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PubMed1997

[Value of automated medical indexing of an image database and a digital radiological library].

We indexed the contents of a radiology server on the web to facilitate access to research documents and to link reference texts to images contained in radiology databases. Indexation also allows case reports to be transformed with no supplementary work into formats compatible with computer-assisted training. Indexation was performed automatically by ADM-Index, the aim being to identify the medical concepts expressed within each medical text. Two types of texts were indexed: medical imaging reference books (Edicerf) and case reports with illustrations and captions (Iconocerf). These documents are now available on a web server with HTML format for Edicerf and on an Oracle database for Iconocerf. When the user consults a chapter of a book or a case report, the indexed terms are displayed in the heading; all reference texts and case reports containing the indexed terms can then be called up instantaneously. The user can express his search in natural language. Indexation follows the same process allowing instantaneous recall of all reference texts and case reports where the same concept appears in the diagnosis or clinical context. By using the context of the case reports as the search index, all case reports involving a common medical concept can be found. The context is interpreted as a question. When the user responds to this question, ADM-Index compares this response with the answer furnished by the reference texts and case reports. Correct or erroneous responses can thus be identified, converting the system into a computer-assisted training tool.

Abstracting and Indexing↗
PubMed1998

An essay on reflection.

From the vantage point of her personal experience, the author examines milestones since the 1960s which have changed the medical library profession and helped shape the Medical Library Association. The advent of automation, including cataloging with OCLC and online literature searching through the SUNY Biomedical Communication Network, was a dramatic event that transformed the work and priorities of librarians, fulfilling the dreams of earlier visionaries. The application of technology in libraries led to an increased demand for education and training for librarians. The Medical Library Association responded with continuing education programs, and a series of important reports influenced how the association filled its role in professional development. Legislation providing federal funding, such as the Medical Library Assistance Act, resulted in a period of expansion for libraries and their services. The Medical Library Association has developed a legislative agenda to influence action in areas such as copyright. In the future, health sciences librarians must take a leadership role.

Education, Continuing↗
PubMedDate not supplied

Automated techniques in haematology.

BACKGROUND: Manual techniques have been mostly in use in developing countries until recently because of its low cost even though it is laborious. Many laboratories are however changing to automated techniques since many samples can be analysed within a short time. It is likely that more laboratories will use these instruments either as semi automated or fully automated multichannel instruments. There is therefore a need for laboratories to become more responsive to the needs of physicians making request by providing help in the presentation and interpretation of results. METHOD: Available literature on automation in Haematology was sourced for using both manual library search and Medline search. RESULTS: Quality control in automated blood cell counts and related topics are extensively researched but there is still dearth of knowledge on automation in other areas of Haematology and on the clinical implications of automation. CONCLUSION: It is therefore necessary to make provision for automated facilities in laboratories in view of the high precision and cost effectiveness of these machines. This review is geared towards a critical look at this technology and its application to disease states.

Autoanalysis↗
PubMed1994

A look at LOANSOME DOC service.

The Pacific Southwest Regional Medical Library (PSRML) launched a project in 1988 to assess the feasibility of electronic linkages between health professionals using GRATEFUL MED--the National Library of Medicine's (NLM) software program for searching the MEDLARS databases--and libraries using DOCLINE, NLM's automated interlibrary loan request-and-referral system. This paper describes the origins of LOANSOME DOC and initial usage experiences. Results of the LOANSOME DOC beta test, including usage statistics, are reported. The paper also describes the mechanics of nationwide implementation of LOANSOME DOC, including guidelines used by the Regional Medical Libraries (RMLs) to refer unaffiliated health professionals to DOCLINE libraries for LOANSOME DOC service. National usage statistics for the first full year of implementation (October 1, 1991, to September 30, 1992) are provided, and user satisfaction surveys conducted in 1993 by two RMLs are examined. Future enhancements to LOANSOME DOC are suggested.

Consumer Behavior↗
PubMed1965

COMPUTERIZED BIBLIOGRAPHIC SERVICES FOR BIOMEDICINE.

By its development of improved media for dissemination of information, the National Library of Medicine is fostering a greater awareness and a better understanding of research and development efforts in behalf of public health and clinical medicine, and a more rapid translation of research into clinical application. The library's transformation from a passive repository of information to an active ally of the researcher, teacher, and clinician has led to increased use of medical library facilities and has stimulated thinking through better communication of published information. The library's success in using automation for bibliographic control of medical literature suggests that other disciplines that have not already developed automated techniques of literature-reference retrieval might profitably do so.

Abstracting and Indexing↗
PubMed1998

Prediction of local structure in proteins using a library of sequence-structure motifs.

We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for finding correlations between protein sequence and local structure, and contains most previously described local sequence-structure correlations as well as new relationships, including a diverging type-II beta-turn, a frayed helix, and a proline-terminated helix. The query sequence is scanned for segments 7 to 19 residues in length that strongly match one of the 82 patterns in the library. Matching segments are assigned the three-dimensional structure characteristic of the corresponding sequence pattern, and backbone torsion angles for the entire query sequence are then predicted by piecing together mutually compatible segment predictions. In predictions of local structure in a test set of 55 proteins, about 50% of all residues, and 76% of residues covered by high-confidence predictions, were found in eight-residue segments within 1.4 A of their true structures. The predictions are complementary to traditional secondary structure predictions because they are considerably more specific in turn regions, and may contribute to ab initio tertiary structure prediction and fold recognition.

Algorithms↗
PubMed1997

Synthetic strategies in combinatorial chemistry.

Different synthetic strategies are required for the two kinds of libraries being developed for combinatoral chemistry. Preparation of a 'focused' library involves conversion of a known synthetic route to the solid-phase or automated format, whereas generation of a 'prospecting' library is driven more by availability of input materials and considerations of structural novelty. While both types can be identified over the history of combinatorial chemistry, elaborating syntheses of novel, nonoligomeric, 'drug-like' molecules for use in prospecting libraries is a relatively recent development.

Chemistry, Organic↗
PubMed1995

Synthetic chemical diversity: solid phase synthesis of libraries of C2 symmetric inhibitors of HIV protease containing diamino diol and diamino alcohol cores.

Solid phase synthesis of non-oligomeric organic compounds has been pursued for high-efficiency generation of large numbers of structurally diverse compounds for drug screening. Known as chemical diversity libraries or combinatorial libraries (when the synthesis is carried out in a combinatorial fashion), these compounds can be used for de novo discovery of drug leads or for expedient structure--activity relationship (SAR) studies. To expand the scope of solid phase synthesis beyond the capability of the traditional method of solid phase synthesis for peptides, a strategy was developed for bi-directional solid phase synthesis starting with diamino alcohol or diamino diol core structures. The strategy relies on using bifunctional linkers to modify the core structures, simultaneously protecting the hydroxyl group or the diol moiety of the core and providing a carboxyl group for attachment of the modified cores to a solid support. The two NH2 groups of the modified cores attached to the solid support were then deprotected and reacted with a wide variety of amine-reactive reagents (carboxylic acids, sulfonyl chlorides, isocyanates, chloroformates, etc.) to extend the molecule in both directions. This strategy was successfully applied to automated parallel synthesis of a library of C2 symmetric inhibitors of HIV protease containing the known symmetry-based diamino diol and diamino alcohol core structures, thus enabling expedient access of large numbers of analogs in this series. A library of over 300 discrete compounds was synthesized using this methodology in order to identify potent (IC50 < 100 nM) HIV protease inhibitors with reduced size. This paper describes the technical aspects of this technology.

Alcohols↗
PubMed1975

Computer-assisted cataloging: experiences at the UCLA Biomedical Library.

The computer-assisted procedures developed in the UCLA Biomedical Library Cataloging Division have been in effect for approximately three years. The system utilizes a Delta Data System cathode ray tube terminal and cassette attachment for on or off-line input of data. Products of the system include catalog card sets arranged in filing order, a monthly Recent Acquisitions List, and computer-generated book catalogs. Planning, personnel, and equipment requirements are discussed, and preliminary cost figures for various parts of the system are given. Potential applications of the automated system on a regional level and in terms of the library's future automation plans are considered.

California↗
PubMed1985

BACS: evolution of an integrated library system toward information management.

The evolution of the Washington University School of Medicine BACS integrated library system toward information management functions is outlined. The creation of a machine-readable database and its extension through telecommunications have consequences that reach beyond the functions of the library as we have perceived them. It is argued that libraries are flexible institutions that, with automation, are likely to enlarge rather than to diminish.

Catalogs, Library↗
PubMed2005

Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor.

Small-molecule kinase inhibitors are predominantly discovered in pure protein assays. We have discovered an inhibitor of Rho-kinase (ROCK) through an image-based, high-throughput screen of cell monolayer wound healing. Using automated microscopy, we screened a library of approximately 16,000 compounds finding many that affected cell migration or cell morphology as well as compounds that blocked mitotic progression. We tested approximately 200 compounds in a series of subassays and chose one, 3-(4-pyridyl)indole (Rockout), for more detailed characterization. Rockout inhibits blebbing and causes dissolution of actin stress fibers, phenocopying Rho-kinase inhibitors. Testing Rho-kinase activity in vitro, Rockout inhibits with an IC50 of 25 microM ( approximately 5-fold less potent than Y-27632) but has a similar specificity profile. We also profile the wound healing assay with a library of compounds with known bioactivities, revealing multiple pathways involved in the biology.

Animals↗
PubMed2002

Universal solid-phase approach for the immobilization, derivatization, and resin-to-resin transfer reactions of boronic acids.

Boronic acid-containing molecules are employed in a broad range of biological, medicinal, and synthetic applications. These compounds, however, tend to be difficult to handle by solution-phase methods. Herein, this problem is addressed with the development of the first general solid-phase approach for the derivatization of functionalized boronic acids. This approach is based on the use of a diethanolamine resin anchor that facilitates boronic acid immobilization by avoiding the need for exhaustive removal of water in the esterification process. The immobilization of a wide variety of boronic acids onto N,N-diethanolaminomethyl polystyrene (DEAM-PS, 1) can be performed within minutes by simple stirring in anhydrous solvents at room temperature. Evidence for the formation of a bicyclic diethanolamine boronate with putative N-B coordination was shown by (1)H NMR analysis of DEAM-PS-supported p-tolylboronic acid. The hydrolytic cleavage of the same model boronic acid from the DEAM-PS resin was studied by UV spectroscopy. Hydrolysis and attachment were shown to occur under a rapidly attained equilibrium, and a large excess of water (>32 equiv) is required to effect a practically quantitative release of boronic acids from DEAM-PS. Despite their relative sensitivity to water and alcohols, DEAM-PS-bound arylboronic acids functionalized with a formyl, a bromomethyl, a carboxyl, or an amino group can be transformed in good to excellent yields into a wide variety of amines, amides, anilides, and ureas, respectively. Ugi multicomponent reactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctional arylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin-to-resin transfer reactions (RRTR). This type of multiresin process helps eliminate time-consuming cleavage and transfer operations, thereby considerably simplifying the outlook of combinatorial library synthesis by manual or automated means. This concept was illustrated by a set of optimized procedures for the Suzuki cross-coupling and the borono-Mannich reactions.

Boronic Acids↗
PubMed2006

Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM): A novel method for biomolecular screening.

Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is a new separation-based affinity method. It has kinetic capabilities exceeding those of surface plasmon resonance (SPR) and does not require immobilization of molecules on the surface. Another distinctive feature of NECEEM is that--if it is combined with an advanced method for the mixing solutions inside a capillary, termed transverse diffusion of laminar flow profiles (TDLFP)--it requires only nanoliter volumes of solutions. The proven applications of NECEEM to biomolecular screening include 1) measuring kinetic and thermodynamic parameters of protein-ligand interactions, 2) quantitative affinity analyses of proteins and hybridization analyses of DNA and RNA, and 3) selection of binding ligands from combinatorial libraries. NECEEM is easy to automate and parallelize. Because of its simplicity and analytical power, NECEEM has the potential to become a workhorse in studies of biomolecular interactions. The author reviews theoretical bases of NECEEM and its applications to biomolecular screening.

Affinity Labels↗
PubMed2004

A step ahead: combining protein purification and correct folding selection.

The success of recombinant protein expression seems unpredictable and even good yields of soluble proteins do not guarantee the correct folding. The search for soluble constructs can be performed by exploiting libraries and speeded up by automation, but these approaches are money and time consuming and the tags used for affinity purification can mask the real stability of the target proteins. The ideal purification protocol would include the structure quality control. A recent paper commented in this article describes a phage-display method to screen for antibodies that are able to re-fold after heat-denaturation and can be selectively affinity-purified only if monodispersed. It turned out that the proteins with high recovery performance after heat-shock were also suitable for efficient recombinant expression.

Editorial↗
PubMed2004

The NLM Indexing Initiative's Medical Text Indexer.

The Medical Text Indexer (MTI) is a program for producing MeSH indexing recommendations. It is the major product of NLM's Indexing Initiative and has been used in both semi-automated and fully automated indexing environments at the Library since mid 2002. We report here on an experiment conducted with MEDLINE indexers to evaluate MTI's performance and to generate ideas for its improvement as a tool for user-assisted indexing. We also discuss some filtering techniques developed to improve MTI's accuracy for use primarily in automatically producing the indexing for several abstracts collections.

Abstracting and Indexing↗
PubMed1991

Comparison of traditional gas chromatography (GC), headspace GC, and the microbial identification library GC system for the identification of Clostridium difficile.

Three gas chromatography (GC) methods were compared for the identification of 52 clinical Clostridium difficile isolates, as well as 17 non-C. difficile Clostridium isolates. Headspace GC and Microbial Identification System (MIS) GC, an automated system which utilizes a software library developed at the Virginia Polytechnic Institute to identify organisms based on the fatty acids extracted from the bacterial cell wall, were compared against the reference method of traditional GC. Headspace GC and MIS were of approximately equivalent accuracy in identifying the 52 C. difficile isolates (52 of 52 versus 51 of 52, respectively). However, 7 of 52 organisms required repeated sample preparation before an identification was achieved by the MIS method. Both systems effectively differentiated C. difficile from non-C. difficile clostridia, although the MIS method correctly identified only 9 of 17. We conclude that the headspace GC system is an accurate method of C. difficile identification, which requires only one-fifth of the sample preparation time of MIS GC and one-half of the sample preparation time of traditional GC.

Bacteriological Techniques↗
PubMed2005

Construction, evaluation and refinement of a large human antibody phage library based on the IgD and IgM variable gene repertoire.

The ability to isolate antibodies against any antigen of interest has become increasingly important as antibodies have proved their utility both in antigen detection, quantification and as specific in vivo targeting agents. To this end, we have constructed a large antibody phage library in the single chain Fv (scFv) phagemid format based on the naive human variable (V) gene repertoire dictated by IgD and IgM. Optimizing each step of the library construction has resulted in a highly diverse and functional library, as assessed by sequencing analysis, large-scale automated expression analysis and antigen screening. Furthermore, the versatile format of the library, which comprises 14 separate sub-libraries, adds considerably flexibility with respect to which part of the antibody repertoire that is to be probed. This versatility has been further exploited to generate a refined antibody library, which exhibits one of the highest prokaryotic expression levels reported to date for a naive repertoire. The construction of the refined library was based on the functional purification of expressed V genes in the context of the protein L interaction with correctly folded V genes of the kappa light chain family. Antigen screening of this library indicated that the functional purification improved the ability to retrieve antigen specific antibodies, but at the cost of potential loss of diversity in the isolated repertoire.

Amino Acid Sequence↗