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Results for “Model interpretability”

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At least 703 records · Page 39Linked to original sources

PubMed1992

A coupled pacemaker-slave model for the insect photoperiodic clock: interpretation of ovarian diapause data in Drosophila melanogaster.

A coupled circadian oscillator model for the insect photoperiodic clock is described which consists of a hierarchically arranged pacemaker and slave. The pacemaker is self-sustained, temperature compensated, and entrainable by the light cycle; the slave is a damping oscillation receiving entrainment from two sources, from the pacemaker via a coupling factor, and also directly from the light. The damping slave oscillation is seen as the "photoperiodic oscillator", equivalent to that proposed earlier by Lewis and Saunders (1987). The present simulations describe the effect of the strength of the coupling factor between hypothetical short- and long-period pacemaker oscillations (modelled on the "clock" mutants perS and perL2 in Drosophila melanogaster) and a slave oscillation with a period of about 24 hours. The output is presented in terms of photoperiodic response curves and Nanda-Hamner, or resonance, plots. With a high coupling strength, the pacemakers strongly entrain the slave, but with a low coupling strength the slave's properties are more evident. The model is presented as a possible explanation for recent ovarian diapause data in D. melanogaster "clock" mutants (Saunders 1990), but also as a more general model for the role of the insect circadian system in seasonal time measurement.

Animals↗

PubMed2005

Supersymmetry and models for two kinds of interacting particles.

We show that Calogero-Sutherland models for interacting particles have a natural supersymmetric extension. For the construction, we use Jacobians that appear in certain superspaces. Some of the resulting Hamiltonians have a direct interpretation as models for two kinds of interacting particles. One model may serve to describe interacting electrons in a lower and upper band of a one-dimensional semiconductor, another model corresponds to two kinds of particles confined to two perpendicular spatial directions with an interaction involving tensor forces.

Journal Article↗

PubMed1979

Inventory responding as a model of people's acceptance of personality interpretations.

The hypothesis was tested that inventory responding modeled the acceptance of personality feedback. A barnum group (n=40) was asked to rate the personal accuracies of a list of personality inventory items and then an equivalent list of bogus personality feedback. The two lines of evidence which supported the model were (a) that the correlation between their inventory ratings and their feedback ratings was not only Significant (p < .001) but achieved a ceiling magnitude, as evidenced by a control group's (n = 40) data; and (b) that the variables influencing, inventory responding exerted an equal influence upon feedback acceptance, Contrary to the model, it was found that feedback was accepted more highly than were the inventory items. Conclusions were that inventory responding, as a model of feedback acceptance, is accurate with respect to individual differences but somewhat inaccurate with respect to overall levels of acceptance due to the additional influences of persuasion. It was also concluded that clients' acceptance or rejection of personality feedback is not evidence of the validity or invalidity, respectively, of assessment devices. A reformulated model of personality feedback acceptance was proposed.

Journal Article↗

PubMed1991

Computer modelling of Tetrahymena axonemes at macromolecular resolution. Interpretation of electron micrographs.

A computer-generated model of the structural arrangement of the complete 9+2 ciliary axoneme of Tetrahymena at macromolecular resolution (4 nm) is presented. The model reconciles detailed information about subcomponents from negative-stained, thin-section and freeze-fracture electron micrographs, integrating the images into a consistent three-dimensional picture. This illuminates problems such as the requirement for compaction of dynein to form the arm, difficulties in visualization of the circumferential links, construction of the central sheath, and the comparative periodicities of the inner and outer arms. The model is pragmatic in that it is flexible and easily changed, as new information becomes available. It is also useful in the development of dynamic concepts, such as a spatial description of the dynein cross-bridge cycle, which is illustrated, or relationships between adjacent doublets during sliding and bending.

Animals↗

PubMed2001

A method to assess the proportion of treatment effect explained by a surrogate endpoint.

Randomized clinical trials are the standard for evaluating new drugs, devices and procedures. Traditional clinical trials entail not only considerable expense, but require considerable time to complete. The use of surrogate endpoints constitutes an effort to control cost and completion time for clinical trials. We propose a method to quantify the proportion of treatment effect explained by a surrogate endpoint based on a general model setting which includes the commonly used linear, logistic and Cox regression models. The interpretation of this quantitative measure is facilitated by graphical displays. To reduce the variability associated with the estimate, a meta-analytic approach is proposed based on random effects models. An example using real clinical trial data is given to illustrate the proposed procedures.

Biometry↗

PubMed2026

Evaluating the pathogenic significance of unique chromosomal variants in craniosynostosis using patient-derived induced pluripotent stem cells and mouse modelling.

PURPOSE: Unravelling causal links between unique structural/copy-number variants (SV/CNV) and associated phenotypes is essential for correct genetic counselling. We investigated two families in which patients with craniosynostosis had SV/CNV potentially dysregulating a fibroblast growth factor (FGF)-encoding gene; a 730 kb dup(4)(q21.21) including FGF5; and a complex 568 kb interspersed 13q12.11 duplication, located 841 kb from FGF9. METHODS: We combined bioinformatic predictions of altered topologically-associating domain (TAD) structure, with experimental analysis (RNA- and ATAC- [assay for transposase-accessible chromatin] sequencing) of patient induced pluripotent stem cell lines (iPSCs) differentiated to neural crest (NCC) and osteoprogenitor (OPC) identities. For the dup(4)(q21.21) we generated a mouse bearing an equivalent rearrangement using CRISPR-Cas9 targeting. RESULTS: TAD analysis suggested potential dysregulation of the FGF5/FGF9 gene by bringing it into a novel genomic milieu. The RNA- and ATAC-seq assays demonstrated FGF5/FGF9 upregulation (2.7-18x) and local opening of chromatin, in 3/4 cell lines. For the dup(4)(q21.21), a causal role was supported by the mouse model, whereas interpretation of the 13q12.11 SV is confounded by a co-existing FOXP2 pathogenic variant. CONCLUSION: Patient iPSC-differentiated NCC and OPC lines, combined with TAD-based modelling to generate testable functional hypotheses, provide valuable functional evidence when evaluating causation of unique SV/CNV in craniosynostosis.

copy-number variant↗

PubMed2005

A framework for investigating thalamocortical activity in multistage information processing.

A framework for investigating information processing in cortico-thalamocortical (cortico-TC) networks is presented, that in part can be used to model and interpret individual changes in electroencephalographic spectra and event-related potentials such as those from the Brain Resource International Database. Scientific work covering neurophysiology, TC firing modes, and TC models are explored in the framework to explain how the brain might process complex information in a multistage process. It is proposed that the thalamus and the cortico-TC system have unique ionic properties and transmission delays (in humans), which are suited to the function of taking "snapshots" or samples of complex environmental stimuli, rather than continuous data streams. This leads to careful and sequential coordination of stimulus and response processes, and increases the probability of information transfer and the resulting information complexity in higher cortical regions. Given the scope of this framework, the multidimensional and standardized Brain Resource International Database provides a pertinent set of measures for both testing hypotheses generated from the model, and for fitting the model to experimental data to investigate mechanisms underlying information processing.

Alpha Rhythm↗

PubMed2002

Using Monte Carlo techniques to judge model prediction accuracy: validation of the pesticide root zone model 3.12.

Individuals from the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force (FEMVTF) Statistics Committee periodically met to discuss the mechanism for conducting an uncertainty analysis of Version 3.12 of the pesticide root zone model (PRZM 3.12) and to identify those model input parameters that most contribute to model prediction error. This activity was part of a larger project evaluating PRZM 3.12. The goal of the uncertainty analysis was to compare site-specific model predictions and field measurements using the variability in each as a basis of comparison. Monte Carlo analysis was used as an integral tool for judging the model's ability to predict accurately. The model was judged on how well it predicts measured values, taking into account the uncertainty in the model predictions. Monte Carlo analysis provides the tool for inferring model prediction uncertainty. We argue that this is a fairer test of the model than a simple one-to-one comparison between predictions and measurements. Because models are known to be imperfect predictors prior to running the model, the inaccuracy in model predictions should be considered when models are judged for their predictive ability. Otherwise, complex models can easily fail a validation test. Few complex models, such as PRZM 3.12, would pass a typical model validation exercise. This paper describes the approaches to the validation of PRZM 3.12 used by the committee and discusses issues in sampling distribution selection and appropriate statistics for interpreting the model validation results.

Forecasting↗

PubMed2005

Improved approach for proteochemometrics modeling: application to organic compound--amine G protein-coupled receptor interactions.

MOTIVATION: Proteochemometrics is a novel technology for the analysis of interactions of series of proteins with series of ligands. We have here customized it for analysis of large datasets and evaluated it for the modeling of the interaction of psychoactive organic amines with all the five known families of amine G protein-coupled receptors (GPCRs). RESULTS: The model exploited data for the binding of 22 compounds to 31 amine GPCRs, correlating chemical descriptions and cross-descriptions of compounds and receptors to binding affinity using a novel strategy. A highly valid model (q2 = 0.76) was obtained which was further validated by external predictions using data for 10 other entirely independent compounds, yielding the high q2ext = 0.67. Interpretation of the model reveals molecular interactions that govern psychoactive organic amines overall affinity for amine GPCRs, as well as their selectivity for particular amine GPCRs. The new modeling procedure allows us to obtain fully interpretable proteochemometrics models using essentially unlimited number of ligand and protein descriptors.

Amines↗

PubMed2003

A causal-model theory of conceptual representation and categorization.

This article presents a theory of categorization that accounts for the effects of causal knowledge that relates the features of categories. According to causal-model theory, people explicitly represent the probabilistic causal mechanisms that link category features and classify objects by evaluating whether they were likely to have been generated by those mechanisms. In 3 experiments, participants were taught causal knowledge that related the features of a novel category. Causal-model theory provided a good quantitative account of the effect of this knowledge on the importance of both individual features and interfeature correlations to classification. By enabling precise model fits and interpretable parameter estimates, causal-model theory helps place the theory-based approach to conceptual representation on equal footing with the well-known similarity-based approaches.

Causality↗

PubMedDate not supplied

Locomotor mode, maximum running speed, and basal metabolic rate in placental mammals.

The locomotor performance (absolute maximum running speed [MRS]) of 120 mammals was analyzed for four different locomotor modes (plantigrade, digitigrade, unguligrade, and lagomorph-like) in terms of body size and basal metabolic rate (BMR). Analyses of conventional species data showed that the MRS of plantigrade and digitigrade mammals and lagomorphs increases with body mass, whereas that of unguligrade mammals decreases with body mass. These trends were confirmed in plantigrade mammals and lagomorphs using phylogenetically independent contrasts. Multiple regression analyses of MRS contrasts (dependent variable) as a function of body mass and BMR contrasts (predictor variables) revealed that BMR was a significant predictor of MRS in the complete data set, as well as in plantigrade and nonplantigrade mammals. However, there was severe multicollinearity in the nonplantigrade model that may influence the interpretation of these models. Although these data show mass-independent correlation between BMR and MRS, they are not necessarily indicative of a cause-effect relationship. However, the analyses do identify a negligible role of body size associated with MRS once phylogenetic and BMR effects are controlled, suggesting that the body size increase in large mammals over time (i.e., Cope's rule) can probably rule out MRS as a driving variable.

Animals↗

PubMed2026

Causal circuit tracing reveals distinct computational architectures in single-cell foundation models: inhibitory dominance, biological coherence, and cross-model convergence.

MOTIVATION: Sparse autoencoders (SAEs) decompose foundation-model activations into interpretable features, but the model-internal causal interactions between those features (i.e. what ablating one feature does to the others, as distinct from the biological causal structure of the underlying cells)-and how those model-internal relationships relate to biological structure-are uncharacterized in single-cell foundation models. RESULTS: We introduce model-internal causal circuit tracing-zeroing one SAE feature at a source layer and measuring the resulting change in all downstream SAE features, for each of 120 source features-and apply it to Geneformer V2-316M and scGPT whole-human across four conditions (96 892 ablation-derived edges, 80 191 forward passes). On annotation-selected source features, edges share GO/KEGG/Reactome/STRING/TRRUST ontology terms at 50.9%-68.5%, a 2.9-6.2× enrichment over a configuration-preserving permutation null (P<.002); on 20 randomly sampled source features this attenuates to 21.5%-26.3%-still 2.5-3.1× above null-quantifying the annotation-selection contribution. Inhibitory dominance (fraction of ablation edges with d<0, i.e. source activation supports downstream target) is 65.5%-89.4%. scGPT produces larger raw per-edge effects (mean |d|=1.40 versus 1.05); after feature-share normalization, Geneformer is stronger (paired gene-pair ratio 0.64 on 33 301 shared pairs). Cross-model consensus yields 1142 architecture-invariant domain pairs (ordered pairs of GO biological-process categories "A→B" each connected by at least one ablation edge in both models; 10.6× enrichment over permutation null; P<.001). Circuit edge magnitude explains <1% of the variance in marginal driver-gene coexpression on the same cells (R2=0.010, n=31 176): the graph encodes structure beyond bivariate correlation. Against a matched-cell-type ENCODE ChIP-seq prior, circuit-predicted transcription factor (TF)→target pairs are enriched 2.06× (Fisher OR 5.84), markedly higher than 1.12× against TRRUST; direct ChIP-seq-supported target pairs show 10-30× larger CRISPRi sign-bias-corrected excess than indirect pairs. Gene-level CRISPRi validation on Replogle K562 and the noncancer RPE1 arm (and a true primary-T-cell control from Shifrut E, Carnevale J, Tobin V et al. Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function. Cell 2018; 175: 1958-71.e15) after sign-bias correction shows excess over baseline of +0.03 and +0.35 percentage points on K562 and RPE1, respectively (baseline already 52%-56% from sign marginals); effect-magnitude Spearman correlations ρ≈0. Bootstrap and per-cell-type stability (N∈{50,100,200}; B cell, CD4 + T, macrophage) give Pearson r≥0.97 on shared edges with 100% sign agreement; edge Jaccard grows monotonically with sample size. The circuit graph is therefore highly reproducible as an effect-size map, cell type specific in edge identity, consistent with coexpression encoding, and weakly but detectably enriched for ChIP-seq-supported direct regulatory edges. AVAILABILITY AND IMPLEMENTATION: https://github.com/Biodyn-AI/bio-sae-circuits (Python). Archival DOI: 10.5281/zenodo.19,633,166 (Zenodo).

Humans↗

PubMed1994

Optimizing performance through process improvement.

Health care professionals have found traditional problem solving and traditional management have not succeeded in "assuring quality." Organizations are changing the way they do business and are utilizing process improvement methodology to improve performance. Based on important functions, select dimensions of performance for processes are measured, evaluated, redesigned, and improved. Once priorities for improvement activities are determined, improvement projects can be implemented utilizing various process improvement models. The PRIDE (process, relevant, interpret, design, execute) model, designed by the authors, is one approach that can be applied in any setting.

Efficiency, Organizational↗

PubMed1988

Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach.

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.

Adolescent↗

PubMed1991

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion.

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.

Animals↗

PubMed2004

Validation of the conceptual anatomical model of the lung airway.

The conceptual anatomical model of the lung airway considers each lung volume divided into ten concentric shells. It specifies the volume of each airway generation in each shell, using Weibel morphometry. This study updates and validates the model and evaluates the errors obtained when using it to estimate inhaled aerosol deposition per generation from spatial imaging data. A comparison of different airway models describing the volume per generation, including data from CT images of a lung cast and a human subject, was performed. A revised version of the conceptual model was created, using the average volume per generation from these data. The new model was applied to derive the aerosol deposition per generation from 24 single photon emission computed tomography (SPECT) studies. Analysis errors were assessed by applying the same calculations but using airway models based on the minimum and maximum volumes per generation. The mean shell position of each generation in the average model was not significantly different from either CT model. However there were differences between the volumes per generation of the different models. The root mean square differences between bronchial airways deposition fraction (generations 2-8) obtained from the maximum and minimum models compared to the new average model was 0.66 percentage points (14%). For the conducting airways deposition fraction (generations 2-15) this was 1.66 percentage points (12%). The conceptual model is consistent with CT measurements of airway geometry. The errors resulting from using a generic airway model to interpret 3D radionuclide image data have been defined.

Humans↗

PubMed1993

Theoretical modelling of the motion and deformation of capsules in shear flows.

Mechanical models for capsules freely suspended in another liquid, are devised to predict the deformation, motion, breakup of one particle and also the rheological flow behaviour of a suspension. The capsule is filled with a newtonian liquid, and is surrounded by a thin deformable membrane having otherwise arbitrary mechanical properties. Initially spherical capsules in simple shear flow, are found to deform and orient with respect to streamlines, while their membrane is continuously rotating around the internal liquid. A dilute suspension of such capsules has a viscoelastic constitutive law which depends on the particle physical properties. It is then possible to use such models to interpret experiments in terms of the mean intrinsic properties of a capsule population.

Capsules↗

PubMed1996

The advanced practice nurse as case manager.

The dynamic interactions of the client, service provided, and payer are complex relationships in today's health care environment. An advanced practice nurse's abilities to care physically and psychosocially for clients and their families are essential within the case management framework. With a holistic view of clients' health status, the nurse case manager develops and carries out advanced practice functions that help achieve the best outcome for the client through effective interactions with clients, payers, and providers. Those functions, illustrated by the Star Case Management Model, include interpretation, advocacy, and surveillance.

Aged↗