value of emerging applications, such as atherosclerotic plaque characterisation and myocardial perfusion and viability assessment, are undergoing intense investigation.

To each genotype a separate strategy--a dynamic game theory model of a general diploid system.

A dynamic game theory model is presented for a diploid system in which each genotype corresponds to a different strategy. The population mates randomly and the strategy, which is determined by a single locus, is expressed only in the male. A general analytic solution for any number of alleles does not appear to be possible, but the cases of two and three alleles are treated in detail. A stability analysis applicable to any number of alleles is presented, so that any equilibria located by numerical methods can be checked for local stability. Computer programs for doing all of these calculations are available from the author.

A three-dimensional representation for base composition of protein-coding DNA sequences.

Multi-dimensional scaling is applied to our codon space data on the protein coding sequences of DNA from a wide variety of organisms in an attempt to find the smallest number of parameters which will accurately represent these sequences. I find that a three-dimensional representation is satisfactory. One of the three resulting co-ordinates separates eukaryotes and their associated viruses from prokaryotes and their associated phages, while an orthogonal co-ordinate separates those organisms capable of synthesizing proteins (eukaryotes and prokaryotes) from those not so capable (viruses and phages). Mitochondria show no relation in our plots to any of these groups.

Computational analysis of models for cotransport.

The order of substrate interaction with a cotransport carrier is studied by numerically fitting theoretical models to empirical data for a Na+-D-glucose pathway. Our analysis is based on a least-squares minimization routine developed at CERN, and uses data derived from tracer flux of substrate under equilibrium exchange conditions. Random, Ordered mirror, and Ordered glide models are considered and the applicability of both Random and Glide systems to the experimental observations is demonstrated. A more detailed study of the Glide model provides an estimation of the relative values of the individual rate constants describing each kinetic step in the mechanism. We argue that parameterization of competing models can result in tests which will distinguish between them, even when these contain many unknowns in the proposed structure of the kinetic mechanism. The essence of this means of model discrimination is the ability to find a single set of parameter values that fits a variety of experimental observations. The ability to obtain numerical estimates of obtain numerical estimates of individual rate constants is also a useful tool in investigation of the kinetic fine structure of the carrier. For the data at hand we conclude that a complete parameterization of the Glide model cannot be attained, possibly due to a heterogeneity in the temperature at which the experiments have been performed. Three solutions to the Glide model are presented, each of which corresponds to a fit of the Glide model to a subset of the experimental data.

A tetrahedral representation of poly-codon sequences and a possible origin of codon degeneracy.

A novel and interesting representation of codon space is introduced in which the 64 codons are grouped and re-arranged as vertices in a tetrahedral lattice. Amino acids are then assigned to the lattice in a suggestive way which, when combined with earlier work, leads to an interesting speculation on the origin and development of the genetic code.

Cluster analysis of genes in codon space.

We construct a "codon space" in which a given DNA sequence can be plotted as a function of its base composition in each of the three codon positions. We demonstrate that the base composition is very highly nonrandom, with sequences from more primitive organisms having the least random compositions. By using cluster analysis on the points plotted in codon space we show that there is a strong correlation between base composition and type of organism, with the most primitive organisms having the highest A or T content in the second and third codon positions. A smooth transition toward lower A + T and higher G + C content is observed in the second and third codon positions as the evolutionary complexity of the organism increases. Besides this general trend, more detailed structure can be observed in the clustering that will become clearer as the data base is increased.

On the informational content of viral DNA.

This paper is concerned primarily with how information is stored in viral DNA. The general problem of defining information content is discussed and a procedure for analysis extended from that of Gatlin (1972) is developed. Long range correlations in base sequences are analyzed for several viral genomes. The relationship of these correlations to the existence of strong codon biases is examined and the consequences discussed.

A thermodynamic theory of codon bias in viral genes.

The relationship between degeneracy in the genetic code and the occurrence of a strong codon bias is examined, with particular reference to a group of viral genomes. The present paper shows how codon bias may have been imposed by thermodynamic considerations at the time the primitive DNA first formed in the primordial soup. Using a four-state Ising-like model with stacking interactions between successive base pairs, we show how primeval periodic DNA polymers could have arisen the remnants of which are still observed in codon biases today.