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At least 973 records · Page 54Linked to original sources

PubMed1994

Time series models based on generalized linear models: some further results.

This paper considers the problem of extending the classical moving average models to time series with conditional distributions given by generalized linear models. These models have the advantage of easy construction and estimation. Statistical modelling techniques are also proposed. Some simulation results and an illustrative example are reported to illustrate the methodology. The models will have potential applications in longitudinal data analysis.

Biometry↗

PubMedDate not supplied

Linking a PBPK model for chloroform with measured breath concentrations in showers: implications for dermal exposure models.

Four issues are addressed in this paper. First, both dermal uptake models and a revised PBPK model are developed and combined into a form appropriate for simulating chloroform breath levels in individuals exposed in showers by inhalation and dermal routes and by the inhalation route only. Second, experimentally measured and previously reported ratios of chloroform concentrations in air and breath to tap-water concentration are used to evaluate the model predictions. Particular attention is given to the implied dermal uptake as measured by these experiments and to whether this is consistent with the recommended value for skin uptake of chloroform that is calculated using EPA guidance. This analysis indicates that the ratio of chloroform dermally absorbed in the shower relative to tap-water concentration is between 0.25 and 0.66 mg per mg/L and that the effective permeability of the skin during a 10-min. shower exposure is between 0.16 and 0.42 cm/hr. Third, the model is used to assess the relationship of dermal and inhalation exposure to metabolized dose in the liver. It is found that, for dermal and inhalation exposures in the shower and under conditions of linear metabolism, the ratio of metabolized dose to water concentration is on the order of 0.41 mg per mg/L. Fourth, the model is used to determine the chloroform concentration at which dermal and inhalation exposures to chloroform would begin to result in nonlinear metabolism. This concentration is found to be in the range of 60 to 100 mg/L.

Breath Tests↗

PubMed1993

[Modeling of the bactericidal effect of spiramycin. Choice of a pharmacodynamic model].

The modelling of in vitro growth curves of Staphylococcus aureus ATCC 6538P at different pHs, of spiramycin killing curves and of the dose-effect relationship was performed. The growth curve was characterised by a Volterra-Kostitzin differential model, the main parameters of which were the bacterial growth rate constant of 0.95 +/- 0.13 h-1 and a lag-time of 0.74 +/- 0.36 h. The Zhi model used for bactericidal kinetics showed the same bacterial killing rate constant from a minimum concentration characteristic of "time-dependent" antibiotics. This differential model incorporated with pharmacokinetic models could lead to a rationale for proper dosage regimens.

Culture Media↗

PubMed1998

[Development of the intratracheal infection model of experimental murine mycobacteriosis: comparison with the intravenous infection model].

An intratracheal infection method of experimental murine mycobacteriosis was developed for an in vivo study of antimycobacterial agents. Two models of intratracheal (IT) and intravenous (i.v.) routes of infection with mycobacteria of the same inoculum dose were compared in terms of the mean survival days of mice or bacterial loads in organs during the course of infection. IT model with either of M. bovis Ravenel, M. tuberculosis Kurono, M. tuberculosis H37Rv or M. intracellular N-256 exhibited a much more distinct lung-specific infection than i.v. model with the same dose of respective mycobacterial strains. The intratracheal infection method presented in this report does not require any special equipment and is a much safer method for the researcher than airborne infection. In this model, following slight anesthetizing of mice, bacillary suspension was injected quantitatively into lungs through the mouth and trachea by using a specially modified needle set with a short fine polyethylene tube. This IT model may be useful not only for the in vivo assessment of anti-mycobacterial agents but also for the comparison of virulence among various mycobacterial strains.

Animals↗

PubMed1998

[Preclinical evaluation of anticancer drugs: a model remaining a model!].

Two criteria are firstly used in the selection of new anticancer agents:--originality of the mechanism of action and significant experimental antitumor activity in an in vivo animal model. Murine tumors grafted in syngenic mice and human tumor xenografts implanted in nude mice are old models which continue to be widely used. Such models are useful but have the tendency to select many false positives (compounds active in mice but inactive in patients). This discrepancy can be explained by differences due to biological materials and also to the methodologies used in laboratories and clinic. Such models will certainly continue to play a major role in the future but they will have to be used in conditions more relevant for clinical extrapolation. Transgenic mice developing in situ tumors constitute new innovative models for in vivo evaluation of anticancer agents. Finally, a putative new class of antitumor agents emerges with the signal transduction modulators: such compounds have antitumor and toxicological properties very different from those of conventional chemotherapeutic agents. If the first representatives prove to be useful in clinic, rules for toxicology, preclinical and clinical evaluation will have to be changed.

Animals↗

PubMed2026

Zebrafish as a versatile model in biomedical research, from disease modeling to regenerative medicine: a review.

Zebrafish are an effective animal model widely utilized in biomedical research. They are known for their rapid reproduction and substantial genetic similarity to humans. Their transparent embryos directly enable the visualization of developmental processes and disease progression. This makes zebrafish invaluable for studying a broad range of human diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Compared with other vertebrate models, zebrafish offer several advantages, including ease of genome editing, cost-effective maintenance, and suitability for high-throughput drug screening. Recent advancements have expanded the use of zebrafish in disease modeling and regenerative medicine, providing deeper insights into the genetic and cellular mechanisms underlying human pathologies. Zebrafish provide a robust platform for evaluating the safety, efficacy, and regenerative potential of both natural and synthetic biomaterials, including hydroxyapatite, bioactive glass nanoparticles, and bioceramics. This capability facilitates the creation of artificial tissues that closely resemble native structures. Additionally, integrating artificial intelligence technologies has improved automated data analysis and phenotyping in zebrafish studies, enhancing both accuracy and throughput. This review highlights current applications of zebrafish in disease modeling, drug discovery, regenerative medicine, and biomaterial assessment, emphasizing their evolving role as a versatile preclinical platform supported by advanced genetic and computational tools.

Animals↗

PubMed2006

Modeling crash outcome probabilities at rural intersections: application of hierarchical binomial logistic models.

It is important to examine the nature of the relationships between roadway, environmental, and traffic factors and motor vehicle crashes, with the aim to improve the collective understanding of causal mechanisms involved in crashes and to better predict their occurrence. Statistical models of motor vehicle crashes are one path of inquiry often used to gain these initial insights. Recent efforts have focused on the estimation of negative binomial and Poisson regression models (and related deviants) due to their relatively good fit to crash data. Of course analysts constantly seek methods that offer greater consistency with the data generating mechanism (motor vehicle crashes in this case), provide better statistical fit, and provide insight into data structure that was previously unavailable. One such opportunity exists with some types of crash data, in particular crash-level data that are collected across roadway segments, intersections, etc. It is argued in this paper that some crash data possess hierarchical structure that has not routinely been exploited. This paper describes the application of binomial multilevel models of crash types using 548 motor vehicle crashes collected from 91 two-lane rural intersections in the state of Georgia. Crash prediction models are estimated for angle, rear-end, and sideswipe (both same direction and opposite direction) crashes. The contributions of the paper are the realization of hierarchical data structure and the application of a theoretically appealing and suitable analysis approach for multilevel data, yielding insights into intersection-related crashes by crash type.

Accidents, Traffic↗

PubMed2006

Dynamic modeling of chemical fate and transport in multimedia environments at watershed scale-I: theoretical considerations and model implementation.

A geo-referenced environmental fate model was developed for analyzing unsteady-state dispersion and distribution of chemicals in multimedia environmental systems. Chemical transport processes were formulated in seven environmental compartments of air, canopy, surface soil, root-zone soil, vadose-zone soil, surface water, and sediment. The model assumed that the compartments were completely mixed and chemical equilibrium was established instantaneously between the sub-compartments within each compartment. A fugacity approach was utilized to formulate the mechanisms of diffusion, advection, physical interfacial transport, and transformation reactions. The governing equations of chemical mass balances in the environmental compartments were solved simultaneously to reflect the interactions between the compartments. A geographic information system (GIS) database and geospatial analysis were integrated into the chemical transport simulation to provide spatially explicit estimations of model parameters at watershed scale. Temporal variations of the environmental properties and source emissions were also considered in the parameter estimations. The outputs of the model included time-dependent chemical concentrations in each compartment and its sub-compartments, and inter-media mass fluxes between adjacent compartments at daily time steps.

Computer Simulation↗

PubMed2002

Geometric and statistical properties of the mean-field hydrophobic-polar model, the large-small model, and real protein sequences.

Lattice models, for their coarse-grained nature, are best suited for the study of the "designability problem," the phenomenon in which most of the about 16 000 proteins of known structure have their native conformations concentrated in a relatively small number of about 500 topological classes of conformations. Here it is shown that on a lattice the most highly designable simulated protein structures are those that have the largest number of surface-core switchbacks. A combination of physical, mathematical, and biological reasons that causes the phenomenon is given. By comparing the most foldable model peptides with protein sequences in the Protein Data Bank, it is shown that whereas different models may yield similar designabilities, predicted foldable peptides will simulate natural proteins only when the model incorporates the correct physics and biology, in this case if the main folding force arises from the differing hydrophobicity of the residues, but does not originate, say, from the steric hindrance effect caused by the differing sizes of the residues.

Amino Acid Sequence↗

PubMed1982

Modeling urban decline: a multilevel economic-demographic model for the Dortmund region.

"Selected results of a multilevel dynamic simulation model of the economic and demographic development of the urban region of Dortmund [Federal Republic of Germany] are presented. In particular, the capability of the model to capture both urban growth and urban decline processes is illustrated. The mechanisms that control spatial growth, decline, or redistribution of activities in the model are first outlined, and a demonstration of how the model reproduces the general pattern of past spatial development follows. Finally, results of simulations covering a wide range of potential overall economic and demographic development in the region are discussed." (summary in FRE, ITA, JPN, )

Demography↗

PubMed2001

Modeling and remodeling in a developing artiodactyl calcaneus: a model for evaluating Frost's Mechanostat hypothesis and its corollaries.

The artiodactyl (mule deer) calcaneus was examined for structural and material features that represent regional differences in cortical bone modeling and remodeling activities. Cortical thickness, resorption and formation surfaces, mineral content (percent ash), and microstructure were quantified between and within skeletally immature and mature bones. These features were examined to see if they are consistent with predictions of Frost's Mechanostat paradigm of mechanically induced bone adaptation in a maturing "tension/compression" bone (Frost, 1990a,b, Anat Rec 226:403-413, 414-422). Consistent with Frost's hypothesis that surface modeling activities differ between the "compression" (cranial) and "tension" (caudal) cortices, the elliptical cross-section of the calcaneal diaphysis becomes more elongated in the direction of bending as a result of preferential (> 95%) increase in thickness of the compression cortex. Regional differences in mineral content and population densities of new remodeling events (NREs = resorption spaces plus newly forming secondary osteons) support Frost's hypothesis that intracortical remodeling activities differ between the opposing cortices: 1.) in immature and mature bones, the compression cortex had attained a level of mineralization averaging 8.9 and 6.8% greater (P < 0.001), respectively, than that of the tension cortex, and 2.) there are on average 350 to 400% greater population densities of NREs in the tension cortices of both age groups (P < 0.0003). No significant differences in cortical thickness, mineral content, porosity, or NREs were found between medial and lateral cortices of the skeletally mature bones, suggesting that no modeling or remodeling differences exist along a theoretical neutral axis. However, in mature bones these cortices differed considerably in secondary osteon cross-sectional area and population density. Consistent with Frost's hypothesis, remodeling in the compression cortex produced bone with microstructural organization that differs from the tension cortex. However, the increased remodeling activity of the tension cortex does not appear to be related to a postulated low-strain environment. Although most findings are consistent with predictions of Frost's Mechanostat paradigm, there are several notable inconsistencies. Additional studies are needed to elucidate the nature of the mechanisms that govern the modeling and remodeling activities that produce and maintain normal bone. It is proposed that the artiodactyl calcaneus will provide a useful experimental model for these studies.

Animals↗

PubMed1986

Six models of heterotopic rat liver transplantation: introducing a reverse circulation model.

Six different models of heterotopic partial (30%) liver transplant techniques were enumerated step-by-step with the special introduction of a so-called nonregenerative model in which the afferent blood supply to the liver graft was the host's systemic blood while the reverse circulation model was to receive the host's portal blood via the suprahepatic vena cava. The reverse circulation model needs further investigation as to its applicability, but the nonregenerative partial liver transplant model certainly deserves attention because of its importance for possible infusion studies using various hepatic nutrients, hormones, and enzymes.

Animals↗

PubMed1994

Modeling perceptual learning with multiple interacting elements: a neural network model describing early visual perceptual learning.

We introduce a neural network model of an early visual cortical area, in order to understand better results of psychophysical experiments concerning perceptual learning during odd element (pop-out) detection tasks (Ahissar and Hochstein, 1993, 1994a). The model describes a network, composed of orientation selective units, arranged in a hypercolumn structure, with receptive field properties modeled from real monkey neurons. Odd element detection is a final pattern of activity with one (or a few) salient units active. The learning algorithm used was the Associative reward-penalty (Ar-p) algorithm of reinforcement learning (Barto and Anandan, 1985), following physiological data indicating the role of supervision in cortical plasticity. Simulations show that network performance improves dramatically as the weights of inter-unit connections reach a balance between lateral iso-orientation inhibition, and facilitation from neighboring neurons with different preferred orientations. The network is able to learn even from chance performance, and in the presence of a large amount of noise in the response function. As additional tests of the model, we conducted experiments with human subjects in order to examine learning strategy and test model predictions.

Humans↗

PubMed2006

Pathway of oxidative folding of a 3-disulfide alpha-lactalbumin may resemble either BPTI model or hirudin model.

Pathways of oxidative folding of disulfide proteins display a high degree of diversity and vary among two extreme models. The BPTI model is defined by limited species of folding intermediates adopting mainly native disulfide bonds. The hirudin model is characterized by highly heterogeneous folding intermediates containing mostly non-native disulfide bonds. alphaLA-IIIA is a 3-disulfide variant of alpha-lactalbumin (alphaLA) with a 3-D conformation essentially identical to that of intact alphaLA. alphaLA-IIIA contains 3 native disulfide bonds of alphaLA, two of them are located at the calcium binding beta-subdomain (Cys61-Cys77 and Cys73-Cys91) and the third bridge is located within the alpha-helical domain of the molecule (Cys28-Cys111). We investigate here the pathway of oxidative folding of fully reduced alphaLA-IIIA with and without stabilization of its beta-subdomain by calcium binding. In the absence of calcium, the folding pathway of alphaLA-IIIA was shown to resemble that of hirudin model. Upon stabilization of beta-sheet domain by calcium binding, the folding pathway of alphaLA-IIIA exhibits a striking similarity to that of BPTI model. Three predominant folding intermediates of alphaLA-IIIA containing exclusively native disulfide bonds were isolated and structurally characterized. Our results further demonstrate that stabilization of subdomains in a protein may dictate its folding pathway and represent a major cause for the existing diversity in the folding pathways of the disulfide-containing proteins.

Amino Acid Sequence↗

PubMed2006

The significance of endogeneity problems in crash models: an examination of left-turn lanes in intersection crash models.

Crash prediction models are used for a variety of purposes including forecasting the expected future performance of various transportation system segments with similar traits. The influence of intersection features on safety have been examined extensively because intersections experience a relatively large proportion of motor vehicle conflicts and crashes compared to other segments in the transportation system. The effects of left-turn lanes at intersections in particular have seen mixed results in the literature. Some researchers have found that left-turn lanes are beneficial to safety while others have reported detrimental effects on safety. This inconsistency is not surprising given that the installation of left-turn lanes is often endogenous, that is, influenced by crash counts and/or traffic volumes. Endogeneity creates problems in econometric and statistical models and is likely to account for the inconsistencies reported in the literature. This paper reports on a limited-information maximum likelihood (LIML) estimation approach to compensate for endogeneity between left-turn lane presence and angle crashes. The effects of endogeneity are mitigated using the approach, revealing the unbiased effect of left-turn lanes on crash frequency for a dataset of Georgia intersections. The research shows that without accounting for endogeneity, left-turn lanes 'appear' to contribute to crashes; however, when endogeneity is accounted for in the model, left-turn lanes reduce angle crash frequencies as expected by engineering judgment. Other endogenous variables may lurk in crash models as well, suggesting that the method may be used to correct simultaneity problems with other variables and in other transportation modeling contexts.

Accidents, Traffic↗

PubMed2001

Use of satellite remote sensing and geographic information systems to model the distribution and abundance of snail intermediate hosts in Africa: a preliminary model for Biomphalaria pfeifferi in Ethiopia.

Geographic information system (GIS) risk models for the snail-borne diseases caused by Schistosoma spp. and Fasciola spp. have recently been developed based on climate and satellite-retrieved data on temperature and vegetation coverage. By using these models, it was possible to describe a relationship between vegetation index (Normalized Differences Vegetation Index (NDVI)), land surface temperature (T(max)) and disease prevalence, but little reference was made to the distribution of the corresponding intermediate host snail. Presence of the intermediate host snail is a key factor determining distribution of the disease in sub-Saharan Africa and a good snail distribution mode would probably mirror the endemic area of schistosomiasis. In the present analysis, it was shown that snail distribution data corresponds with schistosomiasis prevalence data in relation to a forecast model based on NDVI and T(max) data derived from the Advanced Very High Resolution Radiometer (AVHRR) onboard the National Oceanic and Atmospheric Administration satellite series. The 'best fit' model included NDVI values from 125 to 145 and a T(max) data range of 10-32 degrees C. This model included 92.3, 90.4 and 94.6% of the positive snail sample sites in GIS query overlay areas extracted from annual, dry season and wet season composite maps, respectively. For other sites in Africa, other NDVI and T(max) ranges may be more appropriate, depending on the species of snail present, a topic that will be examined in further studies.

Africa↗

PubMed2001

Population pharmacokinetic-pharmacodynamic modelling of S 15535, a 5-HT(1A) receptor agonist, using a behavioural model in rats.

The pharmacokinetic-pharmacodynamic relationship of S 15535 (1-(benzodioxan-5-yl) 4-(indan-2-yl)piperazine) and its active 5-hydroxy metabolite S 32784 (1-(benzodioxan-5-yl) 4-(5-hydroxyindan-2-yl)piperazine), and buspirone as a reference, were studied in male Wistar rats using a behavioural model of anxiety by determining the reduction in the number of fear-induced ultrasonic vocalisations. S 15535 and buspirone were administered p.o. and i.v. S 32784, present in man but not in rat, was administered i.v. The pharmacokinetics and pharmacokinetic-pharmacodynamic relationships were described using non-linear mixed effects modelling. The no-drug effect was constant and all compounds were active in the model, reducing ultrasonic vocalisations immediately after administration. The sigmoid E(max) model was used to describe the pharmacokinetic-pharmacodynamic relationships, with E(max) values of a 90% decrease in baseline ultrasonic vocalisations. Corrected for plasma protein binding, all compounds showed similar potency. The study shows that ultrasonic vocalisations can be considered a suitable endpoint for the anxiolytic effect when used in conjunction with non-linear mixed effects modelling to overcome the limited sampling and effect measurements.

Animals↗

PubMed1996

Relational database model for DNA mutations and a software program for implementation of the model.

A relational database model for describing DNA mutations is presented. The model was developed in conjunction with the human hprt database and was successful in representing over 1800 hprt mutations. Mutants showing aberrant mRNA splicing can be adequately described using the model, as well as mutants showing more than one mutation. The basic aspects of the relational model should be applicable to mutations in a variety of genes. A data entry program developed using Microsoft Access 2.0 is also described that implements the relational model. The data entry program ensures that relational integrity is maintained between the tables and automatically generates key fields as needed. The program also has the ability to convert between the various numbering schemes that are used to describe base pair location in the hprt gene. The program and source code are placed in the public domain so that other experimenters can adapt the program for use with other genes.

Humans↗