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PubMed2005

Mixed immunotherapy and chemotherapy of tumors: modeling, applications and biological interpretations.

We develop and analyze a mathematical model, in the form of a system of ordinary differential equations (ODEs), governing cancer growth on a cell population level with combination immune, vaccine and chemotherapy treatments. We characterize the ODE system dynamics by locating equilibrium points, determining stability properties, performing a bifurcation analysis, and identifying basins of attraction. These system characteristics are useful not only to gain a broad understanding of the specific system dynamics, but also to help guide the development of combination therapies. Numerical simulations of mixed chemo-immuno and vaccine therapy using both mouse and human parameters are presented. We illustrate situations for which neither chemotherapy nor immunotherapy alone are sufficient to control tumor growth, but in combination the therapies are able to eliminate the entire tumor.

Animals↗
PubMed2003

Interpretation of fluorescence decays using a power-like model.

A power-like decay function, characterized by the mean excited-state lifetime and relative variance of lifetime fluctuation around the mean value, was applied in analysis of fluorescence decays measured with the aid of time-correlated single photon counting. We have examined the fluorescence decay, in neutral aqueous medium, of tyrosine (L-tyrosine and N-acetyl-L-tyrosinamide), and of the tyrosine residues in a tryptophan-free protein, the enzyme purine nucleoside phosphorylase from Escherichia coli in a complex with formycin A (an inhibitor), and orthophosphate (a co-substrate). Tryptophan fluorescence decay was examined in neutral aqueous medium for L-tryptophan, N-acetyl-L-tryptophanamide, and for two tryptophan residues in horse liver alcohol dehydrogenase. To detect solvent effect, fluorescence decay of Nz-acetyl-L-tryptophanamide in aqueous medium was compared with that in dioxan. Hitherto, complex fluorescence decays have usually been analyzed with the aid of a multiexponential model, but interpretation of the individual exponential terms (i.e., pre-exponential amplitudes and fluorescence lifetimes), has not been adequately characterized. In such cases the intensity decays were also analyzed in terms of the lifetime distribution as a consequence of an interaction of fluorophore with environment. We show that the power-like decay function, which can be directly obtained from the gamma distribution of fluorescence lifetimes, is simpler and provides good fits to highly complex fluorescence decays as well as to a purely single-exponential decay. Possible interpretation of the power-like model is discussed.

Computer Simulation↗
PubMed2002

Automatic buffer capacity model building for advanced interpretation of titration curves.

An automatic buffer capacity model building algorithm was developed. The objective of this algorithm is to characterize multiple buffer systems from experimental titration curves. Starting from a simple mathematical model that incorporates the available prior knowledge on the buffer system, the model is sequentially extended by incorporating additional monoprotic buffer equations. To select the most appropriate model from the resulting set of automatically built models, a model structure selection technique was constructed from existing methods.

Algorithms↗
PubMed2001

Shape model for the molecular interpretation of the flexoelectric effect.

A mean-field model for the flexoelectric polarization in nematics is presented, based on a continuous description of director deformations coupled to the molecular degrees of freedom via surface interactions. In such a framework, a consistent picture of the flexoelectric effect is obtained, including both dipolar and quadrupolar contributions, with a realistic account of the molecular characteristics of shape and charge distribution. The method is aimed at establishing a quantitative link between chemical structure and flexoelectric response. It provides numerical estimates of the effect and its temperature dependence and allows the recognition of the relevant molecular features for its emergence. Application to some representative systems, comprising mesogenic molecules and photoisomerizable dopants, is considered; it is shown that simple interpretative schemes can be misleading and a comparison with experimental data is reported.

Journal Article↗
PubMed1992

Interpretation of linear regression models that include transformations or interaction terms.

In linear regression analyses, we must often transform the dependent variable to meet the statistical assumptions of normality, variance stability, or linearity. Transformations, however, can complicate the interpretation of results because they change the scale on which the dependent variable is measured. In this setting, the inclusion of product terms or the transformation of some independent (or predictor) variables may further complicate interpretation. In this article, we present some interpretations of linear models that include transformations or product terms. We illustrate these interpretations using regression analyses designed to study determinants of serum testosterone levels. These examples show how one can present results using simple measures, such as medians, and interpret regression parameters.

Epidemiologic Methods↗
PubMedDate not supplied

[Dynamic psychiatric interpretation of a disease model of trichotillomania].

Every patient's "communal existence" allows to interpret deviations of behavior such as trichotillomania as a disturbance of interaction. When the child begins to wangle out of the dual union between mother and child it needs ways to delimitate itself, If the mother does not concede this demarcation (f. i. because she does not want to release the child from the symbiosis and therefore is "overprotecting") the child often becomes a victim of despair and, later on, of perplexity. At last it uses the own body as "Vis-a-vis". The accumulated aggressiveness is then worked off motorically by means of trichotillomania. In this way despair and perplexity in the field of interaction are passed on so to speak "atmospherically" to the mother, who in turn, having arranged treatment, transfers them on to the doctor. It is discussed how the area of irritation can be dissolved.

Aggression↗
PubMed1995

Catch in the primary spines of the sea urchin Eucidaris tribuloides: a brief review and a new interpretation.

Previous models of reversible catch in echinoid spines, as a property of muscle or of collagen, are briefly reviewed and discussed. This brief review offers a new interpretation of catch in primary spines of Eucidaris tribuloides, viewing the collagen and small muscles of the catch ligament working together as a variable-length tendon. In the model presented, changes in ligament length when out of catch are accommodated by sliding of discontinuous, interdigitating and cross-link-stabilized columns of collagen fibrils, the muscle layer external to the ligament effecting spine movement. Catch is viewed as a consequence of contraction of small muscles inserted on the collagen columns within the ligament. Ligament shortening tightens the profuse (ca. 30,000/mm2) and highly ordered collagen insertion loops within the stereoms of the spine base and test, and catch results from the multiplicative effect of these friction sites in series. New data are presented on novel structural cross-links between collagen fibrils. The cross-links stabilize the ligament columns. The central ligament in Eucidaris plays a purely passive mechanical role in maintaining the alignment of the spine-test articulation. It contains no muscle and neither contracts nor undergoes catch; its insertions are simple, unlike the complex stereom insertions of the main ligament.

Animals↗
PubMed1996

Interpreting a medium-resolution model of tubulin: comparison of zinc-sheet and microtubule structure.

We previously used electron crystallography of zinc-induced two-dimensional crystalline sheets of tubulin to construct a medium-resolution three dimensional (3-D) reconstruction (at 6.5 A) of this protein. Here we present an improved model, and extend the interpretation to correlate it to microtubule structure. Secondary sequence predictions and projection density maps of subtilisin-cleaved tubulin provide information on the location of the C-terminal portion, which has been suggested to be involved in the binding of microtubule-associated proteins. The zinc-sheet tubulin model is compared to microtubules in two ways; comparison of electron diffraction from the zinc-sheets to electron diffraction from microtubules, and by docking the zinc-sheet protofilament 3-D model into a helical reconstruction from ice-embedded microtubules. By correlating the zinc-sheet protofilament to a reconstruction of axonemal protofilaments, we assigned polarity to the protofilament in our model. The polarity assignment together with our model for dimer boundaries and the assignment of alpha- and beta-monomers in our reconstruction, provides a microtubule model where the alpha-monomer crowns the plus- (or fast-growing) end of the microtubule and contact is made in the centrosome with gamma-tubulin via the beta-monomer.

Amino Acid Sequence↗
PubMed2002

An approach to the interpretation of backpropagation neural network models in QSAR studies.

An approach to the interpretation of backpropagation neural network models for quantitative structure-activity and structure-property relationships (QSAR/QSPR) studies is proposed. The method is based on analyzing the first and second moments of distribution of the values of the first and the second partial derivatives of neural network outputs with respect to inputs calculated at data points. The use of such statistics makes it possible not only to obtain actually the same characteristics as for the case of traditional "interpretable" statistical methods, such as the linear regression analysis, but also to reveal important additional information regarding the non-linear character of QSAR/QSPR relationships. The approach is illustrated by an example of interpreting a backpropagation neural network model for predicting position of the long-wave absorption band of cyane dyes.

Adsorption↗
PubMedDate not supplied

Interpreter services in pediatric nursing.

A critical part of every encounter between a pediatric nurse and a patient is obtaining accurate patient information. Unique obstacles are encountered when patients and their families have little or no understanding of the English language. Federal and state laws require health care systems that receive governmental funds to provide full language access to services. Both legal and ethical issues can arise when caring for non-English-speaking patients. Often, obtaining accurate patient information and a fully informed consent cannot be done without the use of an interpreter. The interpreter informs the family of all the risks and benefits of a specific avenue of care. When inappropriate interpreter services are used, such as when children in the family or other family members act as interpreters, concerns about accuracy, confidentiality, cultural congruency, and other issues may arise. The purpose of this article is to: (a) explore principles related to the use of medical interpreters, (b) examine different models of interpreter services, and (c) identify available resources to assist providers in accessing interpreter services (e.g., books, online resources, articles, and videos). The case study format will be used to illustrate key points.

Attitude to Health↗
PubMed1981

The random transition model of the cell cycle. A critical review.

The random transition model of the cell cycle has received much attention in recent years in attempts to describe and explain variations in cell cycle times. In this review we suggest statistical procedures for fitting the model to experimental data in place of the invalid techniques currently used. However, we also argue that there have been misconceptions about criteria for quality of fit of the model, and consequent biological interpretations. Other models fit just as well, and the analyses we describe do not provide evidence for any particular biological mechanism.

Animals↗
PubMed1993

A diffusion model of early visual search: theoretical analysis and experimental results.

Meinecke (1989, Exp. 1, cond. HO) showed that the detectability of a visual target embedded in a linear noise array decreases with increasing retinal eccentricity, while the reaction time (RT) of the hits increases. One of the most interesting features of her results was that the RT of the correct rejections is consistently larger than the RT for signals presented near the fovea. This finding suggests that initially visual attention is concentrated near the fixation point and then diffuses across the stimulus array to perform a serial, exhaustive search. We present a diffusion model of early visual-search processes that quantitatively describes this evolution of attention in time and space; in contrast to most previous conceptions, it is based on a genuine relation between the spatial and temporal dimensions of the search processes performed. The model predicts quantitatively both detection performance and RT. We conducted an experiment similar to that of Meinecke (1989), but with an additional variation of the presentation time. All the main features of the 189 predictions could be explained by the model. The interpretation of the four model's parameters is discussed in some detail and compared with previous estimates of the microscopic search speed derived from alternative models. Finally, we consider some possible modifications related to results of Kehrer (1987, 1989), and some generalizations to multi target detection and two-dimensional stimulus arrays.

Adult↗
PubMed2004

Refining the measurement of rate constants in the BIAcore.

When estimating rate constants using the BIAcore surface plasmon resonance (SPR) biosensor, one must have an accurate mathematical model to interpret sensogram data. Several models of differing complexity are discussed, including the effective rate constant (ERC) approach. This model can be shown formally to be good within O(Da) in the limit of small Damköhler number Da, which is the ratio of the reaction rate to the rate of transport to the surface. Numerical results are presented that show that except for very slow reactions, parameter estimates from the ERC model are very close to those estimated using a more complicated model. The BIAcore measures the behavior of an evanescent wave whose signal strength decays as it penetrates into the device. It is shown that this decay does not appreciably affect the sensogram readout at low Da, but at moderate Da can lead to situations where two vastly different rate constants can produce the same short-time sensogram data.

Algorithms↗
PubMed1990

The use of loglinear model to evaluate factors associated with sero-prevalence of Campylobacter fetus in dairy cattle.

Campylobacter fetus is one of the leading infections causing bovine infertility and abortion. In a cross-sectional study, the associations of parity, herd, serological status against Leptospira hardjo and Haemophilus somnus with the sero-prevalence of Campylobacter fetus in dairy cattle were evaluated. Four hundred dairy cows from three herds were included in the study. Blood samples from the cows were collected in December 1986. An enzyme-linked immunosorbant assay (ELISA) was used to determine positive or negative status of cows against Campylobacter fetus , Haemophilus somnus and Leptospira hardjo antigens. Loglinear analysis was used to describe the relationship of four categorical variables with the sero-prevalence of Campylobacter fetus . The final loglinear model was interpreted as a logit model. The final loglinear model included a three-way interaction among Campylobacter fetus , Leptospira hardjo and herd and a two-way interaction between Campylobacter fetus and parity. The adjusted odds of being a positive Campylobacter fetus reading were highest for cows with parity >6 (e.g. 27.8, 95% confidence interval (CI) = 12.9, 60.1); it was next highest for cows in parity <4 (e.g. 18.0, 95% CI = 13.5, 24.2); and it was lowest for cows in parity 4 to 6 (e.g. 13.3, 95% CI 7.3, 24.4). The herd management practice that was associated with the carrier state in early and late parities is identified in the study, and the biological implication of a three-way interaction among Campylobacter fetus , Leptospira hardjo and herd are discussed.

Journal Article↗
PubMed2003

Prediction of the effect of mobile-phase salt type on protein retention and selectivity in anion exchange systems.

This study examines the effect of different salt types on protein retention and selectivity in anion exchange systems. Particularly, linear retention data for various proteins were obtained on two structurally different anion exchange stationary-phase materials in the presence of three salts with different counterions. The data indicated that the effects are, for the most part, nonspecific, although various specific effects could also be observed. Quantitative structure retention relationship (QSRR) models based on support vector machine feature selection and regression models were developed using the experimental chromatographic data in conjunction with various molecular descriptors computed from protein crystal structure geometries. Star plots for each descriptor used in the final model were generated to aid in interpretation. The resulting QSRR models were predictive, with cross-validated r2 values of 0.9445, 0.9676, and 0.8897 for Source 15Q and 0.9561, 0.9876, and 0.9760 for Q Sepharose resins in the presence of three different salts. The predictive power of these models was validated using a set of test proteins that were not used in the generation of these models. Interpretation of the models revealed that particular trends for proteins and salts could be captured using QSRR techniques.

Algorithms↗
PubMed1998

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Animals↗
PubMed2001

Comparative two- and three-dimensional finite element modelling techniques for tibial fractures.

Often the choice of a two-dimensional modelling approach over a three-dimensional approach is made on the basis of available resources, and not on task appropriateness. In the case of simulating the mechanical behaviour of irregular anatomical structures in biomedical engineering, the authenticity of two-dimensional model behaviour and the interpretation of model solutions is of particular concern since little comparable two-dimensional and three-dimensional data have been published. As part of a research programme, a comparison was made between two-dimensional and three-dimensional finite element models (FEMs) that examine the stress-strain environment of a clinical bone fracture and callus. In comparison with the three-dimensional model, the two-dimensional model substantially underestimated peak compressive principal stresses in the callus tissue and peak equivalent strains. This was a consequence of geometrical and structural asymmetry in a plane perpendicular to the two-dimensional model. However, the two-dimensional model predicted similar patterns of stress and strain distribution to the corresponding mid-longitudinal plane of the three-dimensional model, and underestimates of peak stress and strain were much reduced. This confirmed that despite the irregular geometry and structure of the subject, the two-dimensional model provided a valid mechanical simulation in the plane of the fracture that it represented.

Biomechanical Phenomena↗