Flocculation in brewing yeasts: a computer simulation study

A new simulator, INDISIM-FLOC, based on the individual-based simulator INDISIM, is used to examine the predictions of two different models of yeast flocculation. The first, proposed by Calleja is known as the "addition" model. The second, proposed by Stratford is known as the "cascade" model. The simulations show that the latter exhibits a better qualitative agreement with available experimental data.     

Neurite branching pattern formation: modeling and computer simulation.

A model for nerve cell pattern formation is proposed in this paper. The model is based on some experimental results and an assumption that there is a kind of inhibitive interaction between growing neurites on the same nerve cell. In this paper, this interaction is termed lateral inhibition. A group of ordinary differential equations are used to describe the elongation of the terminal neurite segments of individual nerve cells. Computer simulation and comparison of it with in vitro studies are also made in this paper.     

Changes in foot loading following plantar fasciotomy: a computer modeling study

Forward dynamic simulations of a toe-rise task were developed to explore the outcomes of plantar fasciotomy, a surgery commonly performed to relieve heel pain. The specific objectives of this study were to develop such a simulation, validate its predictions, and simulate rising on toes using a model from which the plantar fascia had been removed. Root-mean squared differences between the intact model and measurements of healthy subjects were found to be 0.009 body weights (BW) and 0.055 BW for the horizontal and vertical ground reaction forces and 7.1 mm, 11.3 mm, and 0.48 deg for the horizontal, vertical and rotational positions of the pelvis. Simulated plantar fasciotomy increased passive arch torques by 7.4%, increased metatarsal head contact forces by 18%, and resulted in greater toe flexor activity. These simulations may explain the mechanisms behind plantar fasciotomy complications when patients perform activities that require loading of the plantarflexors and the longitudinal arch.     

The structure of percolated polymer systems: a computer simulation study

We studied the percolation process in a system consisting of long flexible polymer chains and solvent molecules. The polymer chains were approximated by linear sequences of beads on a two-dimensional triangular lattice. The system was athermal and the excluded volume was the only potential. The properties of the model system across the entire range of polymer concentrations were determined by Monte Carlo simulations employing a cooperative motion algorithm (CMA). The scaling behavior and the structure of the percolation clusters are presented and discussed.     

Differential growth and plant tropisms: a study assisted by computer simulation

Tropisms and other movements of a plant organ result from alterations in local rates of cell elongation and a consequent development of a growth differential between its opposite sides. Relative elemental rates of elongation (RELELs) are useful to characterize the pattern of growth along and round an organ. We assume that the value of the RELEL at a given point is dependent on distance from the tip and that the distribution of values along the organ surface can be characterized in terms of the spread and the position of the maximum value. A computer model is described which accommodates these parameters and simulates tropic curvatures due to differential growth. Additional regulatory functions help to return the simulated organ to its original orientation. Particular attention is given to the simulation of root gravitropism because here not only do each of the various growth and regulatory parameters have a known biological counterpart, but some can also be given an actual quantitative value. The growth characteristics relate to the biophysical properties of cells in the elongation zone of the root, while the regulatory functions relate to aspects of the graviperception and transmission systems. We believe that, given a suitably flexible model, computer simulation is a powerful means of characterizing, in a quantitative way, the contribution of each parameter to the elongation of plant organs in general and their tropisms in particular.     

Transcription regulation by steroid hormones: a computer simulation study.

Three-dimensional structures of complexes of 66 amino acid-DNA binding domains of human progesterone (hPR), estrogen (hER) and glucocorticoid (hGR) receptors (proteins), with ten base pair DNA duplexes: d(AGGTCATGCT).d(AGCATGACCT) and d(AGAACATGCT).d(AGCATGTTCT) were obtained using computer modeling and molecular mechanics techniques. Cartesian coordinates for the proteins were obtained from: 1) structural data of hER and hGR by NMR spectroscopy; 2) steric constraints imposed by tetrahedral coordination of the zinc ion to Cys residues, and 3) energy minimization in torsional and cartesian space. The proteins were made to interact with DNA (in B-form) in major groove through alpha-helical linker between the two zinc fingers. The geometry of the complexes was obtained by allowing them to slide, glide, penetrate in to and out of the groove, and to rotate about the helical axis. The complexes were energy minimized. Also maximized was the number of H-bonds between proteins and DNA. The complex structures were refined by molecular mechanics using AMBER 3.0. Structural parameters of DNA were analyzed in each complex and compared with those of native DNA optimized separately. The stereochemical differences of the complexes are discussed.     

Estimation of descriptive parameters of overlapping chromatographic peaks: a simulation study

The characteristics of a non-linear optimization technique for resolution of overlapping chromatographic peaks are examined. A modified Meiron-Marquardt method was used. The estimates of the parameters of overlapping peaks in simulated chromatograms were investigated to indicate the limitations of present mathematical methods and, hopefully, to improve their ultimate utility. Gaussian shapes as well as exponential-Gaussian convolutes were used to simulate the chromatographic peaks. Effects on the overall performance of varying heights, widths, and separation of two peaks were determined. Random additive noise and base line drift were also simulated. For illustrative purposes, the performance of the parameter estimation techniques was expressed in terms of relative errors in estimating the second (or smaller) peak's area, height and location. The results presented indicate the relative importance of noise, skewness, height and width ratios and peak separation on the maximum resolution achievable by numerical methods in an automated chromatographic system.     

Mathematical modeling and computer simulation of isoelectric focusing with electrochemically defined ampholytes

A mathematical model of isoelectric focusing at the steady state has been developed for an M-component system of electrochemically defined ampholytes. The model is formulated from fundamental principles describing the components' chemical equilibria, mass transfer resulting from diffusion and electromigration, and electroneutrality. The model consists of ordinary differential equations coupled with a system of algebraic equations. The model is implemented on a digital computer using FORTRAN-based simulation software. Computer simulation data are presented for several two-component systems showing the effects of varying the isoelectric points and dissociation constants of the constituents.     

Study of DNA base-Li doped SiC nanotubes in aqueous solutions: a computer simulation study

Due to the importance of soluble nanotubes in biological systems, computational research on DNA base functionalized nanotubes is of interest. This study presents the quantitative results of Monte Carlo simulations of Li-doped silicon carbide nanotubes and its nucleic acid base complexes in water. Each species was first modeled by quantum mechanical calculations and then Monte Carlo simulations were applied to study their properties in aqueous solution. Solvation free energies were computed to indicate the solvation behavior of these compounds. The computations show that solvation free energies of the complexes of DNA bases with Li-doped SiC nanotubes are in the order: thymine > cytosine > adenine > guanine. The results of complexation free energies were also used to study the stability of related structures, which indicate that thymine-Li-doped SiC nanotubes produce the most stable compound among the four DNA base complexes.     

Estimating the power of a proposed linkage study: a practical computer simulation approach.

I describe a simulation method to estimate the power to detect linkage given a set of pedigrees of known structure and for which family history data may be available. This method can be applied to autosomal and X-linked dominant diseases; depending on the pedigrees under consideration, it will often be applicable for autosomal and X-linked recessive diseases. This power calculation can most usefully be undertaken after family history data are gathered, but prior to examination and testing of pedigree members to obtain marker information. Of key importance, the power calculation is straightforward to carry out and not too time-consuming; it is practical even on a microcomputer. The result of the power calculation is an objective answer to the question: Will my families be sufficient to demonstrate linkage?     

Adhesion failures determine the pattern of choroidal neovascularization in the eye: a computer simulation study

Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression.     

A computer simulation study of the hydrated proton in a synthetic proton channel

Classical molecular dynamics simulations using the multistate empirical valence bond model for aqueous proton transport were performed to characterize the hydration structure of an excess proton inside a leucine-serine synthetic ion channel, LS2. For such a nonuniform pore size ion channel, it is found that the Zundel ion (H(5)O(2)(+)) solvation structure is generally more stable in narrow channel regions than in wider channel regions, which is in agreement with a recent study on idealized hydrophobic proton channels. However, considerable diversity in the relative stability of the Zundel to Eigen cation (H(9)O(4)(+)) was observed. Three of the five wide channel regions, one located at the channel's center and the other two located near the channel mouths, are found to show extraordinary preference for the Eigen solvation structure. This implies that proton hopping is inhibited in these regions and therefore suggests that these regions may behave as barriers in the proton conducting pathway inside the channel. The proton solvation is also greatly influenced by the local molecular environment of the protein. In particular, the polar side chains of the Ser residues, which are intimately involved in the solvation structure, can greatly influence proton solvation. However, no preference of the influence by the various Ser side chains was found; they can either promote or prevent the formation of certain solvation structures.     

Accuracy analysis for RSA: a computer simulation study on 3D marker reconstruction

In this paper, error analysis of three-dimensional marker coordinates reconstructed from noisy two-dimensional measurement in RSA was performed. Mathematical models to predict error propagation of focus position and object points were derived and computer simulations were performed to validate these models. Two clinical calibration cages were compared by testing the error propagation at each RSA step. The results revealed that errors of reconstructed object points were related to the focus position error, two-dimensional measurement error, position of focus and positions of object points, while errors of reconstructed focus position were determined by the two-dimensional measurement error, number of control points and location of the focus. The maximum difference between the mathematical model and the simulation for the assessment of errors of focus position was 14 microm and the maximum difference of object point positions was 1.1 microm. These differences were small and judged irrelevant, hence the simulations indicated that our models were accurate.     

Self-organization in the ontogeny of multicellular organisms: a computer simulation

The progress in understanding the patterns of evolution of ontogeny is hindered by the fact that many features of ontogeny are counterintuitive (as well as the features of other processes related to self-organization, self-assembly, and spontaneous increase in complexity). The basic principle of ontogeny of multicellular organisms is that it is the process of self-assembly of ordered multicellular structures by means of coordinated behavior of many individual modules (cells), each of which follows the same set of"rules" encoded in the genome. These rules are based on the genetic regulatory networks. We hypothesize that many specific features of ontogeny that seem nontrivial or enigmatic are, in fact, the inevitable consequences of this basic principle. If so, they do not need special explanations. In order to verify this hypothesis, we developed the computer program "Evo-Devo" based on the above principle. The program is designed to model the self-assembly of ordered multicellular structures from an aggregation of dividing cells that originate from a single original cell (zygote). Each cell follows a set of rules of behavior ("genotype") that can be specified arbitrarily by the experimenter, and is the same for all cells in the embryo (each cell is programmed in exactly the same way as all other cells). It is not allowed to specify rules for groups of cells or for the whole embryo: only local rules that should be followed at the level of a single cell are possible. The analysis of phenotypic implementation of different genotypes revealed several features which are present in the ontogeny of real organisms and are regularly reproduced in the model. These include: inherent stochasticity; inescapable necessity of development of stabilizing adaptations based on negative feedback in order to decrease this stochasticity; equifinality (noise resistance) resulting from these adaptations; the ability of ontogeny to respond to major perturbations by generating new morphological structures that differ from the "normal" ones, but have similar level of complexity; the similarity of phenotypic manifestations of different mutations; channeling of possible evolutionary transformations of ontogeny; Waddington's creodes; high probability of destabilization of ontogeny (e.g., because of mutations); the possibility of a new morphological character to appear initially as a rare anomaly (low penetrance of many mutations); pleiotropy of mutations affecting ontogeny; spontaneous emergence of morphogenetic correlations; integrity of the developing organism. The fact that these features are regularly reproduced in the model implies that they are probably the inevitable consequences of the basic principle of ontogeny of multicellular organisms formulated above.     

Concepts of sulfur,carbon, and nitrogen transformations in soil: evaluation by simulation modeling

The dynamics of sulfur immobilization and mineralization in soil were simulated to test hypotheses about their regulation by the availability of carbon and nitrogen. The concept of chemical bond classes was incorporated into the model to account for variation in composition of carbon, nitrogen, and sulfur compounds. Microbial biomass was differentiated into bacteria and fungi, and the element ratios of both groups were assumed to vary. Organic residues were divided between dead microbes plus microbial products, and the more labile fraction of stabilized soil organic matter. Concepts and hypotheses in the model were tested by applying it to data on microbial biomass, sulfate, nitrate, and CO₂ evolution obtained in laboratory incubations of two soils amended with sulfate and cellulose. An important mechanism of regulation tested in the model was the stimulation of sulfohydrolase enzyme production depending on sulfur stress in microbial biomass. The hypothesis that excess sulfate is stored as ester sulfate was supported by model dynamics.     

The effects of geometrical parameters on synaptic transmission: a Monte Carlo simulation study

Monte Carlo simulations of transmitter diffusion and its interactions with postsynaptic receptors have been used to study properties of quantal responses at central synapses. Fast synaptic responses characteristic of those recorded at glycinergic junctions on the teleost Mauthner cell (time to peak approximately 0.3-0.4 ms and decay time constant approximately 3-6 ms) served as the initial reference, and smaller contacts with fewer postsynaptic receptors were also modeled. Consistent with experimental findings, diffusion, simulated using a random walk algorithm and assuming a diffusion coefficient of 0.5-1.0 x 10(-5) cm2 s(-1), was sufficiently fast to account for transmitter removal from the synaptic cleft. Transmitter-receptor interactions were modeled as a two-step binding process, with the double-bound state having opened and closed conformations. Addition of a third binding step only slightly decreased response amplitude but significantly slowed both its rising and decay phases. The model allowed us to assess the sources of response variability and the likelihood of postsynaptic saturation as functions of multiple kinetic and spatial parameters. The method of nonstationary fluctuation analysis, typically used to estimate the number of functional channels at a synapse and single channel current, proved unreliable, presumably because the receptors in the postsynaptic matrix are not uniformly exposed to the same profile of transmitter concentration. Thus, the time course of the probability of channel opening most likely varies among receptors. Finally, possible substrates for phenomena of synaptic plasticity, such as long-term potentiation, were explored, including the diameter of the contact zone, defined by the region of pre- and postsynaptic apposition, the number and distribution of the receptors, and the degree of vesicle filling. Surprisingly, response amplitude is quite sensitive to the size of the receptor-free annulus surrounding the receptor cluster, such that expansion of the contact zone could produce an appreciable increase in quantal size, normally attributed to either the presence of more receptors or the release of more transmitter molecules.