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At least 685 records · Page 38Linked to original sources
PubMed1988

Three-dimensional reconstruction of myocardial contrast perfusion from biplane cineangiograms by means of linear programming techniques.

The assessment of coronary flow reserve from the instantaneous distribution of the contrast agent within the coronary vessels and myocardial muscle at the control state and at maximal flow has been limited by the superimposition of myocardial regions of interest in the two-dimensional images. To overcome these limitations, we are in the process of developing a three-dimensional (3D) reconstruction technique to compute the contrast distribution in cross sections of the myocardial muscle from two orthogonal cineangiograms. To limit the number of feasible solutions in the 3D-reconstruction space, the 3D-geometry of the endo- and epicardial boundaries of the myocardium must be determined. For the geometric reconstruction of the epicardium, the centerlines of the left coronary arterial tree are manually or automatically traced in the biplane views. Next, the bifurcations are detected automatically and matched in these two views, allowing a 3D-representation of the coronary tree. Finally, the circumference of the left ventricular myocardium in a selected cross section can be computed from the intersection points of this cross section with the 3D coronary tree using B-splines. For the geometric reconstruction of the left ventricular cavity, we envision to apply the elliptical approximation technique using the LV boundaries defined in the two orthogonal views, or by applying more complex 3D-reconstruction techniques including densitometry. The actual 3D-reconstruction of the contrast distribution in the myocardium is based on a linear programming technique (Transportation model) using cost coefficient matrices. Such a cost coefficient matrix must contain a maximum amount of a priori information, provided by a computer generated model and updated with actual data from the angiographic views. We have only begun to solve this complex problem. However, based on our first experimental results we expect that the linear programming approach with advanced cost coefficient matrices and computed model will lead to acceptable solutions in the 3D-reconstruction of the myocardial contrast distribution from biplane cineangiograms.

Cineangiography↗
PubMedDate not supplied

Lumped model of terminal aortic impedance in the dog.

The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9 +/- 5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance, Rp, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C). Rp was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents.

Animals↗
PubMedDate not supplied

Validation tools for variable subset regression.

Variable selection is applied frequently in QSAR research. Since the selection process influences the characteristics of the finally chosen model, thorough validation of the selection technique is very important. Here, a validation protocol is presented briefly and two of the tools which are part of this protocol are introduced in more detail. The first tool, which is based on permutation testing, allows to assess the inflation of internal figures of merit (such as the cross-validated prediction error). The other tool, based on noise addition, can be used to determine the complexity and with it the stability of models generated by variable selection. The obtained statistical information is important in deciding whether or not to trust the predictive abilities of a specific model. The graphical output of the validation tools is easily accessible and provides a reliable impression of model performance. Among others, the tools were employed to study the influence of leave-one-out and leave-multiple-out cross-validation on model characteristics. Here, it was confirmed that leave-multiple-out cross-validation yields more stable models. To study the performance of the entire validation protocol, it was applied to eight different QSAR data sets with default settings. In all cases internal and external model performance was good, indicating that the protocol serves its purpose quite well.

Quantitative Structure-Activity Relationship↗
PubMed2005

Feature detection using spikes: the greedy approach.

A goal of low-level neural processes is to build an efficient code extracting the relevant information from the sensory input. It is believed that this is implemented in cortical areas by elementary inferential computations dynamically extracting the most likely parameters corresponding to the sensory signal. We explore here a neuro-mimetic feed-forward model of the primary visual area (VI) solving this problem in the case where the signal may be described by a robust linear generative model. This model uses an over-complete dictionary of primitives which provides a distributed probabilistic representation of input features. Relying on an efficiency criterion, we derive an algorithm as an approximate solution which uses incremental greedy inference processes. This algorithm is similar to 'Matching Pursuit' and mimics the parallel architecture of neural computations. We propose here a simple implementation using a network of spiking integrate-and-fire neurons which communicate using lateral interactions. Numerical simulations show that this Sparse Spike Coding strategy provides an efficient model for representing visual data from a set of natural images. Even though it is simplistic, this transformation of spatial data into a spatio-temporal pattern of binary events provides an accurate description of some complex neural patterns observed in the spiking activity of biological neural networks.

Action Potentials↗
PubMed1990

Routes to chaos in a model of a bursting neuron.

Chaotic regimens have been observed experimentally in neurons as well as in deterministic neuronal models. The R15 bursting cell in the abdominal ganglion of Aplysia has been the subject of extensive mathematical modeling. Previously, the model of Plant and Kim has been shown to exhibit both bursting and beating modes of electrical activity. In this report, we demonstrate (a) that a chaotic regime exists between the bursting and beating modes of the model, and (b) that the model approaches chaos from both modes by a period doubling cascade. The bifurcation parameter employed is the external stimulus current. In addition to the period doubling observed in the model-generated trajectories, a period three "window" was observed, power spectra that demonstrate the approaches to chaos were generated, and the Lyaponov exponents and the fractal dimension of the chaotic attractors were calculated. Chaotic regimes have been observed in several similar models, which suggests that they are a general characteristic of cells that exhibit both bursting and beating modes.

Animals↗
PubMedDate not supplied

Chronic cardiac allograft rejection in a rat model disparate for one single class I MHC molecule is associated with indirect recognition by CD4(+) T cells.

T-cell mediated immune responses play a critical role in chronic allograft dysfunction. The complex nature of allograft rejection, particularly with respect to the vast repertoire of alloantigens and their mode of recognition by T cells, presents a major challenge for the design of well-controlled studies into the immunobiology of chronic rejection. The purpose of this study was to develop a rat model with restricted antigenic specificity that develops chronic rejection without any immunologic manipulation to study the T-cell response. PVG.1U allogeneic hearts disparate for one single class I antigen, RT.1A(u), were transplanted into PVG.R8 rat recipients. Grafts from PVG.R8 were used as syngeneic controls. Chronic rejection was studied by histological analysis of the grafted hearts at various time points posttransplantation (20-100 days). Donor specific alloreactive response was studied in a mixed lymphocyte reaction assay. All allografts survived more than 90 days and showed extensive evidence of chronic rejection, which was characterized by interstitial fibrosis, vasculitis, and occlusive myointimal thickening. Chronic rejection was evident by day 20 and most extensive by day 100 posttransplantation. In marked contrast, syngeneic grafts remained free of chronic lesions. Lymphocytes harvested from graft recipients showed a more vigorous proliferative response to allogeneic splenocytes as compared with that of lymphocytes from nai;ve animals. The proliferative response was primarily mediated by CD4(+) T cells recognizing the RT1.A(a) molecule via the indirect pathway. A single class I disparity in this model generates chronic rejection associated with potent CD4(+) T-cell responses induced by the indirect recognition pathway. The use of this antigenically restricted model may facilitate the design of well-controlled studies for the characterization of immune mechanisms responsible for chronic rejection.

Animals↗
PubMed1999

Application and comparison of two modelling techniques for hospital bed management.

The use of the bed occupancy management and planning system (BOMPS) and the Sorensen multi-phased bed model were used to assess the implications of a hospital expanding its emergency facility. BOMPS flow modelling generates resource utilisation data dependent on the best visual and statistical fit between mixed exponential equations and time of bed occupancy; the Sorensen model creates models based on probabilities and length of stay distributions. Both models identified the presence of two streams of flow. However, there were differences in the number of beds identified as being short and longer stay. The advantage of flow modelling is that it enables decision-makers to pre-test their decisions.

Australia↗
PubMed2000

Appropriate tissue- and cell-specific expression of a single copy human angiotensinogen transgene specifically targeted upstream of the HPRT locus by homologous recombination.

Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this transgenic mouse model is that the human angiotensinogen gene is inserted into the mouse genome as a single copy at a predefined locus and in a specific orientation-a process that can be repeated utilizing other variants of this gene. We establish the validity of this approach by showing that the hAGT(hprt) mice have normal tissue- and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels.

Angiotensinogen↗
PubMed2003

Impact of antimicrobial resistance on health outcomes in the out-patient treatment of adult community-acquired pneumonia: a probability model.

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations.

Adult↗
PubMed2006

Min-max hyperellipsoidal clustering for anomaly detection in network security.

A novel hyperellipsoidal clustering technique is presented for an intrusion-detection system in network security. Hyperellipsoidal clusters toward maximum intracluster similarity and minimum intercluster similarity are generated from training data sets. The novelty of the technique lies in the fact that the parameters needed to construct higher order data models in general multivariate Gaussian functions are incrementally derived from the data sets using accretive processes. The technique is implemented in a feedforward neural network that uses a Gaussian radial basis function as the model generator. An evaluation based on the inclusiveness and exclusiveness of samples with respect to specific criteria is applied to accretively learn the output clusters of the neural network. One significant advantage of this is its ability to detect individual anomaly types that are hard to detect with other anomaly-detection schemes. Applying this technique, several feature subsets of the tcptrace network-connection records that give above 95% detection at false-positive rates below 5% were identified.

Algorithms↗
PubMed1988

Estimation of intramyocardial pressure and coronary blood flow distribution.

To characterize the intramyocardial pressure (IMP) and coronary blood flow distribution in a stenosed coronary circulation, we compared four analog circuits for modeling coronary impedance. The resistor (R)-diode (D) model simulates vascular collapse, and the capacitor (C) simulates compliance effect. Identification of the best model and magnitudes of the endocardial and epicardial IMPs (IMPendo and IMPepi) was done retrospectively using data from studies in 28 anesthetized swine. Performance evaluation was based on comparison of model predicted vs. observed coronary distal pressure (DP) waveforms and endocardial-to-epicardial (endo-epi) flow ratios as determined by radiolabeled microspheres. The R-D-C model gave the best performance at IMPendo = 1.1 times left ventricular pressure (LVP), and IMPepi = 0.1.LVP + 15 mmHg; with good fit to DP (r = 0.98, slope of regression line = 1.0) and estimates of endo-epi flow ratio (r = 0.78, slope = 1.01, P less than 0.02, SEE = 0.21, n = 139). The R-D model gave comparable results even though capacitance was omitted. Although R-C and R models predicted distal coronary pressure well, they failed to predict endo-epi flow ratios (r less than 0.50). The R-D-C and R-D models were applied in seven prospective studies. Both models generated reasonable estimates of endo-epi flow distribution (r = 0.78, n = 50). Thus the R-D-C or R-D models of the stenosed coronary circulation can be used to provide reliable estimates of transmural blood flow distribution.

Animals↗
PubMed1991

A tissue pressure model for palpatory perception of the cranial rhythmic impulse.

A tissue pressure model was developed to provide a possible physiologic basis for the manifestation of the cranial rhythmic impulse (CRI). The model assumes that the sensation described as the CRI is related to activation of slowly adapting cutaneous mechanoreceptors by tissue pressures of both the examiner and the subject, and that the sources of change in these tissue pressures are the combined respiratory and cardiovascular rhythms of both examiner and subject. The model generates rhythmic impulses with patterns similar to those reported for the CRI. Also, a significant correlation was found between frequencies calculated from the model and published values for CRI obtained by palpation. These comparisons suggest that the CRI may arise in soft tissues and represents a complex interaction of at least four different physiologic rhythms.

Humans↗
PubMed2006

Tropical drying trends in global warming models and observations.

Anthropogenic changes in tropical rainfall are evaluated in a multimodel ensemble of global warming simulations. Major discrepancies on the spatial distribution of these precipitation changes remain in the latest-generation models analyzed here. Despite this uncertainty, we find a number of measures, both global and local, on which reasonable agreement is obtained, notably for the regions of drying trend (negative precipitation anomalies). Models agree on the overall amplitude of the precipitation decreases that occur at the margins of the convective zones, with percent error bars of magnitude similar to those for the tropical warming. Similar agreement is found on a precipitation climate sensitivity defined here and on differential moisture increase inside and outside convection zones, a step in a hypothesized causal path leading to precipitation changes. A measure of local intermodel agreement on significant trends indicates consistent predictions for particular regions. Observed rainfall trends in several data sets show a significant summer drying trend in a main region of intermodel agreement: the Caribbean/Central-American region.

Caribbean Region↗
PubMed2006

Neural mechanism for stochastic behaviour during a competitive game.

Previous studies have shown that non-human primates can generate highly stochastic choice behaviour, especially when this is required during a competitive interaction with another agent. To understand the neural mechanism of such dynamic choice behaviour, we propose a biologically plausible model of decision making endowed with synaptic plasticity that follows a reward-dependent stochastic Hebbian learning rule. This model constitutes a biophysical implementation of reinforcement learning, and it reproduces salient features of behavioural data from an experiment with monkeys playing a matching pennies game. Due to interaction with an opponent and learning dynamics, the model generates quasi-random behaviour robustly in spite of intrinsic biases. Furthermore, non-random choice behaviour can also emerge when the model plays against a non-interactive opponent, as observed in the monkey experiment. Finally, when combined with a meta-learning algorithm, our model accounts for the slow drift in the animal's strategy based on a process of reward maximization.

Algorithms↗
PubMed1986

Genetics of Darwinian fitness. III. A generalized approach to age structured selection and life history.

Most models in life history assume that maximization of lambda holds. Demographic genetic theory supports this assumption provided (i) the fecundity of each mating is determined solely by the age and genotype of the female, (ii) the two sexes experience the exact same selection intensities, and (iii) the two sexes are equal in their age specific schedules of survival and fecundity. But these assumptions will often not hold in nature: thus a more general means of analysis closely integrated with a broader genetic treatment is attempted here. First, operators are derived to map sex specific non-overlapping generation models into the more general case in which generations can overlap. Application of such operators then suggests a broader representation of age structured selection in which evolution acts according to a single composite Wrightian topography whose gradient is a weighted mean taken over selective gradients in all of the age classes. Application of this view is straightforward, showing, for example, that (i) the evolutionary maximization of lambda, which is the basis of present optimization theories for life history, is extremely fragile with biological deviation from mathematical assumptions used in its derivation, (ii) the cost of meiosis argument is shown not to conflict with traditional life history theory, although its correct application will depend critically and subtly upon how genic effects on fertility are measured, and (iii) correct weightings for age specific selection converge to those of Hamilton (1966) and Schaffer (1974) only when sex specific differences in fertility and survival are nonexistent or when selection occurs only in the demographically dominant sex. For life history problems beyond assumptions underlying tradition approaches the composite adaptive topography seems to provide a suitable alternate means for analysis.

Adaptation, Physiological↗
PubMed1996

Noninvasive visualization of blood flow in the choriocapillaris of the rat.

PURPOSE: The rat has been used to generate models of various eye diseases. However, methods to study the choriocapillaris noninvasively have been inadequate in this species. Laser-targeted angiography was applied to generate local, repetitive angiograms of the choriocapillaris in the rat and to assess the similarity between the choriocapillaris of the rat and that of the subhuman primate. METHODS: Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously in rats. The liposome contents were then released locally in the choroid by the application of a short, noncoagulating heat pulse provided by an argon laser. Videoangiograms of the downstream spread of the bolus of dye were generated with excitation illumination provided by another output from the argon laser. RESULTS: Laser-targeted angiography demonstrated that the bolus of dye perfused the choriocapillaris. Clusters of choriocapillaris lobules were observed and appeared similar to those described in the primate. Dynamic filling and emptying patterns also were similar to those of the primate. Lobules were filled by a central arteriole and drained by a venous annulus. CONCLUSIONS: This study demonstrates the feasibility of noninvasively studying the choriocapillaris of the living rat using the technique of laser-targeted angiography. It demonstrates as well the similarity between the rat and the primate choriocapillaris, thus indicating that the rat is an acceptable and convenient model for the study of physiological and pathologic changes in the choroidal vasculature.

Animals↗
PubMed2001

Disease model: dissecting the pathogenesis of the measles virus.

Host-pathogen interactions of measles virus (MV), a leading cause of childhood mortality worldwide, are still poorly understood. Using transgenic mice that express the human MV receptor CD46, we generated models to study the pathogenesis of MV infection of the central nervous system (CNS) and immune system. CNS infection in CD46 transgenic mice allows replication and spread throughout neurons, inflammation, and ultimately death of the animals. CD46-transgenic mice can also be used to study immunosuppression, a hallmark of measles. Together with mouse knockout technology and a system for generating recombinant MVs, CD46 transgenic mice will ultimately lead to a better understanding of both viral and host factors contributing to disease.

Animals↗
PubMed1993

The old-age security hypothesis revisited.

"Children's altruism toward parents is allowed in a two-overlapping-generations model with endogenous fertility. Parents raise children because, when retired, they expect gifts from their children who are essentially a capital good. Individuals' behavior between generations is examined by analyzing a Nash equilibrium, which is then compared with a social planner's optimal allocation. The pay-as-you-go public pension program is viewed as the optimal gifts from the optimal allocation when the latter is implemented. The effect on fertility of the introduction of a capital market is also analyzed. The validity of the old-age security hypothesis is shown to depend on the parameters of utility and cost functions."

Behavior↗