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Chaos and irreversibility in simple model systems.

The multifractal link between chaotic time-reversible mechanics and thermodynamic irreversibility is illustrated for three simple chaotic model systems: the Baker Map, the Galton Board, and many-body color conductivity. By scaling time, or the momenta, or the driving forces, it can be shown that the dissipative nature of the three thermostated model systems has analogs in conservative Hamiltonian and Lagrangian mechanics. Links between the microscopic nonequilibrium Lyapunov spectra and macroscopic thermodynamic dissipation are also pointed out. (c) 1998 American Institute of Physics.

Journal Article↗

Lung cancer model system using 3-methylcholanthrene in inbred strains of mice.

A model system has been established for studying lung carcinogenesis using intratracheal instillation of 3-methylcholanthrene in C3H/AnfCum and C57BL/Cum X C3H/AnfCum F1 (hereafter called BC3F1/Cum) mice. The animals in these studies were screened for adventitious agents and were free throughout their lifetime of two important lung viruses, Sendai virus and pneumonia virus of mice. Under these conditions, the occurrence of spontaneous and chemically indiced lung cancers was determined over the lifetime of the animals. Data were analyzed by the actuarial method for lung tumor probability. Probability was found to be dose and time dependent. Over 95% of the 3-methylcholanthrene-treated BC3F1/Cum and over 88% of the C3H/AnfCum mice were found at death to have pulmonary carcinomas. Tumors observed in animals which died up to 40 weeks on test were almost always squamous cell carcinomas (approximately 85%), while tumors which were observed in animals which died after 50 weeks were mainly alveolar adenocarcinomas (approximately 80%). Both tumors types metastasized widely. Spontaneous lung cancers (only alveolar adenocarcinomas were observed) occurred in these two strains at low frequency and were expressed late in life. Thus, the system described affords a suitable model to study the induction, expression, and progression of lung tumors under conditions where a vast majority of animals develop neoplasia.

Animals↗

Impact of pH on the kinetics of acrylamide formation/elimination reactions in model systems.

The effect of pH on acrylamide formation and elimination kinetics was studied in an equimolar (0.1 M) asparagine-glucose model system in phosphate or citrate buffer, heated at temperatures between 120 and 200 degrees C. To describe the experimental data, a simplified kinetic model was proposed and kinetic parameters were estimated by combined nonlinear regression and numerical integration on the data obtained under nonisothermal conditions. The model was subsequently validated in a more realistic potato-based matrix with varying pH. By increasing acidity, the reaction rate constants at T(ref) (160 degrees C) for both acrylamide formation and elimination can significantly be reduced, whereas the temperature dependence of both reaction rate constants increases. The introduction of a lyophilized potato matrix (20%) did not affect the acrylamide formation reaction rate constant at reference temperature (160 degrees C) as compared to the asparagine-glucose model system; the elimination rate constant at T(ref), on the contrary, was almost doubled.

Acrylamide↗

The induction of lamellar stacking by cholesterol in lecithin-bile salt model systems and human bile studied by synchrotron X-radiation.

Small angle X-ray scattering (SAXS) with synchroton radiation was used to investigate interactions among lipid particles in lecithin-bile salt model systems and in native gallbladder biles. In model systems in the absence of cholesterol, isotropic, continuous spectra were found, indicating the absence of periodic structures. In the presence of excess cholesterol, interaction in the form of lamellar stacking was detected by the appearance of discrete diffraction peaks. In the supersaturated cholesterol region of the commonly accepted phase diagram [1], where cholesterol crystals were expected, we found lamellar stacking. The high proportion of cholesterol to bile salts seems to be the common denominator of these models. The lamellar stacking was also found in native unprocessed bile. This effect of cholesterol on lipid structure has not been previously described. Lamellar stacking may contribute to cholesterol solubilization. Its influence on the kinetics of cholesterol crystallization is presently unknown.

Bile↗

A system model of oral glucose absorption: validation on gold standard data.

A reliable model of glucose absorption after oral ingestion may facilitate simulation as well as pathophysiological studies. One of the difficulties for the development and quality assessment of such models has been the lack of gold standard data for their validation. Thus, while data on plasma concentrations of glucose are available, the rates of appearance in plasma of ingested glucose (Ra) were not available to develop such models. Here we utilize the recent availability of Ra data, estimated with a model-independent multiple tracer technique, to formulate a system model of intestinal glucose absorption. Two published and two new models are tested on this new data set. One of the two new models performed best: it is nonlinear, describes the Ra data well and its parameters are estimated with good precision. This model has important potential both in simulation contexts, e.g., it can be incorporated in whole-body models of the glucose regulatory system, as well as in physiological and clinical studies to quantitatively characterize possible impairment of glucose absorption in particular populations such as elderly and diabetic individuals.

Absorption↗

A recipe-based, diet-planning modelling system.

In a recent article in the British Journal of Nutrition, Sklan & Dariel (1993) presented a method for diet planning employing a mixed-integer programming algorithm for meeting nutritional requirements at minimum costs for institutions or individuals. They recognized that most food items are generally consumed in whole units and as such they are represented as integer variables. However, as in most previous studies, they derived the minimum cost diets by optimizing over purchased food items. The present paper presents a computer-assisted, diet-planning modelling system for individuals by optimizing over recipes instead of food items. This is accomplished by restricting the integer programming solutions to those bundles of food that represent reasonably popular meal recipes. The modelling system is composed of three main components: recipe data entry, database management, and the model. The recipe data entry component creates and stores recipes. It also provides nutritional analysis of the recipes. The database management component creates and maintains several databases necessary to build the modelling data file. The modelling component solves the user-specified model. Currently, the model component can solve for the optimal diet by minimizing cost or minimizing cooking and preparation time. The optimal diet is prepared to satisfy the recommended nutritional guidelines for a predefined group of individuals for 1 week. The system currently has 895 popular recipes found in Hawaii. Diet plans generated using this modelling system with differing objectives are discussed and compared.

Computer Simulation↗

A systematic examination of the in vitro Ussing chamber and the in situ single-pass perfusion model systems in rat ileum permeation of model solutes.

In situ and in vitro intestinal absorption in the rat ileum was systematically studied and mechanistically quantified in terms of permeability coefficients (P) of a series of [(3)H]steroids as model transcellular permeants, [(3)H]taurocholate utilizing the active membrane transport systems to define the aqueous boundary layer (ABL), and [(14)C]urea and [(14)C]mannitol as pore-hindered paracellular diffusants. In situ single-pass perfusion experiments were performed in isolated ileal segments and blood samples were collected from the cannulated mesenteric vein. For the in vitro experiments, an excised, serosal and muscular layer-removed, ileal tissue was mounted in the Ussing chamber diffusion cells. In situ and in vitro P values versus logarithm of the partition coefficient in n-octanol/water (log K) of the steroids were characterized by a sigmoidal-shaped curve in which plateau values were attained for the highly lipophilic steroids with log K greater, similar 2.5. The in situ and in vitro transport barriers in series were viewed as ABL/mucosal epithelium and ABL/mucosal epithelium/submucosal tissue, respectively. Within this framework and the use of experimental strategies and theoretical reasoning, the transport barriers of the steroids were quantitatively delineated and the rate-determining barriers identified. In the plateau region, the analyses indicate that the in situ absorption of the lipophilic steroids was essentially ABL controlled, whereas the in vitro absorption was about equally controlled by diffusion across the ABL and submucosal tissue. The in situ and in vitro pore radii of the paracellular route were 7.2 and 9.2 A, respectively, and the difference was likely the result of perturbation of the tight junctions during the in vitro preparation of the ileal tissue.

Algorithms↗

Studies of reaction kinetics in relation to the Tg' of polymers in frozen model systems.

The rates of diffusion-controlled processes in a frozen system can be influenced by the presence of glassy states. One characteristic of cryostabilization by this mechanism is a change in the temperature dependence of reaction rates at the Tg' of the system. The cryostabilization behavior of solutes such as maltodextrin, carboxymethylcellulose (CMC), and sucrose was studied. Three different model reaction systems (enzyme hydrolysis, protein aggregation, and non-enzymatic oxidation) were used. Maltodextrin had a consistent pattern of cryostabilization behavior at temperatures ranging from -3 degrees C to -20 degrees C for all three model systems. Significant retardation effects were evident in the temperature range corresponding to its glassy states. Sucrose did not show a stabilizing effect in the non-proteinaceous model system (the non-enzymatic oxidation reaction). This could partly be due to the absence of the glassy state, since the storage temperatures were above its Tg'. However, in the protein aggregation model system, sucrose was an excellent stabilizer in protecting actomyosin from aggregation. This may be explained by a "solute exclusion" mechanism. CMC did not show any stabilizing effect in the protein aggregation and non-enzymatic oxidation model systems studied, even though it has a Tg' as high as that of maltodextrin. These results demonstrated that although the presence of a glassy state may well have a retarding effect on the rates of diffusion processes, just knowing the Tg' of a polymer is not sufficient for prediction of its stabilization effect in a frozen system.

Actomyosin↗

The sequential migration of neutrophils through endothelium and epithelium: a new model system.

To better understand the mechanisms by which neutrophils migrate into the airways, we constructed a novel in vitro model system with human umbilical vein endothelial cell (HUVE) monolayers grown on top of permeable filters and human lung Type II-like alveolar epithelial cell (A549) monolayers grown on the undersurface of the filters. The sequential migration of human neutrophils through the endothelium (apical to basal movement) and subsequently through the epithelium (basal to apical movement) in response to a stimulus located basally to the epithelium was measured. We found that the neutrophil chemoattractants, formylmethionylleucylphenylalanine (FMLP), leukotriene B4 (LTB4), and interleukin-8 (IL-8), induced dose-responsive migration through the double monolayer-filter complex. The pattern of migration was similar to that observed through either a naked filter or single monolayer-filter complex. Maximal chemotaxis through the double monolayer-filter complex was observed by 3 hours. Thus, we have established an in vitro model system to examine the sequential migration of neutrophils through endothelium and the respiratory epithelium in a manner analogous to that occurring with an in vivo airway stimulus causing neutrophil-rich airway inflammatory responses.

Cell Line↗

A systems model of leadership: WICS.

This article reviews a systems model of leadership. According to the model, effective leadership is a synthesis of wisdom, creativity, and intelligence (WICS). It is in large part a decision about how to marshal and deploy these resources. One needs creativity to generate ideas, academic (analytical) intelligence to evaluate whether the ideas are good, practical intelligence to implement the ideas and persuade others of their worth, and wisdom to balance the interests of all stakeholders and to ensure that the actions of the leader seek a common good. The article relates the current model to other extant models of leadership.

Character↗

Applying a systems model of training to a patient with coronary artery disease.

PURPOSE: The aim of the present study was to apply a systems model of training for athletes to a patient with coronary artery disease (CAD) undergoing phase 3 rehabilitation. METHODS: A patient with CAD underwent 14 wk of training during which exercise was quantified using intensity and duration. Real exercise tolerance was assessed twice a week during this period using a constant-load test. The model exercise tolerance was obtained by convolving the quantified training to real exercise tolerance. The model parameters were obtained by fitting the real exercise tolerance to model exercise tolerance by the least square method. These parameters were then used to calculate the time needed after a training impulse to reach maximal tolerance (tg) and then to return to the pretraining level of tolerance (ti). RESULTS: The results showed that: 1) the fit between real and model exercise tolerances was significant (r = 0.73, P < 0.05), and 2) tg and ti were predicted 17 and 120 d posttraining, respectively. CONCLUSIONS: The application of a systems model of training for athletes to a patient with CAD was successful. We were able to predict the maximal exercise tolerance and the duration of increased tolerance subsequent to the training period.

Adaptation, Physiological↗

An immunochemical assay model system for the sensitive detection of pyruvate dehydrogenase complex (PDHc) and its decarboxylating subunit pyruvate dehydrogenase (E1).

An immunochemical enzyme immunoassay model system was developed and compared for maximum sensitivity with a radioimmunoassay method and the classic enzyme activity method for the detection of pyruvate dehydrogenase complex (PDHc) and its decarboxylating subunit, pyruvate dehydrogenase (E1), isolated from Escherichia coli. Cross-linked large molecular weight antibody-enzyme conjugate systems are compared with heterobifunctional singular antibody conjugates substituted with high levels of horseradish peroxidase. Both polyclonal and monoclonal antibodies generated to the Escherichia coli PDHc and E1 antigens were used to develop a double-antibody sandwich microtiter plate enzyme-linked immunosorbent assay. It is demonstrated that a double sandwich immunochemical assay system can be quantitative for PDHc, can detect PDHc in crude cell lysates and has levels of sensitivity of 2.0.10(-16) mol for the detection of PDHc. This assay model system provides specific antibody selection criteria and coupling methods needed to select specific antisera that cross-react with human PDHc. This rapid and sensitive immunochemical assay method clearly demonstrates that sensitive mass assay systems can be developed for the detection of PDHc. Different from Western blot, this methodology could be used to generate mass assays which could be applied to the rapid detection of mammalian antigens (employing the corresponding antibodies) implicated in a number of pyruvate dehydrogenase deficiencies associated with human disorders.

Antibodies, Monoclonal↗

Folding of beta-sheets in membranes: specificity and promiscuity in peptide model systems.

The interactions that drive the folding of beta-barrel membrane proteins have not been well studied because there have been few available model systems for membrane beta-sheets. In this work, we expand on a recently described model system to explore the contributions of interstrand hydrogen bonds, side-chain/side-chain interactions and side-chain/membrane interactions to beta-sheet formation in membranes. These experiments are based on the observation that the hydrophobic hexapeptide acetyl-Trp-Leu-Leu-Leu-Leu-Leu-OH (AcWLLLLL) folds, cooperatively and reversibly, into oligomeric, antiparallel beta-sheets in phosphatidylcholine membranes. To systematically characterize the important interactions that drive beta-sheet formation in membranes, we have used circular dichroism spectroscopy to determine the membrane secondary structure of each member of a complete host-guest family of related peptides of the form AcWLL-X-LL, where X is one of the natural amino acids. Peptides with hydrophobic X-residues of any size or character (X=Ala, Val, Ile, Leu, Cys, Met, Phe and Trp) form similar beta-sheets in membranes, while peptides with any polar X-residue or Gly or Pro at the X-position are random-coils, even when bound to membranes at high concentrations. The observed membrane sheet preferences correlate poorly with intrinsic sheet propensity scales measured in soluble proteins, but they correlate well with several membrane hydrophobicity scales. These results support the idea that the predominant interactions of the side-chains in membrane-bound beta-sheets are with the membrane lipids, and that backbone hydrogen bonding is the major driving force for the stabilization of beta-sheets in membranes.

Amino Acid Sequence↗

A model system for studying initial events in atherosclerosis.

A model system has been developed which employs the central artery of the rabbit ear, and allows for the study of 1) ultra-structural changes in the arterial endothelium and 2) formation and release of prostacyclin and thromboxane from the arteries in situ. Use of the model should be helpful in evaluating the initial events in atherosclerosis. Both prostacyclin and thromboxane (detected by radioimmunoassay) were formed by arteries in situ in response to infusion of sodium arachidonate.

Animals↗

A theory-based clinical nurse specialist practice exemplar using Neuman's systems model and nursing's taxonomies.

This article illustrates the process of theory-based advanced nursing practice by presenting an exemplar of clinical nurse specialist practice using Neuman's systems model and nursing's taxonomies. A brief explanation of Neuman's systems model is given, and the process of assessment, diagnosis, and planned outcomes/interventions is fully described. A clinical example illustrates the entire process.

Classification↗

Low-density lipoproteins modulate endothelial cells to secrete endothelin-1 in a polarized pattern: a study using a culture model system simulating arterial intima.

We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein alpha-catenin. Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 microgram/ml, ET-1 secretion was significantly increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that ET-1 may be involved in pathophysiological processes such as atherogenesis.

Biological Transport↗

A model system for the study of stimulus - enzyme secretion coupling in rat pancreatic acinar cells.

A superfusion technique was developed as a model system for the study of stimulus-secretion coupling in collagenase-dispersed rat pancreatic acinar cells. Cells (10(7)) were combined with a slurry of Biogel P-4 beads and the mixture was decanted into a plastic column (1.5 cm X 8.5 cm) and perfused with Krebs-Ringer. Amylase activity was determined in sequentially collected effusate fractions and used to estimate the secretory rate. Carbachol, carbachol plus dibutyryl cyclic AMP, cholecystokinin-pancreozymin, and the ionophore A-23187 all stimulated a rapid increase in the rate of secretion. Cell integrity was unaffected by these stimulants as evidenced microscopically and by the lack of lactate dehydrogenase activity in the effusates. Enzymes secreted in response to secretagogues were collected, concentrated, and isoelectrofocused on polyacrylamide gels. A film detection technique was developed to localize amylase activity. The model system has the following advantages: (1) secreted proteolytic products are removed from the vicinity of cells, thereby preventing direct cellular damage and hydrolysis of peptide agonist; (2) the need to add trypsin inhibitors is eliminated and only a minimal addition of albumin (0.001%) is required, thus allowing the separation and distortion-free analysis of secreted proteins; (3) the perfusion conditions can be changed rapidly without disturbing the cells. The model described is therefore well suited to the study of both molecular and kinetic events involved in the enzyme secretory phenomenon in exocrine pancreas.

Amylases↗

Model system for classical fluids out of equilibrium.

A model system for classical fluids out of equilibrium, referred to as a dissipative particles dynamics (DPD) solid, is studied by analytical and simulation methods. The time evolution of a DPD particle is described by a fluctuating heat equation. This DPD solid with transport based on collisional transfer (high-density mechanism) is complementary to the Lorentz gas with only kinetic transport (low-density mechanism). Combination of both models covers the qualitative behavior of transport properties of classical fluids over the full-density range. The heat diffusivity is calculated using a mean-field theory, leading to a linear-density dependence of this transport coefficient, which is exact at high densities. Subleading density corrections are obtained as well. At lower densities the model has a conductivity threshold below which heat conduction is absent. The observed threshold is explained in terms of percolation diffusion on a random proximity network. The geometrical structure of this network is the same as in continuum percolation of completely overlapping spheres, but the dynamics on this network differs from continuum percolation diffusion. Furthermore, the kinetic theory for DPD is extended to the generalized hydrodynamic regime, where the wave-number-dependent decay rates of the Fourier modes of the energy and temperature fields are calculated.

Journal Article↗