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At least 109 records · Page 6Linked to original sources
PubMed1999

Combinatorial biocatalysis: taking the lead from nature.

Combinatorial biocatalysis is an emerging technology in the field of drug discovery. The biocatalytic approach to combinatorial chemistry uses enzymatic, chemoenzymatic, and microbial transformations to generate libraries from lead compounds. Important recent advances in combinatorial biocatalysis include iterative derivatization of small molecules and complex natural products, regioselectively controlled libraries, novel one-pot library syntheses, process automation, and biocatalyst enhancements.

Automation↗
PubMed1997

Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency in organic synthesis.

Recovery and purification difficulties can limit the yield and utility of otherwise successful organic synthesis strategies. A "fluorous synthesis" approach is outlined in which organic molecules are rendered soluble in fluorocarbon solvents by attachment of a suitable fluorocarbon group. Fluorocarbon solvents are usually immiscible in organic solutions, and fluorous molecules partition out of an organic phase and into a fluorous phase in a standard liquid-liquid extraction. Simple yet substantive separations of organic reaction mixtures are achieved without resorting to chromatography. Because fluorous synthesis combines in many respects the favorable purification features of solid-phase synthesis with the favorable reaction, identification, and analysis features of traditional organic synthesis, it should prove valuable in the automated synthesis of libraries of individual pure organic compounds.

Benzamides↗
PubMed1997

Analysis of a sequenced cDNA library from multiple sclerosis lesions.

To identify genes that are expressed in MS pathogenesis, we have analyzed a normalized cDNA library made from mRNA obtained from CNS lesions of a patient with primary progressive MS. Complementary DNA clones obtained from this library were subjected to automated DNA sequencing to generate expressed sequence tags. Analysis of this MS cDNA library revealed the presence of 54 cDNAs that were associated with immune activation and indicated the presence of an ongoing inflammatory response with evidence of both cell-mediated and humoral immune responses. The surprising finding was that 16 of the cDNAs encoded autoantigens associated with seven other autoimmune disorders, while only three of these 16 autoantigen cDNAs were present in a similarly constructed adult brain library. Such aberrant autoantigen expression could provide a source of secondary autoimmune stimulation that could contribute to the ongoing inflammatory response in MS. In addition, two cDNAs were found that mapped to a known MS susceptibility locus (5p14-p12): one encoded an excitatory amino acid transporter and the other a human homologue of the Drosophila disabled gene. This approach to the molecular biology of MS pathogenesis may help to illuminate previously unappreciated aspects of this disease.

Cloning, Molecular↗
PubMed1982

OCLC for the hospital library: the justification plan for hospital administration.

This paper delineates the necessary steps to provide hospital administrators with the information needed to evaluate an automated system, OCLC, for addition to the medical library. Based on experience at the Norton-Children's Hospitals, included are: (1) cost analyses of present technical processing systems and cost comparisons with OCLC; (2) delineation of start-up costs for installing OCLC; (3) budgetary requirements for 1981; (4) the impact of automation on library systems, personnel, and services; (5) potential as a shared service; and (6) preparation of the proposal for administrative review.

Budgets↗
PubMed1997

Multidimensional chromatography coupled with mass spectrometry for target-based screening.

The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.

Amino Acid Isomerases↗
PubMed1993

A human heart cDNA library--the development of an efficient and simple method for automated DNA sequencing.

A direct polymerase chain reaction (PCR) amplification of the human heart cDNA clones was used to generate lambda PCR product. By the use of the first set of primers derived from lambda gt11, each cDNA insert can readily be obtained. Using millipore filters, primers and nucleotides are removed and this purified PCR product can then be subjected to a second set of fluorescent primers in the generation of nucleotides in the auto-cycle reactions for automated DNA sequencing.

Base Sequence↗
PubMed1994

Bibliographic instruction in the hospital library.

The nature of bibliographic instruction in this hospital library continues to evolve. As the library makes easy-to-master, menu-driven tools for online searching available to end users, the demand for this service and the accompanying training increases. The demand for formal sessions covering research techniques is also increasing. Upon request, the library offered an extended research orientation to the housestaff in Obstetrics and Gynecology in May of 1993. An introduction to the use of CD-ROM was included to highlight its usefulness for citation verification, author searches, and for periodic current awareness searches on a particular topic. The UMH Library staff strive to offer the most current and comprehensive facilities and services to their users. These include automated access to the library's book, journal, and audiovisual holdings using the Data Trek system; online bibliographic searching by library staff and end users using CD Plus MEDLINE on CD-ROM and Grateful MED software; participation in clinical rounds to provide research support for clinical care; and several types of bibliographic instruction. In addition to the informal teaching of library research techniques that the library staff offers on a daily basis, the Library at Union Memorial Hospital is pleased to be able to provide a formalized and evolving bibliographic instruction program.

Computer User Training↗
PubMed1991

Integrating CD-ROM Medline with electronic mail: first step in implementing new strategy for online reference library.

Simultaneous ACCESS to and DISSEMINATION of electronically available PROFESSIONAL KNOWLEDGE, in a productive, Cost-of-Ownership effective, and affordable manner are now achievable. Emerging MANAGEMENT-OF-INFORMATION and SYSTEMS-INTEGRATION disciplines are essential contributing factors to devising and implementing NEW STRATEGIES for ONLINE REFERENCE LIBRARIES. Bringing integrated information closer to the ultimate user and RESHAPING the electronic databases and full-text management systems MARKETPLACE are the most significant outcomes. Key technology attributes are advancements in CD-ROM, Networking, and office automation. We have proven this concept by developing an INTERFACE between MEDLINE from COMPACT CAMBRIDGE and ALL-IN-1 from DIGITAL EQUIPMENT CORPORATION. Saved search results are automatically routed to the individual's ALL-IN-1 account where further DOCUMENT MANAGEMENT and electronic mail functions may be performed. A 486Ware system from Logicraft and a five-members VAX-Cluster (respectively), are linked in a DECNet environment that is the foundation of Children's Integrated Hospital Information System. In phase one of the project up to 8 SIMULTANEOUS USERS may access the 8 RECENT YEARS, from any one of 1500 ACCESS POINTS (local and remote), and utilize any one of 150 NETWORKED PRINTERS. Opportunities are now within reach to expand the electronic library services while utilizing progressive methods and taking advantage of the best available technologies.

Boston↗
PubMed2000

Automated purification of His6-tagged proteins allows exhaustive screening of libraries generated by random mutagenesis.

In the course of site-directed mutagenesis or directed evolution experiments, large numbers of protein variants are often generated. To characterize functional properties of individual mutant proteins in vitro, a rapid and reliable protein purification system is required. We have developed an automated method for the parallel purification of 96 different protein variants that takes about two hours. Using a 96-well format, the whole process can be performed automatically by a pipetting robot. Coupled with a suitable assay, again using a 96-well format, all variants can be functionally characterized within a few hours. The protein purification procedure described here is based on the interaction between His6-tagged proteins and Ni-NTA-coated microplates. Typical yields are 3-8 pmol purified protein/well, which is sufficient to analyze most enzymatic activities. Using this procedure, we have purified and characterized variants of the restriction endonuclease EcoRV, which were produced in an effort to enhance the selectivity of this enzyme. For this purpose, three amino acid residues were randomized in a region known from the co-crystal structure to be located at the protein-DNA interface. From a library of about 1200 variants, predominantly single and double mutants, more than 1000 variants were purified and characterized in parallel, which corresponds to an almost complete screening of the library.

Automation↗
PubMed1997

A genome-based resource for molecular cardiovascular medicine: toward a compendium of cardiovascular genes.

BACKGROUND: Large-scale partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of discovering novel genes and characterizing transcription patterns in different tissues. To catalogue the identities and expression levels of genes in the cardiovascular system, we initiated large-scale sequencing and analysis of human cardiac cDNA libraries. METHODS AND RESULTS: Using automated DNA sequencing, we generated 43,285 ESTs from human heart cDNA libraries. An additional 41,619 ESTs were retrieved from public databases, for a total of 84,904 ESTs representing more than 26 million nucleotides of raw cDNA sequence data from 13 independent cardiovascular system-based cDNA libraries. Of these, 55% matched to known genes in the Genbank/EMBL/DDBJ databases, 33% matched only to other ESTs, and 12% did not match to any known sequences (designated cardiovascular system-based ESTs, or CVbESTs). ESTs that matched to known genes were classified according to function, allowing for detection of differences in general transcription patterns between various tissues and developmental stages of the cardiovascular system. In silico Northern analysis of known gene matches identified widely expressed cardiovascular genes as well as genes putatively exhibiting greater tissue specificity or developmental stage specificity. More detailed analysis identified 48 genes potentially overexpressed in cardiac hypertrophy, at least 10 of which were previously documented as differentially expressed. Computer-based chromosomal localizations of 1048 cardiac ESTs were performed to further assist in the search for disease-related genes. CONCLUSIONS: These data represent the most extensive compilation of cardiovascular gene expression information to date. They further demonstrate the untapped potential of genome research for investigating questions related to cardiovascular biology and represent a first-generation genome-based resource for molecular cardiovascular medicine.

Blotting, Northern↗
PubMed1968

Problems of medical subject cataloging.

The subject catalog of the University of Colorado Medical Center Library is examined in considerable detail. Annual revisions of the subject catalog required by annual revisions of the subject heading authority list used, NLM's MeSH, are analyzed in terms of man-hours required for the effort and the effect on the catalog's structure. It is contended that, in a divided catalog, changes of headings on a one-for-one equivalency basis are no more difficult than they would be in a computerized catalog, but that in many-for-one changes the manual catalog and the machine catalog face exactly the same dilemma and in the same magnitude, the only solution in either case being the reexamination of many entries. The proliferation of subheadings is shown to present particularly vexing problems in catalog revision. A plea is made to recognize the MeSH system for what it is, a legitimate compromise between the descriptor-oriented terms of a computer coordinate-indexing system, and the subject-heading-oriented terms of the conventional card catalog.

Automation↗
PubMed1994

Growth patterns in the National Library of Medicine's serials collection and in Index Medicus journals, 1966-1985.

Data from the National Library of Medicine (NLM) automated Master Serials System and its MEDLINE database were used to chart the growth of NLM's serials collection and of the journals indexed in Index Medicus from 1966 to 1985. The number of live serial titles in the subset of NLM's collection examined increased 30% in the twenty years. The average number of articles per Index Medicus journal increased 56%. The average number of articles in U.S. Index Medicus journals grew more rapidly than the average number in journals published elsewhere. The NLM data provide clear evidence that the years from 1966 to 1985 saw a substantial increase in the percentage of the biomedical serial literature published in English. The period from 1966 to 1985 saw substantial but uneven growth in the number of serial titles in the NLM collection and in the average number of articles in Index Medicus journals. Although data on the number of articles published in Index Medicus journals is unlikely to reflect the number of articles in other journals, the pattern of growth in the number of serials held by NLM probably reflects trends in the universe of all biomedical serials.

Abstracting and Indexing↗
PubMed1989

Cloning, sequence analysis and chromosome localization of a Drosophila muscarinic acetylcholine receptor.

Two cDNA clones (3.7 kb and 4.8 kb) encoding a Drosophila muscarinic acetylcholine receptor were isolated from a Drosophila head cDNA library and characterized by automated DNA sequence analysis. The Drosophila muscarinic receptor contains 788 amino acids with a calculated Mr of 84,807 and displays greater than 60% homology with mammalian muscarinic receptors. The muscarinic receptor maps to the tip of the right arm of the second chromosome of the Drosophila genome.

Amino Acid Sequence↗
PubMed1987

Application of a general database manager in a clinical medical librarian program.

The morning report reference file was automated at the Stollerman Library because the manual system was time-intensive to maintain and cumbersome to search. A general database management system (DBMS) was chosen so that it could be used in the future for other data management functions in the library. DBMS features that should be examined before use with a bibliographic application include size limitations, data entry forms, data types, search options, index files, sort options, report generation, query and programming languages, command and/or menu files, file interaction, interface with other software, and documentation. Desired requirements for this application are discussed. It is noted that a general database manager probably will not meet all of the desired requirements. For some bibliographic applications, software specifically designed for bibliographic information management and retrieval should be used. A database for the purposes of searching the morning report reference file and producing a weekly reference list and a yearly index was developed using CONDOR 3. The structure of the database is described, and examples of the reports are given. The system has been in operation since December 1984 and has been well-received by staff and patrons.

Database Management Systems↗
PubMed1989

Adapting IAIMS to a hospital library level.

The Children's Hospital of Michigan Medical Library has adapted several of the Integrated Academic Information Management Systems (IAIMS) concepts and implemented them at a hospital library level. These have included features of network development, electronic interfacing and interlinking, and implementing an integrated information system in the library. The library has incorporated several information systems into library operations, including a variety of in-house, local, and national automated systems and telecommunication networks. Hospital libraries can incorporate IAIMS features and promote an institutional framework of interconnecting communication systems and electronic linkages.

Computer Communication Networks↗