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PubMed1984

[A new model for the quantitative analysis of left ventricular regional function].

A computer-assisted model for quantitative analysis of left ventricular segmental wall motion is presented. In contrast to standard rectangular and radial chord methods, no coordinate and reference system is used. Normal wall motion of 5 ventricular segments in the RAO projection was evaluated in 20 patients with normal ventriculograms. Segmental wall motion abnormalities after myocardial infarction were then analyzed by the computer-assisted method in 60 patients and the results compared with the visual assessment of an experienced cardiologist as standard reference. 96% of all segments with normal motion, 95% of all hypokinetic segments and 100% of all dyskinetic segments were correctly identified by computer analysis. Akinesia, however, was detected only in 25% of all cases and misinterpreted chiefly as hypokinesia. Further refinement of the software should improve detection of akinesia and classification of hypokinesia.

Adult↗
PubMed1999

A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients.

The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine from the blood after an oral load of the amino acid, and dietary tolerance of phenylalanine all agree well with data from normal as well as from phenylketonuric patients and obligate heterozygotes. These calculated values may help in the decision about the degree of restriction of phenylalanine intake that is necessary to achieve a satisfactory clinical outcome in classical patients and in those with milder forms of the disease.

Diet↗
PubMed2006

Speeded old-new recognition of multidimensional perceptual stimuli: modeling performance at the individual-participant and individual-item levels.

Observers made speeded old-new recognition judgments of color stimuli embedded in a multidimensional similarity space. The paradigm used multiple lists but with the underlying similarity structures repeated across lists, to allow for quantitative modeling of the data at the individual-participant and individual-item levels. Correct-rejection response times (RTs) got systematically faster as the similarity of foils to the old study items decreased. There were also intricate patterns of speed-accuracy trade-offs that varied across individual items and participants. An exemplar-based random-walk model provided a good overall quantitative account of the recognition choice probabilities, mean correct RTs, and mean error RTs associated with the individual items on the basis of their positions in multidimensional similarity space. However, the model failed to predict the very long RTs associated with correct rejections of a prototype foil.

Adult↗
PubMed2002

Efficiency, accuracy, and stability issues in discrete-time simulations of single reed wind instruments.

A quantitative study of discrete-time simulations for a single reed physical model is presented. It is shown that when the continuous-time model is discretized, a delay-free path is generated in the computation. A general solution is proposed to this problem, that amounts to operating a geometrical transformation on the equations. The transformed equations are discretized using four different numerical methods. Stability properties of each method are assessed through analysis in the frequency domain. By comparing the discrete and continuous frequency responses, it is studied how the physical parameters are mapped by each method into the discrete-time domain. Time-domain simulations are developed by coupling the four digital reeds to an idealized bore model, Quantitative analysis of the simulations shows that the discrete-time systems produced by the four methods have significantly different behaviors, even when high sampling rates are used. As a result of this study, a general scheme for accurate and efficient time-domain simulations of the single reed model is proposed.

Journal Article↗
PubMed2000

The survival of slow reproducers.

Multicellularity, and the attendant segregation of the germ line, entails the loss of reproductive capacity by the soma: in Volvox carteri, less than 1 cell in 100 contributes to the next generation. However, compensatory advantages are unlikely to be very large (Koufopanou & Bell, 1993. Proc. R. Soc. Lond. (B) 254,107-113). Somewhat similarly, sex implies the generation of males, hence a dramatic reproductive slowdown (Barton & Charlesworth, 1998. Science281, 1986-1990); yet, a compensating (two-fold) advantage of sex has not been found. Here, I try to evaluate the actual cost of maintaining slow reproductive cycles, namely cycles that necessitate the production of "dead end" units such as somatic cells or males. In a quantitative model for the competition of individuals with different, heritable reproductive rates, this cost turns out to be unexpectedly small, and may even sometimes become irrelevant. The bases for this are made fairly clear: thus, when all enjoy high fecundity (e.g. a long reproductive life) the handicap of a slower reproduction vanishes; alternatively, a slight separation of ecological niches may be sufficient for survival of slower but otherwise unchanged reproducers; and finally, inherent to slow reproduction is a low rate of destabilizing genetic change. These facts are largely independent of the formal model details, and are supported by direct computer simulations. They give a quantitative basis for analysing the evolution and prevalence of slow life cycles. The implications of these findings for the evolution of multicellularity are briefly discussed.

Animals↗
PubMed2002

Inhibition of butyrylcholinesterase by phenothiazine derivatives.

The inhibition of horse serum butyrylcholinesterase (EC 3.1.1.8) by 10 phenothiazine or thioxanthene derivatives was studied with a purified enzyme. Most compounds were mixed inhibitors, but for some of them an apparent competitive inhibition was observed. The competitive inhibition constants (K) were in the range 0.05 to 5 microM. The structures of the inhibitors were modeled by geometry optimization with the AM1 semi-empirical molecular orbital method and octanol/water partition coefficients were estimated with the CLOGP software. Quantitative structure-activity relationships identified lipophilicity, molecular volume, and electronic energies as the main determinants of inhibition. This quantitative model suggested hydrophobic and charge-transfer interactions of the phenothiazine ring with a tryptophan residue at the "anionic" site of the enzyme, and a hydrophobic interaction of the lateral chain with nonpolar amino acids.

Animals↗
PubMed2004

Model-based fault diagnosis in continuous dynamic systems.

Traditional fault detection and isolation methods are based on quantitative models which are sometimes difficult and costly to obtain. In this paper, qualitative bond graph (QBG) reasoning is adopted as the modeling scheme to generate a set of qualitative equations. The QBG method provides a unified approach for modeling engineering systems, in particular, mechatronic systems. An input-output qualitative equation derived from QBG formalism performs continuous system monitoring. Fault diagnosis is activated when a discrepancy is observed between measured abnormal behavior and predicted system behavior. Genetic algorithms (GA's) are then used to search for possible faulty components among a system of qualitative equations. In order to demonstrate the performance of the proposed algorithm, we have tested it on a laboratory scale servo-tank liquid process rig. Results of the proposed model-based fault detection and diagnosis algorithm for the process rig are presented and discussed.

Journal Article↗
PubMed1980

Further test of a model for loudness coding after adaptation.

The present study attempted to fit Weiler and Hood's (1977) quantitative model for loudness coding to an additional set of simultaneous dichotic loudness balance (SDLB) adaptation data. The error of prediction for test values 10 dB above adapting intensity for 12 normal-hearing listeners was -2.7 to -4.7 dB, an average of -3.5 dB. Since the error of prediction was so nearly constant (S.D. = +/- 737 dB), it seemed reasonable to attribute it do differences in procedural technique, and to conclude that the loudness model does account for coding in the adaptation results.

Dichotic Listening Tests↗
PubMed1998

Topics in dose-response modeling.

Great uncertainty exists in conducting dose-response assessment for microbial pathogens. The data to support quantitative modeling of dose-response relationships are meager. Our philosophy in developing methodology to conduct microbial risk assessments has been to rely on data analysis and formal inferencing from the available data in constructing dose-response and exposure models. The probability of illness is a complex function of factors associated with the disease triangle: the host, the pathogen, and the environment including the food vehicle and indigenous microbial competitors. The epidemiological triangle and interactions between the components of the triangle are used to illustrate key issues in dose-response modeling that impact the estimation of risk and attendant uncertainty. Distinguishing between uncertainty (what is unknown) and variability (heterogeneity) is crucial in risk assessment. Uncertainty includes components that are associated with (i) parameter estimation for a given assumed model, and (ii) the unknown "true" model form among many plausible alternatives such as the exponential, Beta-Poisson, probit, logistic, and Gompertz. Uncertainty may be grossly understated if plausible alternative models are not tested in the analysis. Examples are presented of the impact of variability and uncertainty on species, strain, or serotype of microbial pathogens; variability in human response to administered doses of pathogens; and effects of threshold and nonthreshold models. Some discussion of the usefulness and limitations of epidemiological data is presented. Criteria for development of surrogate dose-response models are proposed for pathogens for which human data are lacking. Alternative dose-response models which consider biological plausibility are presented for predicting the probability of illness.

Adult↗
PubMed2003

An integrated model of epidermal growth factor receptor trafficking and signal transduction.

Endocytic trafficking of many types of receptors can have profound effects on subsequent signaling events. Quantitative models of these processes, however, have usually considered trafficking and signaling independently. Here, we present an integrated model of both the trafficking and signaling pathway of the epidermal growth factor receptor (EGFR) using a probability weighted-dynamic Monte Carlo simulation. Our model consists of hundreds of distinct endocytic compartments and approximately 13,000 reactions/events that occur over a broad spatio-temporal range. By using a realistic multicompartment model, we can investigate the distribution of the receptors among cellular compartments as well as their potential signal transduction characteristics. Our new model also allows the incorporation of physiochemical aspects of ligand-receptor interactions, such as pH-dependent binding in different endosomal compartments. To determine the utility of this approach, we simulated the differential activation of the EGFR by two of its ligands, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). Our simulations predict that when EGFR is activated with TGF-alpha, receptor activation is biased toward the cell surface whereas EGF produces a signaling bias toward the endosomal compartment. Experiments confirm these predictions from our model and simulations. Our model accurately predicts the kinetics and extent of receptor downregulation induced by either EGF or TGF-alpha. Our results suggest that receptor trafficking controls the compartmental bias of signal transduction, rather than simply modulating signal magnitude. Our model provides a new approach to evaluating the complex effect of receptor trafficking on signal transduction. Importantly, the stochastic and compartmental nature of the simulation allows these models to be directly tested by high-throughput approaches, such as quantitative image analysis.

Cell Line↗
PubMed1999

Stereoscopic occlusion junctions.

Portions of surfaces in a binocularly viewed scene may be 'half occluded', that is, visible in only one eye. The human visual system uses zones of half occlusion to help segment the visual scene and infer figure-ground relationships at object boundaries. We developed a quantitative model of the depth-discontinuity cue provided by half occlusion. Half occlusions are revealed by two-dimensional interocular displacements of binocularly viewed occlusion junctions, such as T junctions. We derived a formula relating this two-dimensional displacement, or 'pseudodisparity', to binocular disparities and orientations of occluding and occluded contours. In human psychophysical experiments, perceived depth and contour orientation quantitatively depended on pseudodisparity, as predicted by our model, implying that the visual system senses quantitative variations in interocular junction position to reconstruct occlusion geometry.

Depth Perception↗
PubMed1997

The human obesity gene map: the 1996 update.

An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.

Animals↗
PubMed2005

A comparison of three modelling approaches for quantitative risk assessment using the case study of Salmonella spp. in poultry meat.

A comprehensive review of both the scientific literature and industry practices was undertaken to identify and quantify all sources of contamination throughout the entire poultry meat production chain by Salmonella spp. This information was used to develop a quantitative risk assessment (QRA) model for Salmonella in the production chain from the breeder farm to the chilled carcass. This was subsequently used as the basis on which to compare the merits of three approaches to QRA modelling in such systems. The original model used a Bayesian Network (BN). The second method was a Markov chain Monte Carlo (MCMC) approach, a numerical Bayesian technique which retained a similar network structure but allowed further development, such as the separation of variability and uncertainty. The third method was a more detailed simulation model. The BN responds immediately to changes, such as entering evidence, because it does not use simulation and can propagate information from any point in the network to all others by Bayesian inference. However, it requires all the variables to be discrete, which introduces errors if continuous variables have to be discretized. These errors can accumulate. The MCMC approach does not require discrete variables while retaining some of the properties of the BN model, such as the ability to draw inferences from evidence. Finally, the simulation offers greater flexibility, such as consideration of the individual carcass, but may be more complex to implement as a result and sacrifices the ability to propagate evidence.

Animals↗
PubMed2001

Determination of vibration-related spinal loads by numerical simulation.

OBJECTIVE: Dynamic spinal loads due to human whole body vibrations are extremely difficult to determine experimentally. However, they can be predicted by numerical simulation. This paper presents an approach for the prediction of dynamic spinal loads caused by whole body vibrations, as well as some basic considerations concerning the process of numerical simulation. BACKGROUND: Long-term whole body vibrations have been found to cause health risks for the lumbar spine. As an increasing percentage of the population is exposed to whole body vibrations at work, more and more people have to face the risk of whole body vibrations-related injury. Knowledge about the actual loads in the lumbar spine is essential when spinal loads are to be compared with spinal strength in order to assess the possible health risks caused by whole body vibrations. METHODS: Since an extrapolation of results to unknown data such as spinal loads can only be done using anatomical models of the human body, a simplified finite-element model is presented which is adaptable to body height, body mass, and posture of any specific subject under investigation. The model has been built by reducing a very detailed, nonlinear finite-element model of seated man in its complexity (number of degrees of freedom). Furthermore, the simplified model has been linearised to avoid nonlinear solution procedures. RESULTS: The model has been verified for vertical and horizontal excitation at the seat. Model results have been compared to measurements on subjects. Individual exposure-effect relationships may be predicted by this model, due to the adaptability to a specific subject. Additionally, a new phenomenological method of eliminating the influence of local skin-accelerometer vibrations on vibration measurements on the skin surface is discussed. This method may provide data about bone acceleration that can be used in the process of model verification. CONCLUSIONS: Integral loading measures, such as spinal loads, may be predicted with simplified finite-element models. Quantitative judgements of these loads may be performed for individual conditions. Linearised models may be used for limited ranges of excitation intensities. Energy dissipation should be modeled by discrete dashpot elements instead of proportional damping. RELEVANCE: In order to assess the risk of an injury to the lumbar spine due to whole body vibrations, spinal loads have to be compared with spinal strength. This paper presents the development and verification of a simplified finite-element model of the human body which is based on human anatomy and therefore well-suited to occupational/clinical biomechanics for the prediction of spinal loads.

Acceleration↗
PubMed1999

Hierarchical models of object recognition in cortex.

Visual processing in cortex is classically modeled as a hierarchy of increasingly sophisticated representations, naturally extending the model of simple to complex cells of Hubel and Wiesel. Surprisingly, little quantitative modeling has been done to explore the biological feasibility of this class of models to explain aspects of higher-level visual processing such as object recognition. We describe a new hierarchical model consistent with physiological data from inferotemporal cortex that accounts for this complex visual task and makes testable predictions. The model is based on a MAX-like operation applied to inputs to certain cortical neurons that may have a general role in cortical function.

Animals↗
PubMed2026

Coarse-grained resource allocation modeling for decoding and rewiring microbial metabolism.

Microbial metabolism is a complex, emergent system driven by the coordinated interplay of intricate and dynamic molecular processes. To elucidate cellular behavior and enable biotechnological applications, quantitative models that address the inherent complexity of metabolism have been developed from a resource allocation perspective. Here, we synthesize recent advances in coarse-grained resource allocation frameworks and their applications in understanding microbial physiology and guiding gene circuit design. These frameworks reveal global regulatory constraints and predict cellular adaptation to nutrient and environmental changes. In addition, they enable the quantification of metabolic costs, the dissection of circuit-host interactions, and the development of strategies for burden mitigation. Collectively, these modeling frameworks provide a powerful platform for uncovering quantitative principles of microbial growth and engineering robust synthetic biological systems.

coarse-grained modeling↗
PubMed2000

Application of a continuous regression model of restenosis to saphenous vein grafts after successful percutaneous transluminal coronary angioplasty or directional coronary atherectomy.

OBJECTIVES: To evaluate a quantitative model of restenosis in patients with vein graft disease undergoing percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). BACKGROUND: A quantitative relationship between acute gain and late loss has been developed to describe the late changes in lumen dimension after native vessel coronary intervention. This same relationship may also be seen after treatment of saphenous vein graft disease. METHODS: Patients with native coronary artery stenoses (CAVEAT-I) or saphenous vein graft lesions (CAVEAT-II) were randomized to either DCA or PTCA, and data from these trials were analyzed retrospectively. Angiographic results of the target lesions were reviewed, and each lesion was assessed for vessel caliber and reference diameter, absolute minimal lumen diameter, percent diameter stenosis, percent stenosis of the cross-sectional area, acute gain and late loss. Linear regression models were used to determine late loss and to detect differences in angiographic outcomes. RESULTS: Vein grafts had significantly larger reference vessel diameters than native coronary arteries; they also had significantly more acute gain and more late loss. Directional coronary atherectomy was associated with a larger acute gain in both studies. Patients undergoing DCA also experienced greater late loss although the effect was statistically significant only in the CAVEAT-I study. After adjusting for the acute gain, the treatment effect on late loss became nonsignificant in both studies. CONCLUSIONS: In patients undergoing DCA or PTCA of saphenous vein graft narrowings, the relationship between late loss and acute gain is also demonstrated, similar to the device-independent relationships seen in native coronary lesions. In CAVEAT-II, larger degrees of acute gain were also associated with higher degrees of late lumen loss.

Aged↗
PubMed1989

Modeling the regulation of the bithorax complex in Drosophila melanogaster: the phenotypic effects of Ubx, abd-A and Abd-B heterozygotic larvae, and a homozygous Ubx- abd A hybrid gene.

As an intermediate step in the development of a defined quantitative model of pattern formation during Drosophila segmentation, we present here a model capable of predicting the experimentally determined levels of gene activity and their phenotypic consequences. In its present form, the model includes only four genes: the three genes of the bithorax complex (Ubx, abd-A and Abd-B) and Antennapedia. It is shown that the model is quite robust, predicting many properties in the behavior of these genes. A previously undescribed property is that all of these genes should phenotypically exhibit some kind of haploinsufficiency when present in only a single dose in the genetic background of the animal. This is shown both by the model and by a new method of quantitatively analyzing the differences in the more obvious cuticular features of the larvae, i.e., the patterns in the ventral denticle belts. The model is also capable of dealing with a complicated genetic situation, a hybrid gene of Ubx and abd-A produced by the C1 deletion.

Animals↗