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PubMed2006

A review of electronic journal acquisition, management, and use in health sciences libraries.

PURPOSE: The paper describes patterns of electronic journal usage in health sciences libraries during the past decade. METHOD: The paper presents a case study, documenting the pattern of acquisition, management, and usage at the Louis Calder Memorial Library of the University of Miami Miller School of Medicine. RESULTS: Health sciences journals were early to offer electronic alternatives to print. As a result, health sciences libraries, their patrons, and the public at large were early to embrace the new versions and continue to embrace the significant changes in scholarly communication they enable. Although the patterns of electronic journals among health sciences libraries and other special and academic libraries have similarities, they also have differences. Broad studies of electronic journals in non-health sciences libraries have been published, but a retrospective review of electronic journals in health sciences libraries has not.

Access to Information↗
PubMed1989

Subpoenas and library operations: rules and recourse.

The subpoena process represents a legal obligation and duty of citizenry and is becoming a fact of life in the operations of many libraries. Regardless of whether a library is directly involved in litigation, the library director may be faced with adjusting operations to compensate for the loss of personnel, collection materials, or other resources in order to accommodate the demands of a subpoena. This paper outlines the formal subpoena process and highlights a number of scenarios by which the library may become a part of the process. The area of computer law, in particular, may present a "growth phase" in library litigation. In addition, recommendations to minimize the service interruptions caused by the subpoena are offered. The director must assist library counsel in formulating a response to challenge, modify, or quash (throw out) the subpoena. Efforts to quash the subpoena require proof that the materials requested are irrelevant to the case, not subpoenaed for "good cause," or that compliance would be unduly oppressive and burdensome. In any case, the library director must be fully prepared to educate counsel on the potential impact of the subpoena.

Libraries↗
PubMed1970

Coordination of regional libraries with Regional Medical Program projects.

The Medical Library Assistance Act authorized the Regional Medical Library Program to improve information services in health fields, as well as other programs designed to help the health worker. Both the RMLP and the Regional Medical Program are based on regional cooperation to enhance the value of available resources, and to enable health workers away from main centers to use them. Services which Regional Medical Libraries must supply are described. As this program develops, more than conventional library services will be provided. Regional Medical Programs stress the continuing education of health-related personnel, and their need for health information; libraries are necessarily involved in such programs. The regions of the RMP are smaller than those of the RMLP, and the smaller regional focus may be an advantage. Specific examples of the coordination of library services and library-oriented programs are given.

Information Services↗
PubMed1981

National rankings as a means of evaluating medical school library programs: a comparative study.

A comparative study was undertaken to assess the reasons for the low rankings received by George Washington University Medical Center library in the Annual Statistics for Medical School Libraries in the United States and Canada. Although internal studies showed the library was successfully satisfying user needs and meeting its primary objectives, the rankings, which include the traditional measures of quality used by accrediting bodies, indicated the contrary. Three hypotheses were postulated to account for the discrepancy. In a matched group of similar libraries: (1) the rankings of an individual library would differ from the national rankings; (2) clustering the variables would change the rankings; and (3) libraries with similar staff size would tend to rank in the same quartile in service and resource variables. All hypotheses were invalidated. Further tests led to the conclusion that the Annual Statistics and other traditional measures of quality are inappropriate and inaccurate methods for evaluating library programs, since they only measure resource allocations and not the effectiveness of those allocations. Alternative evaluation methods are suggested.

Evaluation Studies as Topic↗
PubMed1999

Developing a culture of lifelong learning in a library environment.

Between 1995 and 1996, the Annette and Irwin Eskind Biomedical Library (EBL) at Vanderbilt University Medical Center (VUMC) radically revised the model of service it provides to the VUMC community. An in-depth training program was developed for librarians, who began to migrate to clinical settings and establish clinical librarianship and information brokerage services beyond the library's walls. To ensure that excellent service would continue within the library, EBL's training program was adapted for library assistants, providing them with access to information about a wide variety of work roles and processes over a four to eight-month training period. Concurrently, customer service areas were reorganized so that any question--whether reference or circulation--could be answered at any of four service points, eliminating the practice of passing customers from person to person between the reference and circulation desks. To provide an incentive for highly trained library assistants to remain at EBL, management and library assistants worked together to redesign the career pathway based on defined stages of achievement, self-directed participation in library-wide projects, and demonstrated commitment to lifelong learning. Education and training were the fundamental principles at the center of all this activity.

Career Mobility↗
PubMed2005

Trends in academic health sciences libraries and their emergence as the "knowledge nexus" for their academic health centers.

OBJECTIVES: The objective of this study was to identify trends in academic health sciences libraries (AHSLs) as they adapt to the shift from a print knowledgebase to an increasingly digital knowledgebase. This research was funded by the 2003 David A. Kronick Traveling Fellowship. METHODS: The author spent a day and a half interviewing professional staff at each library. The questionnaire used was sent to the directors of each library in advance of the visit, and the directors picked the staff to be interviewed and set up the schedule. RESULTS: Seven significant trends were identified. These trends are part of the shift of AHSLs from being facility and print oriented with a primary focus on their role as repositories of a print-based knowledgebase to a new focus on their role as the center or "nexus" for the organization, access, and use of an increasingly digital-based knowledgebase. CONCLUSION: This paper calls for a national effort to develop a new model or structure for health sciences libraries to more effectively respond to the challenges of access and use of a digital knowledgebase, much the same way the National Library of Medicine did in the 1960s and 1970s in developing and implementing the National Network of Libraries of Medicine. The paper then concludes with some examples or ideas for research to assist in this process.

Academic Medical Centers↗
PubMed1999

Collection development and outsourcing in academic health sciences libraries: a survey of current practices.

Academic health sciences libraries in the United States and Canada were surveyed regarding collection development trends, including their effect on approval plan and blanket order use, and use of outsourcing over the past four years. Results of the survey indicate that serials market forces, budgetary constraints, and growth in electronic resources purchasing have resulted in a decline in the acquisition of print items. As a result, approval plan use is being curtailed in many academic health sciences libraries. Although use of blanket orders is more stable, fewer than one-third of academic health sciences libraries report using them currently. The decline of print collections suggests that libraries should explore cooperative collection development of print materials to ensure access and preservation. The decline of approval plan use and the need for cooperative collection development may require additional effort for sound collection development. Libraries were also surveyed about their use of outsourcing. Some libraries reported outsourcing cataloging and shelf preparation of books, but none reported using outsourcing for resource selection. The reason given most often for outsourcing was that it resulted in cost savings. As expected, economic factors are driving both collection development and outsourcing practices.

Budgets↗
PubMed1964

MEDLARS AND THE LIBRARY COMMUNITY.

The intention of the National Library of Medicine is to share with other libraries the products and the capabilities developed by the MEDLARS system. MEDLARS will provide bibliographic services of use to other libraries from the central system. The decentralization of the central system to permit libraries with access to computers to establish local machine retrieval systems is also indicated. The implications of such decentralization for the American medical library network and its effect on library evolution are suggested, as are the implications for international development of mechanized storage and retrieval systems.

Abstracting and Indexing↗
PubMed2003

MUC1-derived glycopeptide libraries with improved MHC anchors are strong antigens and prime mouse T cells for proliferative responses to lysates of human breast cancer tissue.

Multi-component glycopeptide libraries and single glycopeptides were used for immunization of mice with the aim of inducing strong T helper cell responses to the repetitive sequence of MUC1 expressed by human tumor cells. The glycopeptides and glycopeptide libraries were modeled upon the native human MUC1 amino acid variable number of tandem repeats sequence by introduction of modifications in the MHC anchor positions to optimally fulfil the binding requirements of the A(d) MHC class II molecule in the BALB/c mouse. The immunogenicity of the MUC1 glycopeptides in BALB/c mice was determined by immunization in complete Freund's adjuvant and assaying lymph node T cells for a proliferative response to the glycopeptide used. Strong proliferative responses with stimulation indices over 50 were obtained with anchor-improved glycopeptide libraries as well as with single glycopeptides. Immunization with one of the glycopeptide libraries primed T cells for a proliferative cross-response to the native MUC1 glycopeptide, which by itself was nonimmunogenic. In addition, immunization with the same glycopeptide library primed T cells for a strong response to lysate of a MUC1-expressing human breast cancer, and immunization with the tumor lysate primed T cells for a response to the glycopeptide library. The T cells responding in the assay for proliferation were restricted to the A(d) MHC class II molecule. The results indicate that immunization with MHC anchor-improved MUC1 glycopeptide libraries can effectively prime T helper cells and may induce long-term memory. The approach may be useful in the design of preventive cancer vaccines for use in humans.

Amino Acid Sequence↗
PubMed2006

Isolation of targeted AAV2 vectors from novel virus display libraries.

Random peptide ligands displayed on viral capsids are emerging tools for selection of targeted gene transfer vectors even without prior knowledge of the potential target cell receptor. We have previously introduced adeno-associated viral (AAV)-displayed peptide libraries that ensure encoding of displayed peptides by the packaged AAV genome. A major limitation of these libraries is their contamination with wild-type (wt) AAV. Here we describe a novel and improved library production system that reliably avoids generation of wt AAV by use of a synthetic cap gene. Selection of targeted AAV vectors from wt-containing and the novel wt-free libraries on cell types with different permissivity for wt AAV2 replication suggested the superiority of the wt-free library. However, from both libraries highly specific peptide sequence motifs were selected which improved transduction of cells with moderate or low permissivity for AAV2 replication. Strong reduction of HeLa cell transduction compared to wt AAV2 and only low level transduction of non-target cells by some selected clones showed that not only the efficiency but also the specificity of gene transfer was improved. In conclusion, our study validates and improves the unique potential of virus display libraries for the development of targeted gene transfer vectors.

Animals↗
PubMed1996

Combinatorial peptide libraries: robotic synthesis and analysis by nuclear magnetic resonance, mass spectrometry, tandem mass spectrometry, and high-performance capillary electrophoresis techniques.

Combinatorial peptide libraries are a new source of compounds from which a large number of pharmacological leads will emerge in the next few years. A large body of literature shows that this approach is of considerable interest in many areas of biological sciences for the search of enzyme substrates and inhibitors, of receptor agonists or antagonists, or of antigen sequences. Nevertheless, the analytical investigation of such complex mixtures as libraries which contain up to millions of individual molecules is still poorly documented. In this work, we present analytical solutions for their characterization. NMR and tandem mass spectrometry (MS/MS) can provide an in deep description of any type of combinatorial libraries, while MS and high-performance capillary electrophoresis can bring a rapid and overall information at the routine level, sufficient to ensure a first assessment of their composition. MS in the fast atom bombardment mode was used to describe the libraries O1X2X3X4X5 or O1X2X3X4 (Oi and Xi are fixed and random residue in position i, respectively). Advantage was taken of the high proton affinity of arginine and of its induction of charge remote fragmentation to interpret the MS spectra of whole libraries and neutral losses (MS/MS) in the model sublibraries ArgGlyX3X4 and NipValX3X4 (Nip,4-nitrophenylalanine). Two-dimensional NMR allowed the incorporation of the individual residues during synthesis to be tested in 24 sublibraries O1X2X3X4. While from the pharmacological point of view, impressive discoveries made with combinatorial peptide libraries have already been reported, our results show that they should be complemented by appropriate analytical tools, crucial for the proper characterization and exploitation of these libraries.

Amino Acid Sequence↗
PubMed1997

A large-insert (130 kbp) bacterial artificial chromosome library of the rice blast fungus Magnaporthe grisea: genome analysis, contig assembly, and gene cloning.

Magnaporthe grisea (Hebert) Barr causes rice blast, one of the most devastating diseases of rice (Oryza sativa) worldwide. This fungus is an ideal organism for studying a number of aspects of plant-pathogen interactions, including infection-related morphogenesis, avirulence, and pathogen evolution. To facilitate M. grisea genome analysis, physical mapping, and positional cloning, we have constructed a bacterial artificial chromosome (BAC) library from the rice infecting strain 70-15. A new method was developed for separation of partially digested large-molecular-weight DNA fragments that facilitated library construction with large inserts. The library contains 9216 clones, with an average insert size of 130 kbp (> 25 genome equivalents) stored in 384-well microtiter plates that can be double spotted robotically on to a single nylon membrane. Several unlinked single-copy DNA probes were used to screen 4608 clones in the library and an average of 13 (minimum of 6) overlapping BAC clones was found in each case. Hybridization of total genomic DNA to the library and analysis of individual clones indicated that approximately 26% of the clones contain single-copy DNA. Approximately 35% of BAC clones contained the retrotransposon MAGGY. The library was used to identify BAC clones containing a adenylate cyclase gene (mac1). In addition, a 550-kbp contig composed of 6 BAC clones was constructed that encompassed two adjacent RFLP markers on chromosome 2. These data show that the BAC library is suitable for genome analysis of M. grisea. Copies of colony hybridization membranes are available upon request.

Ascomycota↗
PubMed1996

Spatiotemporally exact cDNA libraries from quail embryos: a resource for studying neural crest development and neurocristopathies.

The neural crest is of fundamental importance in the developments of the head and peripheral nervous system, in the evolution of the vertebrates, and clinically because it gives rise to developmental abnormalities and neoplasms in humans. We have established a resource for studying the development of the neural crest by systematically constructing cDNA libraries from spatiotemporally exact neural crest and related cell populations. Neural crest populations were obtained from vagal and thoracic axial levels and from branchial arches, at premigratory and early and late migratory stages, at localization stages, and after differentiation into dorsal root ganglion cells, Schwann cells, sympathetic neurons, adrenal medullary cells, and melanocytes. Libraries were constructed using several methods developed to approach the issue of making representative libraries from small amounts of tissue. The fidelity and usefulness of the libraries were tested, and this revealed that they expressed a variety of sequences such as integrins, CAMs, growth factors and their receptors, protein-tyrosine kinases, and phosphatases. Differential display also revealed a unique combination of cDNA species. We then selected libraries spatiotemporally appropriate for epithelium-mesenchyme transformation and probed for TGF-beta-related sequences. As anticipated, we confirmed the presence of TGF-beta 2 and dorsalin-1 but could not detect TGF-beta 1. We also revealed new expression sites, defined by the origin of the libraries, of receptors known to be expressed elsewhere (Tsk 7l; TBRII). We anticipate that this collection of cDNA libraries will be of use in studying normal and abnormal neural crest development, by both homology searches and differential expression approaches, with spatiotemporal expression information being inherent in the initial screen.

Animals↗
PubMed1997

Construction and screening of a cosmid library generated from a somatic cell hybrid bearing human chromosome 15.

A cosmid library has been constructed with DNA isolated from a mouse/human hybrid cell line designated A15, which was previously characterized and shown to retain chromosome 15 as the only human material. The library was generated and stored as 34 independent pools of primary colonies at 8-10,000 colonies per pool. Screening colonies representing pools of this library by hybridization with a human-specific repetitive probe has facilitated the identification of random clones bearing human inserts. To data, 43 unique clones have been isolated and the inserts mapped by fluorescence in situ hybridization (FISH) to chromosome 15. An STS was generated for each of these clones by end sequencing of the inserts. Two of these clones, c36 and MR23, were mapped by FISH to 15q26.1, and end-sequence data revealed homology to different regions of the FES protooncogene. Sequence generated from the other end of the c36 insert was found to match the previously identified and unmapped coding sequence EST00075. In addition to the identification of such random clones, establishment of the library as pools was expected to facilitate the PCR-based identification of unique clones representing specific regions of chromosome 15. Screening of the library pools with primers specific to the FES region led to the recovery of five independent clones facilitating the development of a cosmid contig encompassing the FES gene. One of the cosmids isolated by PCR-based analysis was derived from the same pool as M23 and was subsequently shown to be identical to M23. The data offer the first report of a chromosome 15 cosmid library and demonstrate the value of utilizing pools to evaluate libraries generated from complex sources like somatic cell hybrids.

Animals↗
PubMed1998

Construction and characterization of a 10-fold genome equivalent rat P1-derived artificial chromosome library.

A rat PAC library was constructed in the vector pPAC4 from genomic DNA isolated from female Brown Norway rats. This library consists of 215,409 clones arrayed in 614,384-well microtiter plates. An average insert size of 143 kb was estimated from 217 randomly isolated clones, thus representing approximately 10-fold genome coverage. This coverage provides a very high probability that the library contains a unique sequence in genome screening. Tests on randomly selected clones demonstrated that they are very stable, with only 4 of 130 clones showing restriction digest fragment alterations after 80 generations of serial growth. FISH analysis using 70 randomly chosen PACs revealed no significant chimeric clones. About 7% of the clones analyzed contained repetitive sequences related to centromeric regions that hybridized to some but not all centromeres. DNA plate pools and superpools were made, and high-density filters each containing an array of 8 plates in duplicate were prepared. Library screening on these superpools and appropriate filters with 10 single-locus rat markers revealed an average of 8 positive clones, in agreement with the estimated high genomic coverage of this library and representation of the rat genome. This library provides a new resource for rat genome analysis, in particular the identification of genes involved in models of multifactorial disease. The library and high-density filters are currently available to the scientific community.

Animals↗
PubMed1995

A conformationally homogeneous combinatorial peptide library.

In search for a rational way to convert the information encoded in peptide structures into peptidomimetics, major progress could be made by coupling the power of selection methods, now enormously increased in number as a result of the development of combinatorial peptide libraries, with the rational design of structure-inducing templates for the selectable sequences. The availability of libraries of peptides with predetermined structure would enable selection-driven peptidomimetic design, whereby a conformational model for the peptide pharmacophore would be directly derived from the screening, allowing the design of a suitable non-peptidic scaffold to replace the peptide backbone. We describe here the first example of a conformationally homogeneous combinatorial peptide library, which yields ligands with the expected structure upon selection. The library was built by randomising five positions in the alpha-helical portion of a 26 amino acid Cys2His2 consensus "zinc-finger" motif. Since in zinc-fingers metal coordination and folding are coupled, in our library metal-dependent binding represents a built-in control against the selection of structurally undefined sequences. The alpha-helical library was produced as both fusion with the pVIII protein of filamentous phage and soluble peptides by chemical synthesis, the latter enabling the expansion of the selectable repertoire by the inclusion of non-coded amino acids. The two libraries were independently screened with the same receptor (a monoclonal IgA reactive against the lipopolysaccharide of the human pathogen Shigella flexneri), yielding a very similar consensus. In particular, the peptides defined by both methods showed very strong, zinc-dependent binding to the IgA. The geometrical arrangement of the side-chains of the selected peptide pharmacophore was shown by circular dichroism, Co(II)-complex absorption and high-resolution NMR to be structurally invariant with respect to the parent zinc-finger.

Amino Acid Sequence↗
PubMed1996

Use of a conformationally restricted secondary structural element to display peptide libraries: a two-stranded alpha-helical coiled-coil stabilized by lactam bridges.

A model for an alpha-helical peptide library based on a lactam bridged stabilized two-stranded alpha-helical coiled-coil is described. Sites for library display were incorporated in the middle of the peptide sequence of the most solvent accessible sites of a coiled-coil. A comparison was made between this coiled coil and a native coiled-coil based on the same sequence but lacking the lactam bridges. A lactam bridged peptide where the hydrophobic repeat consisted of all alanine residues, such that the tendency to dimerize would be diminished, was also prepared. This enabled us to determine the role tertiary interactions play in maintaining library positions in a helical conformation. The consensus sequence derived from a Zn finger library screened against an IgA reactive against the lipopolysaccharide of Shigella flexneri was transplanted into the peptides. CD spectroscopy revealed that although both coiled-coils are highly helical at 100 microM, the lactam bridge enhanced dimerization and allow the peptide to maintain its coiled-coil conformation at lower peptide concentrations. The helical content of the alanine based peptide was 69% and was independent of concentration over a range of 1.4 to 1410 microM. Urea denaturation studies indicated that the coiled-coils were considerably more stable than the alanine based peptide and that the lactam bridge coiled-coil was more stable than the native coiled coil by 1.6 kcal/mol. The lactam bridged coiled-coil was found to inhibit binding of the Zn finger peptide to the IgA in a concentration dependent manner with an IC50 of 5.0 microM whereas the peptide lacking the lactam bridges was much less effective in inhibiting binding. The alanine peptide was less active than the lactam bridged coiled-coil but more effective than the native coiled-coil with an IC50 of 16 microM. The versatility of the lactam stabilized coiled-coil template was demonstrated by incorporating five Gly residues into the library display sites. While the native coiled-coil adopted a random conformation the lactam bridged coiled-coil was 59% helical. Incorporation of a Cys-Gly-Gly linker to the N terminus and formation of a disulfide bond stabilized the peptide to the extent that it adopted a highly helical coiled-coil (94%) with a [urea]1/2 value of 5.9 M. Since the five glycine residues represent one of the most destabilizing combinations of amino acids that would be encountered at the five library display sites (with the exception of Pro), this stabilized coiled-coil should maintain its folded conformation regardless of the amino acids occupying the library positions.

Amino Acid Sequence↗
PubMed2002

Construction and preliminary screening of a human phage single-chain antibody library associated with gastric cancer.

BACKGROUND: The aim of this study was to construct a phage library of human single-chain antibodies associated with gastric cancer and screen such a library for CEA binding scFv. MATERIALS AND METHODS: The cDNA library of antibody variable regions was constructed using mRNA from metastatic lymph nodes or spleen of patients with stomach cancer by RT-PCR. These cDNA were assembled into a single-chain format and cloned into phagemid pCANTAB-5 and then transformed into Escherichia coli TG1. The scFv gene library was rescued by M13KO7 helper phage. CEA and the viable CEA-positive gastric cancer cell line MKN-28 were used to screen the phage antibody library. Indirect and tumor cell ELISA was used to determine the specificity of phage antibody. Fixed cell immunofluorescence and live cell FACS analysis were used to further characterize the binding of phage scFv. RESULTS: After transformation into E. coli TG1, 2.5 x 10(7) cfu/microg ampicillin-resistant clones grew. Sequences of those positive insert clones showed that the V(H) genes were derived from the V(H) III subgroup, while the V(L) genes belonged to the V(kappa) III subgroup. After four rounds of panning, the titer of eluted binding phage increased 135- to 158-fold and ELISA results showed that 20/95 clones can bind CEA and 47/95 clones can bind fixed tumor cells. Immunofluorescence and FACS analysis results showed that these phage scFv fragments could bind CEA-positive cells. CONCLUSIONS: We successfully constructed a human phage antibody library from lymph nodes of stomach cancer patients. Such kinds of library prove useful for generating tumor-antigen-specific human antibody fragments.

Amino Acid Sequence↗