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At least 217 records · Page 12Linked to original sources

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↗

A mathematical model of the human respiratory system.

A model of the human respiratory system is proposed which has a satisfactory performance under different physiological conditions. The model comprises a continuous plant and a discrete controller which generates and updates the drive signal to the plant at the end of every breath to represent the Hering-Breuer reflex. Arterial and central medullary sensors are included. The lung volume, dead space volume, cardiac output and cerebral blood flow are time varying. The respiratory work is minimized. The model is examined and simulation results of its performance in hypercapnia, hypoxia, periodic breathing and moderate exercise are presented. The responses presented include the relatively fast transients of Cheyne-Stokes breathing and the slower transients associated with carbon dioxide inhalation.

Blood Circulation↗

Searching on patch networks using correlated random walks: space usage and optimal foraging predictions using Markov chain models.

We describe a novel representation of a discrete correlated random walk as the transition matrix of a Markov chain with the displacements as the states. Such a representation makes it possible to utilize results from the theory of absorbing Markov chains, to make biologically interesting predictions without having to resort to Monte Carlo simulations. Our motivation for constructing such a representation is to explore the relationship between the movement strategy of an animal searching for resources upon a network of patches, and its consequent utilization of space and foraging success. As an illustrative case study, we have determined the optimal movement strategy and the consequent usage of space for a central place forager utilizing a continuous movement space which is discretized as a hexagonal lattice. The optimal movement strategy determines the size of the optimal home range. In this example, the animal uses mnemokinesis, which is a sinuosity regulating mechanism, to return it to the central place. The movement strategy thus refers to the choice of the intrinsic path sinuosity and the strength of the mnemokinetic mechanism. Although the movement space has been discretized as a regular lattice in this example, the method can be readily applied to naturally compartmentalized movement spaces, such as forest canopy networks. This paper is thus an attempt at incorporating results from the theory of random walk-based animal movements into Foraging Theory.

Animals↗

Synthetic multifunctional pores with external and internal active sites for ligand gating and noncompetitive blockage.

Design, synthesis, and multifunctionality of p-octiphenyl beta-barrel pores with external LRL triads and internal HH dyads are described. Molecular recognition of anionic fullerenes > calixarenes > pyrenes by guanidinium arrays at the outer pore surface is shown to result in pore opening, whereas alpha-helix recognition within the topologically matching internal space is shown to result in noncompetitive pore blockage. This experimental evidence for multifunctionality is supported by comparison with pertinent control pores and blockers, by structural studies using FRET from p-octiphenyl donors in the pore to BODIPY acceptors in the bilayer, and by molecular mechanics simulations. Practical usefulness of ligand-gated synthetic multifunctional pores is exemplified with the continuous detection of chemical processes.

Animals↗

Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight.

To determine the influence of a 17-day exposure to real and simulated spaceflight (SF) on cardiorespiratory function during exercise, four male crewmembers of the STS-78 space shuttle flight and eight male volunteers were studied before, during, and after the 17-day mission and 17 days of -6 degrees head-down-tilt bed rest (BR), respectively. Measurements of oxygen uptake, pulmonary ventilation, and heart rate were made during submaximal cycling 60, 30, and 15 days before the SF liftoff and 12 and 7 days before BR; on SF days 2, 8, and 13 and on BR days 2, 8, and 13; and on days 1, 4, 5, and 8 after return to Earth and on days 3 and 7 after BR. During 15 days before liftoff, day 4 after return, and day 8 after return and all BR testing, each subject completed a continuous exercise test to volitional exhaustion on a semirecumbent (SF) or supine (BR) cycle ergometer to determine the submaximal and maximal cardiorespiratory responses to exercise. The remaining days of the SF testing were limited to a workload corresponding to 85% of the peak pre-SF peak oxygen uptake (Vo2 peak) workload. Exposure to and recovery from SF and BR induced similar responses to submaximal exercise at 150 W. Vo2 peak decreased by 10.4% from pre-SF (15 days before liftoff) to day 4 after return and 6.6% from pre-BR to day 3 after return, which was partially (SF: -5.2%) or fully (BR) restored within 1 wk of recovery. Workload corresponding to 85% of the peak pre-SF Vo2 peak showed a rapid and continued decline throughout the flight (SF day 2, -6.2%; SF day 8, -9.0%), reaching a nadir of -11.3% during testing on SF day 13. During BR, Vo2 peak also showed a decline from pre-BR (BR day 2, -7.3%; BR day 8, -7.1%; BR day 13, -9.0%). These results suggest that the onset of and recovery from real and simulated microgravity-induced cardiorespiratory deconditioning is relatively rapid, and head-down-tilt BR appears to be an appropriate model of this effect, both during and after SF.

Adult↗

Fractional Fokker-Planck dynamics: Numerical algorithm and simulations.

Anomalous transport in a tilted periodic potential is investigated numerically within the framework of the fractional Fokker-Planck dynamics via the underlying continuous-time random walk. An efficient numerical algorithm is developed which is applicable for an arbitrary potential. This algorithm is then applied to investigate the fractional current and the corresponding nonlinear mobility in different washboard potentials. Normal and fractional diffusion are compared through their time evolution of the probability density in state space. Moreover, we discuss the stationary probability density of the fractional current values.

Journal Article↗

Dynamics of populations in a changing environment.

We present an individual-based model of a population that lives in a changing environment. The individuals forming the population are subject to mutations and selection pressure. Using Monte Carlo simulations we have shown that, depending on the values of the mutation rate and selection, the population may reach either an active phase (it will survive) or an absorbing phase (it will become extinct). We have determined that the transition between the two states (phases) is continuous. We have shown that when the selection is weaker the population lives in all available space, while if the selection is stronger, it will move to the regions where the living conditions are better, avoiding those with more difficult conditions. The dependence of the mean time to extinction on the rate of mutations has been determined and discussed.

Journal Article↗

Population dynamics in spatially heterogeneous systems with drift: The generalized contact process.

We investigate the time evolution and stationary states of a stochastic, spatially discrete, population model (contact process) with spatial heterogeneity and imposed drift (wind) in one and two dimensions. We consider in particular a situation in which space is divided into two regions: an oasis and a desert (low and high death rates). Carrying out computer simulations we find that the population in the (quasi) stationary state will be zero, localized, or delocalized, depending on the values of the drift and other parameters. The phase diagram is similar to that obtained by Nelson and coworkers from a deterministic, spatially continuous model of a bacterial population undergoing convection in a heterogeneous medium.

Algorithms↗

Integrals for continuous-time Markov chains.

This paper presents a method of evaluating the expected value of a path integral for a general Markov chain on a countable state space. We illustrate the method with reference to several models, including birth-death processes and the birth, death and catastrophe process.

Birth Rate↗

Estimation of cardiac bidomain parameters from extracellular measurement: two dimensional study.

Cardiac tissue conductivity measurements can be used to assess the electrical substrate underlying normal and abnormal wavefront propagation. We describe a method of solving the inverse cardiac bidomain model to estimate average longitudinal and transverse intra and extra-cellular conductivities and fiber angle relative to an electrode array placed arbitrarily on the epi- or endocardial surface. A Newton-Raphson reconstruction method and two Tikhonov-type regularizations were able to stably identify conductivities and fiber angles in tissue models having anisotropies similar to those in real cardiac tissue. The reconstruction methods were tested with data from increasingly realistic two dimensional cardiac bidomain models and performed well both when measurement noise was added, and when simulated experimental and forward model matching was diminished. This approach may be a suitable basis for continuous monitoring of myocardial condition in-vivo via a catheter based electrode array.

Action Potentials↗

A spline-regularized minimal residual algorithm for iterative attenuation correction in SPECT.

In SPECT, regularization is necessary to avoid divergence of the iterative algorithms used for non uniform attenuation compensation. In this paper, we propose a spline-based regularization method for the minimal residual algorithm. First, the acquisition noise is filtered using a statistical model involving spline smoothing so that the filtered projections belong to a Sobolev space with specific continuity and derivability properties. Then, during the iterative reconstruction procedure, the continuity of the inverse Radon transform between Sobolev spaces is used to design a spline-regularized filtered backprojection method, by which the known regularity properties of the projections determine those of the corresponding reconstructed slices. This ensures that the activity distributions estimated at each iteration present regularity properties, which avoids computational noise amplification, thus stabilizing the iterative process. Analytical and Monte Carlo simulations are used to show that the proposed spline-regularized minimal residual algorithm converges to a satisfactory stable solution in terms of restored activity and homogeneity, using at most 25 iterations, whereas the non regularized version of the algorithm diverges. Choosing the number of iterations is therefore no longer a critical issue for this reconstruction procedure.

Algorithms↗

Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt.

Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of spaceflight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 degrees head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

Adult↗

An ultrasonic methodology for muscle cross section measurement to support space flight.

The number one priority for any manned space mission is the health and safety of its crew. The study of the short and long term physiological effects on humans is paramount to ensuring crew health and mission success. One of the challenges associated in studying the physiological effects of space flight on humans, such as loss of bone and muscle mass, has been that of readily attaining the data needed to characterize the changes. The small sampling size of astronauts, together with the fact that most physiological data collection tends to be rather tedious, continues to hinder elucidation of the underlying mechanisms responsible for the observed changes that occur in space. Better characterization of the muscle loss experienced by astronauts requires that new technologies be implemented. To this end, we have begun to validate a 360 degree ultrasonic scanning methodology for muscle measurements and have performed empirical sampling of a limb surrogate for comparison. Ultrasonic wave propagation was simulated using 144 stations of rotated arm and calf MRI images. These simulations were intended to provide a preliminary check of the scanning methodology and data analysis before its implementation with hardware. Pulse-echo waveforms were processed for each rotation station to characterize fat, muscle, bone, and limb boundary interfaces. The percentage error between MRI reference values and calculated muscle areas, as determined from reflection points for calf and arm cross sections, was -2.179% and +2.129%, respectively. These successful simulations suggest that ultrasound pulse scanning can be used to effectively determine limb cross-sectional areas. Cross-sectional images of a limb surrogate were then used to simulate signal measurements at several rotation angles, with ultrasonic pulse-echo sampling performed experimentally at the same stations on the actual limb surrogate to corroborate the results. The objective of the surrogate sampling was to compare the signal output of the simulation tool used as a methodology validation for actual tissue signals. The disturbance patterns of the simulated and sampled waveforms were consistent. Although only discussed as a small part of the work presented, the sampling portion also helped identify important considerations such as tissue compression and transducer positioning for future work involving tissue scanning with this methodology.

Animals↗

A lattice kinetic scheme for incompressible viscous flows with heat transfer.

A lattice kinetic scheme for incompressible viscous flows with heat transfer is developed based on the lattice Boltzmann method. In the new scheme, macroscopic variables are calculated without velocity distribution functions. Thus, the scheme can save computer memory because there is no need to store the velocity distribution functions. Governing equations for the macroscopic variables are obtained by applying the asymptotic theory. The continuity equation, the Navier-Stokes equations, and the convection-diffusion equation for fluid temperature are obtained with relative errors of O(epsilon2), where epsilon is a small parameter that is of the same order as a lattice spacing and is related to a relaxation parameter. In order to verify the accuracy of the scheme, natural convection flows in a square cavity are simulated, and the calculated results are in good agreement with available standard results.

Colloids↗

Melanin granule models for the processes of laser-induced thermal damage in pigmented retinal tissues. I. Modeling of laser-induced heating of melanosomes and selective thermal processes in retinal tissues.

The computer modeling was applied for investigation of the processes of laser-induced tissue damage. The melanin granule models for the processes of laser-induced thermal damage and the results of computer modeling of the optical, thermophysical, and thermochemical processes during selective laser interaction with melanoprotein granules (melanosomes) in retinal pigment epithelium are presented in this paper. Physical-mathematical model and system of equations are formulated which describe thermal interaction processes for "short" laser pulses of duration t (p)<10(-6) s and for " long' pulses of duration t(p) > 10(-6) s. Results of numerical simulation of the processes give the space-time distributions of temperature and degrees of thermodenaturation of the protein molecules inside and around melanosomes and in the volume of irradiated tissues. Energy absorption, heat transfer and thermochemical (thermodenaturation, coagulation) processes occurring during the interaction of laser pulses with pigmented spherical and spheroidal granules in heterogeneous tissues are theoretically investigated. The possibility for selective interaction of short laser pulses with pigmented granules is discussed which results in the formation of denaturation microregions inside and near the pigmented granules (granular thermodenaturation) without origination of a continuous macroscopic thermodenaturation lesion in tissue. Analytical model of heating of single spherical and spheroidal granule under laser pulse is presented. Simple equations for time dependencies of particle temperature are obtained. The presented results are of essential interest for laser applications in and can be used for investigation of laser interaction with pigmented tissues in different fields of laser medicine.

Computer Simulation↗

A study of the effects of prolonged simulated microgravity on the musculature of the lower extremities in man: an introduction.

The reduction of muscle strength and size of the lower extremities has been observed following spaceflight. However, there are virtually no data from direct measurements of muscle tissue which provide a means of understanding the physiological alterations associated with the impaired function. We therefore conducted a study in which eight healthy men underwent 30 days of continuous exposure to 6 degrees headdown tilt as an analogue for space microgravity. We used percutaneous muscle biopsy, computed tomography, anthropometry, and in vivo muscle strength measures under controlled experimental conditions to provide new data about mechanical, structural, and metabolic characteristics of skeletal muscle in man following exposure to microgravity.

Adult↗

High-resolution computer simulation of the dynamics of isoelectric focusing using carrier ampholytes: focusing with concurrent electrophoretic mobilization is an isotachophoretic process.

Focusing of four hemoglobins with concurrent electrophoretic mobilization was studied by computer simulation. A dynamic electrophoresis simulator was first used to provide a detailed description of focusing in a 100-carrier component, pH 6-8 gradient using phosphoric acid as anolyte and NaOH as catholyte. These results are compared to an identical simulation except that the catholyte contained both NaOH and NaCl. A stationary, steady-state distribution of carrier components and hemoglobins is produced in the first configuration. In the second, the chloride ion migrates into and through the separation space. It is shown that even under these conditions of chloride ion flux a pH gradient forms. All amphoteric species acquire a slight positive charge upon focusing and the whole pattern is mobilized towards the cathode. The cathodic gradient end is stable whereas the anodic end is gradually degrading due to the continuous accumulation of chloride. The data illustrate that the mobilization is a cationic isotachophoretic process with the sodium ion being the leading cation. The peak height of the hemoglobin zones decreases somewhat upon mobilization, but the zones retain a relatively sharp profile, thus facilitating detection. The electropherograms that would be produced by whole column imaging and by a single detector placed at different locations along the focusing column are presented and show that focusing can be commenced with NaCl present in the catholyte at the beginning of the experiment. However, this may require detector placement on the cathodic side of the catholyte/sample mixture interface.

Ampholyte Mixtures↗

Hearing and performance during a 70-h exposure to noise simulating the space station environment.

INTRODUCTION: Elevated hearing thresholds have been documented in some astronauts after long-term spaceflights although noise levels were lower than those normally associated with noise-induced hearing loss in ground-based operations. The present study was conducted to determine whether prolonged exposure (70 h) to levels (72 dBA) recorded on the International Space Station (ISS) service module would impact diverse measures of auditory function, as well as cognition and memory, motivation, and cardiovascular function. METHOD: Five mixed gender subgroups of five normal-hearing subjects, aged 20-50 yr, were sequestered for 70 h in an environment that modeled conditions on the ISS. They were assigned to one of three background conditions: quiet (n = 5), continuous noise from the ISS service module (n = 10), or continuous noise during the day only (n = 10). Subjects were tested repeatedly within and across days as individuals or pair mates. RESULTS: There were no negative effects of the noise on any of the outcome measures. Introduction of a delay or noise in a communication channel used in the assessment of speech communicability significantly affected the time taken for joint problem solving by partners. DISCUSSION: The results of this study were not consistent with the observation of hearing loss measured after spaceflights. Nor were changes evident in cognition, motivation, or cardiovascular function. Factors which might account for the discrepancy are discussed.

Adult↗