Modeling and decomposition of HRV signals with wavelet transforms.
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Algorithms↗
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On the mechanism of stomatocyte-echinocyte transformations of red blood cells: experiment and theoretical model.
This study represents an attempt to achieve a better understanding of the stomatocyte-echinocyte transition in the shape of red blood cells. We determined experimentally the index of cell shape at various ionic strengths and osmolarities for native and trypsin-treated human erythrocytes. For every given composition of the outer phase, we calculated the ionic strength in the cells and the transmembrane electric potential using a known theoretical model. Next, we described theoretically the electric double layers formed on both sides of the cell membrane, and derived expressions for the tensions of the two membrane leaflets. Taking into account that the cell-shape index depends on the tension difference between the two leaflets, we fitted the experimental data with the constructed physicochemical model. The model, which agrees well with the experiment, indicates that the tension difference between the two leaflets is governed by the different adsorptions of counterions at the two membrane surfaces, rather than by the direct contribution of the electric double layers to the membrane tension. Thus, with the rise of the ionic strength, the counterion adsorption increases stronger at the outer leaflet, whose stretching surface pressure becomes greater, and whose area expands relative to that of the inner leaflet. Hence, there is no contradiction between the bilayer-couple hypothesis and the electric double layer theory, if the latter is upgraded to account for the effect of counterion-adsorption on the membrane tension. The developed quantitative model can be applied to predict the shape index of cells upon a stomatocyte-discocyte-echinocyte transformation at varying composition of the outer medium.
Adsorption↗
The cryofixation of isolated rat gastric mucosa provides new insights into the functional transformation of gastric parietal cells: an in vitro experimental model study.
Cryofixation is currently accepted as the best initial fixation step to preserve not only the fine structure but also the antigenicity of biological samples. To elucidate the functional transformation of gastric parietal cells, we have newly developed an in vitro experimental model, named the isolated gastric mucosa. In this study, acid secretion of the parietal cell was stimulated with histamine or inhibited with cimetidine, and the samples were cryofixed by plunge freezing for light microscopy or high-pressure freezing for electron microscopy. As a result, the organization of glandular cells was well-preserved and quite similar to freshly excised rat gastric mucosa for at least 2 h after isolation. Immunohistochemistry of H+/K+-ATPase demonstrated a translocation of H+/K+-ATPase from the cytoplasm to the apical membrane associated with histamine-stimulation. In cimetidine-treated mucosa, most of the parietal cells were morphologically in the resting state, showing numerous tubulovesicles in their cytoplasm. In contrast, histamine-stimulated parietal cells exhibited well-developed intracellular canaliculi lined with long microvilli. To the best of our knowledge, the present study is first to demonstrate an electron micrograph that strongly suggests a membrane fusion between the tubulovescile and the apical membrane. Moreover, a stimulation-associated translocation of ezrin was clearly shown from the cytoplasm to the apical region, corresponding to apical microvilli development in the isolated gastric mucosa model. We here describe the preparation of the isolated rat gastric mucosa model, which provides new insights into the functional transformation of parietal cells by the application of cryotechniques.
Animals↗
Model concept for nitrate and nitrite utilization during anoxic transformation in the bulk water phase of municipal wastewater under sewer conditions.
A two-stage anoxic transformation process, involving growth of biomass utilizing two types of different electron acceptors, namely nitrate and nitrite, has been observed. The present water quality modules established for sewer processes cannot account for the two-stage process. This paper outlines the development of a model concept that enables the two-stage anoxic transformation process to be simulated. The proposed model is formulated in a matrix form that is similar to the Activated Sludge Models and Sewer Process Model matrices. The model was successfully applied to simulate changes in nitrate and nitrite concentrations during anoxic transformations in the bulkwater phase of municipal wastewater.
Models, Chemical↗
A model of the early stages of the human visual system: functional and topological transformations performed in the peripheral visual field.
A model of the early stages of the visual system is presented, with particular reference to the region of the visual field outside the fovea and to the class of retinal and lateral geniculate nucleus cells which are most active in the processing of patter information (X-cells). The main neuroanatomical and neurophysiological properties taken into account are: the linear increase of the receptive fields diameter with eccentricity, the constancy of the overlap factor and the topological transformation operated upon the retinal image by the retino-cortical connection. The type of filtering taking place between the retina and the visual cortex is analyzed and some simulations are presented. It is shown that such a filtering is of a bandpass space variant type, with center frequencies that decrease from the center (i.e. the fovea) toward the periphery of the visual field. This processing is "form invariant" under linear scaling of the input. Moreover, considering the properties of the retino-cortical connection, it is shown that the "cortical images" undergo simple shifts whenever the retinal images are scaled or rotated.
Humans↗
Performance of statistical models to predict mental health and substance abuse cost.
BACKGROUND: Providers use risk-adjustment systems to help manage healthcare costs. Typically, ordinary least squares (OLS) models on either untransformed or log-transformed cost are used. We examine the predictive ability of several statistical models, demonstrate how model choice depends on the goal for the predictive model, and examine whether building models on samples of the data affects model choice. METHODS: Our sample consisted of 525,620 Veterans Health Administration patients with mental health (MH) or substance abuse (SA) diagnoses who incurred costs during fiscal year 1999. We tested two models on a transformation of cost: a Log Normal model and a Square-root Normal model, and three generalized linear models on untransformed cost, defined by distributional assumption and link function: Normal with identity link (OLS); Gamma with log link; and Gamma with square-root link. Risk-adjusters included age, sex, and 12 MH/SA categories. To determine the best model among the entire dataset, predictive ability was evaluated using root mean square error (RMSE), mean absolute prediction error (MAPE), and predictive ratios of predicted to observed cost (PR) among deciles of predicted cost, by comparing point estimates and 95% bias-corrected bootstrap confidence intervals. To study the effect of analyzing a random sample of the population on model choice, we re-computed these statistics using random samples beginning with 5,000 patients and ending with the entire sample. RESULTS: The Square-root Normal model had the lowest estimates of the RMSE and MAPE, with bootstrap confidence intervals that were always lower than those for the other models. The Gamma with square-root link was best as measured by the PRs. The choice of best model could vary if smaller samples were used and the Gamma with square-root link model had convergence problems with small samples. CONCLUSION: Models with square-root transformation or link fit the data best. This function (whether used as transformation or as a link) seems to help deal with the high comorbidity of this population by introducing a form of interaction. The Gamma distribution helps with the long tail of the distribution. However, the Normal distribution is suitable if the correct transformation of the outcome is used.
Aged↗
Structure of D-DNA: 8-fold or 7-fold helix?
We have shown that both right- and left-handed uniform helical models (RU and LU models) could be built to give satisfactory agreement with the fibre diffraction data of poly[d(I-C)] in the D-form. Atomic coordinates of these two models are reported in the present work. Molecular transforms of these two models, as well as of the recently published Hoogsteen base-paired 7-fold helical structure of Drew and Dickerson, are given. In view of the work of Drew and Dickerson, attention is drawn to the presence of clear 004 and 008 reflections in the diffraction patterns of poly[d(I-C)] and poly[d(A-T)]. The available data strongly suggest an 8-fold helical structure for the D-form of DNA.
DNA↗
Characterization of tumors produced by signal peptide-basic fibroblast growth factor-transformed cells.
Basic fibroblast growth factor (bFGF) is found in a variety of cells and tissues. We have previously shown that bFGF is a transforming growth factor, but only when fused to a signal peptide (sp-bFGF). Cells expressing the native bFGF are tumorigenic in nude mice only, where the tumors form at a low frequency and grow very slowly as compared to sp-bFGF tumors. The cells transformed by the sp-bFGF growth factor gene cause rapidly growing tumors within 10 days in 100% of syngeneic and nude mice. In nude mice, the tumors are highly vascularized, while the vascularization in immunocompetent syngeneic mice is not as prominent. The syngeneic mice have a characteristic humoral immune response to sp-bFGF tumors, which differs from that mounted against ras-induced tumors. The ability of bFGF to induce tumorigenicity is significant in view of the recent discoveries of three new oncogenes: hst, int-2, and an oncogene from a human colon cancer. In addition to homology with FGF, the proteins encoded by these oncogenes all have a potential signal peptide at the protein's amino terminus, suggesting a mode of action analogous to that of our artificial signal peptide-bFGF (sp-bFGF) transforming growth factor model system.
Animals↗
Intracranial pressure processing with artificial neural networks: prediction of ICP trends.
It is well known that intracranial pressure (ICP) is influenced by an array of predictable and unpredictable factors, which gives rise to a signal heavily loaded with stochastic, i.e. random components. Hence, statistical modelling of this signal has proved to be of limited utility, in spite of the very sophisticated mathematical methods applied. In recent years, neural network algorithms (ANN), which are an alternative to statistical methods, have proved their effectiveness in the prediction of trends, as applied in a variety of medical and non-medical tasks. We therefore attempted to test the efficiency of neural models in the on-line prediction of ICP values, compare their effectiveness to statistically oriented algorithms and combine ANN methods with some newer signal processing algorithms, like wavelet decomposition. Prediction horizons of up to 5 minutes have been tested with various architectures of the neural predictor. For a 3 minute prediction horizon, a satisfactory accuracy of forecasting has been achieved with "plain" ANN, as expressed by the "average relative variance coefficient". This was measured by the ratio of the prediction error obtained, in relation to the error which would occur if a current value were taken as the forecasted one. The prediction quality with statistical autoregressive models has proved unsatisfactory, whilst the result obtained using the ANN model with the wavelet transform incorporated, performed significantly better than the ANN models alone. The prediction quality obtained with the ANN methodology seems to be satisfactory over a short time horizon, though no conclusion can be derived at this stage of the study, as to the clinical utility of this method. In particular, even with this methodology, it is not possible to forecast any sudden dehiscencies of the ICP signal with any practical reliability. From the point of view of modelling theory, such sharp deviations of the signal may be regarded as a "catastrophe". This implies the necessity for a different approach to the ICP signal analysis with the artificial intelligence methodology; one, that is more oriented towards the global properties of the signal.
Cerebral Hemorrhage↗
Application of classical and model-based spectral methods to describe the state of alertness in EEG.
Electrophysiological recordings are considered a reliable method of assessing a person's alertness. Sleep medicine is asked to offer objective methods to measure daytime alertness, tiredness and sleepiness. In this study, EEG signals recorded from 30 subjects were processed by PC-computer using classical and model-based methods. The classical method (fast Fourier transform) and three model-based methods (Burg autoregresse, moving average, least-squares modified Yule-Walker autoregressive moving average methods) were selected for processing EEG signals to discriminate the alertness level of subject. Power spectra of EEG signals were obtained by using these spectrum analysis techniques. These EEG spectra were then used to compare the applied methods in terms of their frequency resolution and the effects in determination of vigilance state of subject. It is found that, FFT and MA methods have low spectral resolution, these two methods are not appropriate for the analysis of the a wake-sleep correlation. Burg AR and least-squares modified Yule-Walker ARMA methods' performance characteristics have been found extremely valuable for the determination of vigilance state of a healthy subject, because of their clear spectra.
Adolescent↗
Quantifying the contribution of actin networks to the elastic strength of fibroblasts.
The structural models created to understand the cytoskeletal mechanics of cells in suspension are described here. Suspended cells can be deformed by well-defined surface stresses in an Optical Stretcher [Guck, J., Ananthakrishnan, R., Mahmood, H., Moon, T.J., Cunningham, C.C., Käs, J., 2001. The optical stretcher: a novel laser tool to micromanipulate cells. Biophys. J. 81(2), 767-784], a two-beam optical trap designed for the contact-free deformation of cells. Suspended cells have a well-defined cytoskeleton, displaying a radially symmetric actin cortical network underlying the cell membrane with no actin stress fibers, and microtubules and intermediate filaments in the interior. Based on experimental data using suspended fibroblasts, we create two structural models: a thick shell actin cortex model that describes cell deformation for a localized stress distribution on these cells and a three-layered model that considers the entire cytoskeleton when a broad stress distribution is applied. Applying the models to data, we obtain a (actin) cortical shear moduli G of approximately 220 Pa for normal fibroblasts and approximately 185 Pa for malignantly transformed fibroblasts. Additionally, modeling the cortex as a transiently crosslinked isotropic actin network, we show that actin and its crosslinkers must be co-localized into a tight shell to achieve these cortical strengths. The similar moduli values and cortical actin and crosslinker densities but different deformabilities of the normal and cancerous cells suggest that a cell's structural strength is not solely determined by cytoskeletal composition but equally importantly by (actin) cytoskeletal architecture via differing cortical thicknesses. We also find that although the interior structural elements (microtubules, nucleus) contribute to the deformed cell's exact shape via their loose coupling to the cortex, it is the outer actin cortical shell (and its thickness) that mainly determines the cell's structural response.
Actins↗
Application of classical and model-based spectral methods to ophthalmic arterial Doppler signals with uveitis disease.
In this study, Doppler signals recorded from ophthalmic artery of 75 subjects were processed by PC-computer using classical and model-based methods. The classical method (fast Fourier transform) and three model-based methods (Burg autoregressive, moving average, least-squares modified Yule-Walker autoregressive moving average methods) were selected for processing ophthalmic arterial Doppler signals with uveitis disease. Doppler power spectra of ophthalmic arterial Doppler signals were obtained by using these spectrum analysis techniques. The variations in the shape of the Doppler spectra as a function of time were presented in the form of sonograms in order to obtain medical information. These Doppler spectra and sonograms were then used to compare the applied methods in terms of their frequency resolution and the effects in determination of uveitis disease.
Adolescent↗
Dispersion of solute by electrokinetic flow through post arrays and wavy-walled channels.
In this work, we simulate electrokinetically driven transport of unretained solute bands in a variety of two-dimensional spatially periodic geometries (post arrays as well as sinuous/varicose channels), in the thin Debye layer limit. Potential flow fields are calculated using either an inverse method or a Schwarz-Christoffel transform, and transport is modeled using a Monte Carlo method in the transformed plane. In this way, spurious "numerical diffusion" transverse to streamlines is completely eliminated, and streamwise numerical diffusion is reduced to arbitrary precision. Late-time longitudinal dispersion coefficients are calculated for Peclet numbers from 0.1 to 3162. In most geometries, a Taylor-Aris-like scaling law for the dispersion coefficient D(L)/D(L0) = 1 + Pe2/alpha underpredicts dispersion when Pe approximately O(alpha1/2) (here D(L0) is the effective axial diffusion coefficient in the periodic geometry). A two-parameter correlation widely used in the porous media literature, D(L)/D(L0) = 1 + Pe(n)/alpha, agrees slightly better, but much better agreement can be obtained using a new quadratic form: D(L)/D(L0) = 1 + Pe/alpha1 + Pe2/alpha2. A quasi-universal relationship for stream-wise dispersion is offered that predicts 96% of the simulation data to within a factor of 2 in all geometries studied. Comparison with previous work shows that in circular post arrays, the dispersion coefficient for electrokinetic flow is a factor of 3-10 less (depending on Pe and relative post size) than for pressure-driven flow.
Journal Article↗
Use of time-series analysis in infectious disease surveillance.
This article reviews the practical aspects of the use of ARIMA (autoregressive, integrated, moving average) modelling of time series as applied to the surveillance of reportable infectious diseases, with special reference to the widely available SSS1 package, produced by the Centers for Disease Control and Prevention. The main steps required by ARIMA modelling are the selection of the time series, transformations of the series, model selection, parameter estimation, forecasting, and updating of the forecasts. The difficulties most likely to be encountered at each step are described and possible solutions are offered. Examples of successful and unsuccessful modelling are presented and discussed. Other methods, such as INAR modelling or Markov chain analysis, which can be applied to situations where ARIMA modelling fails are also dealt with, but they are less practical. ARIMA modelling can be carried out by adequately trained nonspecialists working for local agencies. Its usefulness resides mostly in providing an estimate of the variability to be expected among future observations. This knowledge is helpful in deciding whether or not an unusual situation, possibly an outbreak, is developing.
Communicable Disease Control↗
DNA processing during entry in transformation of Streptococcus pneumoniae.
The current model for processing DNA during entry in the transformation of Streptococcus pneumoniae is that following double-strand cleavage of DNA bound at the cell surface, uptake of one strand proceeds linearly from a newly formed 3'-end with simultaneous degradation of the opposite strand. Two important predictions of this model have been tested in the work reported here: first that the polarity of DNA degradation is the opposite of that for entry, and second that the rate of DNA degradation is (at least) equal to the rate of entry. The processing of DNA during entry was investigated using donor molecules constructed in vitro and labeled in one strand only. With uniformly labeled donor molecules, an amount of label equivalent to that taken up by the cells was recovered in acid-soluble form in the transformation medium. Experiments with 3'- or 5'-end-labeled molecules revealed that whereas essentially all of the 3'-end label was susceptible to degradation, most 5'-end label was resistant. Kinetic analysis of both entry and degradation revealed very similar rates for these processes, about 100 nucleotides s-1 at 31 degrees C, suggesting that they occur concomitantly. Entry and degradation appear to proceed with opposite polarity, 3'-->5' for entry and 5'-->3' for degradation. A prediction of the entry model, that a single-strand interruption would inhibit the uptake of DNA sequences located 5' to the nick, was confirmed experimentally. Therefore, we suggest that an intact sugar phosphate backbone is required by the entry machinery for continuous uptake.
DNA, Bacterial↗
Influence of membrane phospholipid composition and structural organization on spontaneous lipid transfer between membranes.
Investigations were carried out on the influence of phospholipid composition of model membranes on the processes of spontaneous lipid transfer between membranes. Acceptor vesicles were prepared from phospholipids extracted from plasma membranes of control and ras-transformed fibroblasts. Acceptor model membranes with manipulated levels of phosphatidylethanolamine (PE), sphingomyelin and phosphatidic acid were also used in the studies. Donor vesicles were prepared of phosphatidylcholine (PC) and contained two fluorescent lipid analogues, NBD-PC and N-Rh-PE, at a self-quenching concentration. Lipid transfer rate was assessed by measuring the increase of fluorescence in acceptor membranes due to transfer of fluorescent lipid analogues from quenched donor to unquenched acceptor vesicles. The results showed that spontaneous NBD-PC transfer increased upon fluidization of acceptor vesicles. In addition, elevation of PE concentration in model membranes was also accompanied by an increase of lipid transfer to all series of acceptor vesicles. The results are discussed with respect to the role of lipid composition and structural order of cellular plasma membranes in the processes of spontaneous lipid exchange between membrane bilayers.
4-Chloro-7-nitrobenzofurazan↗
Analysis of poultry fertility data.
Single Comb White Leghorn (SCWL) hens were inseminated intravaginally with spermatozoa from either SCWL or subfertile Delaware roosters in three replicate fertility trials. Overall fertility was analyzed with a log odds model following logit transformation. Duration of fertility was analyzed by iterative least squares. Hens inseminated with spermatozoa from SCWL males laid a higher proportion of fertilized eggs over a longer interval than those inseminated with spermatozoa from affected Delawares. Log-odds and logistic models may have advantages over the more traditional methods of evaluation. This is particularly true in regard to the distribution and normalization of error variances via the logit transformation and removal of nonadditivity via logistic regression.
Analysis of Variance↗
Anti-sclerotic effect of transforming growth factor-beta antibody in a mouse model of bleomycin-induced scleroderma.
Recent studies have demonstrated the evidence of the crucial role of transforming growth factor-beta (TGF-beta) in the pathogenesis of tissue fibrosis; however, its precise role has not been fully elucidated. Administration of anti-TGF-beta antibody is shown to be effective for inhibiting lung fibrosis induced by bleomycin in an experimental animal model. We have recently established a mouse model for scleroderma by repeated injections of bleomycin. In this study, we examined whether the suppression of TGF-beta leads to the improvement of dermal sclerotic lesion by using this model. We induced dermal sclerosis in C3H mice by subcutaneous injections of bleomycin (100 microg/ml) for 3 weeks, and separate groups of mice were also injected with bleomycin with either anti-TGF-beta antibody (10 microg/ml) or control normal rabbit serum for 3 weeks. Thus treated skins were harvested and analyzed for histological sclerosis, serum cytokine, and influx of mast cells and eosinophils, both of which are known to release fibrogenic cytokines or several mediators responsible for tissue fibrosis. The result showed that anti-TGF-beta antibody caused a significant reduction in cutaneous sclerosis characterized by histological features and hydroxyproline contents. Examination of tissue sections also revealed a significant suppression of influx of mast cells and eosinophils. Serum interleukin-4 (IL-4) and IL-6 levels determined by enzyme-linked immunosorbent assay exhibited a significant reduction after anti-TGF-beta antibody treatment. Our results suggest that administration of an antibody against TGF-beta is useful in preventing experimental dermal sclerosis induced by bleomycin and raises a possibility of the therapeutic approach of anti-TGF-beta antibody in scleroderma.
Animals↗