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[Computer modelling of gastrulation and neurulation in amphibian embryos based on mechanical tension fields].

The values of cell wall tensions were calculated with an assumption of mechanical equilibrium of every cell apex on schematic diagrams of histological sections of the common frog embryonic tissues. The maps of the main (the strongest) tensions were drawn for the early gastrula and early neurula. The further course of gastrulation and neurulation was simulated with an assumption that the cell apices are displaced due to active contractions of the most tensed cell walls (variant A of the model). In addition, a suggestion was studied that the capacity for contraction falls in the most extended cell walls (variant B). Up to seven steps of model morphogenesis were simulated and the tension field was recalculated at every step. The course of gastrulation and neurulation was reproduced during simulation with sufficient details, including regional peculiarities of neurulation in the trunk and head regions. Both variants gave roughly similar results for gastrulation, whereas variant B ensured a faster course of model morphogenesis for neurulation. A conclusion was drawn that the mechanical tension fields established by the onset of gastrulation and neurulation represent a sufficient informational base for their further course.

Amphibians↗
PubMed1995

Computer model of human lung morphology to complement SPECT analyses.

Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were selectively deposited within the human lung. The targeted delivery to specific sites, such as receptors and sensitive airway cells, would enhance the efficacies of airborne pharmaceuticals. The high spatial discrimination of deposition patterns of inhaled particles can be determined via Single Photon Emission Computer Tomography (SPECT). However, major problems continue to compromise SPECT protocols. Our work focuses on two issues: how can the spatial discrimination be improved; and how are the images to be interpreted? We present a methodology, described by a mathematical model and supercomputer code, for systematically slicing through the human lung in a prescribed manner that is conducive to implementation into SPECT analyses. The lung is divided into concentric shells, or annuli, and the airway generation-by-generation composition of the respective shells determined. This identification was accomplished by superimposing the new shell structure with the 3-D branching network presented by Martonen et al. [23]. Perhaps the key aspect of the model-code is that the supercomputer is instructed to determine the 3-D spatial coordinates of each of the airways (over 16 million) of the lung with respect to the clinician-selected contours of shells within the lung.

Administration, Inhalation↗
PubMed1980

Computer modeling, complex biological systems, and their simplifications.

The amount of information defining a biological system, as specified in its genome, is vastly larger than the amount of information the human mind can handle simultaneously in its short-term memory (7 +/- 2 items at most). In such a situation the mind tends to simplify, linearize, and consider only a few of many variables that may be involved. This may be limiting when an experimenter interprets his own experiments without help from theory or modeling as is common in biology. The Michaelis-Menten model, which is very useful although not necessarily valid, and its linearizations are described as an example of this. The social processes and obligations involved in simplifying complex situations are discussed. Computer simulation provides a method for investigating complex nonlinear systems that does not require excessive simplification of the biological system being studied and whose economics are becoming steadily more favorable.

Computers↗
PubMed1993

Some computational models at the cellular level.

A number of viewpoints on how a cell can be modelled are discussed in this paper in light of the ability it has to process information. The paper begins with a very brief summary of four general types of computation: sequential, parallel, distributed, and emergent. These form the general framework from which a number of comparisons are made. Several metaphors are introduced to enable reflections to be made about cellular computational properties. The most important metaphor, namely the cell as a machine, is discussed, and then a number of other ideas are introduced that complement much current thinking in this area. The idea of networks or circuits in the cell is then developed, as this provides a means of describing the mechanisms within a machine. Following on from this, three further metaphors are applied in order to overcome certain limitations in current machine thinking, cell-as-society, cell-as-text, and cell-as-field.

Animals↗
PubMed1996

Crosstalk between cellular morphology and calcium oscillation patterns. Insights from a stochastic computer model.

Agonist-induced oscillations in the concentration of intracellular free calcium ([Ca2+]i) display a wide variety of temporal and spatial patterns. In non-excitable cells, typical oscillatory patterns are somewhat cell-type specific and range from frequency-encoded, repetitive Ca2+ spikes to oscillations that are more sinusoidal in shape. Although the response of a cell population, even to the same stimulus, is often extremely heterogeneous, the response of the same cell to successive exposures can be remarkably similar. We propose that such "Ca2+ fingerprints' can be a consequence of cell-specific morphological properties. The hypothesis is tested by means of a stochastic computer simulation of a two-dimensional model for oscillatory Ca2+ waves which encompasses the basic elements of the two-pool oscillator introduced by Goldbeter et al. (Goldbeter A., Dupont G., Berridge M.J. Minimal model for signal-induced Ca(2+)-oscillations and for their frequency encoding through protein phosphorylation. Proc Natl Acad Sci USA 1990; 87: 1461-1465). In the framework of our extended spatiotemporal model, single cells can display various oscillation patterns which depend on the agonist dose, Ca2+ diffusibility, and several morphological parameters. These are, for example, size and shape of the cell and the cell nucleus, the amount and distribution of Ca2+ stores, and the subcellular location of the inositol(1,4,5)-trisphosphate-generating apparatus.

Biological Clocks↗
PubMed2005

A computational model of the ribbon synapse.

A model of the ribbon synapse was developed to replicate both pre- and postsynaptic functions of this glutamatergic juncture. The presynaptic portion of the model is rich in anatomical and physiological detail and includes multiple release sites for each ribbon based on anatomical studies of presynaptic terminals, presynaptic voltage at the terminal, the activation of voltage-gated calcium channels and a calcium-dependent release mechanism whose rate varies as a function of the calcium concentration that is monitored at two different sites which control both an ultrafast, docked pool of vesicles and a release ready pool of tethered vesicles. The postsynaptic portion of the program models diffusion of glutamate and the physiological properties of glutamatergic neurotransmission in target cells. We demonstrate the behavior of the model using the retinal bipolar cell to ganglion cell ribbon synapse. The model was constrained by the anatomy of salamander bipolar terminals based on the ultrastructure of these synapses and presynaptic contacts were placed onto realistic ganglion cell morphology activated by a range of ribbon synapses (46-138). These inputs could excite the cell in a manner consistent with physiological observations. This model is a comprehensive, first-generation attempt to assemble our present understanding of the ribbon synapse into a domain that permits testing our understanding of this important structure. We believe that with minor modifications of this model, it can be fine tuned for other ribbon synapses.

Animals↗
PubMed1993

[The development of a computer model in the quantitative assessment of thallium-201 myocardial scintigraphy].

Thallium-201 scintigraphy is a widely used noninvasive procedure for the detection and prognostic assessment of patients with suspected or proven coronary artery disease. Thallium uptake can be evaluated by a visual analysis or by a quantitative interpretation. Quantitative scintigraphy enhances disease detection in individual coronary arteries, provides a more precise estimate of the amount of ischemic myocardium, distinguishing scar from hypoperfused tissue. Due to the great deal of data, analysis, interpretation and comparison of thallium uptake can be very complex. We designed a computer-based system for the interpretation of quantitative thallium-201 scintigraphy data uptake. We used a database (DataEase 4.2-DataEase Italia). Our software has the following functions: data storage; calculation; conversion of numerical data into different definitions classifying myocardial perfusion; uptake data comparison; automatic conclusion; comparison of different scintigrams for the same patient. Our software is made up by 4 sections: numeric analysis, descriptive analysis, automatic conclusion, clinical remarks. We introduced in the computer system appropriate information, "logical paths", that use the "IF ... THEN" rules. The software executes these rules in order to analyze the myocardial regions in the 3 phases of scintigraphic analysis (stress, redistribution, re-injection), in the 3 projections (LAO 45 degrees, LAT,ANT), considering our uptake cutoff, obtaining, finally, the automatic conclusions. For these reasons, our computer-based system could be considered a real "expert system".

Computer Simulation↗
PubMed2004

A computational model for collagen fibre remodelling in the arterial wall.

As the interaction between tissue adaptation and the mechanical condition within tissues is complex, mathematical models are desired to study this interrelation. In this study, a mathematical model is presented to investigate the interplay between collagen architecture and mechanical loading conditions in the arterial wall. It is assumed that the collagen fibres align along preferred directions, situated in between the principal stretch directions. The predicted fibre directions represent symmetrically arranged helices and agree qualitatively with morphometric data from literature. At the luminal side of the arterial wall, the fibres are oriented more circumferentially than at the outer side. The discrete transition of the fibre orientation at the media-adventitia interface can be explained by accounting for the different reference configurations of both layers. The predicted pressure-radius relations resemble experimentally measured sigma-shaped curves. As there is a strong coupling between the collagen architecture and the mechanical loading condition within the tissue, we expect that the presented model for collagen remodelling is useful to gain further insight into the processes involved in vascular adaptation, such as growth and smooth muscle tone adaptation.

Adaptation, Physiological↗
PubMed1982

Computer modeling of tumor hyperthermia (a dynamic lumped parameter model).

The thermal behavior of normal and neoplastic tissue is modeled by a set of coupled ordinary differential equations. The equations lump the tissue and tumor into individual compartments, so that the equations are time dependent. These equations represent an initial step in the development of a comprehensive model which may be used in studying the dynamics and control of the system under normo- and hyperthermic conditions.

Computers↗
PubMed2005

Phase singularities and filaments: simplifying complexity in computational models of ventricular fibrillation.

In the whole heart, millions of cardiac cells are involved in ventricular fibrillation (VF). Experimental studies indicate that VF is sustained by re-entrant activity, and that each re-entrant wave rotates around a filament of phase singularity. Filaments act as organising centres, and offer a way to simplify and quantify the complex spatio-temporal behaviour observed in VF. Where a filament touches the surface of fibrillating myocardium re-entrant activity can be observed, however the behaviour of filaments within bulk ventricular myocardium is difficult to observe directly using present experimental techniques. Large scale computational simulations of VF in three-dimensional (3D) tissue offer a tool to investigate the properties and behaviour of filaments, and the aim of this paper is to review recent advances in this area as well as to compare recent computational studies of fibrillation in whole ventricle geometries.

Animals↗
PubMed2006

Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling.

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.

Adult↗