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At least 1,225 records · Page 68Linked to original sources
PubMed1992

A computational model of the analysis of some first-order and second-order motion patterns by simple and complex cells.

Although spatio-temporal gradient schemes are widely used in the computation of image motion, algorithms are ill conditioned for particular classes of input. This paper addresses this problem. Motion is computed as the space-time direction in which the difference in image illuminance from the local mean is conserved. This method can reliably detect motion in first-order and some second-order motion stimuli. Components of the model can be identified with directionally asymmetric and directionally selective simple cells. A stage in which we compute spatial and temporal derivatives of the difference between image illuminance and the local mean illuminance using a truncated Taylor series gives rise to a phase-invariant output reminiscent of the response of complex cells.

Algorithms↗
PubMed1989

Calculations of the distribution of zinc in a computer model of human serum.

During the last decade, investigators employing a wide variety of separation techniques have reported that serum albumin, rather than serum transferrin, is the major carrier protein for labile zinc. However, in contrast to these studies, a simple comparison of the zinc binding constants for albumin and transferrin suggests a significant role for transferrin with regard to serum zinc transport. In the present study multicomponent equilibrium calculations that incorporate recently determined binding constants for zinc-transferrin as well as equilibrium constants for the binding of bicarbonate, sulfate and phosphate to apotransferrin have been used to model the distribution of labile zinc in normal human serum. Anion binding has a major impact on the predicted zinc distribution, lowering the percentage of zinc bound to transferrin from 56% to 11%. The model gives approximately 1% zinc as low-molecular-weight complexes. The improved model results are in good agreement with biological studies on the distribution of zinc among serum proteins.

Bicarbonates↗
PubMed1995

Proposals for the angiotensin II receptor-bound conformation by comparative computer modeling of AII and cyclic analogs.

A conformational search using high-temperature molecular dynamics on angiotensin II(AII) and on two cyclic S-S bridged analogs, namely [Hcy3,5]AII and [Cys3,5]AII, in conjunction with a cluster analysis based on the similarities of the three-dimensional patterns of the binding and activation elements, had led to putative AII receptor-bound conformations. These conformations are characterized by a compact folded shape of the peptide backbone, and by particular relative positions of the four pharmacophore groups, namely the aromatic moieties of the Tyr4, His6 and Phe8 residues, and the C-terminal carboxyl group. This compact folded shape, arising from attractive electrostatic interactions between the desolvated N- and C-terminal groups, is similar to the crystallographically determined conformation of AII bound to the antibody Fab receptor.

Angiotensin II↗
PubMed2006

A three-dimensional computer model of four hypothetical mechanisms protecting biofilms from antimicrobials.

Four hypothetical mechanisms for protection of biofilms against antimicrobials were incorporated into a three-dimensional model of biofilm growth and development. The model integrated processes of substrate utilization, diffusion, growth, cell migration, death, and detachment in a cellular automaton framework. Compared to simulations of unprotected biofilms, each of the protective mechanisms provided some tolerance to antimicrobial action. When the mechanisms were compared to each other, the behaviors of the four protective mechanisms produced distinct shapes of killing curves, nonuniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns for dispersed biofilm cells. The differences between the protective mechanisms predicted in these simulations could guide the design of experiments to discriminate antimicrobial tolerance mechanisms in biofilms. Each of the mechanisms could be a plausible avenue of biofilm protection.

Anti-Infective Agents↗
PubMed2006

Protein farnesyltransferase: flexible docking studies on inhibitors using computational modeling.

Using MacroModel, peptide, peptidomimetic and non-peptidomimetic inhibitors of the zinc metalloenzyme, farnesyltransferase (FTase), were docked into the enzyme binding site. Inhibitor flexibility, farnesyl pyrophosphate substrate flexibility, and partial protein flexibility were taken into account in these docking studies. In addition to CVFM and CVIM, as well as our own inhibitors FTI-276 and FTI-2148, we have docked other farnesyltransferase inhibitors (FTIs) including Zarnestra, which presently is in advanced clinical trials. The AMBER* force field was employed, augmented with parameters that were derived for zinc. A single binding site model that was derived from the crystal structure of CVFM complexed with farnesyltransferase and farnesylpyrophosphate was used for these studies. The docking results using the lowest energy structure from the simulation, or one of the lowest energy structures, were generally in excellent agreement with the X-ray structures. One of the most important findings of this study is that numerous alternative conformations for the methionine side chain can be accommodated by the enzyme suggesting that the methionine pocket can tolerate groups larger than methionine at the C-terminus of the tetrapeptide and suggesting alternative locations for the placement of side chains that may improve potency.

Alkyl and Aryl Transferases↗
PubMed2006

Computational models for the prediction of polypeptide aggregation propensity.

In amyloid fibrils, beta-strand conformations of polypeptide chains, or segments thereof, are perpendicular to the fibril axis, but knowledge of their three dimensional structure at atomic level of detail is scarce. Two types of computational approaches have been developed recently for investigating the aggregation propensity of peptides and proteins and identifying the segments most prone to form fibrils (hot spots). The physicochemical properties of the natural amino acids (e.g. beta-propensity, hydrophobicity, aromatic content and charge) have been used to derive phenomenological models able to predict changes in aggregation rate upon mutation, as well as absolute rates and hot spots. Applications of these models to entire proteomes have provided evidence that intrinsically disordered proteins are less amyloidogenic than globular proteins. In the second type of approach, amyloidogenic polypeptides have been decomposed into overlapping segments, and atomistic simulations of three or more copies of each segment have been performed to obtain insights into aggregation propensity and structural details of the ordered aggregates (e.g. turn regions).

Chemical Phenomena↗
PubMed2005

On the use of computational models for the quantitative assessment of surgery in congenital heart disease.

The surgical repair of congenital heart disease often involves significant modifications to the circulatory tree. Resections, reconstructions, graft insertions and the deployment of implants and biomedical devices have an impact on local and systemic haemodynamics, which may be difficult to foresee or to assess quantitatively by clinical investigation alone. Mathematical models can be employed to visualise, estimate or predict events and physical quantities that are difficult to observe or measure, and can be successfully applied to the study of the pre- and post-operative physiology of cardiovascular malformations. This paper analyses the potentialities of computation fluid dynamics in this respect, outlining the method, its requirements and its limitations. Examples are given of lumped parameter models, axi-symmetric models, three-dimensional models, fluid-structure interaction simulations and multiscale computing applied to total cavo-pulmonary connection, aortic coarctation and aortic arch reconstruction.

Cardiovascular Surgical Procedures↗
PubMedDate not supplied

Dynamics of active progressive infection with HIV1: data acquisition for computer modeling.

Nineteen adult patients with progressive HIV1 infection, which progressed within 5 years from acute HIV syndrome to final AIDS were studied. Changes in HIV antibody titer, viral RNA load, peripheral T lymphocytes and subpopulations as well as CD4/CD8 cell ratio and cell death (apoptosis) were monitored. The data were collected for comparison with HHV-6 infection, which involves the same cell populations yet patients usually recover, and to serve as a further basis for future computer simulation studies. The results showed progressive increases of viral RNA copies in the patients' plasma even during clinical latency, which correlates with lymphocyte apoptosis and CD4 cell loss. Besides apparent direct CD4 cell destruction, there was indication of a disturbed intrathymic T cell differentiation. Pathologic cell changes in HIV infection continue until final death of the patient and do not return to normal after variable times as in HHV-6 infection. While HHV-6 infection can serve as models for immunostimulation, with or without immune dysregulation in computer simulation studies, HIV infection is a model for immunostimulation with final immune deficiency and cellular aplasia.

Adult↗
PubMed2005

Ultrasound diagnosis of fetal macrosomia: a comparison of weight prediction models using computer simulation.

OBJECTIVE: To assess the frequency of the diagnosis of macrosomia in relation to differing weight estimation formulae in unselected pregnancies. METHODS: Computer modeling techniques were employed. Computer modeling software generated correlated fetal biometry measurements according to published British standards, from 37 to 41 weeks' gestation. For each set of measurements, estimated fetal weights were obtained by a panel of 18 ultrasound weight formulae. The diagnosis of macrosomia was made if the fetal weight estimate was greater than 4500 g. Cohorts of 5000 pregnancies for each week of gestation were studied. RESULTS: The frequency of diagnosis of macrosomia increased progressively with advancing gestational age, with large increases between 40 and 41 weeks. The type of weight estimation formula had a profound influence on the frequency of diagnosis of macrosomia. Five of the formulae tested almost never returned a weight estimate greater than 4500 g. Three formulae yielded false positive rates in excess of 15%. The Hadlock group of formulae yielded frequencies of 0.3% to 14.6%. CONCLUSIONS: Most formulae tend to over-diagnose macrosomia at term. Intervention rates for suspected fetal macrosomia may be influenced by gestational age at the time of scan and the type of fetal weight estimation formula in use.

Birth Weight↗
PubMed2005

The computer modelling of human TRH receptor, TRH and TRH-like peptides.

The aim of this work was to verify the possibility of interactions between the human TRH receptor (an integral membrane protein which belongs to family 1 of G-protein coupled receptors) and TRH-like peptides presented in the prostate gland. These peptides are characterized by substitution of basic amino acid histidine (related to authentic TRH) for neutral or acidic amino acid, such as glutamic acid, phenylalanine, glutamine or tyrosine. The physiological function of TRH-like peptides in peripheral tissues is not precisely known. However, according to our recent experiments, we assume the existence of a local hormonal network formed by TRH-like peptides and TSH in the prostate gland. The network can be associated with circulating thyroid and steroid hormones, and may represent a new regulatory mechanism influencing the proliferative ability of prostatic tissue. A similar network of authentic TRH and TSH was already found in the gastrointestinal tract. The experimentally determined 3D-structures of human TRH receptor (hTRHr) and TRH-like peptides are not available. From this point of view we used de novo modeling procedures of G-protein coupled receptors on an automated protein modeling server used at the Glaxo Wellcome Experimental Research (Geneva, Switzerland). 3D-structures of TRH-like peptides were determined with a computer program CORINA (written by the team of J. Gasteiger, Computer-Chemie-Centrum and Institute for Organic Chemistry, University of Erlangen-Nurenberg, Germany). The generated PDB files with 3D-coordinates were visualized with Swiss-Pdb Viewer Release 3.51 (Glaxo Wellcome). From recent results it is evident that polar amino acids belonging to the extracellular terminus of hTRHr transmembrane regions can participate in interactions between TRH and hTRHr. There is no direct evidence that TRH-like peptides interact with the presented hTRHr model. On the contrary, with respect to the similar 3D-shape and the identity of terminal amino acids, it appears that these interactions are highly probable as well as the nearly 100 % cross-reactions between TRH or TRH-like peptides and antibody specific against authentic TRH. Closed terminal amino acids (pyroglutamic acid and proline-amide) of TRH or TRH-like peptides are important for these interactions. Desamido-TRH or glutamyl metabolites will be repelled by the negative potential of ASP195 (E: D93) and GLU298 (G: E137).

Amino Acid Sequence↗
PubMed1988

A digital computer model for optimal programming of hemodialytic treatment.

A mathematical model of hydroelectrolyte exchanges and arterial pressure regulation in the human body during dialysis has been set up. It is conceived as a tool for a new dialysis unit which will be able to "interpret" the signals supplied by suitable instruments connected to the patient and modify the machine set-points in real time in order to obtain clinical results defined by the physician. The main aim is the prevention of hypotensive episodes during treatment. An experimental protocol has been developed for parameter estimation of each patient during a single dialysis. Clinical tests illustrated the model's ability to fit the patient's state during dialysis. This is the first step in the more general task of validation of the model, necessary for the achievement of a closed-loop dialysis unit.

Computer Simulation↗