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At least 199 records · Page 11Linked to original sources
PubMed1987

ISMOD: an all-subsets regression program for generalized linear models. II. Program guide and examples.

This paper describes a system written to carry out regression analyses under certain generalized linear models that are widely used in biomedical research. These include continuous response models such as the Weibull, log logistic, log normal and Cox proportional hazards models used in survival analysis, and also discrete Poisson, binomial and multinomial response regression models. The system fits models, generates residuals and other diagnostic output, and also has an all-subsets regression feature. This paper describes the ISMOD system and presents examples of its application; Part I describes the models implemented and gives statistical background.

Biometry↗
PubMed1994

A quantitative approach to modeling mammalian myelinated nerve fibers for electrical prosthesis design.

This paper presents an upgraded cable model of mammalian myelinated nerve fibers in an extracellularly applied field. The kinetics of the nodes is based upon voltage clamp data in rat motor fibers at 37 degrees C, while the resting membrane potential is computed with the Goldman equation. The resulting spike shape, conduction velocity, strength/duration behavior, and absolute and relative refractory period are in good quantitative agreement with published experimental data in mammals at normal body temperature and at 20 degrees C. Results at intermediate temperatures however, suggest that the widely used concept of a constant Q10 for the rate constants is invalid. In addition, the model generates realistic abortive spikes towards the end of the absolute refractory period and it can describe the consequences of repetitive firing. The results stress the advantages of a multiple nonlinear node model even if only time aspects of nerve behavior are under study. It turned out, that the model presented here describes in vivo neural properties relevant for electrical prosthesis design better than previous models in literature.

Animals↗
PubMed1981

Effect of ischemia on quantification of local cerebral glucose metabolic rate in man.

The model for quantifying local cerebral glucose metabolic rates originally developed by Sokoloff et al. and modified by Phelps. Huang and co-workers was applied to humans with cerebral ischemia (i.e., stroke). Rate constants for fluorodeoxyglucose were measured in ischemic and nonischemic regions with position computed tomography. Using measured rate constants for ischemia, the model generate more accurate estimates of local cerebral glucose metabolism as compared to the use constants from normal young adults, because the local metabolic rate is significantly underestimated, and temporal instability of the model is observed when normal values are applied to ischemic regions. A method was also developed to test the stability of the local lumped constant. The estimates of the lumped constant showed no or only small variations between ischemic and nonischemic types. Thus, errors introduced in the calculated local cerebral glucose metabolism by inappropriate rate constants appear to be more significant than those caused by any potential change in the lumped constant in ischemia.

Aged↗
PubMed1995

Graph-theoretic approach to RNA modeling using comparative data.

We have examined the utility of a graph-theoretic algorithm for building comparative RNA models. The method uses a maximum weighted matching algorithm to find the optimal set of basepairs given the mutual information for all pairs of alignment positions. In all cases examined, the technique generated models similar to those based on conventional comparative analysis. Any set of pairwise interactions can be suggested including pseudoknots. Here we describe the details of the method and demonstrate its implementation on tRNA where many secondary and tertiary base-pairs are accurately predicted. We also examine the usefulness of the method for the identification of shared structural features in families of RNAs isolated by artificial selection methods such as SELEX.

Algorithms↗
PubMed1982

Reactivation of intestinal epithelial cell brush border motility: ATP-dependent contraction via a terminal web contractile ring.

Various models have been put forward suggesting ways in which brush borders from intestinal epithelial cells may be motile. Experiments documenting putative brush border motility have been performed on isolated brush borders and have generated models suggesting microvillar retraction or microvillar rootlet interactions. The reported Ca++ ATP-induced retraction of microvilli has been shown, instead, to be microvillar dissolution in response to Ca++ and not active brush border motility. I report here studies on the reactivation of motility in intact sheets of isolated intestinal epithelium. Whole epithelial sheets were glycerinated, which leaves the brush border and intercellular junctions intact, and then treated with ATP, PPi, ITP, ADP, GTP, or delta S-ATP. Analysis by video enhanced differential interference-contrast microscopy and thin-section transmission electron microscopy reveals contractions in the terminal web region causing microvilli to be fanned apart in response to ATP and delta S-ATP but not in response to ADP, PPi, ITP, or GTP. Electron microscopy reveals that the contractions occur at the level of the intermediate junction in a circumferential constriction which can pull cells completely apart. This constriction occurs in a location occupied by an actin-containing circumferential band of filaments, as demonstrated by S-1 binding, which completely encircles the terminal web at the level of the intermediate junction. Upon contraction, this band becomes denser and thicker. Since myosin, alpha-actinin and tropomyosin, in addition to actin, have been localized to this region of the terminal web, it is proposed that the intestinal epithelial cell can be motile via a circumferential terminal web contractile ring analogous to the contractile ring of dividing cells.

Adenosine Triphosphate↗
PubMed1991

Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment.

A new principle of sensorimotor control of legged locomotion in an unpredictable environment is proposed on the basis of neurophysiological knowledge and a theory of nonlinear dynamics. Stable and flexible locomotion is realized as a global limit cycle generated by a global entrainment between the rhythmic activities of a nervous system composed of coupled neural oscillators and the rhythmic movements of a musculo-skeletal system including interaction with its environment. Coordinated movements are generated not by slaving to an explicit representation of the precise trajectories of the movement of each part but by dynamic interactions among the nervous system, the musculo-skeletal system and the environment. The performance of a bipedal model based on the above principle was investigated by computer simulation. Walking movements stable to mechanical perturbations and to environmental changes were obtained. Moreover, the model generated not only the walking movement but also the running movement by changing a single parameter nonspecific to the movement. The transitions between the gait patterns occurred with hysteresis.

Animals↗
PubMed1988

The determination of equilibrium constants for heterogeneous macromolecular interactions. Systems forming 2:1 complexes.

In developing a method for analyzing the heterogeneous association nA + mB in equilibrium AnBm, we have specifically investigated the case of n = 2, m = 1 for both the specific case of no appreciable intermediates and the more general case allowing intermediates. Computer-simulated three-dimensional surfaces of the 2:1 model generated from total concentrations of species A and B and the resulting weight-average molecular weights were analyzed with a Gauss-Newton nonlinear least-squares minimization routine. The surfaces generated included normalized random error of varying standard deviations imposed upon both the concentrations and weight-average molecular weights. For comparison purposes, these surfaces were analyzed not only by using the correct 2:1 model, but also by an incorrect (1:1) model and by the other (incorrect) 2:1 model. Except for those situations where the 'experimental' noise was consistently higher than the concentration of one of the species, correct K values were obtained and the correct model was easily distinguished from the incorrect model. The computer routine similarly distinguished between data correctly described as 1:1 and the same data incorrectly analyzed as either 2:1 model. For those cases in which a microscopic Ki value predicts an association such that all species involved for that particular Ki are in appreciable amounts, the Ki value is returned correctly. Correct overall equilibrium constants are also converged upon as long as adequate amounts of A2B, B and A are present.

Kinetics↗
PubMed1993

Dynamic interaction between Leishmania infection in mice and Th1-type CD4+ T-cells: complexity in outcome without a requirement for Th2-type responses.

The interaction between Leishmania parasites and Th1 cells is investigated using a simple mathematical model of immunological responses and parasite population growth within the host. The model generates patterns of resistance and susceptibility to infection that mirror observed trends in experimental infections of mice and of humans exposed to infection in areas of endemic transmission. The heterogeneity in outcome predicted by the model can arise either through differences in the values of the parameters that characterize the genetic background of the host or as a consequence of differences in the size of the infecting inoculum of the parasite. Detailed analyses of equilibrium states and of the time course of infection within a host suggest that a limitation in the availability of precursor T-cells, as a consequence of high levels of recruitment into the activated pool, may play a significant role in the progression of infection in susceptible hosts. A brief discussion is presented of the implications of model prediction for therapeutic intervention.

Animals↗
PubMed1981

Interpretation of current-voltage relationships for "active" ion transport systems: I. Steady-state reaction-kinetic analysis of class-I mechanisms.

This paper develops a simple reaction-kinetic model to describe electrogenic pumping and co- (or counter-) transport of ions. It uses the standard steady-state approach for cyclic enzyme- or carrier-mediated transport, but does not assume rate-limitation by any particular reaction step. Voltage-dependence is introduced, after the suggestion of Läuger and Stark (Biochim. Biophys. Acta 211:458-466, 1970), via a symmetric Eyring barrier, in which the charge-transit reaction constants are written as k12 = ko12 exp(zF delta psi/2RT) and k21 = ko21 exp(-zF delta psi/2RT). For interpretation of current-voltage relationships, all voltage-independent reaction steps are lumped together, so the model in its simplest form can be described as a pseudo-2-state model. It is characterized by the two voltage-dependent reaction constants, two lumped voltage-independent reaction constants (k12, k21), and two reserve factors (ri, ro) which formally take account of carrier states that are indistinguishable in the current-voltage (I-V) analysis. The model generates a wide range of I-V relationships, depending on the relative magnitudes of the four reaction constants, sufficient to describe essentially all I-V datas now available on "active" ion-transport systems. Algebraic and numerical analysis of the reserve factors, by means of expanded pseudo-3-, 4-, and 5-state models, shows them to be bounded and not large for most combinations of reaction constants in the lumped pathway. The most important exception to this rule occurs when carrier decharging immediately follows charge transit of the membrane and is very fast relative to other constituent voltage-independent reactions. Such a circumstance generates kinetic equivalence of chemical and electrical gradients, thus providing a consistent definition of ion-motive forces (e.g., proton-motive force, PMF). With appropriate restrictions, it also yields both linear and log-linear relationships between net transport velocity and either membrane potential or PMF. The model thus accommodates many known properties of proton-transport systems, particularly as observed in "chemiosmotic" or energy-coupling membranes.

Animals↗
PubMed1991

The how and why of what went where in apparent motion: modeling solutions to the motion correspondence problem.

A model that is capable of maintaining the identities of individuated elements as they move is described. It solves a particular problem of underdetermination, the motion correspondence problem, by simultaneously applying 3 constraints: the nearest neighbor principle, the relative velocity principle, and the element integrity principle. The model generates the same correspondence solutions as does the human visual system for a variety of displays, and many of its properties are consistent with what is known about the physiological mechanisms underlying human motion perception. The model can also be viewed as a proposal of how the identities of attentional tags are maintained by visual cognition, and thus it can be differentiated from a system that serves merely to detect movement.

Attention↗
PubMed1986

Evaluation of predictive formulae for determining metabolic rate during cold water immersion.

Five models predicting shivering thermogenesis on the basis of steady state skin and core temperature were evaluated: Hayward et al., Stolwijk and Hardy,; Nadel et al.,; Timbal et al., and Brown and Brengelmann, using the empirical data derived from a cold water immersion study by Morrison et al. A residual analysis indicated that all models generated substantial errors of prediction. The best overall predictors were expressions suggested by Hayward et al., while the predictive equation of Nadel et al. ranked second. Derivation of personal coefficients significantly improved the prediction of all models and a subsequent modification of the standard models, adding temperature derivative terms, further reduced the magnitude of the error. An analysis of the residuals indicated that peripheral and core temperatures should be weighted according to the characteristics of thermosensitive neural structures in these regions.

Body Temperature Regulation↗
PubMed2026

Looked but didn't see: inattentional blindness and yes-bias confabulation in vision-language models.

Previous work showed that many participants fail to notice a gorilla in a video of people playing basketball. Another study found that 83% of trained radiologists failed to report a gorilla figure inserted into a chest CT nodule-search task, even though eye-tracking revealed that most observers had foveated the figure. We ask whether a similar phenomenon exists in contemporary vision-language models (VLMs). We find that (i) VLMs are capable of spotting the gorilla in both still-frame images and videos of lung CT scans; (ii) models display inattentional blindness, which varies according to model generation and type of stimulus presented; (iii) Gemini-3.1-Pro outperforms most other flagship and open-weight VLMs at identifying the presence or absence of the gorilla. We additionally ran a segmentation experiment utilizing two different model classes: a generalist (SAM 3), which found the gorilla but produced little to no results for anatomy-based prompts; a medical specialist (BiomedParse), which produced more promising anatomy-based results but flagged "gorilla" on gorilla-free control videos on 82% of frames. The behavioral signature of inattentional blindness reproduces in VLMs, but a unique confabulation failure mode means that any "did the model see X" claim requires signal-detection analysis with a matched-control false-alarm baseline.

Journal Article↗
PubMed1986

A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing.

A model is presented outlining the molecular and cellular events that occur during the early stages of the wound healing process. The underlying theme is that there is a specific binding interaction between fibrin, the major clot protein, and hyaluronic acid (HA), a constituent of the wound extracellular matrix. This binding interaction, which could also be stabilized by other cross-linking components, provides the driving force to organize a three-dimensional HA matrix attached to and interdigitated with the initial fibrin matrix. The HA-fibrin matrix plays a major role in the subsequent tissue reconstruction processes. We suggest that HA and fibrin have both structural and regulatory functions at different times during the wound healing process. The concentration of HA in blood and in the initial clot is very low. This is consistent with the proposed interaction between HA and fibrin(ogen), which could interfere with either fibrinogen activation or fibrin assembly and cross-linking. We propose that an activator (e.g. derived from a plasma precursor, platelets or surrounding cells) is produced during the clotting reaction and then stimulates one or more blood cell types to synthesize and secrete HA into the fibrin matrix of the clot. We predict that HA controls the stability of the matrix by regulating the degradation of fibrin. The new HA-fibrin matrix increases or stabilizes the volume and porosity of the clot and then serves as a physical support, a scaffold through which cells trapped in the clot or cells infiltrating from the peripheral edge of the wound can migrate. The HA-fibrin matrix also actively stimulates or induces cell motility and activates and regulates many functions of blood cells, which are involved in the inflammatory response, including phagocytosis and chemotaxis. The secondary HA-fibrin matrix itself is then modified as cells continue to migrate into the wound, secreting hyaluronidase and plasminogen activator to degrade the HA and fibrin. At the same time these cells secrete collagen and glycosaminoglycans to make a more differentiated matrix. The degradation products derived from both fibrin and HA are, in turn, important regulatory molecules which control cellular functions involved in the inflammatory response and new blood vessel formation in the healing wound. The proposed model generates a number of testable experimental predictions.

Blood Coagulation↗
PubMed1990

Nonuniform radiolabeling of VLDL apolipoprotein B: implications for the analysis of studies of the kinetics of the metabolism of lipoproteins containing apolipoprotein B.

Radiolabeling of whole lipoproteins or individual apolipoproteins has been an essential tool for the determination of the kinetics of apolipoprotein metabolism in vivo. Mathematical analysis of specific radioactivity (SA) or total radioactivity data has demonstrated the existence of significant complexity in the plasma decay curves of several apolipoproteins. Results obtained during development of methods to study the metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) subclasses isolated according to flotation (Sf) rates from whole radiolabeled (d less than 1.006 g/ml) VLDL suggested nonuniform radiolabeling of apoB in the three Sf subclasses being studied. We therefore determined apoB SA in VLDL Sf subclasses in ten hypertriglyceridemic and five normal subjects. After radioiodination of apoB in whole VLDL, different apoB SA were found in Sf 400-100, Sf 100-60, and Sf 60-20. The pattern of labeling was quite variable among subjects. On average, apoB SA in the VLDL tracer was greatest in Sf 400-100, and least in Sf 60-20. Nonuniform labeling could also be demonstrated in five studies in which samples were obtained 3 min after intravenous injection of the tracer into subjects with a wide range of plasma triglycerides. Nonuniform labeling of apoB in whole VLDL was also demonstrated in two of the subjects by isolating subclasses of their VLDL that did not bind to an anti-apolipoprotein E immunoaffinity column. These results indicate that the usual assumption of homogeneous labeling of apoB may be erroneous. We have derived a simple mathematical formula to study the consequences of this assumption in estimating kinetic parameters. It is shown that an erroneous assumption of homogeneous tracer labeling may significantly underestimate or overestimate the true production rate, even in a simple two-pool model. Identification of labeling characteristics and incorporation of this information into the mathematical analysis of the plasma radioactivity data can improve the accuracy of the analysis as well as the sensitivity of compartmental models generated by such data.

Apolipoproteins B↗
PubMed1995

Magnetic backprojection imaging of the vascular lumen.

Current injected into a phantom model generated a magnetic field which was distorted above a simulated atherosclerotic lesion. The output of a Hall effect magnetic sensor was used in a backprojection to reconstruct the centroid of the simulated blood flow and thus localize the modeled atherosclerotic plaque region.

Arteries↗
PubMed1994

Prediction of runoff transport of fallout 90Sr.

A model is described for the prediction of runoff transfer of fallout 90Sr without recourse to long-term measurements. The values of model parameters can be readily established from few field measurements of the solid/solution partitioning of 90Sr and a natural, atmospherically delivered radionuclide such as 210Pb, and the usually well documented fallout and hydrologic data. The model-generated profiles of 90Sr for two major Canadian watersheds compare favorably to those established through long-term monitoring of receiving waters.

Forecasting↗
PubMed1970

A physical model for muscular behavior.

A model for muscular behavior has been developed by a generalization of the laws governing the viscoelastic behavior of polymeric materials. The model simulates events thought to take place during stretch, loading, and stimulation of muscle, whether smooth or striated. The equations of motion were solved with an analogue computer for several types of perturbation, and stress, strain, and strainrate curves were generated. Model parameters were selected by fitting experimental stress-relaxation data. The resulting equations predicted the frequency dependence of dynamic modulus and phase angle within experimental error. With appropriate boundary conditions and suitable values for model parameters, the computed results also closely resembled experimental curves of contraction velocity vs. time, isometric tension development vs. time, force-velocity curves, and temperature-tension relationships. These results call attention to the relationship between the behavior of various kinds of muscle and open the way for quantifying muscular behavior in general.

Animals↗
PubMed1985

Intellectual development within transracial adoptive families: retesting the confluence model.

The confluence model of intellectual development was estimated for a within-family sample of 321 children from 101 transracial adoptive families. Mental ages of the children and their parents, as well as birth or adoption intervals, were used in a nonlinear least-squares estimation procedure to obtain children's predicted mental ages. Contrary to an earlier report using these data, the confluence model performed quite well, accounting for up to 50% of the variance in mental age. When the relationship between chronological and mental age was taken into account, the predictive power of the model was reduced but not eliminated. The confluence model was also fitted separately to various subsamples. The model generated a good fit to the data from both biological and adopted children and fit the data from early-adopted children much better than the data from later-adopted children. Both findings were taken as evidence that the confluence model provides an environmental account of intellectual development within the family.

Adolescent↗