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Construction of rare restriction site (NotI, SacII and ClaI) linking libraries and sequence-tagged site analysis of single-copy clones from a human chromosome-3-specific library.

We have constructed rare restriction-site (NotI, SacII and ClaI) chromosome 3 (Chr 3)-specific linking libraries in a plasmid-based vector by mass transfer of a lambda phage human Chr-3-specific library (LA03NS01-ATCC57717) into pUC18. Total plasmid DNA isolated from the plasmid-based Chr-3-specific library was digested with either ClaI, NotI or SacII. Linear molecules were separated from undigested circles by pulsed-field polyacrylamide-gel electrophoresis. Purified linear molecules were circularized with T4 DNA ligase and transformed into bacteria. The resulting clones were greatly enriched for sequences recognized by the original restriction endonuclease used for digestion (83 to 95%). These sublibraries are composed of 600 (NotI) 1000 (SacII) or 30,000 (ClaI) clones. Thus, this procedure allows for easy isolation of Chr-3-specific DNA clones containing a variety of rare restriction sites. Sequence-tagged site (STS) data are also presented for five site-specifically mapped Chr-3-specific DNA clones. These studies may facilitate the construction of region specific linking libraries for mapping of various disease-specific loci on Chr 3.

Animals↗

Combinatorial chemistry: libraries from libraries, the art of the diversity-oriented transformation of resin-bound peptides and chiral polyamides to low molecular weight acyclic and heterocyclic compounds.

Combinatorial chemistry has deeply impacted the drug discovery process by accelerating the synthesis and screening of large numbers of compounds having therapeutic and/or diagnostic potential. These techniques offer unique enhancement in the potential identification of new and/or therapeutic candidates. Our efforts over the past 10 years in the design and diversity-oriented synthesis of low molecular weight acyclic and heterocyclic combinatorial libraries derived from amino acids, peptides, and/or peptidomimetics are described. Employing a "toolbox" of various chemical transformations, including alkylation, oxidation, reduction, acylation, and the use of a variety of multifunctional reagents, the "libraries from libraries" concept has enabled the continued development of an ever-expanding, structurally varied series of organic chemical libraries.

Amino Acids↗

Tagged versus untagged libraries: methods for the generation and screening of combinatorial chemical libraries.

Over the past two decades the pharmaceutical industry has been driven by the biological sciences. The discovery and description of the biological mechanisms that underlie disease states accompanied by an unraveling of these mechanisms has provided drug, and more recently biotechnological, companies with a barrage of new therapeutic targets. Paradoxically, as a result of such biological and biochemical advances, new sources of drug leads are in short supply. Considerable efforts in trying to create potential drug candidates has led to the parturition of combinatorial chemical libraries. In this review I will examine some of the main technologies for generating and deducing active components from combinatorial libraries that have been segregated into two schools of thought: (i) the creation and decoding of combinatorial libraries by so-called tagged methodologies, and (ii) the production and deconvolution of chemical libraries by untagged protocols.

Amino Acid Sequence↗

Library subtraction of in vitro cDNA libraries to identify differentially expressed genes in scrapie infection.

We have developed a system where double-stranded cDNA can be amplified using a synthetic oligonucleotide primer and the polymerase chain reaction, generating cDNA libraries in vitro. Using a library subtraction strategy (1), scrapie and control brain in vitro cDNA libraries were used to identify sequences whose expression is modulated in scrapie infection. One of these sequences represents beta-2 microglobulin, while the other two have not been previously described. The use of in vitro libraries offers increased speed and efficiency of construction, and their subtraction is more efficient and powerful, compared with the previous system (1).

Animals↗

The Oryza bacterial artificial chromosome library resource: construction and analysis of 12 deep-coverage large-insert BAC libraries that represent the 10 genome types of the genus Oryza.

Rice (Oryza sativa L.) is the most important food crop in the world and a model system for plant biology. With the completion of a finished genome sequence we must now functionally characterize the rice genome by a variety of methods, including comparative genomic analysis between cereal species and within the genus Oryza. Oryza contains two cultivated and 22 wild species that represent 10 distinct genome types. The wild species contain an essentially untapped reservoir of agriculturally important genes that must be harnessed if we are to maintain a safe and secure food supply for the 21st century. As a first step to functionally characterize the rice genome from a comparative standpoint, we report the construction and analysis of a comprehensive set of 12 BAC libraries that represent the 10 genome types of Oryza. To estimate the number of clones required to generate 10 genome equivalent BAC libraries we determined the genome sizes of nine of the 12 species using flow cytometry. Each library represents a minimum of 10 genome equivalents, has an average insert size range between 123 and 161 kb, an average organellar content of 0.4%-4.1% and nonrecombinant content between 0% and 5%. Genome coverage was estimated mathematically and empirically by hybridization and extensive contig and BAC end sequence analysis. A preliminary analysis of BAC end sequences of clones from these libraries indicated that LTR retrotransposons are the predominant class of repeat elements in Oryza and a roughly linear relationship of these elements with genome size was observed.

Base Sequence↗

Attitudes to LIS education and academic-practitioner liaison: results of a survey of members of the Library Association Health Libraries Group.

A questionnaire survey was conducted by the Library Association Health Libraries Group in October-December 1996. Information practitioners in the health care sector were asked what they considered were the education and research needs of the profession, their opinion of Library and Information Sciences education, and their views on practitioner input to education and research. They were also asked whether they would be prepared to give talks to students and to offer student placements. The results show that there is still a considerable gulf between academics and practitioners, and that although practitioners are enthusiastic about getting more involved in liaison, they are constrained by lack of time and resources. Practical solutions need to be found to encourage greater understanding and closer working relationships, to achieve the benefits of academic-practitioner liaison.

Adult↗

New library buildings. Part VI: Sciences Library, Brown University.

Brown was one of the first universities in the nation to combine its science collections into a single library in the interest of aiding interdisciplinary teaching and research. This paper discusses the evolution of the Sciences Library and its resources, the development of the medical education program, and the physical aspects of the new library building. A fifteen-story tower, housing the collections of the physical, biological, and medical sciences, symbolizes the interdisciplinary approach to teaching and research at Brown University.

Architecture↗

Studies on locus expansion, library representation, and chromosome walking using an efficient method to screen cosmid libraries.

We have developed an efficient screening method to search for clones in cosmid libraries prepared from human genomic DNA. Genomic, cDNA, and cosmid probes have been used to isolate homologous cosmids from human chromosomes 7, 10, 16, 17 and X as part of a search for polymorphic nucleotide sequences. This method has been successfully applied to chromosome walking experiments at the interstitial retinol-binding protein locus on chromosome 10, and may be a useful tool for investigating representation of cloned sequences in cosmid libraries. Our library was prepared in the vector c2RB (Bates and Swift, 1983), but the method is applicable to any cosmid cloning system in which the inserted DNA can be separated from the vector by restriction enzyme digestion. A cosmid library containing five human genome equivalents can be rapidly screened using three to four Southern hybridization filters. This results in substantial labor saving, particularly when screening genomes of high complexity with many different probes. Another advantage of the system is that it allows for the long-term storage of the cosmids so that they can be screened whenever necessary. As a consequence, cosmid screening can be made a routine laboratory procedure.

Blotting, Southern↗

Microwave-assisted "libraries from libraries" approach toward the synthesis of allyl- and C-cyclopropylalkylamides.

Cascade reactions of internal and terminal alkynes, zirconocene hydrochloride, dimethylzinc, and phosphinoyl imines (prepared in one step from aldehydes and diphenylphosphinoyl amide) lead to allylic phosphinoyl amides after aqueous workup. Microwave acceleration allows the completion of this one-pot reaction sequence in 10 min. These allylic amides can be converted into a variety of derivatives, including carbamates and sulfonamides, or reacted prior to workup with diiodomethane to give novel C-cyclopropylalkylamides. A solution-phase "libraries from libraries" approach was used to generate an intermediate 20-member library which was subsequently expanded to a 100-member library by a series of N-functionalizations. The biological activity was evaluated in an assay for competitive binding to the estrogen receptor (ERalpha), revealing three potent lead compounds of a new structural type.

Allyl Compounds↗

Indexing the sequence libraries: software providing a common indexing system for all the standard sequence libraries.

We describe a set of programs for creating and using indexes for the distributed forms of the major sequence libraries. The indexes conform to the specification of those distributed on cd-rom by the EMBL sequence library. The programs create entry name, accession number, author and freetext indexes and a brief directory index. If a suitable application program is given an entry name or accession number these indexes allow rapid retrieval of sequences or annotation. Similarly the author and freetext indexes provide the data for extremely fast searching on author names and "keywords". The indexing programs can create indexes for EMBL, Swiss-Prot, GenBANK, PIR and NRL3d libraries. We also describe the organisation and use of the different sequence libraries and their index files.

Abstracting and Indexing↗

Synthesis of combinatorial libraries of 3,4,5-trisubstituted 2(5H)-furanones. Part Two: Construction of a library of 4-amino-5-alkoxy-2(5H)-furanones.

A three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones has been prepared by applying solution phase combinatorial chemistry techniques. The substituents in the 3-4-5-positions of a butenolide scaffold were varied independently to generate with 3 butenolides, 4 alcohols and 24 amines a library of 288 compounds using a 2 stage synthetic protocol. Typical representives of the library were purified and fully characterized. Biological evaluation resulted in the discovery of a lead structure for a new class of antibiotic agents. The 4-benzylamino-2(5H)-furanone, Dr, of this library has shown a promising antibiotic activity against the multiresistant Staphillococcus aureus (MRSA 96-7778).

Anti-Bacterial Agents↗

Meeting information needs in health policy and public health: priorities for the National Library of Medicine and The National Network of Libraries of Medicine.

Those seeking information in health policy and public health are not as well served as those seeking clinical information. Problems inhibiting access to health policy and public health information include the heterogeneity of professionals seeking the information, the distribution of relevant information across disciplines and information sources, scarcity of synthesized information useful to practitioners, lack of awareness of available services or training in their use, and lack of access to information technology or to knowledgeable librarians and information specialists. Since 1990, the National Library of Medicine and the National Network of Libraries of Medicine have been working to enhance information services in health policy and public health through expanding the coverage of the NLM collection, building new databases, and engaging in targeted outreach and training initiatives directed toward segments of the health policy and public health communities. Progress has been made, but more remains to be done. Recommendations arising from the meeting, Accessing Useful Information: Challenges in Health Policy and Public Health, will help NLM and the National Network of Libraries of Medicine to establish priorities and action plans for the next several years.

Health Policy↗

The way we were: health library life seen through the pages of the Medical Library Bulletin of the Thames Regions, 1974-94.

The Medical Library Bulletin of the Thames Regions reflected the development of health-service libraries over the 20 years it existed. Originally begun as a practical aid to improving services by encouraging co-operation, improving communication and giving instructive advice, it charted the work of health-service librarians and the growth of their services. The articles contained in it covered professional developments and wider political issues as they occurred, and illustrated the extension of the librarians' knowledge and skills. Leslie Morton, Library Adviser to the British Postgraduate Medical Federation, edited almost every issue, starting at a time when there was little guidance or professional literature available for health-service librarians.

History, 20th Century↗

Mechanization of library procedures in a medium-sized medical library: XVI. Computer-assisted cataloging, the first decade.

After ten years of experimentation in computer-assisted cataloging, the Washington University School of Medicine Library has decided to join the Ohio College Library Center network. The history of the library's work preceding this decision is reviewed. The data processing equipment and computers that have permitted librarians to explore different ways of presenting cataloging information are discussed. Certain cataloging processes are facilitated by computer manipulation and printouts, but the intellectual cataloging processes such as descriptive and subject cataloging are not. Networks and shared bibliographic data bases show promise of eliminating the intellectual cataloging for one book by more than one cataloger. It is in this area that future developments can be expected.

Cataloging↗

Using UMLS to map from a library to a clinical classification: Improving the functionality of a digital library.

The Metathesaurus of the Unified Medical Language System (UMLS) offers the possibility of mapping between various medical vocabularies. The Primary Care Electronic Library (PCEL) contains a database of over six thousand Medical Subject Headings (MeSH terms) describing the resources of the electronic library. We were interested to know if it was possible to map from MeSH to the Systemized Nomenclature of Medicine Clinical Terms (SNOMED CT). Such a mapping would aid healthcare professionals to retrieve relevant data from our digital library as it would enable links between clinical systems and indexed material.

Databases, Bibliographic↗

Planning a new library in an age of transition: the Washington University School of Medicine Library and Biomedical Communications Center.

In an era of great technological and socioeconomic changes, the Washington University School of Medicine conceptualized and built its first Library and Biomedical Communications Center in seventy-eight years. The planning process, evolution of the electronic library, and translation of functions into operating spaces are discussed. Since 1983, when the project was approved, a whole range of information technologies and services have emerged. The authors consider the kind of library that would operate in a setting where people can do their own searches, order data and materials through an electronic network, analyze and manage information, and use software to create their own publications.

Facility Design and Construction↗

Medical libraries and computers. The role of medical libraries in medical informatics.

The classic function of health sciences libraries is to build and maintain a knowledge base and to provide timely access to that collective memory for the purpose of learning, teaching, caring for patients, conducting research or managing an organization. The formats and representation of that knowledge base are changing rapidly, as are the methods and techniques for gaining access to information. Medical libraries have long used computers for cataloging and controlling records but are now shifting to acquiring, managing and distributing bibliographic and full-text information to local library "networks."

Computer Communication Networks↗

Library orientation methods: J. Hillis Miller Health Center Library program.

Two orientation devices are described which are currently in use at the J. Hillis Miller Health Center Library. One is a taped tour which requires a portable recorder with earphones attached. Tapes are now available for nursing students, physical therapy students, and Health Center staff. The tour includes location information and description of the card catalog and certain basic index and abstract services. The second orientation device is a short instruction tape on the use of Index Medicus which is attached to the Index Medicus table. This is heard through a telephone apparatus. It is anticipated that the tape technique will be expanded to apply to other students and other library tools. It is also believed that this technique may be used in other libraries. Information about the supplies and equipment used is given as an addendum.

Abstracting and Indexing↗