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At least 1,333 records · Page 74Linked to original sources
PubMed1994

Design and application of a C++ macromolecular class library.

PDBlib is an extensible object oriented class library written in C++ for representing the 3-dimensional structure of biological macromolecules. PDBlib forms the kernel of a larger software framework being developed for assiting in knowledge discovery from macromolecular structure data. The software design strategy used by PDBlib, how the library may be used and several prototype applications that use the library are summarized. PDBlib represents the structural features of proteins, DNA, RNA, and complexes thereof, at a level of detail on a par with that which can be parsed from a Protein Data Bank (PDB) entry. However, the memory resident representation of the macromolecule is independent of the PDB entry and can be obtained from other back-end data sources, for example, existing relational databases and our own object oriented database (OOPDB) built on top of the commercial object oriented database, ObjectStore. At the front-end are several prototype applications that use the library: Macromolecular Query Language (MMQL) is based on a separate class library (MMQLlib) for building complex queries pertaining to macromolecular structure; PDBtool is an interactive structure verification tool; and PDBview, is a structure rendering tool used either as a standalone tool or as part of another application. Each of these software components are described. All software is available via anonymous ftp from cuhhca.hhmi.columbia.edu.

Animals↗
PubMedDate not supplied

Highly specific, cross-reactive sequences recognized by an anti-HBsAg antibody identified from a positional scanning synthetic combinatorial library.

The binding specificity of a monoclonal antibody (MAb 12) known to recognize the surface antigen of hepatitis B virus (HBsAg) was studied using a positional scanning synthetic combinatorial library. A hexapeptide library totaling more than 30 x 10(6) sequences, made up of 120 mixtures having a single position defined with individual amino acids and the remaining five positions composed of mixtures of amino acids, was screened by competitive enzyme-linked immunosorbent assay (ELISA). This led to the identification of Ac-STTSMM-NH2 (IC50 = 170 nM), which specifically inhibited the interaction between HBsAg and MAb 12. One of the most active individual mixtures from the library was Ac-XXXPXX-NH2; however, none of the individual peptides synthesized containing proline at the fourth position showed significant activity (IC50 > 100,000 nM). To identify the individual peptide(s) responsible for the activity of Ac-XXXPXX-NH2, a bidirectional iterative synthesis and selection process was carried out. A completely different but active peptide sequence was identified (Ac-SVGPPH-NH2, IC50 = 165 nM). The two different hexapeptide sequences were prepared as linear homo- and heterodimer peptides in an attempt to improve the antigenicity. Of the four different sequences prepared, one heterodimer (Ac-STTSMMGGGSVGPPH-NH2) was found by ELISA to have a 10-fold improvement in activity over the two individual hexapeptides, and was equal to the inhibitory activity of the protein antigen. The equilibrium affinity constant of the MAb 12 toward this heterodimer sequence was 50-fold higher than the protein antigen when measured in a biosensor system. Since motifs from these two hexapeptides, namely, -STTS- and -GP-, were located in the primary sequence of the protein (residues 114-120, subtype ad), overlapping hexapeptides of this region were synthesized and assayed. The most active hexapeptide, namely, Ac-TTSTGP-NH2 (IC50 = 2.3 microM), was 10-fold less active than either hexapeptide found from the library. Extending the specific motif sequences to eleven residues resulted in an analog (Ac-STTSTGPSRTC-NH2) having an equilibrium affinity constant similar to the heterodimer. The combined use of positional scanning libraries and the iterative synthesis and selection process in this study illustrates the power of these methods for the identification of novel peptides that inhibit anti-protein antibodies. These methods can be directly applied to the development of improved immunodiagnostics.

Amino Acid Sequence↗
PubMed1997

Peptide and nonpeptide lead discovery using robotically synthesized soluble libraries.

The method of combinatorial synthesis of peptide and nonpeptide libraries on solid phase is analyzed and the automation of the mix and divide key step described. A set of amino acids leading to a high molecular diversity is proposed as well as a number of scaffolds for the preparation of variable polyamide libraries. Adequacy of the resin bead quantities to library size and to the ratio of the synthesized peptide types is discussed. Examples of the use of capillary electrophoresis and of spectroscopic methods (MS, MS/MS, and NMR) for the analysis of the library content are given. The iterative deconvolution SURF (synthetic unrandomization of randomized fragments) is compared with positional scanning and the success of coupling of mixtures evaluated. It is concluded that extension of the original mix and divide method and the SURF deconvolution (as proposed by Houghten et al. Nature (London), 354: 84-86 1991) to nonpeptide libraries affords new leads that can be optimized towards useful therapeutics.

Amino Acids↗
PubMed2000

Combining phage display and screening of cDNA expression libraries: a new approach for identifying the target antigen of an scFv preselected by phage display.

A potential method for identifying new tumor-specific antibody structures as well as tumor-associated antigens is by selecting scFv phage libraries on tumor cells. This phage display technique involves multiple rounds of phage binding to target cells, washing to remove non-specific phage and elution to retrieve specific binding phage. Although the binding properties of an isolated tumor-specific scFv can be evaluated by ELISA, FACS and immunohistochemistry, it still remains a challenge to define the corresponding antigen. Here, we provide evidence that the target antigen of a given scFv displayed on phages can be detected in an immobilized lambda phage cDNA expression library containing thousands of irrelevant clones. The library contained CD30-negative breast-cancer specific cDNA as well as human CD30 receptor cDNA. The interaction of anti-CD30 scFv phages and their target antigen after blotting onto nitrocellulose filters was documented under defined conditions. Screening of different ratios between CD30 receptor and breast cancer specific clones (1:1 and 1:200) revealed that the CD30 antigen could be detected by anti-CD30 scFv phages using at least 5x10(12) plaque forming units of filamentous phages per blot. These investigations demonstrate that it is possible to detect the target antigen of a preselected scFv displayed on filamentous phages in lambda phage cDNA expression libraries.

Antibodies, Monoclonal↗
PubMed1989

Use of the polymerase chain reaction for the differential cross screening of libraries cloned into phage-lambda-based vectors.

We describe a simple and rapid method that can be used to identify sequences present in any two DNA libraries (either genomic or cDNA), provided only that the libraries are in different vectors with different cloning sites. This procedure makes use of the polymerase chain reaction (PCR) to amplify the inserts of one library. The product of the PCR reaction is then used to screen a second library to identify sequences which are common to both. We illustrate the use of this method for the systematic isolation of human X-chromosome-linked genomic clones that harbor sequences expressed in human chorioretinal tissue.

Animals↗
PubMed1994

Survey of the attitude of medical and nursing libraries to information literature for patients with gastrointestinal diseases.

Senior staff in libraries at 281 medical schools, postgraduate institutions, schools of nursing and postgraduate medical centres were approached. They were asked to complete a detailed questionnaire on the availability of patient-orientated information and the nature of access by other health care professionals, patients and the public to their facilities. A total of 252 replies was received (response rate 90%). Medical and nursing schools tended to discriminate against each other's staff. Discrimination against patients was more widespread with less than 30% of libraries open to them. This was reflected in the lack of patient information such as booklets and videos. Less than 10% of libraries provided such information. Libraries in schools of nursing were significantly better in the provision of information about self-help groups. Overall there were limited interest in the provision of any service to patients or the general public.

Attitude↗
PubMed2003

Synthetic gene libraries: in search of the optimal diversity.

Directed evolution has proven to be an effective method for evolving proteins with desired properties. A key step is the creation of suitably diverse gene libraries. Two new methods for creating such libraries make sole use of synthesized oligonucleotides and allow researchers to tailor the diversity of a library with greater precision and create libraries with greater diversity than was previously possible. Such increased diversity appears to accelerate directed evolution.

Cloning, Molecular↗
PubMed1998

The National Patient Library. Evidence-based information for consumers.

A National Patient Library, a public/private partnership, is proposed to identify and vet information for consumers. Library staff will help tailor general information to consumers' specific needs. The library includes an electronic network. The principal focus of the library's information is controversial and experimental procedures, pharmaceuticals, and medical devices.

Antineoplastic Agents↗
PubMed2002

Determining the impact of health library services on patient care: a review of the literature.

The impact of health library information has been studied in a number of settings and populations. This review examines both the methods employed and the outcomes reported in a series of impact studies conducted in four countries since the late 1980's. It demonstrates that health library information can affect patient care outcomes in various ways and has high cognitive and clinical value in diagnosing and treating patients. But there remains no agreed technique or methodology for determining the level of this impact. In many cases evaluation of the health library's impact will be located within a central process of evaluation of the greater organization to which the library belongs. Consequently, local ad hoc evaluation is rarely reported outside an organization. The author considers the question of whether it is worthwhile doing an impact study and what form it might take. The author concludes by identifying seminal papers on the topic.

Australia↗
PubMed1993

Costing medical libraries: the feasibility of functional cost analysis.

As a result of organizational changes in the National Health Service (NHS) there is a need for a coherent costing model for NHS libraries, particularly for the smaller libraries based in postgraduate medical centres. One possible model is functional cost analysis, whereby all costs are assigned to library functions representing services to users, such as loans from stock, interlibrary loans, enquiry services, etc. Using data from a 1991 survey of postgraduate centre-based libraries in the North West Thames (NWT) Region of the NHS, the feasibility and appropriateness of functional cost analysis is examined.

Budgets↗
PubMed2002

Integrating medical communication skills with library skills curricula among first year medical students at the University of the West Indies, St. Augustine.

A two-year study designed to integrate the medical communication skills and library skills curricula at the University of the West Indies, St. Augustine is reported. Given that an integrated approach to curriculum development offers benefits to learners and staff. The objective of this study was to explore the feasibility of implementing this approach among Year 1 pre-clinical students in 1997 and 1998. Student performance on an essay question that integrated the application of students' knowledge of written communication and library skills in a final examination performance was assessed. Pre- and post-test results of students' library skills were compared within each year. anova analysis indicated that there was a significant increase in mean scores from pre-test to post-test which suggests that students performed better on a test of their knowledge and application of library skills after instruction, but the unavailability of a control group made this finding inconclusive. The findings are discussed in relation to practical and intellectual issues in curriculum integration. It is concluded that this type of curriculum integration is feasible, creates linkages in the curriculum and does not increase demand on student time.

Cohort Studies↗
PubMed2003

Using SERVQUAL in health libraries across Somerset, Devon and Cornwall.

This study provides the results of a survey conducted in the autumn of 2001 by ten NHS library services across Somerset, Devon and Cornwall. The aim of the project was to measure the service quality of each individual library and to provide an overall picture of the quality of library services within the south-west peninsula. The survey was based on SERVQUAL, a diagnostic tool developed in the 1980s, which measures service quality in terms of customer expectations and perceptions of service. The survey results have provided the librarians with a wealth of information about service quality. The service as a whole is perceived to be not only meeting but also exceeding expectations in terms of reliability, responsiveness, empathy and assurance. For the first time, the ten health library services can measure their own service quality as well as benchmark themselves against others.

Benchmarking↗
PubMed2026

Barcoded mutant library enables high-throughput functional genomics in a filamentous fungus.

Advances in sequencing technology enabling rapid and inexpensive whole-genome sequencing highlight how few genes are functionally characterized. This problem is particularly acute in filamentous fungi, where even in the best studied organisms upward of half of genes are poorly characterized or unannotated. High-throughput tools to identify gene function exist for single-celled organisms, like yeast and bacteria. However, filamentous fungi present challenges to high-throughput gene characterization, including low transformation efficiency and multinucleate cells. Filamentous fungi are critical components of nutrient cycling in ecosystems, form symbioses with plants that improve nutrient uptake, and are devastating human, plant, and animal pathogens causing millions of deaths and substantial crop loss each year. Thus, it is critical to overcome challenges to rapid gene characterization in filamentous fungi. We generated a library of hundreds of millions of uniquely barcoded plasmids containing a broad host-range drug resistance marker for ectopic insertion into filamentous fungal genomes by Agrobacterium tumefaciens. We then optimized A. tumefaciens mediated transformation of the biocontrol agent Trichoderma atroviride and made an insertional mutagenesis library containing 83,311 barcoded insertions, disrupting 5,331 of 11,863 predicted genes. This library enables high-throughput screens to rapidly connect genotype to phenotype. Quantifying relative barcode abundance in the pooled library before and after exposure to experimental conditions identified candidate genes and recovered known pathway components in amino acid biosynthetic, fructose utilization, and xylose utilization pathways. This resource establishes a scalable platform for high-throughput functional genomics in filamentous fungi, enabling investigations of fungal biology to improve medical outcomes, biotechnology, and sustainable agriculture.

Genomics↗
PubMed2006

Interrogating genomes with combinatorial artificial transcription factor libraries: asking zinc finger questions.

Artificial transcription factors (ATFs) are proteins designed to specifically bind and regulate genes. Because of their DNA-binding selectivity and modular organization, arrays of zinc finger (ZF) domains have traditionally been used to build the ATF's DNA-binding domains. ATFs have been designed and constructed to regulate a variety of therapeutic targets. Recently, novel combinatorial technologies have been developed to induce expression of any gene of interest or to modify cellular phenotypes. Large repertoires of ATFs have been generated by recombination of all available sequence-specific ZF lexicons. These libraries comprise millions of ATFs with unique DNA-binding specificities. The ATFs are produced by combinatorial assembly of three- and six-ZF building blocks and are linked to activator or repressor domains. Upon delivery into a cell population, any gene in the human genome can potentially be regulated. ATF library members generate genome-wide, experimental perturbations of gene expression, resulting in a phenotypically diverse population, or cellular library. A variety of phenotypic screenings can be applied to select for cells exhibiting a phenotype of interest. The ATFs are then used as genetic probes to identify the targeted genes responsible for the phenotypic switch. In this review we will summarize several applications of ATF library screenings in gene discovery, biotechnology, and disease therapeutics.

Chromosome Mapping↗
PubMed2005

Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing: identification of novel zinc finger proteins.

We have successfully linked protein library screening directly with the identification of active proteins, without the need for individual purification, display technologies or physical linkage between the protein and its encoding sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping gene libraries that encode zinc finger proteins, randomized variously at the three principal DNA-contacting residues. Expression and screening of the libraries against five possible target DNA sequences generated data points covering a potential 40,000 individual interactions. Comparative analysis of the resulting data enabled direct identification of active proteins. Accuracy of this library analysis methodology was confirmed by both in vitro and in vivo analyses of identified proteins to yield novel zinc finger proteins that bind to their target sequences with high affinity, as indicated by low nanomolar apparent dissociation constants.

Binding Sites↗
PubMed2005

The value and impact of information provided through library services for patient care: a systematic review.

OBJECTIVE: An updated systematic review was carried out of research studies looking at the value and impact of library services on health outcomes for patients and time saved by health professionals. METHODS: A comprehensive systematic search was undertaken of the published literature to September 2003 in ERIC, LISA, MEDLINE, PREMEDLINE, EMBASE, the Cochrane Controlled Trials Register and Google. Some handsearching was carried out, reference lists were scanned and experts in the field were contacted. Twenty-eight research studies of professionally led libraries for health-care staff, including clinical librarian projects, met the inclusion criterion of at least one health or 'time saved' outcome. Papers were critically appraised using internationally accepted criteria. Data were extracted and results were summarised using a narrative format as the studies were heterogeneous and precluded a statistical analysis. RESULTS: There is evidence of impact from both traditional and clinical librarian services. The higher quality studies of traditional services measured impacts of 37-97% on general patient care, 10-31% on diagnosis, 20-51% on choice of tests, 27-45% on choice of therapy and 10-19% on reduced length of stay. Four studies of clinical librarian projects suggested that professionals saved time as a result of clinical librarian input, and two of these studies showed evidence of cost-effectiveness. However, the clinical librarian studies were generally smaller, with poorer quality standards. CONCLUSIONS: Research studies suggest that professionally led library services have an impact on health outcomes for patients and may lead to time savings for health-care professionals. The available studies vary greatly in quality but the better quality studies also suggest positive impacts. Good practice can be gathered from these studies to guide the development of a pragmatic survey for library services that includes the direct effects for patients among the outcome measures.

Biomedical Research↗
PubMed2026

Establishment of a CRISPR-Cas9 Library for Indica Rice and Identification of OsOPR5 (LOC_Os06g11210) as a Regulator of Root Architecture.

Functional characterization of a large number of rice genes remains a major challenge despite the availability of genome sequences and large-scale transcriptomic datasets. CRISPR-Cas9 library is a powerful approach for high-throughput targeted mutagenesis; however, its application in indica rice cultivars remains limited due to low transformation and regeneration efficiencies. In this study, we developed a CRISPR-Cas9 library targeting 12,000 rice genes and evaluated its utility for functional genomics in the indica cultivar MTU-1010. Sanger sequencing and NGS analysis of the plasmid library revealed high sgRNA coverage and more than 80% accuracy. Transformation of the developed library into the indica cultivar MTU-1010 resulted in a high target editing efficiency, with 90% of analyzed transgenic plants carrying mutations at the intended target site. Functional analysis of one homozygous mutant identified a previously uncharacterized role for OsOPR5 (LOC_Os06g11210), a member of the 12-oxophytodienoate reductase family in root architecture. The opr5 mutants exhibited significant reductions in lateral root number, seminal and crown root number, and root length, demonstrating that OsOPR5 positively regulates root system architecture in rice. Notably, endogenous jasmonic acid (JA) and JA-isoleucine levels were not significantly altered in the mutant, suggesting potential functional specialization or redundancy among rice OPR family members for JA accumulation. The root system architecture is a key determinant of water and nutrient acquisition; our results suggest that OsOPR5 may play an important role in adaptation under adverse environmental conditions. Collectively, this study establishes an efficient genome-editing platform for indica rice and identifies OsOPR5 as a novel regulator of root development.

Oryza↗
PubMed2002

Seniors connect: a partnership for training between health care and public libraries.

Kaleida Health Libraries, in partnership with the Buffalo and Erie County Public Library, presented "Seniors Connect: A Health Information Project." The program was funded by the Community Foundation for Greater Buffalo and the Kaleida Health Foundation. The purpose of the project was to teach African-American and Hispanic senior citizens or their caregivers residing in the city of Buffalo how to search the Internet to find quality, accurate, understandable health information. Attendees were taught to distinguish quality information from inaccurate, misleading, and fraudulent material. A total of fourteen training sessions were offered. The Seniors Connect program was initiated with health fair at each branch library, conducted by Kaleida Health staff, to provide an opportunity for participants to learn about health care services available in their community; observe demonstrations of health information searches on the Internet; learn about new treatment modalities for diseases such as diabetes, high cholesterol, thyroid abnormalities, and hypertension; and interact with area health care providers and library staff. The sessions were highly rated by attendees and many participants expressed their gratitude for a program geared specifically toward seniors.

Black or African American↗