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Results for “Model interpretability”

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At least 1,297 records · Page 72Linked to original sources

PubMed2002

PCB sources, transformations, and contributions in recent Fox River, Wisconsin sediments determined from receptor modeling.

The PCB contamination in lower Fox River sediments was investigated in order to identify possible PCB sources, contributions, and transformations, using two receptor models. Congener specific sediment PCB data from sites immediately upstream of DePere dam to Green Bay that had been gathered for the Green Bay/Fox River Mass Balance Study, were used in this analysis. The first receptor model is a self training factor analysis (FA) model with non-negative constraints that was applied to identify the PCB sources and significant congener patterns. The second is a chemical mass balance model (CMB) in which published Aroclor sources, inferred from our FA model, were used to apportion these Aroclors to each sample. The FA model indicated two significant factors, the major one being Aroclor 1242 and the other, a profile dominated by low chlorinated congeners, indicating a possible PCB alteration profile. This profile had significant contributions to samples at or around sites with total PCB concentrations higher than 50 ppm, indicating a potential anaerobic dechlorination activity. It was also deduced from the FA model that very small contributions of more highly chlorinated Aroclors may be present in the system. The results from the CMB model confirmed that the system is dominated by Aroclor 1242. Its average contribution was 95%, with small amounts of Aroclor 1254 (2%) and 1260 (1%). Two of the samples, located in the vicinity of point sources, showed high contributions of Aroclor 1016 by the CMB model. This is interpreted as an altered Aroclor profile resembling the less chlorinated Aroclor 1016. Contributions obtained form the CMB and FA models show similar patterns.

Bacteria, Anaerobic↗

PubMed1997

Biologic synergism and parallelism.

In epidemiologic studies of two binary exposure factors, much attention has been given to the concept of synergism of the factors. The leading dictionary of epidemiology offers two definitions of synergism, one of which this author labels statistical and the other biologic. The epidemiologic literature has been largely concerned with statistical synergism, which is typically measured using additive or multiplicative interaction. This paper focuses on biologic synergism, on the related concept of biologic parallelism, and on the question of how much information can be gleaned about population amounts of biologic synergism and parallelism--information which is of vital interest to epidemiologists. A fundamental identity equates the difference between the amounts of biologic synergism and parallelism to the additive interaction. Two biologic models, the multistage model and the no-hit or immunity model, enhance the interpretation of multiplicative interaction as a measure of statistical synergism, but it is pointed out here that, unfortunately, both models incorporate the strong assumption that there is no parallelism. A third model, the single-hit or vulnerability model, makes the even stronger assumption that there is no biologic synergism and consequently that the additive interaction is equal to minus the amount of parallelism. A consequence of this fact is that a link which has been perceived in the literature to exist between the single-hit model and the additive interaction is false.

Epidemiologic Methods↗

PubMed2003

Rate models for conductance-based cortical neuronal networks.

Population rate models provide powerful tools for investigating the principles that underlie the cooperative function of large neuronal systems. However, biophysical interpretations of these models have been ambiguous. Hence, their applicability to real neuronal systems and their experimental validation have been severely limited. In this work, we show that conductance-based models of large cortical neuronal networks can be described by simplified rate models, provided that the network state does not possess a high degree of synchrony. We first derive a precise mapping between the parameters of the rate equations and those of the conductance-based network models for time-independent inputs. This mapping is based on the assumption that the effect of increasing the cell's input conductance on its f-I curve is mainly subtractive. This assumption is confirmed by a single compartment Hodgkin-Huxley type model with a transient potassium A-current. This approach is applied to the study of a network model of a hypercolumn in primary visual cortex. We also explore extensions of the rate model to the dynamic domain by studying the firing-rate response of our conductance-based neuron to time-dependent noisy inputs. We show that the dynamics of this response can be approximated by a time-dependent second-order differential equation. This phenomenological single-cell rate model is used to calculate the response of a conductance-based network to time-dependent inputs.

Action Potentials↗

PubMed1993

Hypertonic treatment does not affect the radiation yield of interphase chromosome breaks in DNA double-strand break repair-deficient xrs-5 cells.

A DNA double-strand break (DSB) repair-deficient CHO cell line, xrs-5, was used to evaluate the effect of hypertonic treatment on the radiation yield of interphase chromosome breaks, as visualized by means of premature chromosome condensation (PCC). For this purpose, interphase chromosome breaks were measured in plateau-phase G1 cells after exposure to 10 Gy X rays using either the standard protocol for PCC induction or a revised protocol that includes a brief (20 min) treatment in hypertonic medium (500 mM NaCl) during chromosome condensation. Experiments at the chromosome level were complemented by experiments at the DNA and the cellular level performed under similar postirradiation conditions. The results obtained were compared to those reported previously for CHO cells. Radiation yields of interphase chromosome breaks, as measured using standard protocols for PCC induction, were higher in xrs-5 than in CHO cells. However, the yields became similar between the two cell lines when a 20-min incubation in hypertonic medium was introduced immediately after fusion with mitotic cells. This equalization was due to the fact that incubation in hypertonic medium did not affect the radiation yield of interphase chromosome breaks in xrs-5 cells but increased it in CHO cells to levels similar to those measured in xrs-5 cells. This result suggests that xrs-5 cells constitutively express as interphase chromosome breaks a subset of DSBs which in repair-proficient CHO cells requires incubation in hypertonic medium for transformation to interphase chromosome breaks. Rejoining of DSBs, when measured in isotonic medium, was incomplete in xrs-5 cells compared to CHO cells. Rejoining of DSBs normally repaired in xrs-5 cells was completely inhibited during treatment in hypertonic medium. Postirradiation treatment in hypertonic medium affected the survival of xrs-5 cells only modestly, suggesting that the sector of PLD (beta-PLD) which required treatment in hypertonic medium for fixation in repair-proficient CHO cells is fixed constitutively in xrs-5 cells. These results are in agreement with a model developed to interpret results obtained in similar experiments with CHO cells (Iliakis et al., Radiat. Res 135, 160-170, 1993). The model postulates that potentiation in CHO cell killing induced by hypertonic treatment is caused by the transformation of a subset of fast-repairing DSBs to irreparable interphase chromosome breaks and assumes that this transformation is equivalent to fixation of beta-PLD.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1997

Analysis of the contact sites on the CD4 molecule with class II MHC molecule: co-ligand versus co-receptor function.

The CD4 molecule interacts with the alpha2 and beta2 domains of the MHC class II molecules. However, the class II contact sites on CD4 are less clear. Involvement of different regions throughout D1, D2, and D3 domains have been suggested. To further delineate the class II MHC contact sites on CD4, a crystal structure-informed mutagenesis was performed. Alanine scan mutants were generated for exposed residues located throughout D1 and the FG loop of D2, and in the "hinge-like" region, a short and flexible region between D2 and D3. Mutants were tested in a co-ligand (Dd stimulation) and a co-receptor (staphylococcal enterotoxin B stimulation) assay. In the co-ligand assay, TCR and CD4 interact with two distinct ligands (Dd or HLA-DR), while in the co-receptor assay both molecules interact with the same ligand, namely HLA-DR. Results show that residues from both lateral faces of D1 and the FG loop of D2 are implicated in interaction with class II, although a bigger surface of CD4 was involved in co-receptor compared with co-ligand function. The potential involvement of residues on both the top and two side faces of CD4 is consistent with a bivalent model, which involves the interaction between a single CD4 and two class II molecules. Alternatively, our results can be interpreted with a model of a specifically organized CD4 and/or class II oligomerization event. Finally, results from the hinge region mutants revealed a very important role in maintaining the overall structural integrity of CD4, its topology, and function.

CD4 Antigens↗

PubMedDate not supplied

[Cooperative inactivation of glutamate dehydrogenase of 2,2,6,6- tetramethyl-4-oxopiperidine-1-oxyl. Interpretation of results within the scope of a hexamer model with equivalent subunit orientation].

It was shown that the blockage of epsilon-amino group of Lis-126 residue by 2,2,6,6-tetramethyl-4-oxo-piperidine-1-oxyl (TMPO) leads to the cooperative inactivation of glutamate dehydrogenase (L-glutamate-NAD(P)-oxidoreductase, EC 1.4.1.3). The data concerning cooperative inactivation of the enzyme are interpreted by the model of hexamer with identical orientation of subunits. It was shown that the modification of any of enzyme subunits is accompanied by an inactivation of the hexamer's fragment which is a dimer, with subunits interacting reciprocally by means of isological contacts.

Animals↗

PubMed2005

Modeling physiological and anthropometric variables known to vary with body size and other confounding variables.

This review explores the most appropriate methods of identifying population differences in physiological and anthropometric variables known to differ with body size and other confounding variables. We shall provide an overview of such problems from a historical point of view. We shall then give some guidelines as to the choice of body-size covariates as well as other confounding variables, and show how these might be incorporated into the model, depending on the physiological dependent variable and the nature of the population being studied. We shall also recommend appropriate goodness-of-fit statistics that will enable researchers to confirm the most appropriate choice of model, including, for example, how to compare proportional allometric models with the equivalent linear or additive polynomial models. We shall also discuss alternative body-size scaling variables (height, fat-free mass, body surface area, and projected area of skeletal bone), and whether empirical vs. theoretical scaling methodologies should be reported. We shall offer some cautionary advice (limitations) when interpreting the parameters obtained when fitting proportional power function or allometric models, due to the fact that human physiques are not geometrically similar to each other. In conclusion, a variety of different models will be identified to describe physiological and anthropometric variables known to vary with body size and other confounding variables. These include simple ratio standards (e.g., per body mass ratios), linear and additive polynomial models, and proportional allometric or power function models. Proportional allometric models are shown to be superior to either simple ratio standards or linear and additive polynomial models for a variety of different reasons. These include: 1) providing biologically interpretable models that yield sensible estimates within and beyond the range of data; and 2) providing a superior fit based on the Akaike information criterion (AIC), Bayes information criterion (BIC), or maximum log-likelihood criteria (resulting in a smaller error variance). As such, these models will also: 3) naturally lead to a more powerful analysis-of-covariance test of significance, which will 4) subsequently lead to more correct conclusions when investigating population (epidemiological) or experimental differences in physiological and anthropometric variables known to vary with body size.

Anthropometry↗

PubMed2004

[Significance of the mathematical model of cardiac electrical field for the interpretation of experimental data].

BACKGROUND: In concurrence of our recent findings of the elevation of QT dispersion (QTd) in the group of pregnant women, mathematical approaches were developed aimed to give possible geometrical explanation whether the observed changes result from the rotation or from the changed position of the heart. METHODS AND RESULTS: Mathematical model of the cardiac electrical field approximated as a time variable dipole in a homogenous spatial conductor was developed. From the experimental vectocardiographic records, representing time course of the cardiac dipole, body surface potential maps were calculated on the basis of the model. To validate the adequacy of the model, the reconstructed electrocardiograms were compared with the empiric data. To determine the effects of rotation, original empiric VCG data of the control group were transformed accordingly the hypothetic pregnancy related changes. Calculated surface electrocardiograms were then compared with empiric cardiograms of the pregnant women. CONCLUSIONS: Based on the results, several conclusions can be drawn: 1) QT dispersion is associated also with the geometrical relations between the direction of cardiac vector during the terminal phase of repolarization and the direction of axes in the given system of leads. The dispersion then has its typical occurrence at the thoracic surface--minimums of the QT duration are found in the plane perpendicular to the axis of the terminal vector lead. 2) When the duration of repolarization is estimated from the classic thoracic leads within the phisiological variations of terminal-depolarization vector orientations, can exist that in some cases the minimum of QT interval is and in others it is not recorded by the lead system. Value of QT dispersion between these two extremes will be significantly different. 3) In case of the horizontal declination of the heart, the ECG signal in most of the leads of the body surface mapping has a higher voltage than in case of vertical declination due to a smaller angle between axes of the terminal vector and most of the leads. Such fact will contribute to more accurate reading of the T wave end and to the estimation of QT interval, usually with smaller value of QTd. 4) The change of the cardiac electrical field corresponding to the changed position of the heart (rotation) does not result by itself in QTd changes, if it is evaluated from the records from the whole thorax. Obversely, horizontalization of the heart contributes more to the evaluation of lower QTd values, as it is given above. 5) More then the result of geometrical changes, QT dispersion found in the group women in high level of pregnancy is an effect of changes in the T loop morphology, which was observed in this group. Another possible explanation of the observed dispersion is the non-dipolar character of the electrical field changes during pregnancy.

Adult↗

PubMed1995

Simple models for the analysis of binding protein-dependent transport systems.

Mathematical modeling was used to evaluate experimental data for bacterial binding protein-dependent transport systems. Two simple models were considered in which ligand-free periplasmic binding protein interacts with the membrane-bound components of transport. In one, this interaction was viewed as a competition with the ligand-bound binding protein, whereas in the other, it was considered to be a consequence of the complexes formed during the transport process itself. Two sets of kinetic parameters were derived for each model that fit the available experimental results for the maltose system. By contrast, a model that omitted the interaction of ligand-free binding protein did not fit the experimental data. Some applications of the successful models for the interpretation of existing mutant data are illustrated, as well as the possibilities of using mutant data to test the original models and sets of kinetic parameters. Practical suggestions are given for further experimental design.

Adenosine Triphosphate↗

PubMed2006

Modelling competing risks in cancer studies.

Competing risks arise commonly in the analysis of cancer studies. Most common are the competing risks of relapse and death in remission. These two risks are the primary reason that patients fail treatment. In most medical papers the effects of covariates on the three outcomes (relapse, death in remission and treatment failure) are model by distinct proportional hazards regression models. Since the hazards of relapse and death in remission must add to that of treatment failure, we argue that this model leads to internal inconsistencies. We argue that additive models for either the hazard rates or the cumulative incidence functions are more natural and that these models properly partition the effect of a covariate on treatment failure into its component parts. We illustrate the use and interpretation of additive models for the hazard rate or for the cumulative incidence function using data from a study of the efficacy of two preparative regimes for hematopoietic stem cell transplantation.

Adult↗

PubMed1981

A computer model of the evolution of specific maximum lifespan.

To answer the question of why organisms have evolved finite and specific maximum lifespans, I have built and experimentally studied a discrete-event simulation model of the evolution of lifespan. Through natural selection, the model evolves an apparent plateau in maximum lifespan, the height of which is a decreasing function of both the intensity of niche fluctuations and specific fecundity. Evolved lifespan is therefore finite (small and essentially constant over accessible time intervals) and specific. Experiments demonstrate that the plateau is not due to group selection. Instead, it occurs because the rate of increase of maximum lifespan by natural selection - in an environment presenting a finite probability that death will occur prior to reaching the genetically specified maximum - is a decreasing function of maximum lifespan itself and asymptotically approaches zero. This supports in part a class of existing hypotheses that finite lifespan is due to an equilibrium between weak selection, as in the model, and various lifespan-decreasing processes, which however were not simulated in the present experiments. Although the model shows that such counter processes are not strictly necessary for the evolution of finite and specific maximum lifespan, my interpretation of the model's correspondence to organic evolution does imply a counter process, a bias in random genetic drift toward shorter lifespan, that is more general than those previously hypothesized.

Biological Evolution↗

PubMed2002

Derivation of 137Cs deposition density from measurements of 137Cs inventories in undisturbed soils.

The 137Cs inventories in undisturbed soils were measured for 292 locations across the territory of Vietnam. The logarithmic inventory values were regressed against characteristics of sampling sites, such as geographical coordinates, annual rainfall and physico-chemical parameters of soil. The regression model containing latitude and annual rainfall as determinants could explain 76% of the variations in logarithmic inventory values across the territory. The model part was interpreted as the logarithmic 137Cs deposition density. At the 95% confidence level, 137Cs deposition density could be predicted by the model within +/- 7% relative uncertainty. The latitude mean 137Cs deposition density increases northward from 237 Bq m(-2) to 1097 Bq m(-2), while the corresponding values derived from the UNSCEAR (1969) global pattern are 300 Bq m(-2) and 600 Bq m(-2). High 137Cs inputs were found in high-rainfall areas in northern and central parts of the territory.

Cesium↗

PubMed1997

Surface EMG signal processing during isometric contractions.

This paper provides an overview of techniques suitable for the estimation, interpretation and understanding of time variations that affect the surface electromyographic (EMG) signal during sustained voluntary or electrically elicited contractions. These variations concern amplitude variables, spectral variables and muscle fiber conduction velocity, are interdependent and are referred to as the 'fatigue plot'. The fatigue plot provides information suitable for the classification of muscle behavior. In addition, the information obtainable by means of linear electrode arrays is discussed, and applications of mathematical models for the interpretation of array signals are presented. The model approach provides additional ways for the classification of muscle behavior.

Journal Article↗

PubMed1980

On facilitated oxygen diffusion in muscle tissues.

The role of myoglobin in facilitated diffusion of oxygen in muscle in examined in a tissue model that utilizes a central supplying capillary and a tissue cylinder concentric with the central capillary, and that includes the nonlinear characteristics of the oxygen-hemoglobin dissociation reaction. In contrast to previous work, this model exhibits the effect of blood flow and a realistic, though ideal, tissue-capillary geometry. Solutions of the model equations are obtained by a singular-perturbation technique, and numerical results are discussed for model parameters of physiologic interest. In contrast to the findings of Murray, Rubinow, Taylor, and others, fractional order perturbation terms obtained for the "boundary-layer" regions near the supplying capillaries are quite significant in the overall interpretation of the modeling results. Some closed solutions are found for special cases, and these are contrasted with the full singular-perturbation solution. Interpretations are given for parameters of physiologic interest.

Animals↗

PubMed1998

Building manageable rough set classifiers.

An interesting aspect of techniques for data mining and knowledge discovery is their potential for generating hypotheses by discovering underlying relationships buried in the data. However, the set of possible hypotheses is often very large and the extracted models may become prohibitively complex. It is therefore typically desirable to only consider the "strongest" hypotheses, so that smaller models can be obtained that also retain good classificatory capabilities. This paper outlines how rule-based classifiers based on rough set theory and Boolean reasoning that are both small and perform well can be developed. Applied to a real-world medical dataset, the final models are shown to exhibit good performance using only a subset of the available information. Furthermore, the number of resulting rules is low and enables practical a posteriori inspection and interpretation of the models.

Classification↗

PubMed1999

Viscoelasticity modulates resonance in the terminal aortic circulation.

We used an inertance-viscoelastic windkessel model (IVW) to interpret aortic impedance patterns as seen in the terminal aortic circulation of the dog, and to explain evident oscillatory phenomena in flow measurements. This IVW model consists of an inertance, L, connected in series with a viscoelastic windkessel (VW) where the peripheral resistance, Rp, is connected in parallel with a Voigt cell (a resistor, Rd, in series with a capacitor, C) to account for viscoelasticity. Pressure and flow measurements were taken from the terminal aorta, just downstream of the origin of renal arteries, in three anaesthetised open-chest dogs, under a variety of haemodynamic conditions induced by administering a vasoconstrictor agent (methoxamine) and a vasodilator (sodium nitroprusside). Mean pressure ranged from 40 to 140 mm Hg. The resistance Rp was calculated as the ratio of mean pressure to mean flow. Parameters L, C and Rd were estimated by fitting measured to model predicted flow waves. We found that prominent oscillations observed in flow waves, from midsystole to diastole, are related to resonance that occurs at a frequency, f(o), where reactance of inertance of blood motion matches the reactance of arterial compliance. Estimates of f(o) increased from 2.4 to 10 Hz with increasing pressure and showed a correlation with values of static elastic moduli plotted against mean pressure of dogs' peripheral arteries previously reported by others. Viscous losses, Rd, of arterial wall motion limited the amplitude of resonance peak. We conclude that viscoelasticity, rather than pure elasticity, is a key issue to interpret terminal aortic impedance as it relates to resonance.

Animals↗

PubMed1988

Interaction of amphiphiles with integral membrane proteins. II. A simple, minimal model for the nonspecific interaction of amphiphiles with the anion exchanger of the erythrocyte membrane.

In a previous paper we have reported on the structural perturbation of the erythrocyte membrane anion exchanger by a regular series of model amphiphiles, as shown by differential scanning calorimetry (Gruber, H.J. and Low, P.S., Biochim. Biophys. Acta, preceding article). Now the data are interpreted by a model in which the effects of amphiphile structure upon buffer-membrane partitioning are well separated from the dependence of the intrinsic potencies of membrane-bound amphiphiles upon amphiphile structure. The buffer-membrane partitioning situation was demonstrated to regularly change between extremes within a series of homologous amphiphiles, i.e. from a negligible to a predominant fraction of total amphiphile in the sample residing in the membrane. Based upon this demonstration a large number of reports on the chain length dependence of apparent potency could be reinterpreted in terms of chain length profiles of intrinsic potency, allowing for a comparison of the responses of various membrane proteins to homologous series of amphiphiles. The response patterns for chain length variation could be divided into three distinct classes: the intrinsic potency (i) can be independent of chain length over a very wide range of length, (ii) it can be rather independent up to a critical length where a sudden cut-off in potency occurs, or (iii) it can drop monotonically over a wide range of chain length. The intrinsic potency values of saturated fatty acids in destabilizing the anion exchanger were interpreted by very simple assumptions: only direct interactions between amphiphiles and target proteins and a simple amphiphile partition equilibrium between a pool of equivalent low affinity sites on the protein and the bulk lipid matrix. The observed monotonic decay of the intrinsic potency of saturated fatty acids with increasing chain length from C8 to C20 was translated into a constant increment of free energy by which each additional CH2 favors the transfer away from sites on the protein towards the bulk lipid matrix. Arguments were presented suggesting that the direct interaction between amphiphiles and target protein is completely nonspecific for alkyl chain length while the residual specificity for shorter over longer amphiphiles is due to the higher tendency of longer chains to preferentially bind in the bulk lipid matrix. Thus a completely new role of the lipid as a competitor, rather than a mediator, was postulated.

Cell Membrane↗

PubMed1982

Community and job satisfactions: an argument for reciprocal influence based on the principle of stimulus generalization.

The principle of stimulus generalization provided the underlying argument for a test of hypotheses regarding the association of community and job satisfactions and a critique of related theory and research. Two-stage least squares (2SLS) analysis made possible the examination of reciprocal causation, a notion inherent in the theoretical argument. Data were obtained from 276 employees of a Western U.S. coal mine as part of a work attitudes survey. The 2SLS analysis indicated a significant impact of community satisfaction on job satisfaction and an effect of borderline significance of job on community satisfaction. Theory-based correlational comparisons were made on groups of employees residing in four distinct communities, high and low tenure groups, males and females, and different levels in the mine's hierarchy. The pattern of correlations was generally consistent with predictions, but significance tests for differences yielded equivocal support. When considered in the context of previous studies, the data upheld a reciprocal causal model and the explanatory principle of stimulus generalization for understanding the relation of community and job satisfactions. Sample characteristics necessitate cautious interpretation and the model per se might best be viewed as a heuristic framework for more definitive research.

Adult↗