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At least 199 records · Page 11Linked to original sources
PubMed1984

A model for the distribution and clearance of inert substances in subcutaneous tissue.

The subcutaneous space has received attention in recent years as a route for the continuous administration of drugs and implantation of drug delivery systems. Yet little work has been devoted to an examination of the mass transport (distribution) of drugs in the subcutaneous space and the factors that influence their rate of clearance. A mathematical model is developed to describe the spreading and resorption of substances infused into the subcutaneous space. It simulates radial diffusion and flow in the direction of spreading as well as lateral convection into the systemic circulation. An analytic solution is obtained for the distribution of the substance as a function of time and position in the subcutaneous space. Two independent parameters, v (Péclét no.) and H (generalized Biot no.), are found to control the transport. Examples are presented to illustrate the effects of these parameters on the distribution of substances in the subcutaneous space.

Absorption↗
PubMed2004

The measurement of solute diffusion coefficients in dilute liquid alloys: the influence of unit gravity and g-jitter on buoyancy convection.

Liquid diffusion experiments conducted on the MIR space station using the Canadian Space Agency QUELD II processing facility and the microgravity isolation mount (MIM) showed that g-jitter significantly increased the measured solute diffusion coefficients. In some experiments, milli-g forced vibration was superimposed on the sample when isolated from the ambient g-jitter; this resulted in markedly increased solute transport. To further explore the effects arising in these long capillary diffusion couples from the absence of unit-gravity and the presence of the forced g-jitter, the effects of a 1 milli-g forcing vibration on the mass transport in a 1.5 mm diameter long capillary diffusion couple have been simulated. In addition, to increase understanding of the role of unit gravity in determining the extent to which gravity can influence measured diffusion coefficient values, comparative experiments involving gold, silver, and antimony diffusing in liquid lead have been carried out using a similar QUELD II facility to that employed in the QUELD II/MIM/MIR campaign but under terrestrial conditions. It was found that buoyancy-driven convection may still persist in the liquid even when conditions are arranged for a continuously decreasing density gradient up the axis of a vertical long capillary diffusion couple due to the presence of small radial temperature gradients.

Acceleration↗
PubMed1984

Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness.

Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 degrees) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100% during seven days of AO suspension concurrently with a pronounced natriuresis. These results suggest that aldosterone many not be involved in the long term regulation of increased Na+ excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

Adaptation, Physiological↗
PubMed2002

Generalized theory and simulation of spontaneous and super-radiant emissions in electron devices and free-electron lasers.

A unified formulation of spontaneous (shot-noise) and super-radiant emissions in electron devices is presented. We consider an electron beam with an arbitrary temporal current modulation propagating through the interaction region of the electronic device. The total electromagnetic field is presented as a stochastic process and expanded in terms of transverse eigenmodes of the medium (free space or waveguide), in which the field is excited and propagates. Using the waveguide excitation equations, formulated in the frequency domain, an analytical expression for the power spectral density of the electromagnetic radiation is derived. The spectrum of the excited radiation is shown to be composed of two terms, which are the spontaneous and super-radiant emissions. For a continuous, unmodulated beam, the shot noise produces only incoherent spontaneous emission of a power proportional to the flux eI(0) (DC current) of the particles in the electron beam. When the beam is modulated or prebunched, a partially coherent super-radiant emission is also produced with power proportional to the current spectrum /I(omega)/(2). Based on a three-dimensional model, a numerical particle simulation code was developed. A set of coupled-mode excitation equations in the frequency domain are solved self-consistently with the equations of particles motion. The simulation considers random distributions of density and energy in the electron beam and takes into account the statistical and spectral features of the excited radiation. At present, the code can simulate free-electron lasers (FELs) operation in various modes: spontaneous and self-amplified spontaneous emission, super-radiance and stimulated emission, in the linear and nonlinear Compton or Raman regimes. We employed the code to demonstrate spontaneous and super-radiant emission excited when a prebunched electron beam passes through a wiggler of an FEL.

Journal Article↗
PubMed1989

Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.

The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of greater than or equal to 2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.

Aerosols↗
PubMed2004

Selection of beam orientations in intensity-modulated radiation therapy using single-beam indices and integer programming.

While the process of IMRT planning involves optimization of the dose distribution, the procedure for selecting the beam inputs for this process continues to be largely trial-and-error. We have developed an integer programming (IP) optimization method to optimize beam orientation using mean organ-at-risk (MOD) data from single-beam plans. Two test cases were selected in which one organ-at-risk (OAR) and four OARs were simulated, respectively, along with a PTV. Beam orientation space was discretized in 10 degrees increments. For each beam orientation, a single-beam plan without intensity modulation and without constraints on OAR dose was generated and normalized to yield a mean PTV dose of 2 Gy and the corresponding MOD was calculated. The degree of OAR sparing was related to the average OAR MODs resulting from the beam orientations utilized with improvements of up to 10% at some dose levels. On the other hand, OAR DVHs in the IMRT plans were insensitive to beam numbers (in the 6-9 range) for similar average single-beam MODs. These MOD data were input to an IP optimization process, which then selected specified numbers of beam angles as inputs to a treatment planning system. Our results show that sets of beam angles with lower average single-beam MODs produce IMRT plans with better OAR sparing than manually selected beam angles. To optimize beam orientations, weights were assigned to each OAR following MOD input to the IP which was subsequently solved using the branch-and-cut algorithm. Seven-beam orientations obtained from solving the IP were applied to the test case with four OARs and the resulting plan with a dose prescription of 63 Gy was compared with an equi-spaced beam plan. The IP selected beams produced dose-volume improvements of up to 40% for OARs proximal to the PTV. Further improvement in the DVH can be obtained by increasing the weights assigned to these OARs but at the expense of the remaining OARs.

Abdomen↗
PubMed2003

Identification of nonlinear spatiotemporal systems via partitioned filtering.

The problem of identifying continuous spatiotemporal nonlinear systems from noisy and indirect observations is determined by its computational complexity. We propose a solution by means of nonlinear state space filtering along with a state partition technique. The method is demonstrated to be computationally feasible for spatiotemporal data with properties that occur typically in experimental recordings. It is applied to one component of the simulated chaotic data of a two-component reaction diffusion system, yielding estimates of both the unobserved state component and the diffusion constant.

Journal Article↗
PubMed1995

Early and late renin and ANP modifications induced by bedrest.

A number of studies have been devoted to better understand the cardiovascular adaptation to space flights. These studies included hemodynamic and hormonal studies, but few investigations of the rhythms exist in the literature. However, the importance of the modifications of rhythms in true or simulated weightlessness was underlined in some published works. Several factors are probably associated to modify the circadian rhythms. First, there is a reduction or an absence of gravity, an important environmental factor: second, space missions or bed rest simulations are conducted under confinement conditions which may influence many psychological functions. The resulting instability of the circadian state will affect other physiological systems, because circadian variations are a fundamental feature of many biological systems (sleep, endocrine and cardiovascular functions). The present study was undertaken to study the effect of as well as a continuous 28-day bed rest on the rhythms of circulating PRA and ANP, the modification of rhythmicity of systolic and diastolic blood pressure and heart rate during bed rest.

Atrial Natriuretic Factor↗
PubMed2004

Distance underestimation in virtual space is sensitive to gender but not activity-passivity or mode of interaction.

Four groups of undergraduates (half of each gender) experienced a movement along a corridor containing three distinctive objects, in a virtual environment (VE) with wide-screen projection. One group simulated walking along the virtual corridor using a proprietary step-exercise device. A second group moved along the corridor in conventional flying mode, depressing a keyboard key to initiate continuous forward motion. Two further groups observed the walking and flying participants, by viewing their progress on the screen. Participants then had to walk along a real equivalent but empty corridor, and indicate the positions of the three objects. All groups underestimated distances in the real corridor, the greatest underestimates occurring for the middle distance object. Males' underestimations were significantly lower than females' at all distances. However, there was no difference between the active participants and passive observers, nor between walking and flying conditions.

Adolescent↗
PubMed1997

A modified CROPGRO model for simulating soybean growth in controlled environments.

The CROPGRO crop growth model is adapted in order to analyze experimental data from a soybean (cv. Hoyt) experiment conducted at elevated CO2 levels (1200 micromol mol-1) at Kennedy Space Center, FL. The following adaptations to original CROPGRO produced model agreement with gas-exchange data: the input of square-wave temperature and photosynthetically active radiation (PAR) profiles; the input of the appropriate hydroponic substrate PAR albedo; modified biomass partitioning and developmental parameters; an increased leaf area expansion rate through the fifth vegetative node; a decreased specific leaf area after the fifth vegetative node; and an increased incident diffuse PAR fraction over typical field values. The model demonstrated here suggests that with continued development, modified CROPGRO will be a useful tool in the analysis and eventual optimization of legume production in bioregenerative life support systems.

Biomass↗
PubMed2001

Increased coupling between subpopulations in a spatially structured environment can lead to population outbreaks.

Destruction and fragmentation of habitats is widely considered as a major threat to biological diversity. A theoretical framework aimed at understanding and predicting species responses to these destructive processes is still lacking, however. In this paper, the species dynamics in a spatially structured, two-habitat, patchy environment is considered subject to changes in individual migration intensity, i.e. coupling between the habitats. The subpopulation dynamics inside each habitat is assumed to be bistable but with different parameter values. By using space-discrete/continuous metapopulation dynamic models and computer simulations, we show that there can be two principally different regimes of metapopulation dynamics. With increasing intensity in the interplay between subpopulations, the total abundance can either gradually decrease or experience a sudden burst-like increase. This result is shown to be robust to the choice of mathematical models (discrete or continuous). Particularly, both the "self-excitation" and "self-inhibition" regimes of the metapopulation system are robust to variation in habitat size; however, when one of the habitats is much smaller than the other, the "self-excitation" regime can give way to the "self-inhibition" regime and vice versa.

Animals↗
PubMed2005

Using animal movement paths to measure response to spatial scale.

Animals live in an environment that is patchy and hierarchical. I present a method of detecting the scales at which animals perceive their world. The hierarchical nature of habitat causes movement path structure to vary with spatial scale, and the patchy nature of habitat causes movement path structure to vary throughout space. These responses can be measured by a combination of path tortuousity (measured with fractal dimension) versus spatial scale, the variation in tortuousity of small path segments along the movement path, and the correlation between tortuousities of adjacent path segments. These statistics were tested using simulated animal movements. When movement paths contained no spatial heterogeneity, then fractal D and variance continuously increased with scale, and correlation was zero at all scales. When movement paths contained spatial heterogeneity, then fractal D sometimes showed a discontinuity at transitions between domains of scale, variation showed peaks at transitions, and correlations showed a statistically significant positive value at scales smaller than patch size, decreasing to below zero at scales greater than patch size. I illustrated these techniques with movement paths from deer mice and red-backed voles. These new analyses should help understand how animals perceive and react to their landscape structure at various spatial scales, and to answer questions about how habitat structure affects animal movement patterns.

Animals↗
PubMed2003

A comparison of physical mapping algorithms based on the maximum likelihood model.

MOTIVATION: Physical mapping of chromosomes using the maximum likelihood (ML) model is a problem of high computational complexity entailing both discrete optimization to recover the optimal probe order as well as continuous optimization to recover the optimal inter-probe spacings. In this paper, two versions of the genetic algorithm (GA) are proposed, one with heuristic crossover and deterministic replacement and the other with heuristic crossover and stochastic replacement, for the physical mapping problem under the maximum likelihood model. The genetic algorithms are compared with two other discrete optimization approaches, namely simulated annealing (SA) and large-step Markov chains (LSMC), in terms of solution quality and runtime efficiency. RESULTS: The physical mapping algorithms based on the GA, SA and LSMC have been tested using synthetic datasets and real datasets derived from cosmid libraries of the fungus Neurospora crassa. The GA, especially the version with heuristic crossover and stochastic replacement, is shown to consistently outperform the SA-based and LSMC-based physical mapping algorithms in terms of runtime and final solution quality. Experimental results on real datasets and simulated datasets are presented. Further improvements to the GA in the context of physical mapping under the maximum likelihood model are proposed. AVAILABILITY: The software is available upon request from the first author.

Algorithms↗
PubMed2006

MCMC data association and sparse factorization updating for real time multitarget tracking with merged and multiple measurements.

In several multitarget tracking applications, a target may return more than one measurement per target and interacting targets may return multiple merged measurements between targets. Existing algorithms for tracking and data association, initially applied to radar tracking, do not adequately address these types of measurements. Here, we introduce a probabilistic model for interacting targets that addresses both types of measurements simultaneously. We provide an algorithm for approximate inference in this model using a Markov chain Monte Carlo (MCMC)-based auxiliary variable particle filter. We Rao-Blackwellize the Markov chain to eliminate sampling over the continuous state space of the targets. A major contribution of this work is the use of sparse least squares updating and downdating techniques, which significantly reduce the computational cost per iteration of the Markov chain. Also, when combined with a simple heuristic, they enable the algorithm to correctly focus computation on interacting targets. We include experimental results on a challenging simulation sequence. We test the accuracy of the algorithm using two sensor modalities, video, and laser range data. We also show the algorithm exhibits real time performance on a conventional PC.

Algorithms↗
PubMed1986

Joint scintigraphy using technetium-99m pyrophosphate in experimental hemarthrosis.

To determine the validity of a method for induction of experimental hemarthrosis in dogs and for the nuclear imaging of hemarthrosis, serial technetium-99m pyrophosphate [( 99mTc]PYP) flow and blood-pool scans were performed monthly in eight dogs who received bi-weekly injections of autologous blood into their femoro-tibial joints (also called stifle joint). In four control dogs, one joint was injected with saline while the other joint received only a sham injection. In addition, two dogs received intra-articular injections of autologous blood into their right stifle joint and saline into their left stifle joint. These dogs were studied with 99mTcO4 joint scintigraphy at monthly intervals. The dogs were periodically taken out of the study and explored surgically. Pathologic examination of synovial tissue was performed. Serial radiographs were also obtained and correlated with the scan and surgical findings. There was a striking abnormal increase in blood-pool activity of [99mTc]PYP in the treated stifle joints, commencing at the first examination after 1 mo of blood injections and continuing for the length of the study. All radiographs showed only minimal joint space widening and some soft-tissue swelling. On pathologic examination, both grossly and microscopically, there was profuse pannus formation, with intense inflammatory infiltrate replacing much of the subsynovial fat. The scintigraphic findings correlated well with these pathologic findings. This study not only validates this method for simulating hemophilic hemarthrosis but also suggests that [99mTc]PYP joint scintigraphy is a simple, and noninvasive method for monitoring the early changes in hemophilic arthropathy and is superior to pertechnetate imaging for this disease process. Instead of the previously recommended delayed bone images, we recommend, in addition, flow studies to assess joint hypervascularity and immediate static images to visualize the synovium and joint capsule.

Animals↗
PubMed1985

Texture of B-mode echograms: 3-D simulations and experiments of the effects of diffraction and scatterer density.

B-mode echograms were simulated by employing the impulse response method in transmission and reception using a discrete scatterer tissue model, with and without attenuation. The analytic signal approach was used for demodulation of the RF A-mode lines. The simulations were performed in 3-D space and compared to B-mode echograms obtained from experiments with scattering tissue phantoms. The average echo amplitude appeared to increase towards the focus and to decrease beyond it. In the focal zone, the average amplitude increased proportionally to the square root of the scatterer density. The signal to noise ratio (SNR) was found to be independent of depth, i.e., 1.91 as predicted for a Rayleigh distribution of gray levels, although a minimum was found in the focal zone at relatively low scatterer densities. The SNR continuously increased with increasing scatterer density and reached the limit of 1.91 at relatively high densities (greater than 10(4) cm-3). The lateral full width at half maximum (FWHM) of the two dimensional autocovariance function of the speckle increased continuously from the transducer face to far beyond the focus and decreased thereafter due to the diffraction effect. The lateral FWHM decreased proportionally to the logarithm of the scatterer density at low densities and reached a limit at high densities. Introduction of attenuation in the simulated tissue resulted in a much more pronounced depth dependence of the texture. The axial FWHM was independent of the distance to the transducer to a first approximation and decreased slightly with increasing scatterer density until a limit was reached at densities larger than 10(3) cm-3. This limit was in agreement with theory. The experiments confirmed the simulations and it can be concluded that the presented results are of great importance to the understanding of B-mode echograms and to the potential use of the analysis of B-mode texture for tissue characterization.

Mathematics↗
PubMed1990

Role of the hippocampus in temporal and spatial navigation: an adaptive neural network.

The hippocampus has been proposed to participate in either spatial or temporal mapping. As an alternative to these seemingly conflicting views, we hypothesized that the hippocampus computes 'aggregate predictions' of environmental events that are used to control associative learning. Aggregate predictions forecast what event is going to occur, when in time, and where in space. The hypothesis assumes that activity of hippocampal pyramidal neurons is proportional to the instantaneous value of the aggregate prediction, and that the computation of the aggregate prediction is impaired by hippocampal lesions. In order to test the 'aggregate prediction' hypothesis in both spatial and temporal tasks, this paper presents a real-time neural network capable of describing temporal discrimination and spatial learning in a unified fashion. The neural network incorporates detectors that can be tuned to a particular value of continuous temporal or spatial variables. In the temporal domain, computer simulations were carried out for temporal discrimination in classical conditioning and instrumental learning, classical conditioning under different interstimulus intervals (ISIs), and classical conditioning with mixed ISIs. In the spatial domain, computer simulations were carried out for place and cue learning. The paper shows that under the 'aggregate prediction' hypothesis the network correctly describes activity of hippocampal pyramidal neurons and the effect of hippocampal lesions in temporal and spatial learning. These results suggest that, rather than either a temporal or spatial function, the hippocampus is involved in the computation of variables common to both temporal and spatial navigation.

Animals↗
PubMed2006

Nanoliter scale microbioreactor array for quantitative cell biology.

A nanoliter scale microbioreactor array was designed for multiplexed quantitative cell biology. An addressable 8 x 8 array of three nanoliter chambers was demonstrated for observing the serum response of HeLa human cancer cells in 64 parallel cultures. The individual culture unit was designed with a "C" shaped ring that effectively decoupled the central cell growth regions from the outer fluid transport channels. The chamber layout mimics physiological tissue conditions by implementing an outer channel for convective "blood" flow that feeds cells through diffusion into the low shear "interstitial" space. The 2 microm opening at the base of the "C" ring established a differential fluidic resistance up to 3 orders of magnitude greater than the fluid transport channel within a single mold microfluidic device. Three-dimensional (3D) finite element simulation were used to predict fluid transport properties based on chamber dimensions and verified experimentally. The microbioreactor array provided a continuous flow culture environment with a Peclet number (0.02) and shear stress (0.01 Pa) that approximated in vivo tissue conditions without limiting mass transport (10 s nutrient turnover). This microfluidic design overcomes the major problems encountered in multiplexing nanoliter culture environments by enabling uniform cell loading, eliminating shear, and pressure stresses on cultured cells, providing stable control of fluidic addressing, and permitting continuous on-chip optical monitoring.

Bioreactors↗