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At least 487 records · Page 27Linked to original sources
PubMed1992

A computer model of a cochlear-nucleus stellate cell: responses to amplitude-modulated and pure-tone stimuli.

A computer model of a ventral-cochlear-nucleus (VCN) stellate cell with chop-S type response properties is presented and evaluated. The model is based on a simplified model of spike generation preceded by a stage that simulates dendritic low-pass filtering. Input to the model is in the form of simulated auditory-nerve spikes produced by a model of the auditory periphery [Meddis and Hewitt, J. Acoust. Soc. Am. 89, 2866-2882 (1991)]. Outputs from the stellate-cell model are shown to qualitatively replicate a wide range of typical in vivo responses. These include: (a) realistic onset and steady-state rate-level functions, (b) "chopper"-type post-stimulus time histogram responses; (c) typical "chop-S"-type neuron responses characterized by a low coefficient of variance (CV less than 0.3) of interspike intervals as a function of time; (d) level-dependent amplitude-modulation transfer functions; (e) intrinsic oscillations in responses to pure-tone stimuli; (f) amplitude-modulation encoding over a wide dynamic range; and (g) frequency-limited phase locking to pure tones. It is shown that these responses can be explained primarily by the membrane properties of the cells. More specifically, how the model encodes signal amplitude modulation was studied and an explanation was suggested for the generation of the bandpass modulation transfer functions. Such functions are observed neurally in response to amplitude-modulated stimuli presented at moderate to high signal levels.

Animals↗
PubMed1999

A computer model of the spread of hepatitis C virus among injecting drug users.

A number of behavioural and clinical parameters influence the transmission of an infectious agent through direct contact between two individuals. The behavioural parameters encountered in such situations are also likely to exhibit an enormous amount of variability. With the spread of hepatitis C among injecting drug users, the parameters associated with injecting behaviour play an important role in the modelling of the transmission process. Computer simulation modelling is an ideal approach to deal with a large number of parameters as well as high levels of variability without excessive simplification. The simulation model presented in this paper is tested on data from a cohort of injecting drug users and the results obtained are very encouraging from a public health perspective. The model clearly indicates that the rate at which HCV spreads through a population of injecting drug users is extremely sensitive to the interaction rate and to the probability of infection through a single contact with an infective. At the same time it shows that rate of spread is not very sensitive to initial prevalence, which is very encouraging from a public health perspective.

Computer Simulation↗
PubMed1990

Tertiary structure and computer modeling of plant 5S ribosomal RNA.

A new model of secondary and tertiary structure of higher plant 5S rRNA is proposed. It consists of three domains. Domain alpha includes stem I and loop A; domain beta contains stems II and III and loops B and C; domain gamma consists of stems IV and V and loops D and E. We propose that the domains beta and gamma adopt RNA-A like structure due to irregularities caused by the different in size internal loops B and E and the bulges occurring in the model. A suggested bending of RNA could bring single stranded fragments of domains beta and gamma close enough to each other to allow tertiary interactions. The new model of plant 5S rRNA differs from those suggested previously for eukaryotic 5S rRNA, by arrangement of the domains beta and gamma and the base pairing scheme of domain gamma. The model is based on our results of partial digestion obtained with single and double strand specific nucleases. The experimental results were confirmed by computer aided secondary structure prediction analysis of all higher plant 5S rRNAs and computer modeling using energy minimalization approach. Further support of our model have been provided by experiments including alpha sarcin, ribonuclease H and chemical modifications.

Base Sequence↗
PubMed1989

The influence of mediolateral deformity, tibial torsion, and foot position on femorotibial load. Prediction of a musculoskeletal computer model.

The influence of mediolateral deformity, tibial torsion, and different centers of foot support was studied with a three-dimensional computer model that incorporates the significant muscles of the lower extremities needed for quasi-static walking. This theoretical method avoids the variability in gait pattern from the pain and discomfort associated with deformity in patients. The study illustrates the possible importance of the muscle force on the load across the knee and ankle. High strains in the medial gastrocnemius and the medial hamstring created particularly high loads in the medial compartment of the knee. Internal torsion and varus deformity were associated with the highest loads in the medial compartment of the knee, although the peak load for each deformity occurred in different phases of the gait cycle. Both external torsion and valgus deformity generally decreased the load in the medial compartment, but early in the gait cycle external torsion increased the loads on the medial side. In addition, when the center of support of the body was in the forefoot, the loads through the knee were lower than when foot support was at the heel. As expected, if the center of support was on the lateral foot line, the lateral compartment was subjected to more load and, conversely, when the center of support was on the medial part of the foot the medial compartment of the knee was more loaded. Although the predicted forces agree well with those found with other methods, we think that the model is best used to measure the direction of influence of specific factors.

Biomechanical Phenomena↗
PubMedDate not supplied

[Replication of a computer model of auditory hallucinations in schizophrenia].

INTRODUCTION: Abnormal synaptic pruning has been proposed by some authors as a theory to explain schizophrenia. It has been studied in different ways, some of which are computerized models. METHODS: A PC computer with MATLAB version 5.3 and Neural Networks Toolbox programs were used. To reproduce the model we used Elman's network for neuronal unit and McGlashan and Hoffman's network. RESULTS: The corrected percentage of detection improved as synapses were prunned. It increased from 68% to 91 %, reaching the highest detection level when 60% of the synapses were eliminated. Detection capacity was reduced when synaptic elimination continued and the program started detecting words in the absence of input. This was considered as a hallucination. When pruning reached from 80% to 95%, hallucinations occurred more frequently. CONCLUSIONS: The computer simulation model provides a symptom formation model, and also a way of understanding pruning's adaptative utility. When the neuronal units were eliminated (instead of connections), there was only progressive worsening in word perception. This confirms the hypothesis proposed that schizophrenia pathophysiology underlies neuronal connections, not the neurons.

Hallucinations↗
PubMed2004

Filament behavior in a computational model of ventricular fibrillation in the canine heart.

The aim of this paper was to quantify the behavior of filaments in a computational model of re-entrant ventricular fibrillation. We simulated cardiac activation in an anisotropic monodomain with excitation described by the Fenton-Karma model with Beeler-Reuter restitution, and geometry by the Auckland canine ventricle. We initiated re-entry in the left and right ventricular free walls, as well as the septum. The number of filaments increased during the first 1.5 s before reaching a plateau with a mean value of about 36 in each simulation. Most re-entrant filaments were between 10 and 20 mm long. The proportion of filaments touching the epicardial surface was 65%, but most of these were visible for much less than one period of re-entry. This paper shows that useful information about filament dynamics can be gleaned from models of fibrillation in complex geometries, and suggests that the interplay of filament creation and destruction may offer a target for antifibrillatory therapy.

Action Potentials↗
PubMed1982

Cycle length alternation in circus movement tachycardia using an atrioventricular accessory pathway. A study of the role of the atrioventricular node using a computer model of tachycardia.

The possible role of the atrioventricular nodal (AVN) function curve during tachycardia as a cause of cycle length alternation was investigated using a computer model of circus movement tachycardia utilizing an atrioventricular accessory pathway. Two types of AVN function curves during tachycardia were entered into the computer: straight lines of various gradients and representative examples of patient-based AVN function curves obtained during clinical electrophysiologic studies. Perturbations of the tachycardia model were induced by introducing a short cycle, by suddenly prolonging a conduction interval, or by moving the AVN function curve relative to that in stable tachycardia. Using the straight line AVN function curves, stable, sustained cycle length alternation could be induced by perturbation of the tachycardia cycle if the gradient of the line was -1 (slope = 45 degrees). If the gradient was more than -1 (slope less than 45 degrees), the perturbation was damped. If the gradient was less than -1 (slope greater than 45 degrees), the perturbation was amplified, leading to termination of tachycardia by block in the AVN. Similar but more complex responses to perturbation of tachycardia were found using patient-based AVN function curves. Thus, sustained cycle length alternation and amplification or damping of perturbation could be produced. Using physiologic AVN function curves, the response to perturbation of tachycardia depended on the interrelationship of the shape of the AVN function curve, the location of the cycle length of tachycardia on the curve, the magnitude and direction of the perturbation, and the AVN effective refractory period. We conclude that cycle length alternation during tachycardia may be explained by the characteristics of a single antegrade AVN function curve without postulating the presence of additional AVN pathways. The stability of circus movement tachycardias depends on the interaction of several variables.

Atrioventricular Node↗
PubMed2005

Computational models for prediction of IVF/ICSI outcomes with surgically retrieved spermatozoa.

IVF/intracytoplasmic sperm injection (ICSI) using surgically retrieved spermatozoa (SRS) is a key option in the treatment of severe male infertility. It was aimed to develop a computational model for the prediction of this modality's outcome. A dataset of 113 exemplars, derived from patients who underwent IVF/ICSI with SRS, was retrospectively analysed. The dataset, containing input features maternal age, sperm retrieval technique, type of spermatozoa used, type of male factor and output intrauterine pregnancy, was randomized into a modelling ('training') set of 83 and cross-validation ('test') set of 30. neUROn++, a set of C++ programs, was used to model the dataset using linear and quadratic discriminant function analysis, logistic regression, and neural computation. A 4-hidden node neural network was found to have the highest accuracy, with a test set receiver operator characteristic (ROC) curve area of 0.783. Reverse regression of this neural network showed maternal age to be the most significant feature in predicting pregnancy (P = 0.025), followed by sperm type (P = 0.076). Type of male factor (P = 0.47) and sperm retrieval technique (P = 0.88) did not predict outcome. In summary, a neural network of clinical relevance was found to be superior in terms of IVF/ICSI outcome prediction. Future media deployment is planned.

Adult↗
PubMed1998

Computational models for the formation of protocell structures.

There have been various attempts to simulate the self-assembly process of lipid aggregates by computers. However, due to the computationally complex nature of the problem, previous simulations were often conducted with unrealistic simplifications of the molecules' morphology, intermolecular interactions, and the environment in which the lipid molecules interact. In this article, we present a new computational model in which each lipid is simulated by a more realistic amphiphilic particle consisting of a hydrophilic head and a long hydrophobic tail. The intermolecular interactions are approximated by a set of simple forces reflecting physical and chemical properties of lipids, for example, hydrophobicity and electrostatic forces, which are believed to be crucial for the formation of various aggregates. With a set of carefully selected parameters, this model is able to simulate successfully the formation of micelles in an aqueous environment and reversed micelle structures in an oil solvent from an initially randomly distributed set of lipidlike particles. This model can be used to study, at the microscopic level, the self-assembly of different protocell structures in the evolutionary process and the impact of environmental conditions on the formation of these structures. It may be further generalized to simulate the formation of other, more complex structures of amphiphilic molecules such as monolayer and bilayer aggregates.

Catalysis↗
PubMed2001

Computer modeling of human angiogenin-dinucleotide substrate interaction.

Structures of substrate bound human angiogenin complexes have been obtained for the first time by computer modeling. The dinucleotides CpA and UpA have been docked onto human angiogenin using a systematic grid search procedure in torsion and Eulerian angle space. The docking was guided throughout by the similarity of angiogenin-substrate interactions with interactions of RNase A and its substrate. The models were subjected to 1 nanosecond of molecular dynamics to access their stability. Structures extracted from MD simulations were refined by simulated annealing. Stable hydrogen bonds that bridged protein and ligand residues during the MD simulations were taken as restraints for simulated annealing. Our analysis on the MD structures and annealed models explains the substrate specificity of human angiogenin and is in agreement with experimental results. This study also predicts the B2 binding site residues of angiogenin, for which no experimental information is available so far. In the case of one of the substrates, CpA, we have also identified the presence of a water molecule that invariantly bridges the B2 base with the protein. We have compared our results to the RNase A-substrate complex and highlight the similarities and differences.

Amino Acid Sequence↗
PubMed2006

In vivo profiling of focal cortical dysplasia on high-resolution MRI with computational models.

PURPOSE: On MRI, focal cortical dysplasia (FCD) is characterized by a combination of increased cortical thickness, hyperintense signal within the dysplastic lesion, and blurred transition between gray and white matter (GM-WM). The visual identification of these abnormal characteristics may be difficult, and it is unclear to what degree these features occur among different FCD lesions. Our purpose was to investigate the pattern of occurrence of abnormal MRI characteristics in FCD by using a set of computational models and to generate quantitative lesion profiling. METHODS: A set of voxel-wise operators was applied to high-resolution 3D T1-weighted MRI in 23 patients with histologically proven FCD and 39 healthy controls, creating maps of GM thickness, maps of relative intensity highlighting areas with hyperintense signal, and maps of gradient magnitude modeling the GM-WM transition. All FCD lesions were segmented manually on the T1-weighted MRI. RESULTS: FCD volumes ranged from 734 mm3 to 80,726 mm3 (mean, 8,629 mm3 +/- 16,238). The manually segmented FCD lesions were used to estimate features in the lesional area and to determine possible local variations of each feature by means of a histogram. In 78% of the patients, FCD lesions were characterized by simultaneous GM thickening, hyperintense signal, and blurring of the GM-WM transition. Moreover, in all patients, the FCD lesion had at least two of these three characteristics. CONCLUSIONS: The three features occurred regardless of the lesion volume, and they characterized not only large FCD lesions, but also subtle ones that had been overlooked by conventional radiologic inspection before surgery.

Adult↗
PubMed1997

Computer modeling for advanced life support system analysis.

This article discusses the equivalent mass approach to advanced life support system analysis, describes a computer model developed to use this approach, and presents early results from modeling the NASA JSC BioPlex. The model is built using an object oriented approach and G2, a commercially available modeling package Cost factor equivalencies are given for the Volosin scenarios. Plant data from NASA KSC and Utah State University (USU) are used, together with configuration data from the BioPlex design effort. Initial results focus on the importance of obtaining high plant productivity with a flight-like configuration.

Atmosphere↗
PubMed2004

Predicting axonal response to molecular gradients with a computational model of filopodial dynamics.

Axons are often guided to their targets in the developing nervous system by attractive or repulsive molecular concentration gradients. We propose a computational model for gradient sensing and directed movement of the growth cone mediated by filopodia. We show that relatively simple mechanisms are sufficient to generate realistic trajectories for both the short-term response of axons to steep gradients and the long-term response of axons to shallow gradients. The model makes testable predictions for axonal response to attractive and repulsive gradients of different concentrations and steepness, the size of the intracellular amplification of the gradient signal, and the differences in intracellular signaling required for repulsive versus attractive turning.

Algorithms↗
PubMed1996

Effects of premature responses on vulnerability to fibrillation in a computer model.

The purpose of this study was to determine the effects of premature responses on vulnerability to fibrillation using a computer model based on the wavelet hypothesis. The model simulated propagation, nonuniform recovery of excitability, and slow propagation during incomplete recovery. Vulnerability was assessed as the fibrillation threshold, which was defined as the duration of train stimulation required to initiate self-sustained reentrant excitation with multiple excitation fronts. The fibrillation threshold was determined at various premature cycle lengths in the presence of refractory periods of varied range and duration, at various rates, and after compensatory pauses and varied patterns of consecutive premature responses. The fibrillation threshold was found to be reduced by premature responses, and with increasing premature cycle length, there was an initial decrease followed by an increase of fibrillation threshold. The fibrillation threshold was directly related to the duration and indirectly related to the range of the refractory period. The time phase of curves relating premature cycle length and fibrillation threshold was such that premature responses at some cycle lengths were associated with a lower fibrillation threshold in the presence of longer refractory periods, with slower rates, and with an immediately preceding compensatory pause. The mechanism may be important in the proarrhythmia effects of drugs that prolong repolarization and in the bradycardia-tachycardia syndrome. Consecutive premature responses at a constant rate increased the fibrillation threshold in comparison with the initial response, while consecutive responses at an accelerating rate decreased the fibrillation threshold.

Atrial Fibrillation↗
PubMed2024

A computational model for bacteriophage ϕX174 gene expression.

Bacteriophage ϕX174 has been widely used as a model organism to study fundamental processes in molecular biology. However, several aspects of ϕX174 gene regulation are not fully resolved. Here we construct a computational model for ϕX174 and use the model to study gene regulation during the phage infection cycle. We estimate the relative strengths of transcription regulatory elements (promoters and terminators) by fitting the model to transcriptomics data. We show that the specific arrangement of a promoter followed immediately by a terminator, which occurs naturally in the ϕX174 genome, poses a parameter identifiability problem for the model, since the activity of one element can be partially compensated for by the other. We also simulate ϕX174 gene expression with two additional, putative transcription regulatory elements that have been proposed in prior studies. We find that the activities of these putative elements are estimated to be weak, and that variation in ϕX174 transcript abundances can be adequately explained without them. Overall, our work demonstrates that ϕX174 gene regulation is well described by the canonical set of promoters and terminators widely used in the literature.

Gene Expression Regulation, Viral↗
PubMed1999

Modeling computer interest in older adults: the role of age, education, computer knowledge, and computer anxiety.

We proposed a mediation model to examine the effects of age, education, computer knowledge, and computer anxiety on computer interest in older adults. We hypothesized that computer knowledge and computer anxiety would fully mediate the effects of age and education on computer interest. A sample of 330 older adults from local senior-citizen apartment buildings completed a survey that included an assessment of the constructs included in the model. Using structural equation modeling, we found that the results supported the hypothesized mediation model. In particular, the effect of computer knowledge operated on computer interest through computer anxiety. The effect of age was not fully mitigated by the other model variables, indicating the need for future research that identifies and models other correlates of age and computer interest. The most immediate application of this research is the finding that a simple 3-item instrument can be used to assess computer interest in older populations. This will help professionals plan and implement computer services in public-access settings for older adults. An additional application of this research is the information it provides for training program designers.

Age Factors↗
PubMed1995

Dynamics of neurons in the cat lateral geniculate nucleus: in vivo electrophysiology and computational modeling.

1. We investigated the time domain transformation that thalamocortical relay cells of the cat lateral geniculate nucleus (LGN) perform on their retinal input, and used computational modeling to explore the biophysical properties that determine the dynamics of the LGN relay cells in vivo. 2. We recorded simultaneously the input (S potentials) and output (action potentials) of 50 cat LGN relay cells stimulated by drifting sinusoidal gratings of varying temporal frequency. The temporal modulation transfer functions (TMTFs) of the neurons were derived from these data. The burstiness of the LGN spike trains was also assessed using objective criteria. 3. We found that the form of the TMTF was quite variable among cells, ranging from low-pass to strongly band-pass. The optimal temporal frequency of band-pass neurons was between 2 and 8 Hz. In addition, the TMTF of some cells was nonstationary: their temporal tuning changed with time. 4. The temporal tuning of a cell was directly related to the degree of burstiness of its spike train. Tonically firing relay cells had low-pass TMTFs, whereas the most bursty neurons exhibited the most sharply band-pass transfer functions. This was also true for single cells that altered their temporal tuning: a shift to more band-pass tuning was associated with increased burstiness of the spike train, and vice versa. 5. We constructed a computer simulation of the LGN relay cell. The model was a simplified five-channel version of the thalamocortical neuron model of McCormick and Huguenard. It incorporated the quantitative kinetics of the Ca2+ T channel, as well as the Hodgkin-Huxley Na+ and K+ channels, as the only active membrane currents. To simulate the in vivo dynamics of the relay cell, the input to the model consisted of trains of synaptic potentials, recorded as S potentials in our physiological experiments. 6. When the resting membrane potential of the model neuron was relatively depolarized, the model's TMTF was low-pass, with no bursting evident in the simulated spike train. At hyperpolarized resting membrane potentials, however, the modeled TMTF was band-pass, with frequent burst discharges. Thus the biophysical model reproduced not only the range of dynamics seen in real LGN relay cells, but also the dependence of the overall dynamics on the burstiness of the spike train. However, neither of these phenomena could be simulated without the T channel. Thus the simulations demonstrated that the T-type Ca2+ channel was necessary and sufficient to explain the LGN dynamics observed in physiological experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

A computer model for predicting the demand for end-stage renal failure (ESRF) treatment, contract setting and monitoring.

BACKGROUND: The high cost of end-stage renal failure (ESRF) treatment, and the anticipated need for expansion of the service at a time of limited resources for health care expenditure, means that careful planning of such an expansion is necessary. This needs to inform the setting and monitoring of contracts between commissioning organizations and providers of treatment. A spreadsheet based computer model is described which fulfils both of these needs. METHODS: A computer programme was written to run on a commonly available spreadsheet in order to predict the demand for ESRF treatment, set contracts, and monitor in year performance. RESULTS: The model described has facilitated contracting for ESRF services. Purchasers have used it to examine various planning scenarios, while the provider unit has used it to support a business case for further development. Using this model, the predictions for the Sheffield resident population are that the total number of patients on the ESRF treatment programme will increase from a mid-year average of 204 patients in the year 1994-95 to 266 patients in the year 1999-2000, while costs increased over the same time period from 2.37 million pounds to 2.78 million pounds. CONCLUSIONS: A computer spreadsheet based model described is a useful tool for predicting demand, and setting and monitoring contracts, for treatment for ESRF. Problems with the model and potential further developments are discussed.

Competitive Bidding↗