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NCTR computer systems designed for toxicologic experimentation. IV. Experiment information system.

The Experiment Information System (EIS) is a computerized data collection, maintenance, and reporting system for specified information values collected during the lifespan of animals assigned to toxicologic investigations at NCTR. The system records and/or controls experimental variables, which might ultimately affect the results, through the operation and integration of the Diet Preparation Subsystem (DPS), the Environmental Monitoring Subsystem (EMS), the Microbiology Subsystem (MBS), and the Chemistry Data Subsystem (CDS). The fifth component of the EIS, the Experimental Data Collection Subsystem (EDCS), is responsible for handling all data generated by, or attributed to, the animals from assignment until death or removal. Through integration of these five subsystems, the history of an animal while on study is recorded and stored for later recall. In addition, "routine" and "special" reports are made available through the system software which enables stringent control of the experiment by the Principal Investigator, Animal Husbandry, and NCTR Management.

Animals↗
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↗
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°C. Furthermore, K+ and Mg²+ 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°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°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↗
PubMed1992

The ergonomic analysis of a trauma resuscitation room.

Ergonomics is the practical and scientific study of people in relation to their working environment. We describe its application to the operation of a trauma resuscitation room. We used specifically designed computer software. This methodology enables a unique and objective assessment of the design and operation of a clinical system. It may be particularly applicable to other hospital areas where the efficient interaction of staff, patients and equipment is crucial to the optimal clinical outcome.

Equipment and Supplies, Hospital↗
PubMed1992

SCUT: clinical data organization for physicians using pen computers.

The role of computers in assisting physicians with patient care is rapidly advancing. One of the significant obstacles to efficient use of computers in patient care has been the unavailability of reasonably configured portable computers. Lightweight portable computers are becoming more attractive as physician data-management devices, but still pose a significant problem with bedside use. The advent of computers designed to accept input from a pen and having no keyboard present a usable computer platform to enable physicians to perform clinical computing at the bedside. This paper describes a prototype system to maintain an electronic "scut" sheet. SCUT makes use of pen-input and background rule checking to enhance patient care. GO Corporation's PenPoint Operating System is used to implement the SCUT project.

Handwriting↗
PubMed1992

Automated fabrication of mobility aids (AFMA): below-knee CASD/CAM testing and evaluation program results.

In 1988 the Department of Veterans Affairs Rehabilitation Research and Development Service, under the directorship of Margaret J. Giannini, M.D., began a nationally directed computer-aided design and computer-aided manufacturing (CAD/CAM) research program for the Automated Fabrication of Mobility Aids (AFMA). Under this program CAD/CAM research and development centers were established at the Prosthetics Research Study in Seattle, WA; at Northwestern University and the VA Lakeside Medical Center in Chicago, IL; and at the VA Medical Center and New York University Medical Center in New York, NY. These three centers conducted a collaborative program: (a) to introduce CAD/CAM technologies to prosthetists, physicians, therapists, and rehabilitation health care professionals in the United States; (b) to evaluate the feasibility of using CAD/CAM systems in clinical prosthetics settings; (c) to test and evaluate the University College London-Bioengineering Center's and the University of British Columbia-Medical Engineering Resource Unit's respective systems for the computer-aided design and computer-aided manufacture of prosthetic sockets (CASD/CAM) for below-knee amputees; and, (d) to obtain quantitative data for refinement of the CASD/CAM systems tested, and for the development of new, enhanced, more efficacious, and expedient systems.

Adult↗
PubMed1992

Computer-aided radiopharmaceutical design.

The ultimate goal of a QSAR analysis is prediction, which depends on the elaboration of the most appropriate set of molecular descriptors. As such, molecular description is the nucleus of QSAR and in the absence of exhaustive molecular description, rational drug design may be greatly impeded. As previously discussed, computational methods such as quantum mechanics and molecular mechanics provide molecular description at a fundamental level which then enhances the descriptive capability and predictive power of a QSAR analysis. In recognition of these capabilities, semi-empirical molecular orbital methods and molecular mechanics now have been incorporated into or interphased with QSAR programs. Such integrated packages are being successfully used in computer-aided molecular modeling. Computer-aided molecular modeling can provide the three-dimensional structure of a molecule, its chemical and physical characteristics, comparisons of structures of different molecules, and visualization of complexes formed between them. From the foregoing, predictions may be made about how related new molecules may function. Thus, the combination of quantum and/or molecular mechanics and QSAR provides a formidable weapon in the chemist's armamentarium. The molecular modeling approaches are certainly more practical to use than physicochemical methods. They also provide electronic and thermodynamic data that are not available from x-ray crystallographic data. Of course, these techniques are not confined to radiopharmaceutical development and they also could aid in the development of contrast agents for radiography or magnetic resonance imaging. We believe that as computational resources and capabilities increase over the next decade, computer-aided drug design will become a standard procedure in all drug development laboratories.

Binding Sites↗
PubMed1977

The use of photogrammetry in tissue compensator design. Part II: experimental verification of compensator design.

A computer algorithm for designing sheet lead tissue compensators is described. Corrections are made for scatter within the radiation field as well as the shape of the patient for the mantle fields used in treating Hodgkin's disease. The method was tested experimentally with a phantom and found to be clinically acceptable. The advantages of employing this technique with parallel opposed fields are emphasized.

Hodgkin Disease↗
PubMed2026

Toward life with a 19-amino acid alphabet through generative artificial intelligence design.

Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic biology to explore building a cell from a 19-amino acid alphabet. Initial analyses suggested that isoleucine (Ile) may be dispensable, which we confirmed by directly replacing Ile residues in essential proteins in Escherichia coli. Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19-amino acid organism since early evolution.

Escherichia coli↗
PubMed2026

Generative artificial intelligence for enzyme design and biocatalysis.

Sparked by innovations in generative artificial intelligence (AI), the field of protein design has undergone a paradigm shift with an explosion of new models for optimizing existing enzymes or creating them from scratch. After more than one decade of low success rates for computationally designed enzymes, generative AI models are now frequently used for designing proficient enzymes. Here, we provide a comprehensive overview and classification of generative AI models for enzyme design, highlighting models with experimental validation relevant to real-world settings and outlining their respective limitations. We argue that generative AI models now have the maturity to create and optimize enzymes for industrial applications. Wider adoption of generative AI models with experimental feedback loops can speed up the development of biocatalysts and serve as a community assessment to inform the next generation of models.

Biocatalysis↗
PubMed1979

A computer-assisted personnel data system for a hospital department of dietetics. I. Development of the data base.

A data base was developed for a computer-assisted personnel data system for a university hospital department of dietetics which would store data on employees' employment, personnel information, attendance records, and termination. Development of the data base required designing computer programs and files, coding directions and forms for card input, and forms and procedures for on-line transmission. A program was written to compute accrued vacation, sick leave, and holiday time, and to generate historical records.

Computers↗
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↗
PubMed1975

[A computer-directed measuring device to analyse pathological gaits].

The clinical observation of the walk is still the only current way to define the limp, but is obviously quite a rough valuation. Taking advantage of previous studies and recent improvements in electronics, the authors have built a measuring unit-including a computer-designed for daily clinical use. This unit provides in a few minutes the variations of the ground reaction to the human body during the walk, and the displacement of the point to which this reaction is applied. Seven to ten patients per hour may be examined, including previous analysis of the results by the computer.

Computers↗
PubMed2026

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies.

Evolution guides biological systems to populate ecological niches, with viruses among the most successful examples of this principle. Viruses evolved over billions of years to efficiently transfer genetic information. Although viruses are highly diverse, most have converged towards remarkable similarity in the size and shape of their capsids1,2. By contrast, generative models for protein design enable the creation of protein architectures that are absent from nature3-5. Here we investigate whether protein assemblies designed by artificial intelligence can be functionalized to construct nucleic acid transport vehicles that are independent of evolutionary trajectories. By combining natural protein domains with synthetic protein assemblies, we create more than 100 bottom-up RNA transfer vehicles with unique sizes and shapes. These vehicles surpass the RNA transfer efficiency of widely used delivery vehicles by several orders of magnitude. In addition, we demonstrate that their tropism can be programmed by incorporation of computationally designed peptide binders and use them to deliver therapeutically relevant cargo RNAs into a wide range of cellular models. We show the in vivo biodistribution of one of these vehicles in a mouse at near-single-cell resolution, confirm its safety, and use it to perform a gene-editing treatment strategy for Duchenne muscular dystrophy in patient-derived cells and a pig. Our work demonstrates how proteins created by generative artificial intelligence can be harnessed for the rational engineering of RNA transport systems with the desired properties by overcoming the limitations of natural protein diversity.

Journal Article↗
PubMed1992

Tumor necrosis factor-alpha decreases neutrophil chemotaxis to N-formyl-1-methionyl-1-leucyl-1-phenylalanine: analysis of single cell movement.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by mononuclear cells in response to endotoxin, inhibits neutrophil chemotaxis. We analyzed the effects of TNF-alpha on the orientation and movement of individual neutrophils in a chemoattractant gradient. Neutrophils, treated or untreated with TNF-alpha, were observed migrating in a gradient of the chemotactic peptide N-formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP) on a specially constructed chamber (Zigmond bridge). The movement of these cells was videotaped, digitized, and then tracked using a newly designed computer algorithm. The data obtained from this algorithm were then utilized to calculate distance traveled, speed and ability to polarize and migrate in a directed manner for each individual cell. TNF-alpha-treated cells behaved like cells not exposed to fMLP in that they failed to orient in a chemotactic gradient and moved in a manner similar to randomly migrating cells. This study provides unique observations of the effect of TNF-alpha on multiple parameters of PMN migration.

Algorithms↗
PubMed1978

[Highly different values for the plausibility of fatherhood and for the exclusion chance (author's transl)].

More than 1800 HLA-typed mother-child-putative father triplets were biostatistically analyzed on the basis of the Essen-Möller principle. 14 of them had W-values (= probability of paternity) of less than 50%, the lowest value being 4,4%. Using a specially designed computer program, exclusion probabilities between 68 and 96% were calculated. This demonstrates (a) that nonexclusion is not necessarily in every case a positive indication of the paternity of the man involved; and (b) that the probability of exclusion as a biological method of establishing paternity is not a suitable piece of evidence. The W-value (= "probability of paternity"), obtained on the basis of the Essen-Möller principle, provides complete information, and is alone conclusive.--The high proportion of non-fullhouse children among the 14 cases allows the conclusion that the more comprehensive the specificity spectrum of the antiserums used in the typing is, the fewer the number of such cases.

Blood Group Antigens↗