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At least 703 records · Page 39Linked to original sources
PubMedDate not supplied

Heat and mass transfer during the cryopreservation of a bioartificial liver device: a computational model.

Bioartificial liver devices (BALs) have proven to be an effective bridge to transplantation for cases of acute liver failure. Enabling the long-term storage of these devices using a method such as cryopreservation will ensure their easy off the shelf availability. To date, cryopreservation of liver cells has been attempted for both single cells and sandwich cultures. This study presents the potential of using computational modeling to help develop a cryopreservation protocol for storing the three dimensional BAL: Hepatassist. The focus is upon determining the thermal and concentration profiles as the BAL is cooled from 37 degrees C-100 degrees C, and is completed in two steps: a cryoprotectant loading step and a phase change step. The results indicate that, for the loading step, mass transfer controls the duration of the protocol, whereas for the phase change step, when mass transfer is assumed negligible, the latent heat released during freezing is the control factor. The cryoprotocol that is ultimately proposed considers time, cooling rate, and the temperature gradients that the cellular space is exposed to during cooling. To our knowledge, this study is the first reported effort toward designing an effective protocol for the cryopreservation of a three-dimensional BAL device.

Computer Simulation↗
PubMed2003

A computational model of prefrontal control in free recall: strategic memory use in the California Verbal Learning Task.

Several decades of research into the function of the frontal lobes in brain-damaged patients, and more recently in intact individuals using function brain imaging, has delineated the complex executive functions of the frontal cortex. And yet, the mechanisms by which the brain achieves these functions remain poorly understood. Here, we present a computational model of the role of the prefrontal cortex (PFC) in controlled memory use that may help to shed light on the mechanisms underlying one aspect of frontal control: the development and deployment of recall strategies. The model accounts for interactions between the PFC and medial temporal lobe in strategic memory use. The PFC self-organizes its own mnemonic codes using internally derived performance measures. These mnemonic codes serve as retrieval cues by biasing retrieval in the medial temporal lobe memory system. We present data from three simulation experiments that demonstrate strategic encoding and retrieval in the free recall of categorized lists of words. Experiment 1 compares the performance of the model with two control networks to evaluate the contribution of various components of the model. Experiment 2 compares the performance of normal and frontally lesioned models to data from several studies using frontally intact and frontally lesioned individuals, as well as normal, healthy individuals under conditions of divided attention. Experiment 3 compares the model's performance on the recall of blocked and unblocked categorized lists of words to data from Stuss et al. (1994) for individuals with control and frontal lobe lesions. Overall, our model captures a number of aspects of human performance on free recall tasks: an increase in total words recalled and in semantic clustering scores across trials, superiority on blocked lists of related items compared to unblocked lists of related items, and similar patterns of performance across trials in the normal and frontally lesioned models, with poorer overall performance of the lesioned models on all measures. The model also has a number of shortcomings, in light of which we suggest extensions to the model that would enable more sophisticated forms of strategic control.

Brain Injuries↗
PubMed2003

Building a computer model of the Haemobear blood pump.

Further development of the Haemobear blood pump requires theoretical predictions of the dynamic behavior of the rotor. These predictions can be used to compare different rotor geometry at desired operating conditions before a prototype is built. The study focuses on a rotor-dynamic model of the rigid rotor with six degrees of freedom (6-DoF), which is implemented using the Matlab-Simulink software package. The forces acting on the rotor are provided to Simulink in terms of constant values (e.g., gravity force), linear coefficients, or nonlinear functions. These coefficients or functions are obtained using numerical simulation results. Fluid forces and magnetic forces can be calculated using commercial software codes. The output of these codes has to be postprocessed to get the desired values for Simulink. This article will give an overview of how to implement arbitrary physical influences on the rotor in a computational model of the complete pump.

Computer Simulation↗
PubMed1992

A computer model of glycosylated human butyrylcholinesterase.

The three-dimensional structure of human serum butyrylcholinesterase (BuChE) was modeled using a computer-based amino acid replacement strategy and the known coordinates of crystallized acetylcholinesterase (AChE) from Torpedo californica. The BuChE model was then energetically minimized with dynamic iterations of an adopted basis Newton-Raphson algorithm and the program CHARMM. Hypothetical glycosylation of this structure based upon the known carbohydrate composition of the enzyme was also performed. The glycosylated, minimized model predicts that the tertiary structure of BuChE could be very similar to AChE but that the entrance of the narrow channel leading toward its active site triad probably differs. All nine of the known N-linked oligosaccharides of BuChE are predicted to occur away from the putative active site channel and most are located on one face of the monomer.

Butyrylcholinesterase↗
PubMed1987

CAN*TROL: a computer model for designing national cancer control strategies.

Planning national and regional cancer control strategies is difficult. At present, cancer experts and planners rely on global subjective judgment to estimate the effectiveness and cost of different programs, and to set priorities. The complexity of the problem makes this approach vulnerable to oversimplification and error. Computer models can be very powerful aids to planning, enabling decision makers to break a problem into parts for which data exist, and reconstructing the parts to estimate the effect of a virtually limitless variety of cancer control activities, on a large number of important clinical and economic outcomes. CAN*TROL has been developed to serve this need. CAN*TROL has been used in the U.S., Chile and India, and is scheduled for use in several other countries.

Chile↗
PubMedDate not supplied

ModelDB: an environment for running and storing computational models and their results applied to neuroscience.

Research groups within the Human Brain Project are developing technologies to help organize and make accessible the vast quantities of information being accumulated in the neurosciences. The goal of this work is to provide systems that enable this complex information from many diverse sources to be synthesized into a coherent theory of nervous system function. Our initial approach to this problem has been to create several small databases. While addressing the issues of each individual database, we are also considering how each might be incorporated into an integrated cluster of databases. In this paper, we describe a pilot project in which we construct a database of computational models of neuronal function. This database allows models to be created and run and their results reviewed through a World Wide Web interface. Because models encapsulate knowledge in a formal manner about how neuronal systems function, we also discuss how this database forms a natural center for our initial attempts at creating a cluster of related databases. General issues of database development in the context of the Web are also discussed.

Brain↗
PubMed1980

A computer model for the 30S ribosome subunit.

We describe a computer-generated model for the locations of the 21 proteins of the 30S subunit of the E. coli ribosome. The model uses a new method of incorporating experimental measurements based on a mathematical technique called distance geometry. In this paper, we use data from two sources: immunoelectron microscopy and neutron-scattering studies. The data are generally self-consistent and lead to a set of relatively well-defined structures in which individual protein coordinates differ by approximately 20 A from one structure to another. Two important features of this calculation are the use of extended proteins rather than just the centers of mass, and the ability to confine the protein locations within an arbitrary boundary surface so that only solutions with an approximate 30S "shape" are permitted.

Computers↗
PubMed2001

A 915-MHz antenna for microwave thermal ablation treatment: physical design, computer modeling and experimental measurement.

A 915-MHz antenna design that produces specific absorption rate distributions with preferential power deposition in tissues surrounding and including the distal end of the catheter antenna is described. The design features minimal reflected microwave current from the antenna flowing up the transmission line. This cap-choke antenna consists of an annular cap and a coaxial choke which matches the antenna to the coaxial transmission line. The design minimizes heating of the coaxial cable and its performance is not affected by the depth of insertion of the antenna into tissue. The paper provides a comparison of results obtained from computer modeling and experimental measurements made in tissue equivalent phantom materials. There is excellent agreement between numerical modeling and experimental measurement. The cap-choke, matched-dipole type antenna is suitable for intracavitary microwave thermal ablation therapy.

Computer Simulation↗
PubMed1986

Computer modeling of planar myocardial perfusion imaging: effect of heart rate and ejection fraction on wall thickness and chamber size.

Myocardial perfusion imaging is generally performed as a static acquisition without regard for dynamic changes in the cardiac cycle. The effect of heart rate and ejection fraction on the appearance of left ventricular chamber size and wall thickness as perceived in 201Tl scintigrams has not, to our knowledge, been previously studied. A dynamic computer model of the left ventricle was constructed, capable of varying the heart rate and ejection fraction. Parallel slices through the model were convolved with experimentally derived 201Tl point spread functions at corresponding depths to incorporate the effects of scatter and attenuation. Both gated and static left anterior oblique images were created at three clinically encountered heart rates and ejection fractions, with constant end-diastolic volume and left ventricular mass. Results of the study indicate that perceived and quantified wall thickness increases and chamber size decreases appreciably with increasing ejection fraction and (slightly) with increasing heart rate. Thus, evaluation of wall thickness and chamber size in planar images should take into account variations in heart rate and contractility. This is especially pertinent to estimates of left ventricular hypertrophy and chamber size, attempted from nongated myocardial perfusion images.

Computers↗
PubMed1993

Computer modeling studies on the binding of 2',5'-linked dinucleoside phosphates to ribonuclease T1-influence of subsite interactions on the substrate specificity.

The modes of binding of Gp(2',5')A, Gp(2',5')C, Gp(2',5')G and Gp(2',5')U to RNase T1 have been determined by computer modelling studies. All these dinucleoside phosphates assume extended conformations in the active site leading to better interactions with the enzyme. The 5'-terminal guanine of all these ligands is placed in the primary base binding site of the enzyme in an orientation similar to that of 2'-GMP in the RNase T1-2'-GMP complex. The 2'-terminal purines are placed close to the hydrophobic pocket formed by the residues Gly71, Ser72, Pro73 and Gly74 which occur in a loop region. However, the orientation of the 2'-terminal pyrimidines is different from that of 2'-terminal purines. This perhaps explains the higher binding affinity of the 2',5'-linked guanine dinucleoside phosphates with 2'-terminal purines than those with 2'-terminal pyrimidines. A comparison of the binding of the guanine dinucleoside phosphates with 2',5'- and 3',5'-linkages suggests significant differences in the ribose pucker and hydrogen bonding interactions between the catalytic residues and the bound nucleoside phosphate implying that 2',5'-linked dinucleoside phosphates may not be the ideal ligands to probe the role of the catalytic amino acid residues. A change in the amino acid sequence in the surface loop region formed by the residues Gly71 to Gly74 drastically affects the conformation of the base binding subsite, and this may account for the inactivity of the enzyme with altered sequence i.e., with Pro, Gly and Ser at positions 71 to 73 respectively. These results thus suggest that in addition to recognition and catalytic sites, interactions at the loop regions which constitute the subsite for base binding are also crucial in determining the substrate specificity.

Binding Sites↗
PubMed2002

Computational modeling of mass transfer and links to atherosclerosis.

In the context of atherogenesis, mass transport refers to the movement of atherogenic molecules from flowing blood into the artery wall, or vice versa. Although LDL transport clearly plays a role in atherosclerotic plaque development, it is much less clear whether abnormalities in mass transfer patterns are in themselves atherogenic. A powerful way of addressing this question is through computational modeling, which provides detailed descriptions of local mass transport features. Here we briefly review the strategy and some of the pros and cons of such a modeling approach, and then focus on results gained from studies in a variety of arterial geometries. The general picture is that zones of hypoxia (low oxygen transport from blood to wall) and elevated LDL tend to colocalize with each other, and with areas of atherosclerotic lesion development and/or intimal thickening. The picture is complicated by the fact that such zones also tend to have "abnormal" wall shear stress patterns, which are also believed to be atherogenic. Taken together, these results suggest, but do not prove, a role for mass transport in atherogenesis.

Arteries↗
PubMed1997

Amino acid sequence of the alpha subunit and computer modelling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper).

Echicetin, a heterodimeric protein from the venom of Echis carinatus, binds to platelet glycoprotein Ib (GPIb) and so inhibits platelet aggregation or agglutination induced by various platelet agonists acting via GPIb. The amino acid sequence of the beta subunit of echicetin has been reported and found to belong to the recently identified snake venom subclass of the C-type lectin protein family. Echicetin alpha and beta subunits were purified. N-terminal sequence analysis provided direct evidence that the protein purified was echicetin. The paper presents the complete amino acid sequence of the alpha subunit and computer models of the alpha and beta subunits. The sequence of alpha echicetin is highly similar to the alpha and beta chains of various heterodimeric and homodimeric C-type lectins. Neither of the fully reduced and alkylated alpha or beta subunits of echicetin inhibited the platelet agglutination induced by von Willebrand factor-ristocetin or alpha-thrombin. Earlier reports about the inhibitory activity of reduced and alkylated echicetin beta subunit might have been due to partial reduction of the protein.

Amino Acid Sequence↗
PubMed1998

Applying computer modeling to examine complex dynamics and pattern formation of tissue growth.

For research in areas such as developmental biology and cancer, understanding the formation and regrowth of tissue is of great importance. Since complex system behavior makes it difficult to interpret dynamics and pattern formation of tissue growth, it is helpful to have a way to simulate the cell systems and test hypotheses about the mechanisms by which the system is responding. Computer "modeling experiments" can serve this purpose, as we show with an example of the small intestine epithelial cells' response to cytosine arabinoside. This example demonstrates that nonhomogeneities in the cell population can play an important role and emphasizes the need to use a modeling approach, like our spatial modeling, that addresses the differences within the tissue structure. These types of "modeling experiments" can guide researchers with further experiments and provide clues as to how complex cell proliferation behavior is linked to underlying molecular phenomena.

Antimetabolites, Antineoplastic↗
PubMed1999

Serial prostate specific antigen screening for prostate cancer: a computer model evaluates competing strategies.

PURPOSE: We compare prostate specific antigen (PSA) screening strategies in terms of expected years of life saved with screening, number of screens, number of false-positive screens and rates of over diagnosis, defined as detection by PSA screening of patients who would never have been diagnosed without screening. MATERIALS AND METHODS: A computer model of disease progression, clinical diagnosis, PSA growth and PSA screening was used. Under baseline conditions, when screening is not considered, the model replicates clinical diagnosis and disease mortality rates recorded by the Surveillance, Epidemiology and End Results Program of the National Cancer Institute in the mid 1980s. RESULTS: Biannual screening with PSA greater than 4.0 ng./ml. was projected to reduce the number of screens and false-positive tests by almost 50% relative to annual screening while retaining 93% of years of life saved. With annual screening use of an age specific bound for PSA to consider a test positive instead of the standard 4.0 ng./ml. was projected to reduce false-positive screens by 27% and over diagnosis by a third while retaining almost 95% of years of life saved. Sensitivity analyses did not change the relative efficacy of biannual screening. CONCLUSIONS: Under the model assumptions biannual PSA screening is a cost-effective alternative to annual PSA screening for prostate cancer. With annual screening use of an age specific bound for PSA positivity appears to reduce false-positive results and over diagnosis rates sharply relative to a bound of 4 ng./ml. while retaining most of the survival benefits.

Adult↗
PubMed1990

Somatic mutation, affinity maturation and the antibody repertoire: a computer model.

Somatic mutation has been implicated as a significant and possibly primary factor in the maturation of antibody affinity in the humoral immune response. B cells stimulated by antigen experience a hyper-mutation in the gene segments that code for the antigen-binding site of the antibody, creating antibody specificities that did not exist at the time of immunization. Although most of the mutations are likely to be disadvantageous, new specificities with a higher affinity for the antigen are sometimes created. These higher-affinity cells are preferentially selected for proliferation and eventual antibody secretion, resulting in a progressively higher average affinity over time. In this paper we present the results of an investigation of somatic mutation through the use of a computer model. At the basis of the model is a large repertoire of discrete antibodies and antigens, having three-dimensional structures, that exhibit properties similar to those of the real populations. The key factor is that the binding strength between any antibody/antigen pair can be calculated as a function of the complementarity of the (a) size, (b) shape and (c) functional groups that comprise the two structures. The created repertoires are imbedded in a dynamical system model of the immune response to directly evaluate the affect of somatic mutation on affinity maturation. We also present an expanded hypothesis of clonal selection and development to explain how the mutational restrictions imposed by the genetic code and the structure of the antibody repertoire, along with antigen concentration, affinity, and probabilistic factors may interact and contribute to the expansion of specific clones as the response develops over time.

Animals↗
PubMed1998

Object-based attention and occlusion: evidence from normal participants and a computational model.

One way of perceptually organizing a complex visual scene is to attend selectively to information in a particular physical location. Another way of reducing the complexity in the input is to attend selectively to an individual object in the scene and to process its elements preferentially. This latter, object-based attention process was examined, and the predicted superiority for reporting features from 1 relative to 2 objects was replicated in a series of experiments. This object-based process was robust even under conditions of occlusion, although there were some boundary conditions on its operation. Finally, an account of the data is provided via simulations of the findings in a computational model. The claim is that object-based attention arises from a mechanisms that groups together those features based on internal representations developed over perceptual experience and then preferentially gates these features for later, selective processing.

Adolescent↗
PubMed2005

Photochemical surface mapping of C14S-Sml1p for constrained computational modeling of protein structure.

Photochemically generated hydroxyl radicals were used to map solvent-exposed regions in the C14S mutant of the protein Sml1p, a regulator of the ribonuclease reductase enzyme Rnr1p in Saccharomyces cerevisiae. By using high-performance mass spectrometry to characterize the oxidized peptides created by the hydroxyl radical reactions, amino acid solvent-accessibility data for native and denatured C14S Sml1p that revealed a solvent-excluding tertiary structure in the native state were obtained. The data on solvent accessibilities of various amino acids within the protein were then utilized to evaluate the de novo computational models generated by the HMMSTR/Rosetta server. The top five models initially generated by the server all disagreed with both published nuclear magnetic resonance (NMR) data and the solvent-accessibility data obtained in this study. A structural model adjusted to fit the previously reported NMR data satisfied most of the solvent-accessibility constraints. Through minor adjustment of the rotamers of two amino acid side chains for this latter structure, a model that not only provided a lower energy conformation but also completely satisfied previously reported data from NMR and tryptophan fluorescence measurements, in addition to the solvent-accessibility data presented here, was generated.

Amino Acid Sequence↗