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At least 775 records · Page 43Linked to original sources
PubMed1985

Origin and fate of cholesterol in rat plasma lipoproteins in vivo. II. Modelling of cholesterol absorption and its release into plasma lipoproteins.

After a single ingestion of a diet containing 14C-cholesterol, cholesterol radioactivity in the stomachal and intestinal contents, in the different organs and in the very low density lipoproteins (VLDL) and chylomicrons was measured at different times during 2 days. Based on the results, a quantitative model of cholesterol absorption and of its release into the VLDL and chylomicrons has been elaborated. This model takes into account the different processes implied in the turnover of intestinal cholesterol and that of the entire organism. It constitutes a coherent whole (satisfactory simulations for the variables studied, suitable mass balances for each compartment and the absence of major contradictions with preexisting quantitative data). Once again the model demonstrates the important part played by the intestine in rat cholesterol system dynamics. It takes into account the existence of two related exogenous and endogenous cholesterol pools from which the cholesterol released by the intestine into the chylomicrons and VLDL originates. The results suggest the existence of an important esterified cholesterol uptake from other plasma lipoproteins by the chylomicrons.

Animals↗
PubMed2007

Structure of anionic phospholipid coatings on silica by dissipative quartz crystal microbalance.

The adsorption of anionic phospholipids on silica was investigated by the dissipative quartz crystal microbalance (QCM) technique. Liposomes composed of 1 mM 80:20 mol % of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphatidylcholine (POPC)/phosphatidic acid, POPC/phosphatidylglycerol, or POPC/phosphatidylserine in N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) buffer at pH 7.4 (with or without 3 mM of CaCl2) were examined. We have previously demonstrated that similar phospholipid coatings can be used in capillary electrochromatography as a stationary phase for the separation of analytes. In this work, we focus on the formation of the coatings and on the type of lipid structure formed on silica. The QCM investigation comprised qualitative results based on changes in frequency and resistance, and quantitative modeling of the obtained results. The latter was performed using the dissipative QCM, which measures the quartz crystal impedance, combined with equivalent circuit analysis. A previously developed coating and cleaning procedure for phospholipid-coated fused silica capillaries was adopted in this study, and the same silica-coated crystal was used throughout the QCM study. We will demonstrate in this work that the type of lipid structure formed on silica, that is, a rather rigid supported lipid bilayer or a viscoelastic supported vesicle layer (SVL), is highly dependent on the lipid and solvent composition. We also show for the first time that the modeling of the dissipative QCM data can be used to extract a more quantitative picture of an adsorbed SVL, because, so far, published studies have merely used the QCM data in a qualitative sense.

Adsorption↗
PubMed1995

A model of frequency tuning in the basilar papilla of the Tokay gecko, Gekko gecko.

This paper uses the quantitative details of the anatomy of the auditory papilla in the Tokay gecko Gekko gecko (as described in the companion paper) to make a quantitative model predicting the tonotopic organization of two of the three papillar areas. Assuming that hair-cell bundle stiffness is similar to that of other species, a model of resonance frequencies for the apical areas of the papilla was constructed, taking into account factors such as the number of hair cells per resonant unit, their bundle dimensions, the volume of the tectorial mass, etc. The model predicts that the apical pre- and postaxial areas, although anatomically adjacent, respond to different frequency ranges, a phenomenon not yet reported from any vertebrate. The model predicts that together, these areas respond best to frequencies between 1.1 and 5.3 kHz, close to the range found physiologically [Eatock et al. (1981) J. Comp. Physiol. 142, 203-218] (0.8 to 5 kHz) for the high-frequency range for this species. Only physiological experiments tracing responses to specific papillar nerve fibres can confirm or refute these interesting predictions of the model. The model also indicates that, compared to free-standing hair-cell bundles, the semi-isolated tectorial structures called sallets not only lower the range of characteristic frequencies but also increase the frequency selectivity of the attached hair cells.

Acoustic Stimulation↗
PubMed1998

Investigation of the Hammerstein hypothesis in the modeling of electrically stimulated muscle.

To restore functional use of paralyzed muscles by automatically controlled stimulation, an accurate quantitative model of the stimulated muscles is desirable. The most commonly used model for isometric muscle has had a Hammerstein structure, in which a linear dynamic block is preceded by a static nonlinear function. To investigate the accuracy of the Hammerstein model, the responses to a pseudo-random binary sequence (PRBS) excitation of normal human plantarflexors, stimulated with surface electrodes, were used to identify a Hammerstein model but also four local models which describe the responses to small signals at different mean levels of activation. Comparison of the local models with the linearized Hammerstein model showed that the Hammerstein model concealed a fivefold variation in the speed of response. Also, the small-signal gain of the Hammerstein model was in error by factors up to three. We conclude that, despite the past widespread use of the Hammerstein model, it is not an accurate representation of isometric muscle. On the other hand, local models, which are more accurate predictors, can be identified from the responses to short PRBS sequences. The utility of local models for controller design is discussed.

Adult↗
PubMed1995

Middle ear mechanics of type IV and type V tympanoplasty: I. Model analysis and predictions.

An analysis of type IV and type V tympanoplasty procedures was performed using a quantitative model of the acoustic and mechanical properties of the stapes, cochlea, round window shield, and cavum minor air space. Realistic values for the impedance of these structures were determined from anatomic and functional measurements in normal ears. These model values lead to predicted type IV hearing results that match well with the best surgical results over a broad frequency range (125-4000 Hz). A parametric study of alterations in the model impedances reveals that a good hearing result depends on a mobile stapes, proper aeration of the cavum minor air space, and a sufficiently stiff graft shield. Intersubject variations in the cochlear impedance also can have a significant effect on the postsurgical hearing response.

Acoustic Impedance Tests↗
PubMed1987

A theoretical model for peripheral tissue heat transfer using the bioheat equation of Weinbaum and Jiji.

In this paper the new bioheat equation derived in Weinbaum and Jiji is applied to the three layer conceptual model of microvascular surface tissue organization proposed in. A simplified one-dimensional quantitative model of peripheral tissue energy exchange is then developed for application in limb and whole body heat transfer studies. A representative vasculature is constructed for each layer and the enhancement in the local tensor conductivity of the tissue as a function of vascular geometry and blood flow is examined. Numerical solutions for the boundary value problem coupling the three layers are presented and these results used to study the thermal behavior of peripheral tissue for a wide variety of physiological conditions from supine resting state to maximum exercise.

Animals↗
PubMed1979

[Quantitative exercise scintigraphy of the myocardium with 201Tl--methods and normal values (author's transl)].

Quantitative myocardial scintigraphy was performed in 20 normal individuals after maximum exercise and after two hours of rest. A mobile Anger camera with converging collimator and a Data-General computer with a 128 x 128 matrix were used. Quantitative analysis of data was performed on the basis of a 14-halfsegment model. Quantitative normal values after exercise and after redistribution of activity during rest are presented.

Adult↗
PubMed2005

Transcriptional regulation by the numbers: models.

The expression of genes is regularly characterized with respect to how much, how fast, when and where. Such quantitative data demands quantitative models. Thermodynamic models are based on the assumption that the level of gene expression is proportional to the equilibrium probability that RNA polymerase (RNAP) is bound to the promoter of interest. Statistical mechanics provides a framework for computing these probabilities. Within this framework, interactions of activators, repressors, helper molecules and RNAP are described by a single function, the "regulation factor". This analysis culminates in an expression for the probability of RNA polymerase binding at the promoter of interest as a function of the number of regulatory proteins in the cell.

Gene Expression Regulation↗
PubMed1997

Modeling auditory processing of amplitude modulation. I. Detection and masking with narrow-band carriers.

This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615-3622 (1996)]. The new element in the present model is a modulation filterbank, which exhibits two domains with different scaling. In the range 0-10 Hz, the modulation filters have a constant bandwidth of 5 Hz. Between 10 Hz and 1000 Hz a logarithmic scaling with a constant Q value of 2 was assumed. To preclude spectral effects in temporal processing, measurements and corresponding simulations were performed with stochastic narrow-band noise carriers at a high center frequency (5 kHz). For conditions in which the modulation rate (fmod) was smaller than half the bandwidth of the carrier (delta f), the model accounts for the low-pass characteristic in the threshold functions [e.g., Viemeister, J. Acoust. Soc. Am. 66, 1364-1380 (1979)]. In conditions with fmod > delta f/2, the model can account for the high-pass characteristic in the threshold function. In a further experiment, a classical masking paradigm for investigating frequency selectivity was adopted and translated to the modulation-frequency domain. Masked thresholds for sinusoidal test modulation in the presence of a competing modulation masker were measured and simulated as a function of the test modulation rate. In all cases, the model describes the experimental data to within a few dB. It is proposed that the typical low-pass characteristic of the temporal modulation transfer function observed with wide-band noise carriers is not due to "sluggishness" in the auditory system, but can instead be understood in terms of the interaction between modulation filters and the inherent fluctuations in the carrier.

Acoustics↗
PubMed2004

Discrete event modeling of CD4+ memory T cell generation.

Studies of memory T cell differentiation are hampered by a lack of quantitative models to test hypotheses in silico before in vivo experimentation. We created a stochastic computer model of CD4+ memory T cell generation that can simulate and track 10(1)-10(8) individual lymphocytes over time. Parameters for the model were derived from experimental data using naive human CD4+ T cells stimulated in vitro. Using discrete event computer simulation, we identified two key variables that heavily influence effector burst size and the persistent memory pool size: the cell cycle dependent probability of apoptosis, and the postactivation mitosis at which memory T cells emerge. Multiple simulations were performed and varying critical parameters permitted estimates of how sensitive the model was to changes in all of the model parameters. We then compared two hypotheses of CD4+ memory T cell generation: maturation from activated naive to effector to memory cells (model I) vs direct progression from activated naive to memory cells (model II). We find that direct progression of naive to memory T cells does not explain published measurements of the memory cell mass unless postactivation expansion of the memory cell cohort occurs. We conclude that current models suggesting direct progression of activated naive cells to the persistent memory phenotype (model II) do not account for the experimentally measured size of the postactivation CD4+, Ag-specific, memory T cell cohort.

Apoptosis↗
PubMed2000

Genetic support for the evolutionary theory of reproductive transactions in social wasps.

Recent evolutionary models of reproductive partitioning within animal societies (known as 'optimal skew', 'concessions' or 'transactional' models) predict that a dominant individual will often yield some fraction of the group's reproduction to a subordinate as an incentive to stay in the group and help rear the dominant's offspring. These models quantitatively predict how the magnitude of the subordinate's 'staying incentive' will vary with the genetic relatedness between dominant and subordinate, the overall expected group output and the subordinate's expected output if it breeds solitarily. We report that these predictions accord remarkably well with the observed reproductive partitioning between conesting dominant and subordinate queens in the social paper wasp Polistes fuscatus. In particular, the theory correctly predicts that (i) the dominant's share of reproduction, i.e. the skew, increases as the colony cycle progresses and (ii) the skew is positively associated both with the colony's productivity and with the relatedness between dominant and subordinate. Moreover, aggression between foundresses positively correlated with the skew, as predicted by transactional but not alternative tug-of-war models of societal evolution. Thus, our results provide the strongest (quantitative support yet for a unifying model of social evolution.

Animals↗
PubMed1992

Narrow-band sound localization related to external ear acoustics.

Human subjects localized brief 1/6-oct bandpassed noise bursts that were centered at 6, 8, 10, and 12 kHz. All testing was done under binaural conditions. The horizontal component of subjects' responses was accurate, comparable to that for broadband localization, but the vertical and front/back components exhibited systematic errors. Specifically, responses tended to cluster within restricted ranges that were specific for each center frequency. The directional transfer functions of the subjects' external ears were measured for 360 horizontal and vertical locations. The spectra of the sounds that were present in the subjects' ear canals, the "proximal stimulus" spectra, were computed by combining the spectra of the narrow-band sound sources with the directional transfer functions for particular stimulus locations. Subjects consistently localized sounds to regions within which the associated directional transfer function correlated most closely with the proximal stimulus spectrum. A quantitative model was constructed that successfully predicted subjects' responses based on interaural level difference and spectral cues. A test of the model, using techniques adapted from signal detection theory, indicated that subjects tend to use interaural level difference and spectral shape cues independently, limited only by a slight spatial correlation of the two cues. A testing procedure is described that provides a quantitative comparison of various predictive models of sound localization.

Acoustics↗
PubMed1990

Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes.

1. Because induction of associative long-term potentiation (LTP) in the dentate gyrus is thought to depend on Ca2+ influx through channels controlled by N-methyl-D-aspartate (NMDA) receptors, quantitative modeling was performed of synaptically mediated Ca2+ influx as a function of synaptic coactivation. The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP. 2. Ca2+ influx through NMDA-receptor channels was modeled at a synapse on a dendritic spine of a reconstructed hippocampal dentate granule cell when 1-115 synapses on spines at different dendritic locations were activated eight times at frequencies of 10-800 Hz. The resulting change in [Ca2+] in the spine head was estimated from the Ca2+ influx with the use of a model of a dendritic spine that included Ca2+ buffers, pumps, and diffusion. 3. To use a compelling model of synaptic activation, we developed quantitative descriptions of the NMDA and non-NMDA receptor-mediated conductances consistent with available experimental data. The experimental data reported for NMDA and non-NMDA receptor-channel properties and data from other non-LTP experiments that separated the NMDA and non-NMDA receptor-mediated components of synaptic events proved to be limiting for particular synaptic variables. Relative to the non-NMDA glutamate-type receptors, 1) the unbinding of transmitter from NMDA receptors had to be slow, 2) the transition from the bound NMDA receptor-transmitter complex to the open channel state had to be even slower, and 3) the average number of NMDA-receptor channels at a single activated synapse on a single spine head that were open and conducting at a given moment in time had to be very small (usually less than 1). 4. With the use of these quantitative synaptic conductance descriptions. Ca2+ influx through NMDA-receptor channels at a synapse was computed for a variety of conditions. For a constant number of pulses, Ca2+ influx was calculated as a function of input frequency and the number of coactivated synapses. When few synapses were coactivated, Ca2+ influx was small, even for high-frequency activation. However, with larger numbers of coactivated synapses, there was a steep increase in Ca2+ influx with increasing input frequency because of the voltage-dependent nature of the NMDA receptor-mediated conductance. Nevertheless, total Ca2+ influx was never increased more than fourfold by increasing input frequency or the number of coactivated synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2006

Numerical model for DNA loading in microdevices: stacking and autogating effects.

Many electrophoresis-based DNA sequencing and genotyping microdevices rely on field-driven effects to load and preconcentrate the sample. A quantitative model is developed for a broad class of electrophoresis-based microfabricated sample injectors. Quantitative predictions of DNA preconcentration are compared with experimental data and are shown to qualitatively reproduce the detailed time-evolving sample distribution in the injector. The model provides practical guidance on device and protocol design, in order to optimize this critical aspect of microfluidic devices.

DNA↗
PubMed1995

A biophysically based dermatopharmacokinetic compartment model for quantifying percutaneous penetration and absorption of topically applied agents. I. Theory.

We present a general comprehensive mathematical model to stimulate and predict percutaneous absorption and subsequent disposition of chemicals in vivo that is chiefly based on biophysical parameters estimated or measured with in vitro and ex vivo perfused skin preparations. Current physicochemical principles of drug diffusion and partitioning across the skin barrier, solute and solvent concentration dynamics, the influence of solute and solvent on the stratum corneum barrier, and dynamic vascular perfusion effects are integrated in this model. Such a comprehensive approach is necessary to achieve optimal biological relevance in a quantitative model of percutaneous absorption, particularly when a chemical is applied as a binary (solute and solvent) or more complex formulation or chemical mixture. The proposed model should have applications in (a) designing drugs and permeation enhancers for passive or active (e.g., electrically assisted) transdermal drug delivery, (b) assessing the systemic exposure of topical drugs used in dermatology, and (c) integration into other mathematical models being developed to assess the risk after topical exposure to mixtures of environmental pollutants. We also have included experimental data to provide a preliminary illustration of the performance of the model.

Administration, Topical↗
PubMed1994

Human monitoring behavior in a multiple-instrument setting: independent sampling, sequential sampling or arrangement-dependent sampling.

This study aims at contributing to the understanding of human monitoring behavior in multiple instrument settings. Eye movements were recorded so as to test whether sampling behavior is more consistent with traditional normative models (Senders, 1983) or with alternative approaches that emphasize heuristics and strategies rather than quantitative modelling. A core assumption of normative modelling concerns the premise that sampling one instrument is independent of the other instruments in an array. This assumption was tested in three experiments. In a first experiment, subjects monitored four independent continuous stochasts so as to detect critical situations. In a fast condition, two instruments were paired with two relatively fast changing instruments. In a slow condition, the two instruments were paired with two relatively slow changing instruments. Sampling one instrument appeared to be independent of the rates of change of the other instruments in the array. Furthermore, sampling was a function of the information generation rates of the individual instruments. This is in accordance with normative modelling. However, the spatial arrangement of the instruments on the display as well as the presence of a central fixation point strongly affected sampling behavior. In a second experiment, subjects monitored six instruments. In addition, there was no central fixation point. The results indicated again that a perceptual heuristic was used in that the spatial arrangement of the instruments on the display affected sampling behavior. Horizontal transitions occurred more often than would be predicted on the basis of independent sampling. Diagonal transitions occurred less often than would be predicted. Finally, a third experiment tested whether this preference for sampling by means of horizontal eye movements at the expense of diagonal eye movements would, under conflict situations, affect the mean sampling interval of specific instruments. In a four-instrument monitoring task, sampling intervals of two slow and two fast independent instruments were compared in different spatial arrangements. Sampling intervals strongly depended on the arrangement of the instruments on the display. Human monitoring seems to be biased by a tendency towards sampling by means of horizontal transitions at the cost of diagonal transitions. Under certain conditions, this tendency might make sampling intervals unrelated to the information generation rates of the individual instruments.

Adolescent↗
PubMed2002

A novel dynamic model of hematopoietic stem cell organization based on the concept of within-tissue plasticity.

OBJECTIVE: At present, no dynamic quantitative models of stem cell organization are available that fulfill all criteria of the prevalent functional definition of hematopoietic stem cells and, at the same time, provide a consistent explanation of cell kinetic and functional stem cell heterogeneity, reversibility of cellular properties, self-organized regeneration after damage, fluctuating activity and competition of stem cell clones, and microenvironment dependency of stem cell quality. To solve this problem, we propose a new, comprehensive model concept. MATERIALS AND METHODS: A single cell-based stochastic model is described. It makes the novel concept of within-tissue plasticity operational. Within a range of potential options, individual cells may reversibly change their actual set of properties depending on the influence of the local growth environment. Stochastic switching between the growth environments introduces fluctuations that eventually generate heterogeneity. Extensive model simulations are compared with experimental data. RESULTS: Although stemness is not an explicit cellular model property, the system behavior is consistent with the functional definition of stem cells and explains a large set of experimental observations on stem cell function in vivo and in vitro on the level of cell populations and individual cells. Classic results such as the colony-forming unit spleen assay, as well as recent experimental observations on stem cell kinetics, individual clone tracking, and fluctuating clonal contribution, are discussed. CONCLUSIONS: This concept introduces a fundamentally new perspective on stem cell organization treating stemness not as an explicit cellular property but as the result of a dynamic process of self-organization. The model needs to be extended to incorporate lineage specification and tissue plasticity.

Animals↗
PubMed2000

Model selection for a medical diagnostic decision support system: a breast cancer detection case.

There are a number of different quantitative models that can be used in a medical diagnostic decision support system (MDSS) including parametric methods (linear discriminant analysis or logistic regression), non-parametric models (K nearest neighbor, or kernel density) and several neural network models. The complexity of the diagnostic task is thought to be one of the prime determinants of model selection. Unfortunately, there is no theory available to guide model selection. Practitioners are left to either choose a favorite model or to test a small subset using cross validation methods. This paper illustrates the use of a self-organizing map (SOM) to guide model selection for a breast cancer MDSS. The topological ordering properties of the SOM are used to define targets for an ideal accuracy level similar to a Bayes optimal level. These targets can then be used in model selection, variable reduction, parameter determination, and to assess the adequacy of the clinical measurement system. These ideas are applied to a successful model selection for a real-world breast cancer database. Diagnostic accuracy results are reported for individual models, for ensembles of neural networks, and for stacked predictors.

Algorithms↗