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At least 919 records · Page 51Linked to original sources
PubMed1993

Variable compensation chest radiography performed with a computed radiography system: design considerations and initial clinical experience.

The authors describe a variable compensation (VC) technique in which an x-ray equalizer and a computed radiography system are used. The VC technique allows retrospective alteration of equalized chest appearance with maintenance of improved signal-to-noise ratio in dense regions. Two imaging plates are used: one upstream of the patient to record the incident beam profile and one down-stream to record the equalized image. Subtraction of a weighted version of the upstream image from the down-stream image permits alteration of the appearance of the VC image, from the extremes of stimulated-unequalized to highly equalized. VC image appearance was optimized with a real-time workstation. The quality of VC images obtained in 33 patients was evaluated by three chest radiologists. Mediastinal appearance was better on VC equalized images than on conventional screen-film images. The stimulation of the appearance of a conventional radiograph with VC proved useful in interpretation of lung appearances on equalized radiographs.

Aged↗
PubMed2006

[Recent development of computer-aided tissue engineering].

OBJECTIVE: To introduce the recent advances of the application of computer technology in tissue engineering. METHODS: The recent original articles related to computer technology, medical image technology, computer-aided design, the advanced manufacture technology were summarized and systematically analyzed. RESULTS: Computer-aided tissue engineering is a new field on tissue engineering. It is the future direction of tissue engineering study. This article reviews recent development of medical CT/MRI scanning, three-dimensional reconstruction, anatomical modeling, computer-aided design, computer-aided manufacturing, rapid prototyping, RP manufacturing of tissue engineering scaffolds and computer-aided implantation. CONCLUSION: Computer-aided tissue engineering can be used in scaffolds design and fabrication, computer-aided artificial tissue implantation. It is a new field on tissue engineering.

Computer-Aided Design↗
PubMed1996

Design considerations and computer modeling related to the development of molecular scaffolds and peptide mimetics for combinatorial chemistry.

A critical issue in drug discovery utilizing combinatorial chemistry as part of the discovery process is the choice of scaffolds to be used for a proper presentation, in a three-dimensional space, of the critical elements of structure necessary for molecular recognition (binding) and information transfer (agonist/ antagonist). In the case of polypeptide ligands, considerations related to the properties of various backbone structures (alpha-helix, beta-sheets, etc.; phi, psi space) and those related to three-dimensional presentation of side-chain moieties (topography; chi (chi) space) must be addressed, although they often present quite different elements in the molecular recognition puzzle. We have addressed aspects of this problem by examining the three-dimensional structures of chemically different scaffolds at various distances from the scaffold to evaluate their putative diversity. We find that chemically diverse scaffolds can readily become topographically similar. We suggest a topographical approach involving design in chi space to deal with these problems.

Animals↗
PubMed1988

An evaluation of the information interface in the design of computer-driven aids for expressive communication.

Computer-based systems as assistive aids for expressive communication have become increasingly sophisticated. One such system, which provides great flexibility in the specification of an operational configuration and which is highly user-oriented in its design, is discussed here. In particular, attention is directed towards the relationship between the physical signals which constitute the representation of graphic-symbol communication units and the transfer of conceptual information which these symbols ultimately mediate. This relationship is investigated practically with a view to establishing a connection between operational criteria at the functional level and the supporting physical infrastructure at the computational level. This investigation leads to some conclusions not only in terms of design strategy for flexible communication aids, but points to issues of broader significance in the area of computer-based assistive devices for those with special needs.

Communication Devices for People with Disabilities↗
PubMed1994

Computer modeling of siphoning for CSF shunt design evaluation.

A computer model of the cerebrospinal fluid (CSF) compartment and various shunt designs was developed to simulate CSF dynamics, particularly in the upright position in which siphoning is known to occur. This novel mathematical model of the CSF compartment incorporates negative pressure and volume components that permit simulation of siphoning. The model was tested with data from a previously reported animal experiment. The correspondence between the model simulation and the reported intracranial pressure and CSF shunt flow rate was very good. A simulation of a shunted hydrocephalic patient in the recumbent and upright position was then carried out to examine the effects of a standard shunt valve, an externally adjustable valve, a variable resistance valve, and an antisiphon device. The resulting pressure profiles, which conformed to previously reported data, indicate that this model would be useful for the evaluation of current and future shunt designs.

Brain↗
PubMed1994

A new method for predicting binding affinity in computer-aided drug design.

A new semi-empirical method for calculating free energies of binding from molecular dynamics (MD) simulations is presented. It is based on standard thermodynamic cycles and on a linear approximation of polar and non-polar free energy contributions from the corresponding MD averages. The method is tested on a set of endothiapepsin inhibitors and found to give accurate results both for absolute as well as relative free energies.

Aspartic Acid Endopeptidases↗
PubMed2005

Mechanistic insights aid computational short interfering RNA design.

RNA interference is widely recognized for its utility as a functional genomics tool. In the absence of reliable target site selection tools, however, the impact of RNA interference (RNAi) may be diminished. The primary determinants of silencing are influenced by highly coordinated RNA-protein interactions that occur throughout the RNAi process, including short interfering RNA (siRNA) binding and unwinding followed by target recognition, cleavage, and subsequent product release. Recently developed strategies for identification of functional siRNAs reveal that thermodynamic and siRNA sequence-specific properties are crucial to predict functional duplexes (Khvorova et al., 2003; Reynolds et al., 2004; Schwarz et al., 2003). Additional assessments of siRNA specificity reveal that more sophisticated sequence comparison tools are also required to minimize potential off-target effects (Jackson et al., 2003; Semizarov et al., 2003). This chapter reviews the biological basis for current computational design tools and how best to utilize and assess their predictive capabilities for selecting functional and specific siRNAs.

Algorithms↗
PubMed1999

Effective elastic properties for lower limb soft tissues from manual indentation experiment.

Quantitative assessment of the biomechanical properties of limb soft tissues has become more important during the last decade because of the introduction of computer-aided design and computer-aided manufacturing (CAD/CAM) and finite element analysis to the prosthetic socket design. Because of the lack of a clinically easy-to-use apparatus, the site and posture dependences of the material properties of lower limb soft tissues have not been fully reported in the literature. In this study, an ultrasound indentation system with a pen-size hand-held probe developed earlier by the authors was used to obtain the indentation responses of lower limb soft tissues. Indentation tests were conducted on normal young subjects with four females and four males at four sites with three body postures. A linear elastic indentation solution was used to extract the effective Young's modulus from the indentation responses. The determined modulus ranged from 10.4 to 89.2 kPa for the soft tissues tested. These results were in a similar range as those reported in the literature. The thickness of the lower limb soft tissues varied slightly with body posture changes. The Young's modulus determined was demonstrated to be significantly dependent on site, posture, subject and gender. The overall mean modulus of male subjects was 40% larger than that of female subjects. No significant correlation was established between the effective Young's modulus and the thickness of entire soft tissue layers.

Adult↗
PubMed1993

Computer-aided drug design: a free energy perturbation study on the binding of methyl-substituted pterins and N5-deazapterins to dihydrofolate reductase.

Molecular dynamics simulation and free energy perturbation techniques have been used to study the relative binding free energies of 8-methylpterins and 8-methyl-N5-deazapterins to dihydrofolate reductase (DHFR). Methyl-substitution at the 5, 6 and 7 positions in the N-heterocyclic ring gives rise to a variety of ring substituent patterns and biological activity: several of these methyl derivatives of the 8-methyl parent compounds (8-methylpterin and 8-methyl-N5-deazapterin) have been identified as substrates or inhibitors of vertebrate DHFR in previous work. The calculated free energy differences reveal that the methyl-substituted compounds are thermodynamically more stable than the primary compounds (8-methylpterin and 8-methyl-N5-deazapterin) when bound to the enzyme, due largely to hydrophobic hydration phenomena. Methyl substitution at the 5 and/or 7 positions in the 6-methyl-substituted compounds has only a small effect on the stability of ligand binding. Furthermore, repulsive interactions between the 6-methyl substituent and DHFR are minimal, suggesting that the 6-methyl position is optimal for binding. The results also show that similarly substituted 8-methylpterins and 8-methyl-N5-deazapterins have very similar affinities for binding to DHFR. The computer simulation predictions are in broad agreement with experimental data obtained from kinetic studies, i.e. 6,8-dimethylpterin is a more efficient substrate than 8-methylpterin and 6,8-dimethyl-N5-deazapterin is a better inhibitor than 8-methyl-N5-deazapterin.

Animals↗
PubMed2000

Mini-review: computational structure-based design of inhibitors that target protein surfaces.

Finding drugs that inhibit protein-protein interactions is usually difficult. While computer-aided design is used widely to facilitate the drug discovery process for protein targets with well-defined binding pockets, its application to the design of inhibitors targeting a protein surface is very limited. In this mini-review we address two aspects of this issue: firstly, we overview the current state of design methodology for inhibitors specifically targeting protein surfaces, and secondly, we briefly outline recent advances in computational methods for structure-based drug design. These methods are closely related to protein docking and protein recognition, the difference being that in ligand design, ligands are built on a fragment-by-fragment basis. A novel scheme of computational combinatorial ligand design developed for the design of inhibitors that interfere with protein-protein interaction is described in detail. Current applications and limitations of this methodology, as well as its future prospects, are discussed.

Combinatorial Chemistry Techniques↗
PubMed2006

Computer-aided molecular design of highly potent HIV-1 RT inhibitors: 3D QSAR and molecular docking studies of efavirenz derivatives.

Ligand- and structure-based design approaches have been applied to an extended series of 74 efavirenz compounds effectively inhibiting wild type (WT) and mutant type (K103N) HIV-1 reverse transcriptase (RT). For ligand-based approach, three dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), were performed. The starting geometry of efavirenz was obtained from X-ray crystallographic data. The efavirenz derivatives were constructed and fully optimized by ab-initio molecular orbital method at HF/3-21G level. Reliable QSAR models for high predictive abilities were developed. Regarding WT and K103N inhibitions, CoMFA models with r2/cv = 0.651 and 0.678 and CoMSIA models with r2/cv = 0.662 and 0.743 were derived, respectively. The interpretation obtained from the models highlights different structural requirements for inhibition of WT and K103N HIV-1 RT. To elucidate potential binding modes of efavirenz derivatives in the binding pocket of WT and K103N HIV-1 RT, structure-based approach based on computational docking studies of selected efavirenz compounds were performed by using GOLD and FlexX programs. The results derived from docking analysis give additional information and further probe the inhibitor-enzyme interactions. The correlation of the results obtained from 3D QSAR and docking models validate each other and lead to better understanding of the structural requirements for the activity. Therefore, these integrated results are informative to provide key features and a helpful guideline for novel compound design active against HIV-1 RT.

Alkynes↗