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PubMed1992

Dimerization kinetics of the IgE-class antibodies by divalent haptens. II. The interactions between intact IgE and haptens.

Interactions between a monoclonal, DNP-specific IgE molecules (hybridoma A2) and divalent DNP-haptens in solution cause aggregation of the former predominantly into closed rings of two IgE and two divalent haptens (Schweitzer-Stenner, R., A. Licht, I. Lüscher, and I. Pecht. 1987. Biochemistry. 26:3602-3612). The time course of this process was now investigated by titrating the A2-IgE with divalent DNP-haptens having long and rigid oligoproline spacers (di(N epsilon-2,4-dinitrophenyl)-6-amino-hexanoate-aspartyl-(prolyl)n-L-ly- syl; n = 24, 27, 33). Binding was expressed in quenching of the IgE intrinsic tryptophan emission. As shown in the preceding paper, hapten addition to the IgE-A2 at rates faster than a distinct threshold value led to nonequilibrium titrations (NETs) from which kinetic processes slower than 2 s-1 can be resolved. Analysis of these titrations shows that the dimeric rings open at rates of approximately 10(-2) s-1, independent of the divalent hapten's spacer length. The ring closure rate, however, decreases with spacer length. The latter observation was qualitatively rationalized in terms of the diffusion process of a Gaussian chain which relates the ring closure rate constant to the expectation value for the distance between the free ends of the respective open chain.

Animals↗

PubMed2026

Volumetric bone marrow cellularity (VBMC) assessment from routinely processed trephines using three-dimensional x-ray histology and gaussian peak modelling.

Objective.Bone marrow cellularity is routinely estimated from a small number of two-dimensional histology sections, making assessment sensitive to section representativeness, processing artefacts and observer interpretation. Three-dimensional (3D) x-ray histology (XRH), using x-ray computed microtomography (µCT), enables non-destructive whole-block imaging of trephine biopsies. This study evaluated whether XRH combined with Gaussian peak modelling could provide a pragmatic whole-block volumetric bone marrow cellularity (VBMC) estimate from formalin-fixed paraffin-embedded (FFPE) trephine biopsy blocks.Approach.Six routinely processed FFPE bone marrow trephine blocks were imaged using µCT-based XRH at ∼15 µm spatial resolution. VBMC was defined as the red-marrow (RM) fraction of the marrow soft-tissue compartment, RM/(RM + intra-biopsy wax), with wax serving as the volumetric proxy for adipocyte/yellow marrow space. Whole-volume greyscale histograms were modelled using a three-peak Gaussian approach representing intra-biopsy wax, RM and demineralised trabecular matrix. Peak-height and area-under-the-curve metrics were compared with whole-volume 3D segmentation and clinical two-dimensional (2D) cellularity estimates.Main Results.Gaussian peak modelling successfully approximated the segmented tissue-phase distributions. The peak-height-derived VBMC metric showed the closest agreement with whole-volume 3D segmentation, with an average absolute percentage difference of 9.3%, compared with 18.6% for clinical expert 2D cellularity estimates. The area-under-the-curve metric followed similar trends but consistently overestimated VBMC. Clinical 2D cellularity broadly followed whole-biopsy trends but showed one discordant case not explained by slice-position sampling alone. XRH also enabled unrestricted virtual reslicing and visualisation of sectioning-associated artefacts prior to further microtomy.Significance.Pre-sectioning XRH combined with Gaussian peak modelling provides a rapid, segmentation-free route to volumetric cellularity estimation from intact clinical FFPE trephine blocks. The approach supports objective whole-biopsy assessment while remaining compatible with routine histopathology workflows, reflecting the expected limitations of section-based visual estimation despite its role as the current clinical standard. In the near term, it could provide a non-disruptive adjunct to conventional 2D cellularity reporting, pending larger validation studies.

Imaging, Three-Dimensional↗

PubMed1992

[Echodensitometry: a new echographic diagnostic possibility].

The determination and quantification of grey levels in the echography scale, designated by some authors Echodensitometry, is viewed as a new method for diagnosis using ultrasound techniques. This paper advances the results from a study conducted with an echographer equipped with an echographic density measuring device. This model analyzes the number of pixels in the image showing the most frequent level of grey. Normal and pathological parenchymatous urological organs (kidney, prostate and testicle) have been examined. Normal organs show a gaussian distribution of grey with a predominant level of typical grey for each of them. When affected by an acute inflammatory process the organs maintain their gaussian distribution but the predominant grey is lower (darker) due to the edema and the hyperaemia. When the inflammatory process becomes chronic, distribution, although somewhat irregular, is still gaussian but with higher predominance of grey (lighter) probably due to the fibrosis. The tumoral cases of our study also showed a gaussian curve even more irregular and with levels of variable grey. When specific areas of the tumour are analyzed the findings are very distinct depending on whether the areas are hypo or hyperechoic. Hyperechoic areas produce highly irregular maps. Research should be directed to provide more complex, although easy to perform systems of analysis which can correlate adequately with the histological study. It would be desirable that the equipment would be standardized to allow analysis of 'in vitro' images. If and when these objectives can be accomplished we would be able to venture into an echography histological diagnosis, something nowadays yet impossible.

Densitometry↗

PubMed1991

Periaqueductal gray spike trains recorded in frontal or horizontal mesencephalic brain slices from the rat.

Spontaneous spike trains were recorded from the periaqueductal gray matter (PAG) in frontal and horizontal mesencephalic slices in order to compare spontaneous activity of the slice preparation to previous in vivo records. The firing rates resembled those recorded in vivo. They were low notwithstanding the fact that the slicing procedure removed tonic inhibitory input to the PAG. The firing rates increased caudo-rostrally, a fact that had not been reported in vivo, and were lower in frontal sections. Several different spike trains were found, described and classified according to their temporal firing patterns. The spike sequences were usually simple stochastic processes, distributed as a Gaussian function with or without stochastic deletion of spikes.

Animals↗

PubMed1975

On the separation of semiperiodic superimposed point processes: application to electromyographic signals.

A method for the separation of semiperiodic (Gaussian probability distribution of intervals with moderate coefficient of variation) superimposed point processes, to be implemented on a digital computer is described. The efficiency of the filter used for the extraction of the underlying event sequences from the pooled array has been investigated by simulation. Approximately 80 percent of the events belonging to the underlying sequence to be extracted were recovered (with the addition of "impurity events"), still preserving the mean rate and coefficient of variation of the original indicidual sequence concerned. The program was used on an example of an actual electromyographic recording (comprised of a number of motor units discharging simultaneously), resolving the number of motor units involved, their mean rates, and the coefficient of variation of the individual action potential sequences.

Action Potentials↗

PubMed1979

Computed resolution and relative specific radioactivities of radiolabelled proteins synthesized by isolated gastric mucosal cells.

1. By radiolabelling, polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and fluorography, more than 50 soluble proteins in the molecular-weight range 15000-100000 were shown to continue to be synthesized after cells had been isolated from rat gastric mucosa. 2. Densitometric measurements of stained gels and fluorographic films were processed by computer to resolve individual overlapping Gaussian peaks corresponding to the protein bands. 3. Comparison of resolved peak areas of radioactivity and staining showed certain bands to have characteristically high relative specific radioactivities. 4. The computer programs (in FORTRAN) permit the analysis of a single densitometric trace or the simultaneous comparison of a corresponding pair of densitometric records of stained gels, or of fluorographic films, or a combination. Central processing unit time is used economically. 5. The programs identify the Gaussian components that contribute to the records and estimate their means, standard deviations and enclosed areas. These estimates are improved by a piecewise iterative method that minimizes the errors between the calculated and the experimental data. 6. Relative specific radioactivities are calculated as the normalized ratio of the area of a fluorographic film peak and the area of the corresponding stained gel peak. The computer programs have been deposited as Supplementary Publication SUP 50094 (55 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1978) 169, 5.

Animals↗

PubMed1992

Self-organizing maps: stationary states, metastability and convergence rate.

We investigate the effect of various types of neighborhood function on the convergence rates and the presence or absence of metastable stationary states of Kohonen's self-organizing feature map algorithm in one dimension. We demonstrate that the time necessary to form a topographic representation of the unit interval [0, 1] may vary over several orders of magnitude depending on the range and also the shape of the neighborhood function, by which the weight changes of the neurons in the neighborhood of the winning neuron are scaled. We will prove that for neighborhood functions which are convex on an interval given by the length of the Kohonen chain there exist no metastable states. For all other neighborhood functions, metastable states are present and may trap the algorithm during the learning process. For the widely-used Gaussian function there exists a threshold for the width above which metastable states cannot exist. Due to the presence or absence of metastable states, convergence time is very sensitive to slight changes in the shape of the neighborhood function. Fastest convergence is achieved using neighborhood functions which are "convex" over a large range around the winner neuron and yet have large differences in value at neighboring neurons.

Algorithms↗

PubMed1990

Hemispheric processing of spatial frequencies in two commissurotomy patients.

To test the hypothesis that in humans the left brain hemisphere is specialized for processing high spatial frequencies while the right hemisphere is specialized for processing low spatial frequencies, pairs of Gaussian windowed sinusoidal gratings were presented for 167 msec within the left and right visual fields of two commissurotomy patients. The gratings employed had spatial frequencies ranging from 1 to 8 cycles per degree, and horizontal or vertical orientations. The two gratings in each pair were identical in spatial frequency but could differ in orientation. Subjects reported if their orientations were the same or different. Twelve normal controls were also run. Accuracy data provides no indication of a relative advantage for high frequencies in the RVF or low frequencies in the LVF. One commissurotomy subject showed a trend in the reverse direction; the other was better with LVF presentations for all spatial frequencies. Control subjects failed to show a spatial frequency x visual field interaction. These outcomes suggest that at the processing stages required by the task, the hemispheres are not specialized for particular ranges of spatial frequencies.

Adult↗

PubMed1975

The inverse Gaussian distribution as a model of hospital stay.

Properties of the inverse gaussian distribution are presented with comments on fitting the distribution to lentgh-of-stay data. A conceptual framework for the hospitalization process is described; it suggests that the inverse gaussian distribution has considerable potential as both a descriptive and prescriptive model of length of stay, especially in the setting of psychiatric hospitals.

Humans↗

PubMed1990

Fitting density functions and diffusion tensors to three-dimensional drug transport within brain tissue.

In the research on drug transport within brain tissue, typical data sets consist of a collection of volume integrals from various locations in the brain, with each datum measuring the total amount of drug in a sample of tissue. These samples contain medically useful information about the extent and orientation of the distribution of the drug, but extracting this information requires some mathematical analysis. The method of analysis presented here performs a nonlinear regression on the data to fit a multivariate density function (for example, a Gaussian density) to model such transport processes as diffusion and dispersion. The principal components of that density then characterize the size and shape of the distribution of drug.

Algorithms↗

PubMed1992

Steady-state kinetics of solitary batrachotoxin-treated sodium channels. Kinetics on a bounded continuum of polymer conformations.

The underlying principles of the kinetics and equilibrium of a solitary sodium channel in the steady state are examined. Both the open and closed kinetics are postulated to result from round-trip excursions from a transition region that separates the openable and closed forms. Exponential behavior of the kinetics can have origins different from small-molecule systems. These differences suggest that the probability density functions (PDFs) that describe the time dependences of the open and closed forms arise from a distribution of rate constants. The distribution is likely to arise from a thermal modulation of the channel structure, and this provides a physical basis for the following three-variable equation: [formula; see text] Here, A0 is a scaling term, k is the mean rate constant, and sigma quantifies the Gaussian spread for the contributions of a range of effective rate constants. The maximum contribution is made by k, with rates faster and slower contributing less. (When sigma, the standard deviation of the spread, goes to zero, then p(f) = A0 e-kt.) The equation is applied to the single-channel steady-state probability density functions for batrachotoxin-treated sodium channels (1986. Keller et al. J. Gen. Physiol. 88: 1-23). The following characteristics are found: (a) The data for both open and closed forms of the channel are fit well with the above equation, which represents a Gaussian distribution of first-order rate processes. (b) The simple relationship [formula; see text] holds for the mean effective rat constants. Or, equivalently stated, the values of P open calculated from the k values closely agree with the P open values found directly from the PDF data. (c) In agreement with the known behavior of voltage-dependent rate constants, the voltage dependences of the mean effective rate constants for the opening and closing of the channel are equal and opposite over the voltage range studied. That is, [formula; see text] "Bursts" are related to the well-known cage effect of solution chemistry.

Batrachotoxins↗

PubMed2026

Dual-contrastive learning for spatial domain identification in spatial transcriptomics with STAMGC.

Spatial transcriptomics (STs) have become a valuable approach for understanding the growth and development of organisms. Despite the recent emergence of numerous ST models, accurately identifying spatial domains remains challenging owing to the trade-off between preserving local details and reducing noise. Here, we introduce STAMGC, which is a dual-contrastive learning framework built upon graph convolutional networks. This model leverages regional and topological contrastive learning to jointly optimize the model, effectively reducing the noise in spatial domain identification and enhancing the extraction of detailed features. In this study, Gaussian smoothing, originally developed in the image processing field, is introduced to process ST data, providing a foundation for region-level contrastive learning by mitigating spatial discontinuities of gene expression signals. Experimental results indicate that STAMGC outperforms existing methods across multiple data sets according to comprehensive evaluations. Furthermore, STAMGC not only identifies finer structures in the mouse brain but also brings new discoveries for human breast cancer research.

Journal Article↗

PubMed1992

Heterogeneous distributions and dispersive photodissociation rates of benzo[a]pyrene diol-epoxide enantiomer-DNA and -poly(dG-dC).poly(dG-dC) adducts.

Two types of heterogeneity of adducts are illustrated and discussed utilizing non-line narrowed (S2----S0 laser excitation) and line-narrowed (excitation into the (0,0) origin band) fluorescence spectra at low temperatures. The first type (type A) is due to structurally distinct and/or energetically inequivalent conformers. The second one (type B) is provided by an inhomogeneous environment of DNA and polynucleotides. In light of the above, the non-exponential photodissociation kinetics of the (+/-)-anti-BPDE-DNA and -polynucleotide adducts have been reanalyzed in terms of a dispersive first order chemical reaction, where the inhomogeneous effects are explicitly included. It is demonstrated that the DNA structure shows considerable inhomogeneous broadening, and that type B heterogeneity is responsible for the dispersive photodissociation process. The latter is accounted for by a Gaussian distribution of activation energies, with the center of the distribution at approximately 600 meV and the full width at half-maximum equal to approximately 50 meV (approximately 2 kT). Photolabile (+/-)-anti-BPDE-DNA and -polynucleotide adducts are identified as quasi-intercalated (site I) (+)- and (-)-cis-BPDE. The calculated concentrations of cis-BPDE adducts in DNA and polynucleotides from the kinetic data are in very good agreement with the cis-BPDE adduct concentrations obtained from the spectral and/or chemical analysis. The average photodissociation rate and the photodissociation quantum yield of cis- and trans-BPDE adducts are also estimated.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1991

Evaluation of likelihood ratios for complex genetic models.

Although methods for computing likelihoods for simple genetic models on large and complex pedigrees have been known for some time, and although methods for evaluating likelihoods for complex genetic models on small pedigrees have likewise been well known, likelihood evaluation for complex models given data on extended pedigrees has remained an intractable problem. The Gibbs sampler provides a method of Monte Carlo evaluation of likelihood ratios for complex models on extended and/or complex pedigrees. With increasing computer speeds, this approach provides a tractable and efficient approach to many such likelihood evaluation problems in linkage and segregation analysis. In this paper, however, the authors restrict attention to two basic building-blocks of the overall process. The first is the sequential computation of Gaussian likelihoods for multiple random-effects models on extended pedigrees. The second is the use of this in the Monte Carlo evaluation of likelihoods for the classical mixed model of segregation analysis. The implementation of the Gibbs sampler on pedigrees that permits this Monte Carlo evaluation is detailed. An example is then presented, and finally, in the context of this same example, it is also shown how linkage analysis for a quantitative trait falls within this same framework.

Female↗

PubMed1978

[A new method for elimination of artifacts produced by collimator septum effect in gamma-camera images (author's transl)].

Collimator artifacts may be present within the images produced by collimators whose septal width approaches the inherent resolution of the gamma-camera system. As the inherent resolution of the gamma-camera is improved, collimator artifacts become more prominent. The purpose of this study is to eliminate collimator artifacts from gamma-camera images. To eliminate the septum effect produced by high-energy parallel-hole collimators with thick septa, the following method was used: X and Y signals from the detector are made to ride on the triangular waves changing periodically, and resultant position signals obtained by this processing are applied to the corresponding deflection circuits in the CRT display. The oscillation amplitude of processed position signals can be regulated by the frequency and amplitude of the triangular waves. Regulation of the oscillation amplitude of position signals, which would produce maximum reduction of collimator artifacts, was to approach the spatial frequency responses of the overall processed line spread functions obtained experimentally to those of the Gaussian functions with FWHM equal to the geometric resolution calculated from the equation given by Gerber and Miller. In images of a pancreas phantom containing 131I, collimator artifacts were clearly seen in the unprocessed case, but were eliminated in the processed case.

Models, Theoretical↗

PubMedDate not supplied

[Helix-globule transitions of polypeptides selectively reacting with the interface].

An analytical theory of helix-coil transitions for polypeptides in a solution near a flat and homogeneous interface is given. The following cases were considered: a) only the helical parts are absorbtively active; b) only the coiled sections of the chain are active in adsorption. It has been shown that the binding of the polymer chain to the surface is a result of a phase transition of a second order, moreover in case a) the presence of a secondary structure abruptly increases the ability of the macromolecules to bind to the interface. This largely increases the stability of the helical structure of the chain and leads to a practically complete spiralization of the macromolecule. The profile of the conformational transitions was strictly asymmetrical which is typical for the phase transitions. In case b) the process of binding resembles the adsorbtion of the Gaussian coils. In this case the rate of spiralization of the chain decreases in the course of binding and the degradation of the secondary structure is significant even if the helical state in volume is stable. The profile of the transition remains qualitatively similar to the helix-coil transition in volume but is displaced to the region of larger equilibrium constants.

Models, Chemical↗

PubMed1989

Mean and quasideterministic equivalence for linear stochastic dynamics.

In linear, stochastic dynamics it is shown that the quasideterministic population size is equivalent to the mean population size. The quasideterministic dynamics are defined by the conditional infinitesimal mean of the process. The stochastic component of the dynamics includes both Gaussian and Poisson white noise, with amplitude coefficients proportional to the population size. Generalizations are given for nonautonomous coefficients and for distributed Poisson jump amplitudes. A counter example--an exactly integrable nonlinear jump model--shows that the equivalence result does not hold for nonlinear stochastic dynamics.

Linear Models↗

PubMed1977

[K+]o clearance in cortex: a new analytical model.

1. It has been suggested that passive diffusion is the principal mechanism of the clearance of locally elevated extracellular potassium, K+o, in the cerebral cortex. This concept was based on the assumption that elevated K+ could be modeled as a point source. In the present study, the functional role of passive diffusion was reevaluated in the anesthetized cat cortex following local electrical stimulation. 2. The initial spatial distribution of extracellular potassium activity, [K+]o, elevated by monopolar stimulation, could be modeled by a two-dimensional Gaussian function at and below the 500-micron cortical depth. Azimuthal symmetry around the stimulating electrode was assumed and cylindrical spatial coordinates were used. 3. The observed clearance of transiently elevated [K+]o as a function of space and time was much more rapid than that predicted by an analytical model consisting of the homogeneous diffusion equation whose initial condition was the Gaussian spatial distribution of [K+]o at the onset of the clearance process. 4. It is concluded that passive diffusion does not significantly contribute to the rapid clearance of locally elevated extracellular potassium in the cortex. Active uptake of potassium by cortical cells should be more seriously considered as being primarily responsible for the potassium clearance.

Adenosine Triphosphatases↗