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At least 577 records · Page 32Linked to original sources
PubMed1994

Three-dimensional echocardiography for quantitative left ventricular wall motion analysis: a method for reconstruction of endocardial surface and evaluation of regional dysfunction.

A method for quantitative LV wall motion analysis based on 3-D reconstruction of the LV endocardial surface is presented. The reconstruction is based on a minimum of three transthoracic apical 2-D cineloops of the LV, digitally transferred from the ultrasound scanner to a computer. Images are obtained by rotating the transducer around the LV long axis. Endocardial borders are traced with an automatic edge detection algorithm with manual correction. These borders are used with a specially designed computer algorithm for reconstruction of LV cavity 3-D shape, and LV volumes, ejection fraction, and endocardial surface area can be determined. The end-diastolic and end-systolic endocardial surfaces are compared for analysis of regional wall motion. A threshold value is selected to discriminate between normal and abnormal wall motion. Regional wall motion abnormalities are displayed in a bull's eye plot, and the corresponding endocardial surface area is expressed in percent of the total endocardial area. Phase analysis is performed from reconstruction of the endocardial surface throughout the cardiac cycle, and displays regions with abnormal wall motion as being out of phase with LV volume variation. Thus, LV 3-D reconstruction performed by this method can be used for quantitative analysis of wall motion in several clinical situations, and due to the simplicity of processing the data, can be useful outside the research laboratory.

Echocardiography↗
PubMed2006

Cranioplasty after trephination using a novel biodegradable burr hole cover: technical case report.

OBJECTIVE AND IMPORTANCE: We have developed novel biodegradable polymer implants by using the rapid prototyping technology fused deposition modeling. Early results of a clinical pilot study for cranioplasty are presented. CLINICAL PRESENTATION: Five patients with the diagnosis of chronic subdural hematoma were included in the study. After trephination and evacuation of the subdural hematoma, burr holes (diameter, 14 mm) were closed using a biodegradable implant made of polycaprolactone. Implants were computer designed with an upper rim diameter of 16 mm and a 14 mm body diameter with a fully interconnected, honeycomb-like architecture of 400 to 600 microm in pore size. INTERVENTION: Postoperative computed tomographic scans indicated that the plugs were stably anchored in the osseous host environment with no fluid collection detectable. The postoperative course was uneventful, and patients were discharged after 5 days. Follow-up scans after 3, 6, and 12 months showed that the implants were well integrated in the surrounding calvarial bone with new bone filling the porous space. CONCLUSION: These novel polymer scaffolds made of the slow-degrading material polycaprolactone represent a suitable implant for closure of post-trephination defects.

Absorbable Implants↗
PubMed2002

Structure determination of a pseudotripeptide zinc complex with the COSMOS-NMR force field and DFT methods.

A His-X-His pseudotripeptide zinc complex (X is a N-alkyl glycine derivative) similar to the catalytic center of the carbonic anhydrase was computer designed and experimentally synthesized. Using 2D-NMR techniques, all proton, carbon chemical shifts and nuclear overhauser effect signals were assigned. The three-dimensional structure of the complex was determined with the COSMOS (computer simulation of molecular structures) force field by applying 13C bond polarization theory chemical shift pseudo forces and restrictions for NOE distances. From molecular dynamics, simulated annealing simulations and geometry optimizations, the three best force field structures were taken for a final investigation by density functional theory calculations.

Carbon Isotopes↗
PubMed1999

Using computational auditory models to predict simultaneous masking data: model comparison.

In order to develop improved remediation techniques for hearing impairment, auditory researchers must gain a greater understanding of the relation between the psychophysics of hearing and the underlying physiology. One approach to studying the auditory system has been to design computational auditory models that predict neurophysiological data such as neural firing rates [15], [1]. To link these physiologically-based models to psychophysics, theoretical bounds on detection performance have been derived using signal detection theory to analyze the simulated data for various psychophysical tasks [20]. Previous efforts, including our own recent work using the Auditory Image Model, have demonstrated the validity of this type of analysis; however, theoretical predictions often continue to exceed experimentally-measured performance [9], [21]. In this paper, we compare predictions of detection performance across several computational auditory models. We also reconcile some of the previously observed discrepancies by incorporating appropriate signal uncertainty into the optimal detector.

Computer Simulation↗
PubMed2006

The color of rhodopsins at the ab initio multiconfigurational perturbation theory resolution.

We demonstrate that "brute force" quantum-mechanics/molecular-mechanics computations based on ab initio (i.e., first principles) multiconfigurational perturbation theory can reproduce the absorption maxima of a set of modified bovine rhodopsins with an accuracy allowing for the analysis of the factors determining their colors. In particular, we show that the theory accounts for the changes in excitation energy even when the proteins display the same charge distribution. Three color-tuning mechanisms, leading to changes of close magnitude, are demonstrated to operate in these conditions. The first is based on the change of the conformation of the conjugated backbone of the retinal chromophore. The second operates through the control of the distance between the positive charge residing on the chromophore and the carboxylate counterion. Finally, the third mechanism operates through the changes in orientation of the chromophore relative to the protein. These results offer perspectives for the unbiased computational design of mutants or chemically modified proteins with wanted optical properties.

Animals↗
PubMed2000

Rational design of nascent metalloenzymes.

Understanding the early genesis of new enzymatic functions is one of the challenges in protein design, mechanistic enzymology, and molecular evolution. We have experimentally mimicked starting points in this process by introducing primitive iron and oxygen binding sites at various locations in thioredoxin, a small protein lacking metal centers, by using computational design. These rudimentary active sites show emerging enzymatic activities that select to varying degrees between different oxygen chemistries. Even within these nascent enzymes, mechanisms by which different reactions are controlled can be discerned. These involve both stabilizing and destabilizing interactions imposed on the metal center by the surrounding protein matrix.

Catalysis↗
PubMed2006

Rational design of new binding specificity by simultaneous mutagenesis of calmodulin and a target peptide.

Calcium-saturated calmodulin (CaM) binds and influences the activity of a varied collection of target proteins in most cells. This promiscuity underlies the role of CaM as a shared participant in calcium-dependent signal transduction pathways but imposes a handicap on popular CaM-based calcium biosensors, which display an undesired tendency to cross-react with cellular proteins. Designed CaM/target pairs that retain high affinity for one another but lack affinity for wild-type CaM and its natural interaction partners would therefore be useful as sensor components and possibly also as elements of "synthetic" cellular-signaling networks. Here, we have adopted a rational approach to creating suitably modified CaM/target complexes by using computational design methods to guide parallel site-directed mutagenesis of both binding partners. A hierarchical design procedure was applied to suggest a small number of complementary mutations on CaM and on a peptide ligand derived from skeletal-muscle light-chain kinase (M13). Experimental analysis showed that the procedure was successful in identifying CaM and M13 mutants with novel specificity for one another. Importantly, the designed complexes retained an affinity comparable to the wild-type CaM/M13 complex. These results represent a step toward the creation of CaM and M13 derivatives with specificity fully orthogonal to the wild-type proteins and show that qualitatively accurate predictions may be obtained from computational methods applied simultaneously to two proteins involved in multiple-linked binding equilibria.

Amino Acid Sequence↗
PubMed1995

Computer-assisted geometric design of cerebral aneurysms for surgical simulation.

This report presents conceptual aspects and the clinical implications of a computer-assisted geometric design of a cerebral aneurysm and surrounding structures. The technique is based on the approximation power of the parametric spline function, which achieves interpolation and surface fitting of the arterial information obtained by conventional angiography. Computer graphic transformations including shifting, scaling, rotation, and putting different colors in different intensities make it possible to obtain the surgical simulation of a cerebral aneurysm. To our knowledge, this is the first report in which the computer graphic simulation of the surgical view of a cerebral aneurysm is made with a personal computer. Using our method, it may be possible to obtain the surgical simulation of a more complicated view by introducing a navigation system of a new style for conventional open neurosurgery. Concepts and the technical details of the method are described.

Basilar Artery↗
PubMed1994

Discovery of new anticancer drugs by computer-aided drug design.

BACKGROUND: Determination of the three-dimensional molecular structures of proteins, enzymes and nucleic acids is the first step in the development of molecular models of drug-receptor complexes that may be used in the rational computer-aided design of new and sometimes novel inhibitors with altered recognition and receptor-affinity properties. CONCLUSION: This approach provides a rational method for developing drugs that may be highly selective for a particular oncogene or other protein targets.

Antineoplastic Agents↗
PubMed2003

Increased detection of structural templates using alignments of designed sequences.

Protein structure prediction by comparative modeling benefits greatly from the use of multiple sequence alignment information to improve the accuracy of structural template identification and the alignment of target sequences to structural templates. Unfortunately, this benefit is limited to those protein sequences for which at least several natural sequence homologues exist. We show here that the use of large diverse alignments of computationally designed protein sequences confers many of the same benefits as natural sequences in identifying structural templates for comparative modeling targets. A large-scale massively parallelized application of an all-atom protein design algorithm, including a simple model of peptide backbone flexibility, has allowed us to generate 500 diverse, non-native, high-quality sequences for each of 264 protein structures in our test set. PSI-BLAST searches using the sequence profiles generated from the designed sequences ("reverse" BLAST searches) give near-perfect accuracy in identifying true structural homologues of the parent structure, with 54% coverage. In 41 of 49 genomes scanned using reverse BLAST searches, at least one novel structural template (not found by the standard method of PSI-BLAST against PDB) is identified. Further improvements in coverage, through optimizing the scoring function used to design sequences and continued application to new protein structures beyond the test set, will allow this method to mature into a useful strategy for identifying distantly related structural templates.

Algorithms↗
PubMed2003

Rehabilitation of chronic post-stroke visual field defect with computer-assisted training: a clinical and neurophysiological study.

PURPOSE: Our aim was to study whether homonymous visual field defects could be restored in chronic stroke patients (N = 5) using computer-assisted training, and whether the possible beneficial effect could be maintained. Visual evoked potential (VEP) recordings were applied to evaluate whether they could demonstrate the possible training effects at the cortical level. METHODS: We applied a specially designed computer program in the training. Subjective assessment, static and kinetic perimetry, and pattern reversal hemifield VEP recordings were used to detect the possible changes. RESULTS: Two patients showed improvements immediately after the training in static perimetry. Further improvements were detected at a later follow-up in three patients. With kinetic perimetry, improvements were detected in three patients. The visual field defect was detected with VEP recordings in four patients before the training, and improvements could be verified with the method in three patients, two of which clearly improved in the static perimetry as well. CONCLUSIONS: In three patients, the visual defect diminished with the computer-assisted method. It seems evident that visual field defects resulting from stroke can be partially restored even in the chronic phase.

Adolescent↗
PubMed2006

Spatial ability subfactors and their influences on a computer-based information search task.

OBJECTIVE: The present study examined the relationship between two distinct subfactors of spatial ability and performance in an information search task modeled on browsing the Web. BACKGROUND: Previous studies have found relationships between various measures of spatial ability and performance in a wide variety of computer-based tasks. METHOD: In the search task 101 participants (18-29 years of age) searched for the answer to a question by navigating the system. They completed the experimental task as well as a battery of cognitive ability measures that included two different measures of spatial ability. RESULTS: The results indicate that spatial orientation ability was related to performance with tasks that were high in their navigational requirement (engendered by the use of a novel aid), whereas spatial visualization was unrelated to performance in any task condition. CONCLUSION: A closer inspection of the cognitive requirements of a task may reveal what interventions could be most useful when designing computer systems or developing training programs. APPLICATION: Given the unique differences between the different spatial abilities, the current results suggest the design of navigational aids that place less demand on spatial orientation ability.

Adolescent↗
PubMed2005

Assessing mobility in children using a computer adaptive testing version of the pediatric evaluation of disability inventory.

OBJECTIVE: To assess score agreement, validity, precision, and response burden of a prototype computerized adaptive testing (CAT) version of the Mobility Functional Skills Scale (Mob-CAT) of the Pediatric Evaluation of Disability Inventory (PEDI) as compared with the full 59-item version (Mob-59). DESIGN: Computer simulation analysis of cross-sectional and longitudinal retrospective data; and cross-sectional prospective study. SETTING: Pediatric rehabilitation hospital, including inpatient acute rehabilitation, day school program, outpatient clinics, community-based day care, preschool, and children's homes. PARTICIPANTS: Four hundred sixty-nine children with disabilities and 412 children with no disabilities (analytic sample); 41 children without disabilities and 39 with disabilities (cross-validation sample). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Summary scores from a prototype Mob-CAT application and versions using 15-, 10-, and 5-item stopping rules; scores from the Mob-59; and number of items and time (in seconds) to administer assessments. RESULTS: Mob-CAT scores from both computer simulations (intraclass correlation coefficient [ICC] range, .94-.99) and field administrations (ICC=.98) were in high agreement with scores from the Mob-59. Using computer simulations of retrospective data, discriminant validity, and sensitivity to change of the Mob-CAT closely approximated that of the Mob-59, especially when using the 15- and 10-item stopping rule versions of the Mob-CAT. The Mob-CAT used no more than 15% of the items for any single administration, and required 20% of the time needed to administer the Mob-59. CONCLUSIONS: Comparable score estimates for the PEDI mobility scale can be obtained from CAT administrations, with losses in validity and precision for shorter forms, but with a considerable reduction in administration time.

Adolescent↗
PubMed2004

Large-scale grid-enabled lattice Boltzmann simulations of complex fluid flow in porous media and under shear.

Well-designed lattice Boltzmann codes exploit the essentially embarrassingly parallel features of the algorithm and so can be run with considerable efficiency on modern supercomputers. Such scalable codes permit us to simulate the behaviour of increasingly large quantities of complex condensed matter systems. In the present paper, we present some preliminary results on the large-scale three-dimensional lattice Boltzmann simulation of binary immiscible fluid flows through a porous medium, derived from digitized X-ray micro-tomographic data of Bentheimer sandstone, and from the study of the same fluids under shear. Simulations on such scales can benefit considerably from the use of computational steering, and we describe our implementation of steering within the lattice Boltzmann code, called LB3D, making use of the RealityGrid steering library. Our large-scale simulations benefit from the new concept of capability computing, designed to prioritize the execution of big jobs on major supercomputing resources. The advent of persistent computational grids promises to provide an optimal environment in which to deploy these mesoscale simulation methods, which can exploit the distributed nature of computer, visualization and storage resources to reach scientific results rapidly; we discuss our work on the grid-enablement of lattice Boltzmann methods in this context.

Journal Article↗
PubMed1990

Hyperacute T-wave criteria using computer ECG analysis.

Hyperacute T waves (HATWs) have been described as tall-amplitude, primary T-wave abnormalities sometimes seen in the early phases of transmural myocardial infarction. Despite numerous human and animal studies addressing the presence and significance of HATWs, there are no widely held, reliable ECG criteria for their accurate identification. Using a specially designed computer program on a Hewlett-Packard Realm ECG analysis system, we screened 13,393 adult ECGs to identify those having T-wave amplitudes greater than accepted standards (limb leads, greater than 0.5 mV; precordial leads, greater than 1.0 mV). Patients with other known causes of primary and secondary tall T waves were excluded from the study sample. Patients with tall-amplitude T-waves who then developed clinically verifiable myocardial infarction were labeled the HATW group. The HATW group (21) represented 4.1% of the tall T wave group (513) and 0.16% of the entire sample. The remaining patients, who did not meet HATW criteria, were called the early repolarization variant (ERV) group (51). Both groups underwent comparative computer morphology analysis. Nine parameters were statistically significant in discriminating HATWs from early repolarization variants. A combination of J-point position/T-wave amplitude of more than 25%, T-wave amplitude/QRS amplitude of more than 75%, J-point position of more than 0.30 mV, and age of more than 45 years predicted HATWs from a control group with a specificity of 98.0% and a sensitivity of 61.9% and with positive and negative predictive values of 92.9% and 86.2%, respectively. We conclude that HATWs have characterizable discriminating ECG morphology as determined by computer ECG analysis compared with a control group.

Electrocardiography↗
PubMed2002

Computational stabilization of human growth hormone.

Recombinant human growth hormone (hGH) is used worldwide for the treatment of pediatric hypopituitary dwarfism and in children suffering from low levels of hGH. It has limited stability in solution, and because of poor oral absorption, is administered by injection, typically several times a week. Development has therefore focused on more stable or sustained-release formulations and alternatives to injectable delivery that would increase bioavailability and make it easier for patients to use. We redesigned hGH computationally to improve its thermostability. A more stable variant of hGH could have improved pharmacokinetics or enhanced shelf-life, or be more amenable to use in alternate delivery systems and formulations. The computational design was performed using a previously developed combinatorial optimization algorithm based on the dead-end elimination theorem. The algorithm uses an empirical free energy function for scoring designed sequences. This function was augmented with a term that accounts for the loss of backbone and side-chain conformational entropy. The weighting factors for this term, the electrostatic interaction term, and the polar hydrogen burial term were optimized by minimizing the number of mutations designed by the algorithm relative to wild-type. Forty-five residues in the core of the protein were selected for optimization with the modified potential function. The proteins designed using the developed scoring function contained six to 10 mutations, showed enhancement in the melting temperature of up to 16 degrees C, and were biologically active in cell proliferation studies. These results show the utility of our free energy function in automated protein design.

Amino Acid Sequence↗
PubMed1992

Axonal trees and cortical architecture.

In modern computer design considerable care is taken to arrange the components in such a way that wiring is kept to a minimum. Certain features of cortical structure--the mappings, stripes and blobs within areas, and areas themselves--are somewhat reminiscent of the layout of computer components, and suggest that the cortex may also be organized so as to economize on neuronal 'wiring'. One important difference between the brain and a computer is that the wiring in the brain takes the form of elaborate branched structures, namely axonal trees. In this article, it is argued that an assessment of the efficiency of cortical wiring must take account of the branching rules of these trees.

Animals↗
PubMed2003

Influence of a standardized closed soft tissue trauma on resistance to local infection. An experimental study in rats.

PURPOSE: The etiology of local posttraumatic infection in the locomotor system depends on the amount, virulence and pathogenicity of the inoculated microorganisms and the local/systemic host damage due to the type and extent of the accident or iatrogenic trauma. The relative effect of these factors remains unclear. In particular, it is still unclear today whether--in presence of microorganisms--soft tissue damage and its pathophysiological consequences lead to infection after soft tissue trauma, or whether the bacterial contamination is the primarily cause for posttraumatic infection. The aim of the project was to gain information on the consequences of a soft tissue injury in terms of resistance to local infection. Since clinical populations are too heterogeneous, the problem was investigated in a standardized, reduced (no surgery or implants) experimental in vivo model. METHOD: In female Sprague-Dawley-rats with a standardized closed soft tissue trauma to the tibialis anterior muscle (group I: n=13) or without (group II: n=13), we compared the incidence of local infection after a pairwise local, percutaneously injected bacterial challenge with various concentrations of Staphylococcus aureus (2 x 10(4)-2 x 10(6) colony forming units, CFU). The standardized closed soft tissue trauma was created by application of a specially designed, computer controlled impact device. The contaminated soft tissue and the underlying bone were removed under sterile conditions after five days and quantitatively evaluated for bacterial growths. Infection was defined as positive bacterial growth at the soft tissue and/or bone. A stepwise experimental design with an "up-and-down" dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the difference between the infection rates of both groups was performed by two-sided fisher exact test (p<0.05). RESULTS: The overall infection rate was 46%. For the group with soft tissue trauma the ID50 was 1.32 x 10(5) CFU and 1.05 x 10(6) CFU for the group without soft tissue trauma. The infection rate was 69% (9 of 13 animals) for the group with soft tissue trauma and 23% (3 of 13 animals) for the group without soft tissue trauma. This difference is statistically significant (p=0.047). CONCLUSIONS: The infection rate after a standardized closed soft tissue injury was significantly higher and the ID50 lower than without soft tissue trauma. Our results demonstrate that in presence of microorganisms it is not primarily the bacterial contamination but rather the soft tissue damage and its pathophysiological consequences resulting in decreased infection resistance that secondarily lead to infection.

Animals↗