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At least 667 records · Page 37Linked to original sources

Cerebral arteriovenous malformation feeding artery aneurysms: a theoretical model of intravascular pressure changes after treatment.

OBJECTIVE: A quantitative model may be used to estimate the magnitude of expected pressure changes along the vascular tree with shunt ablation and may provide information to assess the hemodynamic risk of arteriovenous malformation (AVM) treatment. METHODS: A computer model of the cerebral circulation was applied to estimate the changes in intravascular pressure, velocity, biomechanical stress, and shear stress that might be expected from either endovascular or surgical ablation of AVMs. Two AVM sizes and two feeding artery constellations were simulated. The effect of different shunt flows on vascular pressure was modeled. In each simulation, AVMs were occluded in a stepwise fashion. The effects of systemic hypertension and hypotension in various vascular zones were also simulated. RESULTS: As large (1000 ml/min) AVMs were occluded, the mean feeding arterial pressure increased from 18 to 68 mm Hg; the percent-occlusion at half-maximal pressure increase was 92%. For medium (500 ml/min) AVMs, feeding arterial pressure increased from 37 to 66 mm Hg; the percent-occlusion at half-maximal pressure increase was 71%. During manipulation of systemic pressure, hemodynamic changes in the circulation close to the nidus were proportionally less than changes in systemic pressure; the degree of proportionality depended on the magnitude of AVM shunt flow. CONCLUSION: In this simulation, shunt obliteration increased pressure in the nidus and feeding arteries with little effect on the proximal circulation. The shunt provided a "buffering" effect, i.e., higher flow fistulas were exposed to smaller variations in intravascular pressure in feeding artery and nidal pressures during manipulation of systemic pressure.

Adult↗

A multi-group model of Schistosoma japonicum transmission dynamics and control: model calibration and control prediction.

Previously we formulated a quantitative model to characterize site-specific schistosomiasis transmission. In this paper, we present a procedure to calibrate the model to data collected in endemic villages of south-western Sichuan, China, with the objective of reducing parametric uncertainty to allow the model to describe local transmission with relative confidence. A Bayesian approach using local epidemiological data and expert opinion is employed to calibrate the model. Results indicate that, after calibration, the output uncertainty is reduced substantially. The calibrated model is then used for prediction of the effects of different intervention options. Simulations reflect a bimodal transmission in both human (early summer and early fall) and snail (late summer and late fall) infections in this area, for which there is some field evidence. Also shown in the simulations are relatively high reinfection rates following chemotherapy in these endemic villages. These results suggest that a sustainable control strategy is essential in reducing transmission, and that transmission can be reduced by chemotherapy, focal snail (e.g. snail clusters) control, and egg control. Our work demonstrates the feasibility of characterizing site-specific schistosomiasis transmission using a mathematical model and a calibration approach that integrates diverse field data, and the use of the calibrated model to design control strategies.

Animals↗

Modelling home televisiting services using systems dynamic theory.

A quantitative model was developed to study the provision of a home televisiting service. Systems dynamic theory was used to describe the relationships between quality of care, accessibility and cost-effectiveness. Input information was gathered from the telemedicine literature, as well as from over 75 sessions of a televisiting service provided by the Severo Ochoa Hospital to 18 housebound patients from three different medical specialties. The model allowed the Severo Ochoa Hospital to estimate the equipment needed to support increased medical contacts for intensive cardiac and other patients.

Adult↗

Electrophysiology of K+ transport by midgut epithelium of lepidopteran insect larvae. IV. A multicompartment model accounts for tetramethylammonium entry into goblet cavities

A quantitative model was developed to explain the kinetics of tetramethylammonium (TMA+) movement into and out of the goblet cavities of posterior midgut cells of Manduca sexta based on the data of the accompanying paper, which indicated that TMA+ does not enter the goblet cavity directly from the lumen. The model has two cellular compartments between the lumen and goblet cavity; these have been tentatively identified as the columnar cell and goblet cell cytoplasm. Five transmembrane pathways are included: from lumen to columnar cell, from columnar cell to goblet cell, from goblet cell cytoplasm to goblet cell cavity, and across the basal membrane of each cell type. These pathways need not be channels; they could use endocytotic or exocytotic mechanisms or, in the case of the cell-to-cell passage, septate junctions. However, in all cases, transfer is proportional to the electrochemical gradient. The model was tested against the results obtained after exposure to TMA+ in short-circuited and open-circuited tissues as well as results from an open-circuited tissue that did not develop a large transepithelial potential. Although driving forces for TMA+ across the membrane barriers were quite different in the different experimental conditions, the transfer coefficients from lumen to columnar cell, from columnar to goblet cell and from both cells across the basal membrane were the same. The only transfer coefficient that changed between short-circuit and open-circuit conditions was that from goblet cell cytoplasm to goblet cavity. This value was high under short-circuit conditions (when K+ transport activity is high), but low under open-circuit conditions (when K+ transport activity is low). The model suggests a hypothesis in which TMA+ enters the goblet cavity by an indirect route across the cell membrane of columnar cells, and thence passes to the goblet cell cytoplasm through intercellular junctions. Results from experiments with cytochalasin E suggest that the actin-based cytoskeleton is involved in limiting cell­cell coupling. In this model, TMA+ passes from the goblet cell cytoplasm to the goblet cavity via the K+/nH+ antiport believed to mediate active transepithelial K+ transport. However, although actively transported K+ is believed to pass from goblet cavity to lumen, TMA+ cannot.

Journal Article↗

Using cell replication data in mathematical modeling in carcinogenesis.

Risk estimation involves the application of quantitative models of dose versus response to carcinogenicity data. Recent advances in biology, computing, and mathematics have led to the application of mathematically complicated, mechanistically based models of carcinogenesis to the estimation of risks. This paper focuses on two aspects of this application, distinguishing between models using available data and the development of new models to keep pace with research developments.

Animals↗

Recent uses of topological indices in the development of in silico ADMET models.

Topological indices are employed in an ever-widening family of quantitative models to describe the structural attributes of compounds as these relate to experimental endpoints in a host of physicochemical and biological processes. This is especially true where attention to ADMET (absorption, distribution, metabolism, excretion and toxicity) properties is a priority, using various training or learning algorithms to construct quantitative structure-activity or -property relationship ADMET models. This review discusses the in silico ADMET approaches used over the past two years, where the majority of descriptors are topological, including comparisons between models and their important descriptors where applicable. ADMET models for aqueous solubility involving several large datasets are reviewed, as are a number of models for human intestinal absorption. Also included is the use of topological indices extended to modeling metabolic stability for the cytochrome P450 cassette of enzymes in an interesting study with compounds measured in a uniform bioassay using human liver S9 homogenate. Finally, in the area of genotoxicity, two recent ADMET models are discussed, one for chromosomal aberrations and another using a large compound dataset for Ames mutagenicity. The latter study involved several thousand compounds, with comparisons of validation results for a number of well-known predictors of mutagenicity.

Animals↗

Structure-metabolism relationships: steric effects and the enzymatic hydrolysis of carboxylic esters.

After a brief review of a number of issues related to the enzymatic hydrolysis of carboxylic esters, scuh as interspecies variability, mechanism, stereospecificity, and activation energy, and after and overview of relevant aspects related to the quantitative modeling of steric effects, the results of a recently developed quantitative structure-metabolism relationship model are discussed. They were obtained for in vitro human blood enzymatic hydrolysis of noncongener esters by introduction of the inaccessible solid angle as a novel measure of steric hindrance.

Animals↗

Measurement of cellular elastic properties by acoustic microscopy.

The acoustic microscope is used to investigate the elastic properties of living biological cells. A quantitative model is developed relating acoustic microscope image contrast to cellular elastic properties. Cytoplasmic acoustic attenuation is measured by focusing the acoustic microscope on the surface of the underlying substrate. Cytoplasmic acoustic impedance is measured by focusing the acoustic microscope on the top surface of the cell. The model allows the acoustic microscope to give quantitative information about cellular elasticity on a subcellular scale.

Acoustics↗

Novel parameter estimation methods for 11C-acetate dual-input liver model with dynamic PET.

The successful investigation of 11C-acetate in positron emission tomography (PET) imaging for marking hepatocellular carcinoma (HCC) has been validated by both clinical and quantitative modeling studies. In the previous quantitative studies, all the individual model parameters were estimated by the weighted nonlinear least squares (NLS) algorithm. However, five parameters need to be estimated simultaneously, therefore, the computational time-complexity is high and some estimates are not quite reliable, which limits its application in clinical environment. In addition, liver system modeling with dual-input function is very different from the widespread single-input system modeling. Therefore, most of the currently developed estimation techniques are not applicable. In this paper, two parameter estimation techniques: graphed NLS (GNLS) and graphed dual-input generalized linear least squares (GDGLLS) algorithms were presented for 11C-acetate dual-input liver model. Clinical and simulated data were utilized to test the proposed algorithms by a systematic statistical analysis. Compared to NLS fitting, these two novel methods achieve better estimation reliability and are computationally efficient, and they are extremely powerful for the estimation of the two potential HCC indicators: local hepatic metabolic rate-constant of acetate and relative portal venous contribution to the hepatic blood flow.

Acetates↗

Short-term cardiovascular oscillations in man: measuring and modelling the physiologies.

Research into cardiovascular variabilities intersects both human physiology and quantitative modelling. This is because respiratory and Mayer wave (or 10 s) cardiovascular oscillations represent the integrated control of a system through both autonomic branches by systemic haemodynamic changes within a fluid-filled, physical system. However, our current precise measurement of short-term cardiovascular fluctuations does not necessarily mean we have an adequate understanding of them. Empirical observation suggests that both respiratory and Mayer wave fluctuations derive from mutable autonomic and haemodynamic inputs. Evidence strongly suggests that respiratory sinus arrhythmia both contributes to and buffers respiratory arterial pressure fluctuations. Moreover, even though virtual abolition of all R-R interval variability by cholinergic blockade suggests that parasympathetic stimulation is essential for expression of these variabilities, respiratory sinus arrhythmia does not always reflect a purely vagal phenomenon. The arterial baroreflex has been cited as the mechanism for both respiratory and Mayer wave frequency fluctuations. However, data suggest that both cardiac vagal and vascular sympathetic fluctuations at these frequencies are independent of baroreflex mechanisms and, in fact, contribute to pressure fluctuations. Results from cardiovascular modelling can suggest possible sources for these rhythms. For example, modelling originally suggested low frequency cardiovascular rhythms derived from intrinsic delays in baroreceptor control, and experimental evidence subsequently corroborated this possibility. However, the complex stochastic relations between and variabilities in these rhythms indicate no single mechanism is responsible. If future study of cardiovascular variabilities is to move beyond qualitative suggestions of determinants to quantitative elucidation of critical physical mechanisms, both experimental design and model construction will have to be more trenchant.

Blood Pressure↗

Modeling pedestal experiments with amplitude instead of contrast.

To provide a comprehensive quantitative model of contrast discrimination, we measured contrast discrimination functions at four mean luminances, four spatial frequencies, three phase relations between test and pedestal gratings, and two temporal frequencies for the test grating. The results confirm previous findings that the shape of the contrast discrimination function varies with three of these variables but is independent of luminance when each discrimination threshold is divided by the detection threshold for the test grating presented alone. The data in this 5-dimensional space can be described quantitatively if expressed in amplitudes instead of contrasts. The resulting model of visual amplitude sensitivity has seven parameters that are specific to a particular observer and are tied to identifiable visual properties. The "pedestal effect" and tests with the pedestal and test gratings out-of-phase can be explained by subthreshold summation but not stimulus uncertainty.

Contrast Sensitivity↗

The solution structure of stilbenoid dendrimers: a small-angle scattering study.

The spatial structure of a stilbenoid dendrimer is investigated by small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) in dilute solution. All measurements are performed in toluene. The dendrimer consists of a stilbenoid scaffold with appended hexyloxy chains. SAXS is mainly sensitive to the dendrimer scaffold whereas SANS intensity, measured in fully deuterated toluene, derives from the solute molecules. The resulting SAXS and SANS intensities are analyzed by comparison with various models. It is found that the model of a circular disk gives the best description of the data. SAXS data demonstrate that the stilbenoid scaffold is flat as expected for benzene rings conjugated through vinylene units. Thus, it can be described by a circular disk with a radius of 1.6 nm and a thickness of 0.7 nm. SANS, on the other hand, shows that the hexyloxy chains are not confined in the plane defined by the core. This is derived from modeling the SANS data with a much thicker circular disk (radius: 2.4 nm, thickness: 1.8 nm). The structure factor S(q), describing the interaction of the dendrimers at higher concentrations, is modeled quantitatively with the "polymer reference interaction site model" (PRISM) integral equation formalism for hard plates such as particles. Here the structural data obtained from the analysis of the SANS data are used so that no new adjustable parameter is necessary for this description.

Journal Article↗

Multicut-HDMR with an application to an ionospheric model.

A new High Dimensional Model Representation (HDMR) tool, Multicut-HDMR, is introduced and applied to an ionospheric electron density model. HDMR is a general set of quantitative model assessment and analysis tools for improving the efficiency of deducing high-dimensional input-output system behavior. HDMR describes an output [f(x)] in terms of its input variables (x = [x(1), x(2), em leader, x(n)]) via a series of finite, hierarchical, correlated function expansions. Various forms of HDMR are constructed for different purposes such as modeling laboratory or field data, or reproducing a complicated mathematical model. The Cut-HDMR technique, which expresses f(x) with respect to a specified reference point x in the input space, is appropriate when the input space is sampled in an orderly fashion. However, if the desired domain of the input space is too large, the HDMR function expansion may not converge, and Cut-HDMR will be unable to accurately approximate f(x). The new Multicut-HDMR technique addresses this problem through the use of multiple reference points in the input space.

Journal Article↗

Modeling transcriptional control in gene networks--methods, recent results, and future directions.

Mathematical models are useful for providing a framework for integrating data and gaining insights into the static and dynamic behavior of complex biological systems such as networks of interacting genes. We review the dynamic behaviors expected from model gene networks incorporating common biochemical motifs, and we compare current methods for modeling genetic networks. A common modeling technique, based on simply modeling genes as ON-OFF switches, is readily implemented and allows rapid numerical simulations. However, this method may predict dynamic solutions that do not correspond to those seen when systems are modeled with a more detailed method using ordinary differential equations. Until now, the majority of gene network modeling studies have focused on determining the types of dynamics that can be generated by common biochemical motifs such as feedback loops or protein oligomerization. For example, these elements can generate multiple stable states for gene product concentrations, state-dependent responses to stimuli, circadian rhythms and other oscillations, and optimal stimulus frequencies for maximal transcription. In the future, as new experimental techniques increase the ease of characterization of genetic networks, qualitative modeling will need to be supplanted by quantitative models for specific systems.

Animals↗

What response times tell of children's behavior on the balance scale task.

Analysis of accuracy of responses to balance scale problems gives a global idea of the cognitive processes that underlie problem-solving behavior on this task. We show that response times (RTs) provide additional detailed information about the kind and duration of these processes. We derive predictions about the RTs from Siegler's (1981) model for the balance scale task, including the counterintuitive prediction that young adults are slower than children in solving particular balance scale problems. The predictions were tested in a study in which 191 6- to 22-year-old participants were presented with a computerized balance scale task. RTs were analyzed with regression models. In addition to qualitative differences between items, we also modeled quantitative differences between items in the regression models. Analyses supported the predictions and provided additional knowledge on the rules. Rule II was reformulated as a rule that always involves the encoding, but not always the correct application of the distance cue. RTs provided evidence for the use of a buggy-rule and not an addition-rule. Finally, a relation between rule inconsistency and increased RT was found.

Adolescent↗

A note on Corballis (1997) and the genetics and evolution of handedness: developing a unified distributional model from the sex-chromosomes gene hypothesis.

A unified, quantitative model for sex, twin, parent, and grandparent influences on handedness is presented. Recent research modeling the evolutionary development of genetic mechanisms for the transmission of handedness on the basis of genotype fitness has appeared to lead to the conclusion that a handedness gene cannot be located on the sex chromosomes. It is shown in this article, however, that this conclusion is not of general validity. The sex-chromosomes hypothesis is developed further, and it is demonstrated that a wide-ranging, detailed, and parsimonious account of the distribution of handedness is obtained when left-handedness is assumed to be associated recessively, and with low penetrance, with genetic variation located on the X chromosome.

Female↗

Continuous-time identification of gene expression models.

One objective of systems biology is to create predictive, quantitative models of the transcriptional regulation networks that govern numerous cellular processes. Gene expression measurements, as provided by microarrays, are commonly used in studies that attempt to infer the regulation underlying these processes. At present, most gene expression models that have been derived from microarray data are based in discrete-time, which have limited applicability to common biological data sets, and may impede the integration of gene expression models with other models of biological processes that are formulated as ordinary differential equations (ODEs). To overcome these difficulties, a continuous-time approach for process identification to identify gene expression models based in ODEs was developed. The approach utilizes the modulating functions method of parameter identification. The method was applied to three simulated systems: (1) a linear gene expression model, (2) an autoregulatory gene expression model, and (3) simulated microarray data from a nonlinear transcriptional network. In general, the approach was well suited for identifying models of gene expression dynamics, capable of accurately identifying parameters for small numbers of data samples in the presence of modest experimental noise. Additionally, numerous insights about gene expression modeling were revealed by the case studies.

Data Interpretation, Statistical↗

A model for DNA sequence evolution within transposable element families.

A quantitative model is proposed for the expected degree of relationship between copies of a family of transposable elements in a finite population of hosts. Special cases of the model (in which the process of homogenization of element copies either is or is not limited by transposition rate) are presented and illustrated, using data on mobile sequences from different species. It is shown that transposition will be expected, in large populations, to result in only a rather distant relationship between transposable elements at different genomic sites. Possible inadequacies of the model are suggested and quantified.

Animals↗