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PubMed1997

The effects of the change in the NRMP matching algorithm. National Resident Matching Program.

CONTEXT: Following 2 years of heated controversy about the resident match, the National Resident Matching Program (NRMP) recently voted to replace the existing matching algorithm with a newly designed applicant-proposing algorithm. OBJECTIVE: To design an applicant-proposing algorithm for the match and compare it with the existing NRMP algorithm to determine how many applicants and residency programs could be expected to receive better or worse matches from the 2 algorithms, how the different algorithms influence the opportunity for strategic behavior, and what advice can be given to participants. DESIGN: Computational experiments compared the newly designed applicant-proposing algorithm with the existing NRMP algorithm on the rank order lists (ROLs) submitted by all applicants and residency programs in the 1987 and 1993 through 1996 NRMP matches. RESULTS: Differences in the matchings produced by the 2 algorithms are small: fewer than 1 in 1000 applicants would have received a different match. Most (but not all) of the few applicants who are matched to different positions by the 2 algorithms do better when the applicant-proposing algorithm is used; the opposite is true for programs. Opportunities for profitable strategic behavior are very rare for both applicants and programs under either algorithm. With either algorithm, both applicants and programs can be advised that trying to get a preferred match by behaving strategically is far more likely to harm than to help them. CONCLUSIONS: The existing NRMP algorithm and the newly designed applicant-proposing algorithm perform similarly. Both algorithms make it sensible for applicants and residency programs to arrange their ROLs based solely on their preferences for possible matches. The choice of algorithms will systematically affect the matches of only a small group of applicants (<0.1%). The NRMP's recent decision to use the applicant-proposing algorithm starting in 1998 reflects a judgment about the impact of this difference on applicants and programs.

Algorithms↗
PubMed1993

Computer-aided socket design for trans-femoral amputees.

Computer-aided socket design (CASD) is a technique for the design of prosthetic sockets using the advantageous features of computer graphics and calculation. This paper describes a computer-aided technique used to design sockets for patients with trans-tibial lower limb amputations.

Amputees↗
PubMed2004

[Computer aid vaccine design: new area of biomedical engineering].

Computer aid vaccine design (CAVD) is a new area of biomedical engineering. This article reviewed the background of the coming of CAVD and its main research contents, methods and applications. Free tools of the trade in CAVD are listed; the implication and the perspective of CAVD are also suggested.

Animals↗
PubMed2003

A convenient method for the computer-aided molecular design of carborane containing compounds.

Computer-aided molecular design (CAMD) of carborane containing compounds is of growing interest for scientists involved in boron neutron capture therapy (BNCT) and other pharmaceutical applications. However, the complex organo-metallic structures of carboranes pose difficulties in modeling and docking of these structures. This is the first report of a new strategy for modeling and docking of carborane containing molecules with the readily available software packages HyperChem, SYBYL and FlexX. It is intended as a guide for boron chemists interested in using CAMD of carborane containing agents for medical applications such as BNCT.

Boranes↗
PubMed2005

Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for computer-aided molecular design III: 2.5D indices for the discovery of antibacterials.

The present work continues our series on the use of MARCH-INSIDE molecular descriptors (parts I and II: J Mol Mod 8:237-245, [2002] and 9:395-407, [2003]). These descriptors encode information pertaining to the distribution of electrons in the molecule based on a simple stochastic approach to the idea of electronegativity equalization (Sanderson's principle). Here, 3D-MARCH-INSIDE molecular descriptors for 667 organic compounds are used as input for a linear discriminant analysis. This 2.5D-QSAR model discriminates between antibacterial compounds and non-antibacterial ones with 92.9% accuracy in training sets. On the other hand, the model classifies 94.0% of the compounds in test set correctly. Additionally, the present QSAR performs similar-to-better than other methods reported elsewhere. Finally, the discovery of a novel compound illustrates the use of the method. This compound, 2-bromo-3-(furan-2-yl)-3-oxo-propionamide has MIC50 of 6.25 and 12.50 microg/mL against Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 27853, respectively while ampicillin, amoxicillin, clindamycin, and metronidazole have, for instance, MIC50 values higher than 250 mug/mL against E. coli. Consequently, the present method may becomes a useful tool for the in silico discovery of antibacterials.

Anti-Bacterial Agents↗
PubMed2003

DNA library design for molecular computation.

A novel approach to designing a DNA library for molecular computation is presented. The method is employed for encoding binary information in DNA molecules. It aims to achieve a practical discrimination between perfectly matched DNA oligomers and those with mismatches in a large pool of different molecules. The approach takes into account the ability of DNA strands to hybridize in complex structures like hairpins, internal loops, or bulge loops and computes the stability of the hybrids formed based on thermodynamic data. A dynamic programming algorithm is applied to calculate the partition function for the ensemble of structures, which play a role in the hybridization reaction. The applicability of the method is demonstrated by the design of a twelve-bit DNA library. The library is constructed and experimentally tested using molecular biology tools. The results show a high level of specific hybridization achieved for all library words under identical conditions. The method is also applicable for the design of primers for PCR, DNA sequences for isothermal amplification reactions, and capture probes in DNA-chip arrays. The library could be applied for integrated DNA computing of twelve-bit instances of NP-complete combinatorial problems by multi-step DNA selection in microflow reactors.

Algorithms↗
PubMed2025

Using Prime Editing Guide Generator (PEGG) for high-throughput generation of prime editing sensor libraries.

Prime editing enables the generation of nearly any small genetic variant. However, the process of prime editing guide RNA (pegRNA) design is challenging and requires automated computational design tools. We developed Prime Editing Guide Generator (PEGG), a fast, flexible, and user-friendly Python package that enables the rapid generation of pegRNA and pegRNA-sensor libraries. Here, we describe the installation and use of PEGG (https://pegg.readthedocs.io) to rapidly generate custom pegRNA-sensor libraries for use in high-throughput prime editing screens.

Gene Editing↗
PubMed2026

Application of emerging technologies in the antiviral field.

Viral diseases pose a serious threat to global public health, agriculture, and biosecurity. Conventional antiviral strategies are often limited by an incomplete understanding of disease mechanisms, poor targeting precision, and slow response times. Emerging technologies are now reshaping the landscape of antiviral research. This review examines the roles of four key frontiers, including organoid models, gene editing, AI-driven molecular design, and synthetic biology. Organoids provide physiologically relevant platforms that model virus-host interactions and disease progression. Viral infections remain a major challenge to human and animal health, agriculture, and biosecurity. Progress in antiviral research is constrained by the complexity of viral pathogenesis, the diversity and rapid evolution of viruses, and the limited translational relevance of some traditional model systems. Recent advances in organoid technology, gene editing, artificial intelligence, and synthetic biology are expanding the toolkit available for antiviral research and development. In this review, we discuss how these four technological frontiers contribute to disease modeling, target discovery, molecular design, and translational innovation. Organoids, in particular, provide physiologically relevant systems for investigating viral infection, tissue tropism, host responses, and pathogenesis. Gene editing tools, such as CRISPR, enable precise manipulation of host and viral genomes, facilitating the development of resistant organisms and next-generation vaccine platforms. AI technologies, including AlphaFold for structure prediction and platforms for de novo protein design, address long-standing bottlenecks in structural biology and offer powerful means to engineer antiviral proteins, antibodies, and vaccine antigens. Synthetic biology, guided by the Design-Build-Test-Learn cycle, integrates computational design, genetic assembly, and functional validation into a cohesive pipeline. Together, these technologies form a synergistic workflow that spans disease modeling, target discovery, molecular design, construction, testing, and iterative optimization. This integrated approach is shifting antiviral development from traditional empirical methods toward more precise, intelligent strategies. The review also highlights ongoing challenges in integration and scalability, stressing that high-quality biological datasets and stronger interdisciplinary collaboration are essential for realizing translational potential. By presenting a cohesive view of these converging methodologies, this review offers a framework to guide the intelligent evolution of antiviral strategies in both human and animal health.

Antiviral↗
PubMed1999

Computer copings for partial coverage.

Partial coverage posterior tooth preparations are very complex surfaces for computer surface digitization, computer design, and manufacture of ceramic copings. The aim of this study was therefore to determine whether the Computer Integrated Crown Reconstruction (Cicero) system was compatible with a proposed partial coverage preparation design and capable of producing ceramic copings. Posterior teeth were prepared for partial coverage copings with deep gingival chamfers in the proximal boxes and around the functional cusps (buccal of mandibular and lingual of maxillary posterior teeth). The nonfunctional cusps (lingual of mandibular and buccal of maxillary posterior teeth) were prepared with broad bevels following the inclined occlusal plane pattern. Optical impressions were taken of stone dies by means of a fast laser-line scanning method that measured the three-dimensional geometry of the partial coverage preparation. Computers digitized the images, and designed and produced the ceramic copings. The Cicero system digitized the partial coverage preparation surfaces precisely with a minor coefficient of variance of 0.2%. The accuracy of the surface digitization, the design, and the computer aided milling showed that the system was capable of producing partial coverage copings with a mean marginal gap of 74 microns. This value was obtained before optimizing the marginal fit by means of porcelain veneering. In summary, Cicero computer technology, i.e., surface digitization, coping design, and manufacture, was compatible with the described partial coverage preparations for posterior teeth.

Bicuspid↗
PubMed2005

One- and two-body decomposable Poisson-Boltzmann methods for protein design calculations.

Successfully modeling electrostatic interactions is one of the key factors required for the computational design of proteins with desired physical, chemical, and biological properties. In this paper, we present formulations of the finite difference Poisson-Boltzmann (FDPB) model that are pairwise decomposable by side chain. These methods use reduced representations of the protein structure based on the backbone and one or two side chains in order to approximate the dielectric environment in and around the protein. For the desolvation of polar side chains, the two-body model has a 0.64 kcal/mol RMSD compared to FDPB calculations performed using the full representation of the protein structure. Screened Coulombic interaction energies between side chains are approximated with an RMSD of 0.13 kcal/mol. The methods presented here are compatible with the computational demands of protein design calculations and produce energies that are very similar to the results of traditional FDPB calculations.

Poisson Distribution↗
PubMed2003

Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for computer-aided molecular design I: discovery of anticancer compounds.

A simple stochastic approach, designed to model the movement of electrons throughout chemical bonds, is introduced. This model makes use of a Markov matrix to codify useful structural information in QSAR. The self-return probabilities of this matrix throughout time ((SR)pi(k)) are then used as molecular descriptors. Firstly, a calculation of (SR)pi(k) is made for a large series of anticancer and non-anticancer chemicals. Then, k-Means Cluster Analysis allows us to split the data series into clusters and ensure a representative design of training and predicting series. Next, we develop a classification function through Linear Discriminant Analysis (LDA). This QSAR discriminates between anticancer compounds and non-active compounds with a correct global classification of 90.5% in the training series. The model also correctly classified 86.07% of the compounds in the predicting series. This classification function is then used to perform a virtual screening of a combinatorial library of coumarins. In this connection, the biological assay of some furocoumarins, selected by virtual screening using the present model, gives good results. In particular, a tetracyclic derivative of 5-methoxypsoralen (5-MOP) has an IC50 against HL-60 tumoral line around 6 to 10 times lower than those for 8-MOP and 5-MOP (reference drugs), respectively. Finally, application of Iso-contribution Zone Analysis (IZA) provides structural interpretation of the biological activity predicted with this QSAR.

Computer Simulation↗
PubMed1991

A computer-aided control, design and image-processing system for electron microscopes.

A computer-control system for electron microscopes is described. The aim is to reduce a complex series of vacuum-system controls to a menu-driven program that simplifies the operation of the microscope. The system also incorporates image processing, notebook, computer-aided design, and communication functions. It is designed around a commercially available computer workstation. This system has been implemented on an institute-built photoelectron microscope of ultrahigh-vacuum design.

Computer Graphics↗
PubMed2003

Genetic design of solids possessing a random-particulate microstructure.

There exists a variety of difficulties in the computational design of macroscopic solid material properties formed by doping a homogeneous base matrix material with randomly distributed particles having different properties. Three primary problems are (1) the wide array of free microdesign variables, such as particle topology, property phase contrasts and volume fraction, which render the associated objective functions to be highly non-convex; (2) that the associated objective functions are not differentiable with respect to design variables, primarily due to prescribed constraints, such as prespecified restrictions on the microscale stress-field behaviour; and (3) the effective responses of various finite-sized samples, of equal volume but of different random particle distributions, exhibit mutual fluctuations, leading to amplified noise in optimization strategies where objective function sensitivities or comparisons are needed. The focus of this paper is the development of a statistical genetic algorithm which can handle difficulties due to non-convexity, lack of regularity and size effects. Theoretical properties of the overall approach are investigated. Semi-analytical and large-scale numerical examples, involving finite-element type discretizations, are given to illustrate its practical application.

Computer-Aided Design↗
PubMed2003

Tautomerism in computer-aided drug design.

Tautomers are often disregarded in computer-aided molecular modeling applications. Little is known about the different tautomeric states of a molecule and they are rarely registered in chemical databases. Tautomeric forms of a molecule differ in shape, functional groups, surface, and hydrogen-bonding pattern. Calculation of physical-chemical properties and molecular descriptors differ from one tautomeric state to the other as it is demonstrated with an example of the log P calculation, similarity index, and the complementarity pattern to the targeted protein. Considering tautomery in ligand-protein interactions therefore has a significant impact on the prediction of the ligand binding using various docking techniques. This article points on hitherto unaddressed issue of tautomerism in computer-aided drug design.

Binding Sites↗
PubMed2006

Flow study of an extracardiac connection with persistent left superior vena cava.

BACKGROUND: Numerous studies have sought to optimize the design of total cavopulmonary connections with a single superior vena cava. This study was directed to the 2% to 4.5% of the population with dual superior venae cavae, investigating the flow fields associated with such total cavopulmonary connection anatomies. Additionally, it demonstrates the potential use of computational designs and simulations as surgical planning tools. METHODS: A 3-dimensional model of a total cavopulmonary connection with bilateral superior venae cavae was reconstructed from a patient's magnetic resonance images and investigated experimentally and numerically to assess the power losses and flow structures within the connection. On the basis of these results, a virtual operation was performed in the computer to improve the original connection design. The modified anatomy was studied numerically. RESULTS: Because of a smooth connection with an extracardiac conduit and no major dimension mismatch between the baffle and the connecting vessels, the original anatomy yielded smooth flow fields, low power losses, and few disturbances. However, a large offset between the inferior vena cava and the left superior vena cava resulted in flow stasis and unbalanced hepatic flow distribution. Shifting the inferior vena cava and positioning it between the 2 superior venae cavae resulted in a 7% decrease in power losses and eliminated the associated flow stasis regions in the main pulmonary artery segment. CONCLUSIONS: This study demonstrates the potential use of computer-aided design and numeric simulations for surgical planning. It shows that locating the inferior vena cava between the superior venae cavae may lead to better-balanced lung perfusion. This may require suturing the right and left superior venae cavae closer to each other during the hemi-Fontan or Glenn stage.

Anastomosis, Surgical↗
PubMed2026

Genomic prospecting and biochemical characterization of a novel thermostable 3-quinuclidinone reductase from hot spring metagenomes for efficient biocatalysis.

This study presents the discovery and characterization of a novel thermophilic 3-quinuclidinone reductase (ScQR) identified through metagenomic mining of hot spring environments. ScQR, a member of the short-chain dehydrogenase/reductase (SDR) superfamily, was heterologously expressed in Escherichia coli, and its catalytic properties were systematically characterized. The enzyme demonstrates exceptional thermal stability, retaining 86% of its activity after 48 hours at 70&#xb0;C. Furthermore, K+ and Mg&#xb2;+ ions significantly enhanced ScQR's activity at specific concentrations. Structural analysis revealed that ScQR adopts a typical SDR fold with a conserved catalytic triad (S141-Y155-K159), and it is NAD(H) dependent. Enzyme assays indicated that ScQR is highly stereoselective for (R)-3-quinuclidinol, with no activity against its enantiomer, (S)-3-quinuclidinol. The enzyme exhibits optimal activity at pH 9 and 85&#xb0;C, making it a promising candidate for industrial applications requiring high thermal stability. Molecular dynamics simulations further revealed that ScQR preserves global structural integrity up to 360 K, whereas higher temperatures induce destabilization, predominantly in the C-terminal region and residues 95-100. In addition, structure-guided computational design enabled by LigandMPNN and UniKP yielded three ScQR variants with improved substrate affinity and catalytic efficiency while maintaining the overall fold and function. This work underscores the power of metagenomics with structure-driven protein design in discovering novel enzymes with unique catalytic properties from extreme environments and establishes ScQR as a promising biocatalyst for biotechnological and pharmaceutical applications.IMPORTANCEThis study reports the discovery of ScQR, a novel thermophilic 3-quinuclidinone reductase identified via metagenomic mining. ScQR represents one of the most heat-resistant members of the SDR superfamily discovered to date, maintaining 86% activity after 48 hours at 70&#xb0;C. These findings establish ScQR as a robust biocatalyst for high-temperature pharmaceutical applications and demonstrate a scalable workflow for optimizing enzymes from extreme environments, offering significant value to the fields of biocatalysis and protein engineering.

computational design↗
PubMed1997

De novo protein design: fully automated sequence selection.

The first fully automated design and experimental validation of a novel sequence for an entire protein is described. A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 x 10(27) possible amino acid sequences for compatibility with the design target, a betabetaalpha protein motif based on the polypeptide backbone structure of a zinc finger domain. A BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence. The solution structure of FSD-1 was solved by nuclear magnetic resonance spectroscopy and indicates that FSD-1 forms a compact well-ordered structure, which is in excellent agreement with the design target structure. This result demonstrates that computational methods can perform the immense combinatorial search required for protein design, and it suggests that an unbiased and quantitative algorithm can be used in various structural contexts.

Algorithms↗
PubMed2001

Promoting patient safety: is technology the solution?

BACKGROUND: On April 30, 2001, the Cleveland Clinic Foundation and Cleveland Clinic Health System Quality Institute sponsored a 1-day conference focused on technology in patient safety. PATIENT SAFETY-A CALL TO ACTION: Kenneth W. Kizer focused on ten high-priority patient safety strategies identified by the National Quality Forum-including implementing recognized "safe practices", recognizing and dealing with professional misconduct, and supporting efforts to create a nonpunitive environment for health care error reporting. CULTURAL IMPLICATIONS OF INTRODUCING NEW TECHNOLOGY: Randolph A. Miller described a computerized clinician order-entry system used to provide decision support, reduce excess test ordering, introduce cost savings, and meet regulations for inpatient radiology and cardiology tests. USING BAR CODES TO ELIMINATE MEDICATION ERRORS: Jeff Ramirez reported on the Veterans Health Administration's use of bar coding technology for point-of-care validation of medication administration, which has resulted in improvements in response time; the efficiency of the dispensing, delivery, and administration process; and patient care. HOW TO MAKE COMPUTERS TEAM PLAYERS: The knowledge base exists to design computers as team players that expand human expertise and help health care practitioners better create safety. Yet David D. Woods challenged the audience to anticipate the changing shape of iatrogenic risk as a result of increasing dependence on automation in health care. TECHNOLOGY AND MEDICATION SYSTEMS: Mark Neuenschwander spoke about automating various steps within the medication use system, through computerized prescriber order entry and bedside scanning. FUTURE TECHNOLOGICAL POSSIBILITIES: Charles Denham suggested how technology may aid health care professionals in their care of patients, such as in using predictive modeling to identify the risks of therapeutic intervention.

Equipment Safety↗