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Protein expression clone repositories for functional proteomics.

The information generated from the sequence of the human genome has inspired efforts to systematically develop organized collections of human cDNA clones for use in expression screens in mammalian cells. These high-throughput cloning initiatives offer significant advantages over the cDNA libraries that have been used in the past, including greater experimental flexibility, immediate identification of hits, information regarding all tested proteins (even for those giving no response) and eventually more comprehensive coverage. Some of the lessons learned and the considerations that underlie the creation of genome-wide cDNA repositories are discussed here. Although still inchoate, these resources are already impacting the manner in which high-throughput functional screens are performed.

Animals↗

Data mining and clinical data repositories: Insights from a 667,000 patient data set.

Clinical repositories containing large amounts of biological, clinical, and administrative data are increasingly becoming available as health care systems integrate patient information for research and utilization objectives. To investigate the potential value of searching these databases for novel insights, we applied a new data mining approach, HealthMiner, to a large cohort of 667,000 inpatient and outpatient digital records from an academic medical system. HealthMiner approaches knowledge discovery using three unsupervised methods: CliniMiner, Predictive Analysis, and Pattern Discovery. The initial results from this study suggest that these approaches have the potential to expand research capabilities through identification of potentially novel clinical disease associations.

Clinical Chemistry Tests↗

The use of a high-FeO olivine rock as a redox buffer in a nuclear waste repository.

Due to the higher stability of the spent nuclear fuel (mainly composed of UO2) under reducing conditions, and in order to enhance the retention/retardation of some key radionuclides, the olivine rock from the Lovasjärvi intrusion has been proposed as a potential redox-active backfill-additive in deep high-level nuclear waste (HLNW) repositories. In this work, two different approaches have been undertaken in order to establish the redox buffer capacity of olivine rock: (1) The capacity of the rock to respond to changes in pH or pe has been demonstrated and the final (pH, pe) coordinates agree with the control exerted by the system Fe(II)/Fe(III). (2) The rate of consumption of oxygen has been determined at different pH values. These rates are higher than the ones reported in the literature for other solids, what would point to the possibility of using this rock as an additive to the backfill material in a HLNW.

Buffers↗

Protocol for a computed tomography scanner performance repository.

An argument is presented for organization of a Computed Tomography Scanner Performance Repository. Performance data on CT scanners would be distributed in statistical form to the radiological community. A Protocol is presented for the uniform collection of data. Results of exposure, resolution and visibility measurements made by the authors are presented for the EMI 5005/U, Pfizer 0200 FS and General Electric CT/T scanners.

Humans↗

Generation and stability of bentonite colloids at the bentonite/granite interface of a deep geological radioactive waste repository.

The possible mechanisms of colloid generation at the near field/far field interface of a radioactive repository have been investigated by means of novel column experiments simulating the granite/bentonite boundary, both in dynamic and in quasi-static water flow conditions. It has been shown that solid particles and colloids can be detached from the bulk and mobilised by the water flow. The higher the flow rate, the higher the concentration of particles found in the water, according to an erosion process. However, the gel formation and the intrinsic tactoid structure of the clay play an important role in the submicron particle generation even in the compacted clay and in a confined system. In fact, once a bentonite gel is formed, in the regions where the clay is contacted with water, clay colloids can be formed even in quasi-static flow conditions. The potential relevance of these colloids in radionuclide transport has been studied by evaluating their stability in different chemical environments. The coagulation kinetics of natural bentonite colloids was experimentally studied as a function of the ionic strength and pH, by means of time-resolved light scattering techniques. It has been shown that these colloids are very stable in low saline (approximately 1 x 10(-3) M) and alkaline (pH > or = 8) waters.

Aluminum Silicates↗

Effect of heterogeneity in fracture permeability on the potential for liquid seepage into a heated emplacement drift of the potential repository.

A numerical model was used to investigate the effect of spatial variability in fracture permeability on liquid seepage and moisture distribution in the vicinity of a waste emplacement drift in the unsaturated zone (UZ) of Yucca Mountain. The model is based on a two-dimensional, cross-sectional, dual-permeability model of the unsaturated zone at Yucca Mountain and uses a stochastic approach to investigate the effect of small-scale heterogeneous features. The studies were conducted using one uniform fracture permeability case, three realizations of stochastically generated fracture permeability, one discrete permeability feature case, and one increased ambient liquid flux case. In all cases, the models predict that completely dry drift conditions will develop above and below the drift in 10-100 years and remain dry for 1000-2000 years. During this period, the models predict no seepage into drifts, although liquid flux above the drifts and within the drift pillars may increase by up to two orders of magnitude above ambient flux. This is because the heat released by the emplaced waste is sufficient to vaporize liquid flux of one to two orders of magnitude higher than present-day ambient flux for over 1000 years. The results also show that unsaturated zone thermal-hydrological (TH) models with uniform layer permeability can adequately predict the evolution of seepage and moisture distribution in the rock mass surrounding the repository drifts. The models further show that although variability in fracture permeability may focus and enhance liquid flow in regions of enhanced liquid saturation (due to condensation above the drifts), vaporization and vapor diffusion can maintain a dry environment within the drifts for thousands of years.

Geological Phenomena↗

Generic performance assessment for a deep repository for low and intermediate level waste in the UK--a case study in assessing radiological impacts on the natural environment.

Concentrations of radionuclides in soil and surface water, taken from a generic performance assessment of a repository for low and intermediate level radioactive waste, assumed to be located in the UK, have been used as the basis for a case study in assessing radiological impacts on the natural environment. Simplified descriptions of the terrestrial and aquatic ecosystem types likely to be impacted have been developed. A scoping assessment has identified (226)Ra, (210)Po, (234)U, (230)Th and (238)U as having the highest potential for impact, with doses from internally incorporated alpha emitters as being potentially of particular importance. These nuclides, together with (36)Cl and (129)I (which have proved to be of importance in radiological risk assessments for humans) were included in a more detailed dose assessment. A basic methodology for dose assessment of ecosystems is described, and has been applied for the defined impacted ecosystems. Paucity of published data on concentration factors prevented a more detailed assessment for terrestrial ecosystems. For the aquatic ecosystem, a more detailed assessment was possible and highest calculated absorbed dose rates (weighted for the likely higher biological effectiveness of alpha radiation) were about 6.5 microGy h(-1). We conclude that harm to the impacted ecosystems is unlikely and make the observation that the lack of concentration factor or transfer factor data for a sufficiently wide range of species, ecosystems and nuclides appears to be the principal obstacle to establishing a comprehensive framework for the application of radiological protection to ecosystems.

Animals↗

Development and application of a sorption data base for the performance assessment of a radwaste repository.

A sorption data base (SDB) provides readily available data for the performance assessment of a radwaste repository when site-specific and/or reference data are needed. The software developed at KAERI, SDB-21C, is a graphic user interface (GUI) program that provides efficient and user-friendly tools for evaluating large amount of sorption data. In addition, the most comprehensive sorption data base that contains about 11,000 NEA data and 2,000 KAERI data was compiled in the program. Besides the simple Kd approach, a parametric model and its compiled data sets are also included in the SDB-21C. In order to evaluate the versatility of SDB-21C, several applications were performed for relevant hypothetical situations.

Adsorption↗

Colloids in the mortar backfill of a cementitious repository for radioactive waste.

Colloids are present in groundwater aquifers and water-permeable engineered barrier systems and may facilitate the migration of radionuclides. A highly permeable mortar is foreseen to be used as backfill for the engineered barrier of the Swiss repository for low- and intermediate-level waste. The backfill is considered to be a chemical environment with some potential for colloid generation and, due to its high porosity, for colloid mobility. Colloid concentration measurements were carried out using an in-situ liquid particle counting system. The in-house developed counting system with three commercially available sensors allowed the detection of single particles and colloids at low concentrations in the size range 50-5000 nm. The counting system was tested using suspensions prepared from certified size standards. The concentrations of colloids with size range 50-1000 nm were measured in cement pore water, which was collected from a column filled with a highly permeable backfill mortar. The chemical composition of the pore water corresponded to a Ca(OH)2-controlled cement system. Colloid concentrations in the backfill pore water were found to be typically lower than approximately 0.1 ppm. The specific (geometric) surface areas of the colloid populations were in the range 240 m2 g(-1) to 770 m2 g(-1). The low colloid inventories observed in this study can be explained by the high ionic strength and Ca concentrations of the cement pore water. These conditions are favourable for colloid-colloid and colloid-backfill interactions and unfavourable for colloid-enhanced nuclide transport.

Colloids↗

Developing and using a data repository for quality improvement: the genesis of IRIS.

BACKGROUND: In 1991 the Inova Health System, a regional hospital system in Fairfax, Virginia, started developing a patient data repository, the Inova Research Information System (IRIS), to support clinical quality improvement, managed care contracting, and technology assessment. BUILDING A DATABASE PROTOTYPE: The prototype was built with the help of five key early user groups; each group, led by an influential physician, was eager to have access to data important to their work in an integrated and standardized electronic format. USING THE DATABASE: IRIS serves as the principal resource that QI committees, risk managers, managed care contracting officers, and others turn to for data to support their studies of the processes of care used and patient outcomes. Clinicians should use data analysis to identify opportunities for QI and implement change in their processes of care as a result. IRIS has already been used to make selected comparisons of patient management. For example, at Inova's largest hospital, for patients with a primary diagnosis of acute myocardial infarction (but without any unrelated secondary diagnoses), the length of stay was significantly shorter (5.5 days) when the attending physician was a cardiologist rather than an internist (7.5 days) or family practitioner (7.7 days). SUMMARY: IRIS represents an architecture of study of patients, clinicians, and administrators--and the outcomes and the results produced. By the end of 1995 three years of integrated clinical and financial data on inpatients will be available, permitting creation of a feed-back loop for continuous clinical and managerial learning.

Confidentiality↗

Radioactively contaminated electric arc furnace dust as an addition to the immobilization mortar in low- and medium-activity repositories.

Electric arc furnace dust (EAFD), generated by the steel-making industry, is in itself an intrinsic hazardous waste; however, the case may also be that scrap used in the process is accidentally contaminated by radioactive elements such as cesium. In this case the resulting EAFD is to be handled as radioactive waste, being duly confined in low- and medium-activity repositories (LMAR). What this paper studies is the reliability of using this radioactive EAFD as an addition in the immobilization mortar of the containers of the LMAR, that is, from the point of view of the durability. Different mixes of mortar containing different percentages of EAFD have been subjected to flexural and compressive strength, initial and final setting time, XRD study, total porosity and pore size distribution, determination of the chloride diffusion coefficient, dimensional stability tests, hydration heat, workability of the fresh mix, and leaching behavior. What is deduced from the results is that for the conditions used in this research, (cement + sand) can be replaced by EAFD upto a ratio [EAFD/(cement + EAFD)] of 46% in the immobilization mortar of LMAR, apparently without any loss in the long-term durability properties of the mortar.

Cementation↗

Effects of Fe(II) and hydrogen peroxide interaction upon dissolving UO2 under geologic repository conditions.

Iron redox cycling is supposed to be one of the major mechanisms that control the geochemical boundary conditions in the near field of a geologic repository for UO2 spent nuclear fuel. This work investigates the impact of reactions between hydrogen peroxide (H2O2) and iron (Fe2+/Fe3+) on UO2 dissolution. The reaction partners were contacted with UO2 in oxygen-free batch reactor tests. The interaction in absence of UO2 gives a stoichiometric redox reaction of Fe2+ and H2O2 when the reactants are present in equal concentration. Predomination of H202 results in its delayed catalytic decomposition. With UO2 present, its dissolution is controlled by either a slow mechanism (as typical for anoxic environments) or uranium peroxide precipitation, depending strongly on the reactant ratio. Uranium peroxide (UO4 x nH2O, m-studtite), detected on UO2 surfaces after exposure to H2O2, was not found on the surfaces exposed to solutions with stoichometric Fe(II)/ H2O2 ratios. This suggests that H2O2 was deactivated in redox reactions before a formation of UO4 took place. ESR measurements employing the spin trapping technique revealed only the DMPO-OH adduct within the first minutes after the reaction start (high initial concentrations of the OH radical); however, in the case of Fe(II) and H2O2 reacting at 10(-4) mol/L with UO2, dissolved oxygen and Fe2+ concentrations indicate the participation of further Fe intermediates and, therefore, Fenton redox activities.

Geological Phenomena↗

The US National Cancer Institute's natural products repository; origins and utility.

The US National Cancer Institute's natural products collection program has been running since 1986 and over the years the materials collected and processed have been stored in a repository that as a result of initial planning, has permitted the establishment of a national resource that is now being utilized as a drug discovery tool for any disease of interest to the NIH by researchers world-wide. This paper describes the history of the program.

Biological Products↗

Rapid freezing of whole blood or buffy coat samples for polymerase chain reaction and cell culture analysis: application to detection of human immunodeficiency virus in blood donor and recipient repositories. The Transfusion Safety Study Group.

Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it was decided to establish a cell repository of cryopreserved buffy coat (BC) samples, and thus far over 20,000 samples have been accumulated from enrolled subjects. To determine if these specimens could be used for polymerase chain reaction, a simple thawing and pelleting technique for recovering hemoglobin-free total white cells (WBCs) was developed. To validate the technique, parallel analysis was conducted of BCs, whole blood (WB), and PBMC samples from human immunodeficiency virus type 1 (HIV-1)-seropositive subjects. Immediate postthaw cell courts of 29 frozen-thawed (F-T) WB and BC samples averaged 90 percent of the prefreeze (input) values. Representative WBC populations were obtained by immediate pelleting. Amplification of HIV-1 gag sequences from F-T BCs and F-T WB was 94 and 75 percent, respectively, which is as sensitive as that obtained with freshly separated PBMC lysates. Quantitative HIV-1 proviral load analysis by serial dilution of 23 F-T BCs and 8 WB lysates showed results comparable to those obtained with lysates of fresh PBMCs. Values for WBC differential and immunophenotyping could be applied to express viral load relative to total WBCs, PBMCs, or CD4+ cells. These results establish the basis for simplified virologic analysis of cryopreserved BC or WB specimens.

Blood Donors↗

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

Animals↗

Progenetix.net: an online repository for molecular cytogenetic aberration data.

UNLABELLED: Through sequencing projects and, more recently, array-based expression analysis experiments, a wealth of genetic data has become accessible via online resources. In contrast, few of the (molecular-) cytogenetic aberration data collected in the last decades are available in a format suitable for data mining procedures. www.progenetix.net is a new online repository for previously published chromosomal aberration data, allowing the addition of band-specific information about chromosomal imbalances to oncologic data analysis efforts. AVAILABILITY: http://www.progenetix.net CONTACT: mbaudis@stanford.edu

Chromosome Aberrations↗

The PDB-Preview database: a repository of in-silico models of 'on-hold' PDB entries.

UNLABELLED: The PDB-Preview database is a dynamic web repository of in-silico predicted three-dimensional (3D) models of experimentally determined structures that are deposited into the PDB but are not yet publicly released, and are kept 'on-hold'. The PDB-Preview database is automatically generated on a weekly basis by the bioinfo.pl meta-server, which uses top-of-the-line fold-recognition methods. The PDB-Preview provides biologists with preliminary fold assignments well before the experimentally determined 3D structures are released. AVAILABILITY: http://bioinfo.pl/PDB-Preview/.

Computer Simulation↗