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At least 19 recordsLinked to original sources

Performance assessment of radioactive waste repositories.

The current plans for permanent disposal of radioactive waste call for its emplacement in deep underground repositories mined from geologically stable rock formations. The U.S. Nuclear Regulatory Commission and U.S. Environmental Protection Agency have established regulations setting repository performance standards for periods of up to 10,000 years after disposal. Compliance with these regulations will be based on a performance assessment that includes (i) identification and evaluation of the likelihood of all significant processes and events that could affect a repository, (ii) examination of the effects of these processes and events on the performance of a repository, and (iii) estimation of the releases of radionuclides, including the associated uncertainties, caused by these processes and events. These estimates are incorporated into a probability distribution function showing the likelihood of exceeding radionuclide release limits specified by regulations.

Evaluation Studies as Topic

Network-based integration of metabolomics data from large-scale repositories.

INTRODUCTION: Public metabolomics data repositories such as MetaboLights and Metabolomics Workbench host rapidly growing volumes of raw data, processed results, and metadata. As data deposition becomes a prerequisite for funding and publication, there is an increasing need for tools that enable integration and joint reanalysis of datasets across studies to maximise reuse and reproducibility. OBJECTIVES: This study aims to enable large-scale integrative meta-analysis of public metabolomics data, exploiting harmonised metabolite annotations to identify robust multi-study metabolite and pathway signatures and to provide global visual overviews of repository content. METHODS: We developed a network-based integration framework operating at both the study (dataset) level and the metabolite or pathway level. Metabolite-level meta-networks integrate studies with shared biological context using co-occurrences of differential metabolites represented as bipartite graphs. Study-level networks compare observed metabolites for overall repository exploration. Networks can be explored interactively using a dedicated Python Dash app available at https://github.com/EloisaRL/Metabolomic-data-analysis-app/tree/main . RESULTS: As an example, the approach was applied to six COVID-19 plasma datasets from MetaboLights generated using LC-MS and NMR. Ten metabolites were identified as differential in at least three studies, including consistently up-regulated pyroglutamic acid, in agreement with the literature. Pathway-level networks provided an overview of shared biological processes across studies. A global network of 1,181 studies in Metabolomics Workbench demonstrated clustering by assay coverage and associated metadata, as expected. CONCLUSION: Network-based integration of harmonised metabolomics data enables robust cross-study analyses and highlights the critical importance of standardised annotation pipelines. Such approaches enhance the reuse, reproducibility, and impact of public metabolomics datasets, accelerating biological discovery.

Metabolomics

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis

An improved environmental pathway model for assessing high-level waste repository risks.

An environmental pathway model useful for assessing the postclosure radiological risks from high-level waste repositories has been developed. The model describes more fully than its predecessors the long-term build-up of radionuclides in the biosphere and is consequently better suited to the analysis of the prolonged radionuclide releases potentially associated with geologic waste repositories. The effect of incorporating the additional features is to alter, in some cases substantially, the predicted population risks associated with a given long-term release of particular radionuclides. The model has been used to evaluate certain assumptions underlying the environmental standard for high-level waste repositories recently issued by the U.S. Environmental Protection Agency.

Humans

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference.

Polygenic indexes (PGIs) - DNA-based predictors of individual phenotypes - have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI's predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository's scope, and introduce novel resources that reduce confounding bias and improve interpretability.

Journal Article

Perceived risk, stigma, and potential economic impacts of a high-level nuclear waste repository in Nevada.

This study investigates the potential impacts of the proposed nuclear waste repository at Yucca Mountain, Nevada, upon tourism, retirement and job-related migration, and business development in Las Vegas and the state. Adverse impacts may be expected to result from perceptions of risk, stigmatization, and socially amplified reactions to "unfortunate events" associated with the repository (major and minor accidents, discoveries of radiation releases, evidence of mismanagement, attempts to sabotage or disrupt the facility, etc.). The conceptual underpinnings of risk perception, stigmatization, and social amplification are discussed and empirical data are presented to demonstrate how nuclear images associated with Las Vegas and the State of Nevada might trigger adverse economic effects. The possibility that intense negative imagery associated with the repository may cause significant harm to Nevada's economy can no longer be ignored by serious attempts to assess the risks and impacts of this unique facility. The behavioral processes described here appear relevant as well to the social impact assessment of any proposed facility that produces, uses, transports, or disposes of hazardous materials.

Humans

Increased intraocular pressure induced by repository corticosteroids.

Twelve patients (14 eyes) had intraocular pressure elevations induced by repository coritcosteroids. The duration and severity of the resulting pressure elevations were directly related to the decreasing solubility of the agent employed. Ten patitens had received intensive topical corticosteroids before injection, resulting in no intraocular pressure elevations during that period. Two patients who developed marked intraocular pressure elevations after repository corticosteroid injection did not manifest a positive response on subsequent topical corticosteroid testing.

Adrenal Cortex Hormones

Prevalence of antibodies to human immunodeficiency virus type 1 among blood donors prior to screening. The Transfusion Safety Study/NHLBI Donor Repository.

The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.

Acquired Immunodeficiency Syndrome

National Institute on Aging cell-line repository.

The National Institute on Aging (NIA) has established, under contract, a cell-line repository. This resource is designed to support NIA grantees, prospective grantees, and other laboratories engaged in cellular aging research. Services of the NIA Cell-Line Repository include storage and distribution of characterized, contaminant-free normal diploid and genetically-marked human cell-lines.

Adult

Comparative intraocular levels of pilocarpine achieved with drops and repository preparations.

The concentrations of pilocarpine in aqueous humor and iris-ciliary body of rabbits following topical treatment with repository preparations or conventional drop therapy were measured using high performance liquid chromatography (HPLC). Higher concentrations of pilocarpine occurred both in aqueous humor and iris-ciliary body following topical administration of the 4% gel product than with 4% drops. At 1 hour after administration, 2% drops produced a higher concentration of pilocarpine in the aqueous humor than occurred with the 1.86% pilocarpine emulsion product; however, isopilocarpine present in the emulsion product entered the aqueous humor in equal amounts with the pilocarpine. At 4 hours, equal concentrations of pilocarpine were present in aqueous humor and iris-ciliary body samples with both the 2% drop and 1.86% emulsion therapy. Pilocarpine concentrations were maintained within the aqueous humor of the eye for longer durations with both the gel and emulsion repository preparations than with comparable drop therapy.

Animals

Use of a simulation model in occupational dose assessment at a high-level radioactive waste repository.

Occupational radiation dose assessment at a nuclear facility can benefit from a systems approach that recognizes the complex dynamics of the facility. A simulation model can be a useful tool for accomplishing this goal. This technique can quantify the uncertainty in estimates of occupational dose equivalent and illustrate the effects of system interactions. A simulation model of operations at a high-level radioactive waste repository together with a radiological dose assessment model were used to illustrate this technique. Annual individual and collective occupational dose equivalents were estimated in the truck cask receiving and handling stations at a repository. The uncertainty of these estimates is shown through the use of complementary cumulative distribution functions. The effects of changing parameters in cask handling operations are examined.

Computer Simulation

An analysis of the portfolio of sites to characterize for selecting a nuclear repository.

The U.S. Department of Energy has selected three sites, from five nominated, to characterize for a nuclear repository to permanently dispose of nuclear waste. This decision was made without the benefit of an analysis of this "portfolio" problem. This paper analyzes different portfolios of three sites for simultaneous characterization and strategies for sequential characterization. Characterization of each site, which involves significant subsurface excavation, is now estimated to cost $1 billion. Mainly because of the high characterization costs, sequential characterization strategies are identified which are the equivalent of $1.7-2.0 billion less expensive than the selected DOE simultaneous characterization of the three sites. If three sites are simultaneously characterized, one portfolio is estimated to be the equivalent of $100-400 million better than the selected DOE portfolio. Because of these potential savings and several other complicating factors that may influence the relative desirability of characterization strategies, a thorough analysis of characterization strategies that addresses the likelihood of finding disqualifying conditions during site characterization, uncertainties, and dependencies in forecast site repository costs, preclosure and postclosure health and safety impacts, potential delays of both sequential and simultaneous characterization strategies, and the environmental, socioeconomic, and health and safety impacts of characterization activities is recommended.

Radioactive Waste

A Patient-Derived Xenograft Repository Capturing Clinical and Molecular Heterogeneity of Large B-cell Lymphoma.

UNLABELLED: Large B-cell lymphomas (LBCL) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need, such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient-derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here, we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART19 progression patient biopsies, which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validated in vivo. SIGNIFICANCE: Here, we describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of LBCL. X-LYMPH includes models of CAR T-cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas. See related commentary by Evgin and Steidl, p. 655.

Humans

Oral vs repository corticosteroid therapy in acute asthma.

Acutely ill asthmatic patients treated in the usual fashion in an emergency room setting and discharged within six hours were studied to determine whether therapy with a single injection of a repository corticosteroid (methylprednisolone sodium acetate) could be as effective as a tapering course of oral corticosteroids in decreasing asthma symptomatology and relapse within seven days. Seventeen patients (18 episodes of asthma) formed the study population. Eight episodes occurred in patients who received depot methylprednisolone (group 1) and ten episodes in patients who received oral corticosteroid treatment (group 2). All patients in both groups improved following emergency room treatment. Relapse occurred in two of ten patients in group 2 and none in group 1. Symptoms attributable to asthma recurred in significantly more patients in group 2 than in group 1 (9 vs 0, p less than .01). Side effects from therapy with corticosteroids were rare. This study indicates that intramuscular repository corticosteroids are at least as effective as oral corticosteroids in the management of the acute asthmatic outpatient, with a distinct advantage with regard to patient compliance.

Acute Disease

Creation of a nuclear magnetic resonance data repository and literature database.

We believe the need exists for an organized and accessible repository of protein nuclear magnetic resonance data. The structure and dynamics of hundreds of proteins are being investigated by NMR. NMR data currently are spread throughout the world and often are not published for lack of journal space. Difficulties in locating, obtaining, and correlating these data with protein structures limits their usefulness to the scientific community. In time, the data may become lost or ignored. To provide a collection point for the results of protein NMR studies and a uniform means of distributing these data, we propose that a data bank be created consisting of two databases: a comprehensive and thoroughly indexed database for the NMR literature and a data repository for the storage of extensive protein NMR data sets. Our current specifications for the types of information to be stored in the NMR databases and their organization for dissemination are defined. The design is intended to be flexible, capable of expanding to include new techniques, new forms of data, and biopolymers other than proteins. This is a proposal to the community of NMR spectroscopists. Only through the active cooperation and support of those in the field of NMR spectroscopy can the proposed data bank succeed.

Database Management Systems

[The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

Delayed-Action Preparations

Cellular repository for blood histamine in normal and nematode-infected rats.

Infections with the nematode N. brasiliensis is associated with a recruitment of intestinal mucosal mast cells (MMC) which increase greatly in numbers. We have studied histamine levels in the gut, whole blood and plasma in relation to MMC of the gut and blood cell morphology during the course of the infection in an attempt to clarify possible relations between circulating blood basophils and MMC. The results show a parallel increase in MMC numbers and histamine content of the gut, remaining high to day 20 after infection. Blood histamine increased from a control level of 30-40 ng/ml to a maximum of 200 ng/ml on day 12 to 14, but returned towards the control level already on day 16 after infection. There was a corresponding increase in plasma histamine to a maximum of 80 ng/ml. The total number of blood neutrophils increased during the early phase of the infection and there was a pronounced eosinophilia from day 10 to 16. No cells containing metachromatic granules were found in a screening comprised of 10,000 cells per specimen. During day 10 to 16 we found a number of coarsely granuled and vacuolated cells. The granules stained darkly by the Giemsa stain but not metachromatically with Toluidine Blue or with Alcian Blue at a low pH. We interpret this as an equivalent to the so-called toxic granulation occurring in human neutrophils. These cells may have been mistaken for basophils by previous investigators. The cellular repository for the high concentration of histamine in the blood is unknown. We suggest, as a working hypothesis, that it is contained in a circulating progenitor for MMC which has the ability to synthesize and, in a loosely bound state store, histamine, but which has not yet acquired the ability to assemble the specific metachromatic granules.

Animals

The development of the U.S. EPA health effects research laboratory frozen blood cell repository program.

We have suggested that proper blood-cell freezing and storage is necessary in longitudinal studies with reduced between tests error, for specimen sharing between laboratories and for convenient scheduling of assays. Our present purpose is to describe the design and use of a prototype computer program, Cryovial, for data-based management of frozen cell repositories. We are pleased to provide, free of charge upon request, a 5.25" (specify 0.36 or 1.2 MB) disk containing all files required to run Cryovial.

Blood Preservation