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PubMed1977

Increased muscle phosphorylase in rats fed high levels of vitamin B6.

The present study was undertaken to test the hypothesis that muscle phosphorylase may function as a repository for vitamin B6 in the animal. Since a repository would be expected to accumulate surplus material, one would predict that phosphorylase, which contains stoichio-metric amounts or pyridoxal phosphate, would increase in muscle of animals surfeited with the vitamin. Rats were fed a vitamin B6-free diet supplemented with pyridoxine providing levels 10, 1.0 and 0.1 of those recommended by the National Research Council (NRC). At the high intake level, muscle phosphorylase and total muscle vitamin B6 increased steadily and in almost constant ratio for at least 6 weeks, whereas both alanine and aspartate transaminase increased initially, but reached a plateau within 2 weeks. At the intermediate level of pyridoxine intake, muscle phosphorylase also increased, but less rapidly than in rats fed the higher level. When vitamin B6 intake was restricted to 10% of the NRC-recommended level, no increase in phosphorylase concentration occurred during a period of 10 weeks. These results support the hypothesis that muscle phosphorylase acts as a reservoir for vitamin B6 in the animal and provide experimental evidence that muscle enzyme content expands as vitamin is accumulated during high dietary intake.

Animals↗

PubMed1999

IXDB, an X chromosome integrated database (update).

Chromosome specific databases are an important research tool as they integrate data from different directions, such as genetic and physical mapping data, expression data, sequences etc. They supplement the genome-wide repositories in molecular biology, such as GenBank, Swiss-Prot or OMIM, which usually concentrate on one type of information. The Integrated X Chromosome Database (IXDB, http://ixdb.mpimg-berlin-dahlem.mpg.de/) is a repository for physical mapping data of the human X chromosome and aims at providing a global view of genomic data at a chromosomal level. We present here an update of IXDB which includes schema extensions for storing submaps and sequence information, additional links to external databases, and the integration of an increasing number of physical and transcript mapping data. The gene data was completely updated according to the approved gene symbols of the HUGO Nomenclature Committee. IXDB receives over 1000 queries per month, an indication that its content is valuable to researchers seeking mapping data of the human X chromosome.

Chromosome Mapping↗

PubMed2002

Predictome: a database of putative functional links between proteins.

The current deluge of genomic sequences has spawned the creation of tools capable of making sense of the data. Computational and high-throughput experimental methods for generating links between proteins have recently been emerging. These methods effectively act as hypothesis machines, allowing researchers to screen large sets of data to detect interesting patterns that can then be studied in greater detail. Although the potential use of these putative links in predicting gene function has been demonstrated, a central repository for all such links for many genomes would maximize their usefulness. Here we present Predictome, a database of predicted links between the proteins of 44 genomes based on the implementation of three computational methods--chromosomal proximity, phylogenetic profiling and domain fusion--and large-scale experimental screenings of protein-protein interaction data. The combination of data from various predictive methods in one database allows for their comparison with each other, as well as visualization of their correlation with known pathway information. As a repository for such data, Predictome is an ongoing resource for the community, providing functional relationships among proteins as new genomic data emerges. Predictome is available at http://predictome.bu.edu.

Animals↗

PubMed2006

The PeptideAtlas project.

The completion of the sequencing of the human genome and the concurrent, rapid development of high-throughput proteomic methods have resulted in an increasing need for automated approaches to archive proteomic data in a repository that enables the exchange of data among researchers and also accurate integration with genomic data. PeptideAtlas (http://www.peptideatlas.org/) addresses these needs by identifying peptides by tandem mass spectrometry (MS/MS), statistically validating those identifications and then mapping identified sequences to the genomes of eukaryotic organisms. A meaningful comparison of data across different experiments generated by different groups using different types of instruments is enabled by the implementation of a uniform analytic process. This uniform statistical validation ensures a consistent and high-quality set of peptide and protein identifications. The raw data from many diverse proteomic experiments are made available in the associated PeptideAtlas repository in several formats. Here we present a summary of our process and details about the Human, Drosophila and Yeast PeptideAtlas builds.

Animals↗

PubMed2006

Mouse Phenome Database (MPD).

The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is a repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice. Strain characteristics data are contributed by members of the scientific community. Electronic access to centralized strain data enables biomedical researchers to choose appropriate strains for many systems-based research applications, including physiological studies, drug and toxicology testing and modeling disease processes. MPD provides a community data repository and a platform for data analysis and in silico hypothesis testing. The laboratory mouse is a premier genetic model for understanding human biology and pathology; MPD facilitates research that uses the mouse to identify and determine the function of genes participating in normal and disease pathways.

Animals↗

PubMed2006

Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together.

Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org.

Databases, Protein↗

PubMed2006

ArrayExpress--a public database of microarray experiments and gene expression profiles.

UNLABELLED: ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts--the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50,000 hybridizations and >1,500,000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. AVAILABILITY: www.ebi.ac.uk/arrayexpress.

Animals↗

PubMed2002

Predictors and impact of atrial fibrillation after isolated coronary artery bypass grafting.

OBJECTIVE: Although an extensive number of studies have attempted to identify predictors of new-onset atrial fibrillation (AFIB) after coronary artery bypass grafting (CABG), a strong predictive model does not exist. Prior studies have included patients recruited from multiple centers with variant AFIB prevalence rates and those who underwent CABG in combination with other surgical procedures. Also, most studies have focused on pre- and perioperative characteristics, with less attention given to the initial postoperative period. The purpose of this study was to comprehensively examine pre-, peri-, and postoperative characteristics that might predict new-onset AFIB in a large sample of patients undergoing isolated CABG in a single medical center, utilizing data readily available to clinicians in electronic data repositories. In addition, length of stay and selected postoperative complications and disposition were compared in patients with AFIB and no AFIB. DESIGN: Retrospective, comparative survey. SETTING: University-affiliated tertiary care hospital. PATIENTS: Patients with new-onset AFIB who underwent isolated standard CABG or minimally invasive direct vision coronary artery bypass were identified from an electronic clinical data repository. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of AFIB in the total sample (n = 814) was 31.9%. Predictors of AFIB included age (p =.0004), number of vessels bypassed (p =.013), vessel location (diagonal [p <.003] or posterior descending artery [p <.001]), and net fluid balance on the operative day (p =.015). Forward stepwise regression analysis produced a model that correctly predicted AFIB in only 24% of cases, with age (14%) and body surface area (9%) providing the most prediction. The incidence of embolic stroke was higher in AFIB (n = 8) vs. no AFIB (n = 4) patients, but stroke preceded AFIB onset in seven of eight cases. Subjects with AFIB had a longer stay (p =.0004), more intensive care unit readmissions (p =.0004), and required more assistance at hospital discharge (p =.017). CONCLUSIONS: Despite attempts to examine comprehensively predictors of new-onset AFIB, we were unable to identify a robust predictive model. Our findings, in combination with prior work, imply that it may not be feasible to predict the development of new-onset AFIB after CABG using data readily available to the bedside clinician. In this sample, stroke was uncommon and, when it occurred, preceded AFIB in all but one case. As anticipated, AFIB increased length of stay, and patients with this complication required more assistance at discharge.

Aged↗

PubMed1997

An analytically based model for the simultaneous leaching-chain decay of radionuclides from contaminated ground surface soil layers.

This paper describes an analytically based method for modeling the time-dependent radionuclide areal densities of contaminated soil surface layers when the soil experiences simultaneous leaching, surface erosion and chain radioactive decay. The model is used to predict time-dependent radionuclide areal densities in a volcanic ash blanket contaminated with spent nuclear fuel particles for the purpose of assessing the risks of radiation exposure from an extrusive volcanic event near a proposed high-level waste repository at Yucca Mountain. The method uses general analytical solutions (an expansion of the Bateman equations) for calculating serial decay, including non-radioactive decay loss terms, in order to calculate time-dependent radionuclide areal densities in the ash blanket. In the presented example, 43 "key" radionuclides are tracked and their concentrations in the blanket are displayed for a 10,000-y time period following the volcanic event. Although the analysis presented herein is for modeling contaminated volcanic ash blankets, the model would work equally well for modeling time-dependent radionuclide contamination of land surfaces in, for example, site decommissioning. It is suggested that the general solutions for serial decay (with non-radioactive decay loss terms) can also be used to model the release of radionuclides from the waste packages under anticipated repository conditions.

Models, Theoretical↗

PubMed2001

An overview of EPA regulation of the safe disposal of transuranic waste at the Waste Isolation Pilot Plant.

In March of 1999, the Waste Isolation Pilot Plant (WIPP) in southeast New Mexico, the world's first deep geological repository for radioactive materials, began receiving defense-related transuranic waste. The WIPP was designed and constructed by the U.S. Department of Energy, but critical to its opening was certification by the U.S. Environmental Protection Agency that the repository complies with the radioactive waste disposal regulations set forth as environmental radiation protection standards (40 CFR Part 191) and compliance criteria (40 CFR Part 194). This paper provides a summary of the regulatory process, including the Environmental Protection Agency's waste containment, groundwater protection, and individual dose regulations for the WIPP; the Department of Energy's performance assessment and the other parts of its compliance certification application; and the Environmental Protection Agency's review and analysis of the compliance certification application and related documentation.

Government Agencies↗

PubMed2004

Management of spent sealed radiation sources.

Spent or disused sealed radiation sources--no longer needed sources--may represent a risk of radiological accident or may be a target for criminal acts in countries where final disposal options are unavailable and where an increasing number of sources are being kept in extended storage. In developing countries, thousands of radium needles, teletherapy sources, oil well logging neutron sources, and miscellaneous industrial radioactive gauges are annually collected as waste and stored in research institutes. The objectives of the study described in this paper are to inventory such sources in Brazil, including those presently in use and those already collected as waste, and to design a dedicated repository where spent sources could be disposed of properly. The inventory of sources in Brazil and the concept of the repository are presented and its feasibility is discussed.

Brazil↗

PubMed2000

One thousand health-related quality-of-life estimates.

OBJECTIVE: Analysts performing cost-effectiveness analyses often do not have the resources to gather original quality-of-life (QOL) weights. Furthermore, variability in QOL for the same health state hampers the comparability of cost-effectiveness analyses. For these reasons, opinion leaders such as the Panel on Cost-Effectiveness in Health and Medicine have called for a national repository of QOL weights. Some authors have responded to the call by performing large primary studies of QOL. We take a different approach, amassing existing data with the hope that it will be combined responsibly in meta-analytic fashion. Toward the goal of developing a national repository of QOL weights to aid cost-effectiveness analysts, 1,000 health-related QOL estimates were gathered from publicly available source documents. METHODS: To identify documents, we searched databases and reviewed the bibliographies of articles, books, and government reports. From each document, we extracted information on the health state, QOL weight, assessment method, respondents, and upper and lower bounds of the QOL scale. Detailed guidelines were followed to ensure consistency in data extraction. RESULTS: We identified 154 documents yielding 1,000 original QOL weights. There was considerable variation in the weights assessed by different authors for the same health state. Methods also varied: 51% of authors used direct elicitation (standard gamble, time tradeoff, or rating scale), 32% estimated QOL based on their own expertise or that of others, and 17% used health status instruments. CONCLUSIONS: This comprehensive review of QOL data should lead to more consistent use of QOL weights and thus more comparable cost-effectiveness analyses.

Attitude to Health↗

PubMed2004

Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach.

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol. RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.

AIDS-Related Opportunistic Infections↗

PubMed2007

Factors affecting dose estimates for long-term performance assessments: case study-Armagosa Valley.

The purpose of this study was to review and evaluate some of the factors that influence the dose estimates to members of the public due to chronic, long-term releases of radioactive materials into the environment. Although the examples discussed are based on data from the Amargosa Valley located near the proposed Yucca Mountain high-level radioactive waste repository, the factors evaluated are common to any such assessment. While it is recognized that such factors include those related to both the environmental transport of radionuclides from the point of release through the environmental media to the receptor, and the influence of his/her location and living habits, the assessments that follow are primarily limited to the latter. The specific goal in all cases was to illustrate how the assumptions and input values relative to certain factors influence the dose estimates and to quantify, to the extent possible, their relative significance. At the same time, it must be recognized that the assessments presented here were limited to doses due to the ingestion of food and water; those due to the inhalation of airborne radionuclides and external exposures were not considered. The factor that proved most important from the standpoint of the overestimation of doses (i.e., conservatism) was the implementation of the regulatory requirements pertaining to the withdrawal of groundwater from the local aquifer. Another significant source of conservatism was the dose estimates provided by the U.S. Department of Energy, assuming that the Reasonably Maximally Exposed Individual (RMEI) resided at the U.S. EPA designated site, 18 km from the repository, vs. the Amargosa Valley, about 35 km away. Also important, for selected radionuclides, was the impact of their effective half-lives on the committed doses, as estimated, in comparison to those that would actually be received. Having lesser impacts were the status of a local aquaculture farm on the intake of C, and the intake of stable iodine on dose estimates for I. On the basis of these evaluations, one can reasonably conclude that the overall conservatism in the dose assessments, based on these sources that were identified, approaches an order of magnitude. The sole factor that led to an underestimation of the doses (i.e., non-conservatism) was the regulatory requirement that the concept of the RMEI, as defined by U.S. EPA, in contrast to that of the Critical Group (CG), as recommended by the International Commission on Radiological Protection, be applied in estimating the doses to potentially affected population groups. Rather than dwell on the differences in the impacts of the application of each of these two concepts, the next step should be to subject each concept to a systematic and rigorous analysis, the goal being to gain an understanding of the range of dose estimates that would be yielded, the underlying reasons for the differences that are observed, and the lessons to be learned in terms of improving the methodologies for estimating doses due to environmental radionuclide releases.

Artifacts↗

PubMed2004

Tracheostomy in thermally injured patients: does diagnosis-related group 483 adequately estimate resource use and hospital costs?

BACKGROUND: This study compares burn and nonburn patients undergoing tracheostomy, all of whom were assigned to diagnosis-related group 483 to determine hospital reimbursement. METHODS: We reviewed the records of all inpatients admitted to our hospital from January 2000 through December 2001 who underwent tracheostomy and who were assigned to diagnosis-related group 483. In addition, we compared our burn patient data with that from three other burn centers and the National Burn Repository. RESULTS: We identified 357 inpatients who had tracheostomies during their hospitalization, only 12 of whom (3.4%) had acute burn injuries. The mean extent of burn in these patients was 43.4% total body surface area. The most frequent primary diagnoses for nonburn patients were injury and poisoning, and circulatory and respiratory disorders. Patients with burn injuries had 39.6 ventilator days, 40.7 intensive care unit days, and 49.2 hospital days compared with 19.8, 17.4, and 29.5 days, respectively, for nonburn patients (p <0.0001). Demographic, resource, and financial data for burn patients treated at the three other burn centers and those reported to the National Burn Repository were not significantly different from burn patients treated at our hospital. Total costs and charges for the care of burn patients were $186,830 and $343,904, respectively, compared with $82,176 and $160,498 for the nonburn patients (p <0.0005). CONCLUSION: Burn patients requiring tracheostomies during their acute hospitalization consume significantly more resources than patients without burn injuries. More appropriate resource-based reimbursement for the care of these patients appears warranted.

Adult↗

PubMed2025

Generation of C9orf72 repeat knock-in iPSC lines for modelling ALS and FTD.

Induced pluripotent stem cell (iPSC) models are powerful tools for neurodegenerative disease modelling, as they allow mechanistic studies in a human genetic environment and they can be differentiated into a range of neuronal and non-neuronal cells. However, these models come with inherent challenges due to line-to-line and clonal variability. To combat this issue, the iPSC Neurodegenerative Disease Initiative (iNDI) has generated an iPSC repository using a single clonal reference line, KOLF2.1J, into which disease-causing mutations and revertants are introduced via gene editing. Here we describe the generation and validation of lines carrying the most common causative mutation for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a repeat expansion in the C9orf72 gene, for the iNDI collection of neurodegenerative iPSC models. We demonstrate that these C9orf72 knock-in lines differentiate efficiently into neurons and display characteristic C9orf72-associated pathologies, including reduced C9orf72 levels and the presence of dipeptide repeat proteins (DPRs) and RNA foci, which increase in abundance over time in culture. These pathologies are not present in revertant cells lacking the repeat expansion. These repeat expansion and revertant cell lines are now available to academic and for-profit institutions through the JAX iPS cell repository and will help to facilitate and standardise iPSC-based ALS/FTD research.

Journal Article↗

PubMed1987

A multiattribute utility analysis of alternative sites for the disposal of nuclear waste.

Five potential sites nominated for the Nation's first geologic repository for disposing of nuclear waste are evaluated using multiattribute utility analysis. The analysis was designed to aid the Department of Energy in its selection of 3 sites for characterization, a detailed data-gathering process that will involve the construction of exploratory shafts for underground testing and that may cost as much as $1 billion per site. The analysis produced insights into the relative advantages and disadvantages of the nominated sites and clarified current uncertainties regarding repository performance.

Decision Making↗

PubMed2005

Improbability of igneous intrusion promoting a critical event in spent nuclear fuel disposed in unsaturated tuff.

In their regulations, the U.S. Environmental Protection Agency and the U.S. Nuclear Regulatory Commission permit the omission of features, events, or processes with probabilities of <10(-4) in 10(4) yr (e.g., a constant frequency of <10(-8) per yr) in assessments of the performance of radioactive waste disposal systems. Igneous intrusion (or "volcanism") of a geologic repository at Yucca Mountain for radioactive waste is one disruptive event that has a probability with a range of uncertainty that straddles this regulatory criterion and is considered directly in performance assessment calculations. A self-sustained nuclear chain reaction (or "criticality") is another potentially disruptive event to consider, although it was never found to be important when evaluating the efficacy of radioactive waste disposal since the early 1970s. The thesis of this article is that the consideration of the joint event--volcanism and criticality--occurring in any 10,000-year period following closure can be eliminated from performance calculations at Yucca Mountain. The probability of the joint event must be less than the fairly well-accepted but low probability of volcanism. Furthermore, volcanism does not "remove" or "fail" existing hydrologic or geochemical constraints at Yucca Mountain that tend to prevent concentration of fissile material. Prior to general corrosion failure of waste packages, the mean release of fissile mass caused by a low-probability, igneous intrusive event is so small that the probability of a critical event is remote, even for highly enriched spent nuclear fuel owned by the U.S. Department of Energy. After widespread failure of packages occurs, the probability of the joint event is less than the probability of criticality because of the very small influence of volcanism on the mean fissile mass release. Hence, volcanism plays an insignificant role in inducing criticality over any 10(4)-yr period. We also argue that the Oklo reactors serve as a natural analogue and provide a rough bound on probability of criticality given favorable hydrologic or geochemical conditions on the scale of the repository that is less than 0.10. Because the product of this bound with the probability of volcanism represents the probability of the joint event and the product is less than 10(-4) in 10(4) yr, consideration of the joint event can be eliminated from performance calculations.

Journal Article↗