Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Libraries”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1976

NLM Medical Library Resource Improvement Grant Program: an evaluation.

The Extramural Programs, NLM, undertook a staff study to evaluate the Medical Library Resource Improvement Grant Program in order to determine impact on hospital library development and to assess factors significant to regional medical library (RML) network development. Initiated in fiscal year 1971, the improvement grant program provides one-year, one-time grant awards of a maximum of $3,000 to assist in establishing a basic collection of books, journals, and other health science information resources for community hospitals and comparable health facilities. Applicants who received grant awards were compared to applicants who did not receive awards and to nonapplicants, using nine dependent variables, four independent variables, and responses to an RML questionnaire. Results show that the applicants who received awards outperformed the other groups, and that the improvement grant program has been successful in stimulating library development. As a result of this study, the improvement grant program will be modified to support consortium arrangements as well as individual institutions, and to extend the period of grant support to two years. Future grant support will be a maximum of $4,000 in the first year, and up to $3,000 with a provision of $1,000 in matching funds from the grantee in the second year.

Economics, Hospital↗
PubMed1998

Structure-property correlations in a combinatorial library of degradable biomaterials.

A combinatorial library of degradable polyarylates was prepared. These polymers are A-B-type copolymers consisting of an alternating sequence of a diphenol and a diacid. The library was prepared by copolymerizing, in all possible combinations, 14 different tyrosine-derived diphenols and eight different aliphatic diacids, resulting in 8 x 14 = 112 distinct polymers. This approach (a) increases the number of available polymeric candidate materials for medical applications, and (b) facilitates the identification of correlations between polymer structure and glass transition temperature, air-water contact angle, mechanical properties, and fibroblast proliferation. The pendent chain and backbone structures were systematically varied by (a) simple homologative variations in the number of methylene groups, (b) substitution of oxygen for methylene groups, and (c) introduction of branched and aromatic structures. The polymers contained within the library exhibited incremental variations in Tg (from 2 degrees C to 91 degrees C) and air-water contact angle (from 64 degrees to 101 degrees ). Fibroblast proliferation (in vitro, serum-containing media) ranged from approximating that measured on tissue culture polystyrene to complete absence of proliferation. Generally, decreased proliferation correlated linearly with increased surface hydrophobicity, except in those polymers derived from oxygen-containing diacids in their backbone which were uniformly good growth substrates even if their surfaces were very hydrophobic. In a selected subgroup of polymers, tensile strength of thin solvent cast films ranged from about 6 to 45 MPa, while Young's modulus (stiffness) ranged from about 0.3 to 1.7 GPa. Combinatorial biomaterial libraries such as these tyrosine-derived polyarylates permit the systematic study of material-dependent biological responses and provide the medical device designer with the option to choose a suitable material from a library of related polymers that encompasses a broad range of properties.

Animals↗
PubMed2004

Dynamic combinatorial carbohydrate libraries: probing the binding site of the concanavalin A lectin.

Dynamic combinatorial chemistry (DCC) has emerged as an efficient approach to receptor/ligand identification based on the generation of combinatorial libraries by reversible interconversion of the library constituents. In this study, the implementation of such libraries on carbohydrate-lectin interactions was examined with the plant lectin Concanavalin A as a target species. Dynamic carbohydrate libraries were generated from a pool of carbohydrate aldehydes and hydrazide linker/scaffold components through reversible acylhydrazone exchange, resulting in libraries containing up to 474 constituents. Dynamic deconvolution allowed the efficient identification of the structural features required for binding to Concanavalin A and the selection of a strong binder, a tritopic mannoside, showing an IC(50)-value of 22 microM.

Binding Sites↗
PubMed2004

Correlation between host-guest binding and host amplification in simulated dynamic combinatorial libraries.

We present a versatile computer model of diverse dynamic combinatorial libraries, and examine how molecular recognition between library members and a template can be used to amplify the best binders. The correlation between host-guest binding and amplification was examined for a set of 50 libraries with >300 components each over a wide range of template and building block concentrations. Depending on these concentrations correlations vary from poor (when using a large excess of template) to good (for very dilute libraries and/or substoichiometric template concentrations), highlighting the need to choose the experimental conditions for dynamic combinatorial libraries thoughtfully.

Journal Article↗
PubMed2005

Efficient solid-phase synthesis of peptide-based phosphine ligands: towards combinatorial libraries of selective transition metal catalysts.

A new methodology for the solid-phase synthesis of peptide-based phosphine ligands has been developed. Solid supported peptide scaffolds possessing either primary or secondary amines were synthesised using commercially available Fmoc-protected amino acids and readily available Fmoc-protected amino aldehydes for reductive alkylation, in standard solid-phase peptide synthesis (SPPS). Phosphine moieties were introduced by phosphinomethylation of the free amines as the final solid-phase synthetic step, immediately prior to complexation with palladium(II), thus avoiding tedious protection/deprotection of the phosphine moieties during the synthesis of the ligands. The extensive use of commercial building blocks and standard SPPS makes this methodology well suited for the generation of solid-phase combinatorial libraries of novel ligands. Furthermore, it is possible to generate several different phosphine ligand libraries for every peptide scaffold library synthesised, by functionalising the scaffold libraries with different phosphine moieties. The synthesised ligands were characterised on solid support by conventional (31)P NMR spectroscopy and, cleaved from the support, as their phosphine oxides by HPLC, (1)H NMR, (31)P NMR and high resolution ESMS. Palladium(II) allyl complexes were generated from the resin bound ligands and to demonstrate their catalytic properties, palladium catalysed asymmetric allylic substitution reactions were performed. Good yields and moderate enantioselectivity was obtained for the selected combination of catalysts and substrate, but most importantly the concept of this new methodology was proven. Screening of ligand libraries should afford more selective catalysts.

Catalysis↗
PubMed2005

PNA encoding (PNA=peptide nucleic acid): from solution-based libraries to organized microarrays.

Microarray-based technologies have attracted attention in chemical biology by virtue of their miniaturized format, which is well suited to probe ligand-protein interactions or investigate enzymatic activity in complex biological mixtures. A number of research groups have reported the preparation of surfaces on microarrays with specific functional groups to chemoselectively attach small molecules from libraries. We have developed an alternative method whereby libraries are encoded with peptide nucleic acid (PNA), such that libraries which exist as mixtures in solution self-assemble into an organized microarray through hybridization to produce readily available DNA arrays. This allows libraries synthesized by split and mix methods to be decoded in a single step. An asset of this method compared to direct spotting is that libraries can be used in solution for bioassays prior to self-assembly into the microarray format.

Combinatorial Chemistry Techniques↗
PubMed1992

Identification of novel peptide antagonists for GPIIb/IIIa from a conformationally constrained phage peptide library.

Methods have recently been developed to present vast libraries of random peptides on the surface of filamentous phage. To introduce a degree of conformational constraint into random peptides, a library of hexapeptides flanked by cysteine residues (capable of forming cyclic disulfides) was constructed. This library was screened using the platelet glycoprotein, IIb/IIIa, which mediates the aggregation of platelets through binding of fibrinogen. A variety of peptides containing the sequence Arg-Gly-Asp or Lys-Gly-Asp were discovered and synthesized. The cyclic, disulfide-bonded forms of the peptides bound IIb/IIIa with dissociation constants in the nanomolar range, while reduced forms or an analogue in which Ser replaced the Cys residues bound considerably less tightly. These results demonstrate the feasibility for introducing conformational constraints into random peptide libraries and also demonstrates the potential for using phage peptide libraries to discover pharmacologically active lead compounds.

Amino Acid Sequence↗
PubMed2004

Comparison of product ion spectra obtained by liquid chromatography/triple-quadrupole mass spectrometry for library search.

Reproducibility of product ion spectra acquired using a liquid chromatography/triple-quadrupole mass spectrometry (LC/MS/MS) instrument over a 4-year period, and with three other LC/MS/MS instruments, one from the same manufacturer and two from a different manufacturer, was examined. The MS/MS spectra of 30 drug substances were generated in positive electrospray ionization mode at low, medium, and high collision energies (20, 35, and 50 eV). Purity and Fit score percentages against a 400-compound LC/MS/MS spectral library were calculated using an algorithm in which fragment intensity ratios and weighting factors were included. The long-term reproducibility study was conducted using a brand A instrument; after 4 years the reproducibility of the product ion spectra was still 94%, expressed as average Purity score. The inter-laboratory study involved two parts. Firstly, two LC/MS/MS spectral libraries, created independently in separate laboratories using brand A instruments, were compared with each other. The average Fit and Purity scores of spectra from one library against the other were better than 93 and 91%, respectively, when the same collision energies were used. Secondly, for the comparison of product ion spectra between brand A and brand B instruments, fragmentation conditions were first standardized for amitriptyline as the standard analyte. The average Fit scores of brand B spectra against the brand A spectral library varied between 79 and 85% at all three collision energies. These results indicate that, after standardizing the instrumental conditions, LC/MS/MS spectral libraries of drug substances are suitable for inter-laboratory use.

Journal Article↗
PubMed2001

Screening combinatorial libraries for optimal enzyme substrates by mass spectrometry.

A method has been developed for the rapid identification of optimal enzyme substrates from combinatorial libraries. This methodology was validated by screening a 361-member N-terminally formylated tripeptide library, f-XXR (X = 19 different amino acids), for optimal substrates of Escherichia coli peptide deformylase (PDF). The library was synthesized on a solid phase via the split-pool synthesis method. The N-terminal formyl group was added by treating the resin with a 1:1 (mol/mol) mixture of HCO(2)H and DCO(2)D in the presence of dicyclohexylcarbodiimide. In a mass spectrum, each member of the library produced a doublet peak (separated by 1.0063 Da). Limited treatment of this library with E. coli PDF resulted in the deformylation of those peptides that are the most efficient substrates of the enzyme. The deformylated products, due to loss of the mass-degenerate formyl group, each generated a singlet peak in the mass spectrum. Thus, the PDF product peaks were readily identified and sequenced via tandem mass spectrometry. The results showed that PDF strongly prefers a norleucine and, to a lesser extent, a phenylalanine as the N-terminal residue, whereas it has little selectivity at the penultimate position. This result is in excellent agreement with the literature data and therefore demonstrates the methodology as an effective approach to the identification of optimal enzyme substrates. This method should be generally applicable to other enzymes as well as synthetic catalysts.

Amidohydrolases↗
PubMed1996

Construction and Characterization of a Magnaporthe grisea Bacterial Artificial Chromosome Library

Diaz-Perez, S. V., Crouch, V. W., and Orbach, M. J. 1996. Construction and characterization of a Magnaporthe grisea bacterial artificial chromosome library. Fungal Genet. Biol. 20, 280-288. A bacterial artificial chromosome (BAC) library of Magnaporthe grisea containing 4128 clones with an average insert size of 66-kb has been constructed. This library represents seven genome equivalents of M. grisea and has been demonstrated to be representative of the genome by screening for the presence of several single-copy genes and DNA markers. The utility of the library for use in map-based cloning projects was shown by the spanning of a nine-cosmid, 207-kb DNA contig with only 3 BAC clones. In addition, using a lys1-3 auxotroph, we have shown that BAC clones at least 113 kb can be transformed into M. grisea to screen for complementation of mutations. Thus, BACs isolated in chromosome walks can be rapidly screened for the presence of the sought after gene. The ease of construction of BAC libraries and of isolation and manipulation of BAC clones makes the BAC system an ideal one for physical analyses of fungal genomes.

Journal Article↗
PubMed1995

Comprehensive epitope analysis of monoclonal anti-proenkephalin antibodies using phage display libraries and synthetic peptides: revelation of antibody fine specificities caused by somatic mutations in the variable region genes.

Filamentous phage libraries, displaying 6, 12 or 20 amino acid residue peptides at the N terminus of coat protein pIII were used to define and localize the epitopes of 15 monoclonal antibodies raised against human proenkephalin, a neuropeptide precursor. Eight monoclonal antibodies (PE14 to PE19, PE23 and PE25), which inhibit each other's binding to proenkephalin, recognized phage clones selected by PE14, PE15, PE19, PE23 and PE25. With the peptide sequences DLL(X)(X)LL (12mer library) and DLL(X)(X)L (6mer library) shared by most of the phage clones it was possible to define the putative antibody epitope 155DLLKELL161 on human proenkephalin. For five antibodies (PE13, PE20 to PE22 and PE24) belonging to another inhibition group, a common consensus motif G(X)D(X)E(X)(X)V(X)(X)R could be defined with help of a 20mer library. The corresponding minimum epitope sequence has been found to be 175GSDNEEEVSKR185. Antibody PE1, raised in a separate fusion, was able to select phage clones from a 12mer and 20mer library, revealing that the sequence 187GGFMRG192 is probably the antibody epitope. The assumed localization of the epitopes was confirmed by screening a set of overlapping synthetic peptides, covering the region of human proenkephalin thought to contain all antibody binding sites. It was found that antibodies, although recognizing the same epitope, gave different binding patterns with the selected phage clones. By analysing the VH chain sequences of these antibodies it could be shown that a varying number of somatic mutations is likely to be the reason for the observed differences in antibody fine specificity.

Amino Acid Sequence↗
PubMed1996

Structurally homogeneous and heterogeneous synthetic combinatorial libraries.

We have designed and synthesized structurally homogeneous and heterogeneous nonpeptide libraries. Structurally homogeneous libraries are characterized by the presence of one common structural unit, a scaffold, in all library compounds (e.g. cyclopentane, cyclohexane, diketopiperazine, thiazolidine). In structurally heterogeneous libraries different organic reactions (acylation, etherification, reductive amination, nucleophilic displacement) were applied to connect bifunctional building blocks unrelated in structure (aromatic hydroxy acids, aromatic hydroxy aldehydes, amino alcohols, diamines, and amino acids). The focus of this communication is to document the use of bifunctional building blocks for the design and synthesis of structurally heterogeneous libraries of N-(alkoxy acyl)amino acids, N,N'-bis-(alkoxy acyl)diamino acids, N-acylamino ethers, N-(alkoxy acyl)amino alcohols, N-alkylamino ethers, and N-(alkoxy aryl)diamines.

Aldehydes↗
PubMed1996

Bifunctional scaffolds as templates for synthetic combinatorial libraries.

A small-molecule synthetic combinatorial library was designed and synthesized that features potential pharmacophores attached to a variety of small cyclic scaffolds. The synthesis of the library involved randomization of three types of building blocks: 20 amino acids, 10 aromatic hydroxy acids and 21 alcohols, totaling a library complexity of 4200 compounds. Mitsunobu polymer-supported etherification was used in the last randomization. The library compounds were attached to beads via an ester-bond linkage enabling both on-bead as well as in-solution screening. When the library was tested against a model target, streptavidin, specific binders were found. The structures of the most active compounds were determined from the fragmentation pattern in MS/MS experiments.

Alcohols↗
PubMed1986

Genetic counterselective procedure to isolate interspecific cell hybrids containing single human chromosomes: construction of cell hybrids and recombinant DNA libraries specific for human chromosomes 3 and 4.

Counterselection against genes on human chromosome 5 was applied to interspecific human-Chinese hamster cell hybrids which retained this and one additional human chromosome in order to generate cell hybrids retaining single, nonselected human chromosomes. Using this procedure, stable cell hybrids which retain human chromosome 3 exclusively or human chromosome 4 exclusively were isolated. Complete recombinant genomic DNA libraries were prepared from each hybrid using the lambda cloning vector EMBL-4. These libraries represent sources of human DNA fragments derived specifically from chromosomes 3 and 4, respectively. Low-copy or unique human DNA fragments isolated from both libraries were analyzed to confirm their chromosomal origin and to determine the complexity of their hybridization patterns to total human DNA. These single human chromosome libraries represent a means to efficiently saturate chromosomes 3 and 4 with informative, polymorphic genetic markers. DNA fragments from the chromosome 4 library will be particularly useful in identifying additional genetic markers close to the Huntington's disease gene. The same genetic counterselective procedure can be utilized to derive several additional cell hybrids with single human chromosomes.

Animals↗
PubMed1997

Phosphorus-based combinatorial libraries: use of amino acid derivatives as synthons.

Phosphorus has been used as a scaffold to prepare combinatorial libraries of phosphoramidates in which one of the diversity elements resulted from derivatives of amino acids. A small library was prepared for analytical and characterization purposes, followed by a larger library of approximately 8800 compounds. Libraries were assembled on solid supports using the conventional pool-and-divide method, followed by cleavage from the supports at the end of the synthesis. Mass spectrometry was used to confirm that library synthesis had been successful. Individual compounds were also prepared to study the stability of compounds of this type.

Amino Acids↗
PubMed2002

Construction of BAC libraries from two apomictic grasses to study the microcolinearity of their apospory-specific genomic regions.

We have constructed bacterial artificial chromosome (BAC) libraries from two grass species that reproduce by apospory, a form of gametophytic apomixis. The library of an apomictic polyhaploid genotype (line MS228-20, with a 2C genome size of approximately 4,500 Mbp) derived from a cross between the obligate apomict, Pennisetum squamulatum, and pearl millet ( P. glaucum) comprises 118,272 clones with an average insert size of 82 kb. The library of buffelgrass ( Cenchrus ciliaris, apomictic line B-12-9, with a 2C genome size of approximately 3,000 Mbp) contains 68,736 clones with an average insert size of 109 kb. Based on the genome sizes of these two lines and correcting for the number for false-positive and organellar clones, library coverages were found to be 3.7 and 4.8 haploid genome equivalents for MS 228-20 and B12-9, respectively. Both libraries were screened by hybridization with six SCARs (sequence-characterized amplified regions), whose tight linkage in a single apospory-specific genomic region had been previously demonstrated in both species. Analysis of these BAC clones indicated that some of the SCAR markers are actually amplifying duplicated regions linked in coupling in both genomes and that restriction enzyme mapping will be necessary to sort out the duplications.

Journal Article↗
PubMed1998

Creating and curating a pediatric radiology digital library to make the internet a useful reference tool for the radiologist.

BACKGROUND: To practice pediatric radiology optimally, radiologists need convenient access to organized and authoritative pediatric radiology information. The Internet has the potential for offering such convenient access, but the majority of information on it is poorly organized and of questionable authority. OBJECTIVE: The goal of this project was to create and curate a pediatric radiology digital library that will make the Internet a useful reference tool for the radiologist at the point-of-care. MATERIALS AND METHODS: A pediatric radiology digital library containing organized and authoritative pediatric radiology information from the Internet was created and has three components : (1) PediatricRadiology.com (http://pediatricradiology.com)--a catalog of pediatric radiology Web sites; (2) The MetaTextbook of Pediatric Radiology (http://www. vh.org/Providers/TeachingFiles/MetatextbookPedRad/MetaTBP edRad.html)--a catalog of pediatric radiology teaching file cases on the Internet; and (3) Paediapedia (http://www.vh. org/Providers/TeachingFiles/PAP/PAPHome.html)--an imaging encyclopedia of pediatric disease. The pediatric radiology digital library is curated regularly. RESULTS: Over 7 months, 223,689 pages of information were read and 26,972 images were viewed in the pediatric radiology digital library by 69,866 individual users, with 20% of the users from outside the United States. CONCLUSION: Creating a pediatric radiology digital library that identifies and organizes authoritative pediatric radiology information and makes it conveniently available can allow radiologists to use the Internet productively as a reference tool.

Child↗
PubMed2000

CpG island libraries from human chromosomes 18 and 22: landmarks for novel genes.

CpG islands are found at the 5' end of approximately 60% of human genes and so are important genomic landmarks. They are concentrated in early-replicating, highly acetylated gene-rich regions. With respect to CpG island content, human Chrs 18 and 22 are very different from each other: Chr 18 appears to be CpG island poor, whereas Chr 22 appears to be CpG island rich. We have constructed and validated CpG island libraries from flow-sorted Chrs 18 and 22 and used these to estimate the difference in number of CpG islands found on these two chromosomes. These libraries contain normalized collections of sequences from the 5' end of genes. Clones from the libraries were sequenced and compared with the sequence databases; one third matched ESTs, thus anchoring these ESTs at the 5' end of their gene. However, it was striking that many clones either had no match or matched only existing CpG island clones. This suggests that a significant proportion of 5' gene sequences are absent from databases, presumably either because they are difficult to clone or the gene is poorly expressed and/or has a restricted expression pattern. This point should be taken into consideration if the currently available libraries are those used for the elucidation of complete, as opposed to partial, gene sequences. The Chr 18 and 22 CpG island libraries are a sequence resource for the isolation of such 5' gene sequences from specific human chromosomes.

Base Sequence↗