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PubMed1998

Efficient scatter modelling for incorporation in maximum likelihood reconstruction.

Definition of a simplified model of scatter which can be incorporated in maximum likelihood reconstruction for single-photon emission tomography (SPET) continues to be appealing; however, implementation must be efficient for it to be clinically applicable. In this paper an efficient algorithm for scatter estimation is described in which the spatial scatter distribution is implemented as a spatially invariant convolution for points of constant depth in tissue. The scatter estimate is weighted by a space-dependent build-up factor based on the measured attenuation in tissue. Monte Carlo simulation of a realistic thorax phantom was used to validate this approach. Further efficiency was introduced by estimating scatter once after a small number of iterations using the ordered subsets expectation maximisation (OSEM) reconstruction algorithm. The scatter estimate was incorporated as a constant term in subsequent iterations rather than modifying the scatter estimate each iteration. Monte Carlo simulation was used to demonstrate that the scatter estimate does not change significantly provided at least two iterations OSEM reconstruction, subset size 8, is used. Complete scatter-corrected reconstruction of 64 projections of 40¿128 pixels was achieved in 38 min using a Sun Sparc20 computer.

Algorithms↗
PubMed2005

Monte Carlo validation of the Dorfman-Berbaum-Metz method using normalized pseudovalues and less data-based model simplification.

RATIONALE AND OBJECTIVES: Two problems of the Dorfman-Berbaum-Metz (DBM) method for analyzing multireader receiver operating characteristic (ROC) studies are that it tends to be conservative and that it can produce AUC estimates outside the parameter space--ie, greater than one or less than zero. Recently it has been shown that the problem of AUC (or other accuracy) estimates outside the parameter space can be eliminated by using normalized pseudovalues, and it has been suggested that less data-based model simplification be used. Our purpose is to empirically investigate if these two modifications--normalized pseudovalues and less data-based model simplification--result in improved performance. MATERIALS AND METHODS: We examine the performance of the DBM procedure using the two proposed modifications for discrete and continuous ratings in a null simulation study comparing modalities with respect to the ROC area. The simulation study includes 144 different combinations of reader and case sample sizes, normal/abnormal case sample ratios, and variance components. The ROC area is estimated using parametric and nonparametric estimation. RESULTS: The DBM procedure with both modifications performs better than either the original DBM procedure or the DBM procedure with only one of the modifications. For parametric estimation with discrete rating data, use of both modifications resulted in the mean type I error (0.043) closest to the nominal .05 level and the smallest range (0.050) and standard deviation (0.0108) across the 144 type I error rates. CONCLUSIONS: We recommend that normalized pseudovalues and less data-based model simplification be used with the DBM procedure.

Algorithms↗
PubMed2002

Mutualism promotes diversity and stability in a simple artificial ecosystem.

This work investigates the effect of ecological interactions between organisms on the evolutionary dynamics of a community. A spatially explicit, individual-based model is presented, in which organisms compete for space and resources. We investigated how introducing the potential for mutualistic relationships (where the presence of one type of organism stimulates the growth of another type, and vice versa) affected the evolutionary dynamics of the system. Without this potential, one or a small number of individual types of organisms dominated the simulated community from the onset. When mutualistic relationships were allowed, many persisting types arose, with new types appearing continually. Furthermore, we investigated how the stability of the community differed when mutualistic relationships were allowed and disallowed. Our results suggest that the existence of mutualistic relationships improved community stability.

Biological Evolution↗
PubMed2006

A structure-based simulation approach for electron paramagnetic resonance spectra using molecular and stochastic dynamics simulations.

Electron paramagnetic resonance (EPR) spectroscopy using site-directed spin-labeling is an appropriate technique to analyze the structure and dynamics of flexible protein regions as well as protein-protein interactions under native conditions. The analysis of a set of protein mutants with consecutive spin-label positions leads to the identification of secondary and tertiary structure elements. In the first place, continuous-wave EPR spectra reflect the motional freedom of the spin-label specifically linked to a desired site within the protein. EPR spectra calculations based on molecular dynamics (MD) and stochastic dynamics simulations facilitate verification or refinement of predicted computer-aided models of local protein conformations. The presented spectra simulation algorithm implies a specialized in vacuo MD simulation at 600 K with additional restrictions to sample the entire accessible space of the bound spin-label without large temporal effort. It is shown that the distribution of spin-label orientations obtained from such MD simulations at 600 K agrees well with the extrapolated motion behavior during a long timescale MD at 300 K with explicit water. The following potential-dependent stochastic dynamics simulation combines the MD data about the site-specific orientation probabilities of the spin-label with a realistic rotational diffusion coefficient yielding a set of trajectories, each more than 700 ns long, essential to calculate the EPR spectrum. Analyses of a structural model of the loop between helices E and F of bacteriorhodopsin are illustrated to demonstrate the applicability and potentials of the reported simulation approach. Furthermore, effects on the motional freedom of bound spin-labels induced by solubilization of bacteriorhodopsin with Triton X-100 are examined.

Algorithms↗
PubMed2001

Ontogeny of plants under various gravity condition.

The results of experiments performed under conditions of microgravity (MG) or under its simulation on the horizontal clinostat (HC) with the callus, seedlings of various species and embryogenic structures have revealed a definite role of gravity as an ecological factor in the processes of cytomorphogenesis, growth, and development. The transformation of differentiated somatic cells of arabidopsis seed into undifferentiated callus was not inhibited under MG, though modifications of the whole callus morphology and of mean cell and nucleus size were observed. The morphogenesis of polar structures such as root-hair bearing cells of Lactuca primary root has been shown to be modified in the course of differentiation under mass acceleration diminished below 0.1 g. Seed germination and seedling morphogenesis under MG follow their normal course, but a significant stimulation of shoot growth with no effect on primary root growth has been determined. A successful in vitro regeneration of Nicotiana tabacum plantlets from leaf cells and subsequent formation of shoots and roots on a continuously rotating HC as well as the formation of viable seeds during seed-to-seed growth of Arabidopsis plants under MG have indicated that gravity plays but a limited role in the processes of embryogenesis and organogenesis.

Arabidopsis↗
PubMed2006

Bayesian inference in a hidden stochastic two-compartment model for feline hematopoiesis.

In this paper, we describe a hidden two-compartment stochastic process used to model the kinetics of feline hematopoietic stem cells (HSCs) in continuous time. Because of the experimental design and data collection scheme, the inferential task presents numerous challenges. While the hematopoietic process evolves in continuous time, the observations are collected only at discrete irregular times and are a probabilistic function of the state of the process. In addition, the animals go through an experimental procedure such that their reserve of HSCs is severely depleted at the start of the observation period. This impedes any approximation of the hematopoietic process with a continuous state-space process (normal approximation of the transition probabilities would be inaccurate when the state of the process, i.e. the number of stem cells, is small). We implement a Markov chain Monte Carlo algorithm that allows us to estimate the posterior distribution of the parameters of the hematopoietic process while maintaining its state-space discrete (i.e. without using any approximation). We show the performance of the algorithm on simulated data. Finally, we apply the algorithm to data on multiple experimental cats and provide estimates of the rates of the fates of feline HSCs. The obtained estimates are in agreement with the estimates obtained with different methods published in the medical literature. However, the proposed approach makes a more efficient use of the data and hence the parameter estimates are much more accurate than the one obtained with the methods previously proposed.

Algorithms↗
PubMed2002

Quantum Monte Carlo with directed loops.

We introduce the concept of directed loops in stochastic series expansion and path-integral quantum Monte Carlo methods. Using the detailed balance rules for directed loops, we show that it is possible to smoothly connect generally applicable simulation schemes (in which it is necessary to include backtracking processes in the loop construction) to more restricted loop algorithms that can be constructed only for a limited range of Hamiltonians (where backtracking can be avoided). The "algorithmic discontinuities" between general and special points (or regions) in parameter space can hence be eliminated. As a specific example, we consider the anisotropic S=1/2 Heisenberg antiferromagnet in an external magnetic field. We show that directed-loop simulations are very efficient for the full range of magnetic fields (zero to the saturation point) and anisotropies. In particular, for weak fields and anisotropies, the autocorrelations are significantly reduced relative to those of previous approaches. The back-tracking probability vanishes continuously as the isotropic Heisenberg point is approached. For the XY model, we show that back tracking can be avoided for all fields extending up to the saturation field. The method is hence particularly efficient in this case. We use directed-loop simulations to study the magnetization process in the two-dimensional Heisenberg model at very low temperatures. For LxL lattices with L up to 64, we utilize the step structure in the magnetization curve to extract gaps between different spin sectors. Finite-size scaling of the gaps gives an accurate estimate of the transverse susceptibility in the thermodynamic limit: chi( perpendicular )=0.0659+/-0.0002.

Journal Article↗
PubMed2006

Hydrodynamic Lyapunov modes and strong stochasticity threshold in Fermi-Pasta-Ulam models.

The existence of a strong stochasticity threshold (SST) has been detected in many Hamiltonian lattice systems, including the Fermi-Pasta-Ulam (FPU) model, which is characterized by a crossover of the system dynamics from weak to strong chaos with increasing energy density epsilon. Correspondingly, the relaxation time to energy equipartition and the largest Lyapunov exponent exhibit different scaling behavior in the regimes below and beyond the threshold value. In this paper, we attempt to go one step further in this direction to explore further changes in the energy density dependence of other Lyapunov exponents and of hydrodynamic Lyapunov modes (HLMs). In particular, we find that for the FPU-beta and FPU-alpha(beta) models the scalings of the energy density dependence of all Lyapunov exponents experience a similar change at the SST as that of the largest Lyapunov exponent. In addition, the threshold values of the crossover of all Lyapunov exponents are nearly identical. These facts lend support to the point of view that the crossover in the system dynamics at the SST manifests a global change in the geometric structure of phase space. They also partially answer the question of why the simple assumption that the ambient manifold representing the system dynamics is quasi-isotropic works quite well in the analytical calculation of the largest Lyapunov exponent. Furthermore, the FPU-beta model is used as an example to show that HLMs exist in Hamiltonian lattice models with continuous symmetries. Some measures are defined to indicate the significance of HLMs. Numerical simulations demonstrate that there is a smooth transition in the energy density dependence of these variables corresponding to the crossover in Lyapunov exponents at the SST. In particular, our numerical results indicate that strong chaos is essential for the appearance of HLMs and those modes become more significant with increasing degree of chaoticity.

Journal Article↗
PubMedDate not supplied

Impact of mineral fouling on hydraulic behavior of permeable reactive barriers.

This paper describes reactive transport simulations conducted to assess the impact of mineral fouling on the hydraulic behavior of continuous-wall permeable reactive barriers (PRBs) employing granular zero-valent iron (ZVI) in carbonate-rich alluvial aquifers. The reactive transport model included a geochemical algorithm for simulating corrosion and mineral precipitation reactions that have been observed in ZVI PRBs. Results of simulations show that porosity and hydraulic conductivity of the ZVI decrease over time and that flows are redistributed throughout the PRB in response to fouling of the pore space. Under typical conditions, only subtle changes occur within the first 10 years (i.e., duration of the current field experience record with PRBs), and the most significant changes do not occur until the PRB has operated for at least 30 years. However, changes can occur sooner (or later) if the rate at which mineral-forming ions are delivered to the PRB is higher (or lower) than that expected under typical conditions (i.e., due to higher/lower flow rate or inflowing ground water that has higher/lower ionic strength). When the PRB is more permeable than the aquifer, the median Darcy flux in the PRB does not change appreciably over time because the aquifer controls the rate of flow through the PRB. However, seepage velocities in the PRB increase, and residence times decrease, due to porosity reductions caused by accumulation of minerals in the pore space. When fouling becomes extensive, bypassing and reductions in flow rate in the PRB occur.

Corrosion↗
PubMed1999

[Diagnosis and treatment of diaphragm traumatic ruptures].

29 patients with traumatic ruptures of left cupola of the diaphragm were studied. Pain, dispnoe, tachycardia more intensive after a meal due to repletion and dislocation of the stomach into pleural cavity and its pressure on the organs of the mediastinum were the main symptoms of the disease. The diagnosis of traumatic rupture of the diaphragm was made on the base of clinical and roentgenological examination. In the acute period of trauma the diagnosis is difficult, especially in combined trauma. In 92.3% of cases the stomach and the bowel move into the pleural cavity, which may simulate pneumothorax or relaxation of the diaphragm. Contrast examination of the gastro-intestinal tract and pleural puncture help in differential diagnosis. All the cases of traumatic ruptures of the diaphragm should be subjected to surgical treatment. Urgent operation is indicated in continuing bleeding, incarceration of organs, acute cardiopulmonary insufficiency due to the collapse of the lung and dislocation of mediastinal organs of into contralateral position. Thoracotomy in VII intercostal space is considered as a valid approach. There were 2 (6.9%) lethal outcomes after 29 operations. Long-term results are quite favourable.

Abdominal Injuries↗
PubMed2003

Reintroducing electrostatics into protein X-ray structure refinement: bulk solvent treated as a dielectric continuum.

Structural refinement of proteins involves the minimization of a target function that combines X-ray data with a set of restraints enforcing stereochemistry and packing. Electrostatic interactions are not ordinarily included in the target function, partly because they cannot be calculated reliably without a description of dielectric screening by solvent in the crystal. With the recent development of accurate implicit solvent models to describe this screening, the question arises as to whether a more detailed target function including electrostatic and solvation terms can yield more accurate structures or somewhat different structures of equivalent accuracy. The Generalized Born (GB) model is one such model that describes the solvent as a dielectric continuum, taking into account its heterogeneous distribution within the crystal. It is used here for X-ray refinements of three protein structures with experimental diffraction data to 2.4, 2.9 and 3.2 A, respectively. In each case, a higher resolution structure is available for comparison. The new target function includes stereochemical restraints, van der Waals, Coulomb and solvation interactions, along with the usual X-ray pseudo-energy term, which employs the likelihood estimator of Pannu and Read. Multiple simulated-annealing refinements were performed in torsion-angle space with a conventional target function and the new GB target function, yielding ensembles of refined structures. The new target function yields structures of similar accuracy, as measured by the free R factor, map/model correlations and deviations from the high-resolution structures. About 10% of side-chain conformations differ between the two sets of refinements, in the sense that the two ensembles of conformations do not completely overlap. Over 75% of the differences correspond to surface side chains. For one of the proteins, the GB set has a greater dispersion, indicating that for this case the conventional target function overestimates the true precision. As GB parameterization continues to improve, we expect that this approach will become increasingly useful.

Aspartate-tRNA Ligase↗
PubMedDate not supplied

Human productivity in space and systems costs.

Human productivity during assembly operations in-orbit is dependent on limits set by fatigue, metabolic rates, learning, and assembly techniques. In order to quantify these effects, tests were conducted in the NASA MSFC Neutral Buoyancy Simulator, in the NASA KC-135 in parabolic flight, and in space with the EASE program during the Shuttle Atlantis mission 61-B . A separate program attempted to relate productivity to system costs. Because of the surprisingly high productivity which had been demonstrated in orbit, it was shown that assembly operations would have only a small effect on system costs at the present level of launch costs. The results of these continuing studies have been reported in a recent paper. They will be briefly summarized here and the results updated to include additional cost elements and to examine the effects of reductions in transportation costs, resulting from advances in technology and from increased demand, on system costs. It is shown that, as launch costs are reduced, the assembly costs could become an increasingly important component of the total system costs.

Cost Allocation↗
PubMedDate not supplied

Application of fast simulated annealing to optimization of conformal radiation treatments.

Applications of simulated annealing to the optimization of radiation treatment plans, in which a set of beam weights are iteratively adjusted so as to minimize a cost function, have been motivated by its potential for finding the global or near-global minimum among multiple minima. However, the method has been found to be slow, requiring several tens of thousands of iterations to optimize 50 to 100 variables. A technique to improve the efficiency for finding a solution is reported, which is generally applicable to the optimization of continuous variables. In previous applications of simulated annealing to treatment planning optimization, only one or two weights are varied each iteration. This approach is to change all weights simultaneously, using random changes that are initially large to coarsely sample the cost function, then are reduced with iteration to probe finer structure. The performance of different methods are compared in optimizing a plan for treatment of the prostate, in which the search space consists of 54 noncoplanar beams and the cost function is based on tumor control and normal tissue complication probabilities. The proposed method yields solutions with similar values of the cost function in only a fraction of the iterations compared either to a fixed single weight adjustment technique, or to a method which combines the Nelder and Mead downhill simplex simulated annealing.

Humans↗
PubMed2000

Multiobjective satisfaction within an interactive evolutionary design environment.

The paper introduces the concept of an Interactive Evolutionary Design System (IEDS) that supports the engineering designer during the conceptual/preliminary stages of the design process. Requirement during these early stages relates primarily to design search and exploration across a poorly defined space as the designer's knowledge base concerning the problem area develops. Multiobjective satisfaction plays a major role, and objectives are likely to be ill-defined and their relative importance uncertain. Interactive evolutionary search and exploration provides information to the design team that contributes directly to their overall understanding of the problem domain in terms of relevant objectives, constraints, and variable ranges. This paper describes the development of certain elements within an interactive evolutionary conceptual design environment that allows off-line processing of such information leading to a redefinition of the design space. Such redefinition may refer to the inclusion or removal of objectives, changes concerning their relative importance, or the reduction of variable ranges as a better understanding of objective sensitivity is established. The emphasis, therefore, moves from a multiobjective optimization over a preset number of generations to a relatively continuous interactive evolutionary search that results in the optimal definition of both the variable and objective space relating to the design problem at hand. The paper describes those elements of the IEDS relating to such multiobjective information gathering and subsequent design space redefinition.

Algorithms↗
PubMed2004

On the influence of training data quality in k-t BLAST reconstruction.

This work investigated how the quality of prior information (i.e., data acquired during the training stage) influences k-t BLAST reconstruction. The impact of several factors, such as the amount of training data, the presence of spatial misregistration in the training data, and the effects of filtering, was investigated with simulations and in vivo data. It is shown that k-t BLAST outperforms sliding window reconstruction, even with very limited training data. By increasing the amount of training data, reconstruction error continues to decrease, albeit by a diminishing amount. However, an increased amount of training data also increases susceptibility to misregistration of the training data. Filtering of the training data with the goal of reducing truncation artifacts had only minor impact on reconstruction errors. Considering the balance among obtaining the most benefit from the training data, minimizing susceptibility to misregistration, and keeping data acquisition to a minimum, it is concluded that in cardiac imaging the training datasets should be limited to 10-20 profiles in k-space for a typical field of view. The training data may be acquired in a separate breathhold without much penalty, if care is taken to minimize misregistration, such as with a navigator.

Adult↗
PubMed1997

On the Way to New Horizons: Telemedicine in Oncology.

Breathtaking insights into carcinogenesis and tumor biology have been gained mainly by recent technical advances in molecular-biological and genetic techniques. Thus, dimensions of earlier diagnosis and the development of new concepts in therapy arise, which were previously unavailable. There is no doubt that through these techniques the future role and tasks of surgical oncology will change. New indications will result, for example, in the context of prophylactic therapy of hereditary malignant disease or the removal of tissue predisposed to tumors. However, modes of therapy orientated toward molecular biology will still be dependent on specialist surgical interventions in the future. Examples are such innovative concepts of therapy as transport of a therapeutic device to or into tumor cells (e.g., gene gun), or even simply obtaining the necessary tumor tissue for therapy (vaccination with transfected autologous tumor cells). Therefore, the future of surgical oncology will be influenced quantitatively as well as conceptually by new qualitative requirements. Improving precision of the surgical intervention will have to go hand-in-hand with a further reduction in surgical trauma. The consistent use of laser, video, computer and communication technology can be seen as an important predeterminant here for optimizing diagnostic and therapeutic procedures. If correctly guided, the professional experience of the individual surgeon and his personal efficiency can also be positively influenced by the swift conversion of society to multimedia and information technology. Major advances in interdisciplinary communication, as one important factor in the choice and the course of suitable complex therapies in oncology, will have to target and help to overcome former weak spots. Communication in and outside one department or hospital, as well as external communication between different medical disciplines and specialists, is being developed further and increasingly refined. The possibilities of modern technology in addition to verbal exchange include visual and interactive "tele"-communication. This renders a new option to the physician, as without direct patient contact he is able to observe, counsel and actively interact - the latter even more so in the future. In oncology the increase of knowledge thus far has gone hand-in-hand with further specialization. This explains the difficulties one encounters in the correct evaluation of relevant data of one specific patient. Telemedicine will help to focus on the advantages of specialist knowledge by rendering access to all available data. These possibilities should furthermore be accessible during a consultation, an examination or in the course of a surgical intervention. Real-time modalities are referred to as telepresence and exceed by far a mere electronic version of the patient's medical folder. Especially in oncology, interdisciplinary collaboration is immensely important for successful therapy. Preoperative diagnostic data are still to be evaluated according to the intraoperative findings. At this decisive moment, it is necessary to involve specialists of other oncological disciplines. Real-time communication devices have to be present in order to transfer image data and clinical observations and ensure the best possible transmission quality to resident and geographically distant experts. With further technological perfection and widespread availability of interactive consultation, other applications include the "second opinion" in the daily routine. Another fascinating option in oncology is offered by visual computer simulation in virtual reality (VR). Medical data are visualized according to the human perception by the means of scenic simulation. From that point of view, VR technologies represent a practicable user interface between computer technology and the individual human being. Through VR, three-dimensional worlds containing virtual objects, which consist of computer-generated data, are created, which the user may explore and liberally interact with. The perfect simulation of realistic settings offers a method of training that may be extended to the field of oncology, as it has been known for a comparatively long period of time from flight simulators in space and air technology. In contrast, medical training is currently achieved mainly by "training-on-the-job." There is well-proven and widely acknowledged certainty of the tremendous influence that the number of surgical interventions-in other words, the training skills of the surgeon-has on the success of a diagnostic or therapeutic intervention. Previously, the subjective experience of the physician acquired from earlier cases determined his efficiency to a large extent. It was, in addition, influenced essentially by perception, "performance on the day" and personal attitude. The goal must be to strengthen the objective criteria as the basis for consistent decision-making processes and clear instructions for therapy. Strict quality management as practiced in air technology has clearly led to a reduction in accidents, and, accordingly, a similar effect is imaginable in oncology with continuous training using VR simulators, leading to improved therapeutic outcome. Other possibilities for use are principally implied and similarly useful for medical school and postgraduate training. The idea of computer-guided medical procedures or medical robots is therefore no longer a mere utopia. Telepresence, telerobotic and VR techniques should, in principle, effectively support the physician in diagnostic processes and therapy. The responsibility for coordination and sensible use of new technological developments will still remain with the physician, such as improving and simplifying medical procedures. Technology should be used according to the situation, not to adapt the patient to a technocratic environment, but to emphasize human treatment of the individual patient. From the opinion of the telephone being a futile technical invention to the other extreme of computed technology as a substitute for the physician (Dr. Cyber), the future role of telemedical techniques and their potential for medical advantage or support, especially in the field of oncology, should be critically viewed and evaluated.

Journal Article↗
PubMed2004

Dual-domain solute transfer and transport processes: evaluation in batch and transport experiments.

Soil macropore networks establish a dual-domain transport scenario in which water and solutes are preferentially channeled through soil macropores while slowly diffusing into and out of the bulk soil matrix. The influence of macropore networks on intra-ped solute diffusion and preferential transport in a soil typical of subsurface-drained croplands in the Midwestern United States was studied in batch- and column-scale experiments. In the batch diffusion studies with soil aggregates, the estimated diffusion radius (length) of the soil aggregates corresponded to the half-spacing of the aggregate fissures, suggesting that the intra-ped fissures reduced the diffusion impedance and preferentially allowed solutes to diffuse into the soil matrix. In the column-scale solute transport experiments, the average diffusion radius (estimated from HYDRUS-2D simulations and a first-order diffusive transfer term) was nearly double that of the batch-scale study. This increase may be attributed to a loss of pore continuity and a compounding of the small diffusion impedance through macropores at the larger scale. The column-scale solute transport experiments also suggest that two preferential networks exist in the soil. At and near soil saturation, a primary network of large macropores (possibly root channels and earthworm burrows) dominate advective transport, causing a high degree of physical and sorption nonequilibrium and simultaneous breakthrough of a nonreactive (bromide) and a reactive (alachlor) solute. As the saturation level decreases, the primary network drains, while transport through smaller macropores (possibly intra-ped features) continues, resulting in a reduced degree of nonequilibrium and separation in the breakthrough curves of bromide and alachlor.

Acetamides↗
PubMed2005

Cell population dynamics modulate the rates of tissue growth processes.

The development and testing of a discrete model describing the dynamic process of tissue growth in three-dimensional scaffolds is presented. The model considers populations of cells that execute persistent random walks on the computational grid, collide, and proliferate until they reach confluence. To isolate the effect of population dynamics on tissue growth, the model assumes that nutrient and growth factor concentrations remain constant in space and time. Simulations start either by distributing the seed cells uniformly and randomly throughout the scaffold, or from an initial condition designed to simulate the migration and cell proliferation phase of wound healing. Simulations with uniform seeding show that cell migration enhances tissue growth by counterbalancing the adverse effects of contact inhibition. This beneficial effect, however, diminishes and disappears completely for large migration speeds. By contrast, simulations with the "wound" seeding mode show a continual enhancement of tissue regeneration rates with increasing cell migration speeds. We conclude that cell locomotory parameters and the spatial distribution of seed cells can have profound effects on the dynamics of the process and, consequently, on the pattern and rates of tissue growth. These results can guide the design of experiments for testing the effectiveness of biomimetic modifications for stimulating tissue growth.

Algorithms↗