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At least 811 records · Page 45Linked to original sources

Prediction of internal electric current distribution from surface application in atrophied muscle tissue.

The use of surface electrical stimulation therapy for clinical rehabilitation has created the need for an improved modeling method to predict internal current density. A method was developed to model quantitatively the current density delivered to an atrophied muscle. Some stimulation protocols do not produce measurable physiological effects, such as muscle contraction. Therefore, traditional response-based current density modeling cannot be used. Additionally, lumped circuit models do not provide the resolution needed to optimize electrode size, shape, and placement. The quantitative approach developed here can be used to optimize electrical stimulation protocols in abnormal muscle tissue. In this study, the finite element method (FEM) is used to model the low intensity electric current stimulation resulting from surface application. FEM provides the ability to model complex tissue properties found in living tissue. A leg of lamb was modeled because its size and level of tissue complexity is similar to that of a human child's thigh. Voltage gradient measurements were made upon a sacrificed leg of lamb during the application of bipolar stimulation. These measurements were made at numerous points in the stimulated leg of lamb and allowed the mapping of the current density. The leg of lamb was then sliced and photographed to be able to create the finite element model. The empirical data compared favorably to the results of the FEM model, thus verifying the method. This FEM model was then modified to study the effects of muscle atrophy on electric current densities. This modeling method will ultimately lead to improved stimulation protocols and better clinical treatment.

Animals↗

Computer modeling of the abdominal aorta using magnetic resonance images.

An approach is described for creating a 3-D computer model of the abdominal aorta from just two projective images. The aorta is modeled by conical segments connecting circular cross sections. Accuracy of this technique is within 1 mm. From the 3-D computer model, quantitative measurements of vessel diameter, length, and position are available for any subset of the arterial structure. Visualization is enhanced by displaying the computer model rather than a direct set of images obtained from different perspectives. Ambiguities from overlapping branches can be resolved by rotating the model or by eliminating the interfering structures. This approach has been applied in both phantom studies, in which quantitative comparisons were made, and in vivo studies, in which qualitative evaluations were made.

Aorta, Abdominal↗

Coding theory based models for protein translation initiation in prokaryotic organisms.

Our research explores the feasibility of using communication theory, error control (EC) coding theory specifically, for quantitatively modeling the protein translation initiation mechanism. The messenger RNA (mRNA) of Escherichia coli K-12 is modeled as a noisy (errored), encoded signal and the ribosome as a minimum Hamming distance decoder, where the 16S ribosomal RNA (rRNA) serves as a template for generating a set of valid codewords (the codebook). We tested the E. coli based coding models on 5' untranslated leader sequences of prokaryotic organisms of varying taxonomical relation to E. coli including: Salmonella typhimurium LT2, Bacillus subtilis, and Staphylococcus aureus Mu50. The model identified regions on the 5' untranslated leader where the minimum Hamming distance values of translated mRNA sub-sequences and non-translated genomic sequences differ the most. These regions correspond to the Shine-Dalgarno domain and the non-random domain. Applying the EC coding-based models to B. subtilis, and S. aureus Mu50 yielded results similar to those for E. coli K-12. Contrary to our expectations, the behavior of S. typhimurium LT2, the more taxonomically related to E. coli, resembled that of the non-translated sequence group.

Bacterial Proteins↗

A model of perceptual classification in children and adults.

The developmental trend from overall-similarity to dimensional-identity classifications is explained by a quantitative model. I begin with the assumption that objects are represented in terms of constituent dimensions and that the representation of objects changes little with development. Given this assumption, the model has three major parts. First, the similarity between objects is a function of the combination of the constituent dimensional differences. I propose developmental change in the likelihood that dimensions are differentially weighted in the calculation of similarity. Second, the perceived similarities between objects are valued for the purpose of constructing classifications. I propose that similarities are valued more dichotomously with age, such that identity becomes increasingly special. Third, the valued similarities are used to choose the best classification of those possible. The model provides good qualitative fits to the extant data. Three experiments examining classifications in 2- to 8-year-olds and in adults support specific new claims of the model. The data and the model provide new insights about development, classification, and similarity.

Adult↗

Modifying the 'pulse-reserve' paradigm for deserts of North America: precipitation pulses, soil water, and plant responses.

The 'pulse-reserve' conceptual model--arguably one of the most-cited paradigms in aridland ecology--depicts a simple, direct relationship between rainfall, which triggers pulses of plant growth, and reserves of carbon and energy. While the heuristics of 'pulses', 'triggers' and 'reserves' are intuitive and thus appealing, the value of the paradigm is limited, both as a conceptual model of how pulsed water inputs are translated into primary production and as a framework for developing quantitative models. To overcome these limitations, we propose a revision of the pulse-reserve model that emphasizes the following: (1) what explicitly constitutes a biologically significant 'rainfall pulse', (2) how do rainfall pulses translate into usable 'soil moisture pulses', and (3) how are soil moisture pulses differentially utilized by various plant functional types (FTs) in terms of growth? We explore these questions using the patch arid lands simulation (PALS) model for sites in the Mojave, Sonoran, and Chihuahuan deserts of North America. Our analyses indicate that rainfall variability is best understood in terms of sequences of rainfall events that produce biologically-significant 'pulses' of soil moisture recharge, as opposed to individual rain events. In the desert regions investigated, biologically significant pulses of soil moisture occur in either winter (October-March) or summer (July-September), as determined by the period of activity of the plant FTs. Nevertheless, it is difficult to make generalizations regarding specific growth responses to moisture pulses, because of the strong effects of and interactions between precipitation, antecedent soil moisture, and plant FT responses, all of which vary among deserts and seasons. Our results further suggest that, in most soil types and in most seasons, there is little separation of soil water with depth. Thus, coexistence of plant FTs in a single patch as examined in this PALS study is likely to be fostered by factors that promote: (1) separation of water use over time (seasonal differences in growth), (2) relative differences in the utilization of water in the upper soil layers, or (3) separation in the responses of plant FTs as a function of preceding conditions, i.e., the physiological and morphological readiness of the plant for water-uptake and growth. Finally, the high seasonal and annual variability in soil water recharge and plant growth, which result from the complex interactions that occur as a result of rainfall variability, antecedent soil moisture conditions, nutrient availability, and plant FT composition and cover, call into question the use of simplified vegetation models in forecasting potential impacts of climate change in the arid zones in North America.

Biomass↗

Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: a simple model.

The rules that govern the activation and autophosphorylation of the multifunctional Ca2+-calmodulin kinase II (CaMKII) by Ca2+ and calmodulin (CaM) are thought to underlie its ability to decode Ca2+ oscillations and to control multiple cellular functions. We propose a simple biophysical model for the activation of CaMKII by Ca2+ and calmodulin. The model describes the transition of the subunits of the kinase between their different possible states (inactive, bound to Ca2+-CaM, phosphorylated at Thr(286), trapped and autonomous). All transitions are described by classical kinetic equations except for the autophosphorylation step, which is modeled in an empirical manner. The model quantitatively reproduces the experimentally demonstrated frequency sensitivity of CaMKII [Science 279 (1998) 227]. We further use the model to investigate the role of several characterized features of the kinase--as well as some that are not easily attainable by experiments--in its frequency-dependent responses. In cellular microdomains, CaMKII is expected to sense very brief Ca2+ spikes; our simulations under such conditions reveal that the enzyme response is tuned to optimal frequencies. This prediction is then confirmed by experimental data. This novel and simple model should help in understanding the rules that govern CaMKII regulation, as well as those involved in decoding intracellular Ca2+ signals.

Biophysical Phenomena↗

Triplet excitation energy transfer in porphyrin-based donor--bridge--acceptor systems with conjugated bridges of varying length: an experimental and DFT study.

A series of donor--bridge--acceptor (D--B--A) systems with varying donor-acceptor distances have been studied with respect to their triplet energy transfer properties. The donor and acceptor moieties, zinc(II), and free-base porphyrin, respectively, were separated by 2-5 oligo-p-phenyleneethynylene units (OPE) giving rise to edge-to-edge separations ranging between 12.7 and 33.4 A. The study was performed in 2-MTHF at 150 K and it was established that triplet excitation energy transfer occurs with high efficiency in all of the studied D--B--A systems. The distance dependence was exponential with an attenuation factor, beta, equal to 0.45 +/- 0.015 A(-1). The experimental study was also supported by quantum mechanical DFT and TD-DFT calculations on a series of closely related model systems. A thorough analysis of the OPE-bridge conformational dynamics led to an equation that quantitatively models the distance dependence of the electronic coupling found in the experimental study.

Journal Article↗

Thermal modeling of the malignant woman's breast.

In this paper the conceptual three-dimensional model of the normal woman's breast presented in Osman and Afify, is developed into a detailed quantitative model of the malignant woman's breast. This model takes into consideration the effect of tumor size and location on the metabolic heat production, blood perfusion rate, and thermal contour plot of the malignant breast for each tumor size, depth, and location. Also the results of this investigation show that a hot spot in the malignant woman's breast thermal contour plot may not be directly related to an embedded tumor beneath the breast surface.

Body Temperature Regulation↗

Performance evaluation of partial differential equation models in electronic speckle pattern interferometry and the delta-mollification phase map method.

The ordinary differential equation (ODE) and partial differential equation (PDE) image- processing methods have been applied to reduce noise and enhance the contrast of electronic speckle pattern interferometry fringe patterns. We evaluate the performance of a few representative PDE denoising models quantitatively with two parameters called image fidelity and speckle index, and then we choose a good denoising model. Combining this denoising model with the ODE enhancement method, we make it possible to perform contrast enhancement and denoising simultaneously. Second, we introduce the delta-mollification method to smooth the unwrapped phase map. Finally, based on PDE image processing, delta mollification and some traditional techniques, an approach of phase extraction from a single fringe pattern is tested for computer-simulated and experimentally obtained fringe patterns. The method works well under a high noise level and limited visibility and can extract accurate phase values.

Journal Article↗

DSM criteria for major depression: evaluating symptom patterns using latent-trait item response models.

BACKGROUND: Expert committees of clinicians have chosen diagnostic criteria for psychiatric disorders with little guidance from measurement theory or modern psychometric methods. The DSM-III-R criteria for major depression (MD) are examined to determine the degree to which latent trait item response models can extract additional useful information. METHOD: The dimensionality and measurement properties of the 9 DSM-III-R criteria plus duration are evaluated using dichotomous factor analysis and the Rasch and 2 parameter logistic item response models. Quantitative liability scales are compared with a binary DSM-III-R diagnostic algorithm variable to determine the ramifications of using each approach. RESULTS: Factor and item response model results indicated the 10 MD criteria defined a reasonably coherent unidimensional scale of liability. However, person risk measurement was not optimal. Criteria thresholds were unevenly spaced leaving scale regions poorly measured. Criteria varied in discriminating levels of risk. Compared to a binary MD diagnosis, item response model (IRM) liability scales performed far better in (i) elucidating the relationship between MD symptoms and liability, (ii) predicting the personality trait of neuroticism and future depressive episodes and (iii) more precisely estimating heritability parameters. CONCLUSIONS: Criteria for MD largely defined a single dimension of disease liability although the quality of person risk measurement was less clear. The quantitative item response scales were statistically superior in predicting relevant outcomes and estimating twin model parameters. Item response models that treat symptoms as ordered indicators of risk rather than as counts towards a diagnostic threshold more fully exploit the information available in symptom endorsement data patterns.

Adolescent↗

Using an excitation-pattern model to predict auditory masking.

This paper evaluates the extent to which auditory masking can be reliably predicted from excitation patterns. For this purpose a quantitative model proposed by Glasberg and Moore [Hear. Res. 47, 103-138 (1990)] was used to calculate excitation patterns evoked by stationary sounds. Model simulations were performed for a number of masking experiments, reported in the literature, by calculating excitation patterns for the masker-alone as well as for the masker-plus-target conditions. As a threshold criterion, a difference between the two patterns of 1 dB at any frequency was imposed. For narrow-band-noise masking patterns, the method yields a fairly precise prediction of experimental data. For other conditions, however, systematic deviations between model predictions and data are observed. For instance, the model does not reproduce the typical tip-tail shape of psychophysical tuning curves. Furthermore, the nonlinearities in level dependence are not correctly described, and the model fails to reproduce a realistic two-tone masking curve.

Acoustic Stimulation↗

Universal behaviour in compressive failure of brittle materials.

Brittle failure limits the compressive strength of rock and ice when rapidly loaded under low to moderate confinement. Higher confinement or slower loading results in ductile failure once the brittle-ductile transition is crossed. Brittle failure begins when primary cracks initiate and slide, creating wing cracks at their tips. Under little to no confinement, wing cracks extend and link together, splitting the material into slender columns which then fail. Under low to moderate confinement, wing crack growth is restricted and terminal failure is controlled by the localization of damage along a narrow band. Early investigations proposed that localization results from either the linkage of wing cracks or the buckling of microcolumns created between adjacent wing cracks. Observations of compressive failure in ice suggest a mechanism whereby localization initiates owing to the bending-induced failure of slender microcolumns created between sets of secondary cracks emanating from one side of a primary crack. Here we analyse this mechanism, and show that it leads to a closed-form, quantitative model that depends only on independently measurable mechanical parameters. Our model predictions for both the brittle compressive strength and the brittle-ductile transition are consistent with data from a variety of crystalline materials, offering quantitative evidence for universal processes in brittle failure and for the broad applicability of the model.

Journal Article↗

Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer.

Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to normotensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.

Animals↗

Quantitative structure-activity relationships of mutagenic activity from quantum topological descriptors: triazenes and halogenated hydroxyfuranones (mutagen-X) derivatives.

The mutagenic activity of 23 triazenes and, in a different set, of 24 halogenated hydroxyfuranones (MX derivatives) is quantitatively related to new features of contemporary molecular wave functions. Nowadays affordable computers are powerful enough to rapidly generate geometry-optimised ab initio wave functions at HF/3-21G*, HF/6-31G* and B3LYP/6-311 + G(2d,p) level for all molecules. The bonds of a common molecular skeleton are described by their ab initio bond lengths and local properties provided by the theory of quantum chemical topology (QCT). The chemometric analysis involves two types: one to generate a statistically validated quantitative model, and one to isolate the active center. In the former a genetic algorithm (GA) selects bond descriptors in order to optimise the cross-validation error, q2, followed by a full partial least squares (PLS) analysis, which also yields randomisation statistics. In the latter type principal components (PCs) are constructed from the original bond descriptors and their variables important to the projection (VIPs) are plotted in a histogram. This analysis suggests a preferred mechanistic pathway for the initial hydroxylation of the triazenes, an issue that has remained ambiguous so far. In the case of the hydroxyfuranones the proposed method aids the elucidation of a mechanistic ambivalence.

Algorithms↗

The rate of DNA evolution: effects of body size and temperature on the molecular clock.

Observations that rates of molecular evolution vary widely within and among lineages have cast doubts on the existence of a single "molecular clock." Differences in the timing of evolutionary events estimated from genetic and fossil evidence have raised further questions about the accuracy of molecular clocks. Here, we present a model of nucleotide substitution that combines theory on metabolic rate with the now-classic neutral theory of molecular evolution. The model quantitatively predicts rate heterogeneity and may reconcile differences in molecular- and fossil-estimated dates of evolutionary events. Model predictions are supported by extensive data from mitochondrial and nuclear genomes. By accounting for the effects of body size and temperature on metabolic rate, this model explains heterogeneity in rates of nucleotide substitution in different genes, taxa, and thermal environments. This model also suggests that there is indeed a single molecular clock, as originally proposed by Zuckerkandl and Pauling [Zuckerkandl, E. & Pauling, L. (1965) in Evolving Genes and Proteins, eds. Bryson, V. & Vogel, H. J. (Academic, New York), pp. 97-166], but that it "ticks" at a constant substitution rate per unit of mass-specific metabolic energy rather than per unit of time. This model therefore links energy flux and genetic change. More generally, the model suggests that body size and temperature combine to control the overall rate of evolution through their effects on metabolism.

Animals↗

Understanding biological complexity: lessons from the past.

Advances in molecular biology now permit complex biological systems to be tracked at an exquisite level of detail. The information flow is so great, however, that using intuition alone to draw connections is unrealistic. Thus, the need to integrate mathematical biology with experimental biology is greater than ever. To achieve this integration, obstacles that have traditionally prevented effective communication between theoreticians and experimentalists must be overcome, so that experimentalists learn the language of mathematics and dynamical modeling and theorists learn the language of biology. Fifty years ago Alan Hodgkin and Andrew Huxley published their quantitative model of the nerve action potential; in the same year, Alan Turing published his work on pattern formation in activator-inhibitor systems. These classic studies illustrate two ends of the spectrum in mathematical biology: the detailed model approach and the minimal model approach. When combined, they are highly synergistic in analyzing the mechanisms underlying the behavior of complex biological systems. Their effective integration will be essential for unraveling the physical basis of the mysteries of life.

Animals↗

Shamanism or science?

The interconnection of the three organismic levels, metabolism, morphology, and biogeography, can now be amplified into a multipart architecture, introducing plant bioactivity through ethnobotany-oriented descriptions. Only via such an integrative model, the diverse organismic levels can be connected within a more holistic, realistic scheme. Construction of qualitative and quantitative models via evolutionarily conceived implantation into dahlgrenograms and Sporne indices, allows ethnobotany to acquire predictive validity. The coherence of such systems was demonstrated by comparison of the vast ethnobotanical Brazilian database by Pio Corrêa with relatively very minute databases referring to three Amazonian Indian societies.

Bolivia↗

Modelling the bacterial chemotaxis receptor complex.

The pathway controlling chemotaxis in Escherichia coli is the simplest and most well understood cell signalling system to date. However, quantitative models based on the available data still fail to reproduce important features of the pathway. Most notably, the observed sensitivity of cells to very small changes in stimulus concentrations cannot be reproduced by conventional models based on the measured concentrations, binding affinities and rate constants of the proteins involved. This discrepancy, together with recent experimental findings, drew our attention to the spatial organization of molecules within the cell and in particular to the clusters of receptors localised at the cell poles. A stochastic simulator for chemical reactions, STOCHSIM, was previously developed to model the chemotaxis pathway at the level of individual molecular interactions. This program has now been extended to incorporate a spatial representation that allows the interaction between molecules in a two-dimensional lattice to be simulated. In silico 'experiments' using this new version of STOCHSIM demonstrate that lateral interactions between clustered receptors can significantly enhance the excitation response. The adaptation reactions may also exploit the proximity of receptor molecules, and a hypothetical mechanism by which this may occur is currently being tested.

Bacterial Physiological Phenomena↗