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At least 721 records · Page 40Linked to original sources
PubMed1967

A nonlinear model for transient responses from light-adapted wolf spider eyes.

A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes.

Action Potentials↗
PubMed2006

Novel quantitative biosystem for modeling physiological fluid shear stress on cells.

The response of microbes to changes in the mechanical force of fluid shear has important implications for pathogens, which experience wide fluctuations in fluid shear in vivo during infection. However, the majority of studies have not cultured microbes under physiological fluid shear conditions within a range commonly encountered by microbes during host-pathogen interactions. Here we describe a convenient batch culture biosystem in which (i) the levels of fluid shear force can be varied within physiologically relevant ranges and quantified via mathematical models and (ii) large numbers of cells can be planktonically grown and harvested to examine the effect of fluid shear levels on microbial genomic and phenotypic responses. A quantitative model based on numerical simulations and in situ imaging analysis was developed to calculate the fluid shear imparted by spherical beads of different sizes on bacterial cell cultures grown in a rotating wall vessel (RWV) bioreactor. To demonstrate the application of this model, we subjected cultures of the bacterial pathogen Salmonella enterica serovar Typhimurium to three physiologically-relevant fluid shear ranges during growth in the RVW and demonstrated a progressive relationship between the applied fluid shear and the bacterial genetic and phenotypic responses. By applying this model to different cell types, including other bacterial pathogens, entire classes of genes and proteins involved in cellular interactions may be discovered that have not previously been identified during growth under conventional culture conditions, leading to new targets for vaccine and therapeutic development.

Bacterial Proteins↗
PubMed2003

Biophysical model of the radiation-induced bystander effect.

PURPOSE: To construct a quantitative model of the radiation-induced bystander effect based on diffusion-type spreading of bystander signal communication between the hit and non-hit cells. Cell inactivation and induced oncogenic transformation by broad- and microbeam irradiation systems are considered. MATERIALS AND METHODS: The biophysical model ByStander Diffusion Modelling (BSDM) postulates that the oncogenic bystander response observed in non-hit cells originates from specific signals received from inactivated cells. The bystander signals are assumed to be protein-like molecules spreading in the culture media by Brownian motion. The bystander signals are assumed to switch cells into a state of cell death (apoptotic/mitotic/necrosis) or induced oncogenic transformation modes. RESULTS: The bystander cell survival observed after treatment with the irradiated conditioned medium (ICM) using the broad-beam and the microbeam irradiation modalities were analysed and interpreted in the framework of the BSDM model. The model predictions for cell inactivation and induced oncogenic transformation frequencies agree well with observed data from micro and broad-beam experiments. In the case of irradiation with constant fraction of cells, transformation frequency for the bystander effect increases with increasing radiation dose. CONCLUSIONS: Bystander modelling based on diffusion of signals is in good agreement with experimental cell survival data and induced oncogenic transformation frequencies. The data confirm the protein-like nature of the bystander signal. Linear extrapolation of the cell response to low doses of radiation might underestimate carcinogenic risk, for example for domestic radon hazards, if the contribution from the bystander effect is neglected. The BSDM predicts that the bystander effect cannot be interpreted solely as a low-dose effect phenomenon. It is shown that the bystander component of radiation response can increase with dose and be observed at high doses as well as at low doses. The validity of this conclusion is supported by analysis of experimental results from high-linear energy transfer microbeam experiments.

Alpha Particles↗
PubMed1995

In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.

The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent phosphorylation. Because of this regulation, GSase has generally been considered to control the rate of glycogen synthesis. This hypothesis is examined in light of recent in vivo NMR experiments on rat and human muscle and is found to be quantitatively inconsistent with the data under conditions of glycogen synthesis. Our first experiments showed that muscle glycogen synthesis was slower in non-insulin-dependent diabetics compared to normals and that their defect was in the glucose transporter/hexokinase (GT/HK) part of the pathway. From these and other in vivo NMR results a quantitative model is proposed in which the GT/HK steps control the rate of glycogen synthesis in normal humans and rat muscle. The flux through GSase is regulated to match the proximal steps by "feed forward" to glucose 6-phosphate, which is a positive allosteric effector of all forms of GSase. Recent in vivo NMR experiments specifically designed to test the model are analyzed by metabolic control theory and it is shown quantitatively that the GT/HK step controls the rate of glycogen synthesis. Preliminary evidence favors the transporter step. Several conclusions are significant: (i) glucose transport/hexokinase controls the glycogen synthesis flux; (ii) the role of covalent phosphorylation of GSase is to adapt the activity of the enzyme to the flux and to control the metabolite levels not the flux; (iii) the quantitative data needed for inferring and testing the present model of flux control depended upon advances of in vivo NMR methods that accurately measured the concentration of glucose 6-phosphate and the rate of glycogen synthesis.

Allosteric Regulation↗
PubMed2003

The engineering of gene regulatory networks.

The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.

Animals↗
PubMed2005

The general surgery model: a more appealing and sustainable alternative for the care of trauma patients.

The contemporary model of trauma care where dedicated trauma/critical care surgeons exclusively manage trauma patients has become progressively unsustainable. Little objective data, however, is available documenting that a better model exists. From September 2002 through August 2003, the trauma model at a 735-bed level I trauma teaching hospital was changed from the contemporary model to a new one where selected general surgeons with Advanced Trauma Life Support (ATLS) certification covered in-house trauma and emergency surgery call on a rotational basis. As well, each pursued elective practices, admitting all inpatients (trauma, emergent, elective) to a single teaching service (formerly the trauma service). Critical care was managed by a separate group of intensivists. The purpose of this study was to objectively compare the two models. Quantitative, financial, and qualitative data were derived from August 2001 to January 2002 (trauma/critical care model) and compared to August 2003 to January 2004 (general surgery model). During the two periods (trauma/critical care vs general surgery), the mean Revised Trauma Score (7.1 vs 7.2; P = 0.029), the mean Injury Severity Score (ISS) (10.9 vs 10.8; P = 0.84), and the percentage of penetrating trauma (12.5% vs 13.2%; P = 0.79) were similar. Differences (trauma/critical care vs general surgery, % increase/P value) included average daily census (24 vs 54, 225%), cases/attending (262 vs 543, 207%), cases/resident (54 vs 262, 485%), charges/attending (353,811 dollars vs 471,725 dollars, 133%), collections/attending (106,143 dollars vs 165,103 dollars, 156%), number of trauma patients (643 vs 748, 116%), trauma mortality (7.3% vs 4.0%; P = 0.007), trauma mortality with ISS >15 (21.7% vs 12.0%; P = 0.035), trauma complications (33.1% vs 17%; P < 0.001), and ICU morbidity (66.8% vs 43.9%; P < .001). The new general surgery model produced superior financial results and better quantitative surgical experience while exceeding trauma and ICU quality outcomes compared to the former trauma/critical care model. These data objectively support a model such as ours--one that is financially sustainable and more professionally attractive.

Adolescent↗
PubMed2003

CoMFA and homology-based models of the glycine binding site of N-methyl-d-aspartate receptor.

Homology modeling was used to build 3D models of the N-methyl-d-aspartate (NMDA) receptor glycine binding site on the basis of an X-ray structure of the water-soluble AMPA-sensitive receptor. The docking of agonists and antagonists to these models was used to reveal binding modes of ligands and to explain known structure-activity relationships. Two types of quantitative models, 3D-QSAR/CoMFA and a regression model based on docking energies, were built for antagonists (derivatives of 4-hydroxy-2-quinolone, quinoxaline-2,3-dione, and related compounds). The CoMFA steric and electrostatic maps were superimposed on the homology-based model, and a close correspondence was marked. The derived computational models have permitted the evaluation of the structural features crucial for high glycine binding site affinity and are important for the design of new ligands.

Binding Sites↗
PubMed2004

Memory retrieval given two independent cues: cue selection or parallel access?

A basic but unresolved issue in the study of memory retrieval is whether multiple independent cues can be used concurrently (i.e., in parallel) to recall a single, common response. A number of empirical results, as well as potentially applicable theories, suggest that retrieval can proceed in parallel, though set forth a model that denies that possibility. In this paper, five quantitative models are developed to test broad candidate principles. In multiple experiments, subjects were trained to retrieve a vocal digit response for each member of a set of letter or color cues. In subsequent test and transfer phases, single cue trials were randomly mixed with dual cue trials on which the two cues always required the same response. For the first few repetitions of each new set of dual cue items, there was no evidence of parallel retrieval over any part of the RT distribution. After more repetitions, dual cue trials were performed faster than single cue trials, but only under conditions that were favorable to development of a "chunked" dual cue representation. These results indicate that associative independence is an important modulating variable that must be heeded in any general model of attention and memory retrieval. Further, the results are most consistent with a model that places the performance bottleneck prior to the retrieval stage of processing.

Choice Behavior↗
PubMed2006

Recognizing DNA.

It has become clear that there is no simple 'code' for protein-DNA recognition and that selecting an optimal binding sequence along the DNA double helix corresponds to more than simply forming a set of specific hydrogen bonds or steric interactions. However, it has been difficult to characterize the so-called indirect components of recognition. While DNA deformation certainly underlies indirect recognition, it is not easy to determine how local fine structure and deformability depend on base sequence or exactly what percentage of recognition should be attributed to such factors. Molecular modelling can help to develop these ideas into a quantitative model, provided the calculations can be carried out fast enough to enable a comprehensive survey of base-sequence effects. I present here some recent results from our group and their consequences for improving our understanding of protein-DNA binding, and their potential for predicting, and eventually modulating, protein-DNA binding.

Base Sequence↗
PubMed2001

Computer modelling of the Swedish two county trial of mammographic screening and trade offs between participation and screening interval.

OBJECTIVES: A computerised model of the Swedish two county trial of mammographic screening was built to explore the applicability of deterministic group modelling for health policy analysis and to examine trade offs between screening interval and population coverage on breast cancer mortality. METHODS: Powersim system dynamics modelling software running on a PC was used. Model inputs were published data on the populations and screening regimens used in the trial, a Swedish female population life table, incidence of breast cancer in Sweden, 95% confidence intervals (95% CIs) for mean sojourn time and screening sensitivity, and survival after diagnosis. RESULTS: The model's output--cumulative mortality from breast cancer--agreed closely with trial results. This was robust to uncertainties in key input variables. Furthermore, with hypothetical screening regimes that had a fixed total number of mammograms over a fixed period a positive association was found between more even distribution of mammograms among a population and reduction in breast cancer mortality. For example, screening 50% of a hypothetical population annually produced a 33% reduction in breast cancer mortality, whereas screening 100% of the population every 2 years produced a 48% reduction. CONCLUSIONS: Deterministic group simulation modelling can be used to build reliable, evidence based quantitative models for policy analysis. This opens health policy simulation modelling to epidemiological researchers and will assist them in identifying important information needs--such as breast cancer survival according to sojourn time (the time between cancer being detectable by screening and becoming symptomatic). Scenarios examining reductions in mortality for a given number of mammograms showed that the more equitable the distribution of screening mammograms, the greater the reduction in deaths from breast cancer.

Adult↗
PubMed1987

Developmental outcome in children exposed to chloride-deficient formula.

The developmental outcome of 2- and 4-year-old children who had been exposed as infants to chloride-deficient formula was studied. A negative dose-response relationship was demonstrated between use of the formula without additional nutritional supplementation and cognitive outcome as measured by the Bayley Scales of Infant Development (Pearson r = -.55, P = .01) at 2 years of age. A similar negative relationship was demonstrated between this exclusive use of the defective formula and perceptual (Pearson r = -.51, P less than .05), motor (Pearson r = -.52, P less than .05), and fine motor (Pearson r = -.75, P less than .002) ability as measured by the McCarthy Scales of Children's Abilities at 4 years of age. When other know predictors of developmental outcome were taken into account by means of multiple linear regression analyses, exclusive formula use emerged as an important predictor of the children's cognitive functioning at 2 years (model R2 = .59, P less than .005) and of quantitative (model R2 = .58, P less than .006), perceptual (model R2 = .63, P less than .009), and fine motor ability (model R2 = .74, P less than .003) at 4 years of age. These data raise concern about the developmental outcome of the children exposed to chloride-deficient formula.

Child, Preschool↗
PubMed1997

Antianxiety profile of ondansetron, a selective 5-HT3 antagonist, in a novel animal model.

The profile of action of ondansetron was assessed in a novel animal model of anxiety. The mirrored chamber is a nonpunishing quantitative model of anxiety which measures approach-conflict behavior. Ondansetron in all the doses tested (0.01, 0.1 and 1 mg/kg i.p.) showed significant anxiolytic action as compared to naive mice, but it was less potent as compared to a well-known anxiolytic, diazepam (1 mg/kg). These results suggest that ondansetron has anxiolytic efficacy in nonconflict paradigms of anxiety, a response not mediated by the conventional neurotransmitter receptors. GABA-benzodiazepine as flumazenil (4 mg/kg), a benzodiazepine receptor antagonist, failed to reverse the behavioral parameters evoked by ondansetron.

Animals↗
PubMed1998

Studies in a modified auxiliary abdominal rat heart transplantation model: preservation with colloid-free University of Wisconsin solution.

BACKGROUND: Current clinical heart preservation is still limited to 6 hours. A suitable heart transplantation model to rapidly screen the effectiveness of new solutions is essential. This study examines a new screening test-a modification of the conventional abdominal rat heart transplantation model that overcomes its serious limitation of lack of quantitative evaluation of function. METHODS: Rat hearts, with an externalized intraventricular balloon-tipped catheter, were transplanted immediately (controls) or flushed and stored in colloid-free University of Wisconsin solution in ice for 6, 9, or 12 hours before transplantation. One and 7 days later this catheter was connected to a pressure transducer and a calibrated syringe. Heart rate, maximum developed pressure, and maximum rate of left ventricular pressure rise were determined. Grafts were prepared for histologic study on day 7. RESULTS: All preserved hearts commenced beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart rate and chamber stiffness (deltaP/deltat) were similar in all groups. The 9- and 12-hour-preserved hearts had significantly (p < 0.05) diminished developed pressure and contractility. On day 7 contractility and developed pressure improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy and necrosis, with extensive cellular infiltrate in the 9- and 12-hour-preserved grafts; other grafts showed no damage. CONCLUSION: This quantitative model provides an ischemia-related gradation of function and greater discrimination than conventional methods. It has refuted previous studies suggesting effective preservation for 20 hours and demonstrated that functional testing is essential in evaluating preservation regimens.

Adenosine↗
PubMed2003

Mathematical model of corneal surface smoothing after laser refractive surgery.

PURPOSE: To construct a quantitative model of corneal surface smoothing after laser ablation for refractive correction. DESIGN: Experimental study, interventional case series, and meta-analysis of literature. METHODS: A theory of epithelial smoothing in response to corneal contour change is derived from differential equations that describe epithelial migration, growth, and loss. Computer simulations calculate the effects on postoperative epithelial thickness, topography, refraction, and spherical aberration. Model parameter is matched with laser in situ keratomileusis (LASIK) outcome in literature and in a retrospective study of primary spherical myopic (77 eyes) and hyperopic (19 eyes) corrections. Surgically induced refractive change was the main outcome measure. RESULTS: Simulated epithelial remodeling after myopic ablation produces central epithelial thickening, reduction in achieved correction, and induction of oblate spherical aberration. Simulation of hyperopic ablation shows peripheral epithelial thickening, a larger reduction in correction, and induction of prolate spherical aberration. Simulation using a minus cylinder laser ablation pattern shows decreased astigmatism correction and increased hyperopic shift. In the LASIK series, linear regression of achieved correction vs ablation setting in hyperopic and minus cylinder corrections shows slopes of 0.97, 0.71, and 0.74, respectively. These clinical results match model predictions when the smoothing constant is set at 0.32, 0.63, and 0.55 mm, respectively. CONCLUSIONS: Epithelial thickness modulations after ablation can be modeled mathematically to explain clinically observed regression and induction of aberration. The cornea appears to smooth over ablated features smaller than approximately 0.5 mm. The model provides an approach for designing ablation patterns that precompensate for the smoothing to improve final outcome.

Astigmatism↗
PubMed2004

Linear and nonlinear functions on modeling of aqueous solubility of organic compounds by two structure representation methods.

Several quantitative models for the prediction of aqueous solubility of organic compounds were developed based on a diverse dataset with 2084 compounds by using multi-linear regression analysis and backpropagation neural networks. The compounds were described by two different structure representation methods: (1) with 18 topological descriptors; and (2) with 32 radial distribution function codes representing the 3D structure of a molecule and eight additional descriptors. The dataset was divided into a training and a test set based on Kohonen's self-organizing neural network. Good prediction results were obtained for backpropagation neural network models: with 18 topological descriptors, for the 936 compounds in the test set, a correlation coefficient of 0.92, and a standard deviation of 0.62 were achieved; with 3D descriptors, for the 866 compounds in the test set, a correlation coefficient of 0.90, and a standard deviation of 0.73 were achieved. The models were also tested by using another dataset, and the relationship of the two datasets was examined by Kohonen's self-organizing neural network.

Molecular Structure↗
PubMedDate not supplied

[Mathematic modeling of the dynamics of the interacting population of the rhizosphere microorganisms].

A quantitative model is proposed to describe the population dynamics of associative nitrogen-fixing microorganisms in the plant rhizosphere as dependent on the rate of carbon substrate exudation by plant roots. By changing the values of the basic model parameters, the effect of various factors on the behavior of two competing populations of rhizospheric microorganism can be studied.

Bacteria↗
PubMedDate not supplied

QSAR modeling based on the bias/variance compromise: a harmonious and parsimonious approach.

Modeling quantitative structure-activity relationships (QSAR) is considered with an emphasis on prediction. An abundance of methods are available to develop such models. Using a harmonious approach that balances the bias and variance of predictions, the best calibration models are identified relative to the bias and variance criteria used. Criteria utilized to determine the adequacy of models are the root mean square error of calibration (RMSEC) and validation (RMSEV), respective R2 values, and the norm of the regression vector. QSAR data from the literature are used to demonstrate concepts. For these data sets and criteria used, it is suggested that models obtained by ridge regression (RR) are more harmonious and parsimonious than models obtained by partial least squares (PLS) and principal component regression (PCR) when the data is mean-centered. The most harmonious RR models have the best bias/variance tradeoff, reflected by the smallest RMSEC, RMSEV, and regression vector norms and the largest calibration and validation R2 values. The most parsimonious RR models have the smallest effective rank.

Least-Squares Analysis↗
PubMed2005

Modelling and interpretation of gas detection using remote laser pointers.

We have developed a quantitative model of the performance of laser pointer style gas leak detectors, which are based on remote detection of backscattered radiation. The model incorporates instrumental noise limits, the reflectivity of the target background surface and a mathematical description of gas leak dispersion in constant wind speed and turbulence conditions. We have investigated optimum instrument performance and limits of detection in simulated leak detection situations. We predict that the optimum height for instruments is at eye level or above, giving an operating range of 10 m or more for most background surfaces, in wind speeds of up to 2.5 ms(-1). For ground based leak sources, we find laser pointer measurements are dominated by gas concentrations over a short distance close to the target surface, making their readings intuitive to end users in most cases. This finding is consistent with the results of field trials.

Data Interpretation, Statistical↗