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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.
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.
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.
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.
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.
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.
Consolidation among providers and the growth of managed care are fueling the development of clinical data repositories. Repositories may be a key to integrated delivery systems' efforts to conduct research to boost outcomes and cut costs.
Health care institutions need complete and accurate data to plan, monitor, and evaluate their oncology programs. Although financial and discharge data are available, clinical repositories generally are not. For oncology, the cancer registry database serves as a clinical repository. The data in the registry are complete, accurate, and readily available. They can be used to plan new services, evaluate existing programs, and monitor patient care.
A radioactive liquid waste repository was found to be a habitat of the rich microbial community with a high catabolic potential. Groundwater from a depth of 162-189 m contained aerobic saprotrophic and anaerobic fermentative, sulfate-reducing, and denitrifying bacteria. Nitrate-reducing bacteria residing in this groundwater were isolated in pure cultures. Based on the results of their physiological studies, 16S rRNA sequencing, and phylogenetic analysis, the microorganisms isolated were ascribed to one phylogenetic branch, the gamma-subclass of gram-negative bacteria. Among six isolates, four belonged to the genus Acinetobacter, whereas two others belonged to the genera Comamonas and Aeromonas. The data obtained indicate that the microflora of the repository can exert a certain effect on the chemical composition of the formation fluids and bearing rocks, as well as on the migration of radionuclides.
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.
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.
Repository corticosteroid was injected into the posterior sub-Tenon space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. There were 12 cases of Behçet's disease, 7 cases of sarcoidosis, one case of tuberculous uveitis, and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated 2 to 7 times at intervals of more than 2 weeks. Twenty-two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Fifteen of the 22 eyes had maintained improved visual acuity over 6 months. Eleven eyes showed no improvement in vision. Most of them already had poor visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon space is of value in the treatment of CME secondary to uveitis. However, we have to beware of the complications of treatment.
The Columbia Clinical Repository is the foundation of the Clinical Information System at the Columbia Presbyterian Medical Center (CPMC). The Repository is implemented as a relational database on an IBM mainframe, using a generic design that employs a small number of tables. Client applications on remote platforms send and receive data through Database Access Modules (DAMs), which support the HL7 protocol, while applications on the mainframe manipulate data through DAMs supporting a locally defined "query template". Implementation using static (compiled) SQL is compared to dynamic (ad hoc) SQL in terms of efficiency and flexibility.
Repository corticosteroid was injected into the posterior sub-Tenon's space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. They included 12 cases of Behçet's disease, 7 cases of Sarcoidosis, one case of tuberculous uveitis and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated twice to seven times at intervals of more than 2 weeks. Twenty two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Eleven eyes showed no improvement in vision. Most of them had already had bad visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon's space was effective in the treatment of CME secondary to uveitis. However, we have to beware of the complications of this treatment.
In late 1992, the 161 bed Grace Hospital of Morganton, North Carolina, USA, entered into a prototype agreement with a major vendor of hospital information systems software to help develop remote delivery of a Clinical Data Repository system. A process for planning and designing the implementation of this system was instituted by the Hospital. As of June 1994, several types of patient data are being collected for storage in the repository; interfaces to existing systems have been created, and progress is being made on designing clinical user presentation formats for long-term, on-line clinical data.
The Web provides a rapid prototyping environment for building platform-independent graphical user interfaces. A Web-based console can be implemented as a suite of CGI scripts that generate HTML code, manipulate files, execute system commands, and invoke external tools. Often these tools share data by reading and writing flat files, which must be explicitly maintained by the CGI programmer. In a repository system, meta-data about each file object are maintained in a database, and access to all data is regulated by a layer of control services. This paper describes the design and implementation of a Web-based Repository Manager (WRM), which provides an application programmer's interface for controlling applications, generating HTML documents, handling Web forms, and managing multi-media data. The WRM is being used to develop a console for the Brain Mapping Framework, a system for visualizing cortical stimulation data obtained during neurosurgery.
Knowledge-based molecular modelling of proteins has proven useful in many instances including the rational design of mutagenesis experiments, but it has been generally limited by the availability of expensive computer hardware and software. To overcome these limitations, we have developed the SWISS-MODEL server for automated knowledge-based protein modelling. The SWISS-MODEL server uses the Brookhaven Protein Data Bank as a source of structural information and automatically generates protein models for sequences which share significant similarities with at least one protein of known 3D-structure. We now use the software framework of the server to generate large collections of protein models. To store these models, we have established the SWISS-MODEL Repository, a new database for protein models generated by theoretical approaches. This repository is directly integrated with SWISS-PROT and other databases through the ExPASy World-Wide Web server (URL is http:(/)/www.expasy.ch).
A national mammography database was proposed, based on a centralized architecture for collecting, monitoring, and auditing mammography data. We have developed an alternative architecture relying on Internet-based distributed queries to heterogeneous databases. This architecture creates a "virtual repository", or a federated database which is constructed dynamically, for each query and makes use of data available in legacy systems. It allows the construction of custom-tailored databases at individual sites that can serve the dual purposes of providing data (a) to researchers through a common mammography repository and (b) to clinicians and administrators at participating institutions. We implemented this architecture in a prototype system at the Brigham and Women's Hospital to show its feasibility. Common queries are translated dynamically into database-specific queries, and the results are aggregated for immediate display or download by the user. Data reside in two different databases and consist of structured mammography reports, coded per BIRADS Standardized Mammography Lexicon, as well as pathology results. We prospectively collected data on 213 patients, and showed that our system can perform distributed queries effectively. We also implemented graphical exploratory analysis tools to allow visualization of results. Our findings indicate that the architecture is not only feasible, but also flexible and scaleable, constituting a good alternative to a national mammography database.