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PubMed2003

Modulation spectra of natural sounds and ethological theories of auditory processing.

The modulation statistics of natural sound ensembles were analyzed by calculating the probability distributions of the amplitude envelope of the sounds and their time-frequency correlations given by the modulation spectra. These modulation spectra were obtained by calculating the two-dimensional Fourier transform of the autocorrelation matrix of the sound stimulus in its spectrographic representation. Since temporal bandwidth and spectral bandwidth are conjugate variables, it is shown that the joint modulation spectrum of sound occupies a restricted space: sounds cannot have rapid temporal and spectral modulations simultaneously. Within this restricted space, it is shown that natural sounds have a characteristic signature. Natural sounds, in general, are low-passed, showing most of their modulation energy for low temporal and spectral modulations. Animal vocalizations and human speech are further characterized by the fact that most of the spectral modulation power is found only for low temporal modulation. Similarly, the distribution of the amplitude envelopes also exhibits characteristic shapes for natural sounds, reflecting the high probability of epochs with no sound, systematic differences across frequencies, and a relatively uniform distribution for the log of the amplitudes for vocalizations. It is postulated that the auditory system as well as engineering applications may exploit these statistical properties to obtain an efficient representation of behaviorally relevant sounds. To test such a hypothesis we show how to create synthetic sounds with first and second order envelope statistics identical to those found in natural sounds.

Animals↗
PubMed1994

Likelihood ratios for DNA identification.

Likelihood ratio (LR) tests are provided for the three alternatives to DNA identity: exclusion, coincidence, and kinship. The coincidence test uses the radius of coalescence to conserve the observed frequency of single band phenotypes. Genotype probabilities under kinship are derived for mating groups, specified relatives, and structured populations; and unbiased estimates of the genetic parameters are provided. The LR is made robust to gene frequency errors by specifying the mean matching probability, and the tolerable loss of information this entails is determined by LR theory. This straightforward application of the seminal work of Jerzy Neyman and Sewall Wright strongly supports the use of LRs and kinship for presentation of DNA evidence by expert witnesses and committees.

Adult↗
PubMed1999

Entropy optimization by the PFANN network: application to blind source separation.

The aim of this paper is to present a study of polynomial functional-link neural units that learn through an information-theoretic-based criterion. First the structure of the neuron is presented and the unsupervised learning theory is explained and discussed, with particular attention being paid to its probability density function and cumulative distribution function approximation capability. Then a neural network formed by such neurons (the polynomial functional-link artificial neural network, or PFANN) is shown to be able to separate out linearly mixed eterokurtic source signals, i.e. signals endowed with either positive or negative kurtoses. In order to compare the performance of the proposed blind separation technique with those exhibited by existing methods, the mixture of densities (MOD) approach of Xu et al, which is closely related to PFANN, is briefly recalled; then comparative numerical simulations performed on both synthetic and real-world signals and a complexity evaluation are illustrated. These results show that the PFANN approach gives similar performance with a noticeable reduction in computational effort.

Artificial Intelligence↗
PubMed1995

Inference of population subdivision from the VNTR distributions of New Zealanders.

A population sample from people of diverse ethnic origins living in New Zealand serves as a database to test methods for inference of population subdivision. The initial null hypothesis, that the population sample is homogeneous across ethnic groups, is easily rejected by likelihood ratio tests. Beyond this, methods for quantifying subdivision can be based on the probability of drawing alleles identical by descent (FST), probabilities of matching multiple locus genotypes, and occurrence of unique alleles. Population genetic theory makes quantitative predictions about the relation between FST, population sizes, and rates of migration and mutation. Some VNTR loci have mutation rates of 10(-2) per generation, but, contrary to theory, we find no consistent association between the degree of population subdivision and mutation rate. Quantification of population substructure also allows us to relate the magnitudes of genetic distances between ethnic groups in New Zealand to the colonization history of the country. The data suggests that the closest relatives to the Maori are Polynesians, and that no severe genetic bottleneck occurred when the Maori colonized New Zealand. One of the central points of contention regarding the application of VNTR loci in forensics is the appropriate means for estimating match probabilities. Simulations were performed to test the merits of the product rule in the face of subpopulation heterogeneity. Population heterogeneity results in large differences in estimates of multilocus genotype frequencies depending on which subpopulation is used for reference allele frequencies, but, of greater importance for forensic purposes, no five locus genotype had an expected frequency greater than 10(-6). Although this implies that a match with an innocent individual is unlikely, in a large urban area such chance matches are going to occur.

Alleles↗
PubMed2003

Framework for bioethical assessment of an article on therapy.

OBJECT: Frameworks for scientific assessment of articles on therapy published in the medical literature have become available and will likely enhance the quality of medical research that is published in peer-reviewed journals. Comprehensive frameworks do not exist for the assessment of bioethical issues pertaining to research on human volunteers. METHODS: The authors have developed a framework consisting of ethical dimensions or questions that they suggest should be applied to assess the bioethical integrity of articles on therapy. Thirteen questions were developed and discussed in the context of current bioethical principles, and examples were applied where possible. CONCLUSIONS: The simple framework the authors have developed offers a method to assess key bioethical issues surrounding an article on therapy and probably defines the minimum standard to which such articles should be held. Many ethical questions cannot yet be answered based on available information or bioethical theories. The authors are not suggesting that their framework is comprehensive; refinements and individualization of it to fit specific studies are probably required by each clinician-researcher who designs a therapy trial and reports its results.

Bioethical Issues↗
PubMed1998

Immunoperoxidase evaluation of lichen planus biopsies for hepatitis C virus.

BACKGROUND: Lichen planus is a papulosquamous dermatosis which has recently been linked to infection with hepatitis C virus. It is unclear whether or not viral antigens may be present in the cutaneous lesions of lichen planus. MATERIALS AND METHODS: Twenty-five paraffin-embedded samples of glabrous lichen planus were evaluated using immunoperoxidase staining for the presence of hepatitis C virions. Control tissues consisted of hepatitis C-infected hepatic tissue (n = 2), normal hepatic tissue (n = 2), normal human skin (n = 1), and two cutaneous biopsies of lichen planus from persons known to be infected with hepatitis C. RESULTS: The sections of hepatitis C-infected liver tissue stained positive for hepatitis C virions. The 25 biopsies of glabrous lichen planus, the two biopsies of lichen planus from hepatitis C patients, the two sections of normal liver, and the one normal skin sample all failed to take up the stain. CONCLUSIONS: Cutaneous lesions of lichen planus are more probably reactive to the underlying infection than a manifestation of skin involvement by this disease. This theory is supported by the histologic findings in a lichenoid drug eruption, which are virtually identical to those of idiopathic lichen planus. Insufficient sensitivity by the immunoperoxidase procedure used is a possible explanation for our results; however, it appears more probable that no virus exists at the sites of cutaneous involvement.

Biopsy↗
PubMed1986

Multi-type Galton-Watson process as a model for proliferating human tumour cell populations derived from stem cells: estimation of stem cell self-renewal probabilities in human ovarian carcinomas.

A mathematical model for proliferation of tumour cell populations is developed. The cell population is assumed to be organized in a hierarchy of decreasing proliferative potential and increasing degree of differentiation. Using some elements of the theory of Multi-type Galton-Watson processes, a method is proposed for the estimation of Psr, the probability of self-renewal of tumour stem cells, from the experimental distribution of clonal unit sizes obtained in cell culture studies. Six data sets from patients with advanced adenocarcinoma of the ovary are used to demonstrate the method. Reasonable estimates are obtained, and the theoretical colony size distributions predicted by the model appear to be in good qualitative agreement with the experimental ones, and lend support to a stem cell model of tumour growth. The possible significance of Psr as a prognostic factor is briefly discussed.

Cell Division↗
PubMed2003

Optimizing admissions to an intensive care unit.

This paper presents a model for optimizing admissions to an intensive care unit (ICU) where the objective is to maximize the expected incremental number of lives saved from operating the ICU. The probability distribution of the number of occupied ICU beds is modeled using queueing theory. Three different admissions policies are considered: first come first served (FCFS), first come firstserved for all referrals whose expected incremental survival benefits gained from ICU admission exceed some hurdle (FCFS-H), and first come first served for all referrals whose expected incremental survival benefits exceed a bed specific hurdle (BSH) that depends upon the number of occupied beds (FCFS-BSH). The model is applied to data describing patients referred to the ICU at Jerusalem's Hebrew University-Hadassah Hospital. After statistically estimating the distribution of expected incremental survival benefits among those referred to the ICU, we show that if only those referrals where ICU admission would improve the probability of survival by at least 19.4 percentage points were admitted, an additional 18 statistical lives would be saved annually compared to the FCFS policy, a relative life saving improvement of 17.9%. Implementing the more complex optimal bed specific hurdle policy would save an additional 1.4 statistical lives annually beyond what can be achieved with FCFS-H, a marginal improvement of only 1.2%.

Decision Support Techniques↗
PubMed1993

Bursts of periodontal destruction and remission, percolation phase shifts, and chaos.

Bursts of periodontal destruction are modelled as percolation-driven phase shift events. Percolation theory, though widely used to study the flow of liquids through porous nonliving materials (e.g., soils and rocks), can be applied to bacterial or toxicological penetration of living tissue in only an approximate sense. However, it seems necessary that some mechanism, fundamentally similar to the percolation phase shift, is required to adequately account for bursts. Percolation theory is therefore offered as a framework for considering such events. A principal finding of percolation theory is the existence of percolation thresholds, such that when P, the independent probability that a subregion is susceptible to an invading substance, is above the threshold, the region will percolate or allow flow through, and when P is below the threshold the region will not percolate. This instantaneous transition, from a structure that will permit percolation to one that will not, is described as a phase shift. In addition, the value of P is postulated to depend on multiple factors which might constitute a chaotic system. The nonproportionality of a percolation phase shift and the nonpredictability of any specific chaotic event suggest that reliable burst predictors may, in theory, not be possible at the level of the individual site.

Disease Susceptibility↗
PubMed1983

Probabilistic automata as a model for epigenesis of cellular networks.

Probabilistic automata are compared with deterministic ones in simulations of growing networks made of dividing interconnected cells. On examples of chains, wheels and tree-like structures made of large numbers of cells it is shown that the number of necessary states in the initial generating cell automaton is reduced drastically when the automaton is probabilistic rather than deterministic. Since the price being paid is a decrease in the accuracy of the generated network, conditions under which reasonable compromises can be achieved are studied. They depend on the degree of redundancy of the final network (defined from the complexity of a deterministic automaton capable of generating it with maximum accuracy), on the "entropy" of the generating probabilistic automaton, and on the effects of different inputs on its transition probabilities (as measured by its "'capacity" in the sense of Shannon's information theory). The results are used to discuss and make more precise the notion of biological specificity. It is suggested that the weak metaphor of a genetic program, classically used to account for the role of DNA in specific genetic determinations, is replaced by that of inputs to biochemical probabilistic automata.

Biological Evolution↗
PubMed1994

A turning point in mathematical learning theory.

This target article by Estes (1950) sparked the mathematical learning theory movement, which took seriously the goal of predicting quantitative details of behavioral data from standard learning experiments. The central constructs of Estes's theory were stimulus variability, stimulus sampling, and stimulus-response association by contiguity, all cast within a framework enabling predictions of response probabilities and latencies. The math models enterprise flourished during the period 1950-1975 and provided successful quantitative accounts of data from Pavlovian and instrumental conditioning, probability learning, verbal learning, concept identification, and other standard learning paradigms. The techniques have been assimilated into the armamentarium of theoretical psychology. Stimulus sampling theory has faded away as it has been transformed into modern descendants such as connectionism and information-processing models of cognition.

History, 20th Century↗
PubMed2000

Levy diffusion in a force field, huber relaxation kinetics, and nonequilibrium thermodynamics: H theorem for enhanced diffusion with Levy white noise

A characteristic functional approach is suggested for Levy diffusion in disordered systems with external force fields. We study the overdamped motion of an ensemble of independent particles and assume that the force acting upon one particle is made up of two additive components: a linear term generated by a harmonic potential and a second term generated by the interaction with the disordered system. The stochastic properties of the second term are evaluated by using Huber's approach to complex relaxation [Phys. Rev. B 31, 6070 (1985)]. We assume that the interaction between a moving particle and the environment can be expressed by the contribution of a large number of relaxation channels, each channel having a very small probability of being open and obeying Poisson statistics. Two types of processes are investigated: (a) Levy diffusion with static disorder for which the fluctuations of the random force are frozen and last forever and (b) diffusion with strong dynamic disorder and independent Levy fluctuations (Levy white noise). In both cases we show that the probability distribution of the position of a diffusing particle tends towards a stationary nonequilibrium form. The characteristic functional of concentration fluctuations is evaluated in both cases by using the theory of random point processes. For large times the fluctuations of the concentration field are stationary and the corresponding probability density functional can be evaluated analytically. In this limit the fluctuations depend on the distribution of the total number of particles but are independent of the initial positions of the particles. We show that the logarithm of the stationary probability functional plays the role of a nonequilibrium thermodynamic potential, which has a structure similar to the Helmholtz free energy in equilibrium thermodynamics: it is made up of the sum of an energetic component, depending on the external mechanical potential, and of an entropic component, depending on the concentration field. We show that the conditions for the existence and stability of the nonequilibrium steady state, which emerges for large times, can be expressed in terms of the stochastic potential. For Levy white noise the average concentration field can be expressed as the solution of a fractional Fokker-Planck equation. We show that the stochastic potential is a Lyapunov function of the fractional Fokker-Planck equation, which ensures that all transient solutions for the average concentration field tend towards a unique stationary form.

Journal Article↗
PubMed1988

X-ray or gamma-ray leukemogenesis at Hiroshima and Nagasaki.

Because of the uncertainty in dosimetry at the Japanese cities, I have recalculated the probability of x-ray or gamma-ray leukemogenesis using the revised doses given by the Livermore group. The theory is of the two hit type. The first hit damages DNA repair capability of base damage. The second hit causes derepression of a two repressor system. Inactivation of the first repressor permits synthesis of the second which will repress the expression of the leukocyte maturation gene. In comparing the observed data, I convert data expressed as mortality per year to leukemia incidence. I also supply evidence of the lack of the importance of chromosomal aberration and consider CML, AML, and ALL data lumped together. Agreement between theory and observation is good.

DNA↗
PubMed1997

Electron transfer and electronic energy relaxation under high hydrostatic pressure.

The following question has been addressed in the present work. How external high (up to 8 kbar) hydrostatic pressure acts on photoinduced intramolecular electron transfer and on exciton relaxation processes? Unlike phenomena, as they are, have been studied in different systems: electron transfer in an artificial Zn-porphyrin-pyromellitimide (ZnP-PM) supramolecular electron donor-acceptor complex dissolved in toluene measured at room temperature; exciton relaxation in a natural photosynthetic antenna protein called FMO protein measured at low temperatures, between 4 and 100 K. Spectrally selective picosecond time-resolved emission technique has been used to detect pressure-induced changes in the systems. The following conclusions have been drawn from the electron transfer study: (i) External pressure may serve as a potential and sensitive tool not only to study, but also to control and tune elementary chemical reactions in solvents; (ii) Depending on the system parameters, pressure can both accelerate and inhibit electron transfer reactions; (iii) If competing pathways of the reaction are available, pressure can probably change the branching ratio between the pathways; (iv) The classical nonadiabatic electron transfer theory describes well the phenomena in the ZnP-PM complex, assuming that the driving force or/and reorganisation energy depend linearly on pressure; (v) A decrease in the ZnP-PM donor-acceptor distance under pressure exerts a minor effect on the electron transfer rate. The effect of pressure on the FMO protein exciton relaxation dynamics at low temperatures has been found marginal. This may probably be explained by a unique structure of the protein [D.E. Trondrud, M.F. Schmid, B.W. Matthews, J. Mol. Biol. 188 (1986) p. 443; Y.-F. Li, W. Zhou, E. Blankenship, J.P. Allen, J. Mol. Biol., submitted]. A barrel made of low compressibility beta-sheets may, like a diving bell, effectively screen internal bacteriochlorophyll a molecules from external influence of high pressure. The origin of the observed slow pico = and subnanosecond dynamics of the excitons at the exciton band bottom remains open. The phenomenon may be due to weak coupling of phonons to the exciton states or/and to low density of the relevant low-frequency ( approximately 50 cm(-1)) phonons. Exciton solvation in the surrounding protein and water-glycerol matrix may also contribute to this effect. Drastic changes of spectral, kinetic and dynamic properties have been observed due to protein denaturation, if the protein was compressed at room temperature and then cooled down, as compared to the samples, first cooled and then pressurised.

Journal Article↗
PubMed2004

Interrupted escape and the emergence of exponential relaxation.

A simple statistical theory of irreversible processes in a subsystem coupled to (or "interrupted" by) a stochastic bath is formulated. The theory does not explicitly invoke time scale separation that underlies the standard description of nonequilibrium phenomena and is intrinsic to the concept of quasiequilibrium in the canonical ensemble. Arbitrary statistics and speed of bath fluctuations are straightforwardly treated by the theory. Except in the case of an extremely slow, nonequilibrium bath, the ultimate statistics of interrupted escape are shown to be Poisson, which is solely a consequence of the stationary nature of interactions in a sufficiently dense system. In the limit of a fast bath, the corresponding relaxation rate is shown to equal the initial rate of decay, thus validating a wide class of Golden Rate type expressions at long times. This true exponentiality thus appears when the time scale separation takes place. The theory also applies to a number of specific phenomena including transport in a fluctuating or disordered medium, gated reactions, the line shape theory, and the quantum Zeno effect. The general nature of motional narrowing phenomena is demonstrated and related to the bath mediated slowing down of a decay process with a nearly deterministic uninterrupted escape probability. The corresponding survival probability is shown also to exhibit discernible oscillations around the exponential background. Mathematical tools necessary for using the theory in specific applications are exposed in some detail.

Journal Article↗
PubMed2002

Microstructure and velocity of field-driven solid-on-solid interfaces: analytic approximations and numerical results.

The local structure of a solid-on-solid interface in a two-dimensional kinetic Ising ferromagnet or attractive lattice-gas model with single-spin-flip Glauber dynamics, which is driven far from equilibrium by an applied field or chemical potential, is studied by an analytic mean-field, nonlinear-response theory [P. A. Rikvold and M. Kolesik, J. Stat. Phys. 100, 377 (2000)], and by dynamic Monte Carlo simulations. The probability density of the height of an individual step in the surface is obtained, both analytically and by simulation. The width of the probability density is found to increase dramatically with the magnitude of the applied field, with close agreement between the theoretical predictions and the simulation results. Excellent agreement between theory and simulations is also found for the field dependence and anisotropy of the interface velocity. The joint distribution of nearest-neighbor step heights is obtained by simulation. It shows increasing correlations with increasing field, similar to the skewness observed in other examples of growing surfaces.

Journal Article↗
PubMed1994

Premelting base pair opening probability and drug binding constant of a daunomycin-poly d(GCAT).poly d(ATGC) complex.

We calculate room temperature thermal fluctuational base pair opening probability of a daunomycin-poly d(GCAT).poly d(ATGC) complex. This system is constructed at an atomic level of detail based on x-ray analysis of a crystal structure. The base pair opening probabilities are calculated from a modified self-consistent phonon approach of anharmonic lattice dynamics theory. We find that daunomycin binding substantially enhances the thermal stability of one of the base pairs adjacent the drug because of strong hydrogen bonding between the drug and the base. The possible effect of this enhanced stability on the drug inhibition of DNA transcription and replication is discussed. We also calculate the probability of drug dissociation from the helix based on the selfconsistent calculation of the probability of the disruption of drug-base H-bonds and the unstacking probability of the drug. The calculations can be used to determine the equilibrium drug binding constant which is found to be in good agreement with observations on similar daunomycin-DNA systems.

Base Composition↗
PubMed1997

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Adult↗