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Results for “quantitative model”

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At least 55 records · Page 3Linked to original sources

PubMed1992

Blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients: prediction by computer modeling.

To establish a qualitative and quantitative model of blood glucose response to stress hormone exposure, healthy subjects (HS) on and off somatostatin (250 micrograms/h) as well as insulin dependent diabetic patients were infused with either epinephrine (E), glucagon (G), cortisol (F), growth hormone (GH) or with a cocktail of these hormones raising plasma stress hormones to values seen in severe diabetic ketoacidosis. The developed input/output model consists of two submodels interconnected in series plus two additional submodels for correction of gains describing both sensitivity of tissue response and utilisation as well as provision of glucose. It was shown and confirmed experimentally that blood glucose response to stress hormones was essentially nonlinear. Furthermore, the mathematical models for healthy subjects and for insulin dependent diabetic patients proved to be of the same structure and differed only in the values of some typical parameters. The model raises the possibility to describe and in part to predict blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients.

Adult↗

PubMed1976

An experimental test of two mathematical models applied to the size-weight illusion.

Two quantitative models, which make different quantitative predictions for the amount of the size-weight illusion, were tested according to the psychophysical methods employed by the respective authors (magnitude estimation versus category ratings). Both models with their corresponding method were supported. This causes uncertainty over Anderson's chaim that the validity of both a model and the applied scale used is sufficiently test by the socalled joint testing procedure.

Humans↗

PubMed1992

A functional model of the human cardiac ventricle.

A quantitative model is presented which accurately reproduces the time activity curve of the human left ventricular blood pool. Four parameters receive numerical values and may be of clinical value.

Heart Ventricles↗

PubMed2026

Quantitative molecular cartography of emergency myelopoiesis reveals conserved modules of hematopoietic activation.

Hematopoietic stem and progenitor cells (HSPCs) respond to infections, inflammation, and regenerative challenges using emergency myelopoiesis (EM) pathways to amplify myeloid cell production. However, it remains unclear how various EM inducers regulate HSPCs using shared or distinct molecular mechanisms. Here, we generate a comprehensive and generalizable cell annotation method (HemaScribe) and a refined quantitative model of hematopoietic differentiation (HemaScape) using single-cell RNA sequencing (scRNA-seq) of murine HSPCs, which we apply to a broad range of EM modalities. We uncover multiple strategies for enhancing myelopoiesis that act at different levels of the HSPC hierarchy and are associated with both unique and shared transcriptional response modules. In particular, we identify a myeloid progenitor-based EM activation module across diverse inflammatory challenges that is conserved in humans and informs outcomes in adult and pediatric acute myeloid leukemia. Our work illuminates fundamental regulatory mechanisms in hematopoietic regeneration that have direct translational applications in disease contexts.

Animals↗

PubMed2024

Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

PURPOSE: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modeling the natural history, and uncovering genotype-phenotype associations. METHODS: A cross-sectional analysis of 90 published and 1 novel case was performed, using a Human-Phenotype-Ontology-based approach. Unsupervised phenotypic clustering was used alongside in silico analyses to identify distinct patient subgroups. RESULTS: The study models the natural history of the HPDL-related disease in a global cohort, clarifying the molecular and phenotypic spectrum and identifying 3 distinct subgroups characterized by differences in onset, clinical trajectories, and survival. It establishes genotype-phenotype associations, showing that the presence of moderately pathogenic missense variants in 1 allele leads to a milder, spastic paraplegic phenotype with later disease onset, whereas biallelic, highly pathogenic missense or truncating variants are associated with a more severe phenotype and reduced life span. CONCLUSION: Quantitative and unbiased natural history modeling in HPDL-related disease reveals significant genotype-phenotype associations, providing a foundation for variant interpretation, anticipatory guidance, and choice of outcome measures in future prospective and functional studies.

Humans↗

PubMed1978

[An in vitro model for the quantitative study of E. histolytica virulence].

An experimental model for the quantitative study of the cytopathic effect of E. histolytica is described. Confluent cultures of the MDCK cell line, which form a monolayer with morphological and electrophysiological features of an epithelium were used. Trophozoites of the strains HM1:IMSS, HM2:IMSS and HM3:IMSS, axenic produced variable degrees of cytopathic effects of MDCK cultures each one characteristic for a given strain. The degree of damage induced by the different strains of amebas was measured quantitatively. The results demonstrate that the degree of the cytopathic effect produced in vitro by the various strains tested correlates with the virulence shown in vivo by the same strains, judged as the size of the inoculum required to induce liver cytopathic effect in newborn hamsters.

Animals↗

PubMed1977

The detection of line segments.

Many simple cells of the visual cortex have long narrow receptive fields, which are strongly excited by lines oriented along their long axis. In the present psychophysical analysis, we assume that there are similar independent 'subunits' which contribute, by probability summation, to the detection of a line. If a line segment is shorter than the subunit length, then extending the line length will increase the sensitivity of all the subunits affected by the line, and a relatively large increase in visual sensitivity will occur, corresponding to this 'physiological summation' within subunits. However, for a line segment which is much longer than the subunit length, the main effect of extending line length is to stimulate more subunits, resulting in a relatively small increase in sensitivity owing to probability summation. Thus a study of sensitivity (reciprocal threshold) as a function of line length may be used to test the subunit model and to estimate the subunit length. Here we use a quantitative model to demonstrate that sensitivity/line length data may be well fitted, assuming independent subunits having a constant length of 8-6'--in good agreement with the length of Adrews' "ff" units.

Adult↗

PubMed2026

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

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

coarse-grained modeling↗

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↗

PubMed1979

Pattern generation in the lobster (Panulirus) stomatogastric ganglion. II. Pyloric network simulation.

1. Results from the companion paper were incorporated into a physiologically realistic computer model of the three principal cell types (PD/AB, LP, PY) of the pyloric network in the stomatogastric ganglion. Parameters for the model were mostly calculated (sometimes estimated) from experimental data rather than fitting the model to observed output patterns. 2. The initial run was successful in predicting several features of the pyloric pattern: the observed gap between PD and LP bursts, the appropriate sequence of the activity periods (PD, LP, PY), and a substantial PY burst not properly simulated by an earlier model. 3. The major discrepancy between model and observed patterns was the too-early occurrence of the PY burst, which resulted in a much shortened LP burst. Motivated by this discrepancy, additional investigations were made of PY properties. A hyperpolarization-enabled depolarization-activated hyperpolarizing conductance change was discovered which may make an important contribution to the late phase of PY activity in the normal burst cycle. Addition of this effect to the model brought its predictions more in line with observed patterns. 4. Other discrepancies between model and observation were instructive and are discussed. The findings force a substantial revision in previously held ideas on pattern production in the pyloric system. More weight must be given to functional properties of individual neurons and less to properties arising purely from network interactions. This shift in emphasis may be necessary in more complicated systems as well. 5. An example has been provided of the value quantitative modeling can be to network physiology. Only through rigorous quantitative testing can qualitative theories of how the nervous system operates be substantiated.

Animals↗

PubMedDate not supplied

[Mechanisms of change in the tonus of depolarized smooth muscle (guinea pig taenia coli) during application of a hyperpolarizing current].

Using double sucrose-gap technique three types of contractile responses of depolarized smooth muscle (guinea-pig taenia-coli) current-induced hyperpolarization were investigated: 1) contractions, 2) relaxations and 3) biphasic responses (relaxation followed by contraction). Every preparation generated generally only one type of responses (of different amplitude) when passing the currents of various strength. These responses were attributed to the changes of calcium fluxes through the cellular membranes under hyperpolarization. The phenomena observed were analysed on the mathematical model. Quantitative analysis showed that description of calcium current changes with equations of Hogkin-Huxley types was not sufficient; the model predicts the existence of non-inactivating channels in the smooth muscle cellular membrane. This very assumption allows to describe correctly all three types of cintractile responses.

Animals↗

PubMed2026

Multiscale Modeling Primer: Focus on Chromatin and Epigenetics.

A central challenge in modern biology is to understand how molecular interactions produce cellular and organismal functions across vast spatiotemporal scales. Nowhere is this challenge more apparent than in the study of chromatin, where meters of DNA compact into a micron-sized nucleus. How this polymer folds is a dynamic process, regulated by epigenetic modifications-chemical changes to DNA and histones that involve only a handful of atoms. These small changes cooperate to produce emergent, higher-order structures that define cellular identity and function. To explain this system, we must integrate static, high-resolution snapshots from techniques like cryo-EM with dynamic, lower-resolution data from microscopy and genomics. Multiscale computational models are essential tools that bridge these experimental gaps and reveal the mechanisms of emergent behavior. However, the communication divide between experimental biologists and quantitative modelers often hampers progress. This primer addresses that gap. It first introduces the fundamental biology of chromatin and epigenetics at an introductory level for non-biologists audiences. We then survey the landscape of computational approaches, from atomistic to systems-level models, and connect them to the experimental data that inform and validate them at an introductory level for non-computationalists. We argue that the next frontier will require us to build integrative models that can predict how molecular perturbations mechanistically alter cellular phenotypes, which will open a new era of chromatin-targeted therapeutics.

Chromatin Dynamics↗

PubMed1975

Studies of energy transport in heart cells. Mitochondrial isoenzyme of creatine phosphokinase: kinetic properties and regulatory action of Mg2+ ions.

1. The kinetic properties of mitochondrial creatine phosphokinase (Km for all substrates and maximal rates of the forward and reverse reaction) have been studied. Since (a) Km value for MgADP- (0.05 mM) and creatine phosphate (0.5 mM) are significantly lower than Km for MgATP2- (0.7 mM) and creatine (5.0 mM) and (b) maximal rate of the reverse reaction (creatine phosphate + ADP leads to ATP + creatine) equal to 3.5 mumol times min-1 times mg-1 is essentially higher than maximal rate of the forward reaction (0.8 mumol times min-1 times mg-1), ATP synthesis from ADP and creatine phosphate is kinetically preferable over the forward reaction. 2. A possible regulatory role of Mg2+ ions in the creatine phosphokinase reaction has been tested. It has been shown that in the presence of all substrates and products of the reaction the ratio of the rates of forward and reverse reactions can be effectively regulated by the concentration of Mg2+ ions. At limited Mg2+ concentrations creatine phosphate is preferably synthesized while at high Mg2+ concentrations (more ATP in the reaction medium) ATP synthesis takes place. 3. The kinetic (mathematical) model of the mitochondrial creatine phosphokinase reaction has been developed. This model accounts for the existence of a variety of molecular forms of adenine nucleotides in solution and the formation of their complexes with magnesium. It is based on the assumption that the mitochondrial creatine phosphokinase reactions mechanism is analogous to that for soluble isoenzymes. 4. The dependence of the overall rate of the creatine phosphokinase reaction on the concentration of total Mg2+ ions calculated from the kinetic model quantitatively correlates with the experimentally determined dependence through a wide range of substrates (ATP, ADP, creatine and creatine phosphate) concentration. The analysis of the kinetic model demonstrates that the observed regulatory effect of Mg2+ on the overall reaction rate can be expained by (a) the sigmoidal variation in the concentration of the MgADP- complex resulting from the competition between ATP AND ADP for Mg2+ and (b) the high affinity of the enzyme to MgADP-. 5. The results predicted by the model for the behavior of mitochondrial creatine phosphokinase under conditions of oxidative phosphorylation point to an intimate functional interaction of mitochondrial creatine phosphokinase and ATP-ADP translocase.

Adenosine Diphosphate↗

PubMed2026

Improving insurance deduction identification: a hybrid artificial intelligence model using machine learning and expert systems.

PURPOSE: Financial challenges in healthcare systems worldwide, especially in low- and middle-income countries like Iran, have increased hospitals' reliance on insurance reimbursements. Unrecognized insurance deductions often cause severe financial shortages, making efficient deduction management crucial. This study aimed to design a hybrid intelligent system for identifying and predicting insurance deductions by combining machine learning and expert system frameworks. DESIGN/METHODOLOGY/APPROACH: A mixed-methods design was applied in four stages. First, a scoping review identified the causes and patterns of insurance deductions. Second, interviews with 15 insurance experts produced a validated checklist and a dataset from inpatient billing records. Third, using the CRISP-DM methodology, machine learning algorithms were developed and tested in SPSS Modeler alongside a fuzzy expert system developed in MATLAB. Finally, the model was validated using the holdout method. FINDINGS: Four categories of deduction drivers were identified: service provision, registration errors, document submission issues, and revenue conversion processes. The CHAID decision tree outperformed other algorithms with a 99% precision rate and the lowest Mean Absolute Error (9.43). A brief assessment of potential overfitting was conducted to ensure that the CHAID model's high accuracy was interpreted cautiously and supported by the validation results. The fuzzy expert system with validated rules was adaptable for deduction classification, especially for cases unsuitable for quantitative modeling. ORIGINALITY/VALUE: The hybrid model improves detection and prevention of deductions, offering actionable insights for hospital administrators, insurers, and policymakers. Its implementation can enhance hospital information systems, streamline claims processing, and optimize revenue management amid financial constraints.

Machine Learning↗

PubMed1978

Model for the incidence of embryonal cancers: application to retinoblastoma.

The two-mutation theory of cancer initiation hypothesizes that some cancers originate after two successive mutations, of which the second mutation is always somatic and the first mutation may be germinal (hereditary cases) or somatic (nonhereditary cases). A quantitative model using the Poisson distribution is developed for ages at diagnosis for hereditary and nonhereditary cases. This model relates age-specific incidence data explicitly to the number of divisions of embryonal cells and to rates of somatic mutations per cell division. A good fit is obtained when the model is applied to data on ages at diagnosis for one such embryonal tumor, retinoblastoma.

Age Factors↗

PubMed1992

A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants.

Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer alpha-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted gamma-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydrocodeinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.

Amino Acid Sequence↗

PubMed1978

Towards a quantitative understanding of the epidemiology of Keystone virus in the eastern United States.

The implications of the Keystone virus--Aedes atlanticus transmission cycle are explored in the context of a quantitative model. Among the variables considered are the vertical transmission rate, the effect of the virus upon vector fertility and survival, vector densities and distributions, the proportion susceptible in the vertebrate population, the attractiveness of different vertebrates to the vector and vector survival rates. The logical relationships between these several variables are explored. It is concluded that the current view of Keystone virus maintenance is quantitatively feasible, and that certain predictions may be made as to the magnitude of several parameters which have not yet been measured. Such predictions allow direct testing of the model. The general structure of the model is such that it may prove useful in describing the epidemiology of other vector-borne infections in which vertical transmission is essential for infection maintenance at certain periods of the year.

Aedes↗

PubMed1979

Using systems theory to organize confusion.

This paper represents an initial step in applying to complex clinical situations the symbolic logic developed by G. Spencer Brown and elaborated by Francisco Varela. This way of modeling turns out to yield an interesting mixture of rigidity, ambiguity, and paradox, perhaps inevitable at our present level of understanding of systems containing feedback. Applying the Brown-Varela concepts seems a useful transitional step toweard the future use of more sophisticated quantitative models such as those of Powers and Forrester.

Adolescent↗