The dead-end elimination theorem and its use in protein side-chain positioning

The prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space1 makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers2??. Nonetheless, an exhaustive combinatorial search is still limited to carefully indentified packing units?? containing a limited number of residues. For larger systems other strategies had to be developed, such as the Monte Carlo Procedure?? and the genetic algorithm and clustering approach?. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains.     

Potentiation of antifungal activity of sesquiterpene dialdehydes againstCandida albicans and two other fungi

The antifungal activity of two drimane sesquiterpene dialdehydes, polygodial (1) and warburganal (2), alone and in combination with several other substances, was examined against three fungi,Candida albicans, Saccharomyces cerevisiae andPityrosporum ovale employing a broth dilution method. Anethole significantly synergized the activity of the two sesquiterpenoids againstC. albicans andS. cerevisiae however, it had only an, additive effect againstP. ovale. By contrast, two antioxidants, ascorbic acid (vitamin C) and BHA (butylated hydroxyanisole), noticeably enhanced the activity of the sesquiterpenoids againstP. ovale, but had no, effect againstC. albicans andS. cerevisiae.     

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

The median procedure for n-trees

Let (X,d) be a metric space The functionM:X ^k 2 ^x defined by is the minimum } is called themedian procedure and has been found useful in various applications involving the notion of consensus Here we present axioms that characterizeM whenX is a certain class of trees (hierarchical classifications), andd is the symmetric difference metricWe would like to thank the referees and Editor for helpful comments     

Secular variation in carbon isotope ratios from Upper Proterozoic successions of Svalbard and East Greenland

Analyses of stratigraphically continuous suites of samples from Upper Proterozoic sedimentary successions of East Greenland, Spitsbergen and Nordaustlandet (Svalbard) provide an approximation to the secular variation in carbon isotope ratios during a geologically and biologically important period of change from around 900 million years ago to the beginning of the Cambrian period. Late Riphean carbonates and organic material show a stratigraphically useful pattern of enrichment in 13C relative to Phanerozoic or earlier Proterozoic samples. Isotopic compositions of isolated samples from other localities are consistent with a worldwide extended interval of enhanced organic burial and consequent net survival of oxidized material, probably O2, just before the initial radiation of metazoans.     

Novel rearrangement of purines

6-Trichloromethyl-9-methylpurine (1) rearranges to 6-dichloromethyl-9-methyl-8-oxopurine (2) in aqueous mild acidic solution. The rearrangement is rationalized in terms of a reaction involving protonation, covalent hydration, prototropic equilibrium and/or a hydride transfer. An alternative mechanism involving a "positive' halogen compound and hypochlorous acid as an intermediary is also proposed. Compound 1 condenses with 4,5-diaminopyrimidine to give the purine-pyrimidine Schiff base pair 4.     

Bolzano,Cauchy and the “new analysis” of the early nineteenth century

Summary In this paper I discuss the development of mathematical analysis during the second and third decades of the nineteenth century; and in particular I assert that the well-known correspondence of new ideas to be found in the writings of Bolzano and Cauchy is not a coincidence, but that Cauchy had read one particular paper of Bolzano and drew on its results without acknowledgement. The reasons for this conjecture involve not only the texts in question but also the state of development of mathematical analysis itself, Cauchy both as personality and as mathematician, and the rivalries which were prevalent in Paris at that time.     

MD Method in Solving Multiple Criteria Decision Problems Arising from Investment Systems

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