Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Computer Graphics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMed1998

Three-dimensional structure of a human Fab with high affinity for tetanus toxoid.

BACKGROUND: The wide range of antibody specificity and affinity results from the differing shapes and chemical compositions of their binding sites. These shapes range from discrete grooves in antibodies elicited by linear oligomers of nucleotides and carbohydrates to shallow depressions or flat surfaces for accommodation of proteins, peptides and large organic compounds. OBJECTIVES: To determine the Fab structure of a high-affinity human antitoxin antibody. To explore structural features which enable the antibody to bind to intact tetanus toxoid, peptides derived from the sequence of the natural immunogen and antigenic mimics identified by combinatorial chemistry. To explain why this Fab shows a remarkable tendency to produce crystals consistently diffracting to d spacings of 1.7-1.8 A. To use this information to engineer a strong tendency to crystallize into the design of other Fabs. STUDY DESIGN: The protein was crystallized in hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG) 8000. Crystals were subjected to X-ray analysis and the three-dimensional structure of the Fab was determined by the molecular replacement method. Interactive computer graphics were employed to fit models to electron density maps, survey the structure in multiple views and discover the crystal packing motif of the protein. RESULTS: Exceptionally large single crystals of this protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter was cut into six irregular pieces, each retaining the features of the original in diffracting to high resolution (1.8 A) with little decay in the X-ray beam. In an individual Fab, the active site is relatively flat and it seems likely that the protein antigen and derivative peptides are tightly held on the outer surface without significant penetration into the interior. There is no free space to accommodate even a dipeptide between VH and VL. One of the unique features of the B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site. The CDR3 of the H chain contributes significantly to this ridge, as well as to adjoining regions projected to be important for the docking of the antigen. Both the ease of crystallization and the favorable diffraction properties are mainly attributable to the tight packing of the protein molecules in the crystal lattice. DISCUSSION: The B7-15A2 active site provides a stable and well defined platform for high affinity docking of proteins, peptides and their mimotopes. The advantages for future developments are suggested by the analysis of the crystal properties. It should be possible to incorporate the features promoting crystallization, close packing and resistance to radiation damage into engineered human antibodies without altering the desired specificities and affinities of their active sites.

Amino Acid Sequence↗
PubMed2002

Haptic reproduction and interactive visualization of a beating heart for cardiovascular surgery simulation.

This paper aims to achieve haptic reproduction and real-time visualization of a beating heart for cardiac surgery simulation. Unlike most forgoing approaches, the authors focus on time series datasets and propose a new framework for interactive simulation of active tissues. The framework handles both detection and response of collisions between a manipulator and a beating virtual heart. Physics-based force feedback of autonomous cardiac motion is also produced based on a stress-pressure model, which is adapted to elastic objects filled with fluid. Time series datasets of an adult man were applied to an integrated simulation system with a force feedback device. The system displays multi-dimensional representation of a beating heart and provides a basic training environment for surgical palpation. Finally, results of measurement and medical assessment confirm the achieved quality and performance of the presented framework.

Algorithms↗
PubMedDate not supplied

Building a flexible protocol information system with ready for use' web-technology.

This paper describes how web technology, currently available, can be used to build a fast and easy flexible protocol information system. The interface design and functionalities of the system were based on experiences with a previous version of a protocol information system (ProtoVIEW). A wide range of diagnostic or therapeutic protocols could be retrieved and viewed with ProtoVIEW. The Web-based version contains all functionalities of the non web-based version plus several new functionalities. The web version contains an X-ray viewer and a great deal of interactivity such as validation of electronic patient data forms. The most important additional function is the context sensitive protocol support that may lead to improved protocol adherence. Finally, the web-based version can be accessed from any working place since patient data and protocols are stored centrally.

Cholestasis↗
PubMed2002

Morphometric analysis of lymphatic vessels in primary biliary cirrhosis.

The purpose of this study was to elucidate the morphometric changes occurring in hepatic lymphatics in primary biliary cirrhosis (PBC). The lymphatic vessels were stained intensely by enzyme-histochemistry for 5'-nucleotidase while blood vessels stained well for alkaline phosphatase (ALP). We performed a morphometric analysis to estimate the number of lymphatic and blood vessels and their areas, using computer graphics software (NIH Image). Both the number of lymphatics and their areas in specimens in patients with PBC at an early stage were found to have increased. Neither the number nor the areas of the blood vessels showed any obvious relationship with the degree of fibrosis of PBC. Our results clarified that the sizes and number of lymphatics are increased even in the early stage of PBC. This is thought to be due to increased lymph production, which is caused by disturbance of the microcirculation associated with portal hypertension.

Journal Article↗
PubMed1999

Effects of age on distally and proximally generated drawing movements: a kinematic analysis of school children and adults.

The effects of age on basic fine motor functions were assessed using a kinematic analysis of simple repetitive drawing movements in a sample of 53 right-handed children aged 7 to 14 years 11 months and 16 adults aged 27 to 54 years with no detectable abnormality with neurological examination. Lines, circles, and half-circles were drawn at a self-chosen and maximum velocity with a pressure-sensitive pen on a computer graphics tablet. Patterns generated by finger, wrist, and arm movements, and those generated by combined finger-wrist movements with and without a change in the drawing direction were analysed. The frequencies of all movement patterns increased until adulthood: 0.1 Hz per year for half-circles, 0.15 to 0.2 Hz per year for circles and lines generated by arm and wrist movements. The greatest increase (0.35 Hz per year) was observed for lines produced by finger movements. Differences in movement frequencies between finger versus wrist or arm movements when drawing lines decreased from about 3 Hz in 7- to 8-year-olds to 0.5 to 1 Hz in adolescents. In adults the difference between maximum finger, wrist, and arm movement frequencies decreased to almost zero. In contrast, the differences in movement patterns with and without change in direction remained stable until adulthood. Based on these results it is hypothesized that the differential effects of finger and more proximally generated movements on age reflect maturation of distinct neuronal sites of the corticostriatal-cerebellar circuit rather than acquisition of motor skills or myelinization of corticospinal pathways.

Adolescent↗
PubMed1991

Effects of ectostriatal lesions on natural concept, pseudoconcept, and artificial pattern discrimination in pigeons.

Pigeons were trained on four different visual discrimination tasks: (1) concept of natural stimuli (food vs. non-food object discrimination); (2) arbitrary classification of natural stimuli (pseudoconcept); (3) concept of artificial stimuli (triangles generated by computer graphics); and (4) discrimination of one pair of artificial stimuli. Then, lesions of the ectostriatum were carried out. The ectostriatal lesions impaired the arbitrary classification of natural stimuli and the concept of artificial pattern but did not impair the natural concept or the simple discrimination of fixed two stimuli. Lesions in the neostriatum did not cause deficits in any discrimination task. The birds had to learn individual stimuli for the arbitrary classification of stimuli and the stimulus generalization test after the artificial pattern concept discrimination indicated that the pigeons formed a concept more complicated than "triangle" in human language. These results suggest that the ectostriatum plays a role in task discrimination that requires much visual processing to classify stimuli.

Animals↗
PubMed2004

Simulating colonial growth of fungi with the Neighbour-Sensing model of hyphal growth.

The Neighbour-Sensing model brings together the basic essentials of hyphal growth kinetics into a vector-based mathematical model in which the growth vector of each virtual hyphal tip is calculated by reference to the surrounding virtual mycelium. The model predicts the growth pattern of many hyphae into three spatial dimensions and has been used to simulate complex fungal fruit body shapes. In this paper we show how the Neighbour-Sensing model can simulate growth in semi-solid substrata like agar or soil, enabling realistic simulation of mycelial colonies of filamentous fungi grown in 'Petri-dish style' experimental conditions. Newly implemented capabilities in the model include: a measurement and logging system within the program that maintains basic statistics about the mycelium it is simulating, this facilitates kinetic experimentation; inclusion of 'substrates' in the data space causing positive or negative tropisms for the growing mycelium; a horizontal plane tropism that provides a way of simulating colonies growing in or on a substratum like agar or soil by imposing a horizontal constraint on the data space the cyberhyphal tips can explore; three categories of hypha--standard hyphae are those that start the simulation, leading hyphae can emerge from the colony peripheral growth zone to take on a leading role, and secondary hyphae are branches that can arise late, far behind the peripheral growth zone, when mature hyphal segments resume branching to in-fill the older parts of the colony. We show how the model can be used to investigate hyphal growth kinetics in silico in experimental scenarios that would be difficult or impracticable in vivo. We also show that the Neighbour-Sensing model can generate sufficiently realistic cord-like structures to encourage the belief that this model is now sufficiently advanced for parameters to be defined that simulate specific in silico cyberfungi. The potential utility of these cyberspecies is that they provide a means to model the morphogenetic effects of a variety of factors, from environmental and nutritional features to mutations, in experimentally realistic situations, offering a valuable addition to the experimental toolkit of all those interested in fungal growth and morphology.

Computer Graphics↗
PubMed2004

Concerted regulation of all hyphal tips generates fungal fruit body structures: experiments with computer visualizations produced by a new mathematical model of hyphal growth.

Filamentous hyphal growth is inherently suited to kinetic analysis, and in many respects the fungal mycelium can be viewed as a very mechanical biological system, which lends itself to mathematical modelling. The mathematics of hyphal tip extension growth are well-established. However, even though a hyphal growth equation can be written with confidence, and we have a good understanding of the effects of tropisms on growth, it is not easy to form a mental picture of the behaviour of large populations of hyphal tips. What is required, and what we believe we have produced, is a mathematical model that is sufficiently sophisticated to produce a realistic visualization of fungal hyphal growth. This provides us with a cyberfungus that can be used for experimentation on the theoretical rules that might govern hyphal patterning, hyphal interactions, and tissue formation and organ development by actually visualizing the virtual hyphal growth patterns that result from different regulatory scenarios. From a series of model experiments the most significant observation is that complex fungal fruit body shapes can be simulated by applying the same regulatory functions to all of the growth points active in a structure at any specific time. No global control of fruit body geometry is necessary. No localized regulation is necessary. The shape of the fruit body emerges from the concerted response of the entire population of hyphal tips, in the same way, to the same signals.

Computer Graphics↗
PubMed1999

Consistency of handwriting movements in dementia of the Alzheimer's type: a comparison with Huntington's and Parkinson's diseases.

Patients with dementia of the Alzheimer's type (DAT) and their matched controls wrote, on a computer graphics tablet, 4 consecutive, cursive letter 'l's, with varying levels of visual feedback: noninking pen and blank paper so that only the hand movements could be seen, noninking pen and lined paper to constrain their writing, goggles to occlude the lower visual field and eliminate all relevant visual feedback, and inking pen with full vision. The kinematic measures of stroke length, duration, and peak velocity were expressed in terms of consistency via a signal-to-noise ratio (M value of each parameter divided by its SD). Irrespective of medication or severity, DAT patients had writing strokes of significantly less consistent lengths than controls', and were disproportionately impaired by reduced visual feedback. Again irrespective of medication or severity, patients' strokes were of significantly less consistent duration, and significantly less consistent peak velocity than controls', independent of feedback conditions. Patients, unlike controls, frequently perseverated, producing more than 4 'l's, or multiple sets of responses, which was not differentially affected by level of visual feedback. The more variable performance of patients supports a degradation of the base motor program, and resembles that of Huntington's rather than Parkinson's disease patients. It may indeed reflect frontal rather than basal ganglia dysfunction.

Aged↗
PubMed1995

Molecular dynamics of the anti-fluorescein 4-4-20 antigen-binding fragment. 1. Computer simulations.

Two 174 ps molecular dynamics simulations of the solvated, 4-4-20 antigen-binding fragment (Fab) were performed: one with antigen (fluorescein) in the antigen-combining site and another with it removed. At the beginning of the second simulation, fluorescein was relocated from the antigen-combining site to a point outside the cutoff distance for nonbonded interactions by applying a "pulling force". Initially, the antigen-combining site collapsed when fluorescein was removed but gradually re-formed as the simulation progressed. In addition, several other differences were observed between the two simulations. These included (i) structural rearrangements of key contact residues in the antigen-combining site, (ii) significant differences in the degree of hydration of the antigen-combining site, (iii) a more acute elbow bend angle in the case of the unliganded form, and (iv) less correlated motions of amino acid residues in the unliganded form. These observations suggested that the Fab without fluorescein exhibited a greater degree of segmental flexibility than the Fab with fluorescein. Time-resolved fluorescence experiments were performed in order to validate this prediction, and the results are described in the following paper [Lim et al. (1995) Biochemistry 34, 6975-6984].

Antigens↗
PubMed1995

Functional role of arginine-11 in the N-terminal helix of skeletal troponin C: combined mutagenesis and molecular dynamics investigation.

The two main structural differences between calmodulin (CaM) and skeletal troponin C (sTnC) are the absence in CaM of (i) the short N-terminal helix in TnC and (ii) the triplet KGK (residues 91-93; numbering according to chicken sTnC). It was recently shown that deletion of both structural groups from sTnC imparted to the resulting construct the CaM-like ability to activate phosphodiesterase (PDE) and to regulate force development in smooth muscle. To continue probing of the structural basis of the differential behavior of sTnC and CaM, residue Arg-11 in rabbit sTnC was mutated to Ala because the interactions of Arg-11 with distal residues in the N-terminal domain seem to link the N-terminal helix to the rest of the structure. The mutant exhibits CaM-like function in its ability to activate PDE (about 50% of CaM at 5 microM concentration). If, in addition, the KGK triplet is also deleted, PDE activation increases to about 80%. Both constructs retain their TnC function to nearly 100%. To explore the mechanistic basis of this remarkable observation, computational simulations of the molecular dynamics (MD) were carried out for both wild-type 4Ca2+.sTnC and the 4Ca2+.R11A mutant, and the results were compared to those from earlier simulations of 4Ca2+.CaM. Two types of structural changes observed from such simulations of the molecular dynamics of CaM had been considered to have a functional role: (i) a compaction to a more globular form and (ii) a reorientation of the Ca-binding domains around the central tether helix.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Amino acid differences at positions 10, 11, and 104 explain the profound catalytic differences between two murine pi-class glutathione S-transferases.

The glutathione S-transferases play a pivotal role in the detoxification of toxic and carcinogenic electrophiles. We have previously reported the isolation of two actively transcribed murine pi-class glutathione S-transferase genes. In this study the two proteins encoded by these genes, Gst p-1 and Gst p-2, were expressed in Escherichia coli and found to exhibit profoundly different catalytic activities, the activity of Gst p-2 toward a panel of electrophilic substrates being 1-3 orders of magnitude lower than that of Gst p-1. In order to establish the basis for the difference between these highly homologous proteins, mutants were generated where specific amino acids had been exchanged. Kinetic analysis of the wild-type and mutant enzymes revealed that the amino acid differences occurring at positions 10 (Val/Ser), 11 (Arg/Pro), and 104 (Val/Gly) are responsible for the reduced enzymatic activity of Gst p-2. This analysis together with computer graphics modeling for Gst p-2 indicated that these changes affected both substrate and glutathione binding to the enzyme.

Amino Acid Sequence↗
PubMed1995

Comparison of MD simulations and NMR experiments for hen lysozyme. Analysis of local fluctuations, cooperative motions, and global changes.

Three 1000 ps molecular dynamics simulations of hen lysozyme have been compared with a range of experimental NMR parameters in order to gain insight into the dynamical properties of the protein and to assess the significance of the motional events observed in the simulations. The simulations, one in vacuum and two in water, were used to estimate interproton distances (for comparison with NOE data), 3JHN alpha and 3J alpha beta coupling constants and 1H-15N order parameters. Comparison of these values with experimental data, particularly NOEs, enabled force field-induced changes to the structure during the simulations to be recognized. It has been shown, however, that these changes can be largely eliminated by slight modifications to the force field. Using a simulation performed in water with this modified force field, it has been found that 1H-15N order parameters calculated for side chain groups in particular correlate well with experimental values and reflect the substantial dependence of these motional properties on the environment, particularly surface exposure, in which the side chain is found. In this case, the simulation then provides models for the motional processes giving rise to the observed experimental data. The results indicate that the order parameter values reflect primarily the number of torsion angles about which rotameric interchange occurs. In addition to local motions, the two different domains of lysozyme have been found to behave differently in the simulations. Possible implications of these differences for the interpretation of unfolding simulations and experimental observations of folding intermediates for lysozyme are discussed.

Animals↗
PubMed1992

Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors.

Succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide corresponding to a common sequence of endogenous thiol protease inhibitors is a noncompetitive reversible inhibitor of papain. In order to elucidate the binding mode of the inhibitor at the atomic level, its complex with papain was crystallized at ca. pH 7.0 using the hanging drop method, and the crystal structure was analyzed at 1.7-A resolution. The crystal has space group P2(1)2(1)2(1), with a = 43.09, b = 102.32, c = 49.69 A, and Z = 4. A total of 47,215 observed reflections were collected on the imaging plates using the same single crystal, and 19,833 unique reflections with Fo > sigma (Fo) were used for structure determination and refinement. The papain structure was determined by use of the atomic coordinates of papain previously reported, and then refined by the X-PLOR program. The inhibitor molecule was located on a difference Fourier map and fitted into the electron density with the aid of computer graphics. The complex structure was finally refined to R = 19.6% including 118 solvent molecules. The X-ray analysis of the complex crystal shows that the inhibitor is located at the R-domain side, not in the center of the binding site created by the R- and L-domains of papain. Such a binding mode of the inhibitor explains well the biological behavior that the inhibitor exhibits against papain. Comparison with the structure of papain-stefin B complex indicates that the structure of the Gln-Val-Val-Ala-Gly sequence itself is not necessarily the essential requisite for inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Glycation of human beta 2-microglobulin in patients with hemodialysis-associated amyloidosis: identification of the glycated sites.

beta 2-Microglobulin (beta 2M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that beta 2M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified beta 2M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 from macrophages, suggesting the potential link of glycation of beta 2M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of beta 2M purified from long-term hemodialysis patients as well as beta 2M incubated with glucose in vitro. Borotritide-treated beta 2M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of beta 2M formed in vivo were found to be almost the same as those of glycated beta 2M in vitro. The primary glycated site was the alpha-amino group of the amino terminal isoleucine. Other minor sites were the epsilon-amino groups of Lys-19, -41, -48, -58, -91, and -94. Computer graphics of the three-dimensional structure of beta 2M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.

Adult↗
PubMed1993

Molecular dynamics simulations of asialoglycoprotein receptor ligands.

Several recent studies have implicated carbohydrates in cell adhesion, inflammation, clearance of glycoproteins from blood circulation, embryonic development, and metastasis among others. Understanding the conformation of these carbohydrate recognition elements and their interaction at the molecular level is essential for the design of oligosaccharide inhibitors/drugs. Given the difficulty in solving carbohydrate structures by X-ray crystallography and since NMR experiments give only time-averaged conformation, molecular dynamics simulations are well suited to determine all the accessible conformations of oligosaccharides. Present communication reports the simulation of some of the oligosaccharide ligands of asialoglycoprotein receptor for 1 ns using Biosym's Insight II molecular modeling package on NCI-FCRDC's Y-MP 8D/8128 supercomputer. Results obtained from these simulations, in addition to explaining the observed differences in the binding affinities of these ligands to the asialoglycoprotein receptor, have led to a modified model for the recognition of the oligosaccharides by the receptor. Accordingly, only the two terminal galactose residues on the 1,3-arm of the triantennary oligosaccharide (GlcNAc2Man3 core of the N-linked oligosaccharides with N-acetyllactosamine in beta 1,2- and beta 1,4-linkages on the 1,3-linked core mannose) are primarily required for recognition, and the terminal galactose on the 1,6-arm (N-acetyllactosamine in beta 1,2-linkage on the 1,6-linked core mannose) provides additional binding energy. It has been shown that the oligosaccharides studied here have significant flexibility and the flexibility is more around the 1,3-linkage than the 1,6-linkage. The need for simulation for longer periods and with multiple initial conformations is also discussed in the present report.

Asialoglycoprotein Receptor↗
PubMed1993

Solute diffusion in lipid bilayer membranes: an atomic level study by molecular dynamics simulation.

To elucidate the mechanism of solute diffusion through lipid bilayer membranes, nearly 4 ns of molecular dynamics simulations of solutes in phospholipid bilayers was conducted. The study, the first atomic level study of solute diffusion in a lipid bilayer, involved four simulations of an all-atom representation of a fully solvated dimyristoylphosphatidylcholine (DMPC) bilayer in the L alpha phase with benzene molecules as solutes, totaling over 7100 atoms. These simulations agree with experimental evidence that the presence of small solutes does not affect bilayer thickness but does result in slight perturbations in the ordering of the hydrocarbon chains. At room temperature, the benzene molecules have essentially isotropic motion and rotate freely. The rate of translational diffusion varies with position within the bilayer and is faster in the center than near the zwitterionic headgroups and is in excellent agreement with experimental values for the diffusion of small solutes in a bilayer. These simulations have elucidated the mechanism of diffusion in a bilayer to be similar to the "hopping" mechanism found for the diffusion of gases through soft polymers. Jumps of up to 8 A can occur in as little as 5 ps whereas average motions for that time period are only approximately 1.5 A. In many cases, the jumps are moderated by torsional changes in the hydrocarbon chains which serve as "gates" between voids through which the benzene molecules move. Comparison of these simulations with another 1000-ps simulation of benzene in a pure alkane provides evidence that lipid bilayers should not be treated as a homogeneous bulk hydrocarbon phase.

Alkanes↗