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[The action of chemical agents at ultralow doses on biological objects].

The published data on the effect of low and ultralow (up to 10(-17] doses of chemical agents on different biological systems have been reviewed. A concept of action of ultralow doses has been proposed on the basis of a notion of complex hierarchical structure of regulation in biological systems where response to strong and weak actions is carried out by different mechanisms and pathways. The times of transport of molecules of biologically active compounds to targets have been calculated on the basis of the principle of the first boundary approach by Brown's particle. Probabilistic models of mechanisms leading to complex dose dependency have been analyzed.

Animals↗
PubMed1990

Relative decompression risk of dry and wet chamber air dives.

The difference in risk of decompression sickness (DCS) between dry chamber subjects and wet, working divers is unknown and a direct test of the difference would be large and expensive. We used probabilistic models and maximum likelihood estimation to examine 797 dry (and generally resting and comfortable) and 244 wet (and generally working and cold) chamber dives from the Defence and Civil Institute of Environmental Medicine, supplemented with 483 wet (working, cold) dives from the Navy Experimental Diving Unit. Several analyses considered whether dry and wet data were distinguishable using several models, whether models obtained from one set of exposure conditions would correctly predict the occurrence of DCS in the other condition, and whether a single wet-dry risk difference parameter was different from zero. Although the two conditions may not produce identical risks, immersion appears to change relative risk of DCS by less than 30% and certainly involves less than a doubling of DCS risk. Uncontrolled differences in exercise and temperature stresses unavoidably complicate interpretation. Several methods are presented to extrapolate results from dry-test subjects in decompression trials to expected at-sea performance.

Data Interpretation, Statistical↗
PubMed1986

Estimation of the distribution of blood vessel diameters from the arteriovenous passage of microspheres.

We present an estimator of the probability density of capillary diameters based on a simple probabilistic model of microsphere passage through a microvascular bed. With this model, an estimate of the density is obtained as the solution of an integral equation. The density is approximated by a linear combination of B-splines with the coefficients restricted to be nonnegative. Equations for maximum likelihood estimates of the coefficients are obtained. The proposed method is applied to data from the dog intestinal circulation.

Animals↗
PubMed1985

Assessment of interaction between carcinogens in long-term factorially designed animal experiments.

Two substances interact if the combined action results in an effect which is greater than, or less than, that of the sum of the effects produced separately by the substances. Finney (1971, Probit Analysis, 3rd ed. Cambridge: Cambridge University Press) proposed a probabilistic model for simple independent action of two substances for the case of dichotomous outcomes. Using Finney's underlying model, we examine tests for interaction between carcinogens or toxic substances for data from long-term 2 x 2 and 2 x 2 x 2 factorially designed animal experiments. The outcome of interest is the occurrence or not of a certain event (for example, the appearance of a tumor) and the time at which the event occurred. The proposed tests are based on the proportional hazards model. We discuss some simple methods for checking the appropriateness of the proportional hazards assumption. Applications of the tests are made to data from a 2 x 2 and a 2 x 2 x 2 experiment.

Animals↗
PubMed1980

Mechanism of primer-template-dependent conversion of dNTP leads to dNMP by T5 DNA polymerase.

T5 DNA polymerase catalyzes both 5' leads to 3' polymerization and 3' leads to 5' hydrolysis in a processive fashion. This knowledge has been utilized to obtain evidence indicating that the enzyme has a single primer-template binding site which can function as either polymerase or exonuclease, perhaps with the cooperation of additional or different side groups. Template-dependent conversion of dNTP leads to dNMP was observed with an excess of either primer-template or enzyme. With primer-template excess, practically all the enzymes were functional as polymerase; with enzyme excess, all primer-templates were extended during the first cycle of catalysis. These observations suggest that turnover takes place at the points of chain growth. Evidence is also provided which demonstrates that the enzyme is capable of switching its direction of catalysis from 3' leads to 5' to 5' leads to 3' without leaving the primer-template. A clear correspondence between the relative amount of hydrolysis of a terminally labeled residue on the primer and the relative amount of turnover suggests that (a) the probability of hydrolysis of a given type of residue in contact with the "active site" is constant, and (b) during each turnover episode enzyme usually takes only one step in the 3' leads to 5' direction. A simple probabilistic model of turnover is discussed.

DNA-Directed DNA Polymerase↗
PubMed1978

Alternatives to Rothman's approach for assessing synergism (or antagonism) in cohort studies.

K.J. Rothman has explored in some detail the issue of assessing the potential presence of synergism (or antagonism) in data generated from either a cohort or a case-control study. Arguing that the "natural" scale for quantifying the joint effects of two or more factors acting in combination is the probability scale, he has proposed a procedure based on a ratio-type index for evaluating two-factor interaction in the presence of non-zero background effects. In this paper, the authors review the rationale underlying Rothman's approach for a cohort study. They then present what they maintain is a simpler and more appropriate test procedure (utilizing a linear contrast of the observed risks) for the additive approximation to his basic probabilistic model of "no interaction." A likelihood ratio test based on his original model is also proposed, as well as a closed form approximation to it. Finally, the assessment of interaction in cohort studies involving exposure factors measured at more than two levels is addressed.

Epidemiology↗
PubMed1980

A left-right identification scale for clinical use.

The contribution of this research is a left-right identification scale which is relatively simple to administer, easy to score, and subject to low error rates. The research is unusual in that, rather than use subjective procedures (i.e., inspect data patterns), a probabilistic model was used to access fit to a linear hierarchy to response data. The resulting validated scale should be of use to researchers and clinicians alike.

Child↗
PubMed1995

Does the time course of bubble evolution explain decompression sickness risk?

A probabilistic model of decompression sickness (DCS) risk based on linear-exponential (LE) kinetics has given the best fit of the human air and nitrox DCS database. To test the hypothesis that its success may be due to the formation of a gas phase during decompression, we developed a physiologically based bubble evolution model using a numerical solution of a partial differential equation system. Because of the computational intensity of this method, it could not be used to fully explore our hypothesis. Consequently, we compared the solution with that of a computationally simpler approximation that was previously published by Van Liew and found the two approaches gave similar results. Using the simpler model, assuming bubble densities of 1 and 1,000 bubbles/cm3, we found a tissue time constant of at least 80 min (equivalent to perfusion of 1/80 ml.g-1.min-1) was required to achieve a delay in bubble dissolution comparable to the prolonged risk of DCS predicted by the LE model. We suggest that the persistence of single bubbles in a uniformly perfused homogeneous tissue alone is unlikely to explain persistent DCS risk.

Blood Flow Velocity↗
PubMed1995

The value of prior knowledge in discovering motifs with MEME.

MEME is a tool for discovering motifs in sets of protein or DNA sequences. This paper describes several extensions to MEME which increase its ability to find motifs in a totally unsupervised fashion, but which also allow it to benefit when prior knowledge is available. When no background knowledge is asserted. MEME obtains increased robustness from a method for determining motif widths automatically, and from probabilistic models that allow motifs to be absent in some input sequences. On the other hand, MEME can exploit prior knowledge about a motif being present in all input sequences, about the length of a motif and whether it is a palindrome, and (using Dirichlet mixtures) about expected patterns in individual motif positions. Extensive experiments are reported which support the claim that MEME benefits from, but does not require, background knowledge. The experiments use seven previously studied DNA and protein sequence families and 75 of the protein families documented in the Prosite database of sites and patterns, Release 11.1.

Algorithms↗
PubMed1994

Mixed Bayesian networks: a mixture of Gaussian distributions.

Mixed Bayesian networks are probabilistic models associated with a graphical representation, where the graph is directed and the random variables are discrete or continuous. We propose a comprehensive method for estimating the density functions of continuous variables, using a graph structure and a set of samples. The principle of the method is to learn the shape of densities from a sample of continuous variables. The densities are approximated by a mixture of Gaussian distributions. The estimation algorithm is a stochastic version of the Expectation Maximization algorithm (Stochastic EM algorithm). The inference algorithm corresponding to our model is a variant of junction three method, adapted to our specific case. The approach is illustrated by a simulated example from the domain of pharmacokinetics. Tests show that the true distributions seem sufficiently fitted for practical application.

Algorithms↗
PubMed1995

Effective access to distributed heterogeneous medical text databases.

INQUERY is an advanced text information retrieval system developed by the Information Retrieval Laboratory of the University of Massachusetts in Amherst. It is based on Bayesian inference networks, which are probabilistic models for reasoning with multiple sources of uncertain evidence. The evidence, in this case, is the presence or absence of words and/or phrases in a document. Evidence is combined into belief that a document is relevant. The INQUERY retrieval engine has been developed with the support of ARPA, NSF, and industrial funding. It has a number of unique features and has achieved excellent results in the TIPSTER and TREC evaluations. Informatics research and application development using INQUERY has recently begun in the medical domain, including a new ARPA initiative concerned with clinical text. The features that we will focus on in this demonstration are: Automatic processing of natural language queries, including the extraction of phrases and specific medical concepts such as drug doses; Document selection through automatic relevance feedback and routing techniques, including the construction of complex queries using the INQUERY query language; The integration of conventional database techniques with text analysis and retrieval; Automatic thesaurus generation and query expansion using the PhraseFinder system; Distributed database access, including automatic database selection and merging of local searches; this will be demonstrated using a collection of medical databases; Retrieval based on passages, rather than whole documents.

Bayes Theorem↗
PubMed1995

[A method of evaluation of the adaptation process].

The problem of adaptation cannot be reasonable well studied without due regard of the principle of reflection. The relationship between adaptation and reflection is realized in, for instance, the adequacy of body reactions to environmental impacts. The paper approaches this problem in the light of thermodynamics. A simple method for accounting the process of adaptation to continuous exposure in specially designed sealed chamber on the pattern of shift work of operators is proposed. The investigation embraced 29 divers aged 20-25 who stayed in shifts for long periods in a chamber with artificially and synthetically sustained air parameters. The investigation demonstrated the effectiveness of the description of adaptation process through probabilistic models with a high level of generalization, and the possibility to predict operator's functioning at various phases of his work cycle.

Adaptation, Physiological↗
PubMed1996

The genetic code and cyclic codes.

We proposed previously a cyclic code made of 22 triplets, which we now call the AB code. It is made up of the following chain: AUGGUGCCAUUCAAGACUAUGA. The letters A, U, C, G represent the classical symbols of the (purine and pyrimidine) bases of the genetic code. This chain presents the following features: (1) when it is in cyclic form, it begins with the initiation codon AUG, ends with the termination codon UGA, and it can be read triplet after triplet by choosing 1 and only 1 representative of each synonymy class in the classical degenerate genetic code made of 64 triplets. The chain, therefore, possesses 1 and only 1 codon for each amino-acid; (2) except for the doublet CG, triplets of the chain begin with the 15 other possible doublets of bases (satisfying the "wobble" hypothesis presented by Crick); (3) it corresponds (except for 1 base) to the "loop" part of the CEnothera mitochondrial Gly-tRNA; (4) it can be modified, without loss of the properties (1) and (2), in such a way as to have 15 bases in common with the loop part of other mitochondrial tRNA's considered as primitive, like Ala-, Pro- and Arg-tRNA; (5) it contains the most frequent triplets, but not the most rare ones, appearing in the genome of numerous species; (6) it exhibits a coherent internal structure with respect to the molecular weight of its triplets. This structure, also found in the loop part of mitochondrial tRNA's, contains an excess of AU bases with respect to GC bases. This fact has no explanation in the classical probabilistic model of the tRNA's. Therefore, we propose the cyclic AB code as a primitive genetic structure with the essential coding properties of the present genetic code.

Codon↗
PubMed1997

Prevalence of infection, mean worm burden and degree of worm aggregation as determinants of prevalence of disease due to intestinal helminths.

Theoretical predictions of disease prevalence due to helminth infections based upon a simple probabilistic model which considers the infection prevalence, the mean worm burden and the degree of worm aggregation are presented. A numerical reappraisal of the likely estimates of the degree of aggregation based upon maximum likelihood estimates of the negative binomial distribution is presented. The prevalence of disease shows a positive relationship with the mean worm burden. This association is hyperbolic when helminth parasites are severely aggregated but is s-shaped when helminth parasites tend to be overdispersed. The prevalence of disease decreases with the degree of worm aggregation when the values of the mean intensity are low; as the mean intensity increases this association becomes positive. The relationship between prevalence of disease and prevalence of infection is hyperbolic for severe degrees of parasite aggregation and is s-shaped for intermediate degrees of aggregation. However, if the mean intensity is low and the degree of aggregation is high there could be a negative relationship between the prevalence of disease and the prevalence of infection. The presence of disease due to helminth parasites is feasible for determined ranges of values of the infection prevalence, mean intensity and the degree of worm clumping.

Animals↗
PubMed1997

Better prediction of protein cellular localization sites with the k nearest neighbors classifier.

We have compared four classifiers on the problem of predicting the cellular localization sites of proteins in yeast and E. coli. A set of sequence derived features, such as regions of high hydrophobicity, were used for each classifier. The methods compared were a structured probabilistic model specifically designed for the localization problem, the k nearest neighbors classifier, the binary decision tree classifier, and the naïve Bayes classifier. The result of tests using stratified cross validation shows the k nearest neighbors classifier to perform better than the other methods. In the case of yeast this difference was statistically significant using a cross-validated paired t test. The result is an accuracy of approximately 60% for 10 yeast classes and 86% for 8 E. coli classes. The best previously reported accuracies for these datasets were 55% and 81% respectively.

Algorithms↗
PubMed1997

Generating benchmarks for multiple sequence alignments and phylogenetic reconstructions.

We present a new probabilistic model of evolution of RNA-, DNA-, or protein-like sequences and a tool rose that implements this model. By insertion, deletion and substitution of characters, a family of sequences is created from a common ancestor. During this artificial evolutionary process, the "true" history is logged and the "correct" multiple sequence alignment is created simultaneously. We also allow for varying rates of mutation within the sequences making it possible to establish so-called sequence motifs. The results are suitable for the evaluation of methods in multiple sequence alignment computation and the prediction of phylogenetic relationships.

Amino Acid Sequence↗
PubMed1981

The bingo model of survivorship: 1. probabilistic aspects.

A "bingo" model is one in which the pattern of survival of a system is determined by whichever of several components, each with its own particular distribution for survival, fails first. The model is motivated by the study of lifespan in animals. A number of properties of such systems are discussed in general. They include the use of a special criterion of skewness that probably corresponds more closely than traditional measures to what the eye observes in casually inspecting data. This criterion is the ratio, r(h), of the probability density at a point an arbitrary distance, h, above the mode to that an equal distance below the mode. If this ratio is positive for all positive arguments, the distribution is considered positively asymmetrical and conversely. Details of the bingo model are worked out for several types of base distributions: the rectangular, the triangular, the logistic, and by numerical methods, the normal, lognormal, and gamma.

Actuarial Analysis↗
PubMed2002

Probabilistic emission and immission modelling: case-study of the combined sewer-WWTP-receiving water system at Dessel (Belgium).

The impact of the combined urban drainage and WWTP system of the village of Dessel (Belgium) on the Witte Nete receiving water is modelled both in terms of emissions and immissions. The hydrodynamic and water quality modelling is performed both in a deterministic and probabilistic way. For the deterministic modelling, detailed physically based and simplified conceptual models are used in a complementary way. In the probabilistic modelling, the different uncertainties in the deterministic model are classified in input uncertainties, parameter uncertainties and model-structure uncertainties. The probabilistic simulation results can be used in risk analysis and management, for the determination of the major uncertainty-sources and priorities in model improvement, for model bias elimination and for efficient model calibration.

Belgium↗