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At least 829 records · Page 46Linked to original sources
PubMed1994

Computer models of the brain--how far can they take us?

The recent developments in computer capacity and algorithms, together with a tremendous growth of data in neuroscience have dramatically improved the possibilities of modeling and simulating certain brain structures and activities with a considerable degree of realism. Although there is still a long way to go, some claim that we will one day be able to create artificial "brains" with similar capacity to the human brain, perhaps even surpassing it. Here we focus on these perspectives, discussing the potentials and limitations of today's computer models, and how far they might be able to take us.

Brain↗
PubMed1991

Computer modelling of Tetrahymena axonemes at macromolecular resolution. Interpretation of electron micrographs.

A computer-generated model of the structural arrangement of the complete 9+2 ciliary axoneme of Tetrahymena at macromolecular resolution (4 nm) is presented. The model reconciles detailed information about subcomponents from negative-stained, thin-section and freeze-fracture electron micrographs, integrating the images into a consistent three-dimensional picture. This illuminates problems such as the requirement for compaction of dynein to form the arm, difficulties in visualization of the circumferential links, construction of the central sheath, and the comparative periodicities of the inner and outer arms. The model is pragmatic in that it is flexible and easily changed, as new information becomes available. It is also useful in the development of dynamic concepts, such as a spatial description of the dynein cross-bridge cycle, which is illustrated, or relationships between adjacent doublets during sliding and bending.

Animals↗
PubMed1993

Systems analysis in cell biology: from the phenomenological description towards a computer model of the intracellular signal transduction network.

In this paper we introduce a systematic approach for the modelling of complex biological systems which is especially useful for the analysis of signal transduction mechanisms in cell biology. It is shown that systems analysis in form of top-down levelled dataflow diagrams provides a powerful tool for the mathematical modelling of the system in terms of a stochastic formulation. Due to the exact formulation, the consistency of the model with the experimental results can be tested by means of a computer simulation. The method termed Structured Biological Modelling (SBM) is illustrated by modelling some aspects of the second messenger network which regulates cell proliferation. As an example for the straightforward development of a mathematical description a stochastic computer model for intracellular Ca2+ oscillations is presented.

Animals↗
PubMedDate not supplied

Requiring on-line medical command for helicopter request prolongs computer-modeled transport time to the nearest trauma center.

INTRODUCTION: Rapid transport from scene to closest trauma center requires optimal use of public safety first responder (FR), basic life support (BLS), advanced life support (ALS), and transport resources (ground or air). In some parts of this regional emergency medical services (EMS) system, on-scene ALS requires contact with on-line medical command (OLMC) to obtain authorization for air medical helicopter (AMH) dispatch, because some EMS medical directors believe that this may decrease overutilization of AMH services. HYPOTHESIS: The hypothesis of this study was that requiring prior OLMC for AMH dispatch prolongs mean time to a trauma center versus either FR or BLS request for AMH. METHODS: Computer mapping programs were used to model the most rapid driving time to the closest trauma center from 167 actual AMH responses to the scene of a motor vehicle accident. In an OLMC-ALS model, only OLMC-ALS can request an AMH. In a BLS model, BLS units arrive on the scene and the crew requests simultaneous dispatch of an ALS response and an AMH. In the FR model, on arrival at the scene, a FR requests simultaneous dispatch of a BLS unit, an ALS unit, and an AMH. RESULTS: The OLMC-ALS model resulted in a longer mean value for time to trauma center by an AMH than did the computer model for all ground transport settings. The FR model yielded a shorter mean time for AMH compared with the mean values for time to trauma center for all settings. Differences in mean values for time in urban settings were small (ground: 42 minutes, air: 36 minutes), whereas those for the suburban (ground: 52 minutes, air: 41 minutes), and those for rural (ground: 69 minutes, air: 47 minutes) were significant clinically. For the BLS model, these differences persisted, but were significant clinically only in the rural setting (ground: 68 minutes, air: 53 minutes). CONCLUSIONS: Optimal use of AMH requires balancing the need for early helicopter dispatch to fully exploit its speed advantage with the disadvantage of expensive overutilization. This computer model indicates that the best person to request AMH varies by venue: in urban settings, the OLMC physician should request AMH dispatch; in suburban venues, BLS should request AMH dispatch; and in rural venues, FRs should request AMH dispatch.

Air Ambulances↗
PubMed2001

Computer-modeling origin of a simple genetic apparatus.

This computer simulation is based on a model of the origin of life proposed by H. Kuhn and J. Waser, where the evolution of short molecular strands is assumed to take place in a distinct spatiotemporal structured environment. In their model, the prebiotic situation is strongly simplified to grasp essential features of the evolution of the genetic apparatus without attempts to trace the historic path. With the tool of computer implementation confining to principle aspects and focused on critical features of the model, a deeper understanding of the model's premises is achieved. Each generation consists of three steps: (i) construction of devices (entities exposed to selection) presently available; (ii) selection; and (iii) multiplication of the isolated strands (R oligomers) by complementary copying with occasional variation by copying mismatch. In the beginning, the devices are single strands with random sequences; later, increasingly complex aggregates of strands form devices such as a hairpin-assembler device which develop in favorable cases. A monomers interlink by binding to the hairpin-assembler device, and a translation machinery, called the hairpin-assembler-enzyme device, emerges, which translates the sequence of R(1) and R(2) monomers in the assembler strand to the sequence of A(1) and A(2) monomers in the A oligomer, working as an enzyme.

Computer Simulation↗
PubMed2005

Neuromusculoskeletal computer modeling and simulation of upright, straight-legged, bipedal locomotion of Australopithecus afarensis (A.L. 288-1).

The skeleton of Australopithecus afarensis (A.L. 288-1, better known as "Lucy") is by far the most complete record of locomotor morphology of early hominids currently available. Even though researchers agree that the postcranial skeleton of Lucy shows morphological features indicative of bipedality, only a few studies have investigated Lucy's bipedal locomotion itself. Lucy's energy expenditure during locomotion has been the topic of much speculation, but has not been investigated, except for several estimates derived from experimental data collected on other animals. To gain further insights into how Lucy may have walked, we generated a full three-dimensional (3D) reconstruction and forward-dynamic simulation of upright bipedal locomotion of this ancient human ancestor. Laser-scanned 3D bone geometries were combined with state-of-the-art neuromusculoskeletal modeling and simulation techniques from computational biomechanics. A detailed full 3D neuromusculoskeletal model was developed that encompassed all major bones, joints (10), and muscles (52) of the lower extremity. A model of muscle force and heat production was used to actuate the musculoskeletal system, and to estimate total energy expenditure during locomotion. Neural activation profiles for each of the 52 muscles that produced a single step of locomotion, while at the same time minimizing the energy consumed per meter traveled, were searched through numerical optimization. The numerical optimization resulted in smooth locomotor kinematics, and the predicted energy expenditure was appropriate for upright bipedal walking in an individual of Lucy's body size.

Animals↗
PubMed1998

Computer modelling of dynamics of Ser92X deoxymyoglobin mutants.

The hydrogen bond between His93 and Ser92, recently discovered in crystal structures of myoglobins (Mbs), may contribute to the oxygen storage capacity of the heme proteins through a stabilization of the proximal ligand. The possible influence of this H-bond on the geometry of the heme proximal side and ligand binding properties of Mb were computationally studied using model proteins with point mutations affecting this bond. The results of the computer modelling of Ser92X (X = Ala, Ile, Thr, Val) mutants of human (H) and sperm whale (SW) Mbs are presented. The OPLS-AMBER-CHARMM forcefield was used in the calculations. Several 10-50 ps molecular dynamics simulations (300 K, in vacuo) were performed. Our results show that the Ser92X mutants are stable molecules. In the wild types and Ser92Thr mutants, the H-bond studied is observed only for a relatively short period of time. It is expected that in both HMb and SW Mb molecules the impact of the proximal histidine interaction with the Ser92(F7) residue on the iron reactivity is rather low. However, the limited torsional flexibility of the proximal histidine imidazole ring was found in hydrogen bonding mutants. This effect may be attributed to the specific long range electrostatic interactions.

Alanine↗
PubMed1992

A computer model of cellular interactions in the immune system.

The power of modern computers allows the modeling and simulation of complex biological systems. The last decade has seen the emergence of a growing number of simulations of the immune system. In this article, Franco Celada and Philip Seiden present a model that, they suggest, is rich enough to allow computer experiments to be used as practical adjuncts to the usual biological experiments, at a saving of cost and time.

Animals↗
PubMed1995

A computational model of auditory perception.

Building functional models of the auditory system that incorporate neurophysiological, behavioral findings is essential to uncovering mechanisms underlying auditory perception. This paper presents results from modeling the echolocation ability of the FM bat, Myotis lucifugus, using MATLAB on a Sun Sparc-10 as a computational and modeling platform. It is shown that the adaptability and versatility of such computational software is ideal for modeling this complex biological system.

Animals↗
PubMed2001

Antibody-ligand interactions: computational modeling and correlation with biophysical measurements.

Several new aspects of computer-assisted molecular modeling strategies and biophysical techniques, such as fluorescence spectroscopy, circular dichroism, and absorption spectroscopy, have proved useful in the analysis and description of antibody-ligand interactions. The molecular features involved in determining the specificity of antibody-ligand interactions, such as electrostatics (e.g. partial charges, salt bridges, p-cation motifs), hydrogen-bonds, polarization, hydrophobic interactions, hydration and solvation effects, entropy, and kinetics can be identified using a battery of biophysical techniques. An understanding of these parameters is essential to our use of antibodies as tools in high throughput screening of chemical libraries for the discovery of novel compounds.

Antibodies↗
PubMed2003

Computational modeling of cell adhesion and movement using a continuum-kinetics approach.

Adhesion of leukocytes to substrate involves the coupling of disparate length and timescales between molecular mechanics and macroscopic transport, and existing models of cell adhesion do not use full cellular information. To address these challenges, a multiscale computational approach for studying the adhesion of a cell on a substrate is developed and assessed. The cellular level model consists of a continuum representation of the field equations and a moving boundary tracking capability to allow the cell to change its shape continuously. At the receptor-ligand level, a bond molecule is mechanically represented by a spring. Communication between the macro/micro- and nanoscale models is facilitated interactively during the computation. The computational model is assessed using an adherent cell, rolling and deforming along the vessel wall under imposed shear flows. Using this approach, we first confirm existing numerical and experimental results. In this study, the intracellular viscosity and interfacial tension are found to directly affect the rolling of a cell. Our results also show that the presence of a nucleus increases the bond lifetime, and decreases the cell rolling velocity. Furthermore, it is found that a cell with a larger diameter rolls faster, and decreases the bond lifetime. This study shows that cell rheological properties have significant effects on the adhesion process contrary to what has been hypothesized in most literature.

Blood Vessels↗
PubMedDate not supplied

The initiator titration model: computer simulation of chromosome and minichromosome control.

The initiator titration model was formulated to explain the initiation control of the bacterial chromosome. In particular, features concerning the replication behaviour of minichromosomes, such as their high copy number and Escherichia coli's ability to coinitiate chromosome and many minichromosome origins, were considered during the formulation of the model. The model is based on the initiator protein DnaA and its binding sites, DnaA boxes, in oriC, in the dnaA promoter and at other positions on the chromosome. Another important factor in the model is the eclipse period created by the hemimethylation of a new oriC which makes it refractory to initiation. The model was analysed by computer simulations using a stochastic approach varying the different input parameters, and the resulting computer cells were compared with data on living E. coli cells. Here we present the outcome of a few of these simulations concerning the eclipse period, in silico-shift experiments blocking initiation or elongation of replication, and introduction of minichromosomes into the computer cells. We also discuss the synthesis of DnaA protein in the computer cells. From our simulations, we conclude that, whether true or not, the model can mimic the in vivo initiation control of E. coli.

Bacterial Proteins↗
PubMed2005

A systems-based computational model for dose-response comparisons of two mode of action hypotheses for ethanol-induced neurodevelopmental toxicity.

Investigations into the potential mechanisms for ethanol-induced developmental toxicity have been ongoing for over 30 years since Fetal Alcohol Syndrome (FAS) was first described. Neurodevelopmental endpoints are particularly sensitive to in utero exposure to alcohol as suggested by the more prevalent alcohol-related neurodevelopmental disorder (ARND). The inhibition of proliferation during neurogenesis and the induction of apoptosis during the period of synaptogenesis have been identified as potentially important mechanisms for ARND. However, it is unclear how these two mechanisms quantitatively relate to the dose and timing of exposure. We have extended our model of neocortical neurogenesis to evaluate apoptosis during synaptogenesis. This model construct allows quantitative evaluation of the relative impacts on neuronal proliferation versus apoptosis during neocortical development. Ethanol-induced lengthening of the cell cycle of neural progenitor cells during rat neocortical neurogenesis (G13-G19) is used to compute the number of neurons lost after exposure during neurogenesis. Ethanol-induced dose-dependent increases in cell death rates are applied to our apoptosis model during rat synaptogenesis (P0-P14), when programmed cell death plays a major role in shaping the future neocortex. At a human blood ethanol concentration that occurs after 3-5 drinks ( approximately 150 mg/dl), our model predicts a 20-30% neuronal deficit due to inhibition of proliferation during neurogenesis, while a similar exposure during synaptogenesis suggests a 7-9% neuronal loss through induction of cell death. Experimental in vitro and in vivo dose-response research and stereological research on long-term neuronal loss after developmental exposure to ethanol is compared to our model predictions. Our computational model allows for quantitative, systems-level comparisons of mechanistic hypotheses for perturbations during specific neurodevelopmental periods.

Animals↗
PubMed2005

Computational modeling of vascular anastomoses.

Recent development of computational technology allows a level of knowledge of biomechanical factors in the healthy or pathological cardiovascular system that was unthinkable a few years ago. In particular, computational fluid dynamics (CFD) and computational structural (CS) analyses have been used to evaluate specific quantities, such as fluid and wall stresses and strains, which are very difficult to measure in vivo. Indeed, CFD and CS offer much more variability and resolution than in vitro and in vivo methods, yet computations must be validated by careful comparison with experimental and clinical data. The enormous parallel development of clinical imaging such as magnetic resonance or computed tomography opens a new way toward a detailed patient-specific description of the actual hemodynamics and structural behavior of living tissues. Coupling of CFD/CS and clinical images is becoming a standard evaluation that is expected to become part of the clinical practice in the diagnosis and in the surgical planning in advanced medical centers. This review focuses on computational studies of fluid and structural dynamics of a number of vascular anastomoses: the coronary bypass graft anastomoses, the arterial peripheral anastomoses, the arterio-venous graft anastomoses and the vascular anastomoses performed in the correction of congenital heart diseases.

Anastomosis, Surgical↗
PubMed1987

Pulsed-field electrophoresis: application of a computer model to the separation of large DNA molecules.

The biased reptation theory has been applied to the pulsed-field electrophoresis of DNA in agarose gels. A computer simulation of the theoretical model that calculates the mobility of large DNA molecules as a function of agarose pore size, DNA chain properties, and electric field conditions has been used to generate mobility curves for DNA molecules in the size range of the larger yeast chromosomes. Pulsed-field electrophoresis experiments resulting in the establishment of an electrophoretic karyotype for yeast, where the mobility of the DNA fragments is a monotonic function of molecular size for the entire size range that is resolved (200-2200 kilobase pairs), has been compared to the theoretical mobility curves generated by the computer model. The various physical mechanisms and experimental conditions responsible for band inversion and improved electrophoretic separation are identified and discussed in the framework of the model.

Chromosomes↗
PubMed2001

Computer modeling of small heat-shock metalloprotease of the human malaria parasite Plasmodium vivax.

We present here computer generated model of N-terminal fragment, amino acids (aa) 36-245, of a Plasmodium vivax heat shock metalloprotease called PVHSP28, whose gene was cloned and characterised earlier. The fragment showed homology with HSPs from many organisms, including Escherichia coli and Haemophilus influenzae. PVHSP28 had the signature sequence 'HEXXH' and 'EXXXD' of Zinc metalloproteases. Being the first malarial HSP possessing metalloprotease activity, PVHSP28 is an ideal target for the design of new anti-malarial drugs. However, except for a small region (aa 62-132) which had 24.6% sequence similarity with 1TAQ (a DNA polymerase), it did not show sequence similarity with any published structures in protein data bank. Hence it could not be modelled using any automated modeling programs. We modelled 36-245 aa of PVHSP28 using predicted secondary structure as well as experimentally determined and predicted properties of the protein on the basis of its amino acid sequence, using various Internet tools and in-house package MODEL. The model was energy minimised using Sander's module of AMBER 5.0, working on a Silicon Graphics machine, with all atom force field.

Amino Acid Sequence↗
PubMed1987

Theoretical effects of fluid infusions during cardiopulmonary resuscitation as demonstrated in a computer model of the circulation.

Recent studies have shown the potential adverse effects of venous volume loading on blood flow during closed chest cardiopulmonary resuscitation (CPR). To examine the effect of arterial and venous infusions, we employed a published computer simulation of the circulation during CPR. This model uses computer simulated electrical networks to model the heart and great vessels. CPR was modeled with compressions at a rate of 80/min and a force of 80 mmHg. Fluid infusions, simulated as current pulses into the abdominal aorta and superior vena cava, were given to measure their effect on myocardial and cranial blood flow. With 600 ml/min infusions into the abdominal aorta, there was a 12% peak increase in myocardial flow and a 3.8% peak increase in cranial flow. Every 100 ml/min increase in infusion from 0 to 900 ml/min produced a 1.4 ml/min linear increase in myocardial flow and a 4.2 ml/min linear increase in cranial flow. In agreement with previous CPR model studies, simulated vasoconstriction of abdominal and lower extremity vessels resulted in increased myocardial and cranial flows. As resistance of these vessels was increased, abdominal aortic infusions resulted in greater flow augmentations. In contrast to arterial results, infusions at 600 ml/min into the vena cava resulted in a 2.2% decrease in myocardial flow and a 0.62% decrease in cranial flow. Rise and fall times for initiation and cessation of flow augmentations were equal to four compression cycles. We conclude that these findings demonstrate the theoretical benefits of rapid arterial infusions during CPR with increases in myocardial and cranial blood flow. This method may provide an early temporary adjunct to myocardial perfusion during CPR.

Cerebrovascular Circulation↗