Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Generative models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources
PubMed2001

Generating data in models including direct and maternal dominance effects.

Algorithms are presented to simulate multiple generations of animal data by a model including direct additive genetic, maternal additive genetic, direct dominance, maternal dominance and permanent environmental effects. Dominance effects were computed as parental subclasses. Testing involved five single trait models that included direct contemporary group and direct additive effects, and different combinations of maternal, permanent environmental, and dominance effects. Simulated populations included 5 generations of animals and 20 contemporary groups per generation. The base population contained 200 sires and 600 dams. Variance components were estimated by Average-Information Restricted Maximum Likelihood (AIREML). No significant bias was observed. The simulation algorithms can be used in research involving dominance models, such as evaluation of mating systems exploiting special combining abilities of prospective parents.

Journal Article↗
PubMed2006

Predicting spike timing of neocortical pyramidal neurons by simple threshold models.

Neurons generate spikes reliably with millisecond precision if driven by a fluctuating current--is it then possible to predict the spike timing knowing the input? We determined parameters of an adapting threshold model using data recorded in vitro from 24 layer 5 pyramidal neurons from rat somatosensory cortex, stimulated intracellularly by a fluctuating current simulating synaptic bombardment in vivo. The model generates output spikes whenever the membrane voltage (a filtered version of the input current) reaches a dynamic threshold. We find that for input currents with large fluctuation amplitude, up to 75% of the spike times can be predicted with a precision of +/-2 ms. Some of the intrinsic neuronal unreliability can be accounted for by a noisy threshold mechanism. Our results suggest that, under random current injection into the soma, (i) neuronal behavior in the subthreshold regime can be well approximated by a simple linear filter; and (ii) most of the nonlinearities are captured by a simple threshold process.

Action Potentials↗
PubMed2002

Complex discrete dynamics from simple continuous population models.

Nonoverlapping generations have been classically modelled as difference equations in order to account for the discrete nature of reproductive events. However, other events such as resource consumption or mortality are continuous and take place in the within-generation time. We have realistically assumed a hybrid ODE bidimensional model of resources and consumers with discrete events for reproduction. Numerical and analytical approaches showed that the resulting dynamics resembles a Ricker map, including the doubling route to chaos. Stochastic simulations with a handling-time parameter for indirect competition of juveniles may affect the qualitative behaviour of the model.

Animals↗
PubMed2026

Construction and evaluation of an independently generated transgenic mouse model carrying mutated human HRAS genes for short-term carcinogenicity assessment.

The study aimed to construct and evaluate an independently generated transgenic mouse model applied to the short-term carcinogenicity assessment. Mutated human HRAS fragment containing an intron point-mutation was inserted into C57BL/6JGpt mice via bacterial artificial chromosome transgenic technology, eventually generating BALB/c;B6J-Tg(hHRAS)16/Gpt mice, abbreviated as HRAS mice. The inserted human HRAS fragment in HRAS mice was characterized, revealing five tandem copies at chromosome 19. Baseline profiles, including biochemical, hematological, immunophenotypic, survival, and carcinogenic data of HRAS mice, were collected. To evaluate the tumor susceptibility in HRAS mice, we applied N-Nitroso-N-methylurea (MNU) to HRAS mice in a short-term carcinogenicity assessment conducted according to Good Laboratory Practice. The genetic characteristics of HRAS mice include five tandem arrays of mutated human HRAS fragments located in genomic coordinate 7,755,606 on chromosome 19 and the duplication of a 9-kilobase genome sequence (genomic coordinate 7,755,606-7,746,509) located on chromosome 19. HRAS mice showed a relatively lower incidence and range of spontaneous tumor formation during long-term observation compared to CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) transgenic mice. The short-term carcinogenicity assessment showed a strong tumor response to MNU, with high incidences of lymphoma (≥ 90%) and stomach squamous cell papilloma (≥ 90%) in both male and female HRAS mice. The HRAS mice showed susceptibility to MNU and exhibited baseline characteristics distinct from those of Tg.rasH2 mice. The co-expression of HRAS and MKI67 at the cellular localization level was found in neoplasms of HRAS mice. These findings preliminarily evaluated the feasibility of HRAS mice applied to the short-term carcinogenicity assessment.

Animals↗
PubMed1985

Experimental test of two models for the generation of oblique saccades.

In this paper, we report a detailed study of the dynamic properties of horizontal, vertical and oblique saccades. These eye movements were measured with an improved version of the double-magnetic induction method in two rhesus monkeys. We found that onsets of orthogonal components of oblique saccades are so well synchronized in the monkey that a common initiation system seems likely. Saccade vectors obeyed a nonlinear peak-velocity/amplitude relationship in all directions. The peak-velocity/duration/amplitude relationship for components was not fixed, but depended on the relative size of the orthogonal component: for a component with a given size, its duration increased and its peak velocity decreased, as the saccade vector to which it contributed turned away from the component direction under consideration. This stretching effect, which reflects a nonlinearity in the system, was negligible for small saccade vectors but became very pronounced in large oblique saccades. These experimental data were confronted with quantitative predictions derived from two different models for the generation of saccades in two dimensions. It appears that a model which assumes the existence of synchronized, but otherwise independent, pulse generators for horizontal and vertical components must be rejected. An alternative model, featuring a nonlinear vectorial pulse generator followed by a decomposition stage which generates component velocity command signals from the vectorial eye velocity signal, provides good fit with the data. According to this common-source model, the two nonlinear phenomena observed, viz., the curvilinear peak-velocity/amplitude relationship of saccades in all directions and component stretching in large oblique saccades, are due to a single nonlinearity in the proposed vectorial pulse generator. A possible neural basis for the common-source model is discussed.

Animals↗
PubMed2003

The RAGENA dynamic model of radon generation, entry and accumulation indoors.

The complexity generated by the existence of a great number of parameters and processes affecting the generation of radon in the source, its transport in the source medium, its entry into a dwelling and its accumulation in the different rooms of a dwelling has led to the development of partial models and experimental studies that are focused on a given aspect. However, in order to model radon levels and dynamics in real houses, it is necessary to take into account all the parameters and processes affecting radon levels. This is the objective of the dynamic RAGENA model of radon generation, entry and accumulation indoors. The model has been adapted to a Mediterranean climate house under dynamic conditions, and the indoor radon and soil radon dynamics have been compared to experimental results. It has been found (i) that the model gives a soil radon dynamics similar to that obtained experimentally, (ii) a remarkable model-experiment agreement indoors and (iii) that the indoor radon dynamics is given by a permanent radon entry from building materials and a dynamic removal through ventilation, which is driven by indoor-outdoor temperature differences and wind speed.

Air Movements↗
PubMed1988

A new local feedback model of the saccadic burst generator.

1. To accommodate the finding that the superior colliculus is an important input to the brain stem pathways that generate saccades (the saccadic burst generator), a new model of the burst generator is proposed. Unlike the model of Robinson (61) from which it was derived, the model attempts to match a neural replica of change in eye position, which is the output of the burst generator, to a neural replica of change in target position, which is the output of the colliculus and the input to the model. 2. The elements of the model correspond to neurons known or thought to be associated with the actual primate saccadic burst generator and are mostly connected together in accord with the results of anatomical and physiological experiments. 3. The model was simulated on a digital computer to compare its behavior with that of the actual burst generator under normal and experimental conditions. Simulated peak burst frequency and saccade duration matched that obtained from monkey excitatory burst neurons and inhibitory burst neurons for saccades up to 15 degrees but did not match at larger sizes; stimulation of the omnipause neurons caused an interruption of the saccade, and the saccade resumed at the end of stimulation as in actual data; the model can generate the abnormally long-duration saccades seen under decreased alertness or various pathologies by changing the burst generator inputs and without having to change any properties of the neurons themselves or their connections; a simulated horizontal and vertical burst generator pair connected only through the omnipause neurons can generate realistic oblique saccades. 4. The implications of the model for higher-order control of the saccadic burst generator are discussed.

Efferent Pathways↗
PubMed2006

Modeling laser-generated guided waves in bonded plates by the finite element method.

The purpose of this research is to develop an effective model of the transient laser-generated guided waves in bonded plates by the finite element (FE) method. The FE parameters, such as the mesh density and the time step size, which are related to wave propagation, are optimized in order to set up a standard, and the correlation between these parameters is discussed. The waveforms in bonded plates with different bonded interface modeled by the spring model are obtained and then compared. The results show that the transient responses are sensitive to the stiffness coefficients characterizing the cohesive quality. Finally, these FE results are compared with analytical and experimental results. All these comparisons confirm the accuracy of the FE method for modeling laser-generated guided waves in bonded plates.

Journal Article↗
PubMed1988

Model to characterize strain generated potentials in bone.

A model has been developed to characterize the strain generated potentials (SGPs) in bone. The model relates the SGP signal to the rotation (reorientation) of the spontaneous dipoles of bone in response to mechanical deformation. The effects of bone structural conditions and the measuring circuitry on the recorded potential are both accounted for by the model.

Animals↗
PubMed2005

Using a generational time-step model to simulate dynamics of adaptation to transgenic corn and crop rotation by western corn rootworm (Coleoptera: Chrysomelidae).

We expanded a simulation model of the population dynamics and genetics of the western corn rootworm for a landscape of corn, soybean, and other crops to study the simultaneous development of resistance to both crop rotation and transgenic corn. Transgenic corn effective against corn rootworm was recently approved in 2003 and may be a very effective new technology for control of western corn rootworm in areas with or without the rotation-resistant variant. In simulations of areas with rotation-resistant populations, planting transgenic corn to only rotated cornfields was a robust strategy to prevent resistance to both traits. In these areas, planting transgenic corn to only continuous fields was not an effective strategy for preventing adaptation to crop rotation or transgenic corn. In areas without rotation-resistant phenotypes, gene expression of the allele for resistance to transgenic corn was the most important factor affecting the development of resistance to transgenic corn. If the allele for resistance to transgenic corn is recessive, resistance can be delayed longer than 15 yr, but if the resistant allele is dominant then resistance usually developed within 15 yr. In a sensitivity analysis, among the parameters investigated, initial allele frequency and density dependence were the two most important factors affecting the evolution of resistance. We compared the results of this simulation model with a more complicated model and results between the two were similar. This indicates that results from a simpler model with a generational time-step can compare favorably with a more complex model with a daily time-step.

Adaptation, Physiological↗
PubMed1994

PANSYM: a symbolic equation generator for mathematical modelling, analysis and control of metabolic and pharmacokinetic systems.

Software is presented for automatic generation of first-order ordinary differential equations (ODE) that arise from lumped parameter representations of metabolic and pharmacokinetic systems. The definition of system structures is accomplished by fractional transfer rates between state variables, together with input/output equations and initial conditions of state variables. General non-linear mathematical expressions can be assigned to all structure definition items. The software parses and interprets the system definitions and generates symbolically the mathematical expression of the model's set of ODE. In addition, symbolic derivatives of state equations are determined with respect to model parameters, state variables and external inputs. These derivatives represent the constituents of systems of sensitivity-differential and adjoint-differential equations that arise in identification and optimal control problems. Finally, output routines generate source code that, once compiled and linked to simulation programs, allows efficient numerical integration of the system of ODE. This software has been developed in PROLOG on Macintosh computers and has been extensively used with the programming environment MATLAB. Possible applications of this software include model building, sensitivity analysis, identification, optimal experiment design and numerical solution of optimal control problems.

Computer Simulation↗
PubMed1993

A multi-generational staff development model for registered nurses.

The paper focuses on a significant nursing initiative for staff development undertaken in South Australia. The initiative arose out of Health Commission funded consultancy which sought to develop a staff development model for registered nurses. The outcome of this consultancy was the development of a multi-generational staff development model, known as the DPS Staff Development Model. This model provides a framework through which staff development activities can be analysed, consolidated and extended. The paper outlines the DPS Staff Development Model, the context in which it was developed and its implications for nursing staff development programmes. The development of the model was premised on a number of assumptions. These included the need to ensure flexibility, longevity, offer a perspective of staff development that is realistic and practical, and facilitate in registered nurses a sense of ownership and personal responsibility with respect to their development. The model comprises six broad areas of focus: the Career Development Model for registered nurses in South Australia, the structure of the model, locations in which staff development occurs, elements which assist in maintaining skills and knowledge, elements which enhance growth and development and the processes and relationships necessary for the successful implementation of staff development programmes.

Career Mobility↗
PubMed2001

Uncertainty, variability and sensitivity analysis applied to the RAGENA model of radon generation, entry and accumulation indoors.

The application of a radon model is useful to understand the processes that drive the radon gas behaviour from its sources to its accumulation indoors. Since in a given inhabited house the detailed knowledge of the values of all the parameters that affect indoor radon levels is not available, the response of the model has to be explored in a reference site in which all the parameters are supposed to be known. We call this site the reference configuration. In this paper we report on the procedure followed to carry out uncertainty, sensitivity and variability analysis of the model response for a reference configuration that corresponds to a single family multi-zone house. We have obtained from the uncertainty analysis that, assuming a normal distribution of all the input parameters with a 10% relative standard deviation (R.S.D.), the model outputs present a R.S.D. in the range 17-22%. The sensitivity analysis reflects, in general, a good behaviour of the model, in the sense that its response describes a realistic behaviour of the system. The variability analysis has shown that the model is applicable to a wide range of situations, and that the most relevant parameters for the reference configuration are: the soil gas-permeability (obtained from the mean soil grain diameter); the ventilation rate of the rooms; the air-exchange rate between the basement and room 2; the soil-indoor pressure difference; the open area; and the concrete radium content.

Journal Article↗
PubMed2003

A toy model for the generation of homochirality during polymerization.

This article examines a toy model of polymerization which though artificial and unphysical has some interesting chiral features. Two key elements, enantiomeric cross inhibition and chiral feedback, are shown to lead to bifurcation, so that the end product can become homo-chiral. We find that the bifurcation is driven by the cross-inhibition but is not strongly dependant on its strength, which for perfect feedback fidelity mainly determines the time scale. We also find that bifurcation with a high degree of chiral polarization remains even when the fidelity of the chiral feedback is substantially less than unity. For small values of the feedback fidelity the polarization drops below unity and at a critical value falls sharply to zero in a 'phase transition'. The value at which this happens depends on the cross-inhibition in a complex way. By comparing the behaviour of polymers differing only in their final length, N, we find that the bifurcation process is enhanced as N increases. The symmetry breaking which we find is clearly a particular manifestation of general bifurcation theory. In addition it has the specific interest that, at least in our model, long homochiral polymers are possible even in the presence of substantial enantiomeric cross-inhibition.

Mathematics↗
PubMed1999

A mathematical model for the intracellular circadian rhythm generator.

A mathematical model for the intracellular circadian rhythm generator has been studied, based on a negative feedback of protein products on the transcription rate of their genes. The study is an attempt at examining minimal but biologically realistic requirements for a negative molecular feedback loop involving considerably faster reactions, to produce (slow) circadian oscillations. The model included mRNA and protein production and degradation, along with a negative feedback of the proteins upon mRNA production. The protein production process was described solely by its total duration and a nonlinear term, whereas also the feedback included nonlinear interactions among protein molecules. This system was found to produce robust oscillations in protein and mRNA levels over a wide range of parameter values. Oscillations were slow, with periods much longer than the time constants of any of the individual system parameters. Circadian oscillations were obtained for realistic values of the parameters. The system was readily entrainable to external periodic perturbations. Two distinct classes of phase response curves were found, viz. with or without a time domain within the circadian cycle in which external perturbations fail to induce a phase shift ("dead zone"). The delay and nonlinearity in the protein production and the cooperativity in the negative feedback (Hill coefficient) were for this model found to be necessary and sufficient to generate robust circadian oscillations. The similarities between model outcomes and empirical findings establish that circadian rhythmicity at the cellular level can plausibly emerge from interactions among molecular systems which are not in themselves rhythmic.

Biological Transport↗
PubMed2002

Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases.

Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.

Alkaline Phosphatase↗
PubMed2003

A quantitative model of the generation of N(epsilon)-(carboxymethyl)lysine in the Maillard reaction between collagen and glucose.

The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glycation endproducts). These have been linked to protein modifications found during aging, diabetes and various amyloidoses. To investigate the contribution of alternative routes to the formation of AGEs, we developed a mathematical model that describes the generation of CML [ N(epsilon)-(carboxymethyl)lysine] in the Maillard reaction between glucose and collagen. Parameter values were obtained by fitting published data from kinetic experiments of Amadori compound decomposition and glycoxidation of collagen by glucose. These raw parameter values were subsequently fine-tuned with adjustment factors that were deduced from dynamic experiments taking into account the glucose and phosphate buffer concentrations. The fine-tuned model was used to assess the relative contributions of the reaction between glyoxal and lysine, the Namiki pathway, and Amadori compound degradation to the generation of CML. The model suggests that the glyoxal route dominates, except at low phosphate and high glucose concentrations. The contribution of Amadori oxidation is generally the least significant at low glucose concentrations. Simulations of the inhibition of CML generation by aminoguanidine show that this compound effectively blocks the glyoxal route at low glucose concentrations (5 mM). Model results are compared with literature estimates of the contributions to CML generation by the three pathways. The significance of the dominance of the glyoxal route is discussed in the context of possible natural defensive mechanisms and pharmacological interventions with the goal of inhibiting the Maillard reaction in vivo.

Collagen↗
PubMed1998

Simulation and parameter estimation study of a simple neuronal model of rhythm generation: role of NMDA and non-NMDA receptors.

Simple neural network models of the Xenopus embryo swimming CPG, based on the one originally developed by Roberts and Tunstall (1990), were used to investigate the role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in conjunction with faster non-NMDA components of synaptic excitation, in rhythm generation. The voltage-dependent NMDA current "follows" the membrane potential, leading to a postinhibitory rebound that is more efficient than one without voltage dependency and allows neurons to fire more than one action potential per cycle. Furthermore, the model demonstrated limited rhythmic activity in the absence of synaptic inhibition, supporting the hypothesis that the NMDA channels provide a basic mechanism for rhythmicity. However, the rhythmic properties induced by the NMDA current were observed only when there was moderate activation of the non-NMDA synaptic channels, suggesting a modulatory role for this component. The simulations also show that the voltage dependency of the NMDA conductance, as well as the fast non-NMDA current, stabilizes the alternation pattern versus synchrony. To verify that these effects and their implications on the mechanism of swimming and transition to other types of activity take place in the real preparation, constraints on parameter values have to be specified. A method to estimate synaptic parameters was tested with generated data. It is shown that a global analysis, based on multiple iterations of the optimization process (Foster et al., 1993), gives a better understanding of the parameter subspace describing network activity than a standard fit with a sensitivity analysis for an individual solution.

Animals↗