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PubMed1991

Structural complexity effects on transverse propagation in a two-dimensional model of myocardium.

A thin sheet of cardiac tissue was modeled as a set of resistively coupled excitable cables with membrane dynamics described by the modified Beeler Reuter model. Transverse connections have a resistance Rn and are regularly distributed with a spacing delta on any given cable, to provide alternating input and output junctions. Flat wave longitudinal propagation corresponds to propagation along a single continuous cable since all units of the network are functionally isolated due to the absence of transverse current flow. Events on a given cable during flat transverse propagation include electrotonic spread of potential from input to output junctions, action potential initiation at input junctions, and collision at output junctions. The propagating two-dimensional transverse wavefront is an undulating transmembrane potential surface with highs at the input junctions and lows at the output junctions. The action potential upstroke is also modulated in a periodic manner with minimum and maximum Vmax at the input and output junctions respectively. Thus, the network is capable of a diversity of dynamic behavior spatially distributed in relation to the specific pattern of transverse connections chosen. Overall, the behavior of the network model is in good agreement with available structural and electrophysiological data on myocardium. In addition, this network topology allows to handle more easily parameters governing propagation and to avoid very large matrices which are costly in computational effort and overall computer time.

Computer Simulation↗
PubMed1990

Determining minimum energy conformations of polypeptides by dynamic programming.

A combinatorial optimization approach is used for solving the multiple-minima problem when determining the low-energy conformations of short polypeptides. Each residue is represented by a finite number of discrete states corresponding to single residue local minima of the energy function. These precomputed values constitute a search table and define the conformational space for discrete minimization by a generalized dynamic programming algorithm that significantly limits the number of intermediate conformations to be generated during the search. Since dynamic programming involves stagewise decisions, it results in buildup-type procedures implemented in two different forms. The first procedure predicts a number of conformations by a completely discrete search and these are subsequently refined by local minimization. The second involves limited continuous local minimization within the combinatorial algorithm, generally restricted to two dihedral angles in a buildup step. Both procedures are tested on 17 short peptides previously studied by other global minimization methods but involving the same potential energy function. The discrete method is extremely fast, but proves to be successful only in 14 of the 17 test problems. The version with limited local minimization finds, however, conformations in all the 17 examples that are close to the ones previously presented in the literature or have lower energies. In addition, results are almost independent of the cutoff energy, the most important parameter governing the search. Although the limited local minimization increases the number of energy evaluations, the method still offers substantial advantages in speed.

Algorithms↗
PubMed1975

Effect of potassium depletion in normal males: an Apollo 15 simulation.

In the course of Apollo 15, physiologic abnormalities, manifested by ectopic activity on the ECG and unusual alterations in excerise tolerance, occurred in the crew of the Lunar Excursion Module. These were associated with decreases in total body potassium, measured by 42K, of 10% and 15%. The possibility of inadequate potassium (K plus) intake existed. A simulation study was performed prior to Apollo 16, corresponding in duration to Apollo 15. Subjects endured the same sleep aberrations and caloric expenditure as the Apollo 15 astronauts. Subjects consumed a diet containing only 15 mEq/d of K plus during the entire 12 d of absolute bedrest. ECG was continuously monitored, body fluid compartments and total body K plus were measured at intervals by radionuclide methods, electrolyte balance was determined daily, and excercise and orthostatic tolerances were determined prior to and after bedrest. In spite of decreases in total body K plus measured by 42K of 14.5% and 10.5%, and by potassium balances of 3.3% and 6.5%, respectively, neither of the two subjects developed symptomatic hypokalemia. Minor ECG abnormalities were noted in one subject. Orthostatic and exercise tolerance showed only those changes expected as a result of bedrest. Muscle strength was unaffected. Study implications and reasons for discrepancies between K plus loss measured by balance techniques and 42K are reviewed.

Adult↗
PubMed2000

Random walks in logarithmic and power-law potentials, nonuniversal persistence, and vortex dynamics in the two-dimensional XY model

The Langevin equation for a particle ("random walker") moving in d-dimensional space under an attractive central force and driven by a Gaussian white noise is considered for the case of a power-law force, F(r) approximately -r(-sigma). The "persistence probability," P0(t), that the particle has not visited the origin up to time t is calculated for a number of cases. For sigma>1, the force is asymptotically irrelevant (with respect to the noise), and the asymptotics of P0(t) are those of a free random walker. For sigma<1, the noise is (dangerously) irrelevant and the asymptotics of P0(t) can be extracted from a weak noise limit within a path-integral formalism employing the Onsager-Machlup functional. The case sigma=1, corresponding to a logarithmic potential, is most interesting because the noise is exactly marginal. In this case, P0(t) decays as a power law, P0(t) approximately t(-straight theta) with an exponent straight theta that depends continuously on the ratio of the strength of the potential to the strength of the noise. This case, with d=2, is relevant to the annihilation dynamics of a vortex-antivortex pair in the two-dimensional XY model. Although the noise is multiplicative in the latter case, the relevant Langevin equation can be transformed to the standard form discussed in the first part of the paper. The mean annihilation time for a pair initially separated by r is given by t(r) approximately r(2) ln(r/a) where a is a microscopic cutoff (the vortex core size). Implications for the nonequilibrium critical dynamics of the system are discussed and compared to numerical simulation results.

Journal Article↗
PubMed2002

The effect of repeated altitude exposures on the incidence of decompression sickness.

INTRODUCTION: Repeated altitude exposures in a single day occur during special operations parachute training, hypobaric chamber training, unpressurized flight, and extravehicular space activity. Inconsistent and contradictory information exists regarding the risk of decompression sickness (DCS) during such hypobaric exposures. HYPOTHESIS: We hypothesized that four short exposures to altitude with and without ground intervals would result in a lower incidence of DCS than a single exposure of equal duration. METHODS: The 32 subjects were exposed to 3 different hypobaric exposures--condition A: 2 h continuous exposure (control); condition B: four 30-min exposures with descent/ascent but no ground interval between the exposures; condition C: four 30-min exposures with descent/ascent and 60 min of ground interval breathing air between exposures. All exposures were to 25,000 ft with 100% oxygen breathing. Subjects were observed for symptoms of DCS, and precordial monitoring of venous gas emboli (VGE) was accomplished with a SONOS 1000 echo-imaging system. RESULTS: DCS occurred in 19 subjects during A (mean onset 70+/-29 min), 7 subjects in B (60+/-34 min), and 2 subjects in C (40+/-18 min). There was a significant difference in DCS incidence between B and A (p = 0.0015) and C and A (p = 0.0002), but no significant difference between B and C. There were 28 cases of VGE in A (mean onset 30+/-23 min), 21 in B (41+/-35 min), and 21 in C (41+/-32 min) with a significant onset curve difference between B and A and between C and A, but not between B and C. Exposure A resulted in four cases of serious respiratory/neurological symptoms, while B had one and C had none. All symptoms resolved during recompression to ground level. CONCLUSION: Data indicate that repeated simulated altitude exposures to 25,000 ft significantly reduce DCS and VGE incidence compared with a single continuous altitude exposure.

Adolescent↗
PubMedDate not supplied

Novel cardiac assist valve with a purge flow in the valve sinus.

Clinical applications of cardiac assist systems continue to have a severe problem, that of thromboembolic complications. The problem originates mainly at the valves, which are usually made of a antithrombogenic material, such as bovine pericardium. However, the valve housing is made of a less suitable material, and wherever the blood flow is stagnant, a thrombus is likely to form. Such stagnant blood flow is found in the space between the housing of the valve and the leaflets, in the sinuses. Consequently, thrombi often are generated in the sinuses. The novel valve design presented in this article avoids the formation of the stagnation zone in the sinuses by a purge flow. This flow is taken from the main flow through the valve and is directed into each sinus of the res purges the sinuses. The purge flow effect is investigated with an experimental method in which the sinus is filled with dye, and washout during the valve action is observed and recorded on videotape, which is compared with washout in a valve without a purge flow. In addition, the purge flow effect is investigated by computational fluid dynamics. Both methods show that the purge flow effectively increases fluid exchange in the sinuses.

Computer Simulation↗
PubMed1980

Contributions of the lymphatic and microvascular systems to fluid absorption from the synovial cavity of the rabbit knee.

1. The trans-synovial flow (Qs) of Ringer solution from the cavity of immobile knee (stifle) joints was determined in anaesthetized rabbits when intra-articular hydrostatic pressure (PJ) was elevated in steps from 2 to 25 cm H2O. 2. It has been demonstrated previously (Levick, 1978) that slope DQs/dPJ shows an abrupt sixfold increase at a 'breaking point' (PB) around 9 . 5 cm H2O, rising from a mean of 0 . 49 microliter.min-1 cm H2O-1 (PJ less than PB) to 2 . 81 microliter.min-1 cm H2O-1 (PJ greater than PB). 3. Perforation of the synovial intima by an intra-articular cannula increased dQs/dPJ below breaking pressure and thus largely abolished the breaking point phenomenon, indicating that the phenomenon might be simulated by a break-down in synovial resistance to flow. 4. Ligation of the femoral lymph trunks draining the joint did not significantly alter the relationship between Qs and PJ. The slope dQs/dPJ was 0 . 60 +/- 0 . 17 microliter.min-1 cm H2O-1 (mean +/- S.E.) below a breaking pressure of 8 . 8--10.5 cm H2O, and 2 . 90 +/- 0 . 64 microliter.min-1 cm H2O-1 above breaking pressure. Thus changes in synovial lymph flow did not explain the breaking point phenomenon. 5. Interruption of synovial blood flow by vascular clamps or by killing the animal reduced, but did not abolish fluid absorption; nor was the breaking point phenomenon abolished. Slope dQs/dPJ increased from 0 . 37 +/- 0 . 06 microliter.min-1 cm H2O-1 below breaking point (10 . 5 +/- 1 . 0 cm H2O) to between 1 . 82 and 0 . 96 +/- 0 . 15 microliter.min-1 cm H2O-1 above breaking pressure. Fluid accumulated in extra-synovial interstitial spaces. 6. When the synovial intima was divested of its surrounding tissues, lymphatic and vascular supplies by extensive dissection, the denuded synovium still showed a marked increase in hydraulic conductivity at normal breaking pressures. The breaking point phenomenon was therefore not caused by changes in extra-synovial interstitial pressure or compliance. 7. It is concluded that fluid absorption from the joint cavity occurs by two parallel pathways viz. the synovial capillary bed and the extra-synovial interstitial spaces. A simple analysis of the system indicates that the breaking point phenomenon cannot be explained by an abrupt increase in synovial conductivity (cf. Edlund, 1949) but is explicable if synovial conductivity (and possibly interstitial conductivity) becomes a continuous function of PJ above breaking pressure. This hypothesis reconciles the non-linear pressure-flow relationship with Starling's hypothesis for fluid absorption from connective tissue spaces (1896).

Absorption↗
PubMed2005

A 3D Monte Carlo analysis of the role of dyadic space geometry in spark generation.

In multiple biological systems, vital intracellular signaling processes occur locally in minute periplasmic subspaces often referred to as signaling microdomains. The number of signaling molecules in these microdomains is small enough to render the notion of continuous concentration changes invalid, such that signaling events are better described using stochastic rather than deterministic methods. Of particular interest is the dyadic cleft in the cardiac myocyte, where short-lived, local increases in intracellular Ca2+ known as Ca2+ sparks regulate excitation-contraction coupling. The geometry of dyadic spaces can alter in disease and development and display significant interspecies variability. We created and studied a 3D Monte Carlo model of the dyadic cleft, specifying the spatial localization of L-type Ca2+ channels and ryanodine receptors. Our analysis revealed how reaction specificity and efficiency are regulated by microdomain geometry as well as the physical separation of signaling molecules into functional complexes. The spark amplitude and rise time were found to be highly dependent on the concentration of activated channels per dyadic cleft and on the intermembrane separation, but not very sensitive to other cleft dimensions. The role of L-type Ca2+ channel and ryanodine receptor phosphorylation was also examined. We anticipate that this modeling approach may be applied to other systems (e.g., neuronal growth cones and chemotactic cells) to create a general description of stochastic events in Ca2+ signaling.

Animals↗
PubMed1995

The old problems of glass and the glass transition, and the many new twists.

In this paper I review the ways in which the glassy state is obtained both in nature and in materials science and highlight a "new twist"--the recent recognition of polymorphism within the glassy state. The formation of glass by continuous cooling (viscous slowdown) is then examined, the strong/fragile liquids classification is reviewed, and a new twist-the possibility that the slowdown is a result of an avoided critical point-is noted. The three canonical characteristics of relaxing liquids are correlated through the fragility. As a further new twist, the conversion of strong liquids to fragile liquids by pressure-induced coordination number increases is demonstrated. It is then shown that, for comparable systems, it is possible to have the same conversion accomplished via a first-order transition within the liquid state during quenching. This occurs in the systems in which "polyamorphism" (polymorphism in the glassy state) is observed, and the whole phenomenology is accounted for by Poole's bond-modified van der Waals model. The sudden loss of some liquid degrees of freedom through such weak first-order transitions is then related to the polyamorphic transition between native and denatured hydrated proteins, since the latter are also glass-forming systems--water-plasticized, hydrogen bond-cross-linked chain polymers (and single molecule glass formers). The circle is closed with a final new twist by noting that a short time scale phenomenon much studied by protein physicists-namely, the onset of a sharp change in d /dT ( is the Debye-Waller factor)--is general for glass-forming liquids, including computer-simulated strong and fragile ionic liquids, and is closely correlated with the experimental glass transition temperature. The latter thus originates in strong anharmonicity in certain components of the vibrational density of states, which permits the system to access the multiple minima of its configuration space. The connection between the anharmonicity in these modes, vibrational localization, the Kauzmann temperature, and the fragility of the liquid is proposed as the key problem in glass science.

Journal Article↗
PubMed2003

AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

Algorithms↗
PubMed1989

Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab')2, and Fab in tumors.

In order to understand the pharmacology of monoclonal antibodies and their conjugates, one must consider both global and microscopic aspects of antibody distribution. Here we present an analysis of antibody distribution in tumors based on the following factors: (a) molecular weight and valence of the antibody; (b) global pharmacokinetic profile following i.v. bolus injection; (c) penetration through the vascular wall; (d) diffusive and convective transport through interstitial space in the tumor; (e) antigen-antibody interaction; (f) antibody metabolism. Partial differential equations were developed to incorporate these factors and then solved numerically using parameter values from animal experiments, from clinical protocols at our institution, from studies of antibody binding characteristics in vitro, and from the literature. Salient findings from this model are that (a) antigen-antibody interaction in the tumor can retard antibody percolation away from blood capillaries, thus constituting a "binding site barrier"; (b) high antibody affinity tends to decrease antibody penetration and result in a more heterogeneous distribution; (c) high molecular weight [IgG greater than F(ab')2 greater than Fab] slows percolation and results in less uniform spatial distribution; (d) the average antibody concentration in the tumor does not increase linearly with antibody dose; (e) raising the rate of antibody metabolism results in low concentration and poor percolation; (f) perhaps most interesting, there is predicted to be a range of antibody dose and affinity within which the specificity ratio and average concentration could be kept high while limiting the heterogeneity of distribution. PERC, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of global and microscopic parameters on the distribution of immunoglobulin in tumors. For calculations presented here, the input data were obtained from experimental sources, and qualitative features of the output proved consistent with the few interpretable observations available. However, detailed validation would require much more data than are currently at hand. The mathematical findings should therefore be considered as aids to concept development and as a set of null hypotheses with which to guide experimentation. Experiments and simulations will continue in tandem. It should be noted that the PERC package (and also the general principles delineated here) can be applied as well to biological ligands other than antibodies.

Antibody Affinity↗
PubMed2002

MELISSA: a loop of interconnected bioreactors to develop life support in space.

The development of a loop of interconnected continuous bioreactors, aimed to provide life support in space, is reported. The complete loop concept consists of four bioreactors and one higher plant compartment. For its realization the continuous and controlled operation of the bioreactors is characterized, up to the pilot scale level, first for each individual reactor, second for the interconnected reactor operation. The results obtained with the two more advanced bioreactors in the Micro Ecological Life Support System Alternative (MELISSA) loop are described more specifically. These reactors consist of a packed-bed reactor working with an immobilized co-culture of Nitrosomonas and Nitrobacter cells, and an external loop gas-lift photobioreactor for the culture of the cyanobacteria Spirulina platensis. Their individual operation for long duration runs has been achieved and characterized, and their interconnected operation at pilot scale is reported.

Bioreactors↗
PubMed2005

Toward a new paradigm in hospital-based pediatric education: the development of an onsite simulator program.

OBJECTIVE: The low incidence of crises in pediatrics, coupled with logistic issues and restricted work hours for trainees, hinders opportunities for frequent practice of crisis management and teamwork skills. We hypothesized that a dedicated simulator suite contiguous to the intensive care unit (ICU) would enhance the frequency and breadth of critical-incident training for a range of clinicians. DESIGN: Descriptive study. SETTING: A tertiary-care pediatric teaching hospital. MEASUREMENTS AND MAIN RESULTS: A realistic pediatric simulator suite was constructed 100 feet from the ICU, at a total base cost of $290,000. The simulation room is an exact replica of an ICU bed space, incorporating high-fidelity mannequin simulators. To capture an even wider audience, a portable unit was also created. Leaders from seven departments-critical care, cardiac intensive care, emergency medicine, transport medicine, anesthesia, respiratory care, and general pediatrics-completed instructor training to ensure effective debriefing techniques. Pediatric staff, including 100% of critical care fellows, 86% of nurses, 90% of respiratory therapists, and 74% of pediatric house staff, participated in >1500 learning encounters per year. All individuals were trained during their normal workday in the hospital. Courses in crisis resource management, skills acquisition, annual review, orientation, and trauma management (1,116, 98, 90, 60, and 60 encounters per year, respectively) were all designed by a multidisciplinary committee to ensure goal-directed education to a range of audiences. Annual costs were on par with those at other centers (approximately 44 dollars per trainee encounter). CONCLUSIONS: An onsite and comprehensive simulation program can significantly increase the opportunities for clinicians from multiple disciplines, in the course of their daily routines, to repetitively practice responses to pediatric medical crises. After an initial capital investment, the training appears to be cost-effective. Hospital-based simulator suites may point the way forward as a new paradigm for the effective education of today's busy clinicians.

Clinical Competence↗
PubMed2025

ScITree: Scalable Bayesian inference of transmission tree from epidemiological and genomic data.

Phylodynamic models capture joint epidemiological-evolutionary dynamics during an outbreak, providing a powerful tool to enhance understanding and management of disease transmission. Existing phylodynamic approaches, however, mostly rely on various non-mechanistic or semi-mechanistic approximations of the underlying epidemiological-evolutionary process. Previous work by Lau and colleagues has shown that full Bayesian mechanistic models, without relying on these approximations, can enable highly accurate joint inference of the epidemiological-evolutionary dynamics including the unobserved transmission tree. However, the Lau method faces major computational bottlenecks. As the volume of genomic data collected during outbreaks continues to grow, it is crucial to develop scalable yet accurate phylodynamic methods. Here we propose a new Bayesian phylodynamic model, overcoming the major scalability issue in the previous method and enabling a readily deployable, yet accurate, phylodynamic modeling framework. Specifically, we develop a scalable spatio-temporal phylodynamic framework for inferring the transmission tree (ScITree) and other key epidemiological parameters considering the infinite sites assumption in modeling mutation on the sequence level, in contrast to the Lau method in which mutation was modeled explicitly on the nucleotide level. Our approach features full Bayesian implementation utilizing an exact likelihood to mechanistically integrate epidemiological and evolutionary processes. We develop a computationally-efficient data-augmentation Markov Chain Monte Carlo algorithm, inferring key model parameters and unobserved dynamics including the transmission tree. We assess performance of our method using multiple simulated outbreak datasets. Our results indicate that our method can achieve high inference accuracy, comparable to the performance of the Lau method. Additionally, our method scales significantly more efficiently for large outbreaks, with computing time increasing linearly with outbreak size, compared to the exponential scaling of the Lau method. We also demonstrate our method's utility by applying our validated modeling framework to a dataset describing a foot-and-mouth disease outbreak in the UK. Our results show that our method is able to generate estimates of the transmission dynamics consistent with those from the prior method, further demonstrating the robustness of our new approach. In summary, our method provides a computationally-efficient, highly scalable, accurate modeling framework for inferring the joint spatio-temporal dynamics of epidemiological and evolutionary processes, facilitating timely and effective outbreak responses in space and time. Our method is implemented in our R package ScITree.

Bayes Theorem↗
PubMedDate not supplied

Genetic programming assisted stochastic optimization strategies for optimization of glucose to gluconic acid fermentation.

This article presents two hybrid strategies for the modeling and optimization of the glucose to gluconic acid batch bioprocess. In the hybrid approaches, first a novel artificial intelligence formalism, namely, genetic programming (GP), is used to develop a process model solely from the historic process input-output data. In the next step, the input space of the GP-based model, representing process operating conditions, is optimized using two stochastic optimization (SO) formalisms, viz., genetic algorithms (GAs) and simultaneous perturbation stochastic approximation (SPSA). These SO formalisms possess certain unique advantages over the commonly used gradient-based optimization techniques. The principal advantage of the GP-GA and GP-SPSA hybrid techniques is that process modeling and optimization can be performed exclusively from the process input-output data without invoking the detailed knowledge of the process phenomenology. The GP-GA and GP-SPSA techniques have been employed for modeling and optimization of the glucose to gluconic acid bioprocess, and the optimized process operating conditions obtained thereby have been compared with those obtained using two other hybrid modeling-optimization paradigms integrating artificial neural networks (ANNs) and GA/SPSA formalisms. Finally, the overall optimized operating conditions given by the GP-GA method, when verified experimentally resulted in a significant improvement in the gluconic acid yield. The hybrid strategies presented here are generic in nature and can be employed for modeling and optimization of a wide variety of batch and continuous bioprocesses.

Artificial Intelligence↗
PubMed1995

Active control in interrupted dynamic spatial orientation: the detection of orientation change.

Gibson (1966, 1979) suggested that an important property of perception is that the observer is active. Two experiments were conducted to examine the benefits of active observation in determining dynamic spatial orientation. Subjects were presented with displays simulating locomotion through a three-dimensional environment. Active observers continuously controlled locomotion, whereas passive observers viewed the display. During the trial, the display was blacked out for a brief period, followed by a static image that was at either the correct or the incorrect orientation following the blackout. Subjects were required to indicate whether they were positioned at the correct extrapolated orientation. The presence or absence of orientation change, the type of change (changes in rotation about the depth axis [roll], horizontal axis [pitch], or forward translation), the duration of the blackout, and the consistency of change were varied. In addition, the experiments used either a compensatory or a pursuit tracking task. Active observers had greater sensitivity than did passive observers in detecting a change for both tracking tasks. Subjects in both experiments exhibited greater sensitivity in detecting inconsistent changes (relative to consistent changes), suggesting that the dynamics specified by optical flow were incorporated in extrapolated orientation. In addition, sensitivity decreased with an increase in blackout duration. The results are discussed in terms of an extrapolation model of perception that incorporates the responses executed by active observers.

Attention↗
PubMed1987

Interstitial distribution of charged macromolecules in the dog lung: a kinetic model.

A mathematic model was constructed to investigate conflicting physiologic data concerning the charge effect of continuous capillaries to macromolecules in the lung. We simulated the equilibration kinetics of lactate dehydrogenase (MR 4.2 nM) isozymes LDH 1 (pI = 5.0) and LDH 5 (pI = 7.9) between plasma and lymph using previously measured permeability coefficients, lung tissue distribution volumes (VA) and plasma concentrations (CP) in lung tissue. Our hypothesis is that the fixed anionic charges in interstitium, basement membrane, and cell surfaces determine equilibration rather than charged membrane effects at the capillary barrier, so the same capillary permeability coefficients were used for both isozymes. Capillary filtration rates and protein fluxes were calculated using conventional flux equations. Initial conditions at baseline and increased left atrial pressures (PLA) were those measured in animal studies. Simulated equilibration of isozymes over 30 h in the model at baseline capillary pressures accurately predicted the observed differences in lymph/plasma concentration ratios (CL/CP) between isotopes at 4 h and equilibration of these ratios at 24 h. Quantitative prediction of isozyme CL/CP ratios was also obtained at increased PLA. However, an additional cation selective compartment representing the surface glycocalyx was required to accurately simulate the initial higher transcapillary clearances of cationic LDH 5. Thus experimental data supporting the negative barrier, positive barrier, and no charge barrier hypotheses were accurately reproduced by the model using only the observed differences in interstitial partitioning of isozymes without differences in capillary selectivity.

Animals↗
PubMed1988

Modeling the effects of exhaust ventilation on 222Rn entry rates and indoor 222Rn concentrations.

Continuous mechanical exhaust ventilation of moderately air-tight residences is common in Scandinavia and has recently been employed in several U.S. residences. Exhaust ventilation decreases the indoor pressure and, thus, increases the pressure difference which drives 222Rn entry. Relatively simple analytical (i.e. closed form) models were developed and used to examine the impacts of exhaust ventilation on 222Rn entry rates and concentrations in houses with either a crawl space or a basement. A more complex finite difference model was also developed for the house with a basement and yielded soil gas entry rates within 16% of those predicted with the analytical model. The models indicate that exhaust ventilation is suitable, but not optimal (from the perspective of indoor 222Rn), for houses with a vented crawl space. Exhaust ventilation is also indicated to be suitable for houses with basements surrounded by relatively impermeable soil (10(-12) m2 or less). If soil permeabilities are between 10(-12) and 10(-10) m2, exhaust ventilation may cause substantial increases in indoor 222Rn when soil gas 222Rn concentrations are above average. If soil permeabilities are greater than 10(-10) m2, exhaust ventilation is indicated to be inappropriate, unless some procedure is employed to inhibit soil gas entry. These conclusions should be considered tentative, since extensive verification of the models is still required.

Air Pollutants, Radioactive↗