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PubMed1992

DNA damage caused by ionizing radiation.

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions, which is known to be important in some situations.

Animals↗

PubMed2002

Analysis of the picosecond magneto-optical phenomena in scattering media of biological interest.

The behaviour of a magneto-optically active biological-like medium under picosecond optical excitation is analysed. The new technique is based on the fact that photons trapped in multiple scattering events inside the magneto-optical medium leave the medium with larger induced rotation angles, as they travel longer distances. Two- and three-dimensional displacements of the photons in the medium are separately analysed. The dependence of this effect on the applied magnetic field strength, the value of the magneto-optical constant of the medium and the standard deviation of the statistical distribution of the photons scattered inside the turbid medium are studied. The best values for the magnetic field and optical parameters of the biological medium are proposed for the experimental observation of the picosecond magneto-optical phenomena in scattering media of biological origin. We also make some prospective studies to evaluate the potential application of the magneto-optical effect as a tool for optical tissue biopsy. Values for the optimum magnetic field intensities and for the expected experimental sensitivity in diverse conditions are reported.

Biophysics↗

PubMedDate not supplied

[Exposure levels of persons involved in cleaning-up after the Chernobyl AES accident and included in the Russian State Medical and Dosimetric Registry].

Theoretical and practical problems related to the dosimetric data verification for recovery workers at the Chernobyl NBB are considered. Approaches and conclusions presented in the paper of L.A. Ilyin at al, (1). By using probability theory it was clearly that the method of dose verification developed in the reviewed paper and based on delta-entropy of statistical distribution failed to be scientifically founded. It does not permit to prove the existence of non-random component in random sampling without additional assumptions. The main conclusion of the reviewed paper, that 60% of individual doses included in the all-russia state medical and dosimetric state registry (ARMDSR) differ from the real exposure doses, is analysed and quantitatively estimated for several group of recovery workers. Our results present evidence that ARMDSR data do not contain a considerable part of "distorted" values even if the above mentioned method to take as valid.

Humans↗

PubMed2006

Simulating deformations of MR brain images for validation of atlas-based segmentation and registration algorithms.

Simulated deformations and images can act as the gold standard for evaluating various template-based image segmentation and registration algorithms. Traditional deformable simulation methods, such as the use of analytic deformation fields or the displacement of landmarks followed by some form of interpolation, are often unable to construct rich (complex) and/or realistic deformations of anatomical organs. This paper presents new methods aiming to automatically simulate realistic inter- and intra-individual deformations. The paper first describes a statistical approach to capturing inter-individual variability of high-deformation fields from a number of examples (training samples). In this approach, Wavelet-Packet Transform (WPT) of the training deformations and their Jacobians, in conjunction with a Markov random field (MRF) spatial regularization, are used to capture both coarse and fine characteristics of the training deformations in a statistical fashion. Simulated deformations can then be constructed by randomly sampling the resultant statistical distribution in an unconstrained or a landmark-constrained fashion. The paper also describes a model for generating tissue atrophy or growth in order to simulate intra-individual brain deformations. Several sets of simulated deformation fields and respective images are generated, which can be used in the future for systematic and extensive validation studies of automated atlas-based segmentation and deformable registration methods. The code and simulated data are available through our Web site.

Algorithms↗

PubMed2004

PLASS: protein-ligand affinity statistical score--a knowledge-based force-field model of interaction derived from the PDB.

We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.

Computational Biology↗

PubMed2003

A versatile wavelet domain noise filtration technique for medical imaging.

In this paper, we propose a robust wavelet domain method for noise filtering in medical images. The proposed method adapts itself to various types of image noise as well as to the preference of the medical expert; a single parameter can be used to balance the preservation of (expert-dependent) relevant details against the degree of noise reduction. The algorithm exploits generally valid knowledge about the correlation of significant image features across the resolution scales to perform a preliminary coefficient classification. This preliminary coefficient classification is used to empirically estimate the statistical distributions of the coefficients that represent useful image features on the one hand and mainly noise on the other. The adaptation to the spatial context in the image is achieved by using a wavelet domain indicator of the local spatial activity. The proposed method is of low complexity, both in its implementation and execution time. The results demonstrate its usefulness for noise suppression in medical ultrasound and magnetic resonance imaging. In these applications, the proposed method clearly outperforms single-resolution spatially adaptive algorithms, in terms of quantitative performance measures as well as in terms of visual quality of the images.

Algorithms↗

PubMed1987

Quantification and localization of galactose-specific binding sites in rat liver during postnatal development.

We investigated the number and distribution of galactose-specific binding sites in developing livers from suckling rats of various ages using Lac-BSA-Au5 (lactosylated bovine serum albumin adsorbed onto colloidal gold particles 5 nm in diameter) as electron-dense ligand, and performing transmission electron microscopy of the specimen. It has been reported that the number of galactose-specific binding sites increases rapidly during organ development post partum (p.p.) and this was ascribed to hepatocyte receptor increase only. We now have investigated in in situ and in vitro experiments whether the binding sites of identical sugar specificity but located on sinusoidal cells show the same increase in expression or are independently regulated. We therefore quantified the number of particles bound by isolated hepatocytes and liver macrophages and found a gradual increase of both binding activities with age, the binding levels of adult liver cells being reached at day 15 p.p. This was confirmed with experiments using in situ prefixed organs thus proving the validity of this finding also for the intact organ. In both sets of experiments--in vitro as well as in vivo--ligand was found binding statistically distributed as single particles on hepatocytes of all ages, whereas on liver macrophages the binding pattern changed during development. On liver macrophages from rats 15 days of age ligand binding occurs in the preclustered pattern described for macrophages from adult rat livers whereas liver macrophages of newborn rats express a different binding pattern: they bind the ligands mostly as single particles with only few and small microaggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2004

Comparison of late luminal loss response pattern after sirolimus-eluting stent implantation or conventional stenting.

BACKGROUND: We investigated the pattern of late luminal loss after sirolimus-eluting or bare stent implantation. METHODS AND RESULTS: The study population comprised 238 patients treated with sirolimus-eluting stents and 526 patients treated with conventional stents. The distribution of late loss of sirolimus stents was largely skewed to the right and differed from the distribution for bare stents. When divided according to the presence of binary restenosis (diameter stenosis >50%), restenotic lesions in the bare stent group (26.0%) had a late loss of 1.40+/-0.64 mm and in the sirolimus group (7.9%) of 1.16+/-0.76 mm. Nonrestenotic lesions in the bare stent group had a late loss of 0.58+/-0.44 mm, whereas the late loss of nonrestenotic lesions in the sirolimus group remained close to zero (-0.05+/-0.33 mm). Differences between poststenting and follow-up measurements in the sirolimus group (late loss) resembled variations observed in repeated angiographic measurements, as assessed from a random sample of 30 segments measured repeatedly. After multivariate adjustment, stent type did not influence the degree of late loss in restenotic lesions. However, nonrestenotic bare stents had a significantly larger estimated luminal loss (0.58 mm; 95% CI, 0.52 to 0.65) than sirolimus-eluting stents, for which the predicted late loss was almost 0 (-0.04 mm; 95% CI, -0.10 to 0.02). CONCLUSIONS: The pattern of late loss after sirolimus-eluting stent implantation follows a peculiar behavior, different from lesions treated with conventional stents. Whether this is explained by an unusual statistical distribution or a biological all-or-none response of restenosis after sirolimus-eluting stenting remains to be investigated.

Aged↗

PubMed1969

Three factors limiting the reliable detection of light by retinal ganglion cells of the cat.

1. Responses of cat retinal ganglion cells have been examined with a view to specifying the characteristics that limit the detection of light stimuli.2. Threshold is defined as the weakest stimulus that can be reliably detected by examination of the output from a retinal ganglion cell; it depends upon (a) the quantum/spike ratio, which is the mean number of additional quantal absorptions required to produce an additional impulse, (b) the temporal course of the response, which determines the time interval within which the maintained discharge is modified, and (c) the statistical distribution of the number of impulses that occur in this time interval in the absence of the stimulus.3. The quantum/spike ratio changes greatly when adapting luminance is changed, and this is the predominant factor accounting for changes in increment threshold.4. The time course of the response changes with adaptation level and area of the stimulus. This may account for the changes in temporal integration that occur in analogous psychophysical experiments.5. Changes in the irregularity of the maintained discharge also affect the threshold of single ganglion cells. This is only a minor factor in the conditions of most of our experiments, but it may be important when unstabilized images and non-equilibrium adaptation conditions are encountered.

Action Potentials↗

PubMed2006

Multisubject activation detection in fMRI by testing correlation of data with a signal subspace.

In this article, a generalized likelihood ratio test is proposed to assess the correlation between multisubject functional MRI (fMRI) time series and bases of a signal subspace for detecting the existence of group activation in each voxel of the brain. The signal subspace is generated by a design matrix using the time series of the desired effects. The proposed method leads to testing the product of eigenvalues of a specific matrix. The eigenvector corresponding to the largest eigenvalue is the weighting vector for the linear combination of time series of various subjects that has the maximum correlation with the signal subspace. In another method, namely, canonical correlation analysis, the largest eigenvalue of the above matrix is tested for activation detection. Surrogate data on resting state (no activation) are generated by randomization and used to estimate the statistical distribution of these parameters under the null hypothesis condition. A postprocessing step is applied to prevent false detection of voxels that are not sufficiently active (among subjects) by defining a minimum ratio for the active population. The proposed methods are applied on simulated and experimental fMRI data, and the results are compared with those of the general linear model (GLM; using the SPM and FMRISTAT toolboxes). The proposed methods showed higher detection sensitivity as compared with the GLM for activation detection in simulated data. Similarly, they detected more activated regions than did the GLM from multisubject experimental fMRI data on a visual (sensorimotor) event-related task.

Algorithms↗

PubMed2003

The relationship between water concentrations and individual uptake of chloroform: a simulation study.

We simulated the relationship between water chloroform concentrations and chloroform uptake in pregnant women to assess the potential extent of exposure measurement error in epidemiologic studies of the health effects of exposure to water disinfection by-products. Data from the literature were used to assign statistical distributions to swimming pool chloroform concentrations, frequency and duration of swimming, showering and bathing, and average tap water consumption. Measured increases in blood chloroform concentrations after these activities were used to estimate average uptake per microgram per liter chloroform in the water, per minute spent in the activity or per liter consumed. Given average tap water chloroform concentrations from a U.K. epidemiologic study, an average daily uptake over 90 days was simulated for 300,000 mothers. The correlation between simulated uptakes and home tap chloroform concentration was 0.6. Mothers who swam regularly received far greater doses than did nonswimmers. Results suggest there will be considerable attenuation in risk estimates and/or power loss in epidemiologic studies if the putative agent is chloroform.

Adult↗

PubMed2000

Statistical discrimination of natural modes of motion in rat exploratory behavior.

We analyze the locomotor behavior of the rat during exploration, and show that digitally collected data (time series of positions) provide a sufficient basis for establishing that the rat uses several distinct modes of motion (first, second, third, and sometimes fourth gear). The distinction between these modes is obtained by first segmenting the time series into sequences of data points occurring between arrests (as ascertained within the resolution of the data acquisition system). The statistical distribution of the maximal amount of motion occurring within each of these episodes is then analyzed and shown to be multi modal. This enables us to decompose motion into distinct modes. In one application of this decomposition we show that the ethological ad hoc notion of stopping behavior corresponds to progression without leaving first gear. We do so by showing that the spatial spread of such progressions is confined to a small 20-50 cm range in a 6.5 m diameter arena. This provides a justification for a construct of 'staying in place'. This construct is not defined in terms of position in objective space, but purely in terms of the rat's own behavior. We test the generality of our method by applying it to mouse exploratory behavior.

Animals↗

PubMed2005

Material sensitivity study on lumbar motion segment (L2-L3) under sagittal plane loadings using probabilistic method.

OBJECTIVE: In this study, the probabilistic responses of a three-dimensional finite element L2-L3 motion segment, with and without posterior elements, tested under sagittal plane loadings, are presented. Understanding the effect of biologic uncertainties and variations on the biomechanical response provides an insight into spinal behavior under normal and degenerated conditions. METHODS: The biologic variability of 19 spinal components (nucleus, annulus, ligament, cortical/cancellous bone, endplate, and ligaments) in the motion segment was incorporated using statistical distributions into the model. A total of 2000 runs were performed using Monte Carlo probabilistic algorithms to compute the probabilistic response. RESULTS: This study establishes the relative importance of the spinal components in resisting the loading modes. The results show that for an intact motion segment, posterior ligaments are more dominant than intervertebral disc in resisting flexion moment. In extension, the capsular ligaments were found to be the most influential parameter. The intervertebral disc (ie, nucleus and annulus) affects the angular response of the disc body segment more than the hard tissues (ie, cortical and cancellous bone). CONCLUSIONS: The application of the probabilistic analysis provides a new approach whereby the influences of inherent uncertainties and variations in biologic structures can be studied and the biomechanical response assessed.

Finite Element Analysis↗

PubMed1983

Principal component analysis: a suitable method for the 3-dimensional study of the shape, dimensions and orientation of dendritic arborizations.

Our study proposes an objective method of describing 3-dimensional dendritic arborizations of neurons in the best possible conditions. The method is based upon a particular exploitation of statistical "principal component analysis". For each arborization, 3 principal axes are calculated which are its axes of inertia. The first two axes define the "principal plane" of the arborization. The shape of the arborization is determined from the statistical distribution of its dendritic points along each of these axes. Shapes are quantified by using an "index of axialization" (a) and an "index of flatness" (p) both of which may vary from zero to 1. The dimensions of the arborization, "length" (1), "width" (w) and "thickness" (t) are also measured along the principal axes. Orientation of arborizations is quantified by considering the orientation of the first principal axis for axialized arborization (a close to 1) and/or the orientation of the principal plane for flattened arborizations (p close to 1). In both cases 2 angles (azimuth and polar angle) are calculated. For spherical arborizations (a and p close to 1), no orientation is significant. The significance level of the defined orientations is evaluated from the values of the shape indices. Several examples are illustrated and other existing methods are discussed.

Animals↗

PubMed1989

Probabilistic approach to obtain hit-size effectiveness functions which relate microdosimetry and radiobiology.

A probabilistic approach has been developed to relate microdosimetry, biological effects, and radiation quality. It is used to derive, and subsequently apply, microdosimetry-based cellular response functions for different biological end points of relevance for radiological protection. The approach makes use of measurable microdosimetry spectra and avoids assumptions concerning the course of mechanisms of radiation action. Instead, it postulates a response function that is, and behaves like, the cumulative probability that a subcellular target structure will respond to a specific target-averaged ionization density. Statistical distributions are applied and their parameters are evaluated to characterize the randomness involved in the localization of sensitive sites and in the reactivity of the whole sensitive structure. The resulting response functions can be used for prediction of the effects of low-level radiation. Such predictions for some selected effects of a stochastic nature (mutagenesis, chromosome abnormalities, etc.) are presented as relative biological effectiveness values based on low doses of radiations with a wide range of linear energy transfer and compared with various quality factor specifications. Cellular response relationships, termed hit-size effectiveness functions, can also be applied directly in radiation protection metrology by incorporating them into the software used to process the readings of microdosimetric spectrometers. The derivation of the functions, rather than their uses in radiation protection, is the principal subject of this report.

Animals↗

PubMed1986

Catalytic enzyme activity concentration in plasma of man, sheep, dog, cat, rabbit, guinea pig, rat and mouse. Approach to a quantitative diagnostic enzymology, I. Communication.

For the most convenient laboratory animals in experimental medicine such as the sheep, dog, cat, rabbit, guinea pig, rat and mouse, the catalytic concentrations of seventeen enzymes and the protein and albumin concentrations in plasma were determined. The corresponding data for man were taken from the literature. The experimental conditions were selected so as to minimize the influence on catalytic activity, variance and statistical distribution pattern of such factors as handling procedures, the choice of blood drawing technique, the choice of anaesthetic agent for distinct species and the preparation procedure of plasma from the blood specimen. Because these considerations have been largely neglected to date in experimental enzymology, normal values for most enzymes require revision and were in some instances established for the first time in certain species. Our use of assay conditions, which were identical for all animal species, satisfies current requirements in clinical chemistry with respect to standardization and optimization of enzyme catalytic activity concentration measurement, and allowed comparison of these enzymes. The catalytic activities established this way will be the basis for a later comparative study of their kinetics of adjustment in plasma.

Adjuvants, Anesthesia↗

PubMed2002

Incorporating measures of variability and uncertainty into the prediction of in vivo hepatic clearance from in vitro data.

The existing procedures for quantitative in vitro-in vivo clearance prediction can be significantly biased either by totally neglecting the existing variability and uncertainty by using mean parameter values or by implementing Monte Carlo simulation with statistical distribution of the parameters reconstructed from very small sets of data. The aim of the present study is to develop a methodology for the prediction of in vivo hepatic clearance in the presence of semiquantitative or qualitative data and accounting for the existing uncertainty and variability. The method consists of two steps: 1) transformation of the information available into fuzzy sets (fuzzification); and 2) computation of the in vivo clearance using arithmetic operations with fuzzy sets. To illustrate the approach, rat hepatocyte and microsomal data for eight benzodiazepine compounds are used. A comparison with a standard Monte Carlo procedure is made. The methodology proposed can be used when Monte Carlo simulation may be biased or cannot be implemented. The obtained fuzzy in vivo clearance can be used subsequently in fuzzy simulations of pharmacokinetic models.

Animals↗

PubMed2005

Improved tracking of time-varying encoding properties of visual neurons by extended recursive least-squares.

Traditional approaches to characterizing the transformation from stimulus to response in sensory systems assume both stationarity of the stimulus and time-invariance of the stimulus/response mapping. However, recent studies of sensory function under natural stimulus conditions have demonstrated important features of neural encoding that are in violation of these assumptions. Many sensory neurons respond to changes in the statistical distribution of the stimulus that are characteristic of the natural environment with corresponding changes in their encoding properties. In this paper, an extended recursive least-squares (ERLS) approach to adaptive estimation from stimulus/response observations is detailed. The ERLS approach improves the tracking ability of standard RLS approaches to adaptive estimation by removing a number of assumptions about the underlying system and the stimulus environment. The ERLS framework also incorporates an adaptive learning rate, so that prior knowledge of the relationship between the stimulus and the adaptive nature of the system under investigation can be used to improve tracking performance. Simulated and experimental neural responses are used to demonstrate the ability of the ERLS approach to track adaptation of encoding properties during a single stimulus/response trial. The ERLS framework lends tremendous flexibility to experimental design, facilitating the investigation of sensory function under naturalistic stimulus conditions.

Action Potentials↗