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Analysis of the effects of measured white blood cell entrance times on hemodynamics in a computer model of a microvascular bed.

To quantify the interdependence of capillary leukocyte plugging and microvascular hemodynamics, experimental measurements were made of the time required for lymphocytes and granulocytes to enter a micropipette. Using standard micropipette deformation techniques, entrance times were found to be a function of both cell diameter and pipette diameter, with no significant dependence on aspiration pressure over the differential pressure range of 200-400 Pa. Experimental results were combined with a computer network model to describe changes in red cell distribution and flow rate resulting from the delayed entrance of leukocytes (WBC) into capillaries. The network model is based on geometrical measurements from the capillary bed of a hamster cremaster muscle (Sarelius et al. 1981) and utilizes previous work describing: 1. preferential cell distribution at a bifurcation, 2. increased apparent viscosity due to the presence of red and white cells, and 3. increased velocities of red and white cells relative to blood. Red and white cell positions within the network were computed at discrete time increments, and WBC plugging was simulated by a temporary cessation of flow in vessels of smaller diameter than the white cell. In contrast with previous studies, the increased viscosity due to the presence of WBCs was found to have an insignificant effect on overall network flow rate. Instead, a major flow reduction occurs only when capillaries are plugged by the white cells. At normal physiological concentrations (1,000 RBC/WBC), time-averaged overall network flow is reduced by 4.4%, based on averaged experimentally measured entrance times, and up to 14.8% if maximal entrance times are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocytes↗

Computer model of hydroponics nutrient solution pH control using ammonium.

A computer simulation of a hydroponics-based plant growth chamber using ammonium to control pH was constructed to determine the feasibility of such a system. In nitrate-based recirculating hydroponics systems, the pH will increase as plants release hydroxide ions into the nutrient solution to maintain plant charge balance. Ammonium is an attractive alternative to traditional pH controls in an ALSS, but requires careful monitoring and control to avoid overdosing the plants with ammonium. The primary advantage of using NH4+ for pH control is that it exploits the existing plant nutrient uptake charge balance mechanisms to maintain solution pH. The simulation models growth, nitrogen uptake, and pH of a l-m2 stand of wheat. Simulation results indicated that ammonium-based control of nutrient solution pH is feasible using a proportional integral controller. Use of a 1 mmol/L buffer (Ka = 1.6 x 10(-6)) in the nutrient solution is required.

Biomass↗

Multiple copy sampling in protein loop modeling: computational efficiency and sensitivity to dihedral angle perturbations.

Multiple copy sampling and the bond scaling-relaxation technique are combined to generate 3-dimensional conformations of protein loop segments. The computational efficiency and sensitivity to initial loop copy dispersion are analyzed. The multicopy loop modeling method requires approximately 20-50% of the computational time required by the single-copy method for the various protein segments tested. An analytical formula is proposed to estimate the computational gain prior to carrying out a multicopy simulation. When 7-residue loops within flexible proteins are modeled, each multicopy simulation can sample a set of loop conformations with initial dispersions up to +/- 15 degrees for backbone and +/- 30 degrees for side-chain rotatable dihedral angles. The dispersions are larger for shorter and smaller for longer and/or surface loops. The degree of convergence of loop copies during a simulation can be used to complement commonly used target functions (such as potential energy) for distinguishing between native and misfolded conformations. Furthermore, this convergence also reflects the conformational flexibility of the modeled protein segment. Application to simultaneously building all 6 hypervariable loops of an antibody is discussed.

Animals↗

Computer modeling from solution data of spinach chloroplast and of Xenopus laevis somatic and oocyte 5 S rRNAs.

Detailed atomic models of a eubacterial 5 S rRNA (spinach chloroplast 5 S rRNA) and of a eukaryotic 5 S rRNA (somatic and oocyte 5 S rRNA from Xenopus laevis) were built using computer graphic. Both models integrate stereochemical constraints and experimental data on the accessibility of bases and phosphates towards several structure-specific probes. The base sequence was first inserted on to three-dimensional structural fragments picked up in a specially devised databank. The fragments were modified and assembled interactively on an Evans & Sutherland PS330. Modeling was finalized by stereochemical and energy refinement. In spite of some uncertainty in the relative spatial orientation of the substructures, the broad features of the models can be generalized and several conclusions can be reached: (1) both models adopt a distorted Y-shape structure, with helices B and D not far from colinearity; (2) no tertiary interactions exist between loop c and region d or loop e; (3) the internal loops, in particular region d, contain several non-canonical base-pairs of A.A, U.U and A.G types; (4) invariant residues appear to be more important for protein or RNA binding than for maintaining the tertiary structure. The models are corroborated by footprinting experiments with ribosomal proteins and by the analysis of various mutants. Such models help to clarify the structure-function relationship of 5 S rRNA and are useful for designing site-directed mutagenesis experiments.

Animals↗

Computational model of a primate arm: from hand position to joint angles, joint torques and muscle forces.

Three-dimensional reaching by non-human primates is an important behavioral paradigm for investigating representations existing in motor control areas of the brain. Most studies to date have correlated neural activity to a few of the many arm motion parameters including: global hand position or velocity, joint angles, joint angular velocities, joint torques or muscle activations. So far, no single study has been able to incorporate all these parameters in a meaningful way that would allow separation of these often highly correlated variables. This paper introduces a three-dimensional, seven degree-of-freedom computational musculoskeletal model of the macaque arm that translates the coordinates of eight tracking markers placed on the arm into joint angles, joint torques, musculotendon lengths and finally into an optimized prediction of muscle forces. This paper uses this model to illustrate how the classic center-out reaching task used by many researchers over the last 20 years is not optimal in separating out intrinsic, extrinsic, kinematic and kinetic variables. However, by using the musculoskeletal model to design and test novel behavioral movement tasks, a priori, it is possible to disassociate the myriad of movement parameters in motor neurophysiological reaching studies.

Algorithms↗

Computer model for municipal solid waste treatment in developing countries.

Many integrated solid waste management (ISWM) models are available but are of little use to developing countries such as India since they do not take into account typical developing countries municipal solid waste characteristics such as high organic content, poor performance of formal sector control and support, high activity of scavengers and waste pickers, etc. The goal of this study is to create a computer program to determine the least cost treatment and disposal system for a given solid waste management problem. To demonstrate its applicability, the model was applied to the Indian city Amritsar. A typical Indian city like Amritsar generates about 500 ton of MSW/d with 45% moisture content, 30% volatile matter, and calorific value of 1500 kcal/kg. The computer model was run for various technologies. Results showthatfor Amritsar city incineration an expenditure of U.S. dollars (USD) 6.62 is incurred, whereas landfilling, composting, and biomethanation digester give an income of USD 0.13, USD 0.20, and USD 0.23 per ton of MSW, respectively. This empirical exercise not only reveals the model's strengths such as highlighting important interdependencies in the waste management sector but also its requirement for quality data.

Bacteria, Anaerobic↗

A computer model for hydrodynamic shearing of DNA-further investigation on distribution of break lengths: Part III.

The distribution of breaks along The DNA strand in hydrodynamic shearing is unknown, and there is no real-world experiment which could directly determine this distribution. This paper presents an extension of the simulation model for hydrodynamic shearing of DNA reported in [1,2]. An empirical model is presented showing a good linear relationship between LAMBDA * and number of fragments from each original strand. The average strand length is directly proportional to the number of fragments per strand. The traditional assumption of uniform random breaks along the DNA strand is supported by this model.

Chemical Phenomena↗

Influence of total hip design on dislocation: a computer model and clinical analysis.

Dislocation following hip arthroplasty remains problematic. While the etiology of dislocation may be multifactorial, implant system design may play a role. Using a computer aided design program, virtual range of motion of several commonly implanted designs was performed with prosthetic interference representing impingement used as an endpoint. Implants with small diameter head size (22 mm) and a larger trunion geometry (type II taper) demonstrated impingement in flexion at less than 90 degrees , suggesting an increased risk for dislocation. To investigate this clinically, we performed a review of a consecutive series of 254 primary hip arthroplasties performed by a single surgeon using an implant with a type II taper (Biomet, Warsaw, IN). At a minimum 2 year followup, 12 patients with 12 hips (4.8%) had at least one episode of dislocation. Stratified by head size, the dislocation rates were 3.6% for 28 mm, 4.8% for 26 mm, and 18.8% for 22 mm bearings. These findings support the notion that computer aided design modeling of implant systems is useful in evaluating range of motion and this technique could be employed during the design of any new implant system.

Arthroplasty, Replacement, Hip↗

Re-entrant cardiac arrhythmias in computational models of long QT myocardium.

The long QT syndrome (LQTS) is an inherited disorder in which repolarization of cardiac ventricular cells is prolonged. Patients with the LQTS are at an increased risk of ventricular cardiac arrhythmias. Two phenotypes of the inherited LQTS are caused by defects in K(+)channels (LQT1 and LQT2) and one by defects in Na(+)channels (LQT3). Patients with LQT1 are more likely to have self-terminating arrhythmias than those with LQT3. The aim of this computational study was to propose an explanation for this finding by comparing the vulnerability of normal and LQT tissue to re-entry, and estimating the likelihood of self-termination by motion of re-entrant waves to an inexcitable boundary in simulated LQT1, LQT2 and LQT3 tissue. We modified a model of mammalian cardiac cells to simulate LQT1 by reducing maximal I(K(s))conductance, LQT2 by reducing maximal I(K(r))conductance, and LQT3 by preventing complete inactivation of I(Na)channels. Each simulated phenotype was incorporated into a computational model of action potential propagation in one- and two-dimensional homogeneous tissue. Simulated LQT tissue was no more vulnerable to re-entry than simulated normal tissue, but the motion of re-entrant waves in simulated LQT1 tissue was between 2 and 5 times greater than the motion of re-entrant waves in simulated LQT2 and LQT3 tissue. These findings suggest that LQT arrhythmias do not result from increased vulnerability to re-entry, and that re-entry once initiated is more likely to self-terminate by moving to an inexcitable tissue boundary in LQT1 than in LQT2 and LQT3. This finding is consistent with clinical observations.

Action Potentials↗

Interactions of animal and computer models in investigations of the "anemia" of space flight.

Previous studies in mice deprived of water have suggested that these animals, like men in space, show hemoconcentration due to plasma volume reductions, a weight loss greater than that due to fluid loss alone, and suppression of red blood cell production. To more fully understand the mechanisms responsible for the suppressed erythropoiesis in dehydrated mice, a mathematical model for erythropoietic regulation has been adapted to this rodent. Computer simulations suggested several new experimental studies to more fully understand the erythroid response to dehydration. The investigations were directed to determining whether dehydration was accompanied by: a) a shortened red blood cell survival, b) altered sensitivity of the erythropoietin (Ep)-producing mechanism, c) a shortened red blood cell transit time, d) changes in the Ep serum half-life, e) changes in hemoglobin P50, and f) reduced renal blood flow. All parameters except changes in renal blood flow were investigated in vivo and incorporated into, or omitted from, the mathematical simulations as directed by experimental findings. The mathematical model is able to realistically simulate the in vivo erythroid response to dehydration making only one, experimentally-untested, assumption. Computer simulations confirm conclusions drawn from the animal studies that the primary cause of the suppressed erythropoiesis in dehydrated mice is the reduced food intake, with hemoconcentration playing a relatively minor role. The interaction between computer simulations and animal experiments is shown to be a powerful approach for formulating and testing hypotheses, designing new experiments, and achieving a clearer understanding of the factors controlling erythropoiesis.

Anemia↗

A high resolution computer model for sound propagation in the human thorax based on the Visible Human data set.

A parallel supercomputer model based on realistic tissue data is developed for sound propagation in the human thorax and the sound propagation behavior is analyzed under various conditions using artificial sound sources. The model uses the Visible Human male data set for a realistic representation of the human thorax. The results were analyzed in time and frequency domains. The analysis suggests that lower frequencies of around 100 Hz are more effectively transmitted through the thorax and that the spatial confinement of sound waves within the thorax results in a resonance effect at around 1500 Hz. The results confirm previous studies that show the size of the thorax plays a significant role in the type of sound generated at the chest wall.

Acoustics↗

Computational models of hair cell bundle mechanics: II. Simplified bundle models.

Simplified versions of hair cell bundles are mechanically modeled. The influence of various geometric and material combinations on bundle stiffness, link tensions and deformation shape are examined. Three models are analyzed within this paper: two stereocilia connected by one link, two stereocilia connected by a biologically realistic set of links, and a column of stereocilia connected by realistic links. Stereocilia are modeled using a distributed parameter model [J. Biomech. Eng. 122, 44]. Some fundamental rules for linking bundles emerge from these tests: (1) Links must have a threshold stiffness value for the bundle to deform as a whole. Beyond this value, the stereocilia are perfectly linked and variations in link stiffness do not significantly effect the bundle stiffness or link tension. (2) Decreasing the relative heights of successive stereocilia may increase link tension while decreasing bundle stiffness. (3) When lateral links exist, the top most lateral links carry the majority of tension. Lower links in single column model appear mechanically insignificant. (4) Extending the length of the bundle in a column does not increase the stiffness once the column reaches a certain length.

Animals↗

DNA -a computer model.

The model of the system DNA-histones functioning like a computer has the following elements: 1. The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the pi electrons of a nucleotide base are excited, an exchange of protons is produced between the 2 complementary bases. The result is the displacement of the double conjugated bonds which facilitate the intermolecular transmission of the electronic wave of excitation by an electromagnetic coupling. 2. Each triplet of nucleotide bases of DNA fixes a certain amino acid (as in the genetic code). Between the nucleotide bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation.

Computers↗