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Sample records for large phage-displayed library

  1. Human antibody fragments specific for the epidermal growth factor receptor selected from large non-immunised phage display libraries.

    Science.gov (United States)

    Souriau, Christelle; Rothacker, Julie; Hoogenboom, Hennie R; Nice, Edouard

    2004-09-01

    Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (ka and kd). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.

  2. Construction and Selection of Affilin® Phage Display Libraries.

    Science.gov (United States)

    Settele, Florian; Zwarg, Madlen; Fiedler, Sebastian; Koscheinz, Daniel; Bosse-Doenecke, Eva

    2018-01-01

    Affilin ® molecules represent a new class of so-called scaffold proteins. The concept of scaffold proteins is to use stable and versatile protein structures which can be endowed with de novo binding properties and specificities by introducing mutations in surface exposed amino acid residues. Complex variations and combinations are generated by genetic methods of randomization resulting in large cDNA libraries. The selection for candidates binding to a desired target can be executed by display methods, especially the very robust and flexible phage display. Here, we describe the construction of ubiquitin based Affilin ® phage display libraries and their use in biopanning experiments for the identification of novel protein ligands.

  3. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  4. Phage display peptide libraries: deviations from randomness and correctives

    Science.gov (United States)

    Ryvkin, Arie; Ashkenazy, Haim; Weiss-Ottolenghi, Yael; Piller, Chen; Pupko, Tal; Gershoni, Jonathan M

    2018-01-01

    Abstract Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library. In a previous study, we implemented next generation sequencing to evaluate a naïve library and discovered severe deviations from randomness in UAG codon over-representation as well as in high G phosphoramidite abundance causing amino acid distribution biases. In this study, we demonstrate that the UAG over-representation can be attributed to the burden imposed on the phage upon the assembly of the recombinant Protein 8 subunits. This was corrected by constructing the libraries using supE44-containing bacteria which suppress the UAG driven abortive termination. We also demonstrate that the overabundance of G stems from variant synthesis-efficiency and can be corrected using compensating oligonucleotide-mixtures calibrated by mass spectroscopy. Construction of libraries implementing these correctives results in markedly improved libraries that display random distribution of amino acids, thus ensuring that enriched peptides obtained in biopanning represent a genuine selection event, a fundamental assumption for phage display applications. PMID:29420788

  5. Construction of human antibody gene libraries and selection of antibodies by phage display.

    Science.gov (United States)

    Frenzel, André; Kügler, Jonas; Wilke, Sonja; Schirrmann, Thomas; Hust, Michael

    2014-01-01

    Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.

  6. Construction of naïve camelids VHH repertoire in phage display-based library.

    Science.gov (United States)

    Sabir, Jamal S M; Atef, Ahmed; El-Domyati, Fotouh M; Edris, Sherif; Hajrah, Nahid; Alzohairy, Ahmed M; Bahieldin, Ahmed

    2014-04-01

    Camelids have unique antibodies, namely HCAbs (VHH) or commercially named Nanobodies(®) (Nb) that are composed only of a heavy-chain homodimer. As libraries based on immunized camelids are time-consuming, costly and likely redundant for certain antigens, we describe the construction of a naïve camelid VHHs library from blood serum of non-immunized camelids with affinity in the subnanomolar range and suitable for standard immune applications. This approach is rapid and recovers VHH repertoire with the advantages of being more diverse, non-specific and devoid of subpopulations of specific antibodies, which allows the identification of binders for any potential antigen (or pathogen). RNAs from a number of camelids from Saudi Arabia were isolated and cDNAs of the diverse vhh gene were amplified; the resulting amplicons were cloned in the phage display pSEX81 vector. The size of the library was found to be within the required range (10(7)) suitable for subsequent applications in disease diagnosis and treatment. Two hundred clones were randomly selected and the inserted gene library was either estimated for redundancy or sequenced and aligned to the reference camelid vhh gene (acc. No. ADE99145). Results indicated complete non-specificity of this small library in which no single event of redundancy was detected. These results indicate the efficacy of following this approach in order to yield a large and diverse enough gene library to secure the presence of the required version encoding the required antibodies for any target antigen. This work is a first step towards the construction of phage display-based biosensors useful in disease (e.g., TB or tuberculosis) diagnosis and treatment. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  7. Selection of binding targets in parasites using phage-display and aptamer libraries in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Renata Rosito Tonelli

    2013-01-01

    Full Text Available Parasite infections are largely dependent on interactions between pathogen and different host cell populations to guarantee a successful infectious process. This is particularly true for obligatory intracellular parasites as Plasmodium, Toxoplasma, Leishmania, to name a few. Adhesion to and entry into the cell are essential steps requiring specific parasite and host cell molecules. The large amount of possible involved molecules poses additional difficulties for their identification by the classical biochemical approaches. In this respect, the search for alternative techniques should be pursued. Among them two powerful methodologies can be employed, both relying upon the construction of highly diverse combinatorial libraries of peptides or oligonucleotides that randomly bind with high affinity to targets on the cell surface and are selectively displaced by putative ligands. These are, respectively, the peptide-based phage display and the oligonucleotide-based aptamer techniques.The phage display technique has been extensively employed for the identification of novel ligands in vitro and in vivo in different areas such as cancer, vaccine development and epitope mapping. Particularly, phage display has been employed in the investigation of pathogen-host interactions. Although this methodology has been used for some parasites with encouraging results, in trypanosomatids its use is, as yet, scanty. RNA and DNA aptamers, developed by the SELEX process (Systematic Evolution of Ligands by Exponential Enrichment, were described over two decades ago and since then contributed to a large number of structured nucleic acids for diagnostic or therapeutic purposes or for the understanding of the cell biology. Similarly to the phage display technique scarce use of the SELEX process has been used in the probing of parasite-host interaction.In this review, an overall survey on the use of both phage display and aptamer technologies in different pathogenic

  8. Selection of binding targets in parasites using phage-display and aptamer libraries in vivo and in vitro.

    Science.gov (United States)

    Tonelli, R R; Colli, W; Alves, M J M

    2012-01-01

    Parasite infections are largely dependent on interactions between pathogen and different host cell populations to guarantee a successful infectious process. This is particularly true for obligatory intracellular parasites as Plasmodium, Toxoplasma, and Leishmania, to name a few. Adhesion to and entry into the cell are essential steps requiring specific parasite and host cell molecules. The large amount of possible involved molecules poses additional difficulties for their identification by the classical biochemical approaches. In this respect, the search for alternative techniques should be pursued. Among them two powerful methodologies can be employed, both relying upon the construction of highly diverse combinatorial libraries of peptides or oligonucleotides that randomly bind with high affinity to targets on the cell surface and are selectively displaced by putative ligands. These are, respectively, the peptide-based phage display and the oligonucleotide-based aptamer techniques. The phage display technique has been extensively employed for the identification of novel ligands in vitro and in vivo in different areas such as cancer, vaccine development, and epitope mapping. Particularly, phage display has been employed in the investigation of pathogen-host interactions. Although this methodology has been used for some parasites with encouraging results, in trypanosomatids its use is, as yet, scanty. RNA and DNA aptamers, developed by the SELEX process (Systematic Evolution of Ligands by Exponential Enrichment), were described over two decades ago and since then contributed to a large number of structured nucleic acids for diagnostic or therapeutic purposes or for the understanding of the cell biology. Similarly to the phage display technique scarce use of the SELEX process has been used in the probing of parasite-host interaction. In this review, an overall survey on the use of both phage display and aptamer technologies in different pathogenic organisms will be

  9. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    Science.gov (United States)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  10. Corruption of phage display libraries by target-unrelated clones: diagnosis and countermeasures.

    Science.gov (United States)

    Thomas, William D; Golomb, Miriam; Smith, George P

    2010-12-15

    Phage display is used to discover peptides or proteins with a desired target property-most often, affinity for a target selector molecule. Libraries of phage clones displaying diverse surface peptides are subject to a selection process designed to enrich for the target behavior and subsequently propagated to restore phage numbers. A recurrent problem is enrichment of clones, called target-unrelated phages or peptides (TUPs), that lack the target behavior. Many TUPs are propagation related; they have mutations conferring a growth advantage and are enriched during the propagations accompanying selection. Unlike other filamentous phage libraries, fd-tet-based libraries are relatively resistant to propagation-related TUP corruption. Their minus-strand origin is disrupted by a large cassette that simultaneously confers resistance to tetracycline and imposes a rate-limiting growth defect that cannot be bypassed with simple mutations. Nonetheless, a new type of propagation-related TUP emerged in the output of in vivo selections from an fd-tet library. The founding clone had a complex rearrangement that restored the minus-strand origin while retaining tetracycline resistance. The rearrangement involved two recombination events, one with a contaminant having a wild-type minus-strand origin. The founder's infectivity advantage spread by simple recombination to clones displaying different peptides. We propose measures for minimizing TUP corruption. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Corruption of phage-display libraries by target-unrelated clones: Diagnosis and countermeasures

    Science.gov (United States)

    Thomas, William D.; Golomb, Miriam; Smith, George P.

    2010-01-01

    Phage display is used to discover peptides or proteins with a desired target property—most often, affinity for a target selector molecule. Libraries of phage clones displaying diverse surface peptides are subject to a selection process designed to enrich for the target behavior, and subsequently propagated to restore phage numbers. A recurrent problem is enrichment of clones, called target-unrelated phage (TUPs), that lack the target behavior. Many TUPs are propagation-related; they have mutations conferring a growth advantage, and are enriched during the propagations accompanying selection. Unlike other filamentous phage libraries, fd-tet-based libraries are relatively resistant to propagation-related TUP corruption. Their minus strand origin is disrupted by a large cassette that simultaneously confers resistance to tetracycline and imposes a rate-limiting growth defect that cannot be bypassed with simple mutations. Nonetheless, a new type of propagation-related TUP emerged in the output of in vivo selections from an fd-tet library. The founding clone had a complex rearrangement that restored the minus strand origin while retaining tetracycline resistance. The rearrangement involved two recombination events, one with a contaminant having a wild-type minus strand origin. The founder’s infectivity advantage spread by simple recombination to clones displaying different peptides. We propose measures for minimizing TUP corruption. PMID:20692225

  12. PuLSE: Quality control and quantification of peptide sequences explored by phage display libraries.

    Science.gov (United States)

    Shave, Steven; Mann, Stefan; Koszela, Joanna; Kerr, Alastair; Auer, Manfred

    2018-01-01

    The design of highly diverse phage display libraries is based on assumption that DNA bases are incorporated at similar rates within the randomized sequence. As library complexity increases and expected copy numbers of unique sequences decrease, the exploration of library space becomes sparser and the presence of truly random sequences becomes critical. We present the program PuLSE (Phage Library Sequence Evaluation) as a tool for assessing randomness and therefore diversity of phage display libraries. PuLSE runs on a collection of sequence reads in the fastq file format and generates tables profiling the library in terms of unique DNA sequence counts and positions, translated peptide sequences, and normalized 'expected' occurrences from base to residue codon frequencies. The output allows at-a-glance quantitative quality control of a phage library in terms of sequence coverage both at the DNA base and translated protein residue level, which has been missing from toolsets and literature. The open source program PuLSE is available in two formats, a C++ source code package for compilation and integration into existing bioinformatics pipelines and precompiled binaries for ease of use.

  13. Modular and aggregation resistant Vh antibodies from a phage display library

    DEFF Research Database (Denmark)

    Friis, Niels Anton; Mandrup, Ole Aalund; Lykkemark, Simon

    2012-01-01

    through immunisation of sharks or camels, or alternatively from recombinant libraries1. The domain antibodies have certain advantages, both pharmacologically and technically. Here we report the construction of a semi-synthetic and highly modular antibody library, based on a human framework (V3-23/D47......Directed evolution of antibodies through phage display is a powerful technique for producing binders of various biological targets. One of the recent innovations in the fi eld is the domain antibody, an antibody consisting only of a single variable domain. These anti bodies can be obtained either......). The antibody scaffold has been codon optimised to improve expression, and the CDR’s have been created using trinucleotide synthesis. These methods give a strict control over the randomisations, and the ability to design a library with minimal aggregation propensity. To facilitate further manipulation, unique...

  14. Novel ZnO-binding peptides obtained by the screening of a phage display peptide library

    Energy Technology Data Exchange (ETDEWEB)

    Golec, Piotr [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Molecular Biology (affiliated with the University of Gdansk) (Poland); Karczewska-Golec, Joanna [University of Gdansk and Medical University of Gdansk, Laboratory of Molecular Bacteriology, Intercollegiate Faculty of Biotechnology (Poland); Los, Marcin; Wegrzyn, Grzegorz, E-mail: wegrzyn@biotech.univ.gda.pl [University of Gdansk, Department of Molecular Biology (Poland)

    2012-11-15

    Zinc oxide (ZnO) is a semiconductor compound with a potential for wide use in various applications, including biomaterials and biosensors, particularly as nanoparticles (the size range of ZnO nanoparticles is from 2 to 100 nm, with an average of about 35 nm). Here, we report isolation of novel ZnO-binding peptides, by screening of a phage display library. Interestingly, amino acid sequences of the ZnO-binding peptides reported in this paper and those described previously are significantly different. This suggests that there is a high variability in sequences of peptides which can bind particular inorganic molecules, indicating that different approaches may lead to discovery of different peptides of generally the same activity (e.g., binding of ZnO) but having various detailed properties, perhaps crucial under specific conditions of different applications.

  15. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    International Nuclear Information System (INIS)

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-01-01

    Highlights: → Successfully selected specific PreS1-interacting peptides by using phage displayed library. → Alignment of the positive phage clones revealed a consensus PreS1 binding motif. → A highly enriched peptide named P7 had a strong binding ability for PreS1. → P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX n HX m HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  16. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Xiao, Gengfu, E-mail: xiaogf@wh.iov.cn [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  17. Performance evaluation of phage-displayed synthetic human single-domain antibody libraries: A retrospective analysis.

    Science.gov (United States)

    Henry, Kevin A; Tanha, Jamshid

    2018-05-01

    Fully human synthetic single-domain antibodies (sdAbs) are desirable therapeutic molecules but their development is a considerable challenge. Here, using a retrospective analysis of in-house historical data, we examined the parameters that impact the outcome of screening phage-displayed synthetic human sdAb libraries to discover antigen-specific binders. We found no evidence for a differential effect of domain type (V H or V L ), library randomization strategy, incorporation of a stabilizing disulfide linkage or sdAb display format (monovalent vs. multivalent) on the probability of obtaining any antigen-binding human sdAbs, instead finding that the success of library screens was primarily related to properties of target antigens, especially molecular mass. The solubility and binding affinity of sdAbs isolated from successful screens depended both on properties of the sdAb libraries (primarily domain type) and the target antigens. Taking attrition of sdAbs with major manufacturability concerns (aggregation; low expression) and sdAbs that do not recognize native cell-surface antigens as independent probabilities, we calculate the overall likelihood of obtaining ≥1 antigen-binding human sdAb from a single library-target screen as ~24%. Successful library-target screens should be expected to yield ~1.3 human sdAbs on average, each with average binding affinity of ~2 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor.

    Science.gov (United States)

    Molek, Peter; Vodnik, Miha; Strukelj, Borut; Bratkovič, Tomaž

    2014-09-26

    Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Random mutagenesis of BoNT/E Hc nanobody to construct a secondary phage-display library.

    Science.gov (United States)

    Shahi, B; Mousavi Gargari, S L; Rasooli, I; Rajabi Bazl, M; Hoseinpoor, R

    2014-08-01

    To construct secondary mutant phage-display library of recombinant single variable domain (VHH) against botulinum neurotoxin E by error-prone PCR. The gene coding for specific VHH derived from the camel immunized with binding domain of botulinum neurotoxin E (BoNT/E) was amplified by error-prone PCR. Several biopanning rounds were used to screen the phage-displaying BoNT/E Hc nanobodies. The final nanobody, SHMR4, with increased affinity recognized BoNT/E toxin with no cross-reactivity with other antigens especially with related BoNT toxins. The constructed nanobody could be a suitable candidate for VHH-based biosensor production to detect the Clostridium botulinum type E. Diagnosis and treatment of botulinum neurotoxins are important. Generation of high-affinity antibodies based on the construction of secondary libraries using affinity maturation step leads to the development of reagents for precise diagnosis and therapy. © 2014 The Society for Applied Microbiology.

  20. Identification of novel inhibitors of Pseudomonas aeruginosa MurC enzyme derived from phage-displayed peptide libraries.

    Science.gov (United States)

    El Zoeiby, Ahmed; Sanschagrin, François; Darveau, André; Brisson, Jean-Robert; Levesque, Roger C

    2003-03-01

    The machinery of peptidoglycan biosynthesis is an ideal site at which to look for novel antimicrobial targets. Phage display was used to develop novel peptide inhibitors for MurC, an essential enzyme involved in the early steps of biosynthesis of peptidoglycan monomer. We cloned and overexpressed the murA, -B and -C genes from Pseudomonas aeruginosa in the pET expression vector, adding a His-tag to their C termini. The three proteins were overproduced in Escherichia coli and purified to homogeneity in milligram quantities. MurA and -B were combinatorially used to synthesize the MurC substrate UDP-N-acetylmuramate, the identity of which was confirmed by mass spectrometry and nuclear magnetic resonance analysis. Two phage-display libraries were screened against MurC in order to identify peptide ligands to the enzyme. Three rounds of biopanning were carried out, successively increasing elution specificity from round 1 to 3. The third round was accomplished with both non-specific elution and competitive elution with each of the three MurC substrates, UDP-N-acetylmuramic acid (UNAM), ATP and L-alanine. The DNA of 10 phage, selected randomly from each group, was extracted and sequenced, and consensus peptide sequences were elucidated. Peptides were synthesized and tested for inhibition of the MurC-catalysed reaction, and two peptides were shown to be inhibitors of MurC activity with IC(50)s of 1.5 and 0.9 mM, respectively. The powerful selection technique of phage display allowed us to identify two peptide inhibitors of the essential bacterial enzyme MurC. The peptide sequences represent the basis for the synthesis of inhibitory peptidomimetic molecules.

  1. A compact phage display human scFv library for selection of antibodies to a wide variety of antigens

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    Kristensen Peter

    2009-01-01

    Full Text Available Abstract Background Phage display technology is a powerful new tool for making antibodies outside the immune system, thus avoiding the use of experimental animals. In the early days, it was postulated that this technique would eventually replace hybridoma technology and animal immunisations. However, since this technology emerged more than 20 years ago, there have only been a handful reports on the construction and application of phage display antibody libraries world-wide. Results Here we report the simplest and highly efficient method for the construction of a highly useful human single chain variable fragment (scFv library. The least number of oligonucleotide primers, electroporations and ligation reactions were used to generate a library of 1.5 × 108 individual clones, without generation of sub-libraries. All possible combinations of heavy and light chains, among all immunoglobulin isotypes, were included by using a mixture of primers and overlapping extension PCR. The key difference from other similar libraries was the highest diversity of variable gene repertoires, which was derived from 140 non-immunized human donors. A wide variety of antigens were successfully used to affinity select specific binders. These included pure recombinant proteins, a hapten and complex antigens such as viral coat proteins, crude snake venom and cancer cell surface antigens. In particular, we were able to use standard bio-panning method to isolate antibody that can bind to soluble Aflatoxin B1, when using BSA-conjugated toxin as a target, as demonstrated by inhibition ELISA. Conclusion These results suggested that by using an optimized protocol and very high repertoire diversity, a compact and efficient phage antibody library can be generated. This advanced method could be adopted by any molecular biology laboratory to generate both naïve or immunized libraries for particular targets as well as for high-throughput applications.

  2. Practical Tips for Construction of Custom Peptide Libraries and Affinity Selection by Using Commercially Available Phage Display Cloning Systems

    Directory of Open Access Journals (Sweden)

    Keisuke Fukunaga

    2012-01-01

    Full Text Available Phage display technology is undoubtedly a powerful tool for affinity selection of target-specific peptide. Commercially available premade phage libraries allow us to take screening in the easiest way. On the other hand, construction of a custom phage library seems to be inaccessible, because several practical tips are absent in instructions. This paper focuses on what should be born in mind for beginners using commercially available cloning kits (Ph.D. with type 3 vector and T7Select systems for M13 and T7 phage, respectively. In the M13 system, Pro or a basic amino acid (especially, Arg should be avoided at the N-terminus of peptide fused to gp3. In both systems, peptides containing odd number(s of Cys should be designed with caution. Also, DNA sequencing of a constructed library before biopanning is highly recommended for finding unexpected bias.

  3. Screening and Identification of Peptides Specifically Targeted to Gastric Cancer Cells from a Phage Display Peptide Library

    Science.gov (United States)

    Sahin, Deniz; Taflan, Sevket Onur; Yartas, Gizem; Ashktorab, Hassan; Smoot, Duane T

    2018-04-25

    Background: Gastric cancer is the second most common cancer among the malign cancer types. Inefficiency of traditional techniques both in diagnosis and therapy of the disease makes the development of alternative and novel techniques indispensable. As an alternative to traditional methods, tumor specific targeting small peptides can be used to increase the efficiency of the treatment and reduce the side effects related to traditional techniques. The aim of this study is screening and identification of individual peptides specifically targeted to human gastric cancer cells using a phage-displayed peptide library and designing specific peptide sequences by using experimentally-eluted peptide sequences. Methods: Here, MKN-45 human gastric cancer cells and HFE-145 human normal gastric epithelial cells were used as the target and control cells, respectively. 5 rounds of biopannning with a phage display 12-peptide library were applied following subtraction biopanning with HFE-145 control cells. The selected phage clones were established by enzyme-linked immunosorbent assay and immunofluorescence detection. We first obtain random phage clones after five biopanning rounds, determine the binding levels of each individual clone. Then, we analyze the frequencies of each amino acid in best binding clones to determine positively overexpressed amino acids for designing novel peptide sequences. Results: DE532 (VETSQYFRGTLS) phage clone was screened positive, showing specific binding on MKN-45 gastric cancer cells. DE-Obs (HNDLFPSWYHNY) peptide, which was designed by using amino acid frequencies of experimentally selected peptides in the 5th round of biopanning, showed specific binding in MKN-45 cells. Conclusion: Selection and characterization of individual clones may give us specifically binding peptides, but more importantly, data extracted from eluted phage clones may be used to design theoretical peptides with better binding properties than even experimentally selected ones

  4. Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

    Science.gov (United States)

    Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

    2018-03-01

    B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

  5. Microcystin-LR nanobody screening from an alpaca phage display nanobody library and its expression and application.

    Science.gov (United States)

    Xu, Chongxin; Yang, Ying; Liu, Liwen; Li, Jianhong; Liu, Xiaoqin; Zhang, Xiao; Liu, Yuan; Zhang, Cunzheng; Liu, Xianjin

    2018-04-30

    Microcystin-LR (MC-LR) is a type of biotoxin that pollutes the ecological environment and food. The study aimed to obtain new nanobodies from phage nanobody library for determination of MC-LR. The toxin was conjugated to keyhole limpet haemocyanin (KLH) and bovine serum albumin (BSA), respectively, then the conjugates were used as coated antigens for enrichment (coated MC-LR-KLH) and screening (coated MC-LR-BSA) of MC-LR phage nanobodies from an alpaca phage display nanobody library. The antigen-specific phage particles were enriched effectively with four rounds of biopanning. At the last round of enrichment, total 20 positive monoclonal phage nanobodies were obtained from the library, which were analyzed after monoclonal phage enzyme linked immunosorbent assay (ELISA), colony PCR and DNA sequencing. The most three positive nanobody genes, ANAb12, ANAb9 and ANAb7 were cloned into pET26b vector, then the nanobodies were expressed in Escherichia coli BL21 respectively. After being purified, the molecular weight (M.W.) of all nanobodies were approximate 15kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The purified nanobodies, ANAb12, ANAb9 and ANAb7 were used to establish the indirect competitive ELISA (IC-ELISA) for MC-LR, and their half-maximum inhibition concentrations (IC 50 ) were 0.87, 1.17 and 1.47μg/L, their detection limits (IC 10 ) were 0.06, 0.08 and 0.12μg/L, respectively. All of them showed strong cross-reactivity (CRs) of 82.7-116.9% for MC-RR, MC-YR and MC-WR, and weak CRs of less than 4.56% for MC-LW, less than 0.1% for MC-LY and MC-LF. It was found that all the IC-ELISAs for MC-LR spiked in tap water samples detection were with good accuracy, stability and repeatability, their recoveries were 84.0-106.5%, coefficient of variations (CVs) were 3.4-10.6%. These results showed that IC-ELISA based on the nanobodies from the alpaca phage display antibody library were promising for high sensitive determination of multiple

  6. Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens

    Directory of Open Access Journals (Sweden)

    Harvinder Talwar

    2015-04-01

    Full Text Available Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB. No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine.

  7. A universal phage display system for the seamless construction of Fab libraries.

    Science.gov (United States)

    Nelson, Renae S; Valadon, Philippe

    2017-11-01

    The construction of Fab phage libraries requires the cloning of domains from both the light and the heavy chain of antibodies. Despite the advent of powerful strategies such as splicing-by-overlap extension PCR, obtaining high quality libraries with excellent coverage remains challenging. Here, we explored the use of type IIS restriction enzymes for the seamless cloning of Fab libraries. We analyzed human, murine and rabbit germline antibody repertoires and identified combinations of restriction enzymes that exhibit very few or no recognition sites in the antibody sequences. We describe three phagemid vectors, pUP-22Hb, pUP-22Mc and pUP-22Rc, which were employed for cloning the Fab repertoire of these hosts using BsmBI and SapI (human) or SapI alone (mouse and rabbit). Using human serum albumin as a model immunization, we built a mouse/human chimeric Fab library and a mouse Fab library in a single step ligation and successfully panned multiple cognate antibodies. The overall process is highly scalable and faster than PCR-based techniques, with a Fab insertion success rate of around 80%. By using carefully chosen overhangs on each end of the antibody domains, this approach paves the way to the universal, sequence- and vector-independent cloning and reformatting of antibody libraries. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Deoxynivalenol-mimic nanobody isolated from a naïve phage display nanobody library and its application in immunoassay.

    Science.gov (United States)

    Qiu, Yu-Lou; He, Qing-Hua; Xu, Yang; Bhunia, Arun K; Tu, Zhui; Chen, Bo; Liu, Yuan-Yuan

    2015-08-05

    In this study, using mycotoxin deoxynivalenol (DON) as a model hapten, we developed a nanobody-based environmental friendly immunoassay for sensitive detection of DON. Two nanobodies (N-28 and N-31) which bind to anti-DON monoclonal antibody (MAb) were isolated from a naive phage display library. These nanobodies are clonable, thermally stable and mycotoxin-free products and can be served as coating antigen mimetics in heterologous immunoassay. The half inhibition concentration (IC50) of the immunoassay developed with N-28 and N-31 was 8.77 ± 0.41 ng mL(-1) and 19.97 ± 0.84 ng mL(-1), respectively, which were 18- and 8-fold more sensitive than the conventional coating antigen (DON-BSA) based immunoassay. In order to better understand the molecular mechanism of antigen mimicry by nanobody, the 3D structure of "nanobody (N-28) - anti-DON MAb" complex was presented and verified by molecular modeling and alanine-scanning mutagenesis. The results showed that hydrogen bond and hydrophobic interaction formed between Thr 102 - Ser 106 of N-28 and CDR H3 residues of anti-DON antibody may contribute to their binding. This novel concept of enhancing sensitivity of immunoassay for DON based on nanobody may provide potential applications in a general method for immunoassay of various food chemical contaminants. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

    Directory of Open Access Journals (Sweden)

    Oliinyk O. S.

    2014-02-01

    Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

  10. Phage-display libraries of murine and human antibody Fab fragments

    DEFF Research Database (Denmark)

    Engberg, J; Andersen, P S; Nielsen, L K

    1996-01-01

    We provide efficient and detailed procedures for construction, expression, and screening of comprehensive libraries of murine or human antibody Fab fragments displayed on the surface of filamentous phage. In addition, protocols for producing and using ultra-electrocompetent cells, for producing Fab...

  11. Production of a Human Antibody Library in the Phage-Display Vector pSEX81.

    Science.gov (United States)

    Welschof, M; Little, M; Dörsam, H

    1998-01-01

    Human monoclonal antibodies (MAbs) are more suitable than MAbs of animal origin for clinical applications because of lower hypersensitivity reactions, less formation of circulating immune complexes and lower anti-immunoglobulin responses The classical production of human MAbs via the hybridoma technique or Epstein-Barr virus (EBV) transformation is limited by the instability of cell lines, low antibody production, and the problems of imununizing humans with certain antigens (1,2). A promising alternative 1s the production of human recombinant antibodies (3). Recombinant DNA technology has made it possible to clone human antibody genes in vectors and to generate antibody expression libraries (4-7). One approach has been to amplify and recombine the IgG repertoire of an "immunized" donor. This has been used to isolate several antibodies related to diseases (8,9). In order to obtain more universal antibody libraries the naive IgM repertoire of several "unimmunized" donors were pooled (10,12). The complexity of the combinatorial libraries has been further increased by creating the so-called "semisynthetic" antibody libraries (22-14).

  12. Basics of Antibody Phage Display Technology.

    Science.gov (United States)

    Ledsgaard, Line; Kilstrup, Mogens; Karatt-Vellatt, Aneesh; McCafferty, John; Laustsen, Andreas H

    2018-06-09

    Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

  13. Novel β-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy

    Science.gov (United States)

    Shukla, Girja S.; Krag, David N.

    2010-01-01

    Novel phage-displayed random linear dodecapeptide (X12) and cysteine-constrained decapeptide (CX10C) libraries constructed in fusion to the amino-terminus of P99 β-lactamase molecules were used for identifying β-lactamase-linked cancer cell-specific ligands. The size and quality of both libraries were comparable to the standards of other reported phage display systems. Using the single-round panning method based on phage DNA recovery, we identified severalβ-lactamase fusion peptides that specifically bind to live human breast cancer MDA-MB-361 cells. The β-lactamase fusion to the peptides helped in conducting the enzyme activity-based clone normalization and cell-binding screening in a very time- and cost-efficient manner. The methods were suitable for 96-well readout as well as microscopic imaging. The success of the biopanning was indicated by the presence of ~40% cancer cell-specific clones among recovered phages. One of the binding clones appeared multiple times. The cancer cell-binding fusion peptides also shared several significant motifs. This opens a new way of preparing and selecting phage display libraries. The cancer cell-specific β-lactamase-linked affinity reagents selected from these libraries can be used for any application that requires a reporter for tracking the ligand molecules. Furthermore, these affinity reagents have also a potential for their direct use in the targeted enzyme prodrug therapy of cancer. PMID:19751096

  14. Isolation of Osteosarcoma-Associated Human Antibodies from a Combinatorial Fab Phage Display Library

    Directory of Open Access Journals (Sweden)

    Carmela Dantas-Barbosa

    2009-01-01

    Full Text Available Osteosarcoma, a highly malignant disease, is the most common primary bone tumor and is frequently found in children and adolescents. In order to isolate antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab library displayed on the surface of phages was used. After three rounds of selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were detected. From these Fabs, five were better characterized, and despite having differences in their VH (heavy chain variable domain and Vκ (kappa chain variable domain regions, they all bound to a protein with the same molecular mass. Further analysis by cell ELISA and immunocytochemistry suggested that the Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in neoplasic cells than in normal tissue. These results suggest that the human Fabs selected in this work are a valuable tool for the study of this neoplasia.

  15. Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naïve human phage display library.

    Science.gov (United States)

    McElhiney, J; Lawton, L A; Porter, A J

    2000-12-01

    Single-chain antibody fragments against the cyanobacterial hepatotoxin microcystin-LR were isolated from a naive human phage display library and expressed in Escherichia coli. In competition enzyme-linked immunosorbent assay (ELISA), the most sensitive antibody clone selected from the library detected free microcystin-LR with an IC(50) value of 4 microM. It was found to cross react with three other microcystin variants - microcystin-RR, microcystin-LW and microcystin-LF - and detected microcystins in extracts of the cyanobacterium Microcystis aeruginosa, found to contain the toxins by high-performance liquid chromatography (HPLC). The quantification of microcystins in these extracts by ELISA and HPLC showed good correlation. Although the antibody isolated in this study was considerably less sensitive than the polyclonal and monoclonal antibodies already available for microcystin detection, phage display technology represents a cheaper, more rapid alternative for the production of anti-microcystin antibodies than the methods currently in use.

  16. [Peptide phage display in biotechnology and biomedicine].

    Science.gov (United States)

    Kuzmicheva, G A; Belyavskaya, V A

    2016-07-01

    To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

  17. Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

    Science.gov (United States)

    Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

    2018-01-16

    Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

  18. Establishment of a sensitive time-resolved fluoroimmunoassay for detection of Bacillus thuringiensis Cry1Ie toxin based nanobody from a phage display library.

    Science.gov (United States)

    Xu, Chongxin; Liu, Xiaoqin; Zhang, Cunzheng; Zhang, Xiao; Zhong, Jianfeng; Liu, Yuan; Hu, Xiaodan; Lin, Manman; Liu, Xianjin

    2017-02-01

    Cry1Ie toxin was an insect-resistant protein used in genetically modified crops (GMC). In this study, a large human VH gene nanobodies phage displayed library was employed to select anti-Cry1Ie toxin antibody by affinity panning. After 5 rounds of panning, total 12 positive monoclonal phage particles were obtained. One of the identified positive phage nanobody was expressed in E.coli BL21 and the purified protein was indicated as a molecular mass of approximately 20 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Then a sensitive indirect competitive time-resolved fluoroimmunoassay (IC-TRFIA) was established for detection of Cry1Ie toxin by the purified protein. The working range of detection for Cry1Ie toxin standards in the IC-TRFIA were 0.08-6.44 ng mL -1 and the medium inhibition of control (IC 50 ) was 0.73 ng mL -1 . It showed a weak cross-reactivity with Cry1Ab toxin (at 5.6%), but did not recognize Cry1B, Cry1C, Cry1F, and Cry2A toxins (were <0.1%). The average recoveries of Cry1Ie toxin from respectively spiked in rice, corn and soil samples were in the range of 83.5%-96.6% and with a coefficient of variation (CV) among 2.0%-8.6%. These results showed the IC-TRFIA was promising for detection of Cry1Ie toxin in agricultural and environmental samples. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Screening for single-chain variable fragment antibodies against multiple Cry1 toxins from an immunized mouse phage display antibody library.

    Science.gov (United States)

    Dong, Sa; Bo, Zongyi; Zhang, Cunzheng; Feng, Jianguo; Liu, Xianjin

    2018-04-01

    Single-chain variable fragment (scFv) is a kind of antibody that possess only one chain of the complete antibody while maintaining the antigen-specific binding abilities and can be expressed in prokaryotic system. In this study, scFvs against Cry1 toxins were screened out from an immunized mouse phage displayed antibody library, which was successfully constructed with capacity of 6.25 × 10 7  CFU/mL. Using the mixed and alternative antigen coating strategy and after four rounds of affinity screening, seven positive phage-scFvs against Cry1 toxins were selected and characterized. Among them, clone scFv-3H9 (MG214869) showing relative stable and high binding abilities to six Cry1 toxins was selected for expression and purification. SDS-PAGE indicated that the scFv-3H9 fragments approximately 27 kDa were successfully expressed in Escherichia coli HB2151 strain. The purified scFv-3H9 was used to establish the double antibody sandwich enzyme-linked immunosorbent assay method (DAS-ELISA) for detecting six Cry1 toxins, of which the lowest detectable limits (LOD) and the lowest quantitative limits (LOQ) were 3.14-11.07 and 8.22-39.44 ng mL -1 , respectively, with the correlation coefficient higher than 0.997. The average recoveries of Cry1 toxins from spiked rice leaf samples were ranged from 84 to 95%, with coefficient of variation (CV) less than 8.2%, showing good accuracy for the multi-residue determination of six Cry1 toxins in agricultural samples. This research suggested that the constructed phage display antibody library based on the animal which was immunized with the mixture of several antigens under the same category can be used for the quick and effective screening of generic antibodies.

  20. Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Xiaoyong; Cai, Cuizan [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Xiao, Fei [Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiong, Yaoling [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Huang, Yadong; Zhang, Qihao [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiang, Qi [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Lou, Guofeng [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Lian, Mengyang [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Su, Zhijian, E-mail: tjnuszj@jnu.edu.cn [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Zheng, Qing, E-mail: tzhengq@jnu.edu.cn [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China)

    2014-03-21

    Highlights: • A specific aFGF-binding peptide AP8 was identified from a phage display library. • AP8 could inhibit aFGF-stimulated cell proliferation in a dose-dependent manner. • AP8 arrested the cell cycle at the G0/G1 phase by suppressing Cyclin D1. • AP8 could block the activation of Erk1/2 and Akt kinase. • AP8 counteracted proliferation and cell cycle via influencing PA2G4 and PCNA. - Abstract: It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.

  1. Production of a phage-displayed single chain variable fragment ...

    African Journals Online (AJOL)

    Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...

  2. Identifying Bacterial Immune Evasion Proteins Using Phage Display.

    Science.gov (United States)

    Fevre, Cindy; Scheepmaker, Lisette; Haas, Pieter-Jan

    2017-01-01

    Methods aimed at identification of immune evasion proteins are mainly rely on in silico prediction of sequence, structural homology to known evasion proteins or use a proteomics driven approach. Although proven successful these methods are limited by a low efficiency and or lack of functional identification. Here we describe a high-throughput genomic strategy to functionally identify bacterial immune evasion proteins using phage display technology. Genomic bacterial DNA is randomly fragmented and ligated into a phage display vector that is used to create a phage display library expressing bacterial secreted and membrane bound proteins. This library is used to select displayed bacterial secretome proteins that interact with host immune components.

  3. Evolution of phage display technology: from discovery to application.

    Science.gov (United States)

    Rahbarnia, Leila; Farajnia, Safar; Babaei, Hossein; Majidi, Jafar; Veisi, Kamal; Ahmadzadeh, Vahideh; Akbari, Bahman

    2017-03-01

    Phage display technology as a selection-based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophage surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies.

  4. Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer

    International Nuclear Information System (INIS)

    Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu; Li, Xiaokun; Wu, Xiaoping

    2013-01-01

    Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163–169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163–169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ► A novel FGF8b-binding peptide P12 was isolated from a phage display library. ► The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ► P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ► P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ► P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer

  5. Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); Li, Xiaokun [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China); Wu, Xiaoping, E-mail: twxp@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China)

    2013-05-01

    Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163–169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163–169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ► A novel FGF8b-binding peptide P12 was isolated from a phage display library. ► The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ► P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ► P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ► P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer.

  6. Recombinant human monoclonal autoantibodies specific for citrulline-containing peptides from phage display libraries derived from patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Raats, J.M.H.; Wijnen, E.M.; Pruijn, G.J.M.; Hoogen, F.H.J. van den; Venrooij, W.J.W. van

    2003-01-01

    OBJECTIVE: To isolate and characterize monoclonal autoantibodies (Mab) directed to citrullinated antigens from patients with rheumatoid arthritis (RA). METHODS: Using lymphocytes from bone marrow or peripheral blood from RA patients, we constructed antibody fragment libraries representing the

  7. Identification of antigenic regions on VP2 of African horsesickness virus serotype 3 by using phage-displayed epitope libraries.

    Science.gov (United States)

    Bentley, L; Fehrsen, J; Jordaan, F; Huismans, H; du Plessis, D H

    2000-04-01

    VP2 is an outer capsid protein of African horsesickness virus (AHSV) and is recognized by serotype-discriminatory neutralizing antibodies. With the objective of locating its antigenic regions, a filamentous phage library was constructed that displayed peptides derived from the fragmentation of a cDNA copy of the gene encoding VP2. Peptides ranging in size from approximately 30 to 100 amino acids were fused with pIII, the attachment protein of the display vector, fUSE2. To ensure maximum diversity, the final library consisted of three sub-libraries. The first utilized enzymatically fragmented DNA encoding only the VP2 gene, the second included plasmid sequences, while the third included a PCR step designed to allow different peptide-encoding sequences to recombine before ligation into the vector. The resulting composite library was subjected to immunoaffinity selection with AHSV-specific polyclonal chicken IgY, polyclonal horse immunoglobulins and a monoclonal antibody (MAb) known to neutralize AHSV. Antigenic peptides were located by sequencing the DNA of phages bound by the antibodies. Most antigenic determinants capable of being mapped by this method were located in the N-terminal half of VP2. Important binding areas were mapped with high resolution by identifying the minimum overlapping areas of the selected peptides. The MAb was also used to screen a random 17-mer epitope library. Sequences that may be part of a discontinuous neutralization epitope were identified. The amino acid sequences of the antigenic regions on VP2 of serotype 3 were compared with corresponding regions on three other serotypes, revealing regions with the potential to discriminate AHSV serotypes serologically.

  8. Biopanning and characterization of peptides with Fe3O4 nanoparticles-binding capability via phage display random peptide library technique.

    Science.gov (United States)

    You, Fei; Yin, Guangfu; Pu, Ximing; Li, Yucan; Hu, Yang; Huang, Zhongbin; Liao, Xiaoming; Yao, Yadong; Chen, Xianchun

    2016-05-01

    Functionalization of inorganic nanoparticles (NPs) play an important role in biomedical applications. A proper functionalization of NPs can improve biocompatibility, avoid a loss of bioactivity, and further endow NPs with unique performances. Modification with vairous specific binding biomolecules from random biological libraries has been explored. In this work, two 7-mer peptides with sequences of HYIDFRW and TVNFKLY were selected from a phage display random peptide library by using ferromagnetic NPs as targets, and were verified to display strong binding affinity to Fe3O4 NPs. Fourier transform infrared spectrometry, fluorescence microscopy, thermal analysis and X-ray photoelectron spectroscopy confirmed the presence of peptides on the surface of Fe3O4 NPs. Sequence analyses revealed that the probable binding mechanism between the peptide and Fe3O4 NPs might be driven by Pearson hard acid-hard base specific interaction and hydrogen bonds, accompanied with hydrophilic interactions and non-specific electrostatic attractions. The cell viability assay indicated a good cytocompatibility of peptide-bound Fe3O4 NPs. Furthermore, TVNFKLY peptide and an ovarian tumor cell A2780 specific binding peptide (QQTNWSL) were conjugated to afford a liner 14-mer peptide (QQTNWSLTVNFKLY). The binding and targeting studies showed that 14-mer peptide was able to retain both the strong binding ability to Fe3O4 NPs and the specific binding ability to A2780 cells. The results suggested that the Fe3O4-binding peptides would be of great potential in the functionalization of Fe3O4 NPs for the tumor-targeted drug delivery and magnetic hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 99mTc-HYNIC-TNF analogues (WH701) derived from phage display peptide libraries for imaging TNF-receptor-positive ovarian carcinoma: Preclinical evaluation

    International Nuclear Information System (INIS)

    Xia, J.S.; Wu, H.; Xiang, Y.; Xia, T.; Li, H.

    2002-01-01

    Aim: In this investigation, 99m Tc-hydrazinonicotinyl-TNF analogs (WH701) was labeled using ethylenediaminediacetic acid (EDDA) as coligand(A number of TNF analogs had been selected and synthesized using random phage-display peptides library in our lab ) and Pharmacokinetics and feasibility studies were performed for its potential use as diagnostic radiopharmaceutical. Material and Methods: The peptide was radiolabeled with 99mTc using HYNIC as a bifunctional chelator and EDDA as coligand. The complexes were characterized by HPLC. The in vitro stability of the radiolabeled peptide WH701 in serum and in phosphate buffer were examined simultaneity. Biodistribution studies were conducted to determine the in vivo characteristics of the complexes. The tumor uptake and image were also conducted in HOC8 tumor-bearing nude mice. Results: The peptide analog permitted efficient incorporation of 99mTc. The preparation of 99mTc-WH701 was stable in vitro. HPLC analysis of the urine samples collected after injection of 99mTc-WH701 showed that the radioactivity elution profile and Rt of the peak were similar to those of the preparation injected. Studies in vivo suggested that the biological activity of the peptide was not compromised. The agent cleared rapidly from the blood. The labeled peptide was shown in the mouse model to localize rapidly and specifically in site of tumor. Images of diagnostic quality could be obtained within 30 min post-administration in all studies. Conclusion: The TNF analogue peptide WH701 can be radiolabeled with 99mTc by HYNIC using EDDA as coligand without loss of affinity, and the 99mTc -WH701 is not degraded in serum and shows radiochemical stability for an extended period of time in vitro. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc -WH701 a promising candidate for tumor imaging. This agent is worthy of further investigation

  10. Isolation of a monoclonal antibody from a phage display library binding the rhesus macaque MHC class I allomorph Mamu-A1*001.

    Directory of Open Access Journals (Sweden)

    Nathan Holman

    Full Text Available Monoclonal antibodies that bind to human leukocyte antigen (HLA are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001. We induced Mamu-A1*001-binding antibodies by alloimmunizing a female Mamu-A1*001-negative rhesus macaque with peripheral blood mononuclear cells (PBMC from a male Mamu-A1*001-positive donor. A Fab phage display library was constructed with PBMC from the alloimmunized macaque and panned to isolate an antibody that binds to Mamu-A1*001 but not to other common rhesus macaque MHC class I molecules. The isolated antibody distinguishes PBMC from Mamu-A1*001-positive and -negative macaques. Additionally, the Mamu-A1*001-specific antibody binds the cynomolgus macaque MHC class I ortholog Mafa-A1*001:01 but not variants Mafa-A1*001:02/03, indicating a high degree of binding specificity. The Mamu-A1*001-specific antibody will be useful for identifying Mamu-A1*001-positive rhesus macaques, for detecting Mamu-A1*001-positive cells in populations of Mamu-A1*001-negative cells, and for examining disease processes that alter expression of Mamu-A1*001 on cell surfaces. Moreover, the alloimmunization process we describe will be useful for isolating additional MHC allomorph-specific monoclonal antibodies or antibodies against other polymorphic host proteins which are difficult to isolate with traditional technologies.

  11. Next-generation phage display: integrating and comparing available molecular tools to enable cost-effective high-throughput analysis.

    Directory of Open Access Journals (Sweden)

    Emmanuel Dias-Neto

    2009-12-01

    Full Text Available Combinatorial phage display has been used in the last 20 years in the identification of protein-ligands and protein-protein interactions, uncovering relevant molecular recognition events. Rate-limiting steps of combinatorial phage display library selection are (i the counting of transducing units and (ii the sequencing of the encoded displayed ligands. Here, we adapted emerging genomic technologies to minimize such challenges.We gained efficiency by applying in tandem real-time PCR for rapid quantification to enable bacteria-free phage display library screening, and added phage DNA next-generation sequencing for large-scale ligand analysis, reporting a fully integrated set of high-throughput quantitative and analytical tools. The approach is far less labor-intensive and allows rigorous quantification; for medical applications, including selections in patients, it also represents an advance for quantitative distribution analysis and ligand identification of hundreds of thousands of targeted particles from patient-derived biopsy or autopsy in a longer timeframe post library administration. Additional advantages over current methods include increased sensitivity, less variability, enhanced linearity, scalability, and accuracy at much lower cost. Sequences obtained by qPhage plus pyrosequencing were similar to a dataset produced from conventional Sanger-sequenced transducing-units (TU, with no biases due to GC content, codon usage, and amino acid or peptide frequency. These tools allow phage display selection and ligand analysis at >1,000-fold faster rate, and reduce costs approximately 250-fold for generating 10(6 ligand sequences.Our analyses demonstrates that whereas this approach correlates with the traditional colony-counting, it is also capable of a much larger sampling, allowing a faster, less expensive, more accurate and consistent analysis of phage enrichment. Overall, qPhage plus pyrosequencing is superior to TU-counting plus Sanger

  12. Antibody phage display applications for nuclear medicine imaging and therapy

    International Nuclear Information System (INIS)

    Winthrop, M.D.; Denardo, G.L.; Denardo, S.J.

    2000-01-01

    Antibody-based constructs genetically engineered from genes of diverse origin provide a remarkable opportunity to develop functional molecular imaging techniques and specific molecular targeted radionuclide therapies. Phage display libraries of antibody fragment genes can be used to select antibody-based constructs that bind any chosen epitope. A large naive human antibody-based library was used to illustrate binding of antibody constructs to a variety of common and unique antigens. Antibody-based libraries from hybridoma cells, lymphocytes from immunized humans or from mice and human antibody repertoires produced in transgenic mice have also been described. Several orders of magnitude of affinity enhancement can be achieved by random or site specific mutations of the selected binding peptide domains of the scFv. Affinities (K d ) as high as 10 - 11 M (10 pM) for affinity-matured scFv have been documented. Such gene libraries thus offer an almost limitless variety of antibody-based molecular binding peptide modules that can be used in creative ways for the construction of new targeting agents for functional or molecular imaging and therapy

  13. Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays.

    Science.gov (United States)

    Chan, Conrad E Z; Chan, Annie H Y; Lim, Angeline P C; Hanson, Brendon J

    2011-10-28

    Rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. Non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. Such libraries can be constructed from a variety of sources e.g. B cell cDNA or synthetically generated, and use a variety of antibody formats, typically scFv or Fab. However, antibody source and format can impact on the quality of antibodies generated and hence the effectiveness of this methodology for the timely production of antibodies. We have carried out a comparative screening of two antibody libraries, a semi-synthetic scFv library and a human-derived Fab library against the protective antigen toxin component of Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown that while the synthetic library produced a diverse collection of specific scFv-phage, these contained a high frequency of unnatural amber stops and glycosylation sites which limited their conversion to IgG, and also a high number which lost specificity when expressed as IgG. In contrast, these limitations were overcome by the use of a natural human library. Antibodies from both libraries could be used to develop sandwich ELISA assays with similar sensitivity. However, the ease and speed with which full-length IgG could be generated from the human-derived Fab library makes screening this type of library the preferable method for rapid antibody generation for diagnostic assay development. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Compositional Bias in Naïve and Chemically-modified Phage-Displayed Libraries uncovered by Paired-end Deep Sequencing.

    Science.gov (United States)

    He, Bifang; Tjhung, Katrina F; Bennett, Nicholas J; Chou, Ying; Rau, Andrea; Huang, Jian; Derda, Ratmir

    2018-01-19

    Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a "naïve" library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

  15. Probing ADAMTS13 Substrate Specificity using Phage Display

    Science.gov (United States)

    Desch, Karl C.; Kretz, Colin; Yee, Andrew; Gildersleeve, Robert; Metzger, Kristin; Agrawal, Nidhi; Cheng, Jane; Ginsburg, David

    2015-01-01

    Von Willebrand factor (VWF) is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2’ and P11’, for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13–VWF exosite interactions outside of VWF73. PMID:25849793

  16. Probing ADAMTS13 substrate specificity using phage display.

    Directory of Open Access Journals (Sweden)

    Karl C Desch

    Full Text Available Von Willebrand factor (VWF is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2' and P11', for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13-VWF exosite interactions outside of VWF73.

  17. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  18. An anti-tumor protein produced by Trichinella spiralis and identified by screening a T7 phage display library, induces apoptosis in human hepatoma H7402 cells

    Science.gov (United States)

    Trichinella spiralis infection confers effective resistance to tumor cell expansion. In this study, a T7 phage cDNA display library was constructed to express genes encoded by T. spiralis. Organic phase multi-cell screening was used to sort through candidate proteins in a transfected human chronic m...

  19. Advances in phage display technology for drug discovery.

    Science.gov (United States)

    Omidfar, Kobra; Daneshpour, Maryam

    2015-06-01

    Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery. This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs. Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.

  20. Development of anti-infectives using phage display: biological agents against bacteria, viruses, and parasites.

    Science.gov (United States)

    Huang, Johnny X; Bishop-Hurley, Sharon L; Cooper, Matthew A

    2012-09-01

    The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

  1. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell

  2. Binding of phage displayed Bacillus subtilis lipase A to a phosphonate suicide inhibitor

    NARCIS (Netherlands)

    Dröge, M.J; Ruggeberg, C.J.; van der Sloot, Almer Martinus; Schimmel, J.; Dijkstra, Durk; Verhaert, R.M D; Reetz, M.T.; Quax, Wim; Droge, MJ; Dijkstra, DS

    2003-01-01

    Phage display can be used as a protein engineering tool to select proteins with desirable binding properties from a library of randomly constructed mutants. Here, we describe the development of this method for the directed evolution of Bacillus subtilis lipase A, an enzyme that has marked properties

  3. Construção de uma biblioteca de fragmentos de anticorpos monoclonais de galinhas com cadeia única (scFv por phage display com reatividade cruzada para estirpes heterólogas do vírus da bronquite infecciosa aviária Construction of an avian single chain monoclonal antibodies (scFv library by phage display that cross-reacted with heterologous avian infectious bronchitis virus strains

    Directory of Open Access Journals (Sweden)

    Camila Cesário Fernandes

    2010-06-01

    bronchitis virus strains (IBV. A phage display library was used, which was prepared previously against the IBV vaccine strain (H120 for the selection of new scFv antibody fragments specific for heterologous IBV strains isolated from outbreaks in Brazil (IBVPR01, IBVPR05 and USA (SE-17. After three cycles of panning, a set of 15 scFv antibodies were expressed in phages and cross-reacted in ELISA with these three viral strains. Western-blotting analysis showed that two of the clones were expressing scFv specific for the nucleoprotein of these IBV strains, as well as to the recombinant form of this protein derived from M41. In conclusion, the recombinant fragments of monoclonal antibodies expressed in phage have a great potential for future use in immunodiagnostic techniques and to study the evolution of infectious bronchitis virus.

  4. Efficient identification of phosphatidylserine-binding proteins by ORF phage display

    International Nuclear Information System (INIS)

    Caberoy, Nora B.; Zhou, Yixiong; Alvarado, Gabriela; Fan, Xianqun; Li, Wei

    2009-01-01

    To efficiently elucidate the biological roles of phosphatidylserine (PS), we developed open-reading-frame (ORF) phage display to identify PS-binding proteins. The procedure of phage panning was optimized with a phage clone expressing MFG-E8, a well-known PS-binding protein. Three rounds of phage panning with ORF phage display cDNA library resulted in ∼300-fold enrichment in PS-binding activity. A total of 17 PS-binding phage clones were identified. Unlike phage display with conventional cDNA libraries, all 17 PS-binding clones were ORFs encoding 13 real proteins. Sequence analysis revealed that all identified PS-specific phage clones had dimeric basic amino acid residues. GST fusion proteins were expressed for 3 PS-binding proteins and verified for their binding activity to PS liposomes, but not phosphatidylcholine liposomes. These results elucidated previously unknown PS-binding proteins and demonstrated that ORF phage display is a versatile technology capable of efficiently identifying binding proteins for non-protein molecules like PS.

  5. Identification of human embryonic progenitor cell targeting peptides using phage display.

    Directory of Open Access Journals (Sweden)

    Paola A Bignone

    Full Text Available Human pluripotent stem (hPS cells are capable of differentiation into derivatives of all three primary embryonic germ layers and can self-renew indefinitely. They therefore offer a potentially scalable source of replacement cells to treat a variety of degenerative diseases. The ability to reprogram adult cells to induced pluripotent stem (iPS cells has now enabled the possibility of patient-specific hPS cells as a source of cells for disease modeling, drug discovery, and potentially, cell replacement therapies. While reprogramming technology has dramatically increased the availability of normal and diseased hPS cell lines for basic research, a major bottleneck is the critical unmet need for more efficient methods of deriving well-defined cell populations from hPS cells. Phage display is a powerful method for selecting affinity ligands that could be used for identifying and potentially purifying a variety of cell types derived from hPS cells. However, identification of specific progenitor cell-binding peptides using phage display may be hindered by the large cellular heterogeneity present in differentiating hPS cell populations. We therefore tested the hypothesis that peptides selected for their ability to bind a clonal cell line derived from hPS cells would bind early progenitor cell types emerging from differentiating hPS cells. The human embryonic stem (hES cell-derived embryonic progenitor cell line, W10, was used and cell-targeting peptides were identified. Competition studies demonstrated specificity of peptide binding to the target cell surface. Efficient peptide targeted cell labeling was accomplished using multivalent peptide-quantum dot complexes as detected by fluorescence microscopy and flow cytometry. The cell-binding peptides were selective for differentiated hPS cells, had little or no binding on pluripotent cells, but preferential binding to certain embryonic progenitor cell lines and early endodermal hPS cell derivatives. Taken

  6. Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility.

    Science.gov (United States)

    Peng, Haiyong; Nerreter, Thomas; Chang, Jing; Qi, Junpeng; Li, Xiuling; Karunadharma, Pabalu; Martinez, Gustavo J; Fallahi, Mohammad; Soden, Jo; Freeth, Jim; Beerli, Roger R; Grawunder, Ulf; Hudecek, Michael; Rader, Christoph

    2017-09-15

    Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

    Directory of Open Access Journals (Sweden)

    Benjamin M Scott

    Full Text Available In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1 yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3 was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1 as a serpin amenable to phage display and suggest the utility of this approach for the selection

  8. Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

    Directory of Open Access Journals (Sweden)

    Xinwei Wang

    Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

  9. Improved Soluble ScFv ELISA Screening Approach for Antibody Discovery Using Phage Display Technology.

    Science.gov (United States)

    Tohidkia, Mohammad R; Sepehri, Maryam; Khajeh, Shirin; Barar, Jaleh; Omidi, Yadollah

    2017-09-01

    Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs. The expression of all scFv Abs was significantly enhanced when scFv clones were cultivated in the terrific broth (TB) medium at the optimum temperature of 30 °C. The protein A-conjugated with horseradish peroxidase (HRP) was found to be a well-suited reagent for the detection of Ag-bound scFvs in comparison with either anti-c-myc Ab or the mixing procedure. Based on our findings, it seems there is no universal media supplement for an improved expression of all scFvs derived from both Tomlinson I and J libraries. We thus propose that expression of scFv fragments in a microplate scale is largely dependent on a variety of parameters, in particular the scFv clones and relevant sequences.

  10. Challenges in Optimizing a Prostate Carcinoma Binding Peptide, Identified through the Phage Display Technology

    Directory of Open Access Journals (Sweden)

    Jürgen Debus

    2011-02-01

    Full Text Available The transfer of peptides identified through the phage display technology to clinical applications is difficult. Major drawbacks are the metabolic degradation and label instability. The aim of our work is the optimization of DUP-1, a peptide which was identified by phage display to specifically target human prostate carcinoma. To investigate the influence of chelate conjugation, DOTA was coupled to DUP-1 and labeling was performed with 111In. To improve serum stability cyclization of DUP-1 and targeted D-amino acid substitution were carried out. Alanine scanning was performed for identification of the binding site and based on the results peptide fragments were chemically synthesized. The properties of modified ligands were investigated in in vitro binding and competition assays. In vivo biodistribution studies were carried out in mice, carrying human prostate tumors subcutaneously. DOTA conjugation resulted in different cellular binding kinetics, rapid in vivo renal clearance and increased tumor-to-organ ratios. Cyclization and D-amino acid substitution increased the metabolic stability but led to binding affinity decrease. Fragment investigation indicated that the sequence NRAQDY might be significant for target-binding. Our results demonstrate challenges in optimizing peptides, identified through phage display libraries, and show that careful investigation of modified derivatives is necessary in order to improve their characteristics.

  11. Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Bifang He

    2013-01-01

    Full Text Available Metuximab is the generic name of Licartin, a new drug for radioimmunotherapy of hepatocellular carcinoma. Although it is known to be a mouse monoclonal antibody against CD147, the complete epitope mediating the binding of metuximab to CD147 remains unknown. We panned the Ph.D.-12 phage display peptide library against metuximab and got six mimotopes. The following bioinformatics analysis based on mimotopes suggested that metuximab recognizes a conformational epitope composed of more than 20 residues. The residues of its epitope may include T28, V30, K36, L38, K57, F74, D77, S78, D79, D80, Q81, G83, S86, N98, Q100, L101, H102, G103, P104, V131, P132, and K191. The homology modeling of metuximab and the docking of CD147 to metuximab were also performed. Based on the top one docking model, the epitope was predicted to contain 28 residues: AGTVFTTV (23–30, I37, D45, E84, V88, EPMGTANIQLH (92–102, VPP (131–133, Q164, and K191. Almost half of the residues predicted on the basis of mimotope analysis also appear in the docking result, indicating that both results are reliable. As the predicted epitopes of metuximab largely overlap with interfaces of CD147-CD147 interactions, a structural mechanism of metuximab is proposed as blocking the formation of CD147 dimer.

  12. Phage Display-Derived Cross-Reactive Neutralizing Antibody against Enterovirus 71 and Coxsackievirus A16.

    Science.gov (United States)

    Zhang, Xiao; Sun, Chunyun; Xiao, Xiangqian; Pang, Lin; Shen, Sisi; Zhang, Jie; Cen, Shan; Yang, Burton B; Huang, Yuming; Sheng, Wang; Zeng, Yi

    2016-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are members of the Picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (HFMD). In recent decades large HFMD outbreaks caused by EV71 and CVA16 have become significant public health concerns in the Asia-Pacific region. Vaccines and antiviral drugs are unavailable to prevent EV71 and CVA16 infection. In the current study, a chimeric antibody targeting a highly conserved peptide in the EV71 VP4 protein was isolated by using a phage display technique. The antibody showed cross-neutralizing capability against EV71 and CVA16 in vitro. The results suggest that this phage display-derived antibody will have great potential as a broad neutralizing antibody against EV71 and CVA16 after affinity maturation and humanization.

  13. TfR Binding Peptide Screened by Phage Display Technology ...

    African Journals Online (AJOL)

    Purpose: To screen an hTfR affinity peptide and investigate its activity in vitro. Methods: hTfR ... Keywords: Peptide, hTfR, Transferrin receptor, Phage display technology, Enhanced green ..... mediated uptake of peptides that bind the human.

  14. Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach

    Directory of Open Access Journals (Sweden)

    Barth Stefan

    2005-01-01

    Full Text Available Abstract Background Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials. Results The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans. Conclusions Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases.

  15. Selection of phage-displayed peptides for the detection of imidacloprid in water and soil.

    Science.gov (United States)

    Liu, Zhiping; Liu, Jianfeng; Wang, Kai; Li, Wenhui; Shelver, Weilin L; Li, Qing X; Li, Ji; Xu, Ting

    2015-09-15

    Imidacloprid is the most widely used neonicotinoid insecticide in the world and shows widespread environment and human exposures. A phage clone designated L7-1 that selectively binds to imidacloprid was selected from a commercial phage display library containing linear 7-mer randomized amino acid residues. Using the clone L7-1, a competitive enzyme-linked immunosorbent assay (ELISA) for imidacloprid was developed. The half-maximum signal inhibition concentration (IC50) and the limit of detection (LOD) of the phage ELISA for imidacloprid were 96 and 2.3 ng ml(-1), respectively. This phage ELISA showed relatively low cross-reactivity with all of the tested compounds structurally similar to imidacloprid, less than 2% with the exception of 6-chloronicotinic acid, a metabolite of imidacloprid that showed 11.5%. The average recoveries of the phage ELISA for imidacloprid in water and soil samples were in the ranges of 74.6 to 86.3% and 72.5 to 93.6%, respectively. The results of the competitive phage ELISA for imidacloprid in the fortified samples agreed well with those of a high-performance liquid chromatography (HPLC) method. The simple phage-displayed peptide technology has been proven to be a convenient and efficient method for the development of an alternative format of ELISA for small molecules. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display.

    Directory of Open Access Journals (Sweden)

    Daniel O Connor

    Full Text Available Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.

  17. Selection of phage-displayed accessible recombinant targeted antibodies (SPARTA): methodology and applications.

    Science.gov (United States)

    D'Angelo, Sara; Staquicini, Fernanda I; Ferrara, Fortunato; Staquicini, Daniela I; Sharma, Geetanjali; Tarleton, Christy A; Nguyen, Huynh; Naranjo, Leslie A; Sidman, Richard L; Arap, Wadih; Bradbury, Andrew Rm; Pasqualini, Renata

    2018-05-03

    We developed a potentially novel and robust antibody discovery methodology, termed selection of phage-displayed accessible recombinant targeted antibodies (SPARTA). This combines an in vitro screening step of a naive human antibody library against known tumor targets, with in vivo selections based on tumor-homing capabilities of a preenriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human antibodies amenable to rapid translation into medical applications. As a proof of concept, we evaluated SPARTA on 2 well-established tumor cell surface targets, EphA5 and GRP78. We evaluated antibodies that showed tumor-targeting selectivity as a representative panel of antibody-drug conjugates (ADCs) and were highly efficacious. Our results validate a discovery platform to identify and validate monoclonal antibodies with favorable tumor-targeting attributes. This approach may also extend to other diseases with known cell surface targets and affected tissues easily isolated for in vivo selection.

  18. Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2.

    Science.gov (United States)

    Keresztessy, Zsolt; Csosz, Eva; Hársfalvi, Jolán; Csomós, Krisztián; Gray, Joe; Lightowlers, Robert N; Lakey, Jeremy H; Balajthy, Zoltán; Fésüs, László

    2006-11-01

    Understanding substrate specificity and identification of natural targets of transglutaminase 2 (TG2), the ubiquitous multifunctional cross-linking enzyme, which forms isopeptide bonds between protein-linked glutamine and lysine residues, is crucial in the elucidation of its physiological role. As a novel means of specificity analysis, we adapted the phage display technique to select glutamine-donor substrates from a random heptapeptide library via binding to recombinant TG2 and elution with a synthetic amine-donor substrate. Twenty-six Gln-containing sequences from the second and third biopanning rounds were susceptible for TG2-mediated incorporation of 5-(biotinamido)penthylamine, and the peptides GQQQTPY, GLQQASV, and WQTPMNS were modified most efficiently. A consensus around glutamines was established as pQX(P,T,S)l, which is consistent with identified substrates listed in the TRANSDAB database. Database searches showed that several proteins contain peptides similar to the phage-selected sequences, and the N-terminal glutamine-rich domain of SWI1/SNF1-related chromatin remodeling proteins was chosen for detailed analysis. MALDI/TOF and tandem mass spectrometry-based studies of a representative part of the domain, SGYGQQGQTPYYNQQSPHPQQQQPPYS (SnQ1), revealed that Q(6), Q(8), and Q(22) are modified by TG2. Kinetic parameters of SnQ1 transamidation (K(M)(app) = 250 microM, k(cat) = 18.3 sec(-1), and k(cat)/K(M)(app) = 73,200) classify it as an efficient TG2 substrate. Circular dichroism spectra indicated that SnQ1 has a random coil conformation, supporting its accessibility in the full-length parental protein. Added together, here we report a novel use of the phage display technology with great potential in transglutaminase research.

  19. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued.

    Science.gov (United States)

    van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I; Lappalainen, Jari P; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J; Verrijp, Kiek; Leenders, William P J

    2016-11-01

    Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells. Such tumor vessel targeting requires the identification of tumor-specific vascular targeting agents (TVTAs).Here we describe a novel TVTA, C-C7, which we identified via in vivo biopanning of a llama nanobody phage display library in an orthotopic mouse model of diffuse glioma. We show that C-C7 recognizes a subpopulation of tumor blood vessels in glioma xenografts and clinical glioma samples. Additionally, C-C7 recognizes macrophages and activated endothelial cells in atherosclerotic lesions. By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified dynactin-1-p150Glued as its binding partner. The interaction was confirmed by co-immunostainings with C-C7 and a commercial anti-dynactin-1-p150Glued antibody, and via co-immunoprecipitation/western blot studies. Normal brain vessels do not express dynactin-1-p150Glued and its expression is reduced under anti-VEGF therapy, suggesting that dynactin-1-p150Glued is a marker for activated endothelial cells.In conclusion, we show that in vivo phage display combined with Y2H screenings provides a powerful approach to identify tumor-targeting nanobodies and their binding partners. Using this combination of methods we identify dynactin-1-p150Glued as a novel targetable protein on activated endothelial cells and macrophages.

  20. Affinity isolation of antigen-specific circulating B cells for generation of phage display-derived human monoclonal antibodies

    DEFF Research Database (Denmark)

    Ditzel, Henrik

    2009-01-01

    A method is described for affinity isolation of antigen-specific circulating B cells of interest for subsequent generation of immune antibody phage display libraries. This approach should overcome the problem of low yields of monoclonal antibodies of interest in the libraries generated from...... peripheral blood lymphocytes caused by the low abundance of antigen-specific B cells in the circulation. The preselection of B cells is based on the specificity of the surface Ig receptor and is accomplished using the antigen of interest conjugated to magnetic beads. This method should significantly increase...... the frequency of antibody phage particles of interest in the library and allow for efficient isolation monoclonal antibodies with the predefined specificity....

  1. Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

    Directory of Open Access Journals (Sweden)

    Blewett Ann

    2008-12-01

    Full Text Available Abstract Background To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme. Results Screening of a phage display 12-mer library using purified P. aeruginosa MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP-MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified the inhibition. The IC50 value of MurFp1 was evaluated at 250 μM, and the Ki was established at 420 μM with respect to the mixed type of inhibition against D-Ala-D-Ala. Conclusion MurFp1 exerts its inhibitory action by interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme. We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural changes for better interaction with the enzyme. We present the first peptide inhibitor of MurF, an enzyme that should be exploited as a target for antimicrobial drug development.

  2. Large-scale DNA Barcode Library Generation for Biomolecule Identification in High-throughput Screens.

    Science.gov (United States)

    Lyons, Eli; Sheridan, Paul; Tremmel, Georg; Miyano, Satoru; Sugano, Sumio

    2017-10-24

    High-throughput screens allow for the identification of specific biomolecules with characteristics of interest. In barcoded screens, DNA barcodes are linked to target biomolecules in a manner allowing for the target molecules making up a library to be identified by sequencing the DNA barcodes using Next Generation Sequencing. To be useful in experimental settings, the DNA barcodes in a library must satisfy certain constraints related to GC content, homopolymer length, Hamming distance, and blacklisted subsequences. Here we report a novel framework to quickly generate large-scale libraries of DNA barcodes for use in high-throughput screens. We show that our framework dramatically reduces the computation time required to generate large-scale DNA barcode libraries, compared with a naїve approach to DNA barcode library generation. As a proof of concept, we demonstrate that our framework is able to generate a library consisting of one million DNA barcodes for use in a fragment antibody phage display screening experiment. We also report generating a general purpose one billion DNA barcode library, the largest such library yet reported in literature. Our results demonstrate the value of our novel large-scale DNA barcode library generation framework for use in high-throughput screening applications.

  3. Chemical Synthesis and In Vitro Evaluation of a Phage Display-Derived Peptide Active against Infectious Salmon Anemia Virus.

    Science.gov (United States)

    Ojeda, Nicolás; Cárdenas, Constanza; Guzmán, Fanny; Marshall, Sergio H

    2016-04-01

    Infectious salmon anemia virus (ISAV) is the etiological agent of the disease by the same name and causes major losses in the salmon industry worldwide. Epizootic ISAV outbreaks have occurred in Norway and, to a lesser degree, in Canada. In 2007, an ISAV outbreak in Chile destroyed most of the seasonal production and endangered the entire Chilean salmon industry. None of the existing prophylactic approaches have demonstrated efficacy in providing absolute protection from or even a palliative effect on ISAV proliferation. Sanitary control measures for ISAV, based on molecular epidemiology data, have proven insufficient, mainly due to high salmon culture densities and a constant presence of a nonpathogenic strain of the virus. This report describes an alternative treatment approach based on interfering peptides selected from a phage display library. The screening of a phage display heptapeptide library resulted in the selection of a novel peptide with significant in vitro antiviral activity against ISAV. This peptide specifically interacted with the viral hemagglutinin-esterase protein, thereby impairing virus binding, with plaque reduction assays showing a significant reduction in viral yields. The identified peptide acts at micromolar concentrations against at least two different pathogenic strains of the virus, without detectable cytotoxic effects on the tested fish cells. Therefore, antiviral peptides represent a novel alternative for controlling ISAV and, potentially, other fish pathogens. Identifying novel methods for the efficient control of infectious diseases is imperative for the future of global aquaculture. The present study used a phage display heptapeptide library to identify a peptide with interfering activity against a key protein of the infectious salmon anemia virus (ISAV). A piscine orthomyxovirus, ISAV is a continuous threat to the commercial sustainability of cultured salmon production worldwide. The complex epidemiological strategy of this

  4. Production of a phage-displayed single chain variable fragment ...

    African Journals Online (AJOL)

    Abstract. Purpose: To develop specific single chain variable fragments (scFv) against ... libraries. The binding ability of the selected scFv antibody fragments against the IBDV particles was ..... Hermelink H, Koscielniak E. A human recombinant.

  5. Phage display selects for amylases with improved low pH starch-binding

    NARCIS (Netherlands)

    Verhaert, RMD; Beekwilder, J; Olsthoorn, R; Quax, WJ; Duin, Jan van

    2002-01-01

    Directed evolution of secreted industrial enzymes is hampered by the lack of powerful selection techniques. We have explored surface display to select for enzyme variants with improved binding performance on complex polymeric substrates. By a combination of saturation mutagenesis and phage display

  6. Isolation of llama antibody fragments for prevention of dandruff by phage display in shampoo

    NARCIS (Netherlands)

    Dolk, E.; Vaart, M. van der; Lutje Hulsik, D.; Vriend, G.; Haard, H. de; Spinelli, S.; Cambillau, C.; Frenken, L.; Verrips, T.

    As part of research exploring the feasibility of using antibody fragments to inhibit the growth of organisms implicated in dandruff, we isolated antibody fragments that bind to a cell surface protein of Malassezia furfur in the presence of shampoo. We found that phage display of llama

  7. Phage display as a promising approach for vaccine development

    OpenAIRE

    Aghebati-Maleki, Leili; Bakhshinejad, Babak; Baradaran, Behzad; Motallebnezhad, Morteza; Aghebati-Maleki, Ali; Nickho, Hamid; Yousefi, Mehdi; Majidi, Jafar

    2016-01-01

    Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mamm...

  8. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display.

    Science.gov (United States)

    Dooley, Helen; Flajnik, Martin F; Porter, Andrew J

    2003-09-01

    The novel immunoglobulin isotype novel antigen receptor (IgNAR) is found in cartilaginous fish and is composed of a heavy-chain homodimer that does not associate with light chains. The variable regions of IgNAR function as independent domains similar to those found in the heavy-chain immunoglobulins of Camelids. Here, we describe the successful cloning and generation of a phage-displayed, single-domain library based upon the variable domain of IgNAR. Selection of such a library generated from nurse sharks (Ginglymostoma cirratum) immunized with the model antigen hen egg-white lysozyme (HEL) enabled the successful isolation of intact antigen-specific binders matured in vivo. The selected variable domains were shown to be functionally expressed in Escherichia coli, extremely stable, and bind to antigen specifically with an affinity in the nanomolar range. This approach can therefore be considered as an alternative route for the isolation of minimal antigen-binding fragments with favorable characteristics.

  9. Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display.

    Science.gov (United States)

    Yuan, Qing; Jordan, Ramon; Brlansky, Ronald H; Istomina, Olga; Hartung, John

    2015-10-01

    Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Antibody based detection assays are commercially available for X. fastidiosa, and are effective at the species, but not at the subspecies level. We have made a library of scFv antibody fragments directed against X. fastidiosa subsp. pauca strain 9a5c (citrus) by using phage display technology. Antibody gene repertoires were PCR-amplified using 23 primers for the heavy chain variable region (V(H)) and 21 primers for the light chain variable region (V(L)). The V(H) and V(L) were joined by overlap extension PCR, and then the genes of the scFv library were ligated into the phage vector pKM19. The library contained 1.2×10(7) independent clones with full-length scFv inserts. In each of 3cycles of affinity-selection with 9a5c, about 1.0×10(12) phage were used for panning with 4.1×10(6), 7.1×10(6), 2.1×10(7) phage recovered after the first, second and third cycles, respectively. Sixty-six percent of clones from the final library bound X. fastidiosa 9a5c in an ELISA. Some of these scFv antibodies recognized strain 9a5c and did not recognize X. fastidiosa strains that cause Pierce's disease of grapevine. Published by Elsevier B.V.

  10. Phage-Displayed Peptides Selected to Bind Envelope Glycoprotein Show Antiviral Activity against Dengue Virus Serotype 2

    Directory of Open Access Journals (Sweden)

    Carolina de la Guardia

    2017-01-01

    Full Text Available Dengue virus is a growing public health threat that affects hundreds of million peoples every year and leave huge economic and social damage. The virus is transmitted by mosquitoes and the incidence of the disease is increasing, among other causes, due to the geographical expansion of the vector’s range and the lack of effectiveness in public health interventions in most prevalent countries. So far, no highly effective vaccine or antiviral has been developed for this virus. Here we employed phage display technology to identify peptides able to block the DENV2. A random peptide library presented in M13 phages was screened with recombinant dengue envelope and its fragment domain III. After four rounds of panning, several binding peptides were identified, synthesized, and tested against the virus. Three peptides were able to block the infectivity of the virus while not being toxic to the target cells. Blind docking simulations were done to investigate the possible mode of binding, showing that all peptides appear to bind domain III of the protein and may be mostly stabilized by hydrophobic interactions. These results are relevant to the development of novel therapeutics against this important virus.

  11. Identification and characterisation of the proteins bound by specific phage-displayed recombinant antibodies (scFv) obtained against Brazil nut and almond extracts.

    Science.gov (United States)

    de la Cruz, Silvia; Madrid, Raquel; García-García, Aina; Alcocer, Marcos; Martín, Rosario; González, Isabel; García, Teresa

    2018-03-01

    Almonds and Brazil nuts are widely consumed allergenic nuts whose presence must be declared according to food labelling regulations. Their detection in food products has been recently achieved by ELISA methods with recombinant antibodies (scFv) isolated against complete Brazil nut and almond protein extracts. The screening of phage-scFv libraries against complete protein extracts confers a series of advantages over the use of purified proteins, as recombinant proteins might alter their native folding. However, using this strategy, the nature of the target detected by phage-displayed antibodies remains unknown, and requires further research to identify whether they are nut allergens or other molecules present in the extract, but not related to their allergenic potential. Electrophoretic, chromatographic, immunological and spectrometric techniques revealed that the Brazil nut (BE95) and almond (PD1F6 and PD2C9) specific phage-scFvs detected conformational epitopes of the Brazil nut and almond 11S globulins, recognised by WHO/IUIS as Ber e 2 and Pru du 6 major allergens. Circular dichroism data indicated that severe heat treatment would entail loss of epitope structure, disabling scFv for target detection. The presence of important Brazil nut and almond allergens (Ber e 2 and Pru du 6) in foodstuffs can be determined by using phage-display antibodies BE95, PD1F6 and PD2C9 as affinity probes in ELISA. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Identification of keratinocyte specific markers using phage display and mass spectrometry

    DEFF Research Database (Denmark)

    Jensen, K.B.; Jensen, O.N.; Ravn, P.

    2003-01-01

    and mass spectrometry that allows identification of cell type-specific protein markers. The most important features of the method are (i) reduction of experimental noise originating from background binding of phage particles and (ii) isolation of affinity binders after a single round of selection, which...... antigens were subsequently identified by mass spectrometry as laminin-5, plectin, and fibronectin. The combination of phage display technology with mass spectrometry methods for protein identification is a general and promising approach for proteomic analysis of cell surface complexity....

  13. Synthesis of tumor necrosis factor α for use as a mirror-image phage display target.

    Science.gov (United States)

    Petersen, Mark E; Jacobsen, Michael T; Kay, Michael S

    2016-06-21

    Tumor Necrosis Factor alpha (TNFα) is an inflammatory cytokine that plays a central role in the pathogenesis of chronic inflammatory disease. Here we describe the chemical synthesis of l-TNFα along with the mirror-image d-protein for use as a phage display target. The synthetic strategy utilized native chemical ligation and desulfurization to unite three peptide segments, followed by oxidative folding to assemble the 52 kDa homotrimeric protein. This synthesis represents the foundational step for discovering an inhibitory d-peptide with the potential to improve current anti-TNFα therapeutic strategies.

  14. Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla Jael Rubner

    2016-01-01

    BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody...... fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers. MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against...

  15. Biotin-tagged proteins: Reagents for efficient ELISA-based serodiagnosis and phage display-based affinity selection.

    Science.gov (United States)

    Verma, Vaishali; Kaur, Charanpreet; Grover, Payal; Gupta, Amita; Chaudhary, Vijay K

    2018-01-01

    The high-affinity interaction between biotin and streptavidin has opened avenues for using recombinant proteins with site-specific biotinylation to achieve efficient and directional immobilization. The site-specific biotinylation of proteins carrying a 15 amino acid long Biotin Acceptor Peptide tag (BAP; also known as AviTag) is effected on a specific lysine either by co-expressing the E. coli BirA enzyme in vivo or by using purified recombinant E. coli BirA enzyme in the presence of ATP and biotin in vitro. In this paper, we have designed a T7 promoter-lac operator-based expression vector for rapid and efficient cloning, and high-level cytosolic expression of proteins carrying a C-terminal BAP tag in E. coli with TEV protease cleavable N-terminal deca-histidine tag, useful for initial purification. Furthermore, a robust three-step purification pipeline integrated with well-optimized protocols for TEV protease-based H10 tag removal, and recombinant BirA enzyme-based site-specific in vitro biotinylation is described to obtain highly pure biotinylated proteins. Most importantly, the paper demonstrates superior sensitivities in indirect ELISA with directional and efficient immobilization of biotin-tagged proteins on streptavidin-coated surfaces in comparison to passive immobilization. The use of biotin-tagged proteins through specific immobilization also allows more efficient selection of binders from a phage-displayed naïve antibody library. In addition, for both these applications, specific immobilization requires much less amount of protein as compared to passive immobilization and can be easily multiplexed. The simplified strategy described here for the production of highly pure biotin-tagged proteins will find use in numerous applications, including those, which may require immobilization of multiple proteins simultaneously on a solid surface.

  16. Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology.

    Directory of Open Access Journals (Sweden)

    Chen Xu

    2010-03-01

    Full Text Available Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC, but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule.

  17. Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials.

    Science.gov (United States)

    Ramaraju, Harsha; Miller, Sharon J; Kohn, David H

    2017-07-01

    Design of biomaterials for cell-based therapies requires presentation of specific physical and chemical cues to cells, analogous to cues provided by native extracellular matrices (ECM). We previously identified a peptide sequence with high affinity towards apatite (VTKHLNQISQSY, VTK) using phage display. The aims of this study were to identify a human MSC-specific peptide sequence through phage display, combine it with the apatite-specific sequence, and verify the specificity of the combined dual-functioning peptide to both apatite and human bone marrow stromal cells. In this study, a combinatorial phage display identified the cell binding sequence (DPIYALSWSGMA, DPI) which was combined with the mineral binding sequence to generate the dual peptide DPI-VTK. DPI-VTK demonstrated significantly greater binding affinity (1/K D ) to apatite surfaces compared to VTK, phosphorylated VTK (VTK phos ), DPI-VTK phos , RGD-VTK, and peptide-free apatite surfaces (p biomaterial surfaces and subsequently increase cell proliferation and differentiation. These new peptides expand biomaterial design methodology for cell-based regeneration of bone defects. This strategy of combining cell and material binding phage display derived peptides is broadly applicable to a variety of systems requiring targeted adhesion of specific cell populations, and may be generalized to the engineering of any adhesion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Generation of a Highly Reactive Chicken-Derived Single-Chain Variable Fragment against Fusarium verticillioides by Phage Display

    Directory of Open Access Journals (Sweden)

    Zu-Quan Hu

    2012-06-01

    Full Text Available Fusarium verticillioides is the primary causal agent of Fusarium ear and kernel rot in maize, producing fumonisin mycotoxins that are toxic to humans and domestic animals. Rapid detection and monitoring of fumonisin-producing fungi are pivotally important for the prevention of mycotoxins from entering into food/feed products. Chicken-derived single-chain variable fragments (scFvs against cell wall-bound proteins from F. verticillioides were isolated from an immunocompetent phage display library. Comparative phage enzyme-linked immunosorbant assays (ELISAs and sequencing analyses identified four different scFv antibodies with high sensitivity. Soluble antibody ELISAs identified two highly sensitive scFv antibodies, FvCA3 and FvCA4, with the latter being slightly more sensitive. Three-dimensional modeling revealed that the FvCA4 may hold a better overall structure with CDRH3, CDRL1 and CDRL3 centered in the core region of antibody surface compared with that of other scFvs. Immunofluorescence labeling revealed that the binding of FvCA4 antibody was localized to the cell walls of conidiospores and hyphae of F. verticillioides, confirming the specificity of this antibody for a surface target. This scFv antibody was able to detect the fungal mycelium as low as 10−2 μg/mL and contaminating mycelium at a quantity of 10−2 mg/g maize. This is the first report that scFv antibodies derived from phage display have a wide application for rapid and accurate detection and monitoring of fumonisin-producing pathogens in agricultural samples.

  19. Use of a Phage-Display Method to Identify Peptides that Bind to a Tin Oxide Nanosheets.

    Science.gov (United States)

    Nakazawa, Hikaru; Seta, Yasuko; Hirose, Tatsuya; Masuda, Yoshitake; Umetsu, Mitsuo

    2018-01-01

    Nanosheets of SnO2 which an n-type semiconductor with a rutile-type crystalline structure are predominantly used as gas sensors. SnO2 nanosheets have a tetragonal crystal structure where growth along the c-axis is suppressed to form a sheet. The major exposed facets of SnO2 nanosheets have {110}, {101} and {211} crystal planes along the a-axis, with the reduced {110} surface having a particularly high surface energy. Identifying peptides that bind to specific crystal planes by using peptide phage-display approach will increase the potential applications of metal oxide nanomaterials by fusing proteins with desirable active sites to peptides that adsorb at high density on the major exposed crystal plane of nanosheets. It may be possible to construct highly sensitive biosensors. The main objective of the present study is to identify peptides that adsorb preferentially to a SnO2 nanosheet by using peptide-phage display approach. Four milligrams of SnO2 nanosheet were mixed with 1011 plaque-forming units of Ph.D.-12 Phage Display Peptide Library. Phage-bound nanosheet particles were washed 10 times with 1 mL of phosphatebuffered saline containing 0.5% Tween 20. Phages bound to the nanosheet were eluted with three different buffers: (1) high-salt buffer containing 2 M NaCl (pH 7.5); (2) acidic buffer containing 200 mM Gly-HCl (pH 2.2); and (3) high-phosphate-ion buffer containing 500 mM NaH2PO4 (pH 7.5). The eluted phages were subjected to four or five rounds of biopanning. At each round, individual plaques were picked from the plates, and the amino acid sequences of the peptides were identified by DNA sequencing. The identified SnO2-binding peptides labeled with fluorescein isothiocyanate were synthesized. Adsorption isotherms were constructed at peptide concentrations ranging from 0.25 to 2.0 µM with 4mg of nanomaterials. We were determined the sequences of 11 clones with the high-salt buffer, 7 with the high-phosphateion buffers, and 6 with the acidic buffer and

  20. Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Seraina Cooksley-Decasper

    Full Text Available To date, no plaque-derived blood biomarker is available to allow diagnosis, prognosis or monitoring of atherosclerotic vascular diseases. In this study, specimens of thrombendarterectomy material from carotid and iliac arteries were incubated in protein-free medium to obtain plaque and control secretomes for subsequent subtractive phage display. The selection of nine plaque secretome-specific antibodies and the analysis of their immunopurified antigens by mass spectrometry led to the identification of 22 proteins. One of them, junction plakoglobin (JUP-81 and its smaller isoforms (referred to as JUP-63, JUP-55 and JUP-30 by molecular weight were confirmed by immunohistochemistry and immunoblotting with independent antibodies to be present in atherosclerotic plaques and their secretomes, coronary thrombi of patients with acute coronary syndrome (ACS and macrophages differentiated from peripheral blood monocytes as well as macrophage-like cells differentiated from THP1 cells. Plasma of patients with stable coronary artery disease (CAD (n = 15 and ACS (n = 11 contained JUP-81 at more than 2- and 14-fold higher median concentrations, respectively, than plasma of CAD-free individuals (n = 13. In conclusion, this proof of principle study identified and verified JUP isoforms as potential plasma biomarkers for atherosclerosis. Clinical validation studies are needed to determine its diagnostic efficacy and clinical utility as a biomarker for diagnosis, prognosis or monitoring of atherosclerotic vascular diseases.

  1. Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology

    Directory of Open Access Journals (Sweden)

    Kotaro Sakamoto

    2017-09-01

    Full Text Available ActRIIB (activin receptor type-2B is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN, growth differentiation factor 11 (GDF11, and bone morphogenetic protein 9 (BMP9. Notably, the protein-protein interaction (PPI between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9, AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

  2. Mapping of epitopes for autoantibodies to the Type 1 diabetes autoantigen IA-2 by peptide phage display and molecular modelling: Overlap of antibody and T-cell determinants

    DEFF Research Database (Denmark)

    A. Dromey, James; Weenink, Sarah M.; Peters, Günther H.J.

    2004-01-01

    IA-2 is a major target of autoimmunity in type 1 diabetes. IA-2 responsive T cells recognize determinants within regions represented by amino acids 787–817 and 841–869 of the molecule. Epitopes for IA-2 autoantibodies are largely conformational and not well defined. In this study, we used peptide......, and aromatic residues and amino acids contributing to the epitope investigated using site-directed mutagenesis. Mutation of each of amino acids Asn858, Glu836, and Trp799 reduced 96/3 Ab binding by >45%. Mutations of these residues also inhibited binding of serum autoantibodies from IA-2 Ab-positive type 1...... phage display and homology modeling to characterize the epitope of a monoclonal IA-2 Ab (96/3) from a human type 1 diabetic patient. This Ab competes for IA-2 binding with Abs from the majority of patients with type 1 diabetes and therefore binds a region close to common autoantibody epitopes. Alignment...

  3. Combining EL4-B5-based B-cell stimulation and phage display technology for the successful isolation of human anti-Scl-70 autoantibody fragments.

    Science.gov (United States)

    Weber, Malte; Weiss, Etienne; Engel, Alfred M

    2003-07-01

    Scl-70 is the major antigen recognised by autoantibodies in the sera of patients with systemic sclerosis (SSc). The autoantibodies that specifically react with Scl-70 are highly characteristic of the disease and represent valuable markers for the diagnosis of SSc. We describe a novel strategy for cloning autoantibody fragments starting with a small blood sample from an SSc patient. B cells isolated from the collected peripheral blood mononuclear cells (PBMCs) were cultured in vitro using the EL4-B5 system. Anti-Scl-70 IgG-producing cells were pooled for RNA preparation followed by the generation of phagemid libraries of approximately 10(7) independent single-chain Fvs (scFvs). The screening of these libraries by phage display allowed us to isolate four anti-Scl-70 scFvs following three rounds of biopanning. About 10 times more starting blood material was needed to generate scFv libraries of similar size from PBMCs of an SSc patient and only two anti-Scl-70 scFvs were isolated after three rounds of phage selection. Together, this work shows that functional autoantibody fragments can be advantageously cloned after in vitro expansion of B cells. The isolated anti-Scl-70 autoantibody fragments represent useful tools for calibrating SSc diagnostic assays.

  4. Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

    Directory of Open Access Journals (Sweden)

    Chinestra Patrick

    2008-03-01

    Full Text Available Abstract Background The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. Results After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L, three scFvs (A8, C1 and D11 were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2, it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence. Conclusion We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated

  5. Discovery of Selective Nanobodies against α-elapitoxin Dpp2c from Black Mamba through Phage Display Screening

    DEFF Research Database (Denmark)

    Milbo, Christina; Laustsen, Andreas Hougaard; Lohse, Brian

    Feared for its highly neurotoxic venom and rapid attack technique, the Black mamba (Dendroaspis polylepis) is Africa’s largest venomous snake. The clinical manifestations of a bitefrom D. polylepis include flaccid paralysis leading to respiratory failure and death due to postsynaptic blockade of ......-neurotoxins. Here, we report the discovery of selective nanobodies targeting α-elapitoxin Dpp2c from D. polylepis through phage display screening....

  6. Quantitative PET Imaging with Novel HER3 Targeted Peptides Selected by Phage Display to Predict Androgen Independent Prostate Cancer Progression

    Science.gov (United States)

    2017-08-01

    Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...3. DATES COVERED 1 Aug 2016 – 31 July 2017 4. TITLE AND SUBTITLE Cancer Progression 5a. CONTRACT NUMBER Quantitative PET Imaging with Novel HER3...Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-16-1-0447 5c

  7. A Novel Affinity Tag, ABTAG, and Its Application to the Affinity Screening of Single-Domain Antibodies Selected by Phage Display

    Directory of Open Access Journals (Sweden)

    Greg Hussack

    2017-10-01

    Full Text Available ABTAG is a camelid single-domain antibody (sdAb that binds to bovine serum albumin (BSA with low picomolar affinity. In surface plasmon resonance (SPR analyses using BSA surfaces, bound ABTAG can be completely dissociated from the BSA surfaces at low pH, over multiple cycles, without any reduction in the capacity of the BSA surfaces to bind ABTAG. A moderate throughput, SPR-based, antibody screening assay exploiting the unique features of ABTAG is described. Anti-carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 sdAbs were isolated from a phage-displayed sdAb library derived from the heavy chain antibody repertoire of a llama immunized with CEACAM6. Following one or two rounds of panning, enriched clones were expressed as ABTAG fusions in microtiter plate cultures. The sdAb-ABTAG fusions from culture supernatants were captured on BSA surfaces and CEACAM6 antigen was then bound to the captured molecules. The SPR screening method gives a read-out of relative expression levels of the fusion proteins and kinetic and affinity constants for CEACAM6 binding by the captured molecules. The library was also panned and screened by conventional methods and positive clones were subcloned and expressed for SPR analysis. Compared to conventional panning and screening, the SPR-based ABTAG method yielded a considerably higher diversity of binders, some with affinities that were three orders of magnitude higher affinity than those identified by conventional panning.

  8. Rapid Isolation of a Single-Chain Antibody against the Cyanobacterial Toxin Microcystin-LR by Phage Display and Its Use in the Immunoaffinity Concentration of Microcystins from Water

    Science.gov (United States)

    McElhiney, Jacqui; Drever, Mathew; Lawton, Linda A.; Porter, Andy J.

    2002-01-01

    A naïve (unimmunized) human semisynthetic phage display library was employed to isolate recombinant antibody fragments against the cyanobacterial hepatotoxin microcystin-LR. Selected antibody scFv genes were cloned into a soluble expression vector and expressed in Escherichia coli for characterization against purified microcystin-LR by competition enzyme-linked immunosorbent assay (ELISA). The most sensitive single-chain antibody (scAb) isolated was capable of detecting microcystin-LR at levels below the World Health Organization limit in drinking water (1 μg liter−1) and cross-reacted with three other purified microcystin variants (microcystin-RR, -LW, and -LF) and the related cyanotoxin nodularin. Extracts of the cyanobacterium Microcystis aeruginosa were assayed by ELISA, and quantifications of microcystins in toxic samples showed good correlation with analysis by high-performance liquid chromatography. Immobilized scAb was also used to prepare immunoaffinity columns, which were assessed for the ability to concentrate microcystin-LR from water for subsequent analysis by high-performance liquid chromatography. Anti-microcystin-LR scAb was immobilized on columns via a hexahistidine tag, ensuring maximum exposure of antigen binding sites, and the performance of the columns was evaluated by directly applying 150 ml of distilled water spiked with 4 μg of purified microcystin-LR. The procedure was simple, and a recovery rate of 94% was achieved following elution in 1 ml of 100% methanol. Large-scale, low-cost production of anti-microcystin-LR scAb in E. coli is an exciting prospect for the development of biosensors and on-line monitoring systems for microcystins and will also facilitate a range of immunoaffinity applications for the cleanup and concentration of these toxins from environmental samples. PMID:12406716

  9. Uses of phage display in agriculture: a review of food-related protein-protein interactions discovered by biopanning over diverse baits.

    Science.gov (United States)

    Kushwaha, Rekha; Payne, Christina M; Downie, A Bruce

    2013-01-01

    This review highlights discoveries made using phage display that impact the use of agricultural products. The contribution phage display made to our fundamental understanding of how various protective molecules serve to safeguard plants and seeds from herbivores and microbes is discussed. The utility of phage display for directed evolution of enzymes with enhanced capacities to degrade the complex polymers of the cell wall into molecules useful for biofuel production is surveyed. Food allergies are often directed against components of seeds; this review emphasizes how phage display has been employed to determine the seed component(s) contributing most to the allergenic reaction and how it has played a central role in novel approaches to mitigate patient response. Finally, an overview of the use of phage display in identifying the mature seed proteome protection and repair mechanisms is provided. The identification of specific classes of proteins preferentially bound by such protection and repair proteins leads to hypotheses concerning the importance of safeguarding the translational apparatus from damage during seed quiescence and environmental perturbations during germination. These examples, it is hoped, will spur the use of phage display in future plant science examining protein-ligand interactions.

  10. Uses of Phage Display in Agriculture: A Review of Food-Related Protein-Protein Interactions Discovered by Biopanning over Diverse Baits

    Directory of Open Access Journals (Sweden)

    Rekha Kushwaha

    2013-01-01

    Full Text Available This review highlights discoveries made using phage display that impact the use of agricultural products. The contribution phage display made to our fundamental understanding of how various protective molecules serve to safeguard plants and seeds from herbivores and microbes is discussed. The utility of phage display for directed evolution of enzymes with enhanced capacities to degrade the complex polymers of the cell wall into molecules useful for biofuel production is surveyed. Food allergies are often directed against components of seeds; this review emphasizes how phage display has been employed to determine the seed component(s contributing most to the allergenic reaction and how it has played a central role in novel approaches to mitigate patient response. Finally, an overview of the use of phage display in identifying the mature seed proteome protection and repair mechanisms is provided. The identification of specific classes of proteins preferentially bound by such protection and repair proteins leads to hypotheses concerning the importance of safeguarding the translational apparatus from damage during seed quiescence and environmental perturbations during germination. These examples, it is hoped, will spur the use of phage display in future plant science examining protein-ligand interactions.

  11. A phage-displayed chicken single-chain antibody fused to alkaline phosphatase detects Fusarium pathogens and their presence in cereal grains

    International Nuclear Information System (INIS)

    Hu, Zu-Quan; Li, He-Ping; Zhang, Jing-Bo; Huang, Tao; Liu, Jin-Long; Xue, Sheng; Wu, Ai-Bo; Liao, Yu-Cai

    2013-01-01

    Graphical abstract: A phage-displayed chicken scFv antibody, FvSG7, binds on the surface antigen of conidiospores and the mycelia of F. verticillioides. Its fusion with alkaline phosphatase (AP) through a 218 linker displayed a 4-fold higher affinity compared with the parent scFv antibody and efficiently detected toxigenic Fusarium pathogens in cereal grains. Highlights: ► Generation of a highly reactive scFv antibody against F. verticillioides. ► Localization of the antibody binding to the surface target of F. verticillioides. ► Expression of the antibody–alkaline phosphatase (AP) fusion linked by a 218 linker. ► The antibody–AP fusion has a higher affinity than the parental antibody. ► The antibody–AP fusion detects toxigenic Fusarium pathogens in cereal grains. -- Abstract: Fusarium and its poisonous mycotoxins are distributed worldwide and are of particular interest in agriculture and food safety. A simple analytical method to detect pathogens is essential for forecasting diseases and controlling mycotoxins. This article describes a proposed method for convenient and sensitive detection of Fusarium pathogens that uses the fusion of single-chain variable fragment (scFv) and alkaline phosphatase (AP). A highly reactive scFv antibody specific to soluble cell wall-bound proteins (SCWPs) of F. verticillioides was selected from an immunized chicken phagemid library by phage display. The antibody was verified to bind on the surface of ungerminated conidiospores and mycelia of F. verticillioides. The scFv–AP fusion was constructed, and soluble expression in bacteria was confirmed. Both the antibody properties and enzymatic activity were retained, and the antigen-binding capacity of the fusion was enhanced by the addition of a linker. Surface plasmon resonance measurements confirmed that the fusion displayed 4-fold higher affinity compared with the fusion's parental scFv antibody. Immunoblot analyses showed that the fusion had good binding capacity to

  12. A phage-displayed chicken single-chain antibody fused to alkaline phosphatase detects Fusarium pathogens and their presence in cereal grains

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zu-Quan [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); Li, He-Ping [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Zhang, Jing-Bo [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Huang, Tao [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Liu, Jin-Long; Xue, Sheng [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); Wu, Ai-Bo [Institute for Agri-food Standards and Testing Technology, Laboratory of Quality and Safety Risk Assessment for Agro-products, Ministry of Agriculture, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Road, Shanghai 201403 (China); Liao, Yu-Cai, E-mail: ycliao06@yahoo.com.cn [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); National Center of Plant Gene Research, Wuhan 430070 (China)

    2013-02-18

    Graphical abstract: A phage-displayed chicken scFv antibody, FvSG7, binds on the surface antigen of conidiospores and the mycelia of F. verticillioides. Its fusion with alkaline phosphatase (AP) through a 218 linker displayed a 4-fold higher affinity compared with the parent scFv antibody and efficiently detected toxigenic Fusarium pathogens in cereal grains. Highlights: ► Generation of a highly reactive scFv antibody against F. verticillioides. ► Localization of the antibody binding to the surface target of F. verticillioides. ► Expression of the antibody–alkaline phosphatase (AP) fusion linked by a 218 linker. ► The antibody–AP fusion has a higher affinity than the parental antibody. ► The antibody–AP fusion detects toxigenic Fusarium pathogens in cereal grains. -- Abstract: Fusarium and its poisonous mycotoxins are distributed worldwide and are of particular interest in agriculture and food safety. A simple analytical method to detect pathogens is essential for forecasting diseases and controlling mycotoxins. This article describes a proposed method for convenient and sensitive detection of Fusarium pathogens that uses the fusion of single-chain variable fragment (scFv) and alkaline phosphatase (AP). A highly reactive scFv antibody specific to soluble cell wall-bound proteins (SCWPs) of F. verticillioides was selected from an immunized chicken phagemid library by phage display. The antibody was verified to bind on the surface of ungerminated conidiospores and mycelia of F. verticillioides. The scFv–AP fusion was constructed, and soluble expression in bacteria was confirmed. Both the antibody properties and enzymatic activity were retained, and the antigen-binding capacity of the fusion was enhanced by the addition of a linker. Surface plasmon resonance measurements confirmed that the fusion displayed 4-fold higher affinity compared with the fusion's parental scFv antibody. Immunoblot analyses showed that the fusion had good binding

  13. Recombinant Polyclonal Antibody Libraries for Breast Cancer Therapy

    National Research Council Canada - National Science Library

    Sharon, Jacqueline

    1999-01-01

    .... In the present study, V region genes for construction of a polyclonal Fab phage display library were obtained from the spleen, bone marrow, and intestine of a BALB/c mouse that had been immunized with BT-20 cells...

  14. Injected phage-displayed-VP28 vaccine reduces shrimp Litopenaeus vannamei mortality by white spot syndrome virus infection.

    Science.gov (United States)

    Solís-Lucero, G; Manoutcharian, K; Hernández-López, J; Ascencio, F

    2016-08-01

    White spot syndrome virus (WSSV) is the most important viral pathogen for the global shrimp industry causing mass mortalities with huge economic losses. Recombinant phages are capable of expressing foreign peptides on viral coat surface and act as antigenic peptide carriers bearing a phage-displayed vaccine. In this study, the full-length VP28 protein of WSSV, widely known as potential vaccine against infection in shrimp, was successfully cloned and expressed on M13 filamentous phage. The functionality and efficacy of this vaccine immunogen was demonstrated through immunoassay and in vivo challenge studies. In ELISA assay phage-displayed VP28 was bind to Litopenaeus vannamei immobilized hemocyte in contrast to wild-type M13 phage. Shrimps were injected with 2 × 10(10) cfu animal(-1) single dose of VP28-M13 and M13 once and 48 h later intramuscularly challenged with WSSV to test the efficacy of the vaccine against the infection. All dead challenged shrimps were PCR WSSV-positive. The accumulative mortality of the vaccinated and challenged shrimp groups was significantly lower (36.67%) than the unvaccinated group (66.67%). Individual phenoloxidase and superoxide dismutase activity was assayed on 8 and 48 h post-vaccination. No significant difference was found in those immunological parameters among groups at any sampled time evaluated. For the first time, phage display technology was used to express a recombinant vaccine for shrimp. The highest percentage of relative survival in vaccinated shrimp (RPS = 44.99%) suggest that the recombinant phage can be used successfully to display and deliver VP28 for farmed marine crustaceans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system.

    Science.gov (United States)

    Krebber, A; Bornhauser, S; Burmester, J; Honegger, A; Willuda, J; Bosshard, H R; Plückthun, A

    1997-02-14

    A prerequisite for the use of recombinant antibody technologies starting from hybridomas or immune repertoires is the reliable cloning of functional immunoglobulin genes. For this purpose, a standard phage display system was optimized for robustness, vector stability, tight control of scFv-delta geneIII expression, primer usage for PCR amplification of variable region genes, scFv assembly strategy and subsequent directional cloning using a single rare cutting restriction enzyme. This integrated cloning, screening and selection system allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell repertoires of mice immunized with ampicillin as well as from all hybridoma cell lines tested to date. As representative examples, cloning of monoclonal antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the insecticide DDT is presented. Several hybridomas whose genes could not be cloned in previous experimental setups, but were successfully obtained with the present system, expressed high amounts of aberrant heavy and light chain mRNAs, which were amplified by PCR and greatly exceeded the amount of binding antibody sequences. These contaminating variable region genes were successfully eliminated by employing the optimized phage display system, thus avoiding time consuming sequencing of non-binding scFv genes. To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed.

  16. Tenured Librarians in Large University Libraries.

    Science.gov (United States)

    Smith, Karen F.; And Others

    1984-01-01

    Based on a 1979 survey of 530 tenured librarians in 33 large academic libraries, this article examines characteristics of tenured librarians (sex, age, marital status, salary, degrees, rank, job titles), criteria and review procedures used in granting tenure, productivity before and after tenure, and mobility. Seven references are included. (EJS)

  17. Phage display used for gene cloning of human recombinant antibody against the erythrocyte surface antigen, rhesus D

    DEFF Research Database (Denmark)

    Dziegiel, M; Nielsen, L K; Andersen, P S

    1995-01-01

    A novel phage display system has been developed for PCR amplification and cloning of the Fab fragments of human immunoglobulin genes. Using this system, we have cloned an antibody from a mouse-human hybridoma cell line directed against the erythrocyte antigen rhesus D. Intact erythrocytes were used...... for absorption of the Fab phages. Soluble Fab fragments produced from the cloned material showed identical performance to the parental antibody in agglutination assays. Gel filtration confirmed that the Fab fragment consists of a kappa-Fd heterodimer. The successful use of intact cells for selection of specific...... Fab phages demonstrates that it is possible to by-pass purification of the antigen of interest. Comparison with published germline sequences demonstrated that the immunoglobulin coding regions had the highest homology to the VH 1.9III and V kappa Hum kappa v325 germline genes, respectively....

  18. Lateral flow assay for rapid detection of white spot syndrome virus (WSSV) using a phage-displayed peptide as bio-recognition probe.

    Science.gov (United States)

    Kulabhusan, Prabir Kumar; Rajwade, Jyutika M; Sahul Hameed, A S; Paknikar, Kishore M

    2017-06-01

    White spot disease caused by the white spot syndrome virus (WSSV) has a major socio-economic impact on shrimp farming in India. It has been realized that a field-usable diagnostic capable of rapid detection of WSSV can prevent huge economic losses in disease outbreaks. In this work, we explored the possibility of using a peptide as bio-recognition probe in a field-usable device for the detection of WSSV from infected shrimps and prawns. A commercially available random phage-display library was screened against rVP28 (a major structural protein of WSSV, expressed as a recombinant protein in Escherichia coli). A bacteriophage clone VP28-4L was obtained, and its binding to purified rVP28 protein as well as WSSV from infected shrimp Litopaeneus vannamei tissue was confirmed by ELISA and western blot. The apparent equilibrium dissociation constant (K d ,app) was calculated to be 810 nM. VP28-4L did not show cross-reactivity with any other shrimp viruses. A 12-mer peptide (pep28, with the sequence 'TFQAFDLSPFPS') displayed on the VP28-4L was synthesized, and its diagnostic potential was evaluated in a lateral flow assay (LFA). Visual detection of WSSV could be achieved using biotinylated-pep28 and streptavidin-conjugated gold nanoparticles. In LFA, 12.5 μg/mL of the virus could be detected from L. vannamei gill tissue homogenate within 20 min. Pep28 thus becomes an attractive candidate in bio-recognition of WSSV in field-usable diagnostic platforms benefitting the aquaculture sector.

  19. A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

    Science.gov (United States)

    Baskar, Sivasubramanian; Suschak, Jessica M; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W; Pavletic, Steven Z; Bishop, Michael R; Rader, Christoph

    2009-11-12

    Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

  20. High-throughput sequencing enhanced phage display identifies peptides that bind mycobacteria

    CSIR Research Space (South Africa)

    Ngubane, NAC

    2013-11-01

    Full Text Available . The displayed peptides are flanked by two cysteine residues, which are oxidized during phage assembly to a disulfide bond, resulting in a loop constrained peptide. We initially used the traditional clone picking method to identify the enriched clones... of the library, 1.236109 heptapeptides, it represented sufficient depth to measure the quantitative enrich- ment of relevant peptides. To confirm successful enrichment during selection, we characterized the reduction in diversity of the pool in the consecutive...

  1. Re-engineering of the PAM1 phage display monoclonal antibody to produce a soluble, versatile anti-homogalacturonan scFv

    DEFF Research Database (Denmark)

    Manfield, I. W.; Bernal Giraldo, Adriana Jimena; Møller, I.

    2006-01-01

    Antibody phage display is an increasingly important alternative method for the production of monoclonal antibodies (mAbs) and involves the expression of antibody fragments (scFvs) at the surface of bacteriophage particles. We have previously used this technique to generate a phage mAb (PAM1phage...

  2. Selection of staphylococcal enterotoxin B (SEB)-binding peptide using phage display technology

    International Nuclear Information System (INIS)

    Soykut, Esra Acar; Dudak, Fahriye Ceyda; Boyaci, Ismail Hakki

    2008-01-01

    In this study, peptides were selected to recognize staphylococcal enterotoxin B (SEB) which cause food intoxication and can be used as a biological war agent. By using commercial M13 phage library, single plaque isolation of 38 phages was done and binding affinities were investigated with phage-ELISA. The specificities of the selected phage clones showing high affinity to SEB were checked by using different protein molecules which can be found in food samples. Furthermore, the affinities of three selected phage clones were determined by using surface plasmon resonance (SPR) sensors. Sequence analysis was realized for three peptides showing high binding affinity to SEB and WWRPLTPESPPA, MNLHDYHRLFWY, and QHPQINQTLYRM amino acid sequences were obtained. The peptide sequence with highest affinity to SEB was synthesized with solid phase peptide synthesis technique and thermodynamic constants of the peptide-SEB interaction were determined by using isothermal titration calorimetry (ITC) and compared with those of antibody-SEB interaction. The binding constant of the peptide was determined as 4.2 ± 0.7 x 10 5 M -1 which indicates a strong binding close to that of antibody

  3. Development of two murine antibodies against Neospora caninum using phage display technology and application on the detection of N. caninum.

    Directory of Open Access Journals (Sweden)

    Jinhua Dong

    Full Text Available Neosporosis, caused by an intracellular parasite, Neospora caninum, is an infectious disease primarily of cattle and dogs. It occurs worldwide and causes huge damages to dairy farms. In this study, we immunized mice with recombinant surface-associated protein 1 of N. caninum (rNcSAG1 and developed two novel monoclonal antibodies, A10 and H3, against NcSAG1 using phage-display technology. Both clones bound to purified rNcSAG1 and the half maximal inhibitory concentrations of A10 and H3 are 50 and 72 nM of rNcSAG1, respectively. In immunofluorescence assays, both A10 and H3 Fabs bound to N. caninum parasites. Direct detection of N. caninum parasites was developed firstly using an enzyme-linked immunosorbent assay (ELISA with A10 and H3. Binding of A10 and H3 antibodies to rNcSAG1 was also inhibited by some certain anti-N. caninum antibodies in the neosporosis-positive cattle sera, suggesting they might bind to the same epitopes of NcSAG1 with those anti-N. caninum antibodies of bovine. These antibodies were demonstrated to have a potential for monitoring the N. caninum parasites in a dairy farm, which may lead to protect livestock from parasite-infection.

  4. Development of highly sensitive detection method for toxins and other pathogenic factors by phage-displayed monoclonal antibody using radioisotopes

    International Nuclear Information System (INIS)

    Izumiya, Hidemasa; Watanabe, Haruo

    2000-01-01

    To prepare anti-Shiga toxin (Stx) antibody, a recombinant strain of E coli that can produce the subunit B of Stx was constructed. DNA fragment coding the Stx subunit B, about 0.2 kb in length was amplified using a plasmid containing Stx gene as the template by PCR. After digesting with a restriction enzyme, the DNA fragment was inserted into pmal-c2 vector (New England Biolabs) to produce a fusion protein with maltose binding protein (MBP). E.coli K12 (DH5α) including the pmal-stx plasmid was cultured in the presence of isopropylthiogalactoside (IPTG) and thus, MBP-stx fusion protein was obtained. After purification by Millipore membrane filter, this fusion protein was used as the antigen. Then, mice BALB/c were immunized by intraperitoneal injection of the suspension of MBP-stx and adjuvant. The antibody purified from the spleen was submitted to phage display system. The phage specifically binding to the antigen was proliferated through repeated infection to E coli and the anti-Stx antibody was obtained from the culture of its colony grown on IPTG plate. Three different colonies specifically responding to the recombinant Stx antigen were obtained. In near future, labeled antibody would be produced by addition of 35 S compound in to the culture medium. (M.N.)

  5. Identification and in vitro characterization of phage-displayed VHHs targeting VEGF

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potential target for cancer treatment because of its role in angiogenesis and its overexpression in most human cancers. Currently, anti-VEGF antibodies have been shown to be promising tools for therapeutic applications. However, large size, poor tumo...

  6. Quantitative PET Imaging with Novel HER3-Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression

    Science.gov (United States)

    2017-12-01

    Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...TYPE Final 3. DATES COVERED 1 Aug 2016 – 19 August 2017 Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5a...highly specific peptide that targets HER3 for prostate cancer imaging. The peptide was labeled with a PET imaging radionuclide and injected into mice

  7. Production and evaluation of antibodies and phage display-derived peptide ligands for immunomagnetic separation of Mycobacterium bovis.

    Science.gov (United States)

    Stewart, Linda D; McNair, James; McCallan, Lyanne; Thompson, Suzan; Kulakov, Leonid A; Grant, Irene R

    2012-05-01

    This study describes the development and optimization of an immunomagnetic separation (IMS) method to isolate Mycobacterium bovis cells from lymph node tissues. Gamma-irradiated whole M. bovis AF2122/97 cells and ethanol-extracted surface antigens of such cells were used to produce M. bovis-specific polyclonal and monoclonal antibodies in rabbits and mice. They were also used to generate M. bovis-specific peptide ligands by phage display biopanning. The various antibodies and peptide ligands obtained were used to coat MyOne tosyl-activated Dynabeads (Life Technologies), singly or in combination, and evaluated for IMS. Initially, M. bovis capture from Middlebrook 7H9 broth suspensions (concentration range, 10 to 10(5) CFU/ml) was evaluated by IMS combined with an M. bovis-specific touchdown PCR. IMS-PCR results and, subsequently, IMS-culture results indicated that the beads with greatest immunocapture capability for M. bovis in broth were those coated simultaneously with a monoclonal antibody and a biotinylated 12-mer peptide. These dually coated beads exhibited minimal capture (mean of 0.36% recovery) of 12 other Mycobacterium spp. occasionally encountered in veterinary tuberculosis (TB) diagnostic laboratories. When the optimized IMS method was applied to various M. bovis-spiked lymph node matrices, it demonstrated excellent detection sensitivities (50% limits of detection of 3.16 and 57.7 CFU/ml of lymph node tissue homogenate for IMS-PCR and IMS-culture, respectively). The optimized IMS method therefore has the potential to improve isolation of M. bovis from lymph nodes and hence the diagnosis of bovine tuberculosis.

  8. A novel method for in Situ detection of hydrolyzable casein fragments in a cheese matrix by antibody phage display technique and CLSM

    DEFF Research Database (Denmark)

    Duan, Zhi; Brüggemann, Dagmar Adeline; Siegumfeldt, Henrik

    2009-01-01

    three small synthetic peptides of the alpha(s1)-casein sequence. These peptides traverse enzymatic cleavage sites of casein during cheese ripening. The specificity of the generated anti-peptide antibodies was determined by ELISA and Western blot. Finally, an immunofluorescent labeling protocol......A novel method to monitor in situ hydrolyzable casein fragments during cheese ripening by using immunofluorescent labeling and confocal laser scanning microscopy (CLSM) was developed. Monoclonal single chain variable fragments of antibody (scFvs) were generated by antibody phage display toward...

  9. Quantitative PCR is a Valuable Tool to Monitor the Performance of DNA-Encoded Chemical Library Selections.

    Science.gov (United States)

    Li, Yizhou; Zimmermann, Gunther; Scheuermann, Jörg; Neri, Dario

    2017-05-04

    Phage-display libraries and DNA-encoded chemical libraries (DECLs) represent useful tools for the isolation of specific binding molecules from large combinatorial sets of compounds. With both methods, specific binders are recovered at the end of affinity capture procedures by using target proteins of interest immobilized on a solid support. However, although the efficiency of phage-display selections is routinely quantified by counting the phage titer before and after the affinity capture step, no similar quantification procedures have been reported for the characterization of DECL selections. In this article, we describe the potential and limitations of quantitative PCR (qPCR) methods for the evaluation of selection efficiency by using a combinatorial chemical library with more than 35 million compounds. In the experimental conditions chosen for the selections, a quantification of DNA input/recovery over five orders of magnitude could be performed, revealing a successful enrichment of abundant binders, which could be confirmed by DNA sequencing. qPCR provided rapid information about the performance of selections, thus facilitating the optimization of experimental conditions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Generation and analyses of human synthetic antibody libraries and their application for protein microarrays

    DEFF Research Database (Denmark)

    Säll, Anna; Walle, Maria; Wingren, Christer

    2016-01-01

    in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities......Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments...... for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity...

  11. Construction of a T7 Human Lung Cancer cDNA Library

    Directory of Open Access Journals (Sweden)

    Wentao YUE

    2008-10-01

    Full Text Available Background and objective Currently, only a limited numbers of tumor markers for non small lung cancer (NSCLC diagnosis, new biomarker, such as serum autoantibody may improve the early detection of lung cancer. Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients. Methods mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas, and then mRNA was reverse transcribed into double stranded cDNA. After digestion, the cDNA was inserted into T7Select 10-3 vector. The phage display cDNA library was constructed by package reaction in vitro and plate proliferation. Plaque assay and PCR were used to evaluate the library.Results Two T7 phage display cDNA library were established. Plaque assay show the titer of lung squamas carcinoma library was 1.8×106 pfu, and the adenocarcinoma library was 5×106 pfu. The phage titer of the amplified library were 3.2×1010 pfu/mL and 2.5×1010 pfu/mL. PCR amplification of random plaque show insert ratio were 100% (24/24 in adenocarcinoma library and 95.8% in human lung squamas carcinoma library (23/24. Insert range from 300 bp to 1 500 bp. Conclusion Two phage display cDNA library from NSCLC were constructed.

  12. Construction of genetically engineered M13K07 helper phage for simultaneous phage display of gold binding peptide 1 and nuclear matrix protein 22 ScFv antibody.

    Science.gov (United States)

    Fatemi, Farnaz; Amini, Seyed Mohammad; Kharrazi, Sharmin; Rasaee, Mohammad Javad; Mazlomi, Mohammad Ali; Asadi-Ghalehni, Majid; Rajabibazl, Masoumeh; Sadroddiny, Esmaeil

    2017-11-01

    The most common techniques of antibody phage display are based on the use of M13 filamentous bacteriophages. This study introduces a new genetically engineered M13K07 helper phage displaying multiple copies of a known gold binding peptide on p8 coat proteins. The recombinant helper phages were used to rescue a phagemid vector encoding the p3 coat protein fused to the nuclear matrix protein 22 (NMP22) ScFv antibody. Transmission electron microscopy (TEM), UV-vis absorbance spectroscopy, and field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray spectroscopy (EDX) analysis revealed that the expression of gold binding peptide 1 (GBP1) on major coat protein p8 significantly enhances the gold-binding affinity of M13 phages. The recombinant bacteriophages at concentrations above 5×10 4 pfu/ml red-shifted the UV-vis absorbance spectra of gold nanoparticles (AuNPs); however, the surface plasmon resonance of gold nanoparticles was not changed by the wild type bacteriophages at concentrations up to 10 12 pfu/ml. The phage ELISA assay demonstrated the high affinity binding of bifunctional bacteriophages to NMP22 antigen at concentrations of 10 5 and 10 6 pfu/ml. Thus, the p3 end of the bifunctional bacteriophages would be able to bind to specific target antigen, while the AuNPs were assembled along the coat of virus for signal generation. Our results indicated that the complex of antigen-bacteriophages lead to UV-vis spectral changes of AuNPs and NMP22 antigen in concentration range of 10-80μg/ml can be detected by bifunctional bacteriophages at concentration of 10 4 pfu/ml. The ability of bifunctional bacteriophages to bind to antigen and generate signal at the same time, makes this approach applicable for identifying different antigens in immunoassay techniques. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Development of a large peptoid-DOTA combinatorial library.

    Science.gov (United States)

    Singh, Jaspal; Lopes, Daniel; Gomika Udugamasooriya, D

    2016-09-01

    Conventional one-bead one-compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built-in imaging component for a certain target is a daunting task, and structure-based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on-bead library of 153,600 Peptoid-DOTA compounds in which the peptoids are the target-recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6-mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on-bead development of large peptidomimetic-DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673-684, 2016. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc.

  14. A variety of human monoclonal antibodies against epidermal growth factor receptor isolated from a phage antibody library.

    Science.gov (United States)

    Kurosawa, Gene; Kondo, Mariko; Kurosawa, Yoshikazu

    2016-11-04

    When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of V H and V L genes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Construction of High-Quality Camel Immune Antibody Libraries.

    Science.gov (United States)

    Romão, Ema; Poignavent, Vianney; Vincke, Cécile; Ritzenthaler, Christophe; Muyldermans, Serge; Monsion, Baptiste

    2018-01-01

    Single-domain antibodies libraries of heavy-chain only immunoglobulins from camelids or shark are enriched for high-affinity antigen-specific binders by a short in vivo immunization. Thus, potent binders are readily retrieved from relatively small-sized libraries of 10 7 -10 8 individual transformants, mostly after phage display and panning on a purified target. However, the remaining drawback of this strategy arises from the need to generate a dedicated library, for nearly every envisaged target. Therefore, all the procedures that shorten and facilitate the construction of an immune library of best possible quality are definitely a step forward. In this chapter, we provide the protocol to generate a high-quality immune VHH library using the Golden Gate Cloning strategy employing an adapted phage display vector where a lethal ccdB gene has to be substituted by the VHH gene. With this procedure, the construction of the library can be shortened to less than a week starting from bleeding the animal. Our libraries exceed 10 8 individual transformants and close to 100% of the clones harbor a phage display vector having an insert with the length of a VHH gene. These libraries are also more economic to make than previous standard approaches using classical restriction enzymes and ligations. The quality of the Nanobodies that are retrieved from immune libraries obtained by Golden Gate Cloning is identical to those from immune libraries made according to the classical procedure.

  16. Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV

    Directory of Open Access Journals (Sweden)

    Hust Michael

    2008-09-01

    Full Text Available Abstract Background Venezuelan equine encephalitis virus (VEEV belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. Results In this work, human anti-VEEV single chain Fragments variable (scFv were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV and Eastern equine encephalitis virus (EEEV antigenic complex, nor did they react with Chikungunya virus (CHIKV, if they were used as detection reagent. Conclusion For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.

  17. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Science.gov (United States)

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw; Potempa, Jan; Riise, Erik

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18) by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15), shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48). Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  18. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Directory of Open Access Journals (Sweden)

    Peter Durand Skottrup

    Full Text Available Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18 by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15, shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48. Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  19. Technique for simultaneous adjustment of large nuclear data libraries

    International Nuclear Information System (INIS)

    Harris, D.R.; Wilson, W.B.

    1975-01-01

    Adjustment of the nuclear data base to agree with integral observations in design work has been limited in part by problems in the required inversion of matrices. It is shown that this inversion problem can be circumvented and arbitrarily large nuclear data libraries can be adjusted simultaneously when the basic data are uncorrelated. The technique is illustrated by adjusting nuclear data to integral observations made on fast reactor benchmark critical assemblies. 3 tables

  20. Synthesis and screening of peptide libraries with free C-termini.

    Science.gov (United States)

    Wang, Yen-Chih; Distefano, Mark D

    2014-01-01

    Peptide libraries are useful tools to investigate the relationship between structure and function of proteins. The creation of peptide libraries with free C-termini presents unique synthetic challenges. In this review, methods for creating peptide libraries using either solid-phase peptide synthesis or phage display are described. Methods for screening such libraries and their application in studying several important biological problems are also reported.

  1. Peptide-binding motif prediction by using phage display library for SasaUBA*0301, a resistance haplotype of MHC class I molecule from Atlantic Salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Zhao, Heng; Hermsen, Trudi; Stet, Rene J M

    2008-01-01

    The structure of the peptide-binding specificity of major histocompatibility complex (MHC) class I has been analyzed extensively in human and mouse. For fish, there are no crystallographic models of MHC molecules, neither are there data on the peptide-binding specificity. In this study, we descri...... and there is a significant association between MHC polymorphism and the disease resistance. Therefore, our study might contribute to designing a peptide vaccine against this viral disease....... class I molecule might have a very similar binding motif at the C-terminus compared with a known mouse class I molecule H2-Kb which has L, or I, V, M at p8. Previous work showed that Atlantic Salmon carrying the allele SasaUBA*0301 are resistant to infectious Salmon aneamia virus...

  2. Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low density lipoprotein receptor family by a peptide isolated from a phage displayed library

    DEFF Research Database (Denmark)

    Jensen, Jan K.; Malmendal, Anders; Schiøtt, Birgit

    2006-01-01

    (DVPCFGWCQDA) was determined by NMR. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the u...

  3. Phage Display Breast Carcinoma cDNA Libraries: Isolation of Clones Which Specifically Bind to Membrane Glycoproteins, Mucins, and Endothelial Cell Surface

    National Research Council Canada - National Science Library

    Yamamoto, Fumiichiro

    2000-01-01

    .... Using blood- group H-expressing glycoprotein fraction as bait, we observed enrichment of phage clones expressing sequences from galectin-3, a lectin with an affinity with the blood-group substance...

  4. Meeting the Information Needs of Interdisciplinary Scholars: Issues for Administrators of Large University Libraries.

    Science.gov (United States)

    Searing, Susan E.

    1996-01-01

    Provides an overview of administrative issues in supporting interdisciplinary library use at large universities. Topics include information resources; cataloging and classification; library services to users, including library use education and reference services; library organization; the campus context; and the politics of interdisciplinarity.…

  5. Construction and Screening of Marine Metagenomic Large Insert Libraries.

    Science.gov (United States)

    Weiland-Bräuer, Nancy; Langfeldt, Daniela; Schmitz, Ruth A

    2017-01-01

    The marine environment covers more than 70 % of the world's surface. Marine microbial communities are highly diverse and have evolved during extended evolutionary processes of physiological adaptations under the influence of a variety of ecological conditions and selection pressures. They harbor an enormous diversity of microbes with still unknown and probably new physiological characteristics. In the past, marine microbes, mostly bacteria of microbial consortia attached to marine tissues of multicellular organisms, have proven to be a rich source of highly potent bioactive compounds, which represent a considerable number of drug candidates. However, to date, the biodiversity of marine microbes and the versatility of their bioactive compounds and metabolites have not been fully explored. This chapter describes sampling in the marine environment, construction of metagenomic large insert libraries from marine habitats, and exemplarily one function based screen of metagenomic clones for identification of quorum quenching activities.

  6. Virtual screening methods as tools for drug lead discovery from large chemical libraries.

    Science.gov (United States)

    Ma, X H; Zhu, F; Liu, X; Shi, Z; Zhang, J X; Yang, S Y; Wei, Y Q; Chen, Y Z

    2012-01-01

    Virtual screening methods have been developed and explored as useful tools for searching drug lead compounds from chemical libraries, including large libraries that have become publically available. In this review, we discussed the new developments in exploring virtual screening methods for enhanced performance in searching large chemical libraries, their applications in screening libraries of ~ 1 million or more compounds in the last five years, the difficulties in their applications, and the strategies for further improving these methods.

  7. Simultaneous display of two large proteins on the head and tail of bacteriophage lambda

    Science.gov (United States)

    2013-01-01

    Background Consistent progress in the development of bacteriophage lambda display platform as an alternative to filamentous phage display system was achieved in the recent years. The lambda phage has been engineered to display efficiently multiple copies of peptides or even large protein domains providing a powerful tool for screening libraries of peptides, proteins and cDNA. Results In the present work we describe an original method for dual display of large proteins on the surface of lambda particles. An anti-CEA single-chain antibody fragment and green fluorescent protein or alkaline phosphatase were simultaneously displayed by engineering both gpD and gpV lambda proteins. Conclusions Here we show that such modified phage particles can be used for the detection of target molecules in vitro and in vivo. Dual expression of functional moieties on the surface of the lambda phage might open the way to generation of a new class of diagnostic and therapeutic targeted nanoparticles. PMID:24073829

  8. Targeting mammalian organelles with internalizing phage (iPhage) libraries

    Science.gov (United States)

    Rangel, Roberto; Dobroff, Andrey S.; Guzman-Rojas, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih

    2015-01-01

    Techniques largely used for protein interaction studies and discovery of intracellular receptors, such as affinity capture complex purification and yeast two-hybrid, may produce inaccurate datasets due to protein insolubility, transient or weak protein interactions, or irrelevant intracellular context. A versatile tool to overcome these limitations as well as to potentially create vaccines and engineer peptides and antibodies as targeted diagnostic and therapeutic agents, is the phage display technique. We have recently developed a new technology for screening internalizing phage (iPhage) vectors and libraries utilizing a ligand/receptor-independent mechanism to penetrate eukaryotic cells. iPhage particles provide a unique discovery platform for combinatorial intracellular targeting of organelle ligands along with their corresponding receptors and to fingerprint functional protein domains in living cells. Here we explain the design, cloning, construction, and production of iPhage-based vectors and libraries, along with basic ligand-receptor identification and validation methodologies for organelle receptors. An iPhage library screening can be performed in ~8 weeks. PMID:24030441

  9. Surveys of Online Information Service in Large Public Libraries.

    Science.gov (United States)

    Woy, James B.

    1983-01-01

    Reports results of 1983 survey of 25 public libraries and 1981 survey of 11 public libraries, both of which focused on facets of online information services--user fees, databases, documentation, equipment, miscellaneous services, and subject areas searched. The 1983 questionnaire and seven sources are appended. (EJS)

  10. Map it @ WSU: Development of a Library Mapping System for Large Academic Libraries

    Directory of Open Access Journals (Sweden)

    Paul Gallagher

    2010-06-01

    Full Text Available The Wayne State Library System launched its library mapping application in February 2010, designed to help locate materials in the five WSU libraries. The system works within the catalog to show the location of materials, as well as provides a web form for use at the reference desk. Developed using PHP and MySQL, it requires only minimal effort to update using a unique call number overlay mechanism. In addition to mapping shelved materials, the system provides information for any of the over three hundred collections held by the WSU Libraries. Patrons can do more than just locate a book on a shelf: they can learn where to locate reserve items, how to access closed collections, or get driving maps to extension center libraries. The article includes a discussion of the technology reviewed and chosen during development, an overview of the system architecture, and lessons learned during development.

  11. DNA-encoded chemical libraries: advancing beyond conventional small-molecule libraries.

    Science.gov (United States)

    Franzini, Raphael M; Neri, Dario; Scheuermann, Jörg

    2014-04-15

    DNA-encoded chemical libraries (DECLs) represent a promising tool in drug discovery. DECL technology allows the synthesis and screening of chemical libraries of unprecedented size at moderate costs. In analogy to phage-display technology, where large antibody libraries are displayed on the surface of filamentous phage and are genetically encoded in the phage genome, DECLs feature the display of individual small organic chemical moieties on DNA fragments serving as amplifiable identification barcodes. The DNA-tag facilitates the synthesis and allows the simultaneous screening of very large sets of compounds (up to billions of molecules), because the hit compounds can easily be identified and quantified by PCR-amplification of the DNA-barcode followed by high-throughput DNA sequencing. Several approaches have been used to generate DECLs, differing both in the methods used for library encoding and for the combinatorial assembly of chemical moieties. For example, DECLs can be used for fragment-based drug discovery, displaying a single molecule on DNA or two chemical moieties at the extremities of complementary DNA strands. DECLs can vary substantially in the chemical structures and the library size. While ultralarge libraries containing billions of compounds have been reported containing four or more sets of building blocks, also smaller libraries have been shown to be efficient for ligand discovery. In general, it has been found that the overall library size is a poor predictor for library performance and that the number and diversity of the building blocks are rather important indicators. Smaller libraries consisting of two to three sets of building blocks better fulfill the criteria of drug-likeness and often have higher quality. In this Account, we present advances in the DECL field from proof-of-principle studies to practical applications for drug discovery, both in industry and in academia. DECL technology can yield specific binders to a variety of target

  12. Generation and analyses of human synthetic antibody libraries and their application for protein microarrays.

    Science.gov (United States)

    Säll, Anna; Walle, Maria; Wingren, Christer; Müller, Susanne; Nyman, Tomas; Vala, Andrea; Ohlin, Mats; Borrebaeck, Carl A K; Persson, Helena

    2016-10-01

    Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. "My Library Was Dukedom Large Enough": Academic Libraries Mediating the Shakespeare Authorship Debate

    Directory of Open Access Journals (Sweden)

    Michael Quinn Dudley

    2013-11-01

    Full Text Available The "Shakespeare Authorship Question" regarding the identity of the poet-playwright has been debated for over 150 years. Now, with the growing list of signatories to the "Declaration of Reasonable Doubt", the creation of a Master's Degree program in Authorship Studies at Brunel University in London, the opening of the Shakespeare Authorship Research Studies Center at the Library of Concordia University in Portland, and the release of two competing high profile books both entitled Shakespeare Beyond Doubt, academic libraries are being presented with a unique and timely opportunity to participate in and encourage this debate, which has long been considered a taboo subject in the academy.

  14. A novel heavy domain antibody library with functionally optimized complementarity determining regions.

    Directory of Open Access Journals (Sweden)

    Ole Aalund Mandrup

    Full Text Available Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.

  15. Methods for the preparation of large quantities of complex single-stranded oligonucleotide libraries.

    Science.gov (United States)

    Murgha, Yusuf E; Rouillard, Jean-Marie; Gulari, Erdogan

    2014-01-01

    Custom-defined oligonucleotide collections have a broad range of applications in fields of synthetic biology, targeted sequencing, and cytogenetics. Also, they are used to encode information for technologies like RNA interference, protein engineering and DNA-encoded libraries. High-throughput parallel DNA synthesis technologies developed for the manufacture of DNA microarrays can produce libraries of large numbers of different oligonucleotides, but in very limited amounts. Here, we compare three approaches to prepare large quantities of single-stranded oligonucleotide libraries derived from microarray synthesized collections. The first approach, alkaline melting of double-stranded PCR amplified libraries with a biotinylated strand captured on streptavidin coated magnetic beads results in little or no non-biotinylated ssDNA. The second method wherein the phosphorylated strand of PCR amplified libraries is nucleolyticaly hydrolyzed is recommended when small amounts of libraries are needed. The third method combining in vitro transcription of PCR amplified libraries to reverse transcription of the RNA product into single-stranded cDNA is our recommended method to produce large amounts of oligonucleotide libraries. Finally, we propose a method to remove any primer binding sequences introduced during library amplification.

  16. Largenet2: an object-oriented programming library for simulating large adaptive networks.

    Science.gov (United States)

    Zschaler, Gerd; Gross, Thilo

    2013-01-15

    The largenet2 C++ library provides an infrastructure for the simulation of large dynamic and adaptive networks with discrete node and link states. The library is released as free software. It is available at http://biond.github.com/largenet2. Largenet2 is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License. gerd@biond.org

  17. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    OpenAIRE

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai; Hizi, Amnon

    2013-01-01

    Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening s...

  18. Characterization of large-insert DNA libraries from soil for environmental genomic studies of Archaea

    DEFF Research Database (Denmark)

    Treusch, Alexander H; Kletzin, Arnulf; Raddatz, Guenter

    2004-01-01

    Complex genomic libraries are increasingly being used to retrieve complete genes, operons or large genomic fragments directly from environmental samples, without the need to cultivate the respective microorganisms. We report on the construction of three large-insert fosmid libraries in total...... (approximately 1% each) have been captured in our libraries. The diversity of putative protein-encoding genes, as reflected by their distribution into different COG clusters, was comparable to that encoded in complete genomes of cultivated microorganisms. A huge variety of genomic fragments has been captured...

  19. Generation of Novel Single-Chain Antibodies by Phage-Display Technology to Direct Imaging Agents Highly Selective to Pancreatic β- or α-Cells In Vivo

    Science.gov (United States)

    Ueberberg, Sandra; Meier, Juris J.; Waengler, Carmen; Schechinger, Wolfgang; Dietrich, Johannes W.; Tannapfel, Andrea; Schmitz, Inge; Schirrmacher, Ralf; Köller, Manfred; Klein, Harald H.; Schneider, Stephan

    2009-01-01

    OBJECTIVE Noninvasive determination of pancreatic β-cell mass in vivo has been hampered by the lack of suitable β-cell–specific imaging agents. This report outlines an approach for the development of novel ligands homing selectively to islet cells in vivo. RESEARCH DESIGN AND METHODS To generate agents specifically binding to pancreatic islets, a phage library was screened for single-chain antibodies (SCAs) on rat islets using two different approaches. 1) The library was injected into rats in vivo, and islets were isolated after a circulation time of 5 min. 2) Pancreatic islets were directly isolated, and the library was panned in the islets in vitro. Subsequently, the identified SCAs were extensively characterized in vitro and in vivo. RESULTS We report the generation of SCAs that bind highly selective to either β- or α-cells. These SCAs are internalized by target cells, disappear rapidly from the vasculature, and exert no toxicity in vivo. Specific binding to β- or α-cells was detected in cell lines in vitro, in rats in vivo, and in human tissue in situ. Electron microscopy demonstrated binding of SCAs to the endoplasmatic reticulum and the secretory granules. Finally, in a biodistribution study the labeling intensity derived from [125I]-labeled SCAs after intravenous administration in rats strongly predicted the β-cell mass and was inversely related to the glucose excursions during an intraperitoneal glucose tolerance test. CONCLUSIONS Our data provide strong evidence that the presented SCAs are highly specific for pancreatic β-cells and enable imaging and quantification in vivo. PMID:19592622

  20. Tumor-targeting peptides from combinatorial libraries*

    Science.gov (United States)

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

  1. An improved yeast transformation method for the generation of very large human antibody libraries.

    Science.gov (United States)

    Benatuil, Lorenzo; Perez, Jennifer M; Belk, Jonathan; Hsieh, Chung-Ming

    2010-04-01

    Antibody library selection by yeast display technology is an efficient and highly sensitive method to identify binders to target antigens. This powerful selection tool, however, is often hampered by the typically modest size of yeast libraries (approximately 10(7)) due to the limited yeast transformation efficiency, and the full potential of the yeast display technology for antibody discovery and engineering can only be realized if it can be coupled with a mean to generate very large yeast libraries. We describe here a yeast transformation method by electroporation that allows for the efficient generation of large antibody libraries up to 10(10) in size. Multiple components and conditions including CaCl(2), MgCl(2), sucrose, sorbitol, lithium acetate, dithiothreitol, electroporation voltage, DNA input and cell volume have been tested to identify the best combination. By applying this developed protocol, we have constructed a 1.4 x 10(10) human spleen antibody library essentially in 1 day with a transformation efficiency of 1-1.5 x 10(8) transformants/microg vector DNA. Taken together, we have developed a highly efficient yeast transformation method that enables the generation of very large and productive human antibody libraries for antibody discovery, and we are now routinely making 10(9) libraries in a day for antibody engineering purposes.

  2. Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N SARS-CoV protein using a phage display approach

    Directory of Open Access Journals (Sweden)

    Grasso Felicia

    2005-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. Methods The human synthetic single-chain fragment variable (scFv ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. Results Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. Conclusion The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.

  3. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    Science.gov (United States)

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai

    2013-01-01

    Abstract Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening strategy by using cells that co-express GFP and CCR5, along with an excess of control cells that do not express these proteins (and are otherwise identical to the CCR5-expressing cells). These control cells are intended to remove most of the phages that bind the cells nonspecifically; thus leading to an enrichment of the phages presenting anti-CCR5-specific antibodies. Subsequently, the CCR5-presenting cells were quantitatively sorted by flow cytometry, and the bound phages were eluted, amplified, and used for further successive selection rounds. Several different clones of human single-chain Fv antibodies that interact with CCR5-expressing cells were identified. The most specific monoclonal antibody was converted to a full-length IgG and bound the second extracellular loop of CCR5. The experimental approach presented herein for screening for CCR5-specific antibodies can be applicable to screen antibody-presenting phage libraries against any cell-surface expressed protein of interest. PMID:23941674

  4. Targeting the active site of the placental isozyme of alkaline phosphatase by phage-displayed scFv antibodies selected by a specific uncompetitive inhibitor

    Directory of Open Access Journals (Sweden)

    Kala Mrinalini

    2005-12-01

    Full Text Available Abstract Background The isozymes of alkaline phosphatase, the tissue non-specific, intestinal and placental, have similar properties and a high degree of identity. The placental isozyme (PLAP is an oncofetal antigen expressed in several malignancies including choriocarcinoma, seminoma and ovarian carcinoma. We had earlier attempted to isolate PLAP-specific scFv from a synthetic human immunoglobulin library but were unable to do so, presumably because of the similarity between the isozymes. In this work, we have employed a PLAP-specific uncompetitive inhibitor, L-Phe-Gly-Gly, to select isozyme specific scFvs. An uncompetitive inhibitor binds to the enzyme in the presence of substrate and stabilizes the enzyme-substrate complex. Several uncompetitive inhibitors have varying degrees of isozyme specificity for human alkaline phosphatase isozymes. A specific uncompetitive inhibitor would be able to unmask conformational differences between the otherwise very similar molecules. Also, such inhibitors would be directed to regions at/close to the active site of the enzyme. In this work, the library was first incubated with PLAP and the bound clones then eluted by incubation with L-Phe-Gly-Gly along with the substrate, para-nitro phenyl phosphate (pNPP. The scFvs were then studied with regard to the biochemical modulation of their binding, isozyme specificity and effect on enzyme activity. Results Of 13 clones studied initially, the binding of 9 was inhibited by L-Phe-Gly-Gly (with pNPP and 2 clones were inhibited by pNPP alone. Two clones had absolute and 2 clones had partial specificity to PLAP. Two clones were cross-reactive with only one other isozyme. Three scFv clones, having an accessible His6-tag, were purified and studied for their modulation of enzyme activity. All the three scFvs inhibited PLAP activity with the kinetics of competitive inhibition. Cell ELISA could demonstrate binding of the specific scFvs to the cell surface expressed PLAP

  5. 68Ga-labeled phage-display selected peptides as tracers for positron emission tomography imaging of Staphylococcus aureus biofilm-associated infections: Selection, radiolabelling and preliminary biological evaluation

    International Nuclear Information System (INIS)

    Nielsen, Karin M.; Kyneb, Majbritt H.; Alstrup, Aage K.O.; Jensen, Jakob J.; Bender, Dirk; Schønheyder, Henrik C.; Afzelius, Pia; Nielsen, Ole L.; Jensen, Svend B.

    2016-01-01

    Introduction: Staphylococcus aureus is a major cause of skin and deep-sited infections, often associated with the formation of biofilms. Early diagnosis and initiated therapy is essential to prevent disease progression and to reduce complications that can be serious. Imaging techniques are helpful combining anatomical with functional data in order to describe and characterize site, extent and activity of the disease. The purpose of the study was to identify and 68 Ga-label peptides with affinity for S. aureus biofilm and evaluate their potential as bacteria-specific positron emission tomography (PET) imaging agents. Methods: Phage-displayed dodecapeptides were selected using an in vitro grown S. aureus biofilm as target. One cyclic (A8) and two linear (A9, A11) dodecapeptides were custom synthesized with 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) conjugated via a lysine linker (K), and for A11 also a glycine–serine–glycine spacer (GSG). The 68 Ga-labeling of A8-K-DOTA, A9-K-DOTA, and A11-GSGK-DOTA were optimized and in vitro bacterial binding was evaluated for 68 Ga-A9-K-DOTA and 68 Ga-A11-GSGK-DOTA. Stability of 68 Ga-A9-K-DOTA was studied in vitro in human serum, while the in vivo plasma stability was analyzed in mice and pigs. Additionally, the whole-body distribution kinetics of 68 Ga-A9-K-DOTA was measured in vivo by PET imaging of pigs and ex vivo in excised mice tissues. Results: The 68 Ga-A9-K-DOTA and 68 Ga-A11-GSGK-DOTA remained stable in product formulation, whereas 68 Ga-A8-K-DOTA was unstable. The S. aureus binding of 68 Ga-A11-GSGK-DOTA and 68 Ga-A9-K-DOTA was observed in vitro, though blocking of the binding was not possible by excess of cold peptide. The 68 Ga-A9-K-DOTA was degraded slowly in vitro, while the combined in vivo evaluation in pigs and mice showed a rapid blood clearance and renal excretion of the 68 Ga-A9-K-DOTA. Conclusion: The preliminary in vitro and in vivo studies of the phage-display S. aureus

  6. Marketing Library and Information Services: Comparing Experiences at Large Institutions.

    Science.gov (United States)

    Noel, Robert; Waugh, Timothy

    This paper explores some of the similarities and differences between publicizing information services within the academic and corporate environments, comparing the marketing experiences of Abbot Laboratories (Illinois) and Indiana University. It shows some innovative online marketing tools, including an animated gif model of a large, integrated…

  7. Phage display selection of fully human antibody fragments to inhibit growth-promoting effects of glycine-extended gastrin 17 on human colorectal cancer cells.

    Science.gov (United States)

    Khajeh, Shirin; Tohidkia, Mohammad Reza; Aghanejad, Ayuob; Mehdipour, Tayebeh; Fathi, Farzaneh; Omidi, Yadollah

    2018-06-09

    Glycine-extended gastrin 17 (G17-Gly), a dominant processing intermediate of gastrin gene, has been implicated in the development or maintenance of colorectal cancers (CRCs). Hence, neutralizing G17-Gly activity by antibody entities can provide a potential therapeutic strategy in the patients with CRCs. To this end, we isolated fully human antibody fragments from a phage antibody library through biopanning against different epitopes of G17-Gly in order to obtain the highest possible antibody diversity. ELISA screening and sequence analysis identified 2 scFvs and 4 V L antibody fragments. Kinetic analysis of the antibody fragments by SPR revealed K D values to be in the nanomolar range (87.9-334 nM). The selected anti-G17-Gly antibody fragments were analyzed for growth inhibition and apoptotic assays in a CRC cell line, HCT-116, which is well-characterized for expressing gastrin intermediate species but not amidated gastrin. The antibody fragments exhibited significant inhibition of HCT-116 cells proliferation ranging from 36.5 to 73% of controls. Further, Annexin V/PI staining indicated that apoptosis rates of scFv H8 and V L G8 treated cells were 45.8 and 63%, respectively. Based on these results, we for the first time, demonstrated the isolation of anti-G17-Gly human scFv and V L antibodies with potential therapeutic applications in G17-Gly-responsive tumors.

  8. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued

    NARCIS (Netherlands)

    van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I.; Lappalainen, Jari P.; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J.; Verrijp, Kiek; Leenders, William P J

    2016-01-01

    Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological

  9. Design of focused and restrained subsets from extremely large virtual libraries.

    Science.gov (United States)

    Jamois, Eric A; Lin, Chien T; Waldman, Marvin

    2003-11-01

    With the current and ever-growing offering of reagents along with the vast palette of organic reactions, virtual libraries accessible to combinatorial chemists can reach sizes of billions of compounds or more. Extracting practical size subsets for experimentation has remained an essential step in the design of combinatorial libraries. A typical approach to computational library design involves enumeration of structures and properties for the entire virtual library, which may be unpractical for such large libraries. This study describes a new approach termed as on the fly optimization (OTFO) where descriptors are computed as needed within the subset optimization cycle and without intermediate enumeration of structures. Results reported herein highlight the advantages of coupling an ultra-fast descriptor calculation engine to subset optimization capabilities. We also show that enumeration of properties for the entire virtual library may not only be unpractical but also wasteful. Successful design of focused and restrained subsets can be achieved while sampling only a small fraction of the virtual library. We also investigate the stability of the method and compare results obtained from simulated annealing (SA) and genetic algorithms (GA).

  10. A Conserved Epitope Mapped with a Monoclonal Antibody against the VP3 Protein of Goose Parvovirus by Using Peptide Screening and Phage Display Approaches.

    Science.gov (United States)

    Li, Chenxi; Liu, Hongyu; Li, Jinzhe; Liu, Dafei; Meng, Runze; Zhang, Qingshan; Shaozhou, Wulin; Bai, Xiaofei; Zhang, Tingting; Liu, Ming; Zhang, Yun

    2016-01-01

    Waterfowl parvovirus (WPV) infection causes high mortality and morbidity in both geese (Anser anser) and Muscovy ducks (Cairina moschata), resulting in significant losses to the waterfowl industries. The VP3 protein of WPV is a major structural protein that induces neutralizing antibodies in the waterfowl. However, B-cell epitopes on the VP3 protein of WPV have not been characterized. To understand the antigenic determinants of the VP3 protein, we used the monoclonal antibody (mAb) 4A6 to screen a set of eight partially expressed overlapping peptides spanning VP3. Using western blotting and an enzyme-linked immunosorbent assay (ELISA), we localized the VP3 epitope between amino acids (aa) 57 and 112. To identify the essential epitope residues, a phage library displaying 12-mer random peptides was screened with mAb 4A6. Phage clone peptides displayed a consensus sequence of YxRFHxH that mimicked the sequence 82Y/FNRFHCH88, which corresponded to amino acid residues 82 to 88 of VP3 protein of WPVs. mAb 4A6 binding to biotinylated fragments corresponding to amino acid residues 82 to 88 of the VP3 protein verified that the 82FxRFHxH88 was the VP3 epitope and that amino acids 82F is necessary to retain maximal binding to mAb 4A6. Parvovirus-positive goose and duck sera reacted with the epitope peptide by dot blotting assay, revealing the importance of these amino acids of the epitope in antibody-epitope binding reactivity. We identified the motif FxRFHxH as a VP3-specific B-cell epitope that is recognized by the neutralizing mAb 4A6. This finding might be valuable in understanding of the antigenic topology of VP3 of WPV.

  11. Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

    Science.gov (United States)

    Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

    2011-07-18

    The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. A generic library for large scale solution of PDEs on modern heterogeneous architectures

    DEFF Research Database (Denmark)

    Glimberg, Stefan Lemvig; Engsig-Karup, Allan Peter

    2012-01-01

    Adapting to new programming models for modern multi- and many-core architectures requires code-rewriting and changing algorithms and data structures, in order to achieve good efficiency and scalability. We present a generic library for solving large scale partial differential equations (PDEs......), capable of utilizing heterogeneous CPU/GPU environments. The library can be used for fast proto-typing of PDE solvers, based on finite difference approximations of spatial derivatives in one, two, or three dimensions. In order to efficiently solve large scale problems, we keep memory consumption...... and memory access low, using a low-storage implementation of flexible-order finite difference operators. We will illustrate the use of library components by assembling such matrix-free operators to be used with one of the supported iterative solvers, such as GMRES, CG, Multigrid or Defect Correction...

  13. Utilizing Web 2.0 Technologies for Library Web Tutorials: An Examination of Instruction on Community College Libraries' Websites Serving Large Student Bodies

    Science.gov (United States)

    Blummer, Barbara; Kenton, Jeffrey M.

    2015-01-01

    This is the second part of a series on Web 2.0 tools available from community college libraries' Websites. The first article appeared in an earlier volume of this journal and it illustrated the wide variety of Web 2.0 tools on community college libraries' Websites serving large student bodies (Blummer and Kenton 2014). The research found many of…

  14. Vascular targeting with peptide libraries

    Energy Technology Data Exchange (ETDEWEB)

    Pasqualini, R. [La Jolla Cancer Research Center The Burnham Inst., La Jolla CA (United States)

    1999-06-01

    The authors have developed an 'in vivo' selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, they have isolate several organ and tumor-homing peptides. They have shown that each of those peptides binds of different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are up regulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animals models decrease toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angio genesis and lead to advances to extend the potential for targeting of drugs, genes and radionuclides in the context of many diseases.

  15. Library

    OpenAIRE

    Dulaney, Ronald E. Jr.

    1997-01-01

    This study began with the desire to design a public town library of the future and became a search for an inkling of what is essential to Architecture. It is murky and full of contradictions. It asks more than it proposes, and the traces of its windings are better ordered through collage than logical synthesis. This study is neither a thesis nor a synthesis. When drawing out the measure of this study it may be beneficial to state what it attempts to place at the ...

  16. Ulysses: accurate detection of low-frequency structural variations in large insert-size sequencing libraries.

    Science.gov (United States)

    Gillet-Markowska, Alexandre; Richard, Hugues; Fischer, Gilles; Lafontaine, Ingrid

    2015-03-15

    The detection of structural variations (SVs) in short-range Paired-End (PE) libraries remains challenging because SV breakpoints can involve large dispersed repeated sequences, or carry inherent complexity, hardly resolvable with classical PE sequencing data. In contrast, large insert-size sequencing libraries (Mate-Pair libraries) provide higher physical coverage of the genome and give access to repeat-containing regions. They can thus theoretically overcome previous limitations as they are becoming routinely accessible. Nevertheless, broad insert size distributions and high rates of chimerical sequences are usually associated to this type of libraries, which makes the accurate annotation of SV challenging. Here, we present Ulysses, a tool that achieves drastically higher detection accuracy than existing tools, both on simulated and real mate-pair sequencing datasets from the 1000 Human Genome project. Ulysses achieves high specificity over the complete spectrum of variants by assessing, in a principled manner, the statistical significance of each possible variant (duplications, deletions, translocations, insertions and inversions) against an explicit model for the generation of experimental noise. This statistical model proves particularly useful for the detection of low frequency variants. SV detection performed on a large insert Mate-Pair library from a breast cancer sample revealed a high level of somatic duplications in the tumor and, to a lesser extent, in the blood sample as well. Altogether, these results show that Ulysses is a valuable tool for the characterization of somatic mosaicism in human tissues and in cancer genomes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries.

    Science.gov (United States)

    Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z

    2009-05-01

    Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

  18. Knowledgeability of Copyright Law among Librarians and Library Paraprofessionals Employed in Adult Services at a Large Public Library System.

    Science.gov (United States)

    Lavelle, Bridget M.

    Since public libraries contain copyrighted works in the form of print, electronic or audiovisual sources, librarians and library paraprofessionals need to possess sufficient knowledge of United States copyright law to meet the information needs of patrons successfully and legally. A literature review revealed that minimal works address this topic.…

  19. Analysis of the binding of pro-urokinase and urokinase-plasminogen activator inhibitor-1 complex to the low density lipoprotein receptor-related protein using a Fab fragment selected from a phage-displayed Fab library

    NARCIS (Netherlands)

    Horn, I. R.; Moestrup, S. K.; van den Berg, B. M.; Pannekoek, H.; Nielsen, M. S.; van Zonneveld, A. J.

    1995-01-01

    The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) mediates endocytosis of a number of structurally unrelated ligands, including complexes of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) or urokinase plasminogen

  20. CERN Library | Mario Campanelli presents "Inside CERN's Large Hadron Collider" | 16 March

    CERN Multimedia

    CERN Library

    2016-01-01

    "Inside CERN's Large Hadron Collider" by Mario Campanelli. Presentation on Wednesday, 16 March at 4 p.m. in the Library (bldg 52-1-052) The book aims to explain the historical development of particle physics, with special emphasis on CERN and collider physics. It describes in detail the LHC accelerator and its detectors, describing the science involved as well as the sociology of big collaborations, culminating with the discovery of the Higgs boson.  Inside CERN's Large Hadron Collider  Mario Campanelli World Scientific Publishing, 2015  ISBN 9789814656641​

  1. Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

    Science.gov (United States)

    Lim, Theam Soon; Chan, Soo Khim

    2016-01-01

    Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Identification of tumor associated single-chain Fv by panning and screening antibody phage library using tumor cells

    Science.gov (United States)

    Nie, Yong-Zhan; He, Feng-Tian; Li, Zhi-Kui; Wu, Kai-Chun; Cao, Yun-Xin; Chen, Bao-Jun; Fan, Dai-Ming

    2002-01-01

    AIM: To study the feasibility of panning and screening phage-displaying recombinant single-chain variable fragment (ScFv) of anti-tumor monoclonal antibodies for fixed whole cells as the carriers of mAb-binding antigens. METHODS: The recombinant phage displaying libraries for anti-colorectal tumor mAb MC3Ab, MC5Ab and anti-gastric tumor mAb MGD1 was constructed. Panning and screening were carried out by means of modified fixation of colorectal and gastric tumor cells expressed the mAb-binding antigens. Concordance of binding specificity to tumor cells between phage clones and parent antibodies was analyzed. The phage of positive clones was identified with competitive ELISA, and infected by E. coli HB2151 to express soluble ScFv. RESULTS: The ratio of positive clones to MC3-ScF-MC5-ScFv and MGD1-ScFv were 60%, 24% and 30%. MC3-ScFv had Mr 32000 confirmed by Western blot. The specificity to antigen had no difference between 4 positive recombinant phage antibodies and MC3Ab. CONCLUSION: The modified process of fixing whole tumor cells is efficient, convenient and feasible to pan and screen the phage-displaying ScFv of anti-tumor monoclonal antibodies. PMID:12174367

  3. The TPAC Digital Library: A Web Application for Publishing Large Catalogs of Earth Science Data

    Science.gov (United States)

    Blain, P.; Pugh, T.

    2010-12-01

    The Tasmanian Partnership for Advanced Computing (TPAC) has developed a rich web-based application that publishes large catalogs of scientific datasets. The TPAC Digital Library provides a user interface for viewing, searching, and accessing the catalog data collections, as well as enabling data services for user access. The product also provides management functions for librarians of digital data collections. The search features allow files to be selected graphically based on geospatial extent, or by file name, variable name, attribute value, and by tag. Alternatively, there is a file manager style interface that provides a direct route to the data. The interface is specifically geared towards discovery and access of earth science data files, which makes it intuitive and easy to navigate. Files can be downloaded, or accessed through OPeNDAP, GridFTP, WCS, Matlab and other interfaces. The digital library can harvest metadata from THREDDS, Hyrax, IPCC catalogs and other instances of the digital library. The product is freely available under an open-source license, and is currently deployed by a small but active user base. It has existed since 2005, and remains under constant development by TPAC and other contributors (including the Australian Bureau of Meteorology). Current development initiatives will allow interoperability with library service protocols, as well as other data archive organizations and scientific bodies for data reference transparency. There is a project in progress that will allow the data collection’s owner to attach attribute information, access rights, and meta-data to the data collection to conform to various user community and service standards. Future releases will allow publishers to attach media rich information about the data collection, as well as additional information about scientific results, and papers and web pages that reference the data collection. The presentation will discuss the current implementation, and future directions.

  4. Construction of a large-scale Burkholderia cenocepacia J2315 transposon mutant library

    Science.gov (United States)

    Wong, Yee-Chin; Pain, Arnab; Nathan, Sheila

    2014-09-01

    Burkholderia cenocepacia, a pathogenic member of the Burkholderia cepacia complex (Bcc), has emerged as a significant threat towards cystic fibrosis patients, where infection often leads to the fatal clinical manifestation known as cepacia syndrome. Many studies have investigated the pathogenicity of B. cenocepacia as well as its ability to become highly resistant towards many of the antibiotics currently in use. In addition, studies have also been undertaken to understand the pathogen's capacity to adapt and survive in a broad range of environments. Transposon based mutagenesis has been widely used in creating insertional knock-out mutants and coupled with recent advances in sequencing technology, robust tools to study gene function in a genome-wide manner have been developed based on the assembly of saturated transposon mutant libraries. In this study, we describe the construction of a large-scale library of B. cenocepacia transposon mutants. To create transposon mutants of B. cenocepacia strain J2315, electrocompetent bacteria were electrotransformed with the EZ-Tn5 transposome. Tetracyline resistant colonies were harvested off selective agar and pooled. Mutants were generated in multiple batches with each batch consisting of ˜20,000 to 40,000 mutants. Transposon insertion was validated by PCR amplification of the transposon region. In conclusion, a saturated B. cenocepacia J2315 transposon mutant library with an estimated total number of 500,000 mutants was successfully constructed. This mutant library can now be further exploited as a genetic tool to assess the function of every gene in the genome, facilitating the discovery of genes important for bacterial survival and adaptation, as well as virulence.

  5. Usability Testing of a Large, Multidisciplinary Library Database: Basic Search and Visual Search

    Directory of Open Access Journals (Sweden)

    Jody Condit Fagan

    2006-09-01

    Full Text Available Visual search interfaces have been shown by researchers to assist users with information search and retrieval. Recently, several major library vendors have added visual search interfaces or functions to their products. For public service librarians, perhaps the most critical area of interest is the extent to which visual search interfaces and text-based search interfaces support research. This study presents the results of eight full-scale usability tests of both the EBSCOhost Basic Search and Visual Search in the context of a large liberal arts university.

  6. Generation of human Fab antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human Fab (fragment antigen binding) antibody libraries. In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final Fab products that are used for cloning.

  7. Generation of human scFv antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human scFv (single chain antibody fragment) libraries using a short linker (GGSSRSS) or a long linker (GGSSRSSSSGGGGSGGGG). In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final scFv products that are used for cloning.

  8. Epitope selection from an uncensored peptide library displayed on avian leukosis virus

    International Nuclear Information System (INIS)

    Khare, Pranay D.; Rosales, Ana G.; Bailey, Kent R.; Russell, Stephen J.; Federspiel, Mark J.

    2003-01-01

    Phage display libraries have provided an extraordinarily versatile technology to facilitate the isolation of peptides, growth factors, single chain antibodies, and enzymes with desired binding specificities or enzymatic activities. The overall diversity of peptides in phage display libraries can be significantly limited by Escherichia coli protein folding and processing machinery, which result in sequence censorship. To achieve an optimal diversity of displayed eukaryotic peptides, the library should be produced in the endoplasmic reticulum of eukaryotic cells using a eukaryotic display platform. In the accompanying article, we presented experiments that demonstrate that polypeptides of various sizes could be efficiently displayed on the envelope glycoproteins of a eukaryotic virus, avian leukosis virus (ALV), and the displayed polypeptides could efficiently attach to cognate receptors without interfering with viral attachment and entry into susceptible cells. In this study, methods were developed to construct a model library of randomized eight amino acid peptides using the ALV eukaryotic display platform and screen the library for specific epitopes using immobilized antibodies. A virus library with approximately 2 x 10 6 different members was generated from a plasmid library of approximately 5 x 10 6 diversity. The sequences of the randomized 24 nucleotide/eight amino acid regions of representatives of the plasmid and virus libraries were analyzed. No significant sequence censorship was observed in producing the virus display library from the plasmid library. Different populations of peptide epitopes were selected from the virus library when different monoclonal antibodies were used as the target. The results of these two studies clearly demonstrate the potential of ALV as a eukaryotic platform for the display and selection of eukaryotic polypeptides libraries

  9. Extracting scientific articles from a large digital archive: BioStor and the Biodiversity Heritage Library.

    Science.gov (United States)

    Page, Roderic D M

    2011-05-23

    The Biodiversity Heritage Library (BHL) is a large digital archive of legacy biological literature, comprising over 31 million pages scanned from books, monographs, and journals. During the digitisation process basic metadata about the scanned items is recorded, but not article-level metadata. Given that the article is the standard unit of citation, this makes it difficult to locate cited literature in BHL. Adding the ability to easily find articles in BHL would greatly enhance the value of the archive. A service was developed to locate articles in BHL based on matching article metadata to BHL metadata using approximate string matching, regular expressions, and string alignment. This article locating service is exposed as a standard OpenURL resolver on the BioStor web site http://biostor.org/openurl/. This resolver can be used on the web, or called by bibliographic tools that support OpenURL. BioStor provides tools for extracting, annotating, and visualising articles from the Biodiversity Heritage Library. BioStor is available from http://biostor.org/.

  10. Building an Undergraduate Book Approval Plan for a Large Academic Library

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2007-05-01

    Full Text Available The University of Alberta Libraries (UAL, working with two book vendors, created large-scale undergraduate book approval plans to deliver new publications. Detailed selections profiles were created for many subject areas, designed to deliver books that would have been obvious choices by subject selectors. More than 5800 monographs were received through the book approval plans during the pilot period. These volumes proved to be highly relevant to users, showing twice as much circulation as other monographs acquired during the same time period. Goals achieved through this project include: release of selectors’ time from routine work, systematic acquisition of a broadly based high-demand undergraduate collection and faster delivery of undergraduate materials. This successful program will be expanded and incorporated into UAL’s normal acquisitions processes for undergraduate materials.

  11. Molecular descriptor data explain market prices of a large commercial chemical compound library

    Science.gov (United States)

    Polanski, Jaroslaw; Kucia, Urszula; Duszkiewicz, Roksana; Kurczyk, Agata; Magdziarz, Tomasz; Gasteiger, Johann

    2016-06-01

    The relationship between the structure and a property of a chemical compound is an essential concept in chemistry guiding, for example, drug design. Actually, however, we need economic considerations to fully understand the fate of drugs on the market. We are performing here for the first time the exploration of quantitative structure-economy relationships (QSER) for a large dataset of a commercial building block library of over 2.2 million chemicals. This investigation provided molecular statistics that shows that on average what we are paying for is the quantity of matter. On the other side, the influence of synthetic availability scores is also revealed. Finally, we are buying substances by looking at the molecular graphs or molecular formulas. Thus, those molecules that have a higher number of atoms look more attractive and are, on average, also more expensive. Our study shows how data binning could be used as an informative method when analyzing big data in chemistry.

  12. Building an Undergraduate Book Approval Plan for a Large Academic Library

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2007-03-01

    Full Text Available The University of Alberta Libraries (UAL, working with two book vendors,created large-scale undergraduate book approval plans to deliver newpublications. Detailed selections profiles were created for many subject areas,designed to deliver books that would have been obvious choices by subjectselectors. More than 5800 monographs were received through the book approvalplans during the pilot period. These volumes proved to be highly relevant tousers, showing twice as much circulation as other monographs acquired duringthe same time period. Goals achieved through this project include: release ofselectors’ time from routine work, systematic acquisition of a broadly based highdemandundergraduate collection and faster delivery of undergraduate materials.This successful program will be expanded and incorporated into UAL’s normalacquisitions processes for undergraduate materials.

  13. High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation

    Directory of Open Access Journals (Sweden)

    Kathrin Tissot

    2011-05-01

    Full Text Available Since the initial description of phage display technology for the generation of human antibodies, a variety of selection methods has been developed. The most critical parameter for all in vitro-based approaches is the quality of the antibody library. Concurrent evolution of the libraries has allowed display and selection technologies to reveal their full potential. They come in different flavors, from naïve to fully synthetic and differ in terms of size, quality, method of preparation, framework and CDR composition. Early on, the focus has mainly been on affinities and thus on library size and diversity. Subsequently, the increased awareness of developability and cost of goods as important success factors has spurred efforts to generate libraries with improved biophysical properties and favorable production characteristics. More recently a major focus on reduction of unwanted side effects through reduced immunogenicity and improved overall biophysical behavior has led to a re-evaluation of library design.

  14. A large synthetic peptide and phosphopeptide reference library for mass spectrometry–based proteomics

    NARCIS (Netherlands)

    Marx, H.; Lemeer, S.; Schliep, J.E.; Matheron, L.I.; Mohammed, S.; Cox, J.; Mann, M.; Heck, A.J.R.; Kuster, B.

    2013-01-01

    We present a peptide library and data resource of >100,000 synthetic, unmodified peptides and their phosphorylated counterparts with known sequences and phosphorylation sites. Analysis of the library by mass spectrometry yielded a data set that we used to evaluate the merits of different search

  15. Service Quality: An Unobtrusive Investigation of Interlibrary Loan in Large Public Libraries in Canada.

    Science.gov (United States)

    Hebert, Francoise

    1994-01-01

    Describes a study that investigated the quality of interlibrary loan services in Canadian public libraries from the library's and the user's perspectives and then compared results. Measures of interlibrary loan performance are reviewed; an alternative conceptualization of service quality is discussed; and SERVQUAL, a measure of service quality, is…

  16. Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries

    Directory of Open Access Journals (Sweden)

    Han Bucong

    2012-11-01

    Full Text Available Abstract Background Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. Results We evaluated support vector machines (SVM as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33% of 13.56M PubChem, 1,496 (0.89% of 168 K MDDR, and 719 (7.73% of 9,305 MDDR compounds similar to the known inhibitors. Conclusions SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

  17. Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries.

    Science.gov (United States)

    Han, Bucong; Ma, Xiaohua; Zhao, Ruiying; Zhang, Jingxian; Wei, Xiaona; Liu, Xianghui; Liu, Xin; Zhang, Cunlong; Tan, Chunyan; Jiang, Yuyang; Chen, Yuzong

    2012-11-23

    Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

  18. VisIVO: A Library and Integrated Tools for Large Astrophysical Dataset Exploration

    Science.gov (United States)

    Becciani, U.; Costa, A.; Ersotelos, N.; Krokos, M.; Massimino, P.; Petta, C.; Vitello, F.

    2012-09-01

    VisIVO provides an integrated suite of tools and services that can be used in many scientific fields. VisIVO development starts in the Virtual Observatory framework. VisIVO allows users to visualize meaningfully highly-complex, large-scale datasets and create movies of these visualizations based on distributed infrastructures. VisIVO supports high-performance, multi-dimensional visualization of large-scale astrophysical datasets. Users can rapidly obtain meaningful visualizations while preserving full and intuitive control of the relevant parameters. VisIVO consists of VisIVO Desktop - a stand-alone application for interactive visualization on standard PCs, VisIVO Server - a platform for high performance visualization, VisIVO Web - a custom designed web portal, VisIVOSmartphone - an application to exploit the VisIVO Server functionality and the latest VisIVO features: VisIVO Library allows a job running on a computational system (grid, HPC, etc.) to produce movies directly with the code internal data arrays without the need to produce intermediate files. This is particularly important when running on large computational facilities, where the user wants to have a look at the results during the data production phase. For example, in grid computing facilities, images can be produced directly in the grid catalogue while the user code is running in a system that cannot be directly accessed by the user (a worker node). The deployment of VisIVO on the DG and gLite is carried out with the support of EDGI and EGI-Inspire projects. Depending on the structure and size of datasets under consideration, the data exploration process could take several hours of CPU for creating customized views and the production of movies could potentially last several days. For this reason an MPI parallel version of VisIVO could play a fundamental role in increasing performance, e.g. it could be automatically deployed on nodes that are MPI aware. A central concept in our development is thus to

  19. Experience of Google's latest deep learning library, TensorFlow, in a large-scale WLCG cluster

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Gen; Smith, Joshua Wyatt; Quadt, Arnulf [II. Physikalisches Institut, Georg-August-Universitaet Goettingen (Germany)

    2016-07-01

    The researchers at the Google Brain team released their second generation's Deep Learning library, TensorFlow, as an open-source package under the Apache 2.0 license in November, 2015. Google has already deployed the first generation's library using DistBlief in various systems such as Google Search, advertising systems, speech recognition systems, Google Images, Google Maps, Street View, Google Translate and many other latest products. In addition, many researchers in high energy physics have recently started to understand and use Deep Learning algorithms in their own research and analysis. We conceive a first use-case scenario of TensorFlow to create the Deep Learning models from high-dimensional inputs like physics analysis data in a large-scale WLCG computing cluster. TensorFlow carries out computations using a dataflow model and graph structure onto a wide variety of different hardware platforms and systems, such as many CPU architectures, GPUs and smartphone platforms. Having a single library that can distribute the computations to create a model to the various platforms and systems would significantly simplify the use of Deep Learning algorithms in high energy physics. We deploy TensorFlow with the Docker container environments and present the first use in our grid system.

  20. Using herbarium-derived DNAs to assemble a large-scale DNA barcode library for the vascular plants of Canada.

    Science.gov (United States)

    Kuzmina, Maria L; Braukmann, Thomas W A; Fazekas, Aron J; Graham, Sean W; Dewaard, Stephanie L; Rodrigues, Anuar; Bennett, Bruce A; Dickinson, Timothy A; Saarela, Jeffery M; Catling, Paul M; Newmaster, Steven G; Percy, Diana M; Fenneman, Erin; Lauron-Moreau, Aurélien; Ford, Bruce; Gillespie, Lynn; Subramanyam, Ragupathy; Whitton, Jeannette; Jennings, Linda; Metsger, Deborah; Warne, Connor P; Brown, Allison; Sears, Elizabeth; Dewaard, Jeremy R; Zakharov, Evgeny V; Hebert, Paul D N

    2017-12-01

    Constructing complete, accurate plant DNA barcode reference libraries can be logistically challenging for large-scale floras. Here we demonstrate the promise and challenges of using herbarium collections for building a DNA barcode reference library for the vascular plant flora of Canada. Our study examined 20,816 specimens representing 5076 of 5190 vascular plant species in Canada (98%). For 98% of the specimens, at least one of the DNA barcode regions was recovered from the plastid loci rbcL and matK and from the nuclear ITS2 region. We used beta regression to quantify the effects of age, type of preservation, and taxonomic affiliation (family) on DNA sequence recovery. Specimen age and method of preservation had significant effects on sequence recovery for all markers, but influenced some families more (e.g., Boraginaceae) than others (e.g., Asteraceae). Our DNA barcode library represents an unparalleled resource for metagenomic and ecological genetic research working on temperate and arctic biomes. An observed decline in sequence recovery with specimen age may be associated with poor primer matches, intragenomic variation (for ITS2), or inhibitory secondary compounds in some taxa.

  1. Exploring Publishing Patterns at a Large Research University: Implications for Library

    Directory of Open Access Journals (Sweden)

    Kathleen Amos

    2012-09-01

    Full Text Available Objective – The research project sought to explore the value of data on publication patterns for decision-making regarding scholarly communications and collection development programs at a research-intensive post-secondary institution, the University of Utah in the United States.Methods – Publication data for prolific University of Utah authors were gathered from Scopus for the year 2009. The availability to University of Utah faculty, staff, and students of the journals in which University of Utah authors published was determined using the University of Utah Libraries’ catalogue; usage was estimated based on publisher-provided download statistics and requests through interlibrary loan; and costs were calculated from invoices, a periodicals directory, and publisher websites and communications. Indicators of value included the cost-per-use of journals to which the University of Utah Libraries subscribed, a comparison of interlibrary loan costs to subscription costs for journals to which the University of Utah Libraries did not subscribe, the relationship between publishing venue and usage, and the relationship between publishing venue and cost-per-use.Results – There were 22 University of Utah authors who published 10 or more articles in 2009. Collectively, these authors produced 275 articles in 162 journals. The University of Utah provided access through library subscriptions to 83% of the journals for which access, usage, and cost data were available, with widely varying usage and at widely varying costs. Cost-per-use and a comparison of interlibrary loan to subscription costs provided evidence of the effectiveness of collection development practices. However, at the individual journal title level, there was little overlap between the various indicators of journal value, with the highest ranked, or most valuable, journals differing depending on the indicator considered. Few of the articles studied appeared in open access journals

  2. Discovery of novel SERCA inhibitors by virtual screening of a large compound library.

    Science.gov (United States)

    Elam, Christopher; Lape, Michael; Deye, Joel; Zultowsky, Jodie; Stanton, David T; Paula, Stefan

    2011-05-01

    Two screening protocols based on recursive partitioning and computational ligand docking methodologies, respectively, were employed for virtual screens of a compound library with 345,000 entries for novel inhibitors of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA), a potential target for cancer chemotherapy. A total of 72 compounds that were predicted to be potential inhibitors of SERCA were tested in bioassays and 17 displayed inhibitory potencies at concentrations below 100 μM. The majority of these inhibitors were composed of two phenyl rings tethered to each other by a short link of one to three atoms. Putative interactions between SERCA and the inhibitors were identified by inspection of docking-predicted poses and some of the structural features required for effective SERCA inhibition were determined by analysis of the classification pattern employed by the recursive partitioning models. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  3. Efficient Computation of Sparse Matrix Functions for Large-Scale Electronic Structure Calculations: The CheSS Library.

    Science.gov (United States)

    Mohr, Stephan; Dawson, William; Wagner, Michael; Caliste, Damien; Nakajima, Takahito; Genovese, Luigi

    2017-10-10

    We present CheSS, the "Chebyshev Sparse Solvers" library, which has been designed to solve typical problems arising in large-scale electronic structure calculations using localized basis sets. The library is based on a flexible and efficient expansion in terms of Chebyshev polynomials and presently features the calculation of the density matrix, the calculation of matrix powers for arbitrary powers, and the extraction of eigenvalues in a selected interval. CheSS is able to exploit the sparsity of the matrices and scales linearly with respect to the number of nonzero entries, making it well-suited for large-scale calculations. The approach is particularly adapted for setups leading to small spectral widths of the involved matrices and outperforms alternative methods in this regime. By coupling CheSS to the DFT code BigDFT, we show that such a favorable setup is indeed possible in practice. In addition, the approach based on Chebyshev polynomials can be massively parallelized, and CheSS exhibits excellent scaling up to thousands of cores even for relatively small matrix sizes.

  4. 15th ACM/IEEE-CS Joint Conference on Digital Libraries: Large, Dynamic and Ubiquitous - The Era of the Digital Library

    CERN Document Server

    2015-01-01

    Big Data is everywhere – from Computational Science to Digital Humanities, from Web Analytics to traditional libraries. While there do exist significant challenges in other areas, for many the biggest issue of all is a digital libraries one – How do we preserve big data collections? How do we provide access to big data collections? What new questions can we pose against our big data collections? These are all digital libraries questions. How can we, the digital libraries community, stand up in the face of these challenges and inform collection builders, curators, and interface developers how to best solve their challenges? What assumptions have we been working under that no longer hold in light of Big Data? These are some of the timely questions we hope to address at JCDL 2015.

  5. A cluster-based strategy for assessing the overlap between large chemical libraries and its application to a recent acquisition.

    Science.gov (United States)

    Engels, Michael F M; Gibbs, Alan C; Jaeger, Edward P; Verbinnen, Danny; Lobanov, Victor S; Agrafiotis, Dimitris K

    2006-01-01

    We report on the structural comparison of the corporate collections of Johnson & Johnson Pharmaceutical Research & Development (JNJPRD) and 3-Dimensional Pharmaceuticals (3DP), performed in the context of the recent acquisition of 3DP by JNJPRD. The main objective of the study was to assess the druglikeness of the 3DP library and the extent to which it enriched the chemical diversity of the JNJPRD corporate collection. The two databases, at the time of acquisition, collectively contained more than 1.1 million compounds with a clearly defined structural description. The analysis was based on a clustering approach and aimed at providing an intuitive quantitative estimate and visual representation of this enrichment. A novel hierarchical clustering algorithm called divisive k-means was employed in combination with Kelley's cluster-level selection method to partition the combined data set into clusters, and the diversity contribution of each library was evaluated as a function of the relative occupancy of these clusters. Typical 3DP chemotypes enriching the diversity of the JNJPRD collection were catalogued and visualized using a modified maximum common substructure algorithm. The joint collection of JNJPRD and 3DP compounds was also compared to other databases of known medicinally active or druglike compounds. The potential of the methodology for the analysis of very large chemical databases is discussed.

  6. Research on the Impact of a Computerized Circulation System on the Performance of a Large College Library. Final Report.

    Science.gov (United States)

    Frohmberg, Katherine A.; Moffett, William A.

    In order to study the effects of introducing an automated circulation system at Oberlin College, Ohio, data were collected from September 1978 until June 1982 on book availability, usage of library facilities, attitudes of library users toward the library, and the efficiency of circulation activities. Data collection methods included circulation…

  7. Plasmids and packaging cell lines for use in phage display

    Science.gov (United States)

    Bradbury, Andrew M.

    2012-07-24

    The invention relates to a novel phagemid display system for packaging phagemid DNA into phagemid particles which completely avoids the use of helper phage. The system of the invention incorporates the use of bacterial packaging cell lines which have been transformed with helper plasmids containing all required phage proteins but not the packaging signals. The absence of packaging signals in these helper plasmids prevents their DNA from being packaged in the bacterial cell, which provides a number of significant advantages over the use of both standard and modified helper phage. Packaged phagemids expressing a protein or peptide of interest, in fusion with a phage coat protein such as g3p, are generated simply by transfecting phagemid into the packaging cell line.

  8. Pitfalls to avoid when using phage display for snake toxins

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Lauridsen, Line Præst; Lomonte, Bruno

    2017-01-01

    Antivenoms against bites and stings from snakes, spiders, and scorpions are associated with immunological side effects and high cost of production, since these therapies are still derived from the serum of hyper-immunized production animals. Biotechnological innovations within envenoming therapies...

  9. Econometric Analysis Suggests Possible Crowding Out of Public Libraries by Book Superstores among Middle Income Families in the 1990s. A review of: Hemmeter, Jeffrey A. “Household Use of Public Libraries and Large Bookstores.” Library & Information Science Research 28.4 (Sept. 2006: 595–616.

    Directory of Open Access Journals (Sweden)

    Stephanie Hall

    2007-09-01

    Full Text Available Objective – To determine the effect of large bookstores (defined as those having 20 or more employees on household library use. Design – Econometric analysis using crosssectional data sets. Setting – The United States of America. Subjects – People in over 55,000 households across the U.S.A. Methods – Data from three 1996 studies were examined using logit and multinomial logit estimation procedures: the NationalCenter for Education Statistics’ National Household Education Survey (NHES and Public Library Survey (PLS, and the U.S. Census Bureau’s County Business Patterns (CBP. The county level results of the NHEStelephone survey were merged with the county level data from the PLS and the CBP. Additionally, data on Internet use at the state level from the Statistical Abstract of the United States were incorporated into the data set. A logit regression model was used to estimate probability of library use based on several independent variables, evaluated at the mean. Main results – In general, Hemmeter found that "with regard to the impact of large bookstores on household library use, largebookstores do not appear to have an effect on overall library use among the general population” (613. While no significant changes in general library use were found among high and low income households where more large bookstores were present, nor in the population taken as a whole, middle income households (between $25,000 and $50,000 in annual income showed notable declines in library use in these situations. These effects were strongest in the areas of borrowing (200% less likely and recreational purposes (161%, but were also present in workrelated use and job searching. Hemmeter also writes that “poorer households use the library more often for job search purposes. The probability of library use for recreation,work, and consumer information increases as income increases. This effect diminishes as households get richer” (611. Finally, home

  10. The Availability of Web 2.0 Tools from Community College Libraries' Websites Serving Large Student Bodies

    Science.gov (United States)

    Blummer, Barbara; Kenton, Jeffrey M.

    2014-01-01

    Web 2.0 tools offer academic libraries new avenues for delivering services and resources to students. In this research we report on a content analysis of 100 US community college libraries' Websites for the availability of Web 2.0 applications. We found Web 2.0 tools utilized by 97% of our sample population and many of these sites contained more…

  11. Development of the adjusted nuclear cross-section library based on JENDL-3.2 for large FBR

    International Nuclear Information System (INIS)

    Yokoyama, Kenji; Ishikawa, Makoto; Numata, Kazuyuki

    1999-04-01

    JNC (and PNC) had developed the adjusted nuclear cross-section library in which the results of the JUPITER experiments were reflected. Using this adjusted library, the distinct improvement of the accuracy in nuclear design of FBR cores had been achieved. As a recent research, JNC develops a database of other integral data in addition to the JUPITER experiments, aiming at further improvement for accuracy and reliability. In 1991, the adjusted library based on JENDL-2, JFS-3-J2 (ADJ91R), was developed, and it has been used on the design research for FBR. As an evaluated nuclear library, however, JENDL-3.2 is recently used. Therefore, the authors developed an adjusted library based on JENDL-3.2 which is called JFS-3-J3.2(ADJ98). It is known that the adjusted library based on JENDL-2 overestimated the sodium void reactivity worth by 10-20%. It is expected that the adjusted library based on JENDL-3.2 solve the problem. The adjusted library JFS-3-J3.2(ADJ98) was produced with the same method as the adjusted library JFS-3-J2(ADJ91R) and used more integral parameters of JUPITER experiments than the adjusted library JFS-3-J2(ADJ91R). This report also describes the design accuracy estimation on a 600 MWe class FBR with the adjusted library JFS-3-J3.2(ADJ98). Its main nuclear design parameters (multiplication factor, burn-up reactivity loss, breeding ratio, etc.) except the sodium void reactivity worth which are calculated with the adjusted library JFS-3-J3.2(ADJ98) are almost the same as those predicted with JFS-3-J2(ADJ91R). As for the sodium void reactivity, the adjusted library JFS-3-J3.2(ADJ98) estimates about 4% smaller than the JFS-3-J2(ADJ91R) because of the change of the basic nuclear library from JENDL-2 to JENDL-3.2. (author)

  12. Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

    Science.gov (United States)

    Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

    2012-02-01

    Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Functional genomics, an integrated approach. Final report for the Trieste component

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew R.M.

    1999-11-01

    Phage display offers the possibility of selecting polypeptides (and the genes which encode them) from libraries of 10 billion or more different polypeptides on the basis of their abilities to bind target proteins and subdomains. The general principle of phage display relies on the coupling of phenotype and genotype in the phage. The specific aims of this project were threefold: (1) to produce a large phagemid antibody library; (2) to develop a general method for deriving antibodies against the protein products of cloned genes; (3) to develop technologies which permit the display of gene fragment libraries on phage. Accomplishments in each of these areas are presented.

  14. High-throughput expression of animal venom toxins in Escherichia coli to generate a large library of oxidized disulphide-reticulated peptides for drug discovery.

    Science.gov (United States)

    Turchetto, Jeremy; Sequeira, Ana Filipa; Ramond, Laurie; Peysson, Fanny; Brás, Joana L A; Saez, Natalie J; Duhoo, Yoan; Blémont, Marilyne; Guerreiro, Catarina I P D; Quinton, Loic; De Pauw, Edwin; Gilles, Nicolas; Darbon, Hervé; Fontes, Carlos M G A; Vincentelli, Renaud

    2017-01-17

    Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening. To date, as an alternative to artificial synthetic chemical libraries, no comprehensive recombinant libraries of natural venom peptides are accessible for high-throughput screening to identify novel therapeutics. In the accompanying paper an efficient system for the expression and purification of oxidized disulphide-reticulated venom peptides in Escherichia coli is described. Here we report the development of a high-throughput automated platform, that could be adapted to the production of other families, to generate the largest ever library of recombinant venom peptides. The peptides were produced in the periplasm of E. coli using redox-active DsbC as a fusion tag, thus allowing the efficient formation of correctly folded disulphide bridges. TEV protease was used to remove fusion tags and recover the animal venom peptides in the native state. Globally, within nine months, out of a total of 4992 synthetic genes encoding a representative diversity of venom peptides, a library containing 2736 recombinant disulphide-reticulated peptides was generated. The data revealed that the animal venom peptides produced in the bacterial host were natively folded and, thus, are putatively biologically active. Overall this study reveals that high-throughput expression of animal venom peptides in E. coli can generate large

  15. The application of magnetic force differentiation for the measurement of the affinity of peptide libraries

    International Nuclear Information System (INIS)

    Shang Hao; Kirkham, Perry M.; Myers, Tina M.; Cassell, Gail H.; Lee, Gil U.

    2005-01-01

    A new method has been developed for measuring the binding affinity of phage displayed peptides and a target protein using magnetic particles. The specific interaction between the phage displayed peptides and the target protein was subject to a force generated by the magnetic particle. The binding affinity was obtained by analyzing the force-bond lifetime

  16. Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.

    Science.gov (United States)

    Xu, Min; Wang, Yemin; Zhao, Zhilong; Gao, Guixi; Huang, Sheng-Xiong; Kang, Qianjin; He, Xinyi; Lin, Shuangjun; Pang, Xiuhua; Deng, Zixin

    2016-01-01

    ABSTRACT Genome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei. This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways. IMPORTANCE Microbial genomes encode numerous cryptic biosynthetic gene clusters for unknown small metabolites with potential biological activities. Several genome mining approaches have been developed to activate and bring these cryptic metabolites to biological tests for future drug discovery. Previous sequence-guided procedures relied on bioinformatic analysis to predict potentially interesting biosynthetic gene clusters. In this study, we describe an efficient approach based on heterologous expression and functional screening of a whole-genome library for the mining of bioactive metabolites from Streptomyces. The usefulness of this function-driven approach was demonstrated by the capture of four large biosynthetic gene clusters for metabolites of various chemical types, including

  17. The Use of OPAC in a Large Academic Library: A Transactional Log Analysis Study of Subject Searching

    Science.gov (United States)

    Villen-Rueda, Luis; Senso, Jose A.; de Moya-Anegon, Felix

    2007-01-01

    The analysis of user searches in catalogs has been the topic of research for over four decades, involving numerous studies and diverse methodologies. The present study looks at how different types of users effect queries in the catalog of a university library. For this purpose, we analyzed log files to determine which was the most frequent type of…

  18. Human recombinant Fab fragment from combinatorial libraries of a B-cell lymphoma patient recognizes core protein of chondroitin sulphate proteoglycan 4.

    Science.gov (United States)

    Egami, Yoko; Narushima, Yuta; Ohshima, Motohiro; Yoshida, Akira; Yoneta, Naruki; Masaki, Yasufumi; Itoh, Kunihiko

    2018-01-01

    CD antigens are well known as therapeutic targets of B-cell lymphoma. To isolate therapeutic antibodies that recognize novel targets other than CD antigens, we constructed a phage display combinatorial antibody Fab library from bone marrow lymphocytes of B-cell lymphoma patient. To eliminate antibodies reactive with known B-cell lymphoma antigen, non-hematopoietic and patient's sera reactive HeLaS3 cells was selected as a target of whole cell panning. Five rounds of panning against live HeLaS3 cells retrieved single Fab clone, termed AHSA (Antibody to HeLa Surface Antigen). Using phage display random peptide library, LSYLEP was identified as an epitope sequence of AHSA. LC-MS/MS analysis of AHSA-precipitated HeLaS3 cell lysates detected several fragments corresponding to the sequence of chondroitin sulphate proteoglycan 4 (CSPG4) core protein. Since LSYLEP sequence was at the position of 313-318 of CSPG4, we considered that CSPG4 was AHSA-associated antigen. Double staining of CSPG4-postive MDA-MB-435S cells with AHSA and anti-CSPG4 rabbit antibody showed identical staining position, and reduced AHSA reactivity was observed in CSPG4-siRNA treated MDA-MB-435S cells. In conclusion, we retrieved a human Fab from antibody library of B-cell lymphoma patient, and identified CSPG4 as a recognizing antigen. AHSA may have potential benefits for development of CSPG4-targeting theranostics for B-cell lymphoma. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  19. Featured Library: Parrish Library

    OpenAIRE

    Kirkwood, Hal P, Jr

    2015-01-01

    The Roland G. Parrish Library of Management & Economics is located within the Krannert School of Management at Purdue University. Between 2005 - 2007 work was completed on a white paper that focused on a student-centered vision for the Management & Economics Library. The next step was a massive collection reduction and a re-envisioning of both the services and space of the library. Thus began a 3 phase renovation from a 2 floor standard, collection-focused library into a single floor, 18,000s...

  20. RESOURCES OF CANADIAN ACADEMIC AND RESEARCH LIBRARIES.

    Science.gov (United States)

    DOWNS, ROBERT B.

    ALTHOUGH IT EMPHASIZES ACADEMIC LIBRARIES, THIS STUDY ALSO INCLUDES THE NATIONAL AND PROVINCIAL LIBRARIES, LARGE PUBLIC LIBRARIES, AND SPECIAL LIBRARIES THAT SERVE CANADIAN SCHOLARS, STUDENTS, AND RESEARCH WORKERS. WITH THE DATA OBTAINED FROM A QUESTIONNAIRE ON LIBRARY STATISTICS AND HOLDINGS, VISITS TO THE LIBRARIES, INTERVIEWS WITH LIBRARIANS…

  1. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria; Lanza Cariccio, Veronica; Benfatto, Salvatore; D'Aliberti, Deborah; Venza, Mario; Borgogni, Erica; Castellino, Flora; Biondo, Carmelo; D'Andrea, Daniel; Grassi, Luigi; Tramontano, Anna; Teti, Giuseppe; Felici, Franco; Beninati, Concetta

    2014-01-01

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  2. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    Directory of Open Access Journals (Sweden)

    Maria Domina

    Full Text Available There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  3. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria

    2014-12-04

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  4. Error Analysis of Deep Sequencing of Phage Libraries: Peptides Censored in Sequencing

    Directory of Open Access Journals (Sweden)

    Wadim L. Matochko

    2013-01-01

    Full Text Available Next-generation sequencing techniques empower selection of ligands from phage-display libraries because they can detect low abundant clones and quantify changes in the copy numbers of clones without excessive selection rounds. Identification of errors in deep sequencing data is the most critical step in this process because these techniques have error rates >1%. Mechanisms that yield errors in Illumina and other techniques have been proposed, but no reports to date describe error analysis in phage libraries. Our paper focuses on error analysis of 7-mer peptide libraries sequenced by Illumina method. Low theoretical complexity of this phage library, as compared to complexity of long genetic reads and genomes, allowed us to describe this library using convenient linear vector and operator framework. We describe a phage library as N×1 frequency vector n=ni, where ni is the copy number of the ith sequence and N is the theoretical diversity, that is, the total number of all possible sequences. Any manipulation to the library is an operator acting on n. Selection, amplification, or sequencing could be described as a product of a N×N matrix and a stochastic sampling operator (Sa. The latter is a random diagonal matrix that describes sampling of a library. In this paper, we focus on the properties of Sa and use them to define the sequencing operator (Seq. Sequencing without any bias and errors is Seq=Sa IN, where IN is a N×N unity matrix. Any bias in sequencing changes IN to a nonunity matrix. We identified a diagonal censorship matrix (CEN, which describes elimination or statistically significant downsampling, of specific reads during the sequencing process.

  5. Using herbarium-derived DNAs to assemble a large-scale DNA barcode library for the vascular plants of Canada1

    Science.gov (United States)

    Kuzmina, Maria L.; Braukmann, Thomas W. A.; Fazekas, Aron J.; Graham, Sean W.; Dewaard, Stephanie L.; Rodrigues, Anuar; Bennett, Bruce A.; Dickinson, Timothy A.; Saarela, Jeffery M.; Catling, Paul M.; Newmaster, Steven G.; Percy, Diana M.; Fenneman, Erin; Lauron-Moreau, Aurélien; Ford, Bruce; Gillespie, Lynn; Subramanyam, Ragupathy; Whitton, Jeannette; Jennings, Linda; Metsger, Deborah; Warne, Connor P.; Brown, Allison; Sears, Elizabeth; Dewaard, Jeremy R.; Zakharov, Evgeny V.; Hebert, Paul D. N.

    2017-01-01

    Premise of the study: Constructing complete, accurate plant DNA barcode reference libraries can be logistically challenging for large-scale floras. Here we demonstrate the promise and challenges of using herbarium collections for building a DNA barcode reference library for the vascular plant flora of Canada. Methods: Our study examined 20,816 specimens representing 5076 of 5190 vascular plant species in Canada (98%). For 98% of the specimens, at least one of the DNA barcode regions was recovered from the plastid loci rbcL and matK and from the nuclear ITS2 region. We used beta regression to quantify the effects of age, type of preservation, and taxonomic affiliation (family) on DNA sequence recovery. Results: Specimen age and method of preservation had significant effects on sequence recovery for all markers, but influenced some families more (e.g., Boraginaceae) than others (e.g., Asteraceae). Discussion: Our DNA barcode library represents an unparalleled resource for metagenomic and ecological genetic research working on temperate and arctic biomes. An observed decline in sequence recovery with specimen age may be associated with poor primer matches, intragenomic variation (for ITS2), or inhibitory secondary compounds in some taxa. PMID:29299394

  6. Teleporting the library?

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2009-01-01

    In 2007, six Danish public libraries established a virtual library, Info Island DK, in Second Life. This article discusses the library project in terms of design. The design processes include the planning and implementation of the virtual library structure and its equipment, as well...... as the organizing and carrying out of activities in the virtual setting. It will be argued that, to a large extent, conventions have determined design and use of the virtual library, and also that design has had an impact on the attitudes and understanding of the participants....

  7. Rapid isolation of IgNAR variable single-domain antibody fragments from a shark synthetic library.

    Science.gov (United States)

    Shao, Cui-Ying; Secombes, Chris J; Porter, Andrew J

    2007-01-01

    The immunoglobulin isotype IgNAR (Novel Antigen Receptor) was discovered in the serum of the nurse shark (Ginglymostoma cirratum) and wobbegong shark (Orectolobus maculates) as a homodimer of two protein chains, each composed of a single variable domain (V) domain and five constant domains. The IgNAR variable domain contains an intact antigen-binding site and functions as an independent domain able to react to antigen with both high specificity and affinity. Here we describe the successful construction of a synthetic phage-displayed library based upon a single anti-lysozyme clone HEL-5A7 scaffold, which was previously selected from an immune IgNAR variable domain library. The complementarity-determining region 3 (CDR3) loop of this clone was varied in both length and composition and the derived library was used to pan against two model proteins, lysozyme and leptin. A single anti-lysozyme clone (Ly-X20) and anti-leptin clone (Lep-12E1) were selected for further study. Both clones were shown to be functionally expressed in Escherichia coli, extremely thermostable and bind to corresponding antigens specifically. The results here demonstrate that a synthetic IgNAR variable domain library based on a single framework scaffold can be used as a route to generate antigen binders quickly, easily and without the need of immunization.

  8. Research Library

    Science.gov (United States)

    Los Alamos National Laboratory Research Library Search Site submit Contact Us | Remote Access Standards Theses/Dissertations Research Help Subject Guides Library Training Video Tutorials Alerts Research Library: delivering essential knowledge services for national security sciences since 1947 Los

  9. MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets.

    Science.gov (United States)

    Kim, Taehyung; Tyndel, Marc S; Huang, Haiming; Sidhu, Sachdev S; Bader, Gary D; Gfeller, David; Kim, Philip M

    2012-03-01

    Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors.

  10. Large-scale Identification of Expressed Sequence Tags (ESTs from Nicotianatabacum by Normalized cDNA Library Sequencing

    Directory of Open Access Journals (Sweden)

    Alvarez S Perez

    2014-12-01

    Full Text Available An expressed sequence tags (EST resource for tobacco plants (Nicotianatabacum was established using high-throughput sequencing of randomly selected clones from one cDNA library representing a range of plant organs (leaf, stem, root and root base. Over 5000 ESTs were generated from the 3’ ends of 8000 clones, analyzed by BLAST searches and categorized functionally. All annotated ESTs were classified into 18 functional categories, unique transcripts involved in energy were the largest group accounting for 831 (32.32% of the annotated ESTs. After excluding 2450 non-significant tentative unique transcripts (TUTs, 100 unique sequences (1.67% of total TUTs were identified from the N. tabacum database. In the array result two genes strongly related to the tobacco mosaic virus (TMV were obtained, one basic form of pathogenesis-related protein 1 precursor (TBT012G08 and ubiquitin (TBT087G01. Both of them were found in the variety Hongda, some other important genes were classified into two groups, one of these implicated in plant development like those genes related to a photosynthetic process (chlorophyll a-b binding protein, photosystem I, ferredoxin I and III, ATP synthase and a further group including genes related to plant stress response (ubiquitin, ubiquitin-like protein SMT3, glycine-rich RNA binding protein, histones and methallothionein. The interesting finding in this study is that two of these genes have never been reported before in N. tabacum (ubiquitin-like protein SMT3 and methallothionein. The array results were confirmed using quantitative PCR.

  11. Data Portal for the Library of Integrated Network-based Cellular Signatures (LINCS) program: integrated access to diverse large-scale cellular perturbation response data

    Science.gov (United States)

    Koleti, Amar; Terryn, Raymond; Stathias, Vasileios; Chung, Caty; Cooper, Daniel J; Turner, John P; Vidović, Dušica; Forlin, Michele; Kelley, Tanya T; D’Urso, Alessandro; Allen, Bryce K; Torre, Denis; Jagodnik, Kathleen M; Wang, Lily; Jenkins, Sherry L; Mader, Christopher; Niu, Wen; Fazel, Mehdi; Mahi, Naim; Pilarczyk, Marcin; Clark, Nicholas; Shamsaei, Behrouz; Meller, Jarek; Vasiliauskas, Juozas; Reichard, John; Medvedovic, Mario; Ma’ayan, Avi; Pillai, Ajay

    2018-01-01

    Abstract The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. In contrast to other large-scale data generation efforts, LINCS Data and Signature Generation Centers (DSGCs) employ a wide range of assay technologies cataloging diverse cellular responses. Integration of, and unified access to LINCS data has therefore been particularly challenging. The Big Data to Knowledge (BD2K) LINCS Data Coordination and Integration Center (DCIC) has developed data standards specifications, data processing pipelines, and a suite of end-user software tools to integrate and annotate LINCS-generated data, to make LINCS signatures searchable and usable for different types of users. Here, we describe the LINCS Data Portal (LDP) (http://lincsportal.ccs.miami.edu/), a unified web interface to access datasets generated by the LINCS DSGCs, and its underlying database, LINCS Data Registry (LDR). LINCS data served on the LDP contains extensive metadata and curated annotations. We highlight the features of the LDP user interface that is designed to enable search, browsing, exploration, download and analysis of LINCS data and related curated content. PMID:29140462

  12. Generation and selection of naïve Fab library for parasitic antigen: Anti-BmSXP antibodies for lymphatic filariasis.

    Science.gov (United States)

    Omar, Noorsharmimi; Hamidon, Nurul Hamizah; Yunus, Muhammad Hafiznur; Noordin, Rahmah; Choong, Yee Siew; Lim, Theam Soon

    2018-05-01

    Phage display has been applied successfully as a tool for the generation of monoclonal antibodies (mAbs). Naive antibody libraries are unique as they are able to overcome several limitations associated with conventional mAb generation methods like the hybridoma technology. Here, we performed an in vitro selection and generation of Fab antibodies against Brugia malayi SXP protein (BmSXP), a recombinant antigen for the detection of lymphatic filariasis. We developed a naïve multi ethnic Fab antibody library with an estimated diversity of 2.99 × 10 9 . The antibody library was used to screen for mAbs against BmSXP recombinant antigen. Soluble monoclonal Fab antibodies against BmSXP were successfully isolated from the naïve library. The Fab antibodies obtained were expressed and analyzed to show its binding capability. The diversity obtained from a pool of donors from various ethnic groups allowed for a diverse antibody library to be generated. The mAbs obtained were also functional in soluble form, which makes it useful for further downstream applications. We believe that the Fab mAbs are valuable for further studies and could also contribute to improvements in the diagnosis of filariasis. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  13. Large-Scale Participation: A Case Study of a Participatory Approach to Developing a New Public Library

    DEFF Research Database (Denmark)

    Dalsgaard, Peter; Eriksson, Eva

    2013-01-01

    In this paper, we present a case study of a participatory project that focuses on interaction in large-scale design, namely, the development of the new Urban Mediaspace Aarhus. This project, which has been under way for ten years, embodies a series of issues that arise when participatory design...

  14. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria

    NARCIS (Netherlands)

    Salzman, NH; de Jong, H; Paterson, Y; Harmsen, HJM; Welling, GW; Bos, NA

    2002-01-01

    Total genomic DNA from samples of intact mouse small intestine, large intestine, caecum and faeces was used as template for PCR amplification of 16S rRNA gene sequences with conserved bacterial primers. Phylogenetic analysis of the amplification products revealed 40 unique 16S rDNA sequences. Of

  15. Development of an Integrated, Computer-Based Bibliographical Data System for a Large University Library. Annual Report to the National Science Foundation from the University of Chicago Library, 1966/67.

    Science.gov (United States)

    Fussler, Herman; Payne, Charles T.

    Part I is a discussion of the following project tasks: A) development of an on-line, real-time bibliographic data processing system; B) implementation in library operations; C) character sets; D) Project MARC; E) circulation; and F) processing operation studies. Part II is a brief discussion of efforts to work out cooperative library systems…

  16. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria.

    Science.gov (United States)

    Salzman, Nita H; de Jong, Hendrik; Paterson, Yvonne; Harmsen, Hermie J M; Welling, Gjalt W; Bos, Nicolaas A

    2002-11-01

    Total genomic DNA from samples of intact mouse small intestine, large intestine, caecum and faeces was used as template for PCR amplification of 16S rRNA gene sequences with conserved bacterial primers. Phylogenetic analysis of the amplification products revealed 40 unique 16S rDNA sequences. Of these sequences, 25% (10/40) corresponded to described intestinal organisms of the mouse, including Lactobacillus spp., Helicobacter spp., segmented filamentous bacteria and members of the altered Schaedler flora (ASF360, ASF361, ASF502 and ASF519); 75% (30/40) represented novel sequences. A large number (11/40) of the novel sequences revealed a new operational taxonomic unit (OTU) belonging to the Cytophaga-Flavobacter-Bacteroides phylum, which the authors named 'mouse intestinal bacteria'. 16S rRNA probes were developed for this new OTU. Upon analysis of the novel sequences, eight were found to cluster within the Eubacterium rectale-Clostridium coccoides group and three clustered within the Bacteroides group. One of the novel sequences was distantly related to Verrucomicrobium spinosum and one was distantly related to Bacillus mycoides. Oligonucleotide probes specific for the 16S rRNA of these novel clones were generated. Using a combination of four previously described and four newly designed probes, approximately 80% of bacteria recovered from the murine large intestine and 71% of bacteria recovered from the murine caecum could be identified by fluorescence in situ hybridization (FISH).

  17. Working in the Library

    CERN Multimedia

    Maximilien Brice

    2009-01-01

    Head Librarian Jens Vigen seeking information on the first discussions concerning the construction of the Large Hadron Collider in the LEP Tunnel (1984), here assisted by two of the library apprentices, Barbara Veyre and Dina-Elisabeth Bimbu (seated).

  18. Microcomputers in the Anesthesia Library.

    Science.gov (United States)

    Wright, A. J.

    The combination of computer technology and library operation is helping to alleviate such library problems as escalating costs, increasing collection size, deteriorating materials, unwieldy arrangement schemes, poor subject control, and the acquisition and processing of large numbers of rarely used documents. Small special libraries such as…

  19. Library Information-Processing System

    Science.gov (United States)

    1985-01-01

    System works with Library of Congress MARC II format. System composed of subsystems that provide wide range of library informationprocessing capabilities. Format is American National Standards Institute (ANSI) format for machine-readable bibliographic data. Adaptable to any medium-to-large library.

  20. CERN Library | Pauline Gagnon presents the book "Who cares about particle physics? : making sense of the Higgs boson, the Large Hadron Collider and CERN" | 15 September

    CERN Multimedia

    CERN Library

    2016-01-01

    "Who cares about particle physics? : making sense of the Higgs boson, the Large Hadron Collider and CERN ", by Pauline Gagnon. Thursday 15 September 2016, 16:00 - 17:30 in the CERN Library (Bldg 52 1-052) *Coffee will be served at 15:30* CERN, the European Laboratory for particle physics, regularly makes the news. What kind of research happens at this international laboratory and how does it impact people's daily lives? Why is the discovery of the Higgs boson so important? Particle physics describes all matter found on Earth, in stars and all galaxies but it also tries to go beyond what is known to describe dark matter, a form of matter five times more prevalent than the known, regular matter. How do we know this mysterious dark matter exists and is there a chance it will be discovered soon? About sixty countries contributed to the construction of the gigantic Large Hadron Collider (LHC) at CERN and its immense detectors. Dive in to discover how international teams of researchers...

  1. Library Computing

    Science.gov (United States)

    Library Computing, 1985

    1985-01-01

    Special supplement to "Library Journal" and "School Library Journal" covers topics of interest to school, public, academic, and special libraries planning for automation: microcomputer use, readings in automation, online searching, databases of microcomputer software, public access to microcomputers, circulation, creating a…

  2. Ligand-directed profiling of organelles with internalizing phage libraries

    Science.gov (United States)

    Dobroff, Andrey S.; Rangel, Roberto; Guzman-Roja, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Bologa, Cristian G.; Oprea, Tudor I.; Brinker, C. Jeffrey; Pasqualini, Renata; Arap, Wadih

    2015-01-01

    Phage display is a resourceful tool to, in an unbiased manner, discover and characterize functional protein-protein interactions, to create vaccines, and to engineer peptides, antibodies, and other proteins as targeted diagnostic and/or therapeutic agents. Recently, our group has developed a new class of internalizing phage (iPhage) for ligand-directed targeting of organelles and/or to identify molecular pathways within live cells. This unique technology is suitable for applications ranging from fundamental cell biology to drug development. Here we describe the method for generating and screening the iPhage display system, and explain how to select and validate candidate internalizing homing peptide. PMID:25640897

  3. Academic Library Administration: A Case Examination of Faculty-Librarian Perceptions of Journal Cancellations and the Decision-Making Process in a Large, Urban Institution.

    Science.gov (United States)

    Walther, James Harmon

    As the academic library plays the roles of intermediary and adjudicator of collection purchases and cancellations, faculty involvement in library resource decisions is not only commonplace, but essential to making such decisions. Faculty involvement in cancellation projects is often enhanced by a thorough explanation of the depth of financial…

  4. The academic library network

    Directory of Open Access Journals (Sweden)

    Jacek Wojciechowski

    2012-01-01

    Full Text Available The efficiency of libraries, academic libraries in particular, necessitates organizational changes facilitating or even imposing co-operation. Any structure of any university has to have an integrated network of libraries, with an appropriate division of work, and one that is consolidated as much as it is possible into medium-size or large libraries. Within thus created network, a chance arises to centralize the main library processes based on appropriate procedures in the main library, highly specialized, more effective and therefore cheaper in operation, including a co-ordination of all more important endeavours and tasks. Hierarchically subordinated libraries can be thus more focused on performing their routine service, more and more frequently providing for the whole of the university, and being able to adjust to changeable requirements and demands of patrons and of new tasks resulting from the new model of the university operation. Another necessary change seems to be a universal implementation of an ov rall programme framework that would include all services in the university’s library networks.

  5. Differential screening of phage-ab libraries by oligonucleotide microarray technology.

    Directory of Open Access Journals (Sweden)

    Paolo Monaci

    Full Text Available A novel and efficient tagArray technology was developed that allows rapid identification of antibodies which bind to receptors with a specific expression profile, in the absence of biological information. This method is based on the cloning of a specific, short nucleotide sequence (tag in the phagemid coding for each phage-displayed antibody fragment (phage-Ab present in a library. In order to set up and validate the method we identified about 10,000 different phage-Abs binding to receptors expressed in their native form on the cell surface (10 k Membranome collection and tagged each individual phage-Ab. The frequency of each phage-Ab in a given population can at this point be inferred by measuring the frequency of its associated tag sequence through standard DNA hybridization methods. Using tiny amounts of biological samples we identified phage-Abs binding to receptors preferentially expressed on primary tumor cells rather than on cells obtained from matched normal tissues. These antibodies inhibited cell proliferation in vitro and tumor development in vivo, thus representing therapeutic lead candidates.

  6. Phage Fab Display Selection In Vitro and In Vivo: Novel Means to Identify New Breast Cancer Avid Compounds

    National Research Council Canada - National Science Library

    Meighan, Mark

    2001-01-01

    .... In this annual report we present preliminary results on the isolation of antibody fragments (Fabs), isolated from phage display libraries, when affinity selected against breast cancer cell lines...

  7. ORIGEN-S data libraries

    International Nuclear Information System (INIS)

    Ryman, J.C.

    1984-01-01

    There are five card-image nuclear data libraries: (1) a small light element library for 253 nuclides, (2) a large light element library for 687 nuclides, (3) an actinide library for 101 nuclides, (4) a small fission product library for 461 nuclides, and (5) a large fission product library for 821 nuclides. The data for each nuclide are contained on five card-image records. The first card image contains decay data (half-life, branching fractions, recoverable energy per decay and the fraction of recoverable energy from photons), percent natural abundance, and radioactivity concentration guides. The last four card images contain cross section and (for fission product nuclides) fission yield data for four reactor types (HTGR, LWR, LMFBR, and MSBR), with one card for each reactor type. The card-image nuclear data libraries are the basic libraries for ORIGEN-S. The code can be run using these libraries directly, or it can be run from a binary data library which (prior to any cross section or other nuclear data updating) was created by running the COUPLE code to convert one or more of these card-image libraries

  8. About the Library - Betty Petersen Memorial Library

    Science.gov (United States)

    branch library of the NOAA Central Library. The library serves the NOAA Science Center in Camp Springs , Maryland. History and Mission: Betty Petersen Memorial Library began as a reading room in the NOAA Science Science Center staff and advises the library on all aspects of the library program. Library Newsletters

  9. Library Use

    DEFF Research Database (Denmark)

    Konzack, Lars

    2012-01-01

    A seminar paper about a survey of role-playing games in public libraries combined with three cases and a presentation of a model.......A seminar paper about a survey of role-playing games in public libraries combined with three cases and a presentation of a model....

  10. Architectural Optimization of Digital Libraries

    Science.gov (United States)

    Biser, Aileen O.

    1998-01-01

    This work investigates performance and scaling issues relevant to large scale distributed digital libraries. Presently, performance and scaling studies focus on specific implementations of production or prototype digital libraries. Although useful information is gained to aid these designers and other researchers with insights to performance and scaling issues, the broader issues relevant to very large scale distributed libraries are not addressed. Specifically, no current studies look at the extreme or worst case possibilities in digital library implementations. A survey of digital library research issues is presented. Scaling and performance issues are mentioned frequently in the digital library literature but are generally not the focus of much of the current research. In this thesis a model for a Generic Distributed Digital Library (GDDL) and nine cases of typical user activities are defined. This model is used to facilitate some basic analysis of scaling issues. Specifically, the calculation of Internet traffic generated for different configurations of the study parameters and an estimate of the future bandwidth needed for a large scale distributed digital library implementation. This analysis demonstrates the potential impact a future distributed digital library implementation would have on the Internet traffic load and raises questions concerning the architecture decisions being made for future distributed digital library designs.

  11. Effect of training data size and noise level on support vector machines virtual screening of genotoxic compounds from large compound libraries.

    Science.gov (United States)

    Kumar, Pankaj; Ma, Xiaohua; Liu, Xianghui; Jia, Jia; Bucong, Han; Xue, Ying; Li, Ze Rong; Yang, Sheng Yong; Wei, Yu Quan; Chen, Yu Zong

    2011-05-01

    Various in vitro and in-silico methods have been used for drug genotoxicity tests, which show limited genotoxicity (GT+) and non-genotoxicity (GT-) identification rates. New methods and combinatorial approaches have been explored for enhanced collective identification capability. The rates of in-silco methods may be further improved by significantly diversified training data enriched by the large number of recently reported GT+ and GT- compounds, but a major concern is the increased noise levels arising from high false-positive rates of in vitro data. In this work, we evaluated the effect of training data size and noise level on the performance of support vector machines (SVM) method known to tolerate high noise levels in training data. Two SVMs of different diversity/noise levels were developed and tested. H-SVM trained by higher diversity higher noise data (GT+ in any in vivo or in vitro test) outperforms L-SVM trained by lower noise lower diversity data (GT+ in in vivo or Ames test only). H-SVM trained by 4,763 GT+ compounds reported before 2008 and 8,232 GT- compounds excluding clinical trial drugs correctly identified 81.6% of the 38 GT+ compounds reported since 2008, predicted 83.1% of the 2,008 clinical trial drugs as GT-, and 23.96% of 168 K MDDR and 27.23% of 17.86M PubChem compounds as GT+. These are comparable to the 43.1-51.9% GT+ and 75-93% GT- rates of existing in-silico methods, 58.8% GT+ and 79% GT- rates of Ames method, and the estimated percentages of 23% in vivo and 31-33% in vitro GT+ compounds in the "universe of chemicals". There is a substantial level of agreement between H-SVM and L-SVM predicted GT+ and GT- MDDR compounds and the prediction from TOPKAT. SVM showed good potential in identifying GT+ compounds from large compound libraries based on higher diversity and higher noise training data.

  12. Combining Phage and Yeast Cell Surface Antibody Display to Identify Novel Cell Type-Selective Internalizing Human Monoclonal Antibodies.

    Science.gov (United States)

    Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2015-01-01

    Using phage antibody display, large libraries can be generated and screened to identify monoclonal antibodies with affinity for target antigens. However, while library size and diversity is an advantage of the phage display method, there is limited ability to quantitatively enrich for specific binding properties such as affinity. One way of overcoming this limitation is to combine the scale of phage display selections with the flexibility and quantitativeness of FACS-based yeast surface display selections. In this chapter we describe protocols for generating yeast surface antibody display libraries using phage antibody display selection outputs as starting material and FACS-based enrichment of target antigen-binding clones from these libraries. These methods should be widely applicable for the identification of monoclonal antibodies with specific binding properties.

  13. Generation and analysis of large-scale expressed sequence tags (ESTs from a full-length enriched cDNA library of porcine backfat tissue

    Directory of Open Access Journals (Sweden)

    Lee Hae-Young

    2006-02-01

    Full Text Available Abstract Background Genome research in farm animals will expand our basic knowledge of the genetic control of complex traits, and the results will be applied in the livestock industry to improve meat quality and productivity, as well as to reduce the incidence of disease. A combination of quantitative trait locus mapping and microarray analysis is a useful approach to reduce the overall effort needed to identify genes associated with quantitative traits of interest. Results We constructed a full-length enriched cDNA library from porcine backfat tissue. The estimated average size of the cDNA inserts was 1.7 kb, and the cDNA fullness ratio was 70%. In total, we deposited 16,110 high-quality sequences in the dbEST division of GenBank (accession numbers: DT319652-DT335761. For all the expressed sequence tags (ESTs, approximately 10.9 Mb of porcine sequence were generated with an average length of 674 bp per EST (range: 200–952 bp. Clustering and assembly of these ESTs resulted in a total of 5,008 unique sequences with 1,776 contigs (35.46% and 3,232 singleton (65.54% ESTs. From a total of 5,008 unique sequences, 3,154 (62.98% were similar to other sequences, and 1,854 (37.02% were identified as having no hit or low identity (Sus scrofa. Gene ontology (GO annotation of unique sequences showed that approximately 31.7, 32.3, and 30.8% were assigned molecular function, biological process, and cellular component GO terms, respectively. A total of 1,854 putative novel transcripts resulted after comparison and filtering with the TIGR SsGI; these included a large percentage of singletons (80.64% and a small proportion of contigs (13.36%. Conclusion The sequence data generated in this study will provide valuable information for studying expression profiles using EST-based microarrays and assist in the condensation of current pig TCs into clusters representing longer stretches of cDNA sequences. The isolation of genes expressed in backfat tissue is the

  14. How Much Is Enough? Examining Computer Science and Civil Engineering Citation Data to Inform Collection Development and Retention Decisions in Three Large Canadian University Libraries

    Science.gov (United States)

    Spence, Michelle; Mawhinney, Tara; Barsky, Eugene

    2012-01-01

    Science and engineering libraries have an important role to play in preserving the intellectual content in research areas of the departments they serve. This study employs bibliographic data from the Web of Science database to examine how much research material is required to cover 90% of faculty citations in civil engineering and computer…

  15. Nigerian Libraries

    African Journals Online (AJOL)

    Bridging the digital divide: the potential role of the National Library of Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Juliana Obiageri Akidi, Joy Chituru Onyenachi, 11-19 ...

  16. Library Locations

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Carnegie Library of Pittsburgh locations including address, coordinates, phone number, square footage, and standard operating hours. The map below does not display...

  17. academic libraries

    African Journals Online (AJOL)

    Information Impact: Journal of Information and Knowledge Management

    Information Impact: Journal of Information and Knowledge Management ... Key words: academic libraries, open access, research, researchers, technology ... European commission (2012) reports that affordable and easy access to the results ...

  18. NSUF Irradiated Materials Library

    Energy Technology Data Exchange (ETDEWEB)

    Cole, James Irvin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    The Nuclear Science User Facilities has been in the process of establishing an innovative Irradiated Materials Library concept for maximizing the value of previous and on-going materials and nuclear fuels irradiation test campaigns, including utilization of real-world components retrieved from current and decommissioned reactors. When the ATR national scientific user facility was established in 2007 one of the goals of the program was to establish a library of irradiated samples for users to access and conduct research through competitively reviewed proposal process. As part of the initial effort, staff at the user facility identified legacy materials from previous programs that are still being stored in laboratories and hot-cell facilities at the INL. In addition other materials of interest were identified that are being stored outside the INL that the current owners have volunteered to enter into the library. Finally, over the course of the last several years, the ATR NSUF has irradiated more than 3500 specimens as part of NSUF competitively awarded research projects. The Logistics of managing this large inventory of highly radioactive poses unique challenges. This document will describe materials in the library, outline the policy for accessing these materials and put forth a strategy for making new additions to the library as well as establishing guidelines for minimum pedigree needed to be included in the library to limit the amount of material stored indefinitely without identified value.

  19. Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries.

    Science.gov (United States)

    Goodchild, Sarah A; Dooley, Helen; Schoepp, Randal J; Flajnik, Martin; Lonsdale, Stephen G

    2011-09-01

    Members of the genus Ebolavirus cause fulminating outbreaks of disease in human and non-human primate populations with a mortality rate up to 90%. To facilitate rapid detection of these pathogens in clinical and environmental samples, robust reagents capable of providing sensitive and specific detection are required. In this work recombinant antibody libraries were generated from murine (single chain variable domain fragment; scFv) and nurse shark, Ginglymostoma cirratum (IgNAR V) hosts immunised with Zaire ebolavirus. This provides the first recorded IgNAR V response against a particulate antigen in the nurse shark. Both murine scFv and shark IgNAR V libraries were panned by phage display technology to identify useful antibodies for the generation of immunological detection reagents. Two murine scFv were shown to have specificity to the Zaire ebolavirus viral matrix protein VP40. Two isolated IgNAR V were shown to bind to the viral nucleoprotein (NP) and to capture viable Zaire ebolavirus with a high degree of sensitivity. Assays developed with IgNAR V cross-reacted to Reston ebolavirus, Sudan ebolavirus and Bundibugyo ebolavirus. Despite this broad reactivity, neither of IgNAR V showed reactivity to Côte d'Ivoire ebolavirus. IgNAR V was substantially more resistant to irreversible thermal denaturation than murine scFv and monoclonal IgG in a comparative test. The demonstrable robustness of the IgNAR V domains may offer enhanced utility as immunological detection reagents in fieldable biosensor applications for use in tropical or subtropical countries where outbreaks of Ebolavirus haemorrhagic fever occur. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  20. Evaluation as a Tool for Developing the Quality of Academic Libraries. Case Study at a Large and Traditional Research Oriented Scandinavian University

    OpenAIRE

    Kaisa Sinikara

    2006-01-01

    The leaders of our universities will ask today if we offer those services that a top university requires and whether the proposed resources for the libraries are worth investing. Establishing the European Higher Education Area (EHEA) requires the establishing of quality systems. Quality assurance systems will be introduced throughout the entire European academic sector and will certainly have significant impact on the development of academic organizations. The collaborative effort to evaluate...

  1. News from the Library: The 'long tail' Library

    CERN Multimedia

    CERN Library

    2012-01-01

    "The term 'long tail' has gained popularity in recent times as describing the retailing strategy of selling a large number of unique items with relatively small quantities sold of each usually in addition to selling fewer popular items in large quantities. The long tail was popularized by Chris Anderson, who mentioned Amazon.com, Apple and Yahoo! as examples of businesses applying this strategy." *   If we leave the business environment and move to the world of libraries, we still see this "long tail". Usually, only a small portion of a library's book collection accounts for the majority of its loans. On the other hand, there are a variety of "niche information needs" that might not be met, as libraries cannot afford to build up huge collections of documents available just-in-case. However, the networked environment of today's libraries can offer a solution. Online networks of libraries ca...

  2. The library

    International Nuclear Information System (INIS)

    1980-01-01

    A specialized library is essential for conducting the research work of the Uranium Institute. The need was recognized at the foundation of the Institute and a full-time librarian was employed in 1976 to establish the necessary systems and begin the task of building up the collection. A brief description is given of the services offered by the library which now contains books, periodicals, pamphlets and press cuttings, focussed on uranium and nuclear energy, but embracing economics, politics, trade, legislation, geology, mining and mineral processing, environmental protection and nuclear technology. (author)

  3. Discovery of Peptidic Anti-cobratoxins by Next Generation Phage Display

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Lynagh, Timothy; Kringelum, Jens Vindahl

    Antivenoms are still being produced by animal immunization protocols and are therefore associated with high immunogenicity for human recipients. Here we report the first step towards discovery of synthetic antitoxins that could be used for development of a fully synthetic antivenom against...

  4. From phage display to plant expression: Fulfilling prerequisites for chicken oral immunotherapy against coccidiosis

    NARCIS (Netherlands)

    Wieland, W.H.

    2004-01-01

    The frequency and spectrum of infections with pathogens harbouring resistance to antibiotics and other drugs has dramatically increased over the last years. One of the main causes is the extensive use of antibiotics and other drugs in human and veterinary medicine. Parasites, such as Eimeria causing

  5. Discovery of Peptide-based Inhibitors against Dendrotoxin B from Black Mamba through Phage Display Screening

    DEFF Research Database (Denmark)

    O. Cob, Saioa; Munk, Andreas; Laustsen, Andreas Hougaard

    The black mamba (Dendroaspis polylepis) is Africa’s most feared snake due to its potent, rapidacting venom and its speed of attack. The most abundant toxins in D. polylepis venom are the Kunitz-type proteinase inhibitors, dendrotoxins, which are unique for mamba. Dendrotoxinsare poorly neutralized...

  6. Development of novel drug delivery systems using phage display technology for clinical application of protein drugs.

    Science.gov (United States)

    Nagano, Kazuya; Tsutsumi, Yasuo

    2016-01-01

    Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony-stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis-related proteins, and a cisplatin resistance-related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will be developed by combining these technologies.

  7. Identification and characterization of a salivary-pellicle-binding peptide by phage display

    NARCIS (Netherlands)

    Cukkemane, N.; Bikker, F.J.; Nazmi, K.; Brand, H.S.; Veerman, E.C.I.

    2014-01-01

    Objective Dental biofilms are associated with oral diseases, making their control necessary. One way to control them is to prevent initial bacterial adherence to the salivary pellicle and thereby eventually decrease binding of late colonizing potential pathogens. The goal of this study was to

  8. Libraries on the MOVE.

    Science.gov (United States)

    Edgar, Jim; And Others

    1986-01-01

    Presents papers from Illinois State Library and Shawnee Library System's "Libraries on the MOVE" conference focusing on how libraries can impact economic/cultural climate of an area. Topics addressed included information services of rural libraries; marketing; rural library development; library law; information access; interagency…

  9. Personal Virtual Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2004-01-01

    Virtual libraries are becoming more and more common. Most states have a virtual library. A growing number of public libraries have a virtual presence on the Web. Virtual libraries are a growing addition to school library media collections. The next logical step would be personal virtual libraries. A personal virtual library (PVL) is a collection…

  10. America's Star Libraries

    Science.gov (United States)

    Lyons, Ray; Lance, Keith Curry

    2009-01-01

    "Library Journal"'s new national rating of public libraries, the "LJ" Index of Public Library Service, identifies 256 "star" libraries. It rates 7,115 public libraries. The top libraries in each group get five, four, or three Michelin guide-like stars. All included libraries, stars or not, can use their scores to learn from their peers and improve…

  11. A borderless Library

    CERN Multimedia

    CERN Library

    2010-01-01

    The CERN Library has a large collection of documents in online or printed format in all disciplines needed by physicists, engineers and technicians. However,  users sometimes need to read documents not available at CERN. But don’t worry! Thanks to its Interlibrary loan and document delivery service, the CERN Library can still help you. Just fill in the online form or email us. We will then locate the document in other institutions and order it for you free of charge. The CERN Library cooperates with the largest libraries in Europe, such as ETH (Eidgenössische Technische Hochschule) in Zurich, TIB (Technische Informationsbibliothek) in Hanover and the British Library in London. Thanks to our network and our expertise in document search, most requests are satisfied in record time: articles are usually served in .pdf version a few hours after the order, and books or other printed materials are delivered within a few days. It is possible to ask for all types of documents suc...

  12. Library Automation.

    Science.gov (United States)

    Husby, Ole

    1990-01-01

    The challenges and potential benefits of automating university libraries are reviewed, with special attention given to cooperative systems. Aspects discussed include database size, the role of the university computer center, storage modes, multi-institutional systems, resource sharing, cooperative system management, networking, and intelligent…

  13. Large Scale Plasmonic nanoCones array For Spectroscopy Detection

    KAUST Repository

    Das, Gobind; Battista, Edmondo; Manzo, Gianluigi; Causa, Filippo; Netti, Paolo; Di Fabrizio, Enzo M.

    2015-01-01

    Advanced optical materials or interfaces are gaining attention for diagnostic applications. However, the achievement of large device interface as well as facile surface functionalization largely impairs their wide use. The present work is aimed to address different innovative aspects related to the fabrication of large area 3D plasmonic arrays, their direct and easy functionalization with capture elements and their spectroscopic verifications through enhanced Raman and enhanced fluorescence techniques. In detail we have investigated the effect of Au-based nanoCones array, fabricated by means of direct nanoimprint technique over large area (mm2), on protein capturing and on the enhancement in optical signal. A selective functionalization of gold surfaces was proposed by using a peptide (AuPi3) previously selected by phage display. In this regard, two different sequences, labeled with fluorescein and biotin, were chemisorbed on metallic surfaces. The presence of Au nanoCones array consents an enhancement in electric field on the apex of cone, enabling the detection of molecules. We have witnessed around 12-fold increase in fluorescence intensity and SERS enhancement factor around 1.75 ×105 with respect to the flat gold surface. Furthermore, a sharp decrease in fluorescence lifetime over nanoCones confirms the increase in radiative emission (i.e. an increase in photonics density at the apex of cones).

  14. Large Scale Plasmonic nanoCones array For Spectroscopy Detection

    KAUST Repository

    Das, Gobind

    2015-09-24

    Advanced optical materials or interfaces are gaining attention for diagnostic applications. However, the achievement of large device interface as well as facile surface functionalization largely impairs their wide use. The present work is aimed to address different innovative aspects related to the fabrication of large area 3D plasmonic arrays, their direct and easy functionalization with capture elements and their spectroscopic verifications through enhanced Raman and enhanced fluorescence techniques. In detail we have investigated the effect of Au-based nanoCones array, fabricated by means of direct nanoimprint technique over large area (mm2), on protein capturing and on the enhancement in optical signal. A selective functionalization of gold surfaces was proposed by using a peptide (AuPi3) previously selected by phage display. In this regard, two different sequences, labeled with fluorescein and biotin, were chemisorbed on metallic surfaces. The presence of Au nanoCones array consents an enhancement in electric field on the apex of cone, enabling the detection of molecules. We have witnessed around 12-fold increase in fluorescence intensity and SERS enhancement factor around 1.75 ×105 with respect to the flat gold surface. Furthermore, a sharp decrease in fluorescence lifetime over nanoCones confirms the increase in radiative emission (i.e. an increase in photonics density at the apex of cones).

  15. MARKETING LIBRARY SERVICES IN ACADEMIC LIBRARIES: A ...

    African Journals Online (AJOL)

    MARKETING LIBRARY SERVICES IN ACADEMIC LIBRARIES: A TOOL FOR SURVIVAL IN THE ... This article discusses the concept of marketing library and information services as an ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  16. Identification of an extensive gene cluster among a family of PPOs in Trifolium pratense L. (red clover using a large insert BAC library

    Directory of Open Access Journals (Sweden)

    Thomas Ann

    2009-07-01

    Full Text Available Abstract Background Polyphenol oxidase (PPO activity in plants is a trait with potential economic, agricultural and environmental impact. In relation to the food industry, PPO-induced browning causes unacceptable discolouration in fruit and vegetables: from an agriculture perspective, PPO can protect plants against pathogens and environmental stress, improve ruminant growth by increasing nitrogen absorption and decreasing nitrogen loss to the environment through the animal's urine. The high PPO legume, red clover, has a significant economic and environmental role in sustaining low-input organic and conventional farms. Molecular markers for a range of important agricultural traits are being developed for red clover and improved knowledge of PPO genes and their structure will facilitate molecular breeding. Results A bacterial artificial chromosome (BAC library comprising 26,016 BAC clones with an average 135 Kb insert size, was constructed from Trifolium pratense L. (red clover, a diploid legume with a haploid genome size of 440–637 Mb. Library coverage of 6–8 genome equivalents ensured good representation of genes: the library was screened for polyphenol oxidase (PPO genes. Two single copy PPO genes, PPO4 and PPO5, were identified to add to a family of three, previously reported, paralogous genes (PPO1–PPO3. Multiple PPO1 copies were identified and characterised revealing a subfamily comprising three variants PPO1/2, PPO1/4 and PPO1/5. Six PPO genes clustered within the genome: four separate BAC clones could be assembled onto a predicted 190–510 Kb single BAC contig. Conclusion A PPO gene family in red clover resides as a cluster of at least 6 genes. Three of these genes have high homology, suggesting a more recent evolutionary event. This PPO cluster covers a longer region of the genome than clusters detected in rice or previously reported in tomato. Full-length coding sequences from PPO4, PPO5, PPO1/5 and PPO1/4 will facilitate

  17. Evaluation as a Tool for Developing the Quality of Academic Libraries. Case Study at a Large and Traditional Research Oriented Scandinavian University

    Directory of Open Access Journals (Sweden)

    Kaisa Sinikara

    2006-10-01

    Full Text Available The leaders of our universities will ask today if we offer those services that a top university requires and whether the proposed resources for the libraries are worth investing. Establishing the European Higher Education Area (EHEA requires the establishing of quality systems. Quality assurance systems will be introduced throughout the entire European academic sector and will certainly have significant impact on the development of academic organizations. The collaborative effort to evaluate European universities is coordinated by ENQA, the European Association for Quality Assurance in Higher education (Standards, 2005. Most European countries have developed a national quality assurance system. The solutions of different countries can be divided into three different classes: 1 Auditing countries[1] (institutional audit, quality audit, evaluation of quality assurance systems, enhancement-led institutional review: England, Scotland, Ireland, France, Finland, 2 Accreditation[2]: Holland, Germany and 3 Combination or another system: Norway, Switzerland, Denmark, Sweden (Audits, 2006.

  18. Library news

    CERN Multimedia

    CERN Library

    2010-01-01

    The CERN Library has been providing electronic access to the "Techniques de l'Ingénieur" database for the past 8 months. As a reminder, this is a multidisciplinary database of over 4000 technical and scientific articles in French, covering a broad range of topics such as mechanical engineering, safety, electronics and the environment. In a few simple steps, you can create your own account, select the types of documents you are interested in and configure your settings so as to receive alerts when articles in your field of activity are published. You can now access this resource from outside CERN using the "remote access to electronic resources" service. Further information is available here. Direct access to the database. Remote access to electronic resources. If you have any questions or comments, don't hesitate to contact us at: library.desk@cern.ch.

  19. Library Benchmarking

    Directory of Open Access Journals (Sweden)

    Wiji Suwarno

    2017-02-01

    Full Text Available The term benchmarking has been encountered in the implementation of total quality (TQM or in Indonesian termed holistic quality management because benchmarking is a tool to look for ideas or learn from the library. Benchmarking is a processof measuring and comparing for continuous business process of systematic and continuous measurement, the process of measuring and comparing for continuous business process of an organization to get information that can help these organization improve their performance efforts.

  20. Antibody repertoire profiling with mimotope arrays

    OpenAIRE

    Pashova, Shina; Schneider, Christoph; von Gunten, Stephan; Pashov, Anastas

    2016-01-01

    Large-scale profiling and monitoring of antibody repertoires is possible through next generation sequencing (NGS), phage display libraries and microarrays. These methods can be combined in a pipeline, which ultimately maps the antibody reactivities onto defined arrays of structures - peptides or carbohydrates. The arrays can help analyze the individual specificities or can be used as complex patterns. In any case, the targets recognized should formally be considered mimotopes unless they are ...

  1. Reference neutron activation library

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-04-01

    almost all the reactions of interest to the other applications mentioned above. However, because these fusion activation libraries are so large (more than 10,000 reactions are common), there are cases where specialized libraries contain or require more accurate information. For this reason the IAEA felt that research in these areas could be helped by developing a library of particularly important activation reactions which would be of benefit to a broad range of applications, some of which are mentioned above.

  2. Reference neutron activation library

    International Nuclear Information System (INIS)

    2002-04-01

    reactions of interest to the other applications mentioned above. However, because these fusion activation libraries are so large (more than 10,000 reactions are common), there are cases where specialized libraries contain or require more accurate information. For this reason the IAEA felt that research in these areas could be helped by developing a library of particularly important activation reactions which would be of benefit to a broad range of applications, some of which are mentioned above

  3. Selection of SARS-Coronavirus-specific B cell epitopes by phage peptide library screening and evaluation of the immunological effect of epitope-based peptides on mice

    International Nuclear Information System (INIS)

    Yu Hua; Jiang Lifang; Fang Danyun; Yan Huijun; Zhou Jingjiao; Zhou Junmei; Liang Yu; Gao Yang; Zhao, Wei; Long Beiguo

    2007-01-01

    Antibodies to SARS-Coronavirus (SARS-CoV)-specific B cell epitopes might recognize the pathogen and interrupt its adherence to and penetration of host cells. Hence, these epitopes could be useful for diagnosis and as vaccine constituents. Using the phage-displayed peptide library screening method and purified Fab fragments of immunoglobulin G (IgG Fab) from normal human sera and convalescent sera from SARS-CoV-infected patients as targets, 11 B cell epitopes of SARS-CoV spike glycoprotein (S protein) and membrane protein (M protein) were screened. After a bioinformatics tool was used to analyze these epitopes, four epitope-based S protein dodecapeptides corresponding to the predominant epitopes were chosen for synthesis. Their antigenic specificities and immunogenicities were studied in vitro and in vivo. Flow cytometry and ELISPOT analysis of lymphocytes as well as a serologic analysis of antibody showed that these peptides could trigger a rapid, highly effective, and relatively safe immune response in BALB/c mice. These findings might aid development of SARS diagnostics and vaccines. Moreover, the role of S and M proteins as important surface antigens is confirmed

  4. News from the Library

    CERN Multimedia

    CERN Library

    2010-01-01

    Even more books available electronically!   For several years now, the Library has been offering a large collection of electronic books in a wide range of disciplines. The books can be accessed by all CERN users with a Nice account and, like printed books, can be borrowed for a given period. In a few clicks of the mouse, you can leaf through and read books and even print parts of them from your computer. The Library catalogue now comprises a total of more than 10,000 different e-books. The long-awaited electronic versions of O'Reilly book titles are now available: 70 titles have recently been added to the Library's collection and many others will follow in the coming weeks. This collection of books, mainly on IT subjects, is widely used in the development field. Their availability on line is thus a clear bonus. But there's no need for fans of paper versions to worry: the Library will continue to expand its collection of printed books. The two collections exist side by side and even complement ea...

  5. How Users Search the Library from a Single Search Box

    Science.gov (United States)

    Lown, Cory; Sierra, Tito; Boyer, Josh

    2013-01-01

    Academic libraries are turning increasingly to unified search solutions to simplify search and discovery of library resources. Unfortunately, very little research has been published on library user search behavior in single search box environments. This study examines how users search a large public university library using a prominent, single…

  6. Leadership Diversity: A Study of Urban Public Libraries

    Science.gov (United States)

    Winston, Mark; Li, Haipeng

    2007-01-01

    Diversity has been identified as a priority in library and information services for some time. The limited published research on diversity programs in libraries, though, has focused on academic libraries. This article represents the results of a study of leadership diversity in large, urban public libraries. In the study of members of the Urban…

  7. Libraries for users services in academic libraries

    CERN Document Server

    Alvite, Luisa

    2010-01-01

    This book reviews the quality and evolution of academic library services. It revises service trends offered by academic libraries and the challenge of enhancing traditional ones such as: catalogues, repositories and digital collections, learning resources centres, virtual reference services, information literacy and 2.0 tools.studies the role of the university library in the new educational environment of higher educationrethinks libraries in academic contextredefines roles for academic libraries

  8. Rebuilding the Mackintosh Library collection

    OpenAIRE

    Buri, David

    2015-01-01

    Summarises progress to date in rebuilding the former Mackintosh Library book and journal collections. Focuses on the need to restore the library's holdings of pre-1985 architectural magazines, and describes the large donation of such material donated by the Royal Incorporation of Architects in Scotland (RIAS) in early 2014. Looks at the history of some of these magazines and their contribution to the architectural profession, and invites further donations of material to help rebuild the Macki...

  9. Reusable libraries for safety-critical Java

    DEFF Research Database (Denmark)

    Rios Rivas, Juan Ricardo; Schoeberl, Martin

    2014-01-01

    The large collection of Java class libraries is a main factor of the success of Java. However, these libraries assume that a garbage-collected heap is used. Safety-critical Java uses scope-based memory areas instead of a garbage-collected heap. Therefore, the Java class libraries are problematic...... to use in safety-critical Java. We have identified common programming patterns in the Java class libraries that make them unsuitable for safety-critical Java. We propose ways to improve the libraries to avoid the impact of the identified problematic patterns. We illustrate these changes by implementing...

  10. Marketing the Virtual Library

    Science.gov (United States)

    Fagan, Jody Condit

    2009-01-01

    Far more people are familiar with their local public or college library facility than their library's website and online resources. In fact, according to a recent survey, 96% of Americans said they had visited a library in person, but less than one-third have visited their online library. Since everyone agrees that online library resources are…

  11. State Virtual Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2003-01-01

    Virtual library? Electronic library? Digital library? Online information network? These all apply to the growing number of Web-based resource collections managed by consortiums of state library entities. Some, like "INFOhio" and "KYVL" ("Kentucky Virtual Library"), have been available for a few years, but others are just starting. Searching for…

  12. Public Libraries in Bangladesh.

    Science.gov (United States)

    Khan, M. H.

    1984-01-01

    Overview of library movement in Bangladesh highlights British (1851-1947) and Pakistan periods (1947-1971), separation of Bangladesh from Pakistan, libraries in development plans (1951-1970), three important public libraries, development of national library, book resources, a library network plan, legislation, finance, leadership, library…

  13. Library usage patterns in the electronic information environment. Electronic journals, Use studies, Libraries, Medical libraries

    Directory of Open Access Journals (Sweden)

    B. Franklin

    2004-01-01

    Full Text Available This paper examines the methodology and results from Web-based surveys of more than 15,000 networked electronic services users in the United States between July 1998 and June 2003 at four academic health sciences libraries and two large main campus libraries serving a variety of disciplines. A statistically valid methodology for administering simultaneous Web-based and print-based surveys using the random moments sampling technique is discussed and implemented. Results from the Web-based surveys showed that at the four academic health sciences libraries, there were approximately four remote networked electronic services users for each in-house user. This ratio was even higher for faculty, staff, and research fellows at the academic health sciences libraries, where more than five remote users for each in-house user were recorded. At the two main libraries, there were approximately 1.3 remote users for each in-house user of electronic information. Sponsored research (grant funded research accounted for approximately 32% of the networked electronic services activity at the health sciences libraries and 16% at the main campus libraries. Sponsored researchers at the health sciences libraries appeared to use networked electronic services most intensively from on-campus, but not from in the library. The purpose of use for networked electronic resources by patrons within the library is different from the purpose of use of those resources by patrons using the resources remotely. The implications of these results on how librarians reach decisions about networked electronic resources and services are discussed.

  14. Quality evaluation of tandem mass spectral libraries.

    Science.gov (United States)

    Oberacher, Herbert; Weinmann, Wolfgang; Dresen, Sebastian

    2011-06-01

    Tandem mass spectral libraries are gaining more and more importance for the identification of unknowns in different fields of research, including metabolomics, forensics, toxicology, and environmental analysis. Particularly, the recent invention of reliable, robust, and transferable libraries has increased the general acceptance of these tools. Herein, we report on results obtained from thorough evaluation of the match reliabilities of two tandem mass spectral libraries: the MSforID library established by the Oberacher group in Innsbruck and the Weinmann library established by the Weinmann group in Freiburg. Three different experiments were performed: (1) Spectra of the libraries were searched against their corresponding library after excluding either this single compound-specific spectrum or all compound-specific spectra prior to searching; (2) the libraries were searched against each other using either library as reference set or sample set; (3) spectra acquired on different mass spectrometric instruments were matched to both libraries. Almost 13,000 tandem mass spectra were included in this study. The MSforID search algorithm was used for spectral matching. Statistical evaluation of the library search results revealed that principally both libraries enable the sensitive and specific identification of compounds. Due to higher mass accuracy of the QqTOF compared with the QTrap instrument, matches to the MSforID library were more reliable when comparing spectra with both libraries. Furthermore, only the MSforID library was shown to be efficiently transferable to different kinds of tandem mass spectrometers, including "tandem-in-time" instruments; this is due to the coverage of a large range of different collision energy settings-including the very low range-which is an outstanding characteristics of the MSforID library.

  15. Afghanistan Digital Library Initiative: Revitalizing an Integrated Library System

    Directory of Open Access Journals (Sweden)

    Yan HAN

    2007-12-01

    Full Text Available This paper describes an Afghanistan digital library initiative of building an integrated library system (ILS for Afghanistan universities and colleges based on open-source software. As one of the goals of the Afghan eQuality Digital Libraries Alliance, the authors applied systems analysis approach, evaluated different open-source ILSs, and customized the selected software to accommodate users’ needs. Improvements include Arabic and Persian language support, user interface changes, call number label printing, and ISBN-13 support. To our knowledge, this ILS is the first at a large academic library running on open-source software.

  16. Multigroup cross section library; WIMS library

    International Nuclear Information System (INIS)

    Kannan, Umasankari

    2000-01-01

    The WIMS library has been extensively used in thermal reactor calculations. This multigroup constants library was originally developed from the UKNDL in the late 60's and has been updated in 1986. This library has been distributed with the WIMS-D code by NEA data bank. The references to WIMS library in literature are the 'old' which is the original as developed by the AEA Winfrith and the 'new' which is the current 1986 WIMS library. IAEA has organised a CRP where a new and fully updated WIMS library will soon be available. This paper gives an overview of the definitions of the group constants that go into any basic nuclear data library used for reactor calculations. This paper also outlines the contents of the WIMS library and some of its shortcomings

  17. LIBRARY SKILL INSTRUCTION IN NIGERIAN ACADEMIC LIBRARIES

    African Journals Online (AJOL)

    DJFLEX

    www.globaljournalseries.com; Info@globaljournalseries.com. LIBRARY SKILL INSTRUCTION IN NIGERIAN ACADEMIC. LIBRARIES. P. C. AZIAGBA AND E. H. UZOEZI. (Received 10, September 2009; Revision Accepted 8, February 2010). ABSTRACT. This survey was undertaken to portray the level of library involvement ...

  18. Nursing educator's satisfaction with library facilities.

    OpenAIRE

    Lenz, E R; Waltz, C F

    1982-01-01

    This study examined nursing faculty perceptions of the importance of adequate library facilities and their satisfaction with them. Library facilities ranked highest in importance among all job characteristics studied, with faculty who had been most productive in terms of publication assigning the highest value to them. A moderate level of satisfaction was found. Faculty most satisfied with library facilities were those teaching in large schools of nursing with graduate programs and open organ...

  19. Design for manufacturability of a VDSM standard cell library

    International Nuclear Information System (INIS)

    Zhou Chong; Zeng Jianping; Chen Lan; Yin Minghui; Zhao Jie

    2012-01-01

    This paper presents a method of designing a 65 nm DFM standard cell library. By reducing the amount of the library largely, the process of optical proximity correction (OPC) becomes more efficient and the need for large storage is reduced. This library is more manufacture-friendly as each cell has been optimized according to the DFM rule and optical simulation. The area penalty is minor compared with traditional library, and the timing, as well as power has a good performance. Furthermore, this library has passed the test from the Technology Design Department of Foundry. The result shows this DFM standard cell library has advantages that improve the yield. (semiconductor integrated circuits)

  20. How libraries use publisher metadata

    Directory of Open Access Journals (Sweden)

    Steve Shadle

    2013-11-01

    Full Text Available With the proliferation of electronic publishing, libraries are increasingly relying on publisher-supplied metadata to meet user needs for discovery in library systems. However, many publisher/content provider staff creating metadata are unaware of the end-user environment and how libraries use their metadata. This article provides an overview of the three primary discovery systems that are used by academic libraries, with examples illustrating how publisher-supplied metadata directly feeds into these systems and is used to support end-user discovery and access. Commonly seen metadata problems are discussed, with recommendations suggested. Based on a series of presentations given in Autumn 2012 to the staff of a large publisher, this article uses the University of Washington Libraries systems and services as illustrative examples. Judging by the feedback received from these presentations, publishers (specifically staff not familiar with the big picture of metadata standards work would benefit from a better understanding of the systems and services libraries provide using the data that is created and managed by publishers.

  1. Libraries and Learning

    Science.gov (United States)

    Rainie, Lee

    2016-01-01

    The majority of Americans think local libraries serve the educational needs of their communities and families pretty well and library users often outpace others in learning activities. But many do not know about key education services libraries provide. This report provides statistics on library usage and presents key education services provided…

  2. Growing Competition for Libraries.

    Science.gov (United States)

    Gibbons, Susan

    2001-01-01

    Describes the Questia subscription-based online academic digital books library. Highlights include weaknesses of the collection; what college students want from a library; importance of marketing; competition for traditional academic libraries that may help improve library services; and the ability of Questia to overcome barriers and…

  3. The library marketing toolkit

    CERN Document Server

    Potter, Ned

    2012-01-01

    A guide that offers coverage of various elements of library marketing and branding for different sectors including archives and academic, public and special libraries. It is suitable for those who are involved in promoting their library or information service, whether at an academic, public or special library or in archives or records management.

  4. Automating the Small Library.

    Science.gov (United States)

    Skapura, Robert

    1987-01-01

    Discusses the use of microcomputers for automating school libraries, both for entire systems and for specific library tasks. Highlights include available library management software, newsletters that evaluate software, constructing an evaluation matrix, steps to consider in library automation, and a brief discussion of computerized card catalogs.…

  5. Math Branding in a Community College Library

    Science.gov (United States)

    Brantz, Malcolm; Sadowski, Edward B.

    2010-01-01

    As a strategy to promote the Arapahoe Community College Library's collections and services, the Library undertook to brand itself as a math resource center. In promoting one area of expertise, math was selected to help address the problem of a large portion of high school graduates' inability to work at college-level math. A "Math…

  6. America's Star Libraries, 2010: Top-Rated Libraries

    Science.gov (United States)

    Lyons, Ray; Lance, Keith Curry

    2010-01-01

    The "LJ" Index of Public Library Service 2010, "Library Journal"'s national rating of public libraries, identifies 258 "star" libraries. Created by Ray Lyons and Keith Curry Lance, and based on 2008 data from the IMLS, it rates 7,407 public libraries. The top libraries in each group get five, four, or three stars. All included libraries, stars or…

  7. Theoretical Foundations for Digital Libraries

    CERN Document Server

    Fox, Edward A; Shen, Rao

    2012-01-01

    In 1991, a group of researchers chose the term digital libraries to describe an emerging field of research, development, and practice. Since then, Virginia Tech has had funded research in this area, largely through its Digital Library Research Laboratory. This book is the first in a four book series that reports our key findings and current research investigations. Underlying this book series are five completed dissertations (Gonçalves, Kozievitch, Murthy, Shen, Torres), nine dissertations underway, and many masters theses. These reflect our experience with a long string of prototype or produc

  8. Floating Collection in an Academic Library: An Audacious Experiment That Succeeded

    Science.gov (United States)

    Coopey, Barbara; Eshbach, Barbara; Notartomas, Trish

    2016-01-01

    Can a floating collection thrive in a large multicampus academic research library? Floating collections have been successful in public libraries for some time, but it is uncommon for academic libraries and unheard of for a large academic library system. This article will discuss the investigation into the feasibility of a floating collection at…

  9. Libraries and Accessibility: Istanbul Public Libraries Case

    Directory of Open Access Journals (Sweden)

    Gül Yücel

    2016-12-01

    Full Text Available In the study; the assessment of accessibility has been conducted in Istanbul public libraries within the scope of public area. Public libraries commonly serve with its user of more than 20 million in total, spread to the general of Turkey, having more than one thousand branches in the centrums and having more than one million registered members. The building principles and standards covering the subjects such as the selection of place, historical and architectural specification of the region, distance to the centre of population and design in a way that the disabled people could benefit from the library services fully have been determined with regulations in the construction of new libraries. There are works for the existent libraries such as access for the disabled, fire safety precautions etc. within the scope of the related standards. Easy access by everyone is prioritized in the public libraries having a significant role in life-long learning. The purpose of the study is to develop solution suggestions for the accessibility problems in the public libraries. The study based on the eye inspection and assessments carried out within the scope of accessibility in the public libraries subsidiary to Istanbul Culture and Tourism Provincial Directorate Library and Publications Department within the provincial borders of Istanbul. The arrangements such as reading halls, study areas, book shelves etc. have been examined within the frame of accessible building standards. Building entrances, ramps and staircases, horizontal and vertical circulation of building etc. have been taken into consideration within the scope of accessible building standards. The subjects such as the reading and studying areas and book shelf arrangements for the library have been assessed within the scope of specific buildings. There are a total of 34 public libraries subsidiary to Istanbul Culture and Tourism Provincial Directorate on condition that 20 ea. of them are in the

  10. Public libraries and lifelong learning

    DEFF Research Database (Denmark)

    Nielsen, Bo Gerner; Borlund, Pia

    2015-01-01

    society as a result of easy and free access to information. A basic understanding of the concept is ‘learning throughout life, either continuously or periodically’. This implies that learning is not restricted to educational institutions, but can also take place in for example the public library. Public...... libraries thus may play an important role in supporting the learning process not the least because lifelong learning is characterised by the inclusion of informal elements of learning, flexible learning opportunities, and a shift towards selfdirected learning. This self-directed learning promotes active...... at teaching? The study reports on data from 12 interviews of purposely selected public librarians and a large-scale e-mail survey (questionnaire). The e-mail survey contained 28 questions and was sent to all staff members in public libraries in Denmark, and resulted in 986 responses. The results show...

  11. Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.

    Science.gov (United States)

    Hur, Byung-ung; Yoon, Jae-bong; Liu, Li-Kun; Cha, Sang-hoon

    2010-11-30

    Specific antibodies that possess a subnanomolar affinity are very difficult to obtain from human naïve immunoglobulin repertoires without the use of lengthy affinity optimization procedures. Here, we designed a hierarchical phage-displayed antibody library system to generate an enormous diversity of combinatorial Fab fragments (6×10(17)) and attempted to isolate high-affinity Fabs against the human epidermal growth factor receptor (EGFR). A primary antibody library, designated HuDVFab-8L, comprising 4.5×10(9) human naïve heavy chains and eight unspecified human naïve light chains was selected against the EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated. Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR expressed on A431 cells, the heavy chain of the Fab was shuffled with a human naïve light chain repertoire with a diversity of 1.4×10(8) and selected a second time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11, recognized an EGFR epitope that was almost the same as that bound by cetuximab and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold higher than that of the FabC225 derived from cetuximab. This variant was also internalized by A431 cells, likely via receptor-mediated endocytosis, and it efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These results demonstrate that the use of our hierarchical antibody library system is advantageous in generating fully human antibodies especially with a therapeutic purpose. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. The laughing librarian a history of American library humor

    CERN Document Server

    Smith, Jeanette C

    2012-01-01

    ""Should be required reading for all librarians and library-school students""--Booklist; ""a must have...recommend""--Library History Buff Blog; ""charts the largely unexplored territory of library wit and satire, both inside and outside the profession""--C&RL News.

  13. McDonald and Company Securities Library User Survey, 1996.

    Science.gov (United States)

    Wolfgram, Derek E.

    The library of McDonald and Company Securities is important to the success of the business and its employees. This study assesses the needs and expectations of the library users, and analyzes how well the current library services are meeting those needs and expectations. A questionnaire was distributed to a large random sample of the firm's…

  14. Security Risks Management in Selected Academic Libraries in Osun ...

    African Journals Online (AJOL)

    The survival of a library depends to a large extent on how secured its collections are. Security of collections constitutes a critical challenge facing academic libraries in Nigeria. It is against this background that this study investigated the security risks management in selected academic libraries in Osun State, Nigeria.

  15. The ARL 2030 Scenarios: A User's Guide for Research Libraries

    Science.gov (United States)

    Association of Research Libraries, 2010

    2010-01-01

    This user's guide was developed to advance local planning at ARL member libraries. It is written for library leaders writ large and for anyone leading or contributing to research library planning processes. Users do not need advanced facilitation skills to benefit from this guide, but facilitators charged with supporting scenario planning will…

  16. Construction of BAC Libraries from Flow-Sorted Chromosomes.

    Science.gov (United States)

    Šafář, Jan; Šimková, Hana; Doležel, Jaroslav

    2016-01-01

    Cloned DNA libraries in bacterial artificial chromosome (BAC) are the most widely used form of large-insert DNA libraries. BAC libraries are typically represented by ordered clones derived from genomic DNA of a particular organism. In the case of large eukaryotic genomes, whole-genome libraries consist of a hundred thousand to a million clones, which make their handling and screening a daunting task. The labor and cost of working with whole-genome libraries can be greatly reduced by constructing a library derived from a smaller part of the genome. Here we describe construction of BAC libraries from mitotic chromosomes purified by flow cytometric sorting. Chromosome-specific BAC libraries facilitate positional gene cloning, physical mapping, and sequencing in complex plant genomes.

  17. Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.

    Science.gov (United States)

    Chang, Yi-Pin; Chu, Yen-Ho

    2014-05-16

    The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

  18. Consortia for Electronic Library Provision in Belgium

    Directory of Open Access Journals (Sweden)

    Julien Van Borm

    2001-07-01

    Full Text Available E-libraries just like the former paper-based libraries will become increasingly essential and indispensable tools in research and education. Library consortia seem to be the way to get e-libraries started all over the world. However, it is unclear yet whether this is going to be a longlasting workable model. The Belgian research libraries follow the international pattern and are rapidly becoming hybrid libraries especially in business, science, applied sciences and biomedicine (the STM disciplines. Still they have large paper bound collections on board and no library is willing to replace these in the near future by a purely electronic collection of journals. The fear of losing the content and thus the „raison d’être“ of the library and the concern for users not yet familiar with e-information sources are the cornerstone for a prudent, yet conservative policy. Increasingly e-information and e-journals are being taken on board. Paper and electronic go side by side in new hybrid libraries partly also due to the market policy set by the publishers in combining paper and electronic in an attempt to keep or improve the annual turnover reached during the past paper period. The transition from paper to electronic occurred in Belgium somewhat later than in other Western European countries. This confirms the position of Belgium often taking up an average position in Western Europe.

  19. Libraries serving dialogue

    CERN Document Server

    Dupont, Odile

    2014-01-01

    This book based on experiences of libraries serving interreligious dialogue, presents themes like library tools serving dialogue between cultures, collections dialoguing, children and young adults dialoguing beyond borders, story telling as dialog, librarians serving interreligious dialogue.

  20. Israeli Special Libraries

    Science.gov (United States)

    Foster, Barbara

    1974-01-01

    Israel is sprinkled with a noteworthy representation of special libraries which run the gamut from modest kibbutz efforts to highly technical scientific and humanities libraries. A few examples are discussed here. (Author/CH)

  1. Marketing library and information services in academic libraries in ...

    African Journals Online (AJOL)

    Marketing library and information services in academic libraries in Niger State, Nigeria. ... This study was designed to investigate the marketing of library services in academic libraries in Niger state, ... EMAIL FULL TEXT EMAIL FULL TEXT

  2. User services in the central library of Juelich Research Center

    International Nuclear Information System (INIS)

    Lapp, E.

    1993-01-01

    The central library is a sci/tech special library providing information for the KFA researchers and staff. The library has a large collection of sci/tech materials to meet the information demands of the KFA employees and over 3.000 external users. Among the outside users are students fromthe universities and polytechnics of the region Aachen, Cologne, Duesseldorf, and industry. The library acquires about 8.000 volumes per year and subscribes to 2000 journals. (orig.)

  3. Managing intellectual capital in libraries beyond the balance sheet

    CERN Document Server

    Kostagiolas, Petros

    2012-01-01

    In the knowledge economy, professionals have to make decisions about non-tangible, non-monetary, and largely invisible resources. Information professionals need to understand the potential uses, contributions, value, structure, and creation of broadly intangible intellectual capital in libraries. In order to fully realize intellectual capital in libraries, new practices and skills are required for library management practitioners and researchers.Managing Intellectual Capital in Libraries provides research advances, guidelines, methods and techniques for managing intellectual capital in a libra

  4. The alternative library

    OpenAIRE

    Collinson, Timothy; Williams, A.

    2004-01-01

    Much time and effort has been devoted to designing and developing library Web sites that are easy to navigate by both new students and experienced researchers. In a review of the Southampton Institute Library it was decided that in addition to updating the existing homepage an alternative would be offered. Drawing on theory relating to user interface design, learning styles and creative thinking, an Alternative Library navigation system was added to the more traditional library homepage. The ...

  5. FENDL multigroup libraries

    International Nuclear Information System (INIS)

    Ganesan, S.; Muir, D.W.

    1992-01-01

    Selected neutron reaction nuclear data libraries and photon-atomic interaction cross section libraries for elements of interest to the IAEA's program on Fusion Evaluated Nuclear Data Library (FENDL) have been processed into MATXSR format using the NJOY system on the VAX4000 computer of the IAEA. This document lists the resulting multigroup data libraries. All the multigroup data generated are available cost-free upon request from the IAEA Nuclear Data Section. (author). 9 refs

  6. Changing State Digital Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2006-01-01

    Research has shown that state virtual or digital libraries are evolving into websites that are loaded with free resources, subscription databases, and instructional tools. In this article, the author explores these evolving libraries based on the following questions: (1) How user-friendly are the state digital libraries?; (2) How do state digital…

  7. School Libraries and Innovation

    Science.gov (United States)

    McGrath, Kevin G.

    2015-01-01

    School library programs have measured success by improved test scores. But how do next-generation school libraries demonstrate success as they strive to be centers of innovation and creativity? These libraries offer solutions for school leaders who struggle to restructure existing systems built around traditional silos of learning (subjects and…

  8. Reforming Prison Libraries.

    Science.gov (United States)

    Coyle, William J.

    1989-01-01

    Discusses the current widespread acceptance of the public library model for prison libraries, in which preferences of the inmates are the chief consideration in programing and collection development. It is argued that this model results in recreational programs and collections that fail to fulfill the prison library's role in education and…

  9. LANL Research Library

    Science.gov (United States)

    Los Alamos National Laboratory The LANL Research Library website has been moved to http ://www.lanl.gov/library/. Please update your bookmarks. If you are not redirected to the new location within 10 http:// | Last Modified: Send email to the Library

  10. Joint-Use Libraries

    Science.gov (United States)

    Casstevens, Susan

    2017-01-01

    The joint-use library is a place where people of all ages, interests, and income levels can find items of interest at no personal cost. The mission of A. H. Meadows Public and High School Library in Midlothian, Texas, is to offer what other public libraries provide: educational and entertainment resources to a community. Yet, the staff also wants…

  11. Learning Boost C++ libraries

    CERN Document Server

    Mukherjee, Arindam

    2015-01-01

    If you are a C++ programmer who has never used Boost libraries before, this book will get you up-to-speed with using them. Whether you are developing new C++ software or maintaining existing code written using Boost libraries, this hands-on introduction will help you decide on the right library and techniques to solve your practical programming problems.

  12. Technostress and Library Values.

    Science.gov (United States)

    Gorman, Michael

    2001-01-01

    Discusses information overload and society's and libraries' responses to technology. Considers eight values that libraries should focus on and how they relate to technology in libraries: democracy, stewardship, service, intellectual freedom, privacy, rationalism, equity of access, and building harmony and balance. (LRW)

  13. Marketing and Library Management.

    Science.gov (United States)

    Murphy, Kurt R.

    1991-01-01

    Examines the role of marketing in the management of libraries. The role of public relations (PR) in the total marketing concept is discussed, surveys that have explored PR efforts in academic and public libraries are described, and changes affecting libraries that marketing efforts could help to manage are discussed. (seven references) (LRW)

  14. Virtual Libraries: Service Realities.

    Science.gov (United States)

    Novak, Jan

    2002-01-01

    Discussion of changes in society that have resulted from information and communication technologies focuses on changes in libraries and a new market for library services with new styles of clients. Highlights client service issues to be considered when transitioning to a virtual library situation. (Author/LRW)

  15. Merchandising Your Library.

    Science.gov (United States)

    Sivulich, Kenneth G.

    1989-01-01

    Discusses library circulation figures as a reflection of the success of library services and describes merchandising techniques that have produced a 137 percent circulation increase at Queens Borough Public Library over the past seven years. Merchandising techniques such as minibranches, displays, signage, dumps, and modified shelving are…

  16. Editorial Library: User Survey.

    Science.gov (United States)

    Surace, Cecily J.

    This report presents the findings of a survey conducted by the editorial library of the Los Angeles Times to measure usage and satisfaction with library service, provide background information on library user characteristics, collect information on patterns of use of the Times' clipping files, relate data on usage and satisfaction parameters to…

  17. Marketing Academic Libraries

    Science.gov (United States)

    Mallon, Melissa, Ed.

    2013-01-01

    Ask any academic librarian if marketing their library and its services is an important task, and the answer will most likely be a resounding "yes!" Particularly in economically troubled times, librarians are increasingly called upon to promote their services and defend their library's worth. Since few academic libraries have in-house marketing…

  18. WIMS-D library update

    International Nuclear Information System (INIS)

    2007-05-01

    WIMS-D (Winfrith Improved Multigroup Scheme-D) is the name of a family of software packages for reactor lattice calculations and is one of the few reactor lattice codes in the public domain and available on noncommercial terms. WIMSD-5B has recently been released from the OECD Nuclear Energy Agency Data Bank, and features major improvements in machine portability, as well as incorporating a few minor corrections. This version supersedes WIMS-D/4, which was released by the Winfrith Technology Centre in the United Kingdom for IBM machines and has been adapted for various other computer platforms in different laboratories. The main weakness of the WIMS-D package is the multigroup constants library, which is based on very old data. The relatively good performance of WIMS-D is attributed to a series of empirical adjustments to the multigroup data. However, the adjustments are not always justified on the basis of more accurate and recent experimental measurements. Following the release of new and revised evaluated nuclear data files, it was felt that the performance of WIMS-D could be improved by updating the associated library. The WIMS-D Library Update Project (WLUP) was initiated in the early 1990s with the support of the IAEA. This project consisted of voluntary contributions from a large number of participants. Several benchmarks for testing the library were identified and analysed, the WIMSR module of the NJOY code system was upgraded and the author of NJOY accepted the proposed updates for the official code system distribution. A detailed parametric study was performed to investigate the effects of various data processing input options on the integral results. In addition, the data processing methods for the main reactor materials were optimized. Several partially updated libraries were produced for testing purposes. The final stage of the WLUP was organized as a coordinated research project (CRP) in order to speed up completion of the fully updated library

  19. FY 2009 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2009 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  20. FY 2010 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2010 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  1. FY 2011 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2011 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  2. FY 2008 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2008 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  3. Beyond Helper Phage: Using "Helper Cells" to Select Peptide Affinity Ligands.

    Directory of Open Access Journals (Sweden)

    M Lisa Phipps

    Full Text Available Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1 ensure efficient display; 2 maximize the ability to select high affinity ligands; and 3 minimize the effect of the display context on binding. The "helper cell" packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report on the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.

  4. library use instruction and the pattern of utilization of library services ...

    African Journals Online (AJOL)

    Global Journal

    The data collected was analysed using descriptive statistics (simple percentage %). ... semesters and it should be an independent credit carrying course under the General Studies ... large and well stocked a library is, if the ..... Online. LIBRARY USE INSTRUCTION AND THE PATTERN OF UTILIZATION OF LIBRARY ...

  5. German Librarianship and Munich Libraries

    Directory of Open Access Journals (Sweden)

    Osman Ümit Özen

    1994-06-01

    Full Text Available There are 27 municipal libraries including the Central Public Library in Munich. The other important libraries in the city are Bayern State National Library, Maximillian University Library, a technical highschool library and the "Deutsches Musuem" Library. All these libraries are financed locally. The author introduces these libraries briefly and compares German libraries with Turkish libraries. He concludes that although theoretically there are not distinctive differences, in practice, buildings and their layout are better in Germany where more variety of services are offered. In Turkey standardization has not been realized yet. Turkey needs to computerize and network to improve the services offered in an efficient way.

  6. Interlibrary loan in primary access libraries: challenging the traditional view.

    Science.gov (United States)

    Dudden, R F; Coldren, S; Condon, J E; Katsh, S; Reiter, C M; Roth, P L

    2000-10-01

    Primary access libraries serve as the foundation of the National Network of Libraries of Medicine (NN/LM) interlibrary loan (ILL) hierarchy, yet few published reports directly address the important role these libraries play in the ILL system. This may reflect the traditional view that small, primary access libraries are largely users of ILL, rather than important contributors to the effectiveness and efficiency of the national ILL system. This study was undertaken to test several commonly held beliefs regarding ILL system use by primary access libraries. Three hypotheses were developed. HI: Colorado and Wyoming primary access libraries comply with the recommended ILL guideline of adhering to a hierarchical structure, emphasizing local borrowing. H2: The closures of two Colorado Council of Medical Librarians (CCML) primary access libraries in 1996 resulted in twenty-three Colorado primary access libraries' borrowing more from their state resource library in 1997. H3: The number of subscriptions held by Colorado and Wyoming primary access libraries is positively correlated with the number of items they loan and negatively correlated with the number of items they borrow. The hypotheses were tested using the 1992 and 1997 DOCLINE and OCLC data of fifty-four health sciences libraries, including fifty primary access libraries, two state resource libraries, and two general academic libraries in Colorado and Wyoming. The ILL data were obtained electronically and analyzed using Microsoft Word 98, Microsoft Excel 98, and JMP 3.2.2. CCML primary access libraries comply with the recommended guideline to emphasize local borrowing by supplying each other with the majority of their ILLs, instead of overburdening libraries located at higher levels in the ILL hierarchy (H1). The closures of two CCML primary access libraries appear to have affected the entire ILL system, resulting in a greater volume of ILL activity for the state resource library and other DOCLINE libraries higher

  7. Library/vendor relationships

    CERN Document Server

    Brooks, Sam

    2014-01-01

    A view of the mutual dependence between libraries and vendorsAs technology advances, libraries are forced to reach beyond their own resources to find effective ways to maintain accuracy and superior service levels. Vendors provide databases and integrated library systems that perform those functions for profit. Library/Vendor Relationships examines the increasing cooperation in which libraries find they must participate in, and vice versa, with the vendors that provide system infrastructure and software. Expert contributors provide insights from all sides of this unique collaboration, offering

  8. Library system of Italy

    Directory of Open Access Journals (Sweden)

    Nataša Gerbec

    2003-01-01

    Full Text Available In the European extent, Italy is the cradle of libraries and library sciences. In the past, Italian national public libraries played an important role through their vast book treasury. But only during the last thirty years have public libraries been developed following the Anglo-American public library model. Italy does not have any uniform or general legislation concerning libraries. On the state level, this area is regulated by some separate acts, while on the regional level there is a collection of various acts and regulations. Libraries are not strictly divided into general categories. It is required that the professionals engaged in Italian libraries should have secondary or university education. The level of their professional tasks depends on the type of library and its capacity. The competency for the development in the field of librarianship is assigned to The Ministry of Cultural and Environment Heritage as well as to its subordinate institutions (Central Institute for the Union catalogue of Italian Libraries and for Bibliographic Information, Central Institute for Book Pathology, Observatory for International Libraries Programmes.

  9. Planning & Urban Affairs Library Manual.

    Science.gov (United States)

    Knobbe, Mary L., Ed.; Lessel, Janice W., Ed.

    Written especially for persons without a library degree who are operating a small urban study or planning agency library on a part-time basis. Subjects covered are: (1) library function and staff function, duties and training; (2) physical layout and equipment of library; (3) establishing and maintaining the library; (4) library administration;…

  10. Special Libraries and Multitype Networks.

    Science.gov (United States)

    Segal, JoAn S.

    1989-01-01

    Describes the history of multitype library networks; examines the reasons why special libraries and other network participants have resisted the inclusion of special libraries in these networks; and discusses the benefits to both special libraries and to other libraries in the network that would result from special library participation. (17…

  11. NOAA Miami Regional Library > Home

    Science.gov (United States)

    Library Collections Open Access Resources Research Tools E-resources NOAA S. and NOAA N.E. Library Institutional Repository DIVE INTO About the Library | Collections | Research Tools | Library Services & NOAA Miami Regional Library @ AOML & NHC NOAA Miami Regional Library at National Hurricane

  12. Libraries in society

    DEFF Research Database (Denmark)

    Kristiansson, Michael; Skouvig, Laura Henriette Christine

    2008-01-01

    The purpose of the paper is to investigate the phenomenon of openness in relation to library development. The term openness is presented and related to library development from historical and theoretical perspectives. The paper elaborates on the differences over time on to how openness has been...... understood in a library setting. Historically, openness in form of the open shelves played a crucial role in developing the modern public library. The paper examines this openness-centred library policy as adopted by Danish public libraries in the beginning of the 20th century by applying the theories...... by Michel Foucault on discourse and power to the introduction of open shelves. Furthermore, the paper discusses current challenges facing the modern public library in coping with openness issues that follow from changes in society and advances in technology. These influences and developments are not least...

  13. The participatory public library

    DEFF Research Database (Denmark)

    Rasmussen, Casper Hvenegaard

    2016-01-01

    of theoretical approaches and practical examples to obtain a varied understanding of user participation in public libraries. Research fields outside library and information science have developed a wide range of theoretical approaches on user participation. Examples from cultural policy, museum studies......Purpose From collection to connection has been a buzzword in the library world for more than a decade. This catchy phrase indicates that users are seen not only as borrowers, but as active participants. The aim of this paper is to investigate and analyse three questions in relation to user...... participation in public libraries in a Nordic perspective. How can participation in public libraries be characterised? Why should libraries deal with user participation? What kinds of different user participation can be identified in public libraries? Design/methodology/approach The paper uses a selection...

  14. Flight Software Math Library

    Science.gov (United States)

    McComas, David

    2013-01-01

    The flight software (FSW) math library is a collection of reusable math components that provides typical math utilities required by spacecraft flight software. These utilities are intended to increase flight software quality reusability and maintainability by providing a set of consistent, well-documented, and tested math utilities. This library only has dependencies on ANSI C, so it is easily ported. Prior to this library, each mission typically created its own math utilities using ideas/code from previous missions. Part of the reason for this is that math libraries can be written with different strategies in areas like error handling, parameters orders, naming conventions, etc. Changing the utilities for each mission introduces risks and costs. The obvious risks and costs are that the utilities must be coded and revalidated. The hidden risks and costs arise in miscommunication between engineers. These utilities must be understood by both the flight software engineers and other subsystem engineers (primarily guidance navigation and control). The FSW math library is part of a larger goal to produce a library of reusable Guidance Navigation and Control (GN&C) FSW components. A GN&C FSW library cannot be created unless a standardized math basis is created. This library solves the standardization problem by defining a common feature set and establishing policies for the library s design. This allows the libraries to be maintained with the same strategy used in its initial development, which supports a library of reusable GN&C FSW components. The FSW math library is written for an embedded software environment in C. This places restrictions on the language features that can be used by the library. Another advantage of the FSW math library is that it can be used in the FSW as well as other environments like the GN&C analyst s simulators. This helps communication between the teams because they can use the same utilities with the same feature set and syntax.

  15. E-book Reader Devices and Libraries

    Directory of Open Access Journals (Sweden)

    Pažur, I.

    2011-03-01

    Full Text Available Most library studies thematically related to electronic books don't consider readers of electronic books. Only in recent years librarians conduct studies in which they want to find out readers' opinions about the possibilities, advantages and disadvantages of reading using e-readers, as well as their possible application in the libraries.User studies of e-readers have shown that their opinion is generally positive, but great attachment to traditional books is still present, e-readers are still seen only as an additional tool for reading. Sony with its e-reader (the latest Reader model Daily and Reader Store online bookstore (http://ebookstore.sony.com/is the only one who cooperate with libraries and has made lending electronic books possible. Cooperation was launched in 2009th,and the New York Public Library was the first library that offered such a service.Cooperation between Sony and libraries, indicates clearly what the near future could be if other online booksellers / publishers begin to follow the model of lending e-books through the libraries over the network. However it is possible that a large online bookstores / publishers consider that the further price reduction of e-readers and electronic books will constantly increase their sales, and in that case lending e-books will be unnecessary.Are the libraries ready for this scenario?

  16. Assessing Library Automation and Virtual Library Development in Four Academic Libraries in Oyo, Oyo State, Nigeria

    Science.gov (United States)

    Gbadamosi, Belau Olatunde

    2011-01-01

    The paper examines the level of library automation and virtual library development in four academic libraries. A validated questionnaire was used to capture the responses from academic librarians of the libraries under study. The paper discovers that none of the four academic libraries is fully automated. The libraries make use of librarians with…

  17. Wikis in Libraries

    Directory of Open Access Journals (Sweden)

    Matthew Bejune

    2007-09-01

    Full Text Available Wikis have recently been adopted to support a variety of collaborative activities within libraries. This article and its companion wiki, LibraryWikis (http://librarywikis.pbwiki.com/, seek to document the phenomenon of wikis in libraries. This subject is considered within the framework of computer-supported cooperative work (CSCW. The author identified thirty-three library wikis and developed a classification schema with four categories: (1 collaboration among libraries (45.7 percent; (2 collaboration among library staff (31.4 percent; (3 collaboration among library staff and patrons (14.3 percent; and (4 collaboration among patrons (8.6 percent. Examples of library wikis are presented within the article, as is a discussion for why wikis are primarily utilized within categories I and II and not within categories III and IV. It is clear that wikis have great utility within libraries, and the author urges further application of wikis in libraries.

  18. News from the Library

    CERN Multimedia

    CERN Library

    2010-01-01

    The LHC Library to be merged with the Central Library. Not everyone knows that CERN Scientific Information Service currently counts three physical libraries on site. The Central Library is located in Building 52 and there are two satellite libraries located respectively in building 30 (the LHC Library) and in building 864 on Prévessin site (the SPS Library). Moreover, the Legal Service Library is located in Building 60. In the past, there have been at CERN up to 6 satellite libraries; they were essential at a time when information was only in paper form and having multiple copies of documents located in several places at CERN was useful to facilitate scientific research. Today, this need is less critical as most of our resources are online. That is why, following a SIPB (Scientific Information Policy Board) decision, the collections of the LHC Library will be merged this summer with the Central collection. This reorganization and centralization of resources will improve loan services. The SP...

  19. [Screening serum response special antibodies of U251 cell line from surface display phage antibody library].

    Science.gov (United States)

    Yu, Min; Tan, De-Yong; Qian, Wei; Lai, Jian-Hua; Sun, Gui-Lin

    2004-05-01

    U251 cell is a sensitive cell line to serum, which stops at G0 phase of cell cycle in no-serum medium, and recovers growth when the serum is added into no-serum medium. The cell can express corresponding proteins in different phase of cell cycle. Therefore it is very signification for the study of cell cycle regulation mechanism that explores these proteins. In this paper, the mouse antibody phage display library was added into the bottle in which the serum starvation U251 cells had been cultured, and the special antibody phages were absorbed. Then the absorbed antibody phages were amplified by adding E. coli TG1 and helper phage M13K07. Amplified antibody phages were added into bottle in which the serum cultured cell after serum starvation (follow named as serum recovered cells) were incubated, so that the cell absorbed the no-special antibody phages for the serum starvation cell and the special antibody phages were in supernatant. The remaining no-special antibody phages in the supernatant were discarded by repeating above program 3-4 times. The pure special antibody phages were gotten, and amplified by adding the host cell E. coli TG1 and helper phage M13K07. Then the host bacterium infected special antibody phage was spread on the plate medium with ampicillin, and the monoclonal antibody phages were gotten. Using same as above program, the monoclonal antibody phages absorbed specially for serum recovered U251 cells were obtained when the serum recovered cells instead of serum starvation cells and serum starvation cells instead of serum recovered cells. In this study, ninety-six positive monoclonal antibody phages that absorbed specially the serum starvation cells and eighty-two positive monoclonal antibody phages that absorbed specially the serum recovered cells were obtained. By using cell immunochemistry assay, two special signification antibodies were obtained. one (No.11) was the strong response in serum starvation cells, the other (No.2) was the strong

  20. Access to IEEE Electronic Library

    CERN Multimedia

    2007-01-01

    From 2007, the CERN Library now offers readers online access to the complete IEEE Electronic Library (Institute of Electrical and Electronics Engineers). This new licence gives unlimited online access to all IEEE and IET (previously IEE) journals and proceedings as well as all current IEEE standards and selected archived ones. Some of the titles offer volumes back to 1913. This service currently represents more than 1,400,000 full-text articles! This leading engineering information resource replaces the previous service, a sub-product of the IEEE database called 'IEEE Enterprise', which offered online access to the complete collection of IEEE journals and proceedings, but with limited features. The service had become so popular that the CERN Working Group for Acquisitions recommended that the Library subscribe to the complete IEEE Electronic Library for 2007. Usage statistics for recent months showed there was a demand for the service from a large community of CERN users and we were aware that many users h...

  1. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 34; Issue 2 ... (peptides A, B, C, and D) were selected using a phage display 12-mer peptide library. ... School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu 214122, ...

  2. Profesional medical library education in the United States in relation to the qualifications of medical library manpower in Ohio.

    Science.gov (United States)

    Rees, A M; Rothenberg, L; Denison, B

    1968-10-01

    THE PRESENT SYSTEM OF EDUCATION FOR MEDICAL LIBRARY PRACTICE IN THE UNITED STATES CONSISTS OF FOUR MAJOR COMPONENTS: graduate degree programs in library science with specialization in medical librarianship; graduate degree programs in library science with no such specialization; postgraduate internships in medical libraries; continuing education programs. Data are presented illustrating the flow of graduates along these several educational pathways into medical library practice.The relevance of these educational components to the current medical library work force is discussed with reference to manpower data compiled for Ohio. The total number of medical library personnel in Ohio in 1968 is 316. Of this total, only forty-two (approximately 14 percent) have received any formal library training. Seventy persons have only a high school education. From these figures, it is concluded that there is no standard or essential qualification which is universally accepted as educational preparation for work in medical libraries; that the comparative sophistication of the educational programs in medical librarianship has yet to be reflected widely in general medical library practice; that an increasingly large number of non-professional or ancillary personnel are being, and will continue to be, utilized in medical libraries; that large numbers of untrained persons have sole responsibility for medical libraries; and that appropriate educational programs will have to be designed specifically for this type of personnel.

  3. Heroes and Holidays: The Status of Diversity Initiatives at Liberal Arts College Libraries

    Science.gov (United States)

    Gilbert, Julie

    2016-01-01

    Studies about diversity initiatives in academic libraries have primarily focused on large research libraries. But what kinds of diversity work occur at smaller libraries? This study examines the status of diversity initiatives, especially those aimed at students, at national liberal arts college libraries. Results from a survey of library…

  4. Isolation of Mal d 1 and Api g 1 - specific recombinant antibodies from mouse IgG Fab fragment libraries - Mal d 1-specific antibody exhibits cross-reactivity against Bet v 1.

    Science.gov (United States)

    Haka, Jaana; Niemi, Merja H; Iljin, Kristiina; Reddy, Vanga Siva; Takkinen, Kristiina; Laukkanen, Marja-Leena

    2015-05-27

    Around 3-5% of the population suffer from IgE-mediated food allergies in Western countries and the number of food-allergenic people is increasing. Individuals with certain pollen allergies may also suffer from a sensitisation to proteins in the food products. As an example a person sensitised to the major birch pollen allergen, Bet v 1, is often sensitised to its homologues, such as the major allergens of apple, Mal d 1, and celery, Api g 1, as well. Development of tools for the reliable, sensitive and quick detection of allergens present in various food products is essential for allergic persons to prevent the consumption of substances causing mild and even life-threatening immune responses. The use of monoclonal antibodies would ensure the specific detection of the harmful food content for a sensitised person. Mouse IgG antibody libraries were constructed from immunised mice and specific recombinant antibodies for Mal d 1 and Api g 1 were isolated from the libraries by phage display. More detailed characterisation of the resulting antibodies was carried out using ELISA, SPR experiments and immunoprecipitation assays. The allergen-specific Fab fragments exhibited high affinity towards the target recombinant allergens. Furthermore, the Fab fragments also recognised native allergens from natural sources. Interestingly, isolated Mal d 1-specific antibody bound also to Bet v 1, the main allergen eliciting the cross-reactivity syndrome between the birch pollen and apple. Despite the similarities in Api g 1 and Bet v 1 tertiary structures, the isolated Api g 1-specific antibodies showed no cross-reactivity to Bet v 1. Here, high-affinity allergen-specific recombinant antibodies were isolated with interesting binding properties. With further development, these antibodies can be utilised as tools for the specific and reliable detection of allergens from different consumable products. This study gives new preliminary insights to elucidate the mechanism behind the pollen

  5. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum

    DEFF Research Database (Denmark)

    Christiansen, Anders; Kringelum, Jens Vindahl; Hansen, Christian Skjødt

    2015-01-01

    of the bioinformatic approach was demonstrated by identifying epitopes of a prominent peanut allergen, Ara h 1, in sera from patients with severe peanut allergy. The identified epitopes were confirmed by high-density peptide micro-arrays. The present study demonstrates that high-throughput sequencing can empower phage...

  6. Analysis of pectic epitopes recognised by hybridoma and phage display monoclonal antibodies using defined oligosaccharides, polysaccharides, and enzymatic degradation

    DEFF Research Database (Denmark)

    Willats, William George Tycho; Limberg, G.; Buchholt, H.C.

    2000-01-01

    occurs where specific but undefined methyl-esterification patterns are present on HG domains, although fully de-esterified HG samples contain sub-optimal JIM5 epitopes. The persistence of mAb binding to epitopes in pectic antigens, with 41% blockwise esterification (P41) and 43% random esterification (F...

  7. Phage display of the Equine arteritis virus nsp1 ZF domain and examination of its metal interactions

    DEFF Research Database (Denmark)

    Oleksiewicz, Martin B.; Snijder, E.J.; Normann, Preben

    2004-01-01

    be inhibited by an anti-nsp 1 serum, or by mutation of residues predicted to be important for zinc coordination. Finally, binding was abolished by low concentrations (0.1%) Tween 20, and rescued by including Zn2+, Ni2+ or Cu2+, but not Mg2+, in the binding buffer, suggesting that formation of secondary...

  8. The Library International Partnerweek 2011

    DEFF Research Database (Denmark)

    Presentation at the Library International Partnerweek, held at Copenhagen Technical Library at the Copenhagen University College of Engineering. Participant: Ms. Carmen Priesto Estravid from Madrid Technical University, E.U.I.T. Obras Públicas, Library. Spain Ms.Tuulikki Hattunen from TUAS Library....... Finland Ms. Anitta Ôrm from Kemi-Tornio UAS Library. Finland Mr. Manfred Walter from HTW-Berlin. Germany Mr. Peter Hald from Copenhagen Technical Library. Denmark Mr. Ole Micahelsen from Copenhagen Technical Library. Denmark...

  9. STP: A mathematically and physically consistent library of steam properties

    International Nuclear Information System (INIS)

    Aguilar, F.; Hutter, A.C.; Tuttle, P.G.

    1982-01-01

    A new FORTRAN library of subroutines has been developed from the fundamental equation of Keenan et al. to evaluate a large set of water properties including derivatives such as sound speed and isothermal compressibility. The STP library uses the true saturation envelope of the Keenan et al. fundamental equation. The evaluation of the true envelope by a continuation method is explained. This envelope, along with other design features, imparts an exceptionally high degree of thermodynamic and mathematical consistency to the STP library, even at the critical point. Accuracy and smoothness, library self-consistency, and designed user convenience make the STP library a reliable and versatile water property package

  10. KAERI photonuclear library

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jong Hwa; Lee, Young Ouk; Han, Yin Iu

    2000-03-01

    This report contains summary information and figures depicting the KAERI photonuclear data library that extends up to 140 MeV of incident photon. The library consists of 143 isotopes from C-12 to Bi-209, providing the photoabsorption cross section and the emission spectra for neutron, proton, deuteron, triton, alpha particles, and all residual nuclides in ENDF6 format. The contents of this report and ENDF-6 format data library are available at http://atom.kaeri.re.kr/.

  11. The CERN Library

    CERN Multimedia

    Hester, Alec G

    1968-01-01

    Any advanced research centre needs a good Library. It can be regarded as a piece of equipment as vital as any machine. At the present time, the CERN Library is undergoing a number of modifications to adjust it to the changing scale of CERN's activities and to the ever increasing flood of information. This article, by A.G. Hester, former Editor of CERN COURIER who now works in the Scientific Information Service, describes the purposes, methods and future of the CERN Library.

  12. The Personal Virtual Library

    CERN Document Server

    Le Meur, Jean-Yves

    1998-01-01

    Looking for "library" in the usual search engines of the World Wide Web gives: "Infoseek found 3,593,126 pages containing the word library" and it nicely proposes: "Search only within these 3,59 3,126 pages ?" "Yahoo! Found 1299 categories and 8669 sites for library" "LycOs: 1-10 von 512354 relevanten Ergebnissen" "AltaVista: About 14830527 documents match your query" and at the botto m: "Word count: library: 15466897" ! Excite: Top 10 matches and it does not say how many can be browsed... "Library" on the World Wide Web is really popular. At least fiveteen million pages ar e supposed to contain this word. Half of them may have disappeared by now but one more hit will be added once the search robots will have indexed this document ! The notion of Personal Library i s a modest attempt, in a small environment like a library, to give poor users lost in cyber-libraries the opportunity to keep their own private little shelves - virtually. In this paper, we will l ook at the usual functionalities of library systems...

  13. Integrated circuit cell library

    Science.gov (United States)

    Whitaker, Sterling R. (Inventor); Miles, Lowell H. (Inventor)

    2005-01-01

    According to the invention, an ASIC cell library for use in creation of custom integrated circuits is disclosed. The ASIC cell library includes some first cells and some second cells. Each of the second cells includes two or more kernel cells. The ASIC cell library is at least 5% comprised of second cells. In various embodiments, the ASIC cell library could be 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more comprised of second cells.

  14. NEIC Library Services

    Science.gov (United States)

    The National Enforcement Investigation Center (NEIC) Environmental Forensic Library partners with NEIC's forensic scientists to retrieve, validate and deliver information to develop methods, defensible regulations, and environmental measurements.

  15. Library and Education

    Directory of Open Access Journals (Sweden)

    Gheorghe Buluţă

    2011-01-01

    Full Text Available The psycho-social phenomena generated by mass-media and the new information and communication technologies at the level of the young generations have led to new communication practices that bypass libraries and revolutionized the intellectual labor practices, with texts being rather used than read. In this context, our article examines the need to increase the library's role in developing the quality of education and research and brings to attention a few possible solutions which include a partnership between various types of libraries and between librarians' associations and NGOs to facilitate education through library and safeguard reading.

  16. Libraries and licensing

    Directory of Open Access Journals (Sweden)

    Maja Žumer

    2001-01-01

    Full Text Available In the mid 90s, the abundance of various electronic publications exposed libraries to the problems of licensing electronic content. Various licensing principles have been prepared recently to help libraries in the process; it can be said that in general, the knowledge of licensing issues has improved in libraries of all types. Libraries form consortia in order to gain stronger negotiating positions and obtain better conditions.In the article, new licensing principles are presented in more detail, as well as some domestic and foreign experiences with consortia forming.

  17. International Youth Library

    Directory of Open Access Journals (Sweden)

    Osman Ümit Özen

    1994-03-01

    Full Text Available International Youth Library, the biggest youth library in the world, was founded in 1948 in Munich, Germany, by Jella Lepman. She aimed to unite all the children of the world through books by establishing this library. IYL is still trying to achieve this end supporting scholarship programmes in children’s literature research, participating in or organizing meetings on children’s literature, and working with other national and international organizations deeding with children’s literature. Unfortunately the library is facing some problems recently which have risen from economic difficulties which also inhibits promotional activities.

  18. Public Relations in Special Libraries.

    Science.gov (United States)

    Rutkowski, Hollace Ann; And Others

    1991-01-01

    This theme issue includes 11 articles on public relations (PR) in special libraries. Highlights include PR at the Special Libraries Association (SLA); sources for marketing research for libraries; developing a library image; sample PR releases; brand strategies for libraries; case studies; publicizing a consortium; and a bibliography of pertinent…

  19. Music Libraries: Centralization versus Decentralization.

    Science.gov (United States)

    Kuyper-Rushing, Lois

    2002-01-01

    Considers the decision that branch libraries, music libraries in particular, have struggled with concerning a centralized location in the main library versus a decentralized collection. Reports on a study of the Association of Research Libraries that investigated the location of music libraries, motivation for the location, degrees offered,…

  20. Audiobooks between libraries and market

    DEFF Research Database (Denmark)

    Worsøe-Schmidt, Lisbeth

    of the relationship between commercial and non-commercial players. The digital audiobook or talking book is the latest step in a long history connected to the developing of different technologies to record sound. The audiobook is probably best viewed as a hybrid medium that brings together the forms of literature......, the cd and the portable disc-player -- non-commercial players took the lead in development as well as production and distribution of audiobooks. Digitization has led to increased commercial sales of audiobooks, which are now the fastest growing segment in publishing. An increasing share of audiobooks...... are not sold in bookstores to end-users but lent by a modern form of rental library. In Scandinavia, a rather special situation exists since a very large proportion of e-books and audiobooks is disseminated through public libraries. Strangely, while the lending of digital e-books caused a veritable war between...

  1. Library Systems: FY 2013 Public Libraries Survey (Administrative Entity)

    Data.gov (United States)

    Institute of Museum and Library Services — Find key information on library systems around the United States.These data include imputed values for libraries that did not submit information in the FY 2013 data...

  2. Library Systems: FY 2012 Public Libraries Survey (Administrative Entity)

    Data.gov (United States)

    Institute of Museum and Library Services — Find key information on library systems around the United States.These data include imputed values for libraries that did not submit information in the FY 2012 data...

  3. Library Systems: FY 2014 Public Libraries Survey (Administrative Entity Data)

    Data.gov (United States)

    Institute of Museum and Library Services — Find key information on library systems around the United States.These data include imputed values for libraries that did not submit information in the FY 2014 data...

  4. Cross-section libraries and kerma factors

    International Nuclear Information System (INIS)

    Little, R.C.; MacFarlane, R.E.; Seamon, R.E.

    1991-01-01

    A large amount of data is required in order to accurately simulate various aspects of Cold Neutron Sources using radiation transport codes such as MCNP and TWODANT. In particular, the following types of data are needed: couple neutron/photon transport libraries, neutron thermal S(α,β) data, response function data (including energy deposition), and proton interaction data. This paper concentrates on the coupled neutron/photon transport libraries and energy deposition. Data libraries available to radiation transport codes are obtained as a result of efforts in many areas, including differential and integral measurements, theoretical model codes, data evaluations, data processing, and data testing. A wide variety of data libraries are available to users of radiation transport codes, including pointwise and multigroup libraries. At Los Alamos, the authors generally recommend the use of data libraries derived from ENDF/B-V. It is often important to know how much energy is deposited in various regions of a device. This problem is typically modeled in radiation transport codes by folding the calculated fluences with an energy-dependent 'heating number'. The heating number represents the average energy deposited locally per collision. Calculation of these heating numbers from evaluated data libraries is fraught with difficulty. Many past difficulties related to energy deposition should be resolved by the release of ENDF/B-VI

  5. Encyclopedia and library in the contemporary age

    Directory of Open Access Journals (Sweden)

    Paolo Traniello

    2017-06-01

    Full Text Available With the publication of the Encyclopédie of Diderot and D’Alembert, which dates from 1751, the concept of library is declined in a negative sense, as a closing tool and impediment in the hands of the State, compared to the Encyclopedia, considered the book of the people. The constitution of the public library (the british Public Libraries Act is dated 1850, funded with public money, determines to change and both realities, Library and Encyclopedia, begin to interact contributing to the development of contemporary culture. Such as the Library, the Encyclopedia also supposes a work of organization of knowledge through classifications. From this point of view, both institutions seem closer in a purpose that unites them. In view of the information revolution, the Library should help reduce complexity of digital information and should play, against the vastness of the network, a role similar to what the Enlightenment Encyclopedia has assigned to itself in the face of large library collections, which were seen as points of accumulation, and also as points of the knowledge’s dispersion.

  6. Special Libraries in Singapore.

    Science.gov (United States)

    Leong, Alice

    1979-01-01

    Distinguishes five main categories of special libraries in Singapore: those of private organizations, foreign governments, government departments, statutory boards, and regional organizations. Statistical data are provided for library holdings, professional staff employment, and subject profiles, and suggestions for improving various aspects of…

  7. Iranian Library Update.

    Science.gov (United States)

    Harvey, John F.

    1979-01-01

    Discusses the state of Iranian libraries since the revolution: the printing industry flourishes because of obsolete copyright laws, and the government is attempting to dewesternize media and education. Also considered are budget cuts, the revolution's cost to libraries, and its effect on individual librarians. (SW)

  8. The Memory Library

    DEFF Research Database (Denmark)

    Olesen-Bagneux, Ole

    2014-01-01

    of classification and retrieval processes is presented. The key element is to understand the library both as a physical structure and as a structure in the memory of the Alexandrian scholars. In this article, these structures are put together so to propose a new interpretation of the library....

  9. Privacy and Library Records

    Science.gov (United States)

    Bowers, Stacey L.

    2006-01-01

    This paper summarizes the history of privacy as it relates to library records. It commences with a discussion of how the concept of privacy first originated through case law and follows the concept of privacy as it has affected library records through current day and the "USA PATRIOT Act."

  10. Hospital Library Administration.

    Science.gov (United States)

    Cramer, Anne

    The objectives of a hospital are to improve patient care, while the objectives of a hospital library are to improve services to the staff which will support their efforts. This handbook dealing with hospital administration is designed to aid the librarian in either implementing a hospital library, or improving services in an existing medical…

  11. Munitions Classification Library

    Science.gov (United States)

    2016-04-04

    members of the community to make their own additions to any, or all, of the classification libraries . The next phase entailed data collection over less......Include area code) 04/04/2016 Final Report August 2014 - August 2015 MUNITIONS CLASSIFICATION LIBRARY Mr. Craig Murray, Parsons Dr. Thomas H. Bell, Leidos

  12. TRAC Searchable Research Library

    Science.gov (United States)

    2016-05-01

    Relational Data Modeling (VRDM) computational paradigm. VRDM has the key attributes of being cloud available, using domain semantics for configured...Figure 1. Methodology for TRAC Searchable Research Library Development. ........................... 5 Figure 2. The conceptual model for the cloud ...TRAC Searchable Research Library project was initiated by TRAC- HQ to address a current capability gap in the TRAC organization. Currently TRAC does not

  13. XML in Libraries.

    Science.gov (United States)

    Tennant, Roy, Ed.

    This book presents examples of how libraries are using XML (eXtensible Markup Language) to solve problems, expand services, and improve systems. Part I contains papers on using XML in library catalog records: "Updating MARC Records with XMLMARC" (Kevin S. Clarke, Stanford University) and "Searching and Retrieving XML Records via the…

  14. Merchandising Techniques and Libraries.

    Science.gov (United States)

    Green, Sylvie A.

    1981-01-01

    Proposes that libraries employ modern booksellers' merchandising techniques to improve circulation of library materials. Using displays in various ways, the methods and reasons for weeding out books, replacing worn book jackets, and selecting new books are discussed. Suggestions for learning how to market and 11 references are provided. (RBF)

  15. Library Consortia in Hungary

    Science.gov (United States)

    Csajbok, Edit; Szluka, Peter; Vasas, Livia

    2012-01-01

    During the last two decades many Hungarian libraries have developed considerably, beyond what was considered possible prior to 1989 and the beginning of events signaling the end of Communism in the country. Some of the modernization of library services has been realized through participation in cooperative agreements. Many smaller and larger…

  16. Increasing Library Effectiveness

    Science.gov (United States)

    Klement, Susan

    1977-01-01

    Libraries could benefit from the businesslike approach of an entrepreneur. Characteristics of entrepreneurial behavior of value to libraries include: moderate risk-taking as a function of skill, not chance; energetic instrumental activity; insistence upon individual responsibility; knowledge of results of decisions; anticipation of future…

  17. Library Classification 2020

    Science.gov (United States)

    Harris, Christopher

    2013-01-01

    In this article the author explores how a new library classification system might be designed using some aspects of the Dewey Decimal Classification (DDC) and ideas from other systems to create something that works for school libraries in the year 2020. By examining what works well with the Dewey Decimal System, what features should be carried…

  18. An Online Library Catalogue.

    Science.gov (United States)

    Alloro, Giovanna; Ugolini, Donatella

    1992-01-01

    Describes the implementation of an online catalog in the library of the National Institute for Cancer Research and the Clinical and Experimental Oncology Institute of the University of Genoa. Topics addressed include automation of various library functions, software features, database management, training, and user response. (10 references) (MES)

  19. Libraries and Lenin.

    Science.gov (United States)

    Lynn, Karen

    This instructional unit combines a study of the Soviet leader V. I. Lenin with a study of libraries. Lenin was selected as the focus because of his support of books and libraries and because he oversaw a revolution that altered the political and social structure of Russia and the balance of power throughout the world. Included are lesson plan…

  20. Chief Information Officer > Library

    Science.gov (United States)

    DCIO R&A DCIO CS In the News Library Contact us Library Policies CIO Charter DoD CIO Charter that many laws, and DoD policies and procedures apply to or include the use of IbC, even when such use Service Site Registry Policies Education and Training Terms of Service Agreements Site Registry Policies

  1. Marketing and health libraries.

    Science.gov (United States)

    Wakeham, Maurice

    2004-12-01

    To present an overview of the concepts of marketing and to examine ways in which they can be applied to health libraries. A review was carried out of literature relating to health libraries using LISA, CINAHL, BNI and Google. Marketing is seen as a strategic management activity aimed at developing customer relationships. Concepts such as the 'four Ps' (product, price, place and promotion), marketing plans, the marketing mix, segmentation, promotion and evaluation are identified and discussed in relation to health libraries. In increasingly complex health service and information environments, the marketing and promotion of library services is becoming more important if those services are to justify the resources given to them. Marketing techniques are equally applicable to physical and digital library services.

  2. Motivation and library management

    Directory of Open Access Journals (Sweden)

    Tatjana Likar

    2000-01-01

    Full Text Available The present article deals with motivation, its relation to management and its role and use in librarianship in our country and abroad. The countries where librarianship is well developed started to deal with library management and questions of motivation of library workers decades ago, whereas elsewhere the subject is at its start. The prerequisite for modern policy making is attention to the elements of modern library management. Librarians, library managers and directors of libraries should create a work environment providing long term satisfaction with work by means of certain knowledge and tools. The level of motivation of the staff is influenced by the so called higher factors deriving from the work process itself and related to work contents: achieve¬ment, recognition, trust and work itself. Extrinsic factors (income, interpersonal relations, technology of administration, company policy, working conditions, work con¬trol, personal security, job security and position... should exercise lesser impact on the level of motivation.

  3. Public libraries in the library regions in the year 2009

    Directory of Open Access Journals (Sweden)

    Milena Bon

    2011-01-01

    Full Text Available Purpose: Regional public libraries were initiated in 2003 to connect professional activities of libraries within regional networks and to ensure coordinated library development in a region in cooperation with the Library System Development Centre at the National and University Library performing a coordinating role. The article analyses the performance of public libraries and their integration in regional library networks in order to find out the level of development of conditions of performance of public libraries.Methodology/approach: Statistical data for the year 2009 were the basis for the overview of library activities of ten library regions with regard to applicable legislation and library standards. The level of regional library activities is compared to the socio-economic situation of statistical regions thus representing a new approach to the presentation of Slovenian’s public libraries’ development.Results: Absolute values indicate better development of nine libraries in the central Slovenia region while relative values offer a totally different picture. Four libraries in the region of Nova Gorica prove the highest level of development.Research limitation: Research is limited to the year 2009 and basic statistical analysis.Originality/practical implications: Findings of the analysis are useful for public libraries to plan their development strategy within a region and for financial bodies to provide for adequate financing for library activities in a specific region. The basic condition for successful public library performance is the even and harmonized development of conditions of performance as recommended by library standards.

  4. EPA Library Network Communication Strategies

    Science.gov (United States)

    To establish Agency-wide procedures for the EPA National Library Network libraries to communicate, using a range of established mechanisms, with other EPA libraries, EPA staff, organizations and the public.

  5. A lightweight communication library for distributed computing

    International Nuclear Information System (INIS)

    Groen, Derek; Rieder, Steven; Zwart, Simon Portegies; Grosso, Paola; Laat, Cees de

    2010-01-01

    We present MPWide, a platform-independent communication library for performing message passing between computers. Our library allows coupling of several local message passing interface (MPI) applications through a long-distance network and is specifically optimized for such communications. The implementation is deliberately kept lightweight and platform independent, and the library can be installed and used without administrative privileges. The only requirements are a C++ compiler and at least one open port to a wide-area network on each site. In this paper we present the library, describe the user interface, present performance tests and apply MPWide in a large-scale cosmological N-body simulation on a network of two computers, one in Amsterdam and the other in Tokyo.

  6. Adiabatic quantum-flux-parametron cell library adopting minimalist design

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Naoki, E-mail: takeuchi-naoki-kx@ynu.jp [Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya, Yokohama 240-8501 (Japan); Yamanashi, Yuki; Yoshikawa, Nobuyuki [Institute of Advanced Sciences, Yokohama National University, 79-5 Tokiwadai, Hodogaya, Yokohama 240-8501 (Japan); Department of Electrical and Computer Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya, Yokohama 240-8501 (Japan)

    2015-05-07

    We herein build an adiabatic quantum-flux-parametron (AQFP) cell library adopting minimalist design and a symmetric layout. In the proposed minimalist design, every logic cell is designed by arraying four types of building block cells: buffer, NOT, constant, and branch cells. Therefore, minimalist design enables us to effectively build and customize an AQFP cell library. The symmetric layout reduces unwanted parasitic magnetic coupling and ensures a large mutual inductance in an output transformer, which enables very long wiring between logic cells. We design and fabricate several logic circuits using the minimal AQFP cell library so as to test logic cells in the library. Moreover, we experimentally investigate the maximum wiring length between logic cells. Finally, we present an experimental demonstration of an 8-bit carry look-ahead adder designed using the minimal AQFP cell library and demonstrate that the proposed cell library is sufficiently robust to realize large-scale digital circuits.

  7. Adiabatic quantum-flux-parametron cell library adopting minimalist design

    International Nuclear Information System (INIS)

    Takeuchi, Naoki; Yamanashi, Yuki; Yoshikawa, Nobuyuki

    2015-01-01

    We herein build an adiabatic quantum-flux-parametron (AQFP) cell library adopting minimalist design and a symmetric layout. In the proposed minimalist design, every logic cell is designed by arraying four types of building block cells: buffer, NOT, constant, and branch cells. Therefore, minimalist design enables us to effectively build and customize an AQFP cell library. The symmetric layout reduces unwanted parasitic magnetic coupling and ensures a large mutual inductance in an output transformer, which enables very long wiring between logic cells. We design and fabricate several logic circuits using the minimal AQFP cell library so as to test logic cells in the library. Moreover, we experimentally investigate the maximum wiring length between logic cells. Finally, we present an experimental demonstration of an 8-bit carry look-ahead adder designed using the minimal AQFP cell library and demonstrate that the proposed cell library is sufficiently robust to realize large-scale digital circuits

  8. Libraries Today, Libraries Tomorrow: Contemporary Library Practices and the Role of Library Space in the L

    Directory of Open Access Journals (Sweden)

    Ana Vogrinčič Čepič

    2013-09-01

    Full Text Available ABSTRACTPurpose: The article uses sociological concepts in order to rethink the changes in library practices. Contemporary trends are discussed with regard to the changing nature of working habits, referring mostly to the new technology, and the (emergence of the third space phenomenon. The author does not regard libraries only as concrete public service institutions, but rather as complex cultural forms, taking in consideration wider social context with a stress on users’ practices in relation to space.Methodology/approach: The article is based on the (self- observation of the public library use, and on the (discourse analysis of internal library documents (i.e. annual reports and plans and secondary sociological literature. As such, the cultural form approach represents a classic method of sociology of culture.Results: The study of relevant material in combination with direct personal experiences reveals socio-structural causes for the change of users’ needs and habits, and points at the difficulty of spatial redefinition of libraries as well as at the power of the discourse.Research limitations: The article is limited to an observation of users’ practices in some of the public libraries in Ljubljana and examines only a small number of annual reports – the discoveries are then further debated from the sociological perspective.Originality/practical implications: The article offers sociological insight in the current issues of the library science and tries to suggest a wider explanation that could answer some of the challenges of the contemporary librarianship.

  9. Gender, Technology, and Libraries

    Directory of Open Access Journals (Sweden)

    Melissa Lamont

    2009-09-01

    Full Text Available Information technology (IT is vitally important to many organizations, including libraries. Yet a review of employment statistics and a citation analysis show that men make up the majority of the IT workforce, in libraries and in the broader workforce. Research from sociology, psychology, and women’s studies highlights the organizational and social issues that inhibit women. Understanding why women are less evident in library IT positions will help inform measures to remedy the gender disparity.

  10. CRNL library serials list

    International Nuclear Information System (INIS)

    Alburger, T.P.

    1982-04-01

    A list of 1900 serial publications (periodicals, society transactions and proceedings, annuals and directories, indexes, newspapers, etc.) is presented with volumes and years held by the Main Library. This library is the largest in AECL as well as one of the largest scientific and technical libraries in North America, and functions as a Canadian resource for nuclear information. A main alphabetical list is followed by broad subject field lists representing research interests, and lists of abstract and index serials, general bibliographic serials, conference indexes, press releases, English translations, and original language journals

  11. FRDS.Broker Library

    DEFF Research Database (Denmark)

    2018-01-01

    The FRDS.Broker library is a teaching oriented implementation of the Broker architectural pattern for distributed remote method invocation. It defines the central roles of the pattern and provides implementations of those roles that are not domain/use case specific. It provides a JSON based (GSon...... library) Requestor implementation, and implementations of the ClientRequestHandler and ServerRequestHandler roles in both a Java socket based and a Http/URI tunneling based variants. The latter us based upon the UniRest and Spark-Java libraries. The Broker pattern and the source code is explained...

  12. Outsourcing the law firm library: the UK experience

    OpenAIRE

    Brown, Fiona

    2017-01-01

    Since 2009, a number of large and leading UK law firms have outsourced their in-house law library and research service to outsource service providers. Integreon, the leading provider of these services in the UK, commenced operations in Australia in 2011. Since that time, a number of other providers of outsourced law library and legal research services have attracted a number of top-tier Australian law firms as clients. These outsource providers are not currently providing law library and lega...

  13. SOL: A Library for Scalable Online Learning Algorithms

    OpenAIRE

    Wu, Yue; Hoi, Steven C. H.; Liu, Chenghao; Lu, Jing; Sahoo, Doyen; Yu, Nenghai

    2016-01-01

    SOL is an open-source library for scalable online learning algorithms, and is particularly suitable for learning with high-dimensional data. The library provides a family of regular and sparse online learning algorithms for large-scale binary and multi-class classification tasks with high efficiency, scalability, portability, and extensibility. SOL was implemented in C++, and provided with a collection of easy-to-use command-line tools, python wrappers and library calls for users and develope...

  14. SCHOOL COMMUNITY PERCEPTION OF LIBRARY APPS AGAINTS LIBRARY EMPOWERMENT

    Directory of Open Access Journals (Sweden)

    Achmad Riyadi Alberto

    2017-07-01

    Full Text Available Abstract. This research is motivated by the development of information and communication technology (ICT in the library world so rapidly that allows libraries in the present to develop its services into digital-based services. This study aims to find out the school community’s perception of library apps developed by Riche Cynthia Johan, Hana Silvana, and Holin Sulistyo and its influence on library empowerment at the library of SD Laboratorium Percontohan UPI Bandung. Library apps in this research belong to the context of m-libraries, which is a library that meets the needs of its users by using mobile platforms such as smartphones,computers, and other mobile devices. Empowerment of library is the utilization of all aspects of the implementation of libraries to the best in order to achieve the expected goals. An analysis of the schoolcommunity’s perception of library apps using the Technology Acceptance Model (TAM includes: ease of use, usefulness, usability, usage trends, and real-use conditions. While the empowerment of the library includes aspects: information empowerment, empowerment of learning resources, empowerment of human resources, empowerment of library facilities, and library promotion. The research method used in this research is descriptive method with quantitative approach. Population and sample in this research is school community at SD Laboratorium Percontohan UPI Bandung. Determination of sample criteria by using disproportionate stratified random sampling with the number of samples of 83 respondents. Data analysis using simple linear regression to measure the influence of school community perception about library apps to library empowerment. The result of data analysis shows that there is influence between school community perception about library apps to library empowerment at library of SD Laboratorium Percontohan UPI Bandung which is proved by library acceptance level and library empowerment improvement.

  15. The USF Libraries Virtual Library Project: A Blueprint for Development.

    Science.gov (United States)

    Metz-Wiseman, Monica; Silver, Susan; Hanson, Ardis; Johnston, Judy; Grohs, Kim; Neville, Tina; Sanchez, Ed; Gray, Carolyn

    This report of the Virtual Library Planning Committee (VLPC) is intending to serve as a blueprint for the University of South Florida (USF) Libraries as it shifts from print to digital formats in its evolution into a "Virtual Library". A comprehensive planning process is essential for the USF Libraries to make optimum use of technology,…

  16. Croatian library leaders’ views on (their library quality

    Directory of Open Access Journals (Sweden)

    Kornelija Petr Balog

    2014-04-01

    Full Text Available The purpose of this paper is to determine and describe the library culture in Croatian public libraries. Semi-structured interviews with 14 library directors (ten public and four academic were conducted. The tentative discussion topics were: definition of quality, responsibility for quality, satisfaction with library services, familiarization with user perspective of library and librarians, monitoring of user expectations and opinions. These interviews incorporate some of the findings of the project Evaluation of library and information services: public and academic libraries. The project investigates library culture in Croatian public and academic libraries and their preparedness for activities of performance measurement. The interviews reveal that library culture has changed positively in the past few years and that library leaders have positive attitude towards quality and evaluation activities. Library culture in Croatian libraries is a relatively new concept and as such was not actively developed and/or created. This article looks into the library culture of Croatian libraries, but at the same time investigates whether there is any trace of culture of assessment in them. Also, this article brings the latest update on views, opinions and atmosphere in Croatian public and academic libraries.

  17. National Libraries Section. General Research Libraries Division. Papers.

    Science.gov (United States)

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on national library services and activities, which were presented at the 1983 International Federation of Library Associations (IFLA) conference, include: (1) "The National Library of China in its Gradual Application of Modern Technology," a discussion by Zhu Nan and Zhu Yan (China) of microform usage and library automation; (2)…

  18. Library Science Education: A New Role for Academic Libraries

    Science.gov (United States)

    Wesley, Threasa L.

    2018-01-01

    Many individuals working in library and information organizations do not hold a master of library science (MLS) degree or other specialized library science credential. Recognizing that this professional gap could be addressed by diversified educational opportunities, the W. Frank Steely Library at Northern Kentucky University in Highland Heights…

  19. Virtual screening of compound libraries.

    Science.gov (United States)

    Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João

    2009-01-01

    During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.

  20. Controlling hospital library theft.

    Science.gov (United States)

    Cuddy, Theresa M; Marchok, Catherine

    2003-04-01

    At Capital Health System/Fuld Campus (formerly Helene Fuld Medical Center), the Health Sciences Library lost many books and videocassettes. These materials were listed in the catalog but were missing when staff went to the shelves. The hospital had experienced a downsizing of staff, a reorganization, and a merger. When the library staff did an inventory, $10,000 worth of materials were found to be missing. We corrected the situation through a series of steps that we believe will help other libraries control their theft. Through regularly scheduling inventories, monitoring items, advertising, and using specific security measures, we have successfully controlled the library theft. The January 2002 inventory resulted in meeting our goal of zero missing books and videocassettes. We work to maintain that goal.

  1. Marketing the Library.

    Science.gov (United States)

    Dragon, Andrea C.

    1979-01-01

    Describes the positive action using marketing strategies that libraries must take to capture their share of the post-Proposition 13 tax dollar. Strategies discussed relate to price, product, promotion, and place. (JD)

  2. LIBRARY MANAGEMNT INFORMATION SYSTEM

    Directory of Open Access Journals (Sweden)

    Magnolia Tilca

    2013-06-01

    Full Text Available The focus of any educational institution is the content and services of the university library. The mission of the library is to obtain, organize, preserve and update the information with the greatest possible accuracy, minimum effort and time. This requires automation of the library’s operations. This paper presents a software application for managing the activity of the territorial "Vasile Goldiş" West University library. The application is developed using Visual Basic for Application programming language and using the database management system Microsoft Access 2010. The goal of this application is to optimize the inner workings of local library and to meet the requests of the institution and of the readers.

  3. Mainstreaming the New Library.

    Science.gov (United States)

    Keeler, Elizabeth

    1982-01-01

    This discussion of methods of integrating the corporate library into the mainstream of affairs highlights three major elements of the process: marketing, production, and advertising. Professionalism and the information seeking behavior of clients are noted. Five references are provided. (EJS)

  4. Research in the Library

    National Research Council Canada - National Science Library

    2004-01-01

    ... devoted to a similar purpose. Over the past 100 years, the Library has been growing and developing to support the unique educational and research programs of the College, and its collections are, therefore, strong in the areas...

  5. Presidential Electronic Records Library

    Data.gov (United States)

    National Archives and Records Administration — PERL (Presidential Electronic Records Library) used to ingest and provide internal access to the Presidential electronic Records of the Reagan, Bush, and Clinton...

  6. Iowa DNR - NRGIS Library

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — The Natural Resources Geographic Information System (NRGIS) Library is a Geographic Information System (GIS) repository developed and maintained by the GIS Section...

  7. The library assessment cookbook

    CERN Document Server

    Dobbs, Aaron W

    2017-01-01

    The Library Assessment Cookbook features 80 practical, easy-to-implement recipes divided into nine sections. This Cookbook will help librarians of all levels of experience measure and demonstrate their institutional value.

  8. Unified accelerator libraries

    International Nuclear Information System (INIS)

    Malitsky, Nikolay; Talman, Richard

    1997-01-01

    A 'Universal Accelerator Libraries' (UAL) environment is described. Its purpose is to facilitate program modularity and inter-program and inter-process communication among heterogeneous programs. The goal ultimately is to facilitate model-based control of accelerators

  9. Archives Library Information Center

    Data.gov (United States)

    National Archives and Records Administration — ALIC is an online library catalog of books, periodicals, and other materials contained in Archives I and II and book collections located in other facilities.

  10. Foreign Data Library

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Foreign Data Library consists of meteorological data from nations other than the United States. The data are on original observational forms, in publications,...

  11. Web design for libraries

    CERN Document Server

    Rubenstein, Charles

    2014-01-01

    Having a clear, attractive, and easy-to-navigate website that allows users to quickly find what they want is essential for any organization-including a library. This workbook makes website creation easy-no HTML required.

  12. Nigerian School Library Journal

    African Journals Online (AJOL)

    The Nigerian School Library Journal is a scholarly publication of the Nigerian ... media resources management, reading development, e-learning/m-learning, and other ... Team management in the 21 century: A human relations theory angle ...

  13. Medical Library Association

    Science.gov (United States)

    ... Next Generation Data Sciences Challenges in Health and Biomedicine Fri November 3, 2017 The Medical Library Association ... Next Generation Data Science Challenges in Health and Biomedicine. MLA's comments and recommendations will help formulate strategic ...

  14. The Library as Publisher.

    Science.gov (United States)

    Field, Roy

    1979-01-01

    Presents a guide to for-profit library publishing of reprints, original manuscripts, and smaller items. Discussed are creation of a publications panel to manage finances and preparation, determining prices of items, and drawing up author contracts. (SW)

  15. Marketing and health libraries

    OpenAIRE

    Wakeham, Maurice

    2004-01-01

    AIM: To present an overview of the concepts of marketing and to examine ways in which they can be applied to health libraries.\\ud METHODS: A review was carried out of literature relating to health libraries using LISA, CINAHL, BNI and Google.\\ud RESULTS: Marketing is seen as a strategic management activity aimed at developing customer relationships. Concepts such as the 'four Ps' (product, price, place and promotion), marketing plans, the marketing mix, segmentation, promotion and evaluation ...

  16. The LAW library

    International Nuclear Information System (INIS)

    Green, N.M.; Parks, C.V.; Arwood, J.W.

    1989-01-01

    The 238 group LAW library is a new multigroup library based on ENDF/B-V data. It contains data for 302 materials and will be distributed by the Radiation Shielding Information Center, located at Oak Ridge National Laboratory. It was generated for use in neutronics calculations required in radioactive waste analyses, though it has equal utility in any study requiring multigroup neutron cross sections

  17. Digital library usability studies

    CERN Document Server

    Eden, Bradford Lee

    2005-01-01

    Each summer, circulation staff in my library inventories a section of the stacks andbrings collection issues to the attention of appropriate bibliographers. Since I amresponsible for the economics collection, I see an array of government documents thathave managed to elude the cataloging process. Many of these titles are decades old,having squatted in the library undisturbed and uncirculated since our online catalogwas implemented in 1990.

  18. Outsourcing in libraries

    Directory of Open Access Journals (Sweden)

    Matjaž Žaucer

    1999-01-01

    Full Text Available Like other organisations more flexible libraries tend to conform to the changing environment as this is the only way to be successful and effective. They are expected to offer "more for less" and they are reorganising and searching the ways to reduce the costs. Outsourcing is one of possible solutions. The article deals with the possibilities of outsourcing in libraries, higher quality of their work eoneentrated on principal activities and gives some experienees in this field.

  19. Design of Concept Libraries for C++

    KAUST Repository

    Sutton, Andrew

    2012-01-01

    We present a set of concepts (requirements on template arguments) for a large subset of the ISO C++ standard library. The goal of our work is twofold: to identify a minimal and useful set of concepts required to constrain the library\\'s generic algorithms and data structures and to gain insights into how best to support such concepts within C++. We start with the design of concepts rather than the design of supporting language features; the language design must be made to fit the concepts, rather than the other way around. A direct result of the experiment is the realization that to simply and elegantly support generic programming we need two kinds of abstractions: constraints are predicates on static properties of a type, and concepts are abstract specifications of an algorithm\\'s syntactic and semantic requirements. Constraints are necessary building blocks of concepts. Semantic properties are represented as axioms. We summarize our approach: concepts = constraints + axioms. This insight is leveraged to develop a library containing only 14 concepts that encompassing the functional, iterator, and algorithm components of the C++ Standard Library (the STL). The concepts are implemented as constraint classes and evaluated using Clang\\'s and GCC\\'s Standard Library test suites. © 2012 Springer-Verlag.

  20. The IAEA library and documentation services

    International Nuclear Information System (INIS)

    1963-01-01

    The library was established in 1958 and has since acquired a large and steadily increasing collection of nuclear science literature. The collection can be divided into three broad categories: (a) books, (b) periodicals, and (c) technical reports and official documents. There are at present approximately 19000 books in the library. The books cover all aspects of nuclear science and technology as well as some relevant branches of economics, law and other subjects. In addition, there are numerous reference books, both on science and on other subjects related to the work of the Agency. The library receives 7 00 periodicals, mostly of a scientific or technical nature. Sixty-three per cent of the periodicals are obtained by subscription and some 30 per cent as presentation copies. The rest of the periodicals are received under an exchange of publications. Of particular interest to research workers is a comprehensive collection of abstracting journals. The technical reports and documents are usually obtained from Member Governments and other international organizations, including the United Nations and the specialized agencies. There are nearly 50 000 reports, some 30 000 of which are on microcards. As international organizations and Member States supply the library with their documents and other publications on atomic energy on a routine basis, the collection in the library now represents much of the world's unclassified material on different branches of nuclear science and technology. The library also possesses about 5000 reprints and translations of technical reports

  1. Library Services Funding Assessment

    Science.gov (United States)

    Lorig, Jonathan A.

    2004-01-01

    The Glenn Technical Library is a science and engineering library that primarily supports research activities at the Glenn Research Center, and provides selected services to researchers at all of the NASA research centers. Resources available in the library include books, journals, CD-ROMs, and access to various online sources, as well as live reference and inter-library loan services. The collection contains over 77,000 books, 800,000 research reports, and print or online access to over 1,400 journals. Currently the library operates within the Logistics and Technical Information Division, and is funded as an open-access resource within the GRC. Some of the research units at the GRC have recently requested that the library convert to a "pay-for-services" model, in which individual research units could fund only those journal subscriptions for which they have a specific need. Under this model, the library would always maintain a certain minimum level of pooled-expense services, including the ready reference and book collections, and inter-library loan services. Theoretically the "pay-for-services" model would encourage efficient financial allocation, and minimize the extent to which paid journal subscriptions go unused. However, this model also could potentially negate the benefits of group purchases for journal subscriptions and access. All of the major journal publishers offer package subscriptions that compare favorably in cost with the sum of individual subscription costs for a similar selection of titles. Furthermore, some of these subscription packages are "consortium" purchases that are funded collectively by the libraries at multiple NASA research centers; such consortia1 memberships would be difficult for the library to pay, if enough GRC research units were to withdraw their pooled contributions. cost of collectively-funded journal access with the cost of individual subscriptions. My primary task this summer is to create the cost dataset framework, and

  2. Libraries from the Inside Out.

    Science.gov (United States)

    Cohen, Elaine; And Others

    1989-01-01

    This annual report on library facilities and furnishings includes articles on: (1) designing libraries that are both handsome and functional; (2) functional use of color and light in library interior design; (3) creating user-friendly libraries; and (4) the seven deadly sins of architects. An eight-page section of photographs is included. (MES)

  3. Tomorrow's Library: The American View.

    Science.gov (United States)

    Dempsey, Mary A.

    1998-01-01

    Explores the continuing role of the public library in society, discussing the mission of the library (highlights the Chicago Public Library's new mission statement), funding collections and buildings, technology, capital improvements, challenges to intellectual freedom, librarian education, library outreach, and private-sector partnerships. (PEN)

  4. Interior Design Trends in Libraries.

    Science.gov (United States)

    Sager, Don, Ed.

    2000-01-01

    Four contributing authors discuss perspectives on current trends in library interior design. Articles include: "Trends in Library Furnishings: A Manufacturer's Perspective" (Andrea Johnson); "Libraries, Architecture, and Light: The Architect's Perspective" (Rick McCarthy); "The Library Administrator's Perspective" (Chadwick Raymond); and "The…

  5. A Constitution for Danish Libraries.

    Science.gov (United States)

    Nielsen, O. Perch

    This overview of the history of legislation governing the Danish library system from 1920 to the present: describes the various kinds of libraries in Denmark, explores the current controversies surrounding the roles of several supervisory library bodies, and details recent recommendations of the Danish Library Commission. (FM)

  6. Hispanic College Students Library Experience

    Science.gov (United States)

    Lumley, Risa; Newman, Eric; Brown, Haakon T.

    2015-01-01

    This study looks at undergraduate Hispanic students' interpretations and current perceptions of the academic library's purpose, usefulness and value. What are the reasons to use the library? What are the barriers to use? This study will examine academic libraries' move toward electronic library materials and what it means for Hispanic students.…

  7. Library Anxiety of Teacher Trainees

    Science.gov (United States)

    Sharma, Savita; Attri, Poonam

    2018-01-01

    This study investigates the library anxiety in Teacher Trainees and found it to be a prevalent phenomenon in students. The five dimensions of library anxiety, namely, barriers with staff, affective barriers, comfort with the library, knowledge of the library, and mechanical barriers have been identified. The sample of the study constituted 58…

  8. Service Innovation In Academic Libraries

    DEFF Research Database (Denmark)

    Scupola, Ada; Nicolajsen, Hanne Westh

    2010-01-01

    Purpose – The purpose of this article is to investigate whether management and employees in academic libraries involve users in library service innovations and what these user roles are. Design/methodology/approach – The article first reviews the literature focusing on innovation, new product...... development, new service development and library science with specific focus on users and management. Subsequently the research uses a case study approach to investigate management and customer involvement in a Danish academic library. Findings – Results from the case study show that academic libraries...... in academic library service innovations on the basis of an in-depth case study of a Danish academic library....

  9. University Rankings: How Well Do They Measure Library Service Quality?

    Science.gov (United States)

    Jackson, Brian

    2015-01-01

    University rankings play an increasingly large role in shaping the goals of academic institutions and departments, while removing universities themselves from the evaluation process. This study compares the library-related results of two university ranking publications with scores on the LibQUAL+™ survey to identify if library service quality--as…

  10. Is There a Global Role for Metropolitan City Libraries?

    Science.gov (United States)

    Mason, Marilyn Gell

    1994-01-01

    Discusses the potential for linking large metropolitan public libraries to international interlibrary loan networks. Issues involved in international networking, including funding, standards, network connectivity, and protectionism, are discussed. Examples of libraries capable of participating and brief descriptions of their collections are given.…

  11. Medium-resolution isaac newton telescope library of empirical spectra

    NARCIS (Netherlands)

    Sanchez-Blazquez, P.; Peletier, R. F.; Jimenez-Vicente, J.; Cardiel, N.; Cenarro, A. J.; Falcon-Barroso, J.; Gorgas, J.; Selam, S.; Vazdekis, A.

    2006-01-01

    A new stellar library developed for stellar population synthesis modelling is presented. The library consists of 985 stars spanning a large range in atmospheric parameters. The spectra were obtained at the 2.5-m Isaac Newton Telescope and cover the range lambda lambda 3525-7500 angstrom at 2.3

  12. Library Information System Time-Sharing (LISTS) Project. Final Report.

    Science.gov (United States)

    Black, Donald V.

    The Library Information System Time-Sharing (LISTS) experiment was based on three innovations in data processing technology: (1) the advent of computer time-sharing on third-generation machines, (2) the development of general-purpose file-management software and (3) the introduction of large, library-oriented data bases. The main body of the…

  13. Mechanisation and Automation of Information Library Procedures in the USSR.

    Science.gov (United States)

    Batenko, A. I.

    Scientific and technical libraries represent a fundamental link in a complex information storage and retrieval system. The handling of a large volume of scientific and technical data and provision of information library services requires the utilization of computing facilities and automation equipment, and was started in the Soviet Union on a…

  14. THE TERMINOLOGY OF LIBRARY SCIENCE

    OpenAIRE

    Љиљана Матић

    2014-01-01

    The master’s thesis entitled The Terminology of Library Science presents the general state of the terminology of library science in the Serbian language and analyses the terminological system which was formed in the last couple of decades in relation to library and information science. The terminology of library science is seen as a characteristic of professional language. The research is conducted on a corpus which excludes sources relating extremely to either library science or information ...

  15. Library and information services: impact on patient care quality.

    Science.gov (United States)

    Marshall, Joanne Gard; Morgan, Jennifer Craft; Thompson, Cheryl A; Wells, Amber L

    2014-01-01

    The purpose of this paper is to explore library and information service impact on patient care quality. A large-scale critical incident survey of physicians and residents at 56 library sites serving 118 hospitals in the USA and Canada. Respondents were asked to base their answers on a recent incident in which they had used library resources to search for information related to a specific clinical case. Of 4,520 respondents, 75 percent said that they definitely or probably handled patient care differently using information obtained through the library. In a multivariate analysis, three summary clinical outcome measures were used as value and impact indicators: first, time saved; second, patient care changes; and third, adverse events avoided. The outcomes were examined in relation to four information access methods: first, asking librarian for assistance; second, performing search in a physical library; third, searching library's web site; or fourth, searching library resources on an institutional intranet. All library access methods had consistently positive relationships with the clinical outcomes, providing evidence that library services have a positive impact on patient care quality. Electronic collections and services provided by the library and the librarian contribute to patient care quality.

  16. User Categorization of Public Library Collections

    NARCIS (Netherlands)

    Boter, J.; Wedel, M.

    2005-01-01

    To help users find their way around the large number of titles available, public libraries organize the collection by placing titles on shelves by genre, by adding classification codes in their online catalogs, and by pictograms on book covers. However, users may have different perceptions of how

  17. Library 3.0 intelligent libraries and apomediation

    CERN Document Server

    Kwanya, Tom; Underwood, Peter

    2015-01-01

    The emerging generation of research and academic library users expect the delivery of user-centered information services. 'Apomediation' refers to the supporting role librarians can give users by stepping in when users need help. Library 3.0 explores the ongoing debates on the "point oh” phenomenon and its impact on service delivery in libraries. This title analyses Library 3.0 and its potential in creating intelligent libraries capable of meeting contemporary needs, and the growing role of librarians as apomediators. Library 3.0 is divided into four chapters. The first chapter introduces and places the topic in context. The second chapter considers "point oh” libraries. The third chapter covers library 3.0 librarianship, while the final chapter explores ways libraries can move towards '3.0'.

  18. Shoestring Digital Library: If Existing Digital Library Software Doesn't Suit Your Needs, Create Your Own

    Science.gov (United States)

    Weber, Jonathan

    2006-01-01

    Creating a digital library might seem like a task best left to a large research collection with a vast staff and generous budget. However, tools for successfully creating digital libraries are getting easier to use all the time. The explosion of people creating content for the web has led to the availability of many high-quality applications and…

  19. Automated recycling of chemistry for virtual screening and library design.

    Science.gov (United States)

    Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian

    2012-07-23

    An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.

  20. Application of LOD Technology in German Libraries and Archives

    Directory of Open Access Journals (Sweden)

    Dong Jie

    2017-12-01

    Full Text Available [Purpose/significance] Linked Open Data (LOD has been widely used in large industries, as well as non-profit organizations and government organizations. Libraries and archives are ones of the early adopters of LOD technology. Libraries and archives promote the development of LOD. Germany is one of the developed countries in the libraries and archives industry, and there are many successful cases about the application of LOD in the libraries and archives. [Method/process] This paper analyzed the successful application of LOD technology in German libraries and archives by using the methods of document investigation, network survey and content analysis. [Result/conclusion] These cases reveal in the traditional field of computer science the relationship among research topics related to libraries and archives such as artificial intelligence, database and knowledge discovery. Summing up the characteristics and experience of German practice can provide more reference value for the development of relevant practice in China.

  1. Generation and analysis of a large-scale expressed sequence Tag database from a full-length enriched cDNA library of developing leaves of Gossypium hirsutum L.

    Directory of Open Access Journals (Sweden)

    Min Lin

    Full Text Available BACKGROUND: Cotton (Gossypium hirsutum L. is one of the world's most economically-important crops. However, its entire genome has not been sequenced, and limited resources are available in GenBank for understanding the molecular mechanisms underlying leaf development and senescence. METHODOLOGY/PRINCIPAL FINDINGS: In this study, 9,874 high-quality ESTs were generated from a normalized, full-length cDNA library derived from pooled RNA isolated from throughout leaf development during the plant blooming stage. After clustering and assembly of these ESTs, 5,191 unique sequences, representative 1,652 contigs and 3,539 singletons, were obtained. The average unique sequence length was 682 bp. Annotation of these unique sequences revealed that 84.4% showed significant homology to sequences in the NCBI non-redundant protein database, and 57.3% had significant hits to known proteins in the Swiss-Prot database. Comparative analysis indicated that our library added 2,400 ESTs and 991 unique sequences to those known for cotton. The unigenes were functionally characterized by gene ontology annotation. We identified 1,339 and 200 unigenes as potential leaf senescence-related genes and transcription factors, respectively. Moreover, nine genes related to leaf senescence and eleven MYB transcription factors were randomly selected for quantitative real-time PCR (qRT-PCR, which revealed that these genes were regulated differentially during senescence. The qRT-PCR for three GhYLSs revealed that these genes express express preferentially in senescent leaves. CONCLUSIONS/SIGNIFICANCE: These EST resources will provide valuable sequence information for gene expression profiling analyses and functional genomics studies to elucidate their roles, as well as for studying the mechanisms of leaf development and senescence in cotton and discovering candidate genes related to important agronomic traits of cotton. These data will also facilitate future whole-genome sequence

  2. Supports for libraries'restoration from the Great East Japan Earthquake : Challenges we address at Miyagi Prefectural Library

    Science.gov (United States)

    Kumagai, Shinichiro

    This article overviews the situations of damage and reconstruction of mainly public libraries in Miyagi Prefecture about 9 months after the Great East Japan Earthquake. Serious damage of library buildings was due not only to the tsunami or seismic sea wave but to violent shaking, the latter less reported by the media. We at the Miyagi Prefectural Library implemented reconstruction assistance for regional public libraries in both direct and indirect ways. Among them, we report in detail on the support we offered until the Minami-sanriku Town Library reopened its service. We highlight a prefectural library's role, acting between supporters and those supportees, to consider the necessity of middle organizations. We clarify what challenges we face and examine how best to provide assistance in case of large-scale disasters.

  3. DOLIB: Distributed Object Library

    Energy Technology Data Exchange (ETDEWEB)

    D' Azevedo, E.F.

    1994-01-01

    This report describes the use and implementation of DOLIB (Distributed Object Library), a library of routines that emulates global or virtual shared memory on Intel multiprocessor systems. Access to a distributed global array is through explicit calls to gather and scatter. Advantages of using DOLIB include: dynamic allocation and freeing of huge (gigabyte) distributed arrays, both C and FORTRAN callable interfaces, and the ability to mix shared-memory and message-passing programming models for ease of use and optimal performance. DOLIB is independent of language and compiler extensions and requires no special operating system support. DOLIB also supports automatic caching of read-only data for high performance. The virtual shared memory support provided in DOLIB is well suited for implementing Lagrangian particle tracking techniques. We have also used DOLIB to create DONIO (Distributed Object Network I/O Library), which obtains over a 10-fold improvement in disk I/O performance on the Intel Paragon.

  4. DOLIB: Distributed Object Library

    Energy Technology Data Exchange (ETDEWEB)

    D`Azevedo, E.F.; Romine, C.H.

    1994-10-01

    This report describes the use and implementation of DOLIB (Distributed Object Library), a library of routines that emulates global or virtual shared memory on Intel multiprocessor systems. Access to a distributed global array is through explicit calls to gather and scatter. Advantages of using DOLIB include: dynamic allocation and freeing of huge (gigabyte) distributed arrays, both C and FORTRAN callable interfaces, and the ability to mix shared-memory and message-passing programming models for ease of use and optimal performance. DOLIB is independent of language and compiler extensions and requires no special operating system support. DOLIB also supports automatic caching of read-only data for high performance. The virtual shared memory support provided in DOLIB is well suited for implementing Lagrangian particle tracking techniques. We have also used DOLIB to create DONIO (Distributed Object Network I/O Library), which obtains over a 10-fold improvement in disk I/O performance on the Intel Paragon.

  5. Information Literacy and the Public Library

    DEFF Research Database (Denmark)

    Nielsen, Bo Gerner; Borlund, Pia

    2013-01-01

    This paper reports on the results of an empirical study of Danish public librarians’ conceptions of information literacy and user education in order to support and optimize lifelong learning of library users. The study builds on data from interviews of purposely selected public librarians...... and a large-scale e-mail survey (questionnaire). The results show that the public librarians consider the public library an important place for learning, but also that they do not share a common understanding of the concepts of information literacy and lifelong learning. The study further reveals a diversity...

  6. USGS Digital Spectral Library splib06a

    Science.gov (United States)

    Clark, Roger N.; Swayze, Gregg A.; Wise, Richard A.; Livo, K. Eric; Hoefen, Todd M.; Kokaly, Raymond F.; Sutley, Stephen J.

    2007-01-01

    ), one simply needs a diagnostic absorption band. The mapping system uses continuum-removed reference spectral features fitted to features in observed spectra. Spectral features for such algorithms can be obtained from a spectrum of a sample containing large amounts of contaminants, including those that add other spectral features, as long as the shape of the diagnostic feature of interest is not modified. If, however, the data are needed for radiative transfer models to derive mineral abundances from reflectance spectra, then completely uncontaminated spectra are required. This library contains spectra that span a range of quality, with purity indicators to flag spectra for (or against) particular uses. Acquiring spectral measurements and performing sample characterizations for this library has taken about 15 person-years of effort. Software to manage the library and provide scientific analysis capability is provided (Clark, 1980, 1993). A personal computer (PC) reader for the library is also available (Livo and others, 1993). The program reads specpr binary files (Clark, 1980, 1993) and plots spectra. Another program that reads the specpr format is written in IDL (Kokaly, 2005). In our view, an ideal spectral library consists of samples covering a very wide range of materials, has large wavelength range with very high precision, and has enough sample analyses and documentation to establish the quality of the spectra. Time and available resources limit what can be achieved. Ideally, for each mineral, the sample analysis would include X-ray diffraction (XRD), electron microprobe (EM) or X-ray fluorescence (XRF), and petrographic microscopic analyses. For some minerals, such as iron oxides, additional analyses such as Mossbauer would be helpful. We have found that to make the basic spectral measurements, provide XRD, EM or XRF analyses, and microscopic analyses, document the results, and complete an entry of one spectral library sample, all takes about

  7. The CASTOR shower library

    International Nuclear Information System (INIS)

    Mundim Filho, Luiz Martins; Carvalho, Wagner de Paula

    2012-01-01

    Full text: CASTOR (Centaur And Strange Object Research) is an electromagnetic (EM) and hadronic (HAD) calorimeter, based on tungsten and quartz plates, operating in the CMS Detector (Compact Muon Solenoid) at LHC. The calorimeter detects Cerenkov radiation and is positioned around the beam pipe in the very forward region of CMS (at 14.38 m from the interaction point), covering the pseudo-rapidity range between -6.6 ≤ η≤-5.1 . It is longitudinally segmented into 14 sections, 2 for the EM and 12 for the HAD parts and is 16-fold azimuthally symmetric around the beam pipe. A Shower Library is needed for CASTOR Monte Carlo simulation, as the full simulation of showers takes a long time and the high multiplicity of particles in the forward region makes this simulation very time consuming. The Shower Library is used as a look-up table in the form of a ROOT file, so that when a simulated particle enters the detector with a certain energy and direction, characterized by the azimuthal angle φ and the pseudo-rapidity η, instead of making the full simulation of the shower in CASTOR, it is substituted by one already stored in the Shower Library. Showers corresponding to two types of particles are included in the Shower Library: electrons (or photons) and charged pions. The software implemented to make the Shower Library is described, as well as the validation of this library and timing studies. This package has been developed in the context of the official software of the CMS Collaboration, CMSSW. (author)

  8. WIMS Library updating

    International Nuclear Information System (INIS)

    Ravnik, M.; Trkov, A.; Holubar, A.

    1992-01-01

    At the end of 1990 the WIMS Library Update Project (WLUP) has been initiated at the International Atomic Energy Agency. The project was organized as an international research project, coordinated at the J. Stefan Institute. Up to now, 22 laboratories from 19 countries joined the project. Phase 1 of the project, which included WIMS input optimization for five experimental benchmark lattices, has been completed. The work presented in this paper describes also the results of Phase 2 of the Project, in which the cross sections based on ENDF/B-IV evaluated nuclear data library have been processed. (author) [sl

  9. Astrophysical opacity library

    International Nuclear Information System (INIS)

    Huebner, W.F.; Merts, A.L.; Magee, N.H. Jr.; Argo, M.F.

    1977-08-01

    The astrophysical elements opacity library includes equation of state data, various mean opacities, and 2000 values of the frequency-dependent extinction coefficients in equally spaced intervals u identical with hν/kT from 0 to 20 for 41 degeneracy parameters eta from -28 (nondegenerate) to 500 and 46 temperatures kT from 1 eV to 100 keV. Among available auxiliary quantities are the free electron density, mass density, and plasma cutoff frequency. A library-associated program can produce opacities for mixtures with up to 20 astrophysically abundant constituent elements at 4 levels of utility for the user

  10. Application Portable Parallel Library

    Science.gov (United States)

    Cole, Gary L.; Blech, Richard A.; Quealy, Angela; Townsend, Scott

    1995-01-01

    Application Portable Parallel Library (APPL) computer program is subroutine-based message-passing software library intended to provide consistent interface to variety of multiprocessor computers on market today. Minimizes effort needed to move application program from one computer to another. User develops application program once and then easily moves application program from parallel computer on which created to another parallel computer. ("Parallel computer" also include heterogeneous collection of networked computers). Written in C language with one FORTRAN 77 subroutine for UNIX-based computers and callable from application programs written in C language or FORTRAN 77.

  11. Future of research libraries

    CERN Document Server

    Naryandas, Narakesari; Kindström, Daniel

    2014-01-01

    Research libraries have been an integral part of the scholarly communication system since that system emerged in its present form. They now face a period of unprecedentedly drastic and rapid change. This is caused, first and foremost, by the migration of much scholarly material to digital formats, raising the question of the future purpose of the 'library space'. Together with this come transfigurational changes to the communication change of recorded information, with the roles of authors , publishers, database producers and librarians and archivists all in a state of flux. Finally, new forms

  12. Wordpress for libraries

    CERN Document Server

    Haefele, Chad

    2015-01-01

    WordPress is not only the most popular blogging software in the world, but it is also a powerful content management system that runs more than 23 percent of all websites. The current version alone has been downloaded almost 20 million times, and the WordPress community has built more than 38,000 plugins to extend and enhance the system. Libraries are using this technology to create community-oriented websites, blogs, subject guides, digital archives, and more. This hands-on, practical book walks readers through the entire process of setting up a WordPress website for their library,

  13. Enterprise Reference Library

    Science.gov (United States)

    Bickham, Grandin; Saile, Lynn; Havelka, Jacque; Fitts, Mary

    2011-01-01

    Introduction: Johnson Space Center (JSC) offers two extensive libraries that contain journals, research literature and electronic resources. Searching capabilities are available to those individuals residing onsite or through a librarian s search. Many individuals have rich collections of references, but no mechanisms to share reference libraries across researchers, projects, or directorates exist. Likewise, information regarding which references are provided to which individuals is not available, resulting in duplicate requests, redundant labor costs and associated copying fees. In addition, this tends to limit collaboration between colleagues and promotes the establishment of individual, unshared silos of information The Integrated Medical Model (IMM) team has utilized a centralized reference management tool during the development, test, and operational phases of this project. The Enterprise Reference Library project expands the capabilities developed for IMM to address the above issues and enhance collaboration across JSC. Method: After significant market analysis for a multi-user reference management tool, no available commercial tool was found to meet this need, so a software program was built around a commercial tool, Reference Manager 12 by The Thomson Corporation. A use case approach guided the requirements development phase. The premise of the design is that individuals use their own reference management software and export to SharePoint when their library is incorporated into the Enterprise Reference Library. This results in a searchable user-specific library application. An accompanying share folder will warehouse the electronic full-text articles, which allows the global user community to access full -text articles. Discussion: An enterprise reference library solution can provide a multidisciplinary collection of full text articles. This approach improves efficiency in obtaining and storing reference material while greatly reducing labor, purchasing and

  14. Knowledge management for libraries

    CERN Document Server

    Forrestal, Valerie

    2015-01-01

    Libraries are creating dynamic knowledge bases to capture both tacit and explicit knowledge and subject expertise for use within and beyond their organizations. In this book, readers will learn to move policies and procedures manuals online using a wiki, get the most out of Microsoft SharePoint with custom portals and Web Parts, and build an FAQ knowledge base from reference management applications such as LibAnswers. Knowledge Management for Libraries guides readers through the process of planning, developing, and launching th

  15. AutoWIG: automatic generation of python bindings for C++ libraries

    Directory of Open Access Journals (Sweden)

    Pierre Fernique

    2018-04-01

    Full Text Available Most of Python and R scientific packages incorporate compiled scientific libraries to speed up the code and reuse legacy libraries. While several semi-automatic solutions exist to wrap these compiled libraries, the process of wrapping a large library is cumbersome and time consuming. In this paper, we introduce AutoWIG, a Python package that wraps automatically compiled libraries into high-level languages using LLVM/Clang technologies and the Mako templating engine. Our approach is automatic, extensible, and applies to complex C++ libraries, composed of thousands of classes or incorporating modern meta-programming constructs.

  16. Library resources on the Internet

    Science.gov (United States)

    Buchanan, Nancy L.

    1995-07-01

    Library resources are prevalent on the Internet. Library catalogs, electronic books, electronic periodicals, periodical indexes, reference sources, and U.S. Government documents are available by telnet, Gopher, World Wide Web, and FTP. Comparatively few copyrighted library resources are available freely on the Internet. Internet implementations of library resources can add useful features, such as full-text searching. There are discussion lists, Gophers, and World Wide Web pages to help users keep up with new resources and changes to existing ones. The future will bring more library resources, more types of library resources, and more integrated implementations of such resources to the Internet.

  17. Changing libraries, encountering the law

    Directory of Open Access Journals (Sweden)

    Isabelle Giannattasio

    2004-10-01

    Full Text Available The technical and legal issues associated with digital material, originally the concern principally of audiovisual librarians, now impact upon library management in general. Three factors, occurring simultaneously, have driven the digital agenda for library managers: the high profile accorded to the accomplishment of mission; the ever-increasing complexity of copyright legislation; and the Internet which has served as a catalyst for deregulation and globalisation. The purpose of this short article is to explore both the opportunities and the obstacles posed by these factors across three core areas of digital collection management: conservation, access and development. I shall draw upon the Bibliothèque nationale de France (BnF in this context. The BnF is a national library containing heritage collections, largely legal deposit and used for research purposes,. and also collections aimed at a far wider public.. The Audiovisual department is in charge of phonograms, videograms, multimedia and electronic documents. The collection was originally created in 1911 by the linguist Ferdinand Brunot of the Sorbonne University as 'Les Archives de la parole'. Subsequently the collection has been further developed mainly with published records, mostly as legal deposit. The collection now has over one million documents, in all kinds of technical devices and carriers. In France, three institutions share the audiovisual heritage collections: the BnF for documents, the Centre National de la Cinématographie (CNC for film, and the Institut national de l'Audiovisuel for radio and television archives. In the BnF audiovisual collections are enlarged by legal deposit, by acquisitions and by donations. But whereas we own the carriers - a material property -, we do not own the intellectual property in the work. The protection of authors' rights and neighbouring rights are central to the actions we have to perform in order to accomplish our missions of conservation and

  18. Small Molecule Library Synthesis Using Segmented Flow

    Directory of Open Access Journals (Sweden)

    Christina M. Thompson

    2011-11-01

    Full Text Available Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 mL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently.

  19. Library Standards: Evidence of Library Effectiveness and Accreditation.

    Science.gov (United States)

    Ebbinghouse, Carol

    1999-01-01

    Discusses accreditation standards for libraries based on experiences in an academic law library. Highlights include the accreditation process; the impact of distance education and remote technologies on accreditation; and a list of Internet sources of standards and information. (LRW)

  20. Staff development and library services in academic libraries in ...

    African Journals Online (AJOL)

    Staff development and library services in academic libraries in Bayelsa and Delta States. ... Information Impact: Journal of Information and Knowledge Management ... Descriptive survey research design was used for this study, data was ...

  1. More library mashups exploring new ways to deliver library data

    CERN Document Server

    2015-01-01

    Nicole Engard follows up her ground-breaking 2009 book Library Mashups with a fresh collection of mashup projects that virtually any library can emulate, customize, and build upon. In More Library Mashups, Engard and 24 creative library professionals describe how they are mashing up free and inexpensive digital tools and techniques to improve library services and meet everyday (and unexpected) challenges. Examples from libraries of all types are designed to help even non-programmers share and add value to digital content, update and enhance library websites and collections, mashup catalog data, connect to the library's automation system, and use emerging tools like Serendip-o-matic, Umlaut, and Libki to engage users, staff, and the community.

  2. Designing Mobile Technology to Enhance Library Space Use: Findings from an Undergraduate Student Competition

    Science.gov (United States)

    Ward, David; Hahn, Jim; Mestre, Lori S.

    2015-01-01

    To explore how libraries might integrate student perspectives and needs into their mobile development workflow, one large academic research library developed a fun, collaborative design methodology in order to stimulate student creativity. As part of a national IMLS (Institute for Museums and Library Services) grant, "The Student/Library…

  3. Provosts' Perceptions of Academic Library Value and Preferences for Communication: A National Study

    Science.gov (United States)

    Murray, Adam; Ireland, Ashley

    2018-01-01

    While many studies have been conducted under the auspices of calculating academic library value, there are no large-scale studies into the perceptions that college or university provosts have of library value, nor are there studies into how provosts prefer library value data to be communicated. This study addresses that gap through a national…

  4. For Better or Worse: Using Wikis and Blogs for Staff Communication in an Academic Library

    Science.gov (United States)

    Costello, Kristen; Del Bosque, Darcy

    2010-01-01

    This case study from the University of Nevada, Las Vegas, University Libraries, which has one main library, three branches, and more than 110 staff, illustrates one approach to using new technologies as additional methods for internal communication. At large academic libraries, communication within the organization can be challenging. The…

  5. Renewing library Web sites CMS at libraries

    CERN Document Server

    Vida, A

    2006-01-01

    The use of the Internet has a ten-year history in Hungary. In the beginning, users were surfing on textual Web sites with the browser Lynx (1991), then a range of graphic browsers appeared: Mosaic (1993) , Netscape (1994), and finally Internet Explorer (1995). More and more institutions, including libraries decided to enter the World Wide Web with their own homepage. The past ten years have brought enormous changes and new requirements in the way that institutional homepages are designed. This article offers an overview of the development phases of Web sites, presents the new tools necessary for the state-of-the-art design and gives advice on their up-to-date maintenance.

  6. Library of INCA

    OpenAIRE

    Bergman, Aeron

    2013-01-01

    LIBRARY OF INCA. Åpning: 25. august 2012. (18.00 til 21.00) Utstillingsperiode: 25. august - 22. september. Utstillere: Aurora Harris, Frido Evers, Lina Persson, Per-Oskar Leu, Cary Loren, Inger Wold Lund, Hamilton Poe. Kuratorer: Aeron Bergman and Alejandra Salinas. Visningssted: INCA - Institute for Neo Connotative Action, Detroit, USA.

  7. News from the Library

    CERN Multimedia

    CERN Library

    2010-01-01

    A third of the world’s current literature in electrical engineering is available on your CERN desktop Looking for a technical standard on software reviews and audits? Is it referred to as "IEEE color books"? Want to download and read NOW the latest version of IEEE 802? Whenever a need for a technical standard or specification arises in your activity, the Library is here to serve you. For IEEE standards it is particularly easy; the whole collection is available for immediate download. Indeed, since 2007, the CERN Library offers readers online access to the complete IEEE Electronic Library (Institute of Electrical and Electronics Engineers). This licence gives unlimited online access to all IEEE and IET journals and proceedings, starting from the first issue. But not everyone knows that this resource gives also access to all current IEEE standards as well as a selection of archival ones. The Library is now working on the integration of a selection of these standards in our onlin...

  8. School Library Nostalgias

    Science.gov (United States)

    Hochman, Jessica

    2016-01-01

    This paper explores nostalgia as both a limiting cultural force in the lives of school librarians and a practice that can be used to more accurately portray library work. The stereotype of the shushing, lone school librarian, based on restorative nostalgia, is related to a nostalgic oversimplification of the school librarian's historical role.…

  9. Virtual Libraries: Service Realities.

    Science.gov (United States)

    Novak, Jan

    This paper discusses client service issues to be considered when transitioning to a virtual library situation. Themes related to the transitional nature of society in the knowledge era are presented, including: paradox and a contradictory nature; blurring of boundaries; networks, systems, and holistic thinking; process/not product, becoming/not…

  10. Women, Power, and Libraries.

    Science.gov (United States)

    Schuman, Patricia Glass

    1984-01-01

    Discusses the concept of power in the context of women and the library profession, citing views of power by Max Weber, John Kenneth Galbraith, Letty Cottin Pogrebin, and Rosabeth Moss Kantor. Male power and female submission, defining power, organizing for power, and sharing power are highlighted. A 12-item bibliography is included. (EJS)

  11. In the CERN Library

    CERN Multimedia

    CERN PhotoLab

    1963-01-01

    Seen in this picture is Noria Christophoridou, librarian of the Greek Atomic Energy Commission, who has been sent by her government to CERN for a year to widen her experience of library and documentation services. In the photograph she is providing information to Kurt Gottfried, a CERN visiting scientist from Harvard University, who is spending a year with CERN's Theory Division

  12. Library Budget Primer.

    Science.gov (United States)

    Warner, Alice Sizer

    1993-01-01

    Discusses the advantages and disadvantages of six types of budgets commonly used by many different kinds of libraries. The budget types covered are lump-sum; formula; line or line-item; program; performance or function; and zero-based. Accompanying figures demonstrate the differences between four of the budget types. (three references) (KRN)

  13. The Virtual Library

    Science.gov (United States)

    Valenza, Joyce Kasman

    2006-01-01

    Today's school libraries must meet student needs as both a physical and virtual space. Existing both offline and online, they must offer around-the-clock access as well as instruction and guidance that support the face-to-face interactions of students with librarians and classroom teachers. Although students are often technologically proficient,…

  14. CitEST libraries

    Directory of Open Access Journals (Sweden)

    Maria Luísa P. Natividade Targon

    2007-01-01

    Full Text Available In order to obtain a better understanding of what is citrus, 33 cDNA libraries were constructed from different citrus species and genera. Total RNA was extracted from fruits, leaves, flowers, bark, seeds and roots, and subjected or not to different biotic and abiotic stresses (pathogens and drought and at several developmental stages. To identify putative promoter sequences, as well as molecular markers that could be useful for breeding programs, one shotgun library was prepared from sweet orange (Citrus sinensis var. Olimpia. In addition, EST libraries were also constructed for a citrus pathogen, the oomycete Phythophthora parasitica in either virulent or avirulent form. A total of 286,559 cDNA clones from citrus were sequenced from their 5’ end, generating 242,790 valid reads of citrus. A total of 9,504 sequences were produced in the shotgun library and the valid reads were assembled using CAP3. In this procedure, we obtained 1,131 contigs and 4,083 singletons. A total of 19,200 cDNA clones from P. parasitica were sequenced, resulting in 16,400 valid reads. The number of ESTs generated in this project is, to our knowledge, the largest citrus sequence database in the world.

  15. Virtual digital library

    Science.gov (United States)

    Thoma, George R.

    1996-03-01

    The virtual digital library, a concept that is quickly becoming a reality, offers rapid and geography-independent access to stores of text, images, graphics, motion video and other datatypes. Furthermore, a user may move from one information source to another through hypertext linkages. The projects described here further the notion of such an information paradigm from an end user viewpoint.

  16. Alleviating Library Anxiety

    Science.gov (United States)

    Nicol, Erica Carlson

    2009-01-01

    As librarians work to make their services more user-centered, to put forward their best and most approachable faces in order to meet user needs, they are still met with students who approach them hesitantly and apologize for asking them questions, and by students who are obviously intimidated by the libraries in which they work. A good part of…

  17. Fission product data library

    International Nuclear Information System (INIS)

    Hep, J.; Valenta, V.

    1975-01-01

    Reprints of values from BIBFP for 39 isotopes for which either a mistake in the BIBFP Library or updated values in the literature have been found, are given. Most corrections concern the branching ratios for isotopes which are the precursors of delayed neutron emitters

  18. Nigerian Libraries: Submissions

    African Journals Online (AJOL)

    Author Guidelines. Contributions to the Nigerian Libraries for publication should not be more than 5,0000 words. They should be double-spaced typed in A4 paper size. Foot notes should be avoided ... Magazine: Fatima, G (date of publication) article title, magazine title, volume(issue), page(s). Website: Uchenna, O. (date ...

  19. Library Online Systems.

    Science.gov (United States)

    Folda, Linda; And Others

    1989-01-01

    Issues related to library online systems are discussed in six articles. Topics covered include staff education through vendor demonstrations, evaluation of online public access catalogs, the impact of integrated online systems on cataloging operations, the merits of smart and dumb barcodes, and points to consider in planning for the next online…

  20. Electrical equipment design library

    International Nuclear Information System (INIS)

    1994-01-01

    This book guides the design supervision, construction order for electrical equipment. The contents of this library are let's use electricity like this, leading-in-pole and casual power, electric pole install below 300KVA, electric pole install below 301∼1000KVA, electric pole install exceed 1000KVA, rooftop install exceed 1000KVA, CUBICLE type, 154KV services. It adds an appendix.