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At least 343 records · Page 19Linked to original sources
PubMed1993

The steady expiratory pressure-flow relation in a model pulmonary bifurcation.

Experiments were conducted over a range of Reynolds numbers from 50 to 8000 to study the pressure-flow relationship for a single bifurcation in a multi-generation model during steady expiratory flow. Using the energy equation, the measured static pressure drop was decomposed into separate components due to fluid acceleration and viscous energy dissipation. The frictional pressure drop was found to closely approximate that for an equivalent length of curved tube with the same curvature ratio as in the model bifurcation. The sensitivity of these results to changes in airway cross-sectional shape, non-planar configuration, and flow regime (laminar-turbulent) was investigated. In separate experiments using dye visualization and hot-wire anemometry, a transition to turbulent flow was observed at Reynolds numbers between 1000 and 1500. Transition had very little effect on the pressure-flow relation.

Acceleration↗
PubMed2000

Metastatic burden in nude mice organs measured using prostate tumor PC-3 cells expressing the luciferase gene as a quantifiable tumor cell marker.

BACKGROUND: Sensitive procedures for quantitative measurement of tumor cell spread as a function of time and primary tumor size are necessary to generate models of metastasis and formulate therapies. METHODS: Prostate carcinoma cells PC-3.luc expressing the luciferase gene were intramuscularly inoculated in nude mice to generate experimental tumors. Metastatic cells in target organs were easily counted by their capacity to produce light. RESULTS: Tumor cells were very mobile and migrated to all the target organs examined: lymph nodes, brain, bone, lungs, liver, kidney, spleen, testicles, prostate, seminal vesicle, and scrotum. Organ colonization started very early, 14 days after inoculation, when primary tumors were very small and produced an amount of light equivalent to that generated by 2 x 10(4) tumor cells in vitro (tumor cell equivalents, TCEs). Tumor cell burden could be quantitatively described by power functions of time or primary tumor light-producing capacity. The ratio of metastatic TCEs to primary tumor TCEs clustered around organ characteristic values: 10(-3) for femur and lumbar lymph nodes, 10(-6) for the spleen, and 10(-3) for the added set of organs. CONCLUSIONS: Dispersal of PC-3 tumor cells from IM experimental tumors started early before the third week postinoculation and when primary tumors had 2 x 10(4) TCEs. Tumor cells were found widely spread in all the organs tested. The possibility of easily quantifying tumor cell burden should make this approach useful for the study of metastasis and the development of antimetastatic therapies.

Adenocarcinoma↗
PubMed1999

Disease-marker associations: power and heterogeneity in independent population samples.

We applied generalized transmission disequilibrium testing (TDT) models in combined replicates 1 through 5 from each of four simulated population samples. All analyses were conducted without knowledge of the generating models. To assess power and consistency of results within and between samples, analyses were repeated in all 25 replicates combined and in each replicate. With the exception of sample-specific findings for locus D, power was generally low to detect linkage in a genome scan or to confirm linkages detected by allele sharing in affected relatives, due to lack of linkage disequilibrium. We proposed likelihood ratio and Wald tests to detect heterogeneity among samples in disease-marker associations. Pooling data across heterogeneous populations may not improve power of the TDT method.

Genetic Linkage↗
PubMed1992

Simulation of Doppler ultrasound signals for a laminar, pulsatile, nonuniform flow.

A simulation for Doppler ultrasound quadrature signals from pulsatile, nonuniform flow is presented. It is an extension of an earlier simulation presented by Jones and Giddens (1990a) which was valid for laminar, uniform, steady flow and which included the stochastic characteristics introduced by scattering particles which enter and leave the sample volume at random times. Fourier transform and autoregressive spectral analysis techniques are used to compare the simulated signals to Doppler signals collected from an in vitro flow setup. Power spectra, Doppler frequency estimates and standard deviations of these estimates serve as standards of comparison. Results show that the simulation model generates realistic quadrature signals. The study improves the understanding of the physics of the Doppler process and shows that it can be modeled for complex flow conditions. The input parameters of the simulation are the Doppler instrument parameters and flow characteristics. This allows the simulation to be used for transducer design as well as in the study of the applicability of signal analysis techniques to Doppler ultrasound.

Blood Flow Velocity↗
PubMed1995

Transbilayer pores formed by beta-barrels: molecular modeling of pore structures and properties.

Transmembrane beta-barrels, first observed in bacterial porins, are possible models for a number of membrane channels. Restrained molecular dynamics simulations based on idealized C alpha beta templates have been used to generate models of such beta-barrels. Model beta-barrels have been analyzed in terms of their conformational, energetic, and pore properties. Model beta-barrels formed by N = 4, 8, 12 and 16 anti-parallel Ala10 strands have been developed. For each N, beta-barrels with shear numbers S = N to 2N have been modeled. In all beta-barrel models the constituent beta-strands adopt a pronounced right-handed twist. Interstrand interactions are of approximately equal stability for all models with N > or = 8, whereas such interactions are weaker for the N = 4 beta-barrels. In N = 4 beta-barrels the pore is too narrow (minimum radius approximately 0.6 A) to allow ion permeation. For N > or = 8, the pore radius depends on both N and S; for a given value of N an increase in S from N to 2N is predicted to result in an approximately threefold increase in pore conductance. Calculated maximal conductances for the beta-barrel models are compared with experimental values for porins and for K+ channels.

Alanine↗
PubMed1991

Functional interactions in the brain: use of correlations between regional metabolic rates.

Correlation coefficients between pairs of regional metabolic rates have been used to study patterns of functional associations among brain regions in humans and animals. An overview is provided concerning the additional information about brain functioning this type of analysis yields. A computer simulation model is presented for the purpose of giving a partial validation for correlational analysis. The model generates a set of simulated metabolic data upon which correlational analysis is performed. Because the underlying pattern of functional couplings in the model is known, these simulations demonstrate that the correlation coefficient between normalized metabolic rates is proportional to the strength of the functional coupling constant and that correlational analysis yields information on regional involvement in neural systems not evident in the pattern of absolute metabolic values.

Adult↗
PubMed1999

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

Gene Frequency↗
PubMed2000

Lung delivery of aerosolized dextran.

The ability of nebulizers to deliver dextran (nominal molecular mass, 4,000 g/mol) to the lung as an inhaled aerosol is evaluated by in vitro experimental methods and mathematical models. Dextran in isotonic saline was aerosolized by four nebulizer types (Pari LC STAR, Hudson T-Updraft II, Acorn II, and Sonix 2000) at dextran concentrations </= 400 mg/ml and with 2.5- and 4-ml volume fills. Aerosols inhaled during breath simulation were characterized by in-line phase Doppler anemometry, filter collection, osmometry, and gravimetry. Mathematical models were used to estimate amounts of the characterized aerosols depositing in the different regions of lung models, and mathematical models of mucous thickness were then developed to estimate initial concentrations of the depositing dextran in the mucus of each conducting airway generation. Models of three subjects (4 yr old, 8 yr old, and adult) were used. The high viscosity of the dextran solutions tested (up to seven times that of water) negatively impacts nebulization, and results in poor performance with most delivery systems tested. Our results suggest that airway mucosal dextran concentrations associated with efficacy in previous animal and in vitro models are achievable with reasonable delivery times (</= 12 min) with only one of the delivery systems/formulations tested: the Pari LC STAR nebulizer, using a 2. 5-ml volume fill and a dextran concentration of 200 mg/ml.

Administration, Inhalation↗
PubMed1997

A neural model of multimodal adaptive saccadic eye movement control by superior colliculus.

How does the saccadic movement system select a target when visual, auditory, and planned movement commands differ? How do retinal, head-centered, and motor error coordinates interact during the selection process? Recent data on superior colliculus (SC) reveal a spreading wave of activation across buildup cells the peak activity of which covaries with the current gaze error. In contrast, the locus of peak activity remains constant at burst cells, whereas their activity level decays with residual gaze error. A neural model answers these questions and simulates burst and buildup responses in visual, overlap, memory, and gap tasks. The model also simulates data on multimodal enhancement and suppression of activity in the deeper SC layers and suggests a functional role for NMDA receptors in this region. In particular, the model suggests how auditory and planned saccadic target positions become aligned and compete with visually reactive target positions to select a movement command. For this to occur, a transformation between auditory and planned head-centered representations and a retinotopic target representation is learned. Burst cells in the model generate teaching signals to the spreading wave layer. Spreading waves are produced by corollary discharges that render planned and visually reactive targets dimensionally consistent and enable them to compete for attention to generate a movement command in motor error coordinates. The attentional selection process also helps to stabilize the map-learning process. The model functionally interprets cells in the superior colliculus, frontal eye field, parietal cortex, mesencephalic reticular formation, paramedian pontine reticular formation, and substantia nigra pars reticulata.

Animals↗
PubMed1989

Ecological modelling in an evolutionary context.

I argue that one of the strong features in disciplines like molecular biology and cosmology is the extent ot which they use a powerful theoretical framework to generate and test quantitative predictions. Studies of biological evolution can exploit a similar advantage by integrating our current understanding of physiological and sociobiological processes to generate models of much greater sophistication than has commonly been the practice hitherto. I illustrate this with a number of examples drawn from the evolutionary biology of human and nonhuman primates.

Animals↗
PubMed1988

Three-dimensional reconstruction of myocardial contrast perfusion from biplane cineangiograms by means of linear programming techniques.

The assessment of coronary flow reserve from the instantaneous distribution of the contrast agent within the coronary vessels and myocardial muscle at the control state and at maximal flow has been limited by the superimposition of myocardial regions of interest in the two-dimensional images. To overcome these limitations, we are in the process of developing a three-dimensional (3D) reconstruction technique to compute the contrast distribution in cross sections of the myocardial muscle from two orthogonal cineangiograms. To limit the number of feasible solutions in the 3D-reconstruction space, the 3D-geometry of the endo- and epicardial boundaries of the myocardium must be determined. For the geometric reconstruction of the epicardium, the centerlines of the left coronary arterial tree are manually or automatically traced in the biplane views. Next, the bifurcations are detected automatically and matched in these two views, allowing a 3D-representation of the coronary tree. Finally, the circumference of the left ventricular myocardium in a selected cross section can be computed from the intersection points of this cross section with the 3D coronary tree using B-splines. For the geometric reconstruction of the left ventricular cavity, we envision to apply the elliptical approximation technique using the LV boundaries defined in the two orthogonal views, or by applying more complex 3D-reconstruction techniques including densitometry. The actual 3D-reconstruction of the contrast distribution in the myocardium is based on a linear programming technique (Transportation model) using cost coefficient matrices. Such a cost coefficient matrix must contain a maximum amount of a priori information, provided by a computer generated model and updated with actual data from the angiographic views. We have only begun to solve this complex problem. However, based on our first experimental results we expect that the linear programming approach with advanced cost coefficient matrices and computed model will lead to acceptable solutions in the 3D-reconstruction of the myocardial contrast distribution from biplane cineangiograms.

Cineangiography↗
PubMedDate not supplied

Lumped model of terminal aortic impedance in the dog.

The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9 +/- 5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance, Rp, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C). Rp was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents.

Animals↗
PubMed1990

Routes to chaos in a model of a bursting neuron.

Chaotic regimens have been observed experimentally in neurons as well as in deterministic neuronal models. The R15 bursting cell in the abdominal ganglion of Aplysia has been the subject of extensive mathematical modeling. Previously, the model of Plant and Kim has been shown to exhibit both bursting and beating modes of electrical activity. In this report, we demonstrate (a) that a chaotic regime exists between the bursting and beating modes of the model, and (b) that the model approaches chaos from both modes by a period doubling cascade. The bifurcation parameter employed is the external stimulus current. In addition to the period doubling observed in the model-generated trajectories, a period three "window" was observed, power spectra that demonstrate the approaches to chaos were generated, and the Lyaponov exponents and the fractal dimension of the chaotic attractors were calculated. Chaotic regimes have been observed in several similar models, which suggests that they are a general characteristic of cells that exhibit both bursting and beating modes.

Animals↗
PubMed1999

Application and comparison of two modelling techniques for hospital bed management.

The use of the bed occupancy management and planning system (BOMPS) and the Sorensen multi-phased bed model were used to assess the implications of a hospital expanding its emergency facility. BOMPS flow modelling generates resource utilisation data dependent on the best visual and statistical fit between mixed exponential equations and time of bed occupancy; the Sorensen model creates models based on probabilities and length of stay distributions. Both models identified the presence of two streams of flow. However, there were differences in the number of beds identified as being short and longer stay. The advantage of flow modelling is that it enables decision-makers to pre-test their decisions.

Australia↗
PubMed2000

Appropriate tissue- and cell-specific expression of a single copy human angiotensinogen transgene specifically targeted upstream of the HPRT locus by homologous recombination.

Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this transgenic mouse model is that the human angiotensinogen gene is inserted into the mouse genome as a single copy at a predefined locus and in a specific orientation-a process that can be repeated utilizing other variants of this gene. We establish the validity of this approach by showing that the hAGT(hprt) mice have normal tissue- and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels.

Angiotensinogen↗
PubMed1988

Estimation of intramyocardial pressure and coronary blood flow distribution.

To characterize the intramyocardial pressure (IMP) and coronary blood flow distribution in a stenosed coronary circulation, we compared four analog circuits for modeling coronary impedance. The resistor (R)-diode (D) model simulates vascular collapse, and the capacitor (C) simulates compliance effect. Identification of the best model and magnitudes of the endocardial and epicardial IMPs (IMPendo and IMPepi) was done retrospectively using data from studies in 28 anesthetized swine. Performance evaluation was based on comparison of model predicted vs. observed coronary distal pressure (DP) waveforms and endocardial-to-epicardial (endo-epi) flow ratios as determined by radiolabeled microspheres. The R-D-C model gave the best performance at IMPendo = 1.1 times left ventricular pressure (LVP), and IMPepi = 0.1.LVP + 15 mmHg; with good fit to DP (r = 0.98, slope of regression line = 1.0) and estimates of endo-epi flow ratio (r = 0.78, slope = 1.01, P less than 0.02, SEE = 0.21, n = 139). The R-D model gave comparable results even though capacitance was omitted. Although R-C and R models predicted distal coronary pressure well, they failed to predict endo-epi flow ratios (r less than 0.50). The R-D-C and R-D models were applied in seven prospective studies. Both models generated reasonable estimates of endo-epi flow distribution (r = 0.78, n = 50). Thus the R-D-C or R-D models of the stenosed coronary circulation can be used to provide reliable estimates of transmural blood flow distribution.

Animals↗
PubMed1991

A tissue pressure model for palpatory perception of the cranial rhythmic impulse.

A tissue pressure model was developed to provide a possible physiologic basis for the manifestation of the cranial rhythmic impulse (CRI). The model assumes that the sensation described as the CRI is related to activation of slowly adapting cutaneous mechanoreceptors by tissue pressures of both the examiner and the subject, and that the sources of change in these tissue pressures are the combined respiratory and cardiovascular rhythms of both examiner and subject. The model generates rhythmic impulses with patterns similar to those reported for the CRI. Also, a significant correlation was found between frequencies calculated from the model and published values for CRI obtained by palpation. These comparisons suggest that the CRI may arise in soft tissues and represents a complex interaction of at least four different physiologic rhythms.

Humans↗
PubMed1986

Genetics of Darwinian fitness. III. A generalized approach to age structured selection and life history.

Most models in life history assume that maximization of lambda holds. Demographic genetic theory supports this assumption provided (i) the fecundity of each mating is determined solely by the age and genotype of the female, (ii) the two sexes experience the exact same selection intensities, and (iii) the two sexes are equal in their age specific schedules of survival and fecundity. But these assumptions will often not hold in nature: thus a more general means of analysis closely integrated with a broader genetic treatment is attempted here. First, operators are derived to map sex specific non-overlapping generation models into the more general case in which generations can overlap. Application of such operators then suggests a broader representation of age structured selection in which evolution acts according to a single composite Wrightian topography whose gradient is a weighted mean taken over selective gradients in all of the age classes. Application of this view is straightforward, showing, for example, that (i) the evolutionary maximization of lambda, which is the basis of present optimization theories for life history, is extremely fragile with biological deviation from mathematical assumptions used in its derivation, (ii) the cost of meiosis argument is shown not to conflict with traditional life history theory, although its correct application will depend critically and subtly upon how genic effects on fertility are measured, and (iii) correct weightings for age specific selection converge to those of Hamilton (1966) and Schaffer (1974) only when sex specific differences in fertility and survival are nonexistent or when selection occurs only in the demographically dominant sex. For life history problems beyond assumptions underlying tradition approaches the composite adaptive topography seems to provide a suitable alternate means for analysis.

Adaptation, Physiological↗