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Manufacturing immunity to disease in a test tube: the magic bullet realized.

Although it took over one hundred years, Ehrlich's concept of the magic bullet is now a reality. Today, therapeutic antibodies are, arguably, the most important class of new drugs for the treatment of illnesses ranging from Alzheimer's disease to cancer. The emergence of therapeutic antibodies had to wait for advances in immunochemistry that allowed construction of antibodies in vitro. The centerpiece of the new technology is the combinatorial antibody library, which essentially allows one to synthesize an artificial immune system with a diversity that exceeds that of the natural repertoire. The construction of such libraries was perceived to be difficult because, if the natural immune system was to be used as the starting material, construction of the libraries would entail protocols that are the opposite of usual cloning. In gene cloning one starts with complexity and reduces it to a singularity. In the generation of diversity by construction of combinatorial antibody libraries, one starts with a collection of clones, randomly expands their complexity, and then returns them to recoverable singularities. The methods developed to accomplish this seemingly formidable task now allow construction of antibodies in a test tube to any antigen. These synthetic antibodies may be qualitatively and quantitatively superior to those of nature.

Antibodies↗

A survey of UK clinical librarianship: February 2004.

AIM: This article will describe a survey carried out in February 2004, the aim of which was to summarize the form and content of clinical librarian (CL) and other similar outreach information services to UK health professionals in the acute (secondary or tertiary) sector. OBJECTIVES: (i) To survey the activities and views of UK information professionals offering information services involving the librarians' presence in the clinical setting, (ii) to develop a tool to explore critical aspects of this form of information work, (iii) to create a contacts database for UK CLs, to be made available on the Internet. METHODOLOGY: All known information specialists/librarians offering CL or similar services were surveyed. The semi-structured questionnaire was piloted. Respondents were asked to consider their activity over a period of 4 weeks. RESULTS: Twenty-six people responded to the invitation to take part and met the inclusion criteria. CONCLUSIONS: A summary of a 'typical' clinical librarian revealed by this survey is given, with a major conclusion that there is a very mixed picture of activity. Opinion on how far CLs should go in fully appraising search results is uncertain. The survey suggests reasons for this and the developments that may influence change are discussed. Recommendations for future research and development are offered.

Clinical Medicine↗

Do you Mini-Med School? Leveraging library resources to improve Internet consumer health information literacy.

Popular for engaging public interest in medical science while promoting health awareness, Mini-Med School (MMS) programs also afford important if largely unrealized opportunities to improve the health information literacy of attendees. With a growing population using the Internet to make health decisions, needed venues for improving Internet Consumer Health Information (CHI) literacy may be found in the MMS platform. Surveyed directors of MMS programs understand the need to include CHI, and successful programs at SUNY Stony Brook and elsewhere demonstrate the potential for collaboration with affiliated health sciences libraries to integrate CHI instruction into MMS curricula.

Academic Medical Centers↗

Quantitative reviewing: the literature review as scientific inquiry.

The literature review process is conceptualized as a form of scientific inquiry that involves methodological requirements and inferences similar to those employed in primary research. Five stages of quantitative reviewing that parallel stages in primary investigation are identified and briefly described. They include problem formation, data collection, data evaluation, analysis and interpretation, and reporting the results. The first two stages provide information and guidelines relevant to reviewers' employing traditional narrative procedures or conducting reviews of qualitative research literature. The final three stages relate specifically to the methodology of quantitative reviewing. The argument is made that quantitative reviewing procedures represent a paradigm shift that can assist researchers and clinicians in occupational therapy to establish a scientific data base that will serve to guide theory development and validate clinical practice.

Data Collection↗

LATCH at the Washington Hospital Center, 1967-1975.

Immediate access to needed information is essential if medical personnel are to provide quality health care. At the Washington Hospital Center, Literature Attached to Charts, LATCH, was created in 1967 to provide the required information quickly. As a collection of a few relevant articles attached to the patient's chart, it supplies current literature on some aspect of the patient's illness. Following an account of the program's inception, an analysis of 1,935 LATCH requests for the years 1968--1975 reveals that new physicians, that is, interns and first-year residents, requested LATCHes most often. Requests in areas of internal medicine were the most common. The data also show that the program has been well received by its users. LATCH has affected the medical library in several ways. The program has been partially responsible for increases in staff, in the number of journal subscriptions, and in the number of literature searches requested. The program has also brought about greater access to the collection via the card catalog. An important effect has been the tremendous development of professional expertise in the staff preparing the LATCH.

Humans↗

Endosperm-preferred expression of maize genes as revealed by transcriptome-wide analysis of expressed sequence tags.

The transcriptome-wide endosperm-preferred expression of maize genes was addressed by analyzing a large database of expressed sequence tags (ESTs). We generated 30,531 high quality sequence-reads from the 5'-ends of cDNA libraries from maize endosperm harvested at 10, 15, and 20 days after pollination. A further 196,900 maize sequence-reads retrieved from public databases were added to this endosperm collection to generate MAIZEST, a database with tools for data storage and analysis. MAIZEST contains 227,431 ESTs, one third of which represents developing endosperm and the remaining two-thirds represent transcripts from 49 cDNA libraries constructed from different organs and tissues. Assembling the MAIZEST ESTs generated 29,206 putative transcripts, of which a set of 4032 assembled sequences was composed exclusively of sequences derived from endosperm cDNA libraries. After sequence analysis using overlapping parameters, a sub-set of 2403 assembled sequences was functionally annotated and revealed a wide variety of putative new genes involved in endosperm development and metabolism.

Expressed Sequence Tags↗

Toward a functional annotation of the human genome using artificial transcription factors.

We have developed a novel, high-throughput approach to collecting randomly perturbed gene-expression profiles from the human genome.A human 293 cell library that stably expresses randomly chosen zinc-finger transcription factors was constructed, and the expression profile of each cell line was obtained using cDNA microarray technology.Gene expression profiles from a total of 132 cell lines were collected and analyzed by (1) a simple clustering method based on expression-profile similarity, and (2) the shortest-path analysis method. These analyses identified a number of gene groups, and further investigation revealed that the genes that were grouped together had close biological relationships. The artificial transcription factor-based random genome perturbation method thus provides a novel functional genomic tool for annotation and classification of genes in the human genome and those of many other organisms.

Antigens, Neoplasm↗

MEDLINE in the UK: pioneering the past, present and future.

This article provides a brief history of the development of the MEDLINE database and its huge impact within the UK, from its inception to the present time. The origins of MEDLINE can be traced back to a collection of books in the US Surgeon General's Office during the American Civil War and John Shaw Billings' decision, during 1867, to make this Library as complete as possible. From these beginnings, Index Medicus was developed in the early years of the 20th century, and electronic versions of the database began with the computerized on-demand search service MEDLARS in 1964 and then via CD-ROM and Internet Grateful Med to the web-based and free-to-all service, PubMed, in 1997. The response to PubMed was immediate and startling with usage increasing from 7 million searches per annum in 1996 to 400 million searches per annum in 2001 and the service continues to improve. MEDLINE providers are now offering mapping of natural language queries to the sophisticated indexing vocabulary (Medical Subject Headings, MeSH) and the provision of specific filters for different types of publication to improve searching efficiency, as well as links to full-text versions of the papers where available. The next steps are likely to involve an increased blurring of database and full-text boundaries, incorporating seamless access to the best available evidence within MEDLINE and a wide range of other information resources within a single search and to an increasing amount of full-text via various open-archive initiatives. As ever, the US National Library of Medicine is in the vanguard of research and further applications of its MEDLINE database for users within the UK will be awaited with great interest.

Grateful Med↗

Neutron tomography developments and applications.

Neutron radiography has been in use as a nondestructive testing technique for the past 50 years. The neutrons' unique ability to image certain elements and isotopes that are either completely undetectable or poorly detected by other NDI methods makes neutron radiography an important tool for the NDI community. Neutron radiography like other imaging techniques takes a number of different forms (i.e., film, radioscopic, transfer methods, tomography, etc.) This paper will describe the neutron tomography system developed at the University of California, Davis McClellan Nuclear Radiation Center (UC Davis/MNRC), and the applications for both research and commercial uses. The neutron radiography system at the UC Davis/MNRC has been under development for 4 years. The initial system was developed to find very low concentrations of hydrogen (i.e., <200 ppm). In order to achieve these low detection levels, it was necessary to perform both pre- and post-processing of the tomographs. The pre-processing steps include corrections for spatial resolution and random noise effects. Images are corrected for systematic noise errors and beam hardening. From these data the attenuation coefficient is calculated. The post-processing steps include alignment of the collected images, determining the center of mass, and, finally, using the filtered back-projection routine from the Donner Algorithms Library to obtain the final images. Since its initial development, the tomography system has been used very successfully to find low levels of hydrogen in a metal matrix. Further uses of the system have been to verify the exact placement, in three dimensions, of "O-rings" in large metal valve bodies, and to map the location and extent of veins in porous and high-density rocks of various different kinds. These examples show that neutron tomography is becoming a needed inspection technique for the 21st century.

Journal Article↗

A transcriptomics resource for wheat functional genomics.

Grain development, germination and plant development under abiotic stresses are areas of biology that are of considerable interest to the cereal community. Within the Investigating Gene Function programme we have produced the resources required to investigate alterations in the transcriptome of hexaploid wheat during these developmental processes. We have single pass sequenced the cDNAs of between 700 and 1300 randomly picked clones from each of 35 cDNA libraries representing highly specific stages of grain and plant development. Annotated sequencing results have been stored in a publicly accessible, online database at http://www.cerealsdb.uk.net. Each of the tissue stages used has also been photographed in detail, resulting in a collection of high-quality micrograph images detailing wheat grain development. These images have been collated and annotated in order to produce a web site focused on wheat development (http://www.wheatbp.net/). We have also produced high-density microarrays of a publicly available wheat unigene set based on the 35 cDNA libraries and have completed a number of microarray experiments which validate their quality.

Journal Article↗

"In-house likeness": comparison of large compound collections using artificial neural networks.

Binary classification models able to discriminate between data sets of compounds are useful tools in a range of applications from compound acquisition to library design. In this paper we investigate the ability of artificial neural networks to discriminate between compound collections from various sources aiming at developing an "in-house likeness" scoring scheme (i.e. in-house vs external compounds) for compound acquisition. Our analysis shows atom-type based Ghose-Crippen fingerprints in combination with artificial neural networks to be an efficient way to construct such filters. A simple measure of the chemical overlap between different compound collections can be derived using the output scores from the neural net models.

Combinatorial Chemistry Techniques↗

Standards for academic visual science libraries. Association of Visual Science Librarians.

These standards are a revised and updated version of the Guidelines and Standards for Visual Science Libraries Serving Optometric Institutions, a paper first issued by the Association of Visual Science Librarians (AVSL) in 1976. Their purpose is to provide minimum standards as an aid to accreditation bodies and to institutions initiating library service. In this revision, the Standards and Guidelines have been separated physically so that current information can be updated more frequently and easily. The Standards are a qualitative statement about the minimum levels of staff, collections, and services that should be expected from visual science libraries; the Guidelines contain suggested lists of journals and other quantitative data subject to frequent change. The Guidelines are available separately from the AVSL.

Architecture↗

A wing expressed sequence tag resource for Bicyclus anynana butterflies, an evo-devo model.

BACKGROUND: Butterfly wing color patterns are a key model for integrating evolutionary developmental biology and the study of adaptive morphological evolution. Yet, despite the biological, economical and educational value of butterflies they are still relatively under-represented in terms of available genomic resources. Here, we describe an Expression Sequence Tag (EST) project for Bicyclus anynana that has identified the largest available collection to date of expressed genes for any butterfly. RESULTS: By targeting cDNAs from developing wings at the stages when pattern is specified, we biased gene discovery towards genes potentially involved in pattern formation. Assembly of 9,903 ESTs from a subtracted library allowed us to identify 4,251 genes of which 2,461 were annotated based on BLAST analyses against relevant gene collections. Gene prediction software identified 2,202 peptides, of which 215 longer than 100 amino acids had no homology to any known proteins and, thus, potentially represent novel or highly diverged butterfly genes. We combined gene and Single Nucleotide Polymorphism (SNP) identification by constructing cDNA libraries from pools of outbred individuals, and by sequencing clones from the 3' end to maximize alignment depth. Alignments of multi-member contigs allowed us to identify over 14,000 putative SNPs, with 316 genes having at least one high confidence double-hit SNP. We furthermore identified 320 microsatellites in transcribed genes that can potentially be used as genetic markers. CONCLUSION: Our project was designed to combine gene and sequence polymorphism discovery and has generated the largest gene collection available for any butterfly and many potential markers in expressed genes. These resources will be invaluable for exploring the potential of B. anynana in particular, and butterflies in general, as models in ecological, evolutionary, and developmental genetics.

Animals↗

Getting more from IR-microscopy of resin-bound libraries.

A linear pixel-array detector was employed to create spatially resolved multi-layered IR-images of a large collection of polymer beads supporting carbonyl and nitrile monomers. The feasibility of creating multi-layered IR-images with nitrile IR-band separation of 4 cm(-1) was demonstrated, an important issue when considering that many monomers used to develop combinatorial libraries are structurally analogous and therefore occupy very similar positions in the IR-spectrum. Strategies for obtaining high quality spectral data from both imaging and mapping IR-microscopes without compromising on sample area, analysis time, or spatial resolution are also described.

Combinatorial Chemistry Techniques↗

[Acquisition of a large collection of medical theses defended in Paris from 1798 to 1860].

The Library of the Institute and Museum of the History of Science of Florence has recently enriched its special Collections with the acquisition of a set of medical theses, theses presented and defended in Paris between 1798 and 1860. This extraordinary collection, some 10,000 items, documents the development of the medical sciences in nineteenth century France and Europe.

Academic Dissertations as Topic↗

Sourcing faecal pollution from onsite wastewater treatment systems in surface waters using antibiotic resistance analysis.

AIMS: To identify the sources of faecal contamination in investigated surface waters and to determine the significance of onsite wastewater treatment systems (OWTS) as a major contributor to faecal contamination. METHODS AND RESULTS: Antibiotic resistance patterns (ARP) were established for a library of 717 known Escherichia coli source isolates obtained from human, domesticated animals, livestock and wild sources. Eight commonly used antibiotics, including amoxicillin, cephalothin, erythromycin, gentamicin, ofloxacin, chlortetracycline, tetracycline and moxalactam, at four different concentrations were used to obtain ARPs for E. coli isolates. Discriminant analysis (DA) was used to differentiate between the ARP of sources isolates. The developed ARP library was found to be adequate for discriminating human from nonhuman isolates, and was used to classify 256 enumerated E. coli isolates collected from monitored surface water locations. CONCLUSIONS: The resulting ARP DA indicated that a majority of the faecal contamination in more rural areas was nonhuman; however, the percentage of human isolates increased significantly in urbanized areas using OWTS for wastewater treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study signifies the feasibility of using ARP for source tracking faecal contamination in surface waters, and linking faecal contamination to OWTS. The information will enable regulatory authorities to implement appropriate management practices to reduce the contamination of water resources caused by high densities and failing OWTS.

Amoxicillin↗

Dynamic generation of surgery specific simulators -- a feasibility study.

Most of the current surgical simulators rely on preset anatomical virtual environments (VE). The functionality of a simulator is typically fixed to anatomy-based specific tasks. This rigid design principle makes it difficult to reuse an existing simulator for different surgeries. It also makes it difficult to simulate procedures for specific patients, since their anatomical features or anomalies cannot be easily replaced in the VE. In this paper, we demonstrate the reusability of a modular skill-based simulator, LapSkills, which allows dynamic generation of surgery-specific simulations. Task and instrument modules are easily reused from LapSkills and the three-dimensional VE can be replaced with other anatomical models. We build a nephrectomy simulation by reusing the simulated vessels and the clipping and cutting task modules from LapSkills. The VE of the kidney is generated with our anatomical model generation tools and then inserted into the simulation (while preserving the established tasks and evaluation metrics). An important benefit for the created surgery and patient-specific simulations is that reused components remain validated. We plan to use this faster development process to generate a simulation library containing a wide variety of laparoscopic surgical simulations. Incorporating the simulations into surgical training programs will help collect data for validating them.

Computer Simulation↗

Preparing librarians to meet the challenges of today's health care environment.

OBJECTIVE: Refine the understanding of the desirable skills for health sciences librarians as a basis for developing a training program model that reflects the fundamental changes in health care delivery and information technology. DESIGN: A four-step needs assessment process: focus groups developed lists of desirable skills; the research team organized candidate skills into a taxonomy; a survey of a random sample of librarians and library users assessed perception of importance of individual skills; and the research team framed, as a unifying hypothesis, a training model. SURVEY METHODS: The survey was distributed to random samples of 150 librarians, stratified by type of library, and 150 library users, stratified by type of use. A non-randomized sample was obtained by mounting the survey on a World Wide Web server. The survey instrument included 96 distinct skills organized into 13 categories. Respondents rated the importance of each skill on a Likert scale and provided a separate ranking by identifying the ten most important skills for the profession. RESULTS: Among the participants, 51% of librarians and 36% of library users responded to the survey. All categories of skills were rated above the midpoint of priority on the Likert scale. All groups rated personality characteristics and skills as most important, with an understanding of the health sciences, education, and research being rated comparably to technical skills. CONCLUSIONS: Health sciences librarians need a new educational model that provides them with broad-based tools to discover new roles and new resources for acquiring individual skills as the need arises. A unifying training model would involve trainees in developing their learning plan in a way that promotes proactive inquiry and self-directed learning, and it would rotate the trainees through projects to provide skills and an understanding of end-user work processes.

Curriculum↗