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Sample records for competitive protein-binding radioassay

  1. Optimalization of the competitive protein binding assays of functional metabolites of cholecalciferol

    Energy Technology Data Exchange (ETDEWEB)

    Justova, V.; Starka, L. (Karlova Univ., Prague (Czechoslovakia). 3. Interni Klinika)

    1982-03-16

    Competitive protein binding assays of metabolites of vitamin D were compared using different plasmatic binding proteins from normal and pathological subjects and tritium tracer techniques. The conditions of competitive protein binding assays are optimalized in respect to their routine clinical use.

  2. Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay.

    Science.gov (United States)

    Alexander, N M

    1976-06-01

    Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed.

  3. Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of {sup 186}Re-MAG3-conjugated bisphosphonate ({sup 186}Re-MAG3-HBP), an agent for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan)]|[Kanazawa University, Advanced Science Research Center, Kanazawa (Japan); Mukai, Takahiro [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan)]|[Kyushu University, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Kawai, Keiichi [Kanazawa University, Graduate School of Medical Sciences, Kanazawa (Japan)]|[University of Fukui, Biomedical Imaging Research Center, Yoshida, Fukui (Japan); Takamura, Norito [Kyushu University of Health and Welfare, School of Pharmaceutical Sciences, Nobeoka (Japan); Hanaoka, Hirofumi; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hashimoto, Kazuyuki [Japan Atomic Energy Agency, Tokai-mura, Ibaraki (Japan); Shiba, Kazuhiro; Mori, Hirofumi [Kanazawa University, Advanced Science Research Center, Kanazawa (Japan)

    2009-01-15

    We have developed a {sup 186}Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate ({sup 186}Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of {sup 186}Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of {sup 99m}Tc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution. The displacement effects of several protein-binding inhibitors on the protein binding of {sup 186}Re-MAG3-HBP were investigated. Biodistribution experiments were performed by intravenously administering {sup 186}Re-MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or saline. The protein binding of {sup 186}Re-MAG3-HBP in rat serum, human serum, and a human serum albumin solution was significantly decreased by the addition of ceftriaxone, which has high affinity for binding site I on serum albumin. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of {sup 186}Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein. (orig.)

  4. The MAJORANA Demonstrator Radioassay Program

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N.; Arnquist, Isaac J.; Avignone, F. T.; Back, Henning O.; Barabash, Alexander S.; Bertrand, F.; Boswell, M.; Bradley, A. W.; Brudanin, V.; Busch, Matthew; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Yuen-Dat; Christofferson, C. D.; Chu, P. H.; Cuesta, C.; Detwiler, Jason A.; Dunmore, J. A.; Efremenko, Yuri; Ejiri, H.; Elliott, S.; Finnerty, P.; Galindo-Uribarri, A.; Gehman, Victor M.; Gilliss, T.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I.; Guiseppe, V. E.; Henning, R.; Hoppe, Eric W.; Howard, S.; Howe, M. A.; Jasinski, B. R.; Johnson, R. A.; Keeter, K.; Kidd, M. F.; Kochetov, Oleg; Konovalov, S.; Kouzes, Richard T.; Laferriere, Brian D.; Leon, Jonathan D.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Martin, R. D.; Massarcyk, R.; Meijer, S. J.; Mertens, S.; Miller, M. L.; Orrell, John L.; O' Shaughnessy, C.; Overman, Nicole R.; Poon, Alan W.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, Keith; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, Alexis G.; Shanks, B.; Shirchenko, M.; Snavely, Kyle J.; Snyder, N.; Steele, David; Suriano, Anne-Marie; Tedeschi, D.; Trimble, J. E.; Varner, R. L.; Vasilyev, Sergey; Vetter, K.; Vorren, Kris R.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, Chang-Hong; Yumatov, Vladimir; Zhitnikov, I.

    2016-05-03

    The Majorana collaboration is constructing the Majorana Demonstrator at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope 76Ge, to demonstrate the feasibility of a large-scale Ge detector experiment to search for neutrinoless double beta decay. The long half-life of this postulated process requires that the apparatus be extremely low in radioactive isotopes whose decays may produce backgrounds to the search. The radioassay program conducted by the collaboration to ensure that the materials comprising the apparatus are suffciently pure is described. The resulting measurements of the radioactiveisotope contamination for a number of materials studied for use in the detector are reported.

  5. The MAJORANA DEMONSTRATOR radioassay program

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Shanghai Jiao Tong University, Shanghai (China); Arnquist, I.J. [Pacific Northwest National Laboratory, Richland, WA (United States); Avignone, F.T. [Department of Physics and Astronomy, University of South Carolina, Columbia, SC (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States); Back, H.O. [Department of Physics, North Carolina State University, Raleigh, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Barabash, A.S. [National Research Center, “Kurchatov Institute” Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Bertrand, F.E. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Boswell, M. [Los Alamos National Laboratory, Los Alamos, NM (United States); Bradley, A.W. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Brudanin, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Busch, M. [Department of Physics, Duke University, Durham, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Buuck, M. [Center for Experimental Nuclear Physics and Astrophysics, and Department of Physics, University of Washington, Seattle, WA (United States); Byram, D. [Department of Physics, University of South Dakota, Vermillion, SD (United States); Caldwell, A.S. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Chan, Y.-D. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Christofferson, C.D. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Chu, P.-H. [Los Alamos National Laboratory, Los Alamos, NM (United States); and others

    2016-08-21

    The MAJORANA collaboration is constructing the MAJORANA DEMONSTRATOR at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope {sup 76}Ge, to demonstrate the feasibility of a large-scale Ge detector experiment to search for neutrinoless double beta decay. The long half-life of this postulated process requires that the apparatus be extremely low in radioactive isotopes whose decays may produce backgrounds to the search. The radioassay program conducted by the collaboration to ensure that the materials comprising the apparatus are sufficiently pure is described. The resulting measurements from gamma-ray counting, neutron activation and mass spectroscopy of the radioactive-isotope contamination for the materials studied for use in the detector are reported. We interpret these numbers in the context of the expected background for the experiment.

  6. The MAJORANA DEMONSTRATOR radioassay program

    Science.gov (United States)

    Abgrall, N.; Arnquist, I. J.; Avignone, F. T.; Back, H. O.; Barabash, A. S.; Bertrand, F. E.; Boswell, M.; Bradley, A. W.; Brudanin, V.; Busch, M.; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Chu, P.-H.; Cuesta, C.; Detwiler, J. A.; Dunmore, J. A.; Efremenko, Yu.; Ejiri, H.; Elliott, S. R.; Finnerty, P.; Galindo-Uribarri, A.; Gehman, V. M.; Gilliss, T.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I. S.; Guiseppe, V. E.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Jasinski, B. R.; Johnson, R. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Martin, R. D.; Massarczyk, R.; Meijer, S.; Mertens, S.; Miller, M. L.; Orrell, J. L.; O'Shaughnessy, C.; Overman, N. R.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, A. G.; Shanks, B.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Steele, D.; Suriano, A. M.; Tedeschi, D.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, C.-H.; Yumatov, V.; Zhitnikov, I.

    2016-08-01

    The MAJORANA collaboration is constructing the MAJORANA DEMONSTRATOR at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope 76Ge, to demonstrate the feasibility of a large-scale Ge detector experiment to search for neutrinoless double beta decay. The long half-life of this postulated process requires that the apparatus be extremely low in radioactive isotopes whose decays may produce backgrounds to the search. The radioassay program conducted by the collaboration to ensure that the materials comprising the apparatus are sufficiently pure is described. The resulting measurements from gamma-ray counting, neutron activation and mass spectroscopy of the radioactive-isotope contamination for the materials studied for use in the detector are reported. We interpret these numbers in the context of the expected background for the experiment.

  7. Measurement quality assurance for radioassay laboratories

    Energy Technology Data Exchange (ETDEWEB)

    McCurdy, D.E. [Yankee Atomic Environmental Laboratory, Boston, MA (United States)

    1993-12-31

    Until recently, the quality of U.S. radioassay laboratory services has been evaluated by a limited number of governmental measurement assurance programs (MAPs). The major programs have been limited to the U.S. Department of Energy (DOE), the U.S. Environmental Protection Agency (EPA) and the U.S. Nuclear Regulatory Commission (NRC). In 1988, an industry MAP was established for the nuclear power utility industry through the U.S. Council for Energy Awareness/National Institute of Standards and Technology (USCEA/NIST). This program functions as both a MAP for utility laboratories and/or their commercial contractor laboratories, and as a traceability program for the U.S. radioactive source manufacturers and the utility laboratories. Each of these generic MAPs has been initiated and is maintained to serve the specific needs of the sponsoring agency or organization. As a result, there is diversification in their approach, scope, requirements, and degree of traceability to NIST. In 1987, a writing committee was formed under the American National Standards Institute (ANSI) N42.2 committee to develop a standard to serve as the basis document for the creation of a national measurement quality assurance (MQA) program for radioassay laboratories in the U.S. The standard is entitled, {open_quotes}Measurement Quality Assurance For Radioassay Laboratories.{open_quotes} The document was developed to serve as a guide for MQA programs maintained for the specialized sectors of the radioassay community, such as bioassay, routine environmental monitoring, environmental restoration and waste management, radiopharmaceuticals, and nuclear facilities. It was the intent of the writing committee to develop a guidance document that could be utilized to establish a laboratory`s specific data quality objectives (DQOs) that govern the operational requirements of the radioassay process, including mandated protocols and recommendations.

  8. Detergent activation of the binding protein in the folate radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, S.I.; Holm, J.; Lyngbye, J.

    1982-01-01

    A minor cow's whey protein associated with ..beta..-lactoglobulin is used as binding protein in the competitive radioassay for serum and erythrocyte folate. Seeking to optimize the assay, we tested the performance of binder solutions of increasing purity. The folate binding protein was isolated from cow's whey by means of CM-Sepharose CL-6B cation-exchange chromatography, and further purified on a methotrexate-AH-Sepharose 4B affinity matrix. In contrast to ..beta..-lactoglobulin, the purified protein did not bind folate unless the detergents cetyltrimethylammonium (10 mmol/Ll) or Triton X-100 (1 g/L) were present. Such detergent activation was not needed in the presence of serum. There seems to be a striking analogy between these phenomena and the well-known reactivation of certain purified membrane-derived enzymes by surfactants (lipids/detergents).

  9. Protein Binding Pocket Dynamics.

    Science.gov (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  10. Protein binding assay for hyaluronate

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, B.E.; Underhill, C.B.

    1986-11-01

    A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity, and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, they used a competition assay in which the binding of a set amount of (/sup 3/H)hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. They have found that this method is sensitive to 1 ..mu..g or less of hyaluronate, and is unaffected by the presence of proteins.

  11. Marshall Island radioassay quality assurance program an overview

    Energy Technology Data Exchange (ETDEWEB)

    Conrado, C.L.; Hamilton, T.F.; Kehl, S.R.; Robison, W.L.; Stoker, A.C.

    1998-09-01

    The Lawrence Livermore National Laboratory has developed an extensive quality assurance program to provide high quality data and assessments in support of the Marshall Islands Dose Assessment and Radioecology Program. Our quality assurance objectives begin with the premise of providing integrated and cost-effective program support (to meet wide-ranging programmatic needs, scientific peer review, litigation defense, and build public confidence) and continue through from design and implementation of large-scale field programs, sampling and sample preparation, radiometric and chemical analyses, documentation of quality assurance/quality control practices, exposure assessments, and dose/risk assessments until publication. The basic structure of our radioassay quality assurance/quality control program can be divided into four essential elements; (1) sample and data integrity control; (2) instrument validation and calibration; (3) method performance testing, validation, development and documentation; and (4) periodic peer review and on-site assessments. While our quality assurance objectives are tailored towards a single research program and the evaluation of major exposure pathways/critical radionuclides pertinent to the Marshall Islands, we have attempted to develop quality assurance practices that are consistent with proposed criteria designed for laboratory accre

  12. Haptenation: Chemical Reactivity and Protein Binding

    Directory of Open Access Journals (Sweden)

    Itai Chipinda

    2011-01-01

    Full Text Available Low molecular weight chemical (LMW allergens are commonly referred to as haptens. Haptens must complex with proteins to be recognized by the immune system. The majority of occupationally related haptens are reactive, electrophilic chemicals, or are metabolized to reactive metabolites that form covalent bonds with nucleophilic centers on proteins. Nonelectrophilic protein binding may occur through disulfide exchange, coordinate covalent binding onto metal ions on metalloproteins or of metal allergens, themselves, to the major histocompatibility complex. Recent chemical reactivity kinetic studies suggest that the rate of protein binding is a major determinant of allergenic potency; however, electrophilic strength does not seem to predict the ability of a hapten to skew the response between Th1 and Th2. Modern proteomic mass spectrometry methods that allow detailed delineation of potential differences in protein binding sites may be valuable in predicting if a chemical will stimulate an immediate or delayed hypersensitivity. Chemical aspects related to both reactivity and protein-specific binding are discussed.

  13. Competition

    NARCIS (Netherlands)

    Boone, J.

    2000-01-01

    Competition has been modelled in the literature in a number of ways.What do these different parametrizations of competition have in common?For instance, it turns out that it is not always the case that a rise in competition reduces price cost margins, industry wide profits or concentration.All param

  14. Competition.

    Science.gov (United States)

    Chambers, D W

    1997-01-01

    Our ambivalence toward competition can be traced to an unspoken preference for certain types of competition which give us an advantage over the types we value less. Four types are defined (a) pure (same rules, same objectives), (b) collaborative (same rules, shared objective), (c) market share (different rules, same objectives), and (d) market growth (different rules, value added orientation). The defining characteristics of the four types of competition are respectively: needing a referee, arguing over the spoils, differentiation and substitutability, and customer focus. Dentistry has features of all four types of competition, thus making it difficult to have a meaningful discussion or frame a coherent policy on this topic.

  15. Competition

    NARCIS (Netherlands)

    F. Bridoux

    2014-01-01

    Competition traditionally refers to the actions that firms take in a product market to outperform rivals in attracting customers and generating revenues. Yet, competition extends beyond product markets to other arenas such as factor markets, where firms compete for resources, and the political arena

  16. Protein binding prodrugs : Synthesis and protein binding studies of didanonsine derivates

    OpenAIRE

    Olberg, Dag Erlend

    2004-01-01

    A novel series of 5 -O-ester prodrugs of the anti-HIV drug 2 ,3 -dideoxyinosine (ddI,didanosine) were synthesized for the purpose of increasing protein binding. Hope was that these derivates would exhibit superior pharmacodynamic and pharmacokinetic properties against HIV-infection than the parent drug, didanosine. Ten compounds were synthesized, five fatty acid derivates and five dicarboxylic acid monoester derivates. The fatty acid- and dicarboxylic acid derivates had the sam...

  17. High-throughput prediction of RNA, DNA and protein binding regions mediated by intrinsic disorder.

    Science.gov (United States)

    Peng, Zhenling; Kurgan, Lukasz

    2015-10-15

    Intrinsically disordered proteins and regions (IDPs and IDRs) lack stable 3D structure under physiological conditions in-vitro, are common in eukaryotes, and facilitate interactions with RNA, DNA and proteins. Current methods for prediction of IDPs and IDRs do not provide insights into their functions, except for a handful of methods that address predictions of protein-binding regions. We report first-of-its-kind computational method DisoRDPbind for high-throughput prediction of RNA, DNA and protein binding residues located in IDRs from protein sequences. DisoRDPbind is implemented using a runtime-efficient multi-layered design that utilizes information extracted from physiochemical properties of amino acids, sequence complexity, putative secondary structure and disorder and sequence alignment. Empirical tests demonstrate that it provides accurate predictions that are competitive with other predictors of disorder-mediated protein binding regions and complementary to the methods that predict RNA- and DNA-binding residues annotated based on crystal structures. Application in Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila melanogaster proteomes reveals that RNA- and DNA-binding proteins predicted by DisoRDPbind complement and overlap with the corresponding known binding proteins collected from several sources. Also, the number of the putative protein-binding regions predicted with DisoRDPbind correlates with the promiscuity of proteins in the corresponding protein-protein interaction networks. Webserver: http://biomine.ece.ualberta.ca/DisoRDPbind/.

  18. Competition

    Institute of Scientific and Technical Information of China (English)

    吕思思

    2007-01-01

    <正> The term competition reminds me of asoul-stirring fight between a mother monkeyand a crocodile,The crocodile caught her babywhen the baby was drinking water in a pool,Inthe end,the mother got her baby,but herbaby’s body only,She lost her child forever,just for a mouthful of water.Such is competition,cruel and merciless,But if we see the other side of the coin,we’ll

  19. Grafting of protein-protein binding sites

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of ligand protein to be grafted are identified and suitable positions in scaffold protein for grafting these key residues are sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding Ca and Cb atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position. And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein by statistical analysis of rigid binding data sets.

  20. Competition

    CERN Multimedia

    Staff Association

    2017-01-01

    Get ready for the Easter Egg Hunt! The Staff Association is organising a competition from 10 to 21 April 2017. There are several Go Sport gift vouchers to win, with a value of 50 € each. Try your luck! Count the number of different eggs that we have hidden on our website. Then indicate your answer in the online form. To participate, you just need to be a member of the Staff Association. Winners will be randomly drawn among the correct answers.

  1. Competition

    CERN Multimedia

    Staff Association

    2016-01-01

      The Staff Association is organising a competition from 13 to 21 December 2016. There are several Go Sport vouchers to win with a value of 50 € each. Try your luck! To participate, you just have to be a member of the Staff Association and take the online quiz: https://ap-vote.web.cern.ch/content/jeu-concours-de-noel. The winners will be drawn among the correct answers.

  2. Competition

    CERN Multimedia

    Staff Association

    2016-01-01

      The Staff Association is organising a competition from April 11 to 20. There are several Go Sport gift vouchers with a value of 50 € each to win. Try your luck! To participate, you just have to be a member of the Staff Association and take the online quiz: https://ap-vote.web.cern.ch/content/jeu-concours. The winners will be drawn among the correct answers.

  3. Use of vitamin B/sub 12/ radioassay in the analysis of biological materials, mainly of foods

    Energy Technology Data Exchange (ETDEWEB)

    Kralova, B.; Rauch, P.; Cerna, J. (Inst. of Chemical Technology, Prague (Czechoslovakia). Dept. of Biochemistry and Microbiology; Research Inst. of Food Industry, Prague (Czechoslovakia))

    1982-01-01

    Vitamin B/sub 12/ was determined in biological materials by three basically different methods: microbiological assay with Lactobacillus leichmannii, microbiological assay with Escherichia coli and radioassay. The method with E. coli has a relatively low sensitivity to vitamin B/sub 12/ and in some cases of vitamin B/sub 12/ determination in microbial materials it can be used only after a separation of the interfering substances by gel chromatography. The procedure is suitable for orientational determinations of vitamin B/sub 12/ because it is very little affected by external factors. The assay with L. leichmannii is universal owing to its high specifity and sensitivity to vitamin B/sub 12/. The main disadvantage of the latter procedure depends on the high requirements for a clean atmosphere which can be maintained in laboratories in industrial areas only with difficulties. These limitations do not apply to the quick and sensitive radioassay. The radioassay can be used after a suitable adjustment of the working procedure for large series of analyses of biological materials without any preliminary separational techniques.

  4. PRELIMINARY STUDY OF EXTRACTABLE PROTEIN BINDING USING MALEIC ANHYDRIDE COPOLYMER

    Institute of Scientific and Technical Information of China (English)

    Thirawan Nipithakul; Ladawan Watthanachote; Nanticha Kalapat

    2012-01-01

    A preliminary study of using maleic anhydride copolymer for protein binding has been carried out.The polymeric films were prepared by compression of the purified resin and annealing the film to induce efficient back formation of the anhydride groups.The properties of the film surface were analyzed by attenuated total reflection Fourier transforms infrared spectroscopy and water contact angle measurements.The protein content was determined by Bradford assay.To obtain optimum conditions,immersion time for protein binding was examined.Results revealed that proteins can be successfully immobilized onto the film surface via covalent linkage.The efficiency of the covalent binding of the extractable protein to maleic anhydride-polyethylene film was estimated at 69.87 μtg/cm2,although the film had low anhydride content (3%) on the surface.

  5. QSAR Models for the Prediction of Plasma Protein Binding

    Directory of Open Access Journals (Sweden)

    Zeshan Amin

    2013-02-01

    Full Text Available Introduction: The prediction of plasma protein binding (ppb is of paramount importance in the pharmacokinetics characterization of drugs, as it causes significant changes in volume of distribution, clearance and drug half life. This study utilized Quantitative Structure – Activity Relationships (QSAR for the prediction of plasma protein binding. Methods: Protein binding values for 794 compounds were collated from literature. The data was partitioned into a training set of 662 compounds and an external validation set of 132 compounds. Physicochemical and molecular descriptors were calculated for each compound using ACD labs/logD, MOE (Chemical Computing Group and Symyx QSAR software packages. Several data mining tools were employed for the construction of models. These included stepwise regression analysis, Classification and Regression Trees (CART, Boosted trees and Random Forest. Results: Several predictive models were identified; however, one model in particular produced significantly superior prediction accuracy for the external validation set as measured using mean absolute error and correlation coefficient. The selected model was a boosted regression tree model which had the mean absolute error for training set of 13.25 and for validation set of 14.96. Conclusion: Plasma protein binding can be modeled using simple regression trees or multiple linear regressions with reasonable model accuracies. These interpretable models were able to identify the governing molecular factors for a high ppb that included hydrophobicity, van der Waals surface area parameters, and aromaticity. On the other hand, the more complicated ensemble method of boosted regression trees produced the most accurate ppb estimations for the external validation set.

  6. Schistosoma mansoni: quantification of skin penetration and early migration by differential external radioassay and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Georgi, J.R. (New York State College of Veterinary Medicine, Ithaca (USA))

    1982-04-01

    Eleven gamma-emitting radionuclides (/sup 49/Sc, /sup 54/Mn, /sup 59/Fe, /sup 60/Co, /sup 65/Zn, /sup 75/Se (as selenomethionine, selenocystine, selenite and selenate), /sup 109/Cd, /sup 125/Sb, /sup 133/Ba, /sup 137/Cs and /sup 203/Hg) were screened as labelling agents for Schistosoma mansoni cercariae by incubation of infected Biomphalaria glabrata snails in radioactive solution. Only (/sup 75/Se)methionine yielded satisfactorily labelled cercariae. Differential external radioassay, a new technique employing partial body shielding within a total body counter, permitted separate estimation of tail and body radioactivity of conscious mice previously exposed by tail immersion to /sup 75/Se-labelled cercariae, with measurements repeated as often as desired. Approximately 39% of the /sup 75/Se present in emergent cercariae was retained by schistosomula transformed in vitro but this was subject to considerable variation, especially in schistosomula transformed in vivo. Secreted or catabolized label from penetrant cercariae and schistosomula was rapidly removed from the skin by the bloodstream. Numbers of schistosomula in tail skin were directly proportional to the number of reduced silver foci counted on tail autoradiograms; only a very small fraction of tail radioactivity represented unbound ('spurious') label. Migration of schistosomula away from skin was 50% complete at 3.8-4.3 days, as determined by probit analysis of autoradiographic data.

  7. Decreased protein binding of moxifloxacin in patients with sepsis?

    Directory of Open Access Journals (Sweden)

    Dorn, Christoph

    2017-02-01

    Full Text Available The mean (SD unbound fraction of moxifloxacin in plasma from patients with severe sepsis or septic shock was determined by ultrafiltration to 85.5±3.0% (range 81.9 and 91.6% indicating a decreased protein binding of moxifloxacin in this population compared with the value of 58–60% provided in the Summary of Product Characteristics. However, previous investigations neglected the influence of pH and temperature on the protein binding of moxifloxacin. Maintaining physiological conditions (pH 7.4, 37°C – as in the present study – the unbound fraction of moxifloxacin in plasma from healthy volunteers was 84%. In contrast, the unbound fraction of moxifloxacin was 77% at 4°C and 66–68% in unbuffered plasma or at pH 8.5 in fair agreement with previously published data. PK/PD parameters e.g. AUC/MIC or ratios between interstitial fluid and free plasma concentrations, which were obtained assuming a protein binding rate of moxifloxacin of 40% or more, should be revised.

  8. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  9. RNA-protein binding kinetics in an automated microfluidic reactor.

    Science.gov (United States)

    Ridgeway, William K; Seitaridou, Effrosyni; Phillips, Rob; Williamson, James R

    2009-11-01

    Microfluidic chips can automate biochemical assays on the nanoliter scale, which is of considerable utility for RNA-protein binding reactions that would otherwise require large quantities of proteins. Unfortunately, complex reactions involving multiple reactants cannot be prepared in current microfluidic mixer designs, nor is investigation of long-time scale reactions possible. Here, a microfluidic 'Riboreactor' has been designed and constructed to facilitate the study of kinetics of RNA-protein complex formation over long time scales. With computer automation, the reactor can prepare binding reactions from any combination of eight reagents, and is optimized to monitor long reaction times. By integrating a two-photon microscope into the microfluidic platform, 5-nl reactions can be observed for longer than 1000 s with single-molecule sensitivity and negligible photobleaching. Using the Riboreactor, RNA-protein binding reactions with a fragment of the bacterial 30S ribosome were prepared in a fully automated fashion and binding rates were consistent with rates obtained from conventional assays. The microfluidic chip successfully combines automation, low sample consumption, ultra-sensitive fluorescence detection and a high degree of reproducibility. The chip should be able to probe complex reaction networks describing the assembly of large multicomponent RNPs such as the ribosome.

  10. Determination of vitamin D in fortified and nonfortified milk powder and infant formula using a specific radioassay after purification by high-performance liquid chromatography

    NARCIS (Netherlands)

    Berg, H. van den; Boshuis, P.G.; Schreurs, W.H.P.

    1986-01-01

    A reliable and sensitive radioassay is described for the determination of vitamin D in milk powder and infant formula. After saponification of the sample interfering compounds like sterols are removed by digitonin precipitation and chromatography on small columns packed with alumina. [3H] Vitamin D

  11. Determination of vitamin D in fortified and nonfortified milk powder and infant formula using a specific radioassay after purification by high-performance liquid chromatography

    NARCIS (Netherlands)

    Berg, H. van den; Boshuis, P.G.; Schreurs, W.H.P.

    1986-01-01

    A reliable and sensitive radioassay is described for the determination of vitamin D in milk powder and infant formula. After saponification of the sample interfering compounds like sterols are removed by digitonin precipitation and chromatography on small columns packed with alumina. [3H] Vitamin D

  12. SCOWLP classification: Structural comparison and analysis of protein binding regions

    Directory of Open Access Journals (Sweden)

    Anders Gerd

    2008-01-01

    Full Text Available Abstract Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions

  13. Differential plasma protein binding to metal oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Zhou J; Mortimer, Gysell; Minchin, Rodney F [School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072 (Australia); Schiller, Tara; Musumeci, Anthony; Martin, Darren, E-mail: r.minchin@uq.edu.a [Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072 (Australia)

    2009-11-11

    Nanoparticles rapidly interact with the proteins present in biological fluids, such as blood. The proteins that are adsorbed onto the surface potentially dictate the biokinetics of the nanomaterials and their fate in vivo. Using nanoparticles with different sizes and surface characteristics, studies have reported the effects of physicochemical properties on the composition of adsorbed plasma proteins. However, to date, few studies have been conducted focusing on the nanoparticles that are commonly exposed to the general public, such as the metal oxides. Using previously established ultracentrifugation approaches, two-dimensional gel electrophoresis and mass spectrometry, the current study investigated the binding of human plasma proteins to commercially available titanium dioxide, silicon dioxide and zinc oxide nanoparticles. We found that, despite these particles having similar surface charges in buffer, they bound different plasma proteins. For TiO{sub 2}, the shape of the nanoparticles was also an important determinant of protein binding. Agglomeration in water was observed for all of the nanoparticles and both TiO{sub 2} and ZnO further agglomerated in biological media. This led to an increase in the amount and number of different proteins bound to these nanoparticles. Proteins with important biological functions were identified, including immunoglobulins, lipoproteins, acute-phase proteins and proteins involved in complement pathways and coagulation. These results provide important insights into which human plasma proteins bind to particular metal oxide nanoparticles. Because protein absorption to nanoparticles may determine their interaction with cells and tissues in vivo, understanding how and why plasma proteins are adsorbed to these particles may be important for understanding their biological responses.

  14. Competitive binding radioassays for 1 -25(OH)2 vitamin D; comparative evaluation of two receptor assays and a radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Jallet, P.; Bidet, M.; Audran, M.

    1985-01-01

    The performances of a 1 ,25-dihydroxy vitamin D assay using the cytosol receptor of bovine thymus gland were evaluated and compared to the results obtained with an assay based on cytosol receptor of chick intestine and with a radioimmunoassay.

  15. The role of the EPA radiation quality assurance program in the measurement quality assurance accreditation program for radioassay laboratories

    Energy Technology Data Exchange (ETDEWEB)

    Grady, T.M. [Environmental Monitoring Systems Laboratory, Las Vegas, NV (United States)

    1993-12-31

    As the nature and extent of radiological contamination becomes better documented and more public, radioanalytical laboratories are faced with a constantly expanding variety of new and difficult analytical requirements. Concurrent with those requirements is the responsibility to provide customers, regulatory officials, or the public with defensible data produced in an environment of verifiable, controlled quality. To meet that need, a quality assurance accreditation program for radioassay laboratories has been proposed by the American National Standards Institute (ANSI). The standard will provide the organizational framework and functional requirements needed to assure the quality of laboratory outputs. Under the proposed program, the U.S. Environmental Protection Agency`s (EPA`s) Laboratory Intercomparison Program plays a key role as a reference laboratory. The current and proposed roles of the EPA Intercomparison Program are discussed, as are the functional relationships between EPA, the accreditating organization, and the service and monitoring laboratories.

  16. Convolutional neural network architectures for predicting DNA–protein binding

    Science.gov (United States)

    Zeng, Haoyang; Edwards, Matthew D.; Liu, Ge; Gifford, David K.

    2016-01-01

    Motivation: Convolutional neural networks (CNN) have outperformed conventional methods in modeling the sequence specificity of DNA–protein binding. Yet inappropriate CNN architectures can yield poorer performance than simpler models. Thus an in-depth understanding of how to match CNN architecture to a given task is needed to fully harness the power of CNNs for computational biology applications. Results: We present a systematic exploration of CNN architectures for predicting DNA sequence binding using a large compendium of transcription factor datasets. We identify the best-performing architectures by varying CNN width, depth and pooling designs. We find that adding convolutional kernels to a network is important for motif-based tasks. We show the benefits of CNNs in learning rich higher-order sequence features, such as secondary motifs and local sequence context, by comparing network performance on multiple modeling tasks ranging in difficulty. We also demonstrate how careful construction of sequence benchmark datasets, using approaches that control potentially confounding effects like positional or motif strength bias, is critical in making fair comparisons between competing methods. We explore how to establish the sufficiency of training data for these learning tasks, and we have created a flexible cloud-based framework that permits the rapid exploration of alternative neural network architectures for problems in computational biology. Availability and Implementation: All the models analyzed are available at http://cnn.csail.mit.edu. Contact: gifford@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307608

  17. Interspecies In Vitro Evaluation of Stereoselective Protein Binding for 3,4-Methylenedioxymethamphetamine

    Directory of Open Access Journals (Sweden)

    Wan Raihana Wan Aasim

    2017-01-01

    Full Text Available Abuse of 3,4-methylenedioxymethamphetamine (MDMA is becoming more common worldwide. To date, there is no information available on stereoselectivity of MDMA protein binding in humans, rats, and mice. Since stereoselectivity plays an important role in MDMA’s pharmacokinetics and pharmacodynamics, in this study we investigated its stereoselectivity in protein binding. The stereoselective protein binding of rac-MDMA was investigated using two different concentrations (20 and 200 ng/mL in human plasma and mouse and rat sera using an ultrafiltration technique. No significant stereoselectivity in protein binding was observed in both human plasma and rat serum; however, a significant stereoselective binding (p<0.05 was observed in mouse serum. Since the protein binding of MDMA in mouse serum is considerably lower than in humans and rats, caution should be exercised when using mice for in vitro studies involving MDMA.

  18. In vitro plasma protein binding and aqueous aggregation behavior of astaxanthin dilysinate tetrahydrochloride.

    Science.gov (United States)

    Zsila, Ferenc; Fitos, Ilona; Bikádi, Zsolt; Simonyi, Miklós; Jackson, Henry L; Lockwood, Samuel F

    2004-11-01

    The tetrahydrochloride salt of astaxanthin di-L-lysinate (lys(2)AST) is a highly water-dispersible astaxanthin-amino acid conjugate, with an aqueous dispersibility of > or = 181.6 mg/mL. The statistical mixture of stereoisomers has been well characterized as an aqueous-phase superoxide anion scavenger, effective at micromolar (microM) concentrations. In the current study, the aqueous aggregation behavior and in vitro plasma protein binding [with fatty-acid-free human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP)] were investigated with a suite of techniques, including circular dichroism (CD) and UV-vis spectroscopy, ultrafiltration, competitive ligand displacement, and fluorescence quenching. Induced CD bands obtained in Ringer buffer solution of HSA demonstrated high affinity monomeric binding of the compound at low ligand per protein (L/P) ratios (in aqueous solution alone the carotenoid molecules formed card-pack aggregates). The binding constant ( approximately 10(6)M(-1)) and the binding stoichiometry (approximately 0.2 per albumin molecule) were calculated from CD titration data. CD displacement and ultrafiltration experiments performed with marker ligands of HSA indicated that the ligand binding occurred at a site distinct from the main drug binding sites of HSA (i.e., Sites I and II). At intermediate L/P ratios, both monomeric and aggregated ("chirally complexed") binding occurred simultaneously at distinct sites of the protein. At high L/P ratios, chiral complexation predominantly occurred on the asymmetric protein template. The tentative location of the chirally-complexed aggregation on the HSA template was identified as the large interdomain cleft of HSA, where carotenoid derivatives have been found to bind previously. Only weak binding to AGP was observed. These results suggest that parenteral use of this highly potent, water-dispersible astaxanthin-amino acid conjugate will result in plasma protein association, and plasma protein binding at

  19. [Determination of plasma protein binding rate of arctiin and arctigenin with ultrafiltration].

    Science.gov (United States)

    Han, Xue-Ying; Wang, Wei; Tan, Ri-Qiu; Dou, De-Qiang

    2013-02-01

    To determine the plasma protein binding rate of arctiin and arctigenin. The ultrafiltration combined with HPLC was employed to determine the plasma protein binding rate of arctiin and arctigenin as well as rat plasma and healthy human plasma proteins. The plasma protein binding rate of arctiin with rat plasma at the concentrations of 64. 29, 32.14, 16.07 mg x L(-1) were (71.2 +/- 2.0)%, (73.4 +/- 0.61)%, (78.2 +/- 1.9)%, respectively; while the plasma protein binding rate of arctiin with healthy human plasma at the above concentrations were (64.8 +/- 3.1)%, (64.5 +/- 2.5)%, (77.5 +/- 1.7)%, respectively. The plasma protein binding rate of arctigenin with rat plasma at the concentrations of 77.42, 38.71, 19.36 mg x L(-1) were (96.7 +/- 0.41)%, (96.8 +/- 1.6)%, (97.3 +/- 0.46)%, respectively; while the plasma protein binding rate of arctigenin with normal human plasma at the above concentrations were (94.7 +/- 3.1)%, (96.8 +/- 1.6)%, (97.9 +/- 1.3)%, respectively. The binding rate of arctiin with rat plasma protein was moderate, which is slightly higher than the binding rate of arctiin with healthy human plasma protein. The plasma protein binding rates of arctigenin with both rat plasma and healthy human plasma are very high.

  20. Simultaneous radioassays of bacterial production and mercury methylation in the periphyton of a tropical and a temperate wetland.

    Science.gov (United States)

    Guimarães, J R D; Mauro, J B N; Meili, M; Sundbom, M; Haglund, A L; Coelho-Souza, S A; Hylander, L D

    2006-10-01

    Laboratory radioassays were made to study mercury (Hg) methylation together with bacterial production in the periphyton of two aquatic macrophytes, the submerged Myriophyllum spicatum, from a constructed wetland in Sweden and the floating Eichhornia crassipes, from a eutrophied tropical lake in Brazil. Time course incubations were made by addition of (203)HgCl(2) and the methylmercury formed was extracted at pre-defined time intervals. Bacterial production ((14)C-leucine incorporation) was measured at the same time intervals, with plants removed from parallel incubations made with and without addition of cold HgCl(2). For E. crassipes, higher methylmercury production was observed at elevated bacterial production, whereas for M. spicatum, the bacterial production was significantly lower, and Hg methylation was below the detection limit. The combined results confirm the importance of microbial processes for Hg methylation, although other factors are known to influence this process in complex ways. The addition of Hg did not significantly influence bacterial production, while the incubation temperatures used (25 and 35 degrees C) resulted in different methylation rates. Radiotracer techniques for measurements of bacterial production such as (14)C-leucine uptake can provide useful insights into the Hg cycle in aquatic environments, and our data suggest that they may be used as a proxy of mercury methylation potentials.

  1. Didanosine Prodrugs : Synthesis, protein binding, bioanalytical method development and pharmacokinetic studies

    OpenAIRE

    Høyem, Sverre

    2008-01-01

    A series of prodrugs of 2´, 3´-dideoxyinosine (didanosine, ddI) were synthesized in an effort to alter different pharmacokinetic properties. The 5`OH function of ddI was esterified with three different carboxylic diacids. The diacids used was adipic acid, azelaic acid, dodecanedioic acid. The synthesis was optimized in order to develop a high yielding and regioselective synthesis. Protein binding studies, using ultrafiltration, showed an increased protein binding compared to ddI itself....

  2. Membrane-protein binding measured with solution-phase plasmonic nanocube sensors.

    Science.gov (United States)

    Wu, Hung-Jen; Henzie, Joel; Lin, Wan-Chen; Rhodes, Christopher; Li, Zhu; Sartorel, Elodie; Thorner, Jeremy; Yang, Peidong; Groves, Jay T

    2012-12-01

    We describe a solution-phase sensor of lipid-protein binding based on localized surface plasmon resonance (LSPR) of silver nanocubes. When silica-coated nanocubes are mixed in a suspension of lipid vesicles, supported membranes spontaneously assemble on their surfaces. Using a standard laboratory spectrophotometer, we calibrated the LSPR peak shift due to protein binding to the membrane surface and then characterized the lipid-binding specificity of a pleckstrin homology domain protein.

  3. Using RNase sequence specificity to refine the identification of RNA-protein binding regions

    OpenAIRE

    Wang Xinguo; Li Lang; Shen Changyu; Wang Guohua; Wang Xin; Mooney Sean D; Edenberg Howard J; Sanford Jeremy R; Liu Yunlong

    2008-01-01

    Abstract Massively parallel pyrosequencing is a high-throughput technology that can sequence hundreds of thousands of DNA/RNA fragments in a single experiment. Combining it with immunoprecipitation-based biochemical assays, such as cross-linking immunoprecipitation (CLIP), provides a genome-wide method to detect the sites at which proteins bind DNA or RNA. In a CLIP-pyrosequencing experiment, the resolutions of the detected protein binding regions are partially determined by the length of the...

  4. Estimation of angiotensin-converting enzyme inhibitors protein binding degree using chromatographic hydrophobicity data

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna

    2015-01-01

    Full Text Available Introduction. Angiotensin-converting enzyme (ACE inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure. Objective. Selected ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril were studied in order to establish a fast and easy estimation method of their plasma protein binding degree based on their lipophilicity data. Methods. Chromatographic hydrophobicity data (parameter C0 were obtained on cellulose layers under conditions of normal-phase thin-layer chromatography (NPTLC, using different binary solvent systems. The ACE inhibitors lipophilicity descriptors (logP values were calculated using the software package Virtual Computational Chemistry Laboratory. The ACE inhibitors plasma protein binding data were collected from relevant literature. Results. ACE inhibitors protein binding data varied from negligible (lisinopril to 99% (fosinopril. The calculated lipophilicity descriptors, logPKOWWIN values ranged from -0.94 (lisinopril to 6.61 (fosinopril. Good correlations were established between plasma protein binding values and calculated logPKOWWIN values (R2=0.8026 as well as chromatographic hydrophobicity data, C0 parameters (R2=0.7662. Even though good correlation coefficients (R2 were obtained in both relations, unacceptable probability value with p>0.05 was found in relation between protein binding data and calculated logPKOWWIN values. Subsequently, taking into consideration the request for probability value lower than 0.05, a better relationship was observed between protein binding data and chromatographically obtained hydrophobicity parameters C0 values. Conclusion. Cellulose layers are easily available and cost effective sorbent to assess hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and plasma protein binding estimation are important parameters in evaluating bioavailability of these drugs. [Projekat Ministarstva

  5. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element.

    Science.gov (United States)

    Mao, Grace; Brody, James P

    2007-11-09

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014s(-1). We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase.

  6. Automation of plasma protein binding assay using rapid equilibrium dialysis device and Tecan workstation.

    Science.gov (United States)

    Ye, Zhengqi; Zetterberg, Craig; Gao, Hong

    2017-03-14

    Binding of drug molecules to plasma proteins is an important parameter in assessing drug ADME properties. Plasma protein binding (PPB) assays are routinely performed during drug discovery and development. A fully automated PPB assay was developed using rapid equilibrium dialysis (RED) device and Tecan workstation coupled to an automated incubator. The PPB assay was carried out in unsealed RED plates which allowed the assay to be fully automated. The plasma pH was maintained at 7.4 during the 6-h dialysis under 2% CO2 condition. The samples were extracted with acetonitrile and analyzed by liquid chromatography tandem mass spectrometry. The percent bound results of 10 commercial drugs in plasma protein binding were very similar between the automated and manual assays, and were comparable to literature values. The automated assay increases laboratory productivity and is applicable to high-throughput screening of drug protein binding in drug discovery.

  7. Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available detected in plasma was higher than that of uncoated PLGA particles, indicating that systemic circulation time can also be increased with oral formulations. The difference in the in vitro protein binding as a result of the different poloxamers used versus...

  8. Stability, protein binding and clearance studies of [99mTc]DTPA. Evaluation of a commercially available dry-kit

    DEFF Research Database (Denmark)

    Rehling, M

    1988-01-01

    the quality of a commercial [99mTc]DTPA preparation (C.I.S., France) with reference to stability, protein binding and accuracy of the determined plasma clearance values as a measure of GFR. The stability of the preparations was studied by thin-layer chromatography, the in vitro protein binding by Sephadex...

  9. A novel injection strategy of flurbiprofen axetil by inhibiting protein binding with 6-methoxy-2-naphthylacetic acid.

    Science.gov (United States)

    Ogata, Kenji; Takamura, Norito; Tokunaga, Jin; Ikeda, Tetsuya; Setoguchi, Nao; Tanda, Kazuhiro; Yamasaki, Tetsuo; Nishio, Toyotaka; Kawai, Keiichi

    2016-04-01

    Flurbiprofen axetil (FPA) is an injection product and a prodrug of a non-steroidal anti-inflammatory drug (NSAID). After injection, it is rapidly hydrolyzed to the active form, flurbiprofen (FP). Since frequent injections of FPA can lead to abnormal physiology, an administration strategy is necessary to ensure there is enhancement of the analgesic efficiency of FP after a single dose and to reduce the total number of doses. FP strongly binds to site II of albumin, and thus the free (unbound) FP concentration is low. This study focused on 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone (a prodrug of NSAID). We performed ultrafiltration experiments and pharmacokinetics analysis in rats to investigate whether the inhibitory effect of 6-MNA on FP binding to albumin increased the free FP concentration in vitro and in vivo. Results indicated that 6-MNA inhibited the binding of FP to albumin competitively. When 6-MNA was injected in rats, there was a significant increase in the free FP concentration and the area under concentration-time curve (AUC) calculated from the free FP concentration, while there was a significant decrease in the total (bound + free) FP concentration and the AUC calculated from the total FP concentration. These findings indicate that 6-MNA inhibits the protein binding of FP in vivo. This suggests that the frequency of FPA injections can be reduced when administered with nabumetone, as there is increase in the free FP concentration associated with pharmacological effect.

  10. Mechanisms of photoisomerization of polyenes in confined media: from organic glasses to protein binding cavities.

    Science.gov (United States)

    Liu, Robert S H; Yang, Lan-Ying; Liu, Jin

    2007-01-01

    Photochemical reactivities of model organic systems (stilbene and diphenylbutadiene) in organic glasses were first examined and compared with those in solution and in organized media. These observations were in turn compared with reactivities of polyene chromophores in protein binding cavities (specifically PYP, rhodopsin and bacteriorhodopsin). The obvious conclusion is that the preference for the most volume-conserving Hula-twist mechanism isomerization in organic glasses is because of the close interaction between the guest and the host molecules. In organized media (zeolites, crystals and protein binding cavities), the residual empty space coupled with any specific guest-host interactions that are characteristic of a given system, could lead to involvement of the more volume-demanding one-bond-flip (i.e. torsional relaxation) or bicycle-pedal or an extended HT process in photoisomerization.

  11. A general approach to visualize protein binding and DNA conformation without protein labelling.

    Science.gov (United States)

    Song, Dan; Graham, Thomas G W; Loparo, Joseph J

    2016-01-01

    Single-molecule manipulation methods, such as magnetic tweezers and flow stretching, generally use the measurement of changes in DNA extension as a proxy for examining interactions between a DNA-binding protein and its substrate. These approaches are unable to directly measure protein-DNA association without fluorescently labelling the protein, which can be challenging. Here we address this limitation by developing a new approach that visualizes unlabelled protein binding on DNA with changes in DNA conformation in a relatively high-throughput manner. Protein binding to DNA molecules sparsely labelled with Cy3 results in an increase in fluorescence intensity due to protein-induced fluorescence enhancement (PIFE), whereas DNA length is monitored under flow of buffer through a microfluidic flow cell. Given that our assay uses unlabelled protein, it is not limited to the low protein concentrations normally required for single-molecule fluorescence imaging and should be broadly applicable to studying protein-DNA interactions.

  12. Prediction of protein binding sites in protein structures using hidden Markov support vector machine

    Directory of Open Access Journals (Sweden)

    Lin Lei

    2009-11-01

    Full Text Available Abstract Background Predicting the binding sites between two interacting proteins provides important clues to the function of a protein. Recent research on protein binding site prediction has been mainly based on widely known machine learning techniques, such as artificial neural networks, support vector machines, conditional random field, etc. However, the prediction performance is still too low to be used in practice. It is necessary to explore new algorithms, theories and features to further improve the performance. Results In this study, we introduce a novel machine learning model hidden Markov support vector machine for protein binding site prediction. The model treats the protein binding site prediction as a sequential labelling task based on the maximum margin criterion. Common features derived from protein sequences and structures, including protein sequence profile and residue accessible surface area, are used to train hidden Markov support vector machine. When tested on six data sets, the method based on hidden Markov support vector machine shows better performance than some state-of-the-art methods, including artificial neural networks, support vector machines and conditional random field. Furthermore, its running time is several orders of magnitude shorter than that of the compared methods. Conclusion The improved prediction performance and computational efficiency of the method based on hidden Markov support vector machine can be attributed to the following three factors. Firstly, the relation between labels of neighbouring residues is useful for protein binding site prediction. Secondly, the kernel trick is very advantageous to this field. Thirdly, the complexity of the training step for hidden Markov support vector machine is linear with the number of training samples by using the cutting-plane algorithm.

  13. Protein-binding affinity of leucaena condensed tannins of differing molecular weights.

    Science.gov (United States)

    Huang, Xiao Dan; Liang, Juan Boo; Tan, Hui Yin; Yahya, Rosiyah; Long, Ruijun; Ho, Yin Wan

    2011-10-12

    Depending on their source, concentration, chemical structure, and molecular weight, condensed tannins (CTs) form insoluble complexes with protein, which could lead to ruminal bypass protein, benefiting animal production. In this study, CTs from Leuceana leucocephala hybrid were fractionated into five fractions by a size exclusion chromatography procedure. The molecular weights of the CT fractions were determined using Q-TOF LC-MS, and the protein-binding affinities of the respective CT fractions were determined using a protein precipitation assay with bovine serum albumin (BSA) as the standard protein. The calculated number-average molecular weights (M(n)) were 1348.6, 857.1, 730.1, 726.0, and 497.1, and b values (the b value represents the CT quantity that is needed to bind half of the maximum precipitable BSA) of the different molecular weight fractions were 0.381, 0.510, 0.580, 0.636, and 0.780 for fractions 1, 2, 3, 4, and 5, respectively. The results indicated that, in general, CTs of higher molecular weight fractions have stronger protein-binding affinity than those of lower molecular weights. However, the number of hydroxyl units within the structure of CT polymers also affects the protein-binding affinity.

  14. OB protein binds specifically to the choroid plexus of mice and rats.

    Science.gov (United States)

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-05-28

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor.

  15. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  16. An integrated bioanalytical platform for supporting high-throughput serum protein binding screening.

    Science.gov (United States)

    Zhang, Jun; Shou, Wilson Z; Vath, Marianne; Kieltyka, Kasia; Maloney, Jennifer; Elvebak, Larry; Stewart, Jeremy; Herbst, John; Weller, Harold N

    2010-12-30

    Quantification of small molecules using liquid chromatography/tandem mass spectrometry (LC/MS/MS) on a triple quadrupole mass spectrometer has become a common practice in bioanalytical support of in vitro adsorption, distribution, metabolism and excretion (ADME) screening. The bioanalysis process involves primarily three indispensable steps: MS/MS optimization for a large number of new chemical compounds undergoing various screening assays in early drug discovery, high-throughput sample analysis with LC/MS/MS for those chemically diverse compounds using the optimized MS/MS conditions, and post-acquisition data review and reporting. To improve overall efficiency of ADME bioanalysis, an integrated system was proposed featuring an automated and unattended MS/MS optimization, a staggered parallel LC/MS/MS for high-throughput sample analysis, and a sophisticated software tool for LC/MS/MS raw data review as well as biological data calculation and reporting. The integrated platform has been used in bioanalytical support of a serum protein binding screening assay with high speed, high capacity, and good robustness. In this new platform, a unique sample dilution scheme was also introduced. With this dilution design, the total number of analytical samples was reduced; therefore, the total operation time was reduced and the overall throughput was further improved. The performance of the protein binding screening assay was monitored with two controls representing high and low binding properties and an acceptable inter-assay consistency was achieved. This platform has been successfully used for the determination of serum protein binding in multiple species for more than 4000 compounds.

  17. Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics.

    Science.gov (United States)

    Tan, Cheng; Terakawa, Tsuyoshi; Takada, Shoji

    2016-07-13

    Protein binding to DNA changes the DNA's structure, and altered DNA structure can, in turn, modulate the dynamics of protein binding. This mutual dependency is poorly understood. Here we investigated dynamic couplings among protein binding to DNA, protein sliding on DNA, and DNA bending by applying a coarse-grained simulation method to the bacterial architectural protein HU and 14 other DNA-binding proteins. First, we verified our method by showing that the simulated HU exhibits a weak preference for A/T-rich regions of DNA and a much higher affinity for gapped and nicked DNA, consistent with biochemical experiments. The high affinity was attributed to a local DNA bend, but not the specific chemical moiety of the gap/nick. The long-time dynamic analysis revealed that HU sliding is associated with the movement of the local DNA bending site. Deciphering single sliding steps, we found the coupling between HU sliding and DNA bending is akin to neither induced-fit nor population-shift; instead they moved concomitantly. This is reminiscent of a cation transfer on DNA and can be viewed as a protein version of polaron-like sliding. Interestingly, on shorter time scales, HU paused when the DNA was highly bent at the bound position and escaped from pauses once the DNA spontaneously returned to a less bent structure. The HU sliding is largely regulated by DNA bending dynamics. With 14 other proteins, we explored the generality and versatility of the dynamic coupling and found that 6 of the 15 assayed proteins exhibit the polaron-like sliding.

  18. Beta atomic contacts: identifying critical specific contacts in protein binding interfaces.

    Science.gov (United States)

    Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C H

    2013-01-01

    Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts.

  19. Beta atomic contacts: identifying critical specific contacts in protein binding interfaces.

    Directory of Open Access Journals (Sweden)

    Qian Liu

    Full Text Available Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts.

  20. Relating the shape of protein binding sites to binding affinity profiles: is there an association?

    Directory of Open Access Journals (Sweden)

    Bitter István

    2010-10-01

    Full Text Available Abstract Background Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses. Results PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors. Conclusions This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that

  1. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity.

    Science.gov (United States)

    Enoch, S J; Ellison, C M; Schultz, T W; Cronin, M T D

    2011-10-01

    Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the electrophilic reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated electrophilic reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated electrophilic reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.

  2. Improving the prediction of protein binding sites by combining heterogeneous data and Voronoi diagrams

    Directory of Open Access Journals (Sweden)

    Fernandez-Fuentes Narcis

    2011-08-01

    Full Text Available Abstract Background Protein binding site prediction by computational means can yield valuable information that complements and guides experimental approaches to determine the structure of protein complexes. Predictions become even more relevant and timely given the current resolution of protein interaction maps, where there is a very large and still expanding gap between the available information on: (i which proteins interact and (ii how proteins interact. Proteins interact through exposed residues that present differential physicochemical properties, and these can be exploited to identify protein interfaces. Results Here we present VORFFIP, a novel method for protein binding site prediction. The method makes use of broad set of heterogeneous data and defined of residue environment, by means of Voronoi Diagrams that are integrated by a two-steps Random Forest ensemble classifier. Four sets of residue features (structural, energy terms, sequence conservation, and crystallographic B-factors used in different combinations together with three definitions of residue environment (Voronoi Diagrams, sequence sliding window, and Euclidian distance have been analyzed in order to maximize the performance of the method. Conclusions The integration of different forms information such as structural features, energy term, evolutionary conservation and crystallographic B-factors, improves the performance of binding site prediction. Including the information of neighbouring residues also improves the prediction of protein interfaces. Among the different approaches that can be used to define the environment of exposed residues, Voronoi Diagrams provide the most accurate description. Finally, VORFFIP compares favourably to other methods reported in the recent literature.

  3. Arrest of rolling circle amplification by protein-binding DNA aptamers.

    Science.gov (United States)

    Wang, Lida; Tram, Kha; Ali, Monsur M; Salena, Bruno J; Li, Jinghong; Li, Yingfu

    2014-02-24

    Certain DNA polymerases, such as ϕ29 DNA polymerase, can isothermally copy the sequence of a circular template round by round in a process known as rolling circle amplification (RCA), which results in super-long single-stranded (ss) DNA molecules made of tandem repeats. The power of RCA reflects the high processivity and the strand-displacement ability of these polymerases. In this work, the ability of ϕ29DNAP to carry out RCA over circular templates containing a protein-binding DNA aptamer sequence was investigated. It was found that protein-aptamer interactions can prevent this DNA polymerase from reading through the aptameric domain. This finding indicates that protein-binding DNA aptamers can form highly stable complexes with their targets in solution. This novel observation was exploited by translating RCA arrest into a simple and convenient colorimetric assay for the detection of specific protein targets, which continues to showcase the versatility of aptamers as molecular recognition elements for biosensing applications.

  4. Development and Application of an HPLC Method for Erlotinib Protein Binding Studies

    Directory of Open Access Journals (Sweden)

    Soheila Bolandnazar

    2013-08-01

    Full Text Available Purpose: The aim of the present study was to develop a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection for erlotinib hydrochloride quantification, which is applicable for protein binding studies. Methods: Ultrafilteration method was used for protein binding study of erlotinib hydrochloride. For sample analysis a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 332 nm was developed. The mobile phase was a mixture of methanol, acetonitril and potassium dihydrogen phosphate buffer (15:45:40 %v/v set at flow rate of 1.3 ml/min. Results: The run time for erlotinib hydrochloride was approximately 6 minutes. The calibration curve was linear over the range of 320-20000 ng/ml with acceptable intra- and inter-day precision and accuracy. The intra-day and inter-day precisions were less than 10% and the accuracies of intra and inter-day assays were within the range of 97.20-104.83% and 98.8-102.2% respectively. Conclusion: Based on the obtained results, a simple, accurate and precise reversed-phase isocratic HPLC method with UV detection has been optimized and validated for the determination of erlotinib hydrochloride in biological samples.

  5. Correlation of antispermatozoal antibody with infertility in immunized female rabbits using /sup 14/C-protein A in a filter radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Eng, L.A.; Metz, C.B.

    1986-09-01

    The meaningful detection of antisperm antibody in immunologically infertile females has been confounded by the many methods of assay that exist. With many of these methods there is poor correlation of assay results with infertility. In this report, female rabbits were rendered partially or completely infertile by immunization with sperm fractions. A filter radioassay for antisperm antibody was developed that consists of incubating 10(7) sperm with sperm from immunized rabbits and /sup 14/C-Protein A, a long-lived and versatile indirect radiolabel for many antibodies of the IgG class. The spermatozoa are washed by rapid vacuum filtration on polycarbonate membrane filters instead of by time-consuming centrifugation. The filters with the collected spermatozoa are then counted in a liquid scintillation counter. Sera from female rabbits isoimmunized with sperm antigens show a highly significant correlation (r = -0.904; p less than 0.001) between assay results and infertility as measured by the percentage of eggs that underwent cleavage after artificial insemination.

  6. Protein-protein binding detection with nanoparticle photonic crystal enhanced microscopy (NP-PCEM).

    Science.gov (United States)

    Zhuo, Yue; Tian, Limei; Chen, Weili; Yu, Hojeong; Singamaneni, Srikanth; Cunningham, Brian T

    2014-01-01

    We demonstrate a novel microscopy-based biosensing approach that utilizes a photonic crystal (PC) surface to detect protein-protein binding with the functionalized nanoparticles as tags. This imaging approach utilizes the measurement of localized shifts in the resonant wavelength and resonant reflection magnitude from the PC biosensor in the presence of individual nanoparticles. Moreover, it substantially increases the sensitivity of the imaging approach through tunable localized surface plasmon resonant frequency of the nanoparticle matching with the resonance of the PC biosensor. Experimental demonstrations of photonic crystal enhanced microscopy (PCEM) imaging with single nanoparticle resolution are supported by Finite-Difference Time-Domain (FDTD) computer simulations. The ability to detect the surface adsorption of individual nanoparticles as tags offers a route to single molecule biosensing with photonic crystal biosensor in the future.

  7. A Low Protein Binding Cationic Poly(2-oxazoline) as Non-Viral Vector

    KAUST Repository

    He, Zhijian

    2015-04-02

    © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Developing safe and efficient non-viral gene delivery systems remains a major challenge. We present a new cationic poly(2-oxazoline) (CPOx) block copolymer for gene therapy that was synthesized by sequential polymerization of non-ionic 2-methyl-2-oxazoline and a new 2-oxazoline monomer, 2-(N-methyl, N-Boc-amino)-methyl-2-oxazoline, followed by deprotection of the pendant secondary amine groups. Upon mixing with plasmid DNA (pDNA), CPOx forms small (diameter ≈80 nm) and narrowly dispersed polyplexes (PDI <0.2), which are stable upon dilution in saline and against thermal challenge. These polyplexes exhibited low plasma protein binding and very low cytotoxicity in vitro compared to the polyplexes of pDNA and poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL). CPOx/pDNA polyplexes at N/P = 5 bound considerably less plasma protein compared to polyplexes of PEG-b-PLL at the same N/P ratio. This is a unique aspect of the developed polyplexes emphasizing their potential for systemic delivery in vivo. The transfection efficiency of the polyplexes in B16 murine melanoma cells was low after 4 h, but increased significantly for 10 h exposure time, indicative of slow internalization of polyplexes. Addition of Pluronic P85 boosted the transfection using CPOx/pDNA polyplexes considerably. The low protein binding of CPOx/pDNA polyplexes is particularly interesting for the future development of targeted gene delivery.

  8. Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Auler Jr. J.O.

    1997-01-01

    Full Text Available Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB, 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m2 body surface area (BSA, and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m2 BSA (mean ± SD. Sodium diclofenac (1 mg/kg, im Voltaren 75® twice a day was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX were: 25% VAS (CPB vs 10% VAS (control, P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences

  9. Dynamics of the BH3-Only Protein Binding Interface of Bcl-xL.

    Science.gov (United States)

    Liu, Xiaorong; Beugelsdijk, Alex; Chen, Jianhan

    2015-09-01

    The balance and interplay between pro-death and pro-survival members of the B-cell lymphoma-2 (Bcl-2) family proteins play key roles in regulation of the mitochondrial pathway of programmed cell death. Recent NMR and biochemical studies have revealed that binding of the proapoptotic BH3-only protein PUMA induces significant unfolding of antiapoptotic Bcl-xL at the interface, which in turn disrupts the Bcl-xL/p53 interaction to activate apoptosis. However, the molecular mechanism of such regulated unfolding of Bcl-xL is not fully understood. Analysis of the existing Protein Data Bank structures of Bcl-xL in both bound and unbound states reveal substantial intrinsic heterogeneity at its BH3-only protein binding interface. Large-scale atomistic simulations were performed in explicit solvent for six representative structures to further investigate the intrinsic conformational dynamics of Bcl-xL. The results support that the BH3-only protein binding interface of Bcl-xL is much more dynamic compared to the rest of the protein, both unbound and when bound to various BH3-only proteins. Such intrinsic interfacial conformational dynamics likely provides a physical basis that allows Bcl-xL to respond sensitively to detailed biophysical properties of the ligand. The ability of Bcl-xL to retain or even enhance dynamics at the interface in bound states could further facilitate the regulation of its interactions with various BH3-only proteins such as through posttranslational modifications. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. Stability, protein binding and clearance studies of [99mTc]DTPA. Evaluation of a commercially available dry-kit

    DEFF Research Database (Denmark)

    Rehling, M

    1988-01-01

    [99mTc]DTPA has achieved widespread use for the measurement of glomerular filtration rate (GFR) with the single injection plasma clearance technique and for gamma-camera renography. However, the quality of the commercial preparations varies. The purpose of the present investigation was to study...... the quality of a commercial [99mTc]DTPA preparation (C.I.S., France) with reference to stability, protein binding and accuracy of the determined plasma clearance values as a measure of GFR. The stability of the preparations was studied by thin-layer chromatography, the in vitro protein binding by Sephadex...... filtration after incubation with human serum albumin and in vivo protein binding by filtration of human plasma. The accuracy of the plasma clearance values was investigated by comparison with the simultaneously measured plasma clearance of [51Cr]EDTA. There was no detectable free pertechnetate or hydrolysed...

  11. Combination of native and denaturing PAGE for the detection of protein binding regions in long fragments of genomic DNA

    Directory of Open Access Journals (Sweden)

    Metsis Madis

    2008-06-01

    Full Text Available Abstract Background In a traditional electrophoresis mobility shift assay (EMSA a 32P-labeled double-stranded DNA oligonucleotide or a restriction fragment bound to a protein is separated from the unbound DNA by polyacrylamide gel electrophoresis (PAGE in nondenaturing conditions. An extension of this method uses the large population of fragments derived from long genomic regions (approximately 600 kb for the identification of fragments containing protein binding regions. With this method, genomic DNA is fragmented by restriction enzymes, fragments are amplified by PCR, radiolabeled, incubated with nuclear proteins and the resulting DNA-protein complexes are separated by two-dimensional PAGE. Shifted DNA fragments containing protein binding sites are identified by using additional procedures, i. e. gel elution, PCR amplification, cloning and sequencing. Although the method allows simultaneous analysis of a large population of fragments, it is relatively laborious and can be used to detect only high affinity protein binding sites. Here we propose an alternative and straightforward strategy which is based on a combination of native and denaturing PAGE. This strategy allows the identification of DNA fragments containing low as well as high affinity protein binding regions, derived from genomic DNA ( Results We have combined an EMSA-based selection step with subsequent denaturing PAGE for the localization of protein binding regions in long (up to10 kb fragments of genomic DNA. Our strategy consists of the following steps: digestion of genomic DNA with a 4-cutter restriction enzyme (AluI, BsuRI, TruI, etc, separation of low and high molecular weight fractions of resultant DNA fragments, 32P-labeling with Klenow polymerase, traditional EMSA, gel elution and identification of the shifted bands (or smear by denaturing PAGE. The identification of DNA fragments containing protein binding sites is carried out by running the gel-eluted fragments alongside

  12. Pretreatment of plasma samples by a novel hollow fiber centrifugal ultrafiltration technique for the determination of plasma protein binding of three coumarins using acetone as protein binding releasing agent.

    Science.gov (United States)

    Li, Junmei; Shi, Qingwen; Jiang, Ye; Liu, Yan

    2015-09-15

    A novel and practical sample pretreatment method based on hollow fiber centrifugal ultrafiltration (HFCF-UF) was developed to determine plasma protein binding by using HPLC. The samples for analyzing unbound and total concentrations could be prepared in parallel simultaneously by the same device. It only required centrifugation for a short time and the filtrate could be injected directly for HPLC analysis without further treatment. Coumarins were selected as the model drugs. Acetone was chosen as the releasing agent to free the binding drug from the drug-protein complex for the total drug concentration determination. Non-specific bindings (NSBs) between the analytes and hollow fiber membrane materials were investigated. The type and volume of protein binding releaser were optimized. Additionally, centrifugal speed and centrifugal time were considered. Under the optimized conditions, the absolute recovery rates of the unbound and total concentrations were in the range of 97.5-100.9% for the three analytes. The limits of detection were in the range of 0.0135-0.0667μgmL(-1). In vitro plasma protein binding of the three coumarins was determined at three concentrations using the validated method and the relative standard deviations (RSDs) were less than 3.4%. Compared with traditional method, the HFCF-UF method is simple to run, no specialized equipment requirement and is a more accurate plasma pretreatment procedure with almost excellent drug-protein binding equilibrium. Therefore, this method can be applied to determine the plasma protein binding in clinical practice. It also provides a reliable alternative for accurate monitoring of unbound or total drug concentration in therapeutic drug monitoring (TDM).

  13. Sequence-based prediction of protein-binding sites in DNA: comparative study of two SVM models.

    Science.gov (United States)

    Park, Byungkyu; Im, Jinyong; Tuvshinjargal, Narankhuu; Lee, Wook; Han, Kyungsook

    2014-11-01

    As many structures of protein-DNA complexes have been known in the past years, several computational methods have been developed to predict DNA-binding sites in proteins. However, its inverse problem (i.e., predicting protein-binding sites in DNA) has received much less attention. One of the reasons is that the differences between the interaction propensities of nucleotides are much smaller than those between amino acids. Another reason is that DNA exhibits less diverse sequence patterns than protein. Therefore, predicting protein-binding DNA nucleotides is much harder than predicting DNA-binding amino acids. We computed the interaction propensity (IP) of nucleotide triplets with amino acids using an extensive dataset of protein-DNA complexes, and developed two support vector machine (SVM) models that predict protein-binding nucleotides from sequence data alone. One SVM model predicts protein-binding nucleotides using DNA sequence data alone, and the other SVM model predicts protein-binding nucleotides using both DNA and protein sequences. In a 10-fold cross-validation with 1519 DNA sequences, the SVM model that uses DNA sequence data only predicted protein-binding nucleotides with an accuracy of 67.0%, an F-measure of 67.1%, and a Matthews correlation coefficient (MCC) of 0.340. With an independent dataset of 181 DNAs that were not used in training, it achieved an accuracy of 66.2%, an F-measure 66.3% and a MCC of 0.324. Another SVM model that uses both DNA and protein sequences achieved an accuracy of 69.6%, an F-measure of 69.6%, and a MCC of 0.383 in a 10-fold cross-validation with 1519 DNA sequences and 859 protein sequences. With an independent dataset of 181 DNAs and 143 proteins, it showed an accuracy of 67.3%, an F-measure of 66.5% and a MCC of 0.329. Both in cross-validation and independent testing, the second SVM model that used both DNA and protein sequence data showed better performance than the first model that used DNA sequence data. To the best of

  14. JWA protein binds to α-tubulin in PC12 cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Hairong; LI Aiqun; LI Aiping; ZHOU Jianwei

    2004-01-01

    Our previous study elucidated that JWA protein was a newly identified microtubule-associated protein (MAP), which combined to and co-localized with β-tubulin.In the present study, we designed a series of experiments to explore if any interactions between JWA protein and α-tubulin existed and how JWA protein would functionally link to α-tubulin, especially in cell mitosis. Results of coimmunoprecipitation, gene transfection and immunofluorescence microscopy from PC12 and HEK293 cells provided strong evidence for a linkage between JWA protein and α-tubulin. Our data showed that JWA protein bound to α-tubulin stably no matter whether α-tubulin was polymerized or not. In addition, by using antisense oligonucleotides, cell cycle blocking agents and hypothermia disposal techniques,we also found the interaction between JWA protein and α-tubulin. The further analysis using flow cytometry and confocal microscopy showed that both proteins co-existed in PC12 cells and were independent on the cell cycle. In conclusion, JWA protein is a newly identified microtubuleassociated protein, binds to α-tubulin, and probably plays an important role in regulation of microtubular stability.

  15. Synthesis, characterization, DNA binding, DNA cleavage, protein binding and cytotoxic activities of Ru(II) complexes.

    Science.gov (United States)

    Thota, Sreekanth; Vallala, Srujana; Yerra, Rajeshwar; Rodrigues, Daniel Alencar; Raghavendra, Nulgumnalli Manjunathaiah; Barreiro, Eliezer J

    2016-01-01

    We report on the synthesis of novel Ru(II) compounds (Ru-1 to Ru-8) bearing R-pdc, 4-Cl-pbinh ligands (where R=4-CF3, 4-F, 4-OH pdc=3-phenyl-5-(1H-pyrrol-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide, pbinh=phenoxybenzylidene isonicotinyl hydrazides) and their in vitro antitumor activity toward the cell lines murine leukemia L1210, human lymphocyte CEM, human epithelial cervical carcinoma HeLa, BEL-7402 and Molt4/C8. Some of the complexes exhibited more potent antiproliferative activity against cell lines than the standard drug cisplatin. Ruthenium complex Ru-2 displayed potent cytotoxicity with than that of cisplatin. DNA-binding, DNA cleavage and protein binding properties of ruthenium complexes with these ligands are reported. Interactions of these ruthenium complexes with DNA revealed an intercalative mode of binding between them. Synchronous fluorescence spectra proved that the interaction of ruthenium complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter.

  16. Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells

    Directory of Open Access Journals (Sweden)

    Ma Isabel Salazar

    2013-01-01

    Full Text Available An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS, characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa and two less apparent proteins (100 and 130 kDa. Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1 that DENV-2 exhibited a direct tropism for human neurons and (2 that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2.

  17. Recognition of anesthetic barbiturates by a protein binding site: a high resolution structural analysis.

    Directory of Open Access Journals (Sweden)

    Simon Oakley

    Full Text Available Barbiturates potentiate GABA actions at the GABA(A receptor and act as central nervous system depressants that can induce effects ranging from sedation to general anesthesia. No structural information has been available about how barbiturates are recognized by their protein targets. For this reason, we tested whether these drugs were able to bind specifically to horse spleen apoferritin, a model protein that has previously been shown to bind many anesthetic agents with affinities that are closely correlated with anesthetic potency. Thiopental, pentobarbital, and phenobarbital were all found to bind to apoferritin with affinities ranging from 10-500 µM, approximately matching the concentrations required to produce anesthetic and GABAergic responses. X-ray crystal structures were determined for the complexes of apoferritin with thiopental and pentobarbital at resolutions of 1.9 and 2.0 Å, respectively. These structures reveal that the barbiturates bind to a cavity in the apoferritin shell that also binds haloalkanes, halogenated ethers, and propofol. Unlike these other general anesthetics, however, which rely entirely upon van der Waals interactions and the hydrophobic effect for recognition, the barbiturates are recognized in the apoferritin site using a mixture of both polar and nonpolar interactions. These results suggest that any protein binding site that is able to recognize and respond to the chemically and structurally diverse set of compounds used as general anesthetics is likely to include a versatile mixture of both polar and hydrophobic elements.

  18. Epidural ropivacaine hydrochloride during labour: protein binding, placental transfer and neonatal outcome.

    LENUS (Irish Health Repository)

    Porter, J M

    2012-02-03

    This study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma alpha1-acid glycoprotein concentration, (ii) to examine the effects of changes in plasma alpha1-acid glycoprotein concentration on plasma protein binding and placental transfer of ropivacaine, and (iii) to examine the association between umbilical venous ropivacaine concentration and neurobehavioural function in the neonate. Multiparous patients undergoing induction of labour received a continuous epidural infusion of 0.1% ropivacaine following an epidural bolus. A significant association was demonstrated between maternal plasma alpha1-acid glycoprotein concentration and 1\\/free fraction of ropivacaine 60 min after starting ropivacaine administration (r(2) = 0.77) but not at delivery. No significant correlation was demonstrable between maternal unbound ropivacaine concentration and either neonatal (cord) ropivacaine concentration or UV\\/MV (a measure of placental transfer). Thirty minutes after delivery, 9\\/10 neonates had neurological and adaptive capacity scores < 35, whereas only three infants had scores < 35 at 2 h. All scores exceeded 35 16 h after delivery. No association between mean (SD) umbilical venous ropivacaine concentration [0.09 (0.08) mg x l(-1)] and neurological and adaptive capacity scores was demonstrated.

  19. The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.; Gomes Guimaraes, B.

    2008-01-01

    Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstroms resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.

  20. Towards an easy access to Annexin-A5 protein binding block copolymer micelles

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Vanessa; Giacomelli, Cristiano [Laboratoire de Chimie des Polymeres Organiques (LCPO-ENSCPB), Universite Bordeaux 1, 16 Av. Pey Berland, 33607 Pessac Cedex (France); Brisson, Alain R. [Laboratoire d' Imagerie Moleculaire et Nano-Bio-Technologie-(IECB)-Universite Bordeaux 1, 2 Rue Robert Escarpit, 33607 Pessac Cedex (France)], E-mail: a.brisson@iecb.u-bordeaux.fr; Borsali, Redouane [Laboratoire de Chimie des Polymeres Organiques (LCPO-ENSCPB), Universite Bordeaux 1, 16 Av. Pey Berland, 33607 Pessac Cedex (France)], E-mail: borsali@cermav.cnrs.fr

    2008-05-01

    The formation of Annexin-A5 decorated (bio-functionalized) nanoparticles is of particular interest in micelle-mediated target drug delivery, in vivo magnetic resonance imaging, and controlled fabrication of biochips. This work describes an easy access to the synthesis and manipulation of block copolymer nano-objects exhibiting Annexin-A5 protein binding ability. Well-defined spherical micelles containing negatively charged phosphonic diacid groups - which are potential binding sites for Annexin-A5 proteins - at their hydrophilic periphery originate from the self-assembly of polystyrene-b-poly(2-phosphatethyl methacrylate-stat-2-hydroxyethyl methacrylate) (PS-b-P(PEMA-stat-HEMA)) amphiphilic macromolecules in aqueous media. PS-b-P(PEMA-stat-HEMA) can be prepared in a three-step phosphorylation/silylation/methanolysis procedure applied to PS-b-PHEMA precursors synthesized via Atom Transfer Radical Polymerization (ATRP). The herein discussed approach allows precise control over micellar dimensions and properties such as core radius (i.e., loading capacity), corona width, and density of phosphate groups at the micelle periphery.

  1. Clorazepate dipotassium and diazepam in renal insufficiency: serum concentrations and protein binding of diazepam and desmethyldiazepam.

    Science.gov (United States)

    Ochs, H R; Rauh, H W; Greenblatt, D J; Kaschell, H J

    1984-01-01

    5 patients with chronic renal failure on maintenance hemodialysis and 5 healthy matched controls received single 20-mg intravenous doses of clorazepate dipotassium. Clearance of pharmacologically active unbound desmethyldiazepam was reduced in renal failure patients as opposed to controls, and free fraction in serum was greater. Since desmethyldiazepam distribution was reduced in renal patients, elimination half-life was actually shorter than in controls (36 vs. 57 h). In 10 dialysis patients receiving chronic diazepam treatment (5-15 mg/day), steady-state concentrations of diazepam (56 ng/ml) and desmethyldiazepam (77 ng/ml) were significantly lower than in age- and weight-matched controls receiving similar doses (189 and 216 ng/ml, respectively). However after correction for the higher free fractions of both compounds in renal patients as opposed to controls, steady-state concentrations of unbound drug were found to be similar between groups. Interpretation of kinetic variables and steady-state serum concentrations of extensively protein-bound drugs requires consideration of alterations in protein binding that may occur in disease states.

  2. A Comparison Study for DNA Motif Modeling on Protein Binding Microarray.

    Science.gov (United States)

    Wong, Ka-Chun; Li, Yue; Peng, Chengbin; Wong, Hau-San

    2016-01-01

    Transcription factor binding sites (TFBSs) are relatively short (5-15 bp) and degenerate. Identifying them is a computationally challenging task. In particular, protein binding microarray (PBM) is a high-throughput platform that can measure the DNA binding preference of a protein in a comprehensive and unbiased manner; for instance, a typical PBM experiment can measure binding signal intensities of a protein to all possible DNA k-mers (k = 8∼10). Since proteins can often bind to DNA with different binding intensities, one of the major challenges is to build TFBS (also known as DNA motif) models which can fully capture the quantitative binding affinity data. To learn DNA motif models from the non-convex objective function landscape, several optimization methods are compared and applied to the PBM motif model building problem. In particular, representative methods from different optimization paradigms have been chosen for modeling performance comparison on hundreds of PBM datasets. The results suggest that the multimodal optimization methods are very effective for capturing the binding preference information from PBM data. In particular, we observe a general performance improvement if choosing di-nucleotide modeling over mono-nucleotide modeling. In addition, the models learned by the best-performing method are applied to two independent applications: PBM probe rotation testing and ChIP-Seq peak sequence prediction, demonstrating its biological applicability.

  3. A Comparison Study for DNA Motif Modeling on Protein Binding Microarray

    KAUST Repository

    Wong, Ka-Chun

    2015-06-11

    Transcription Factor Binding Sites (TFBSs) are relatively short (5-15 bp) and degenerate. Identifying them is a computationally challenging task. In particular, Protein Binding Microarray (PBM) is a high-throughput platform that can measure the DNA binding preference of a protein in a comprehensive and unbiased manner; for instance, a typical PBM experiment can measure binding signal intensities of a protein to all possible DNA k-mers (k=810). Since proteins can often bind to DNA with different binding intensities, one of the major challenges is to build motif models which can fully capture the quantitative binding affinity data. To learn DNA motif models from the non-convex objective function landscape, several optimization methods are compared and applied to the PBM motif model building problem. In particular, representative methods from different optimization paradigms have been chosen for modeling performance comparison on hundreds of PBM datasets. The results suggest that the multimodal optimization methods are very effective for capturing the binding preference information from PBM data. In particular, we observe a general performance improvement using di-nucleotide modeling over mono-nucleotide modeling. In addition, the models learned by the best-performing method are applied to two independent applications: PBM probe rotation testing and ChIP-Seq peak sequence prediction, demonstrating its biological applicability.

  4. Evolving Transcription Factor Binding Site Models From Protein Binding Microarray Data

    KAUST Repository

    Wong, Ka-Chun

    2016-02-02

    Protein binding microarray (PBM) is a high-throughput platform that can measure the DNA binding preference of a protein in a comprehensive and unbiased manner. In this paper, we describe the PBM motif model building problem. We apply several evolutionary computation methods and compare their performance with the interior point method, demonstrating their performance advantages. In addition, given the PBM domain knowledge, we propose and describe a novel method called kmerGA which makes domain-specific assumptions to exploit PBM data properties to build more accurate models than the other models built. The effectiveness and robustness of kmerGA is supported by comprehensive performance benchmarking on more than 200 datasets, time complexity analysis, convergence analysis, parameter analysis, and case studies. To demonstrate its utility further, kmerGA is applied to two real world applications: 1) PBM rotation testing and 2) ChIP-Seq peak sequence prediction. The results support the biological relevance of the models learned by kmerGA, and thus its real world applicability.

  5. Plasma Protein Binding of Anisomelic Acid: Spectroscopy and Molecular Dynamic Simulations.

    Science.gov (United States)

    Senthilkumar, Rajendran; Marimuthu, Parthiban; Paul, Preethy; Manojkumar, Yesaiyan; Arunachalam, Sankaralingam; Eriksson, John E; Johnson, Mark S

    2016-12-27

    Anisomelic acid (AA) is a macrocyclic cembranolide compound extracted from Anisomeles herbal species. Recently, we have shown that AA possesses both anticancer and antiviral activity. However, to date, the plasma protein binding properties of AA are unknown. Here, we describe the molecular interactions of AA with two serum proteins, human serum albumin (HSA) and bovine serum albumin (BSA), adopting multiple physicochemical methods. Besides, molecular docking and dynamics simulations were performed to predict the interaction mode and the dynamic behavior of AA with HSA and BSA. The experimental results revealed that hydrophobic forces play a significant part in the interaction of AA to HSA and BSA. The outcomes of the principal components analysis (PCA) of the poses based on root-mean-squared distances showed less variation in AA-HSA, opposed to what is seen for BSA-AA. Furthermore, binding free energies estimated for AA-HSA and AA-BSA complexes at different temperatures (298, 303, 308, and 313 K) based on molecular mechanics-generalized Born surface area (MMGBSA) approaches were well correlated with our experimental results.

  6. A robust assay to measure DNA topology-dependent protein binding affinity.

    Science.gov (United States)

    Litwin, Tamara R; Solà, Maria; Holt, Ian J; Neuman, Keir C

    2015-04-20

    DNA structure and topology pervasively influence aspects of DNA metabolism including replication, transcription and segregation. However, the effects of DNA topology on DNA-protein interactions have not been systematically explored due to limitations of standard affinity assays. We developed a method to measure protein binding affinity dependence on the topology (topological linking number) of supercoiled DNA. A defined range of DNA topoisomers at equilibrium with a DNA binding protein is separated into free and protein-bound DNA populations using standard nitrocellulose filter binding techniques. Electrophoretic separation and quantification of bound and free topoisomers combined with a simple normalization procedure provide the relative affinity of the protein for the DNA as a function of linking number. Employing this assay we measured topology-dependent DNA binding of a helicase, a type IB topoisomerase, a type IIA topoisomerase, a non-specific mitochondrial DNA binding protein and a type II restriction endonuclease. Most of the proteins preferentially bind negatively supercoiled DNA but the details of the topology-dependent affinity differ among proteins in ways that expose differences in their interactions with DNA. The topology-dependent binding assay provides a robust and easily implemented method to probe topological influences on DNA-protein interactions for a wide range of DNA binding proteins.

  7. Competitive Intelligence.

    Science.gov (United States)

    Bergeron, Pierrette; Hiller, Christine A.

    2002-01-01

    Reviews the evolution of competitive intelligence since 1994, including terminology and definitions and analytical techniques. Addresses the issue of ethics; explores how information technology supports the competitive intelligence process; and discusses education and training opportunities for competitive intelligence, including core competencies…

  8. On-column entrapment of alpha1-acid glycoprotein for studies of drug-protein binding by high-performance affinity chromatography.

    Science.gov (United States)

    Anguizola, Jeanethe; Bi, Cong; Koke, Michelle; Jackson, Abby; Hage, David S

    2016-08-01

    An on-column approach for protein entrapment was developed to immobilize alpha1-acid glycoprotein (AGP) for drug-protein binding studies based on high-performance affinity chromatography. Soluble AGP was physically entrapped by using microcolumns that contained hydrazide-activated porous silica and by employing mildly oxidized glycogen as a capping agent. Three on-column entrapment methods were evaluated and compared to a previous slurry-based entrapment method. The final selected method was used to prepare 1.0 cm × 2.1 mm I.D. affinity microcolumns that contained up to 21 (±4) μg AGP and that could be used over the course of more than 150 sample applications. Frontal analysis and zonal elution studies were performed on these affinity microcolumns to examine the binding of various drugs with the entrapped AGP. Site-selective competition studies were also conducted for these drugs. The results showed good agreement with previous observations for these drug-protein systems and with binding constants that have been reported in the literature. The entrapment method developed in this study should be useful for future work in the area of personalized medicine and in the high-throughput screening of drug interactions with AGP or other proteins. Graphical abstract On-column protein entrapment using a hydrazide-activated support and oxidized glycogen as a capping agent.

  9. Interplay between excited-state intramolecular proton transfer and charge transfer in flavonols and their use as protein-binding-site fluorescence probes

    Energy Technology Data Exchange (ETDEWEB)

    Sytnik, A.; Gormin, D.; Kasha, M. (Florida State Univ., Tallahassee, FL (United States))

    1994-12-06

    A comparative study is presented of competitive fluorescences of three flavonols, 3-hydroxyflavone, 3,3[prime],4[prime],7-tetrahydroxyflavone (fisetin), and 4[prime]-diethylamino-3-hydroxyflavone (DHF). The normal fluorescence S[sub 1] [yields] S[sub 0] (400-nm region) is largely replaced by the proton-transfer tautomer fluorescence S[prime][sub 1] [yields] S[prime][sub 0] in the 550-nm region for all three of the flavonols in aprotic solvents at room temperature. For DHF in polar solvents the normal fluorescence becomes a charge-transfer fluorescence (460-500 nm) which competes strongly with the still dominant proton-transfer fluorescence (at 570 nm). In protic solvents, and at 77 K, the interference with intramolecular hydrogen bonding gives rise to greatly enhanced normal fluorescence, lowering the quantum yield of proton-transfer fluorescence. The utility of DHF as a discriminating fluorescence probe for protein binding sites is suggested by the strong dependence of the charge-transfer fluorescence on polarity of the environment and by various static and dynamic parameters of the charge-transfer and proton-transfer fluorescence which can be determined. 49 refs., 6 figs., 1 tab.

  10. Technical note: effects of forage protein-binding polyphenols on chemistry of dairy excreta.

    Science.gov (United States)

    Powell, J M; Broderick, G A; Grabber, J H; Hymes-Fecht, U C

    2009-04-01

    Forage chemistry can affect intake, digestion, milk production, and manure excretion. Although information is available on the effects of forage protein-binding polyphenols on small ruminant production and manure excretion, little information is available for dairy cattle. The objective of this study was to compare fecal and urinary N excretion of diets formulated with alfalfa (Medicago sativa L.) silage versus condensed tannin-containing birdsfoot trefoil (Lotus corniculatus) or o-quinone-containing red clover (Trifolium pratense L.) silages. Significantly higher concentrations of N were excreted in urine by lactating Holstein dairy cows fed red clover and low-tannin birdsfoot trefoil (8.2 g/L) than by cows fed high-tannin birdsfoot trefoil or alfalfa (7.1 g/L). Fecal N concentrations were similar (33.6 g/kg) among all diets. Dairy cows fed red clover had lower rates of urinary N excretion (5.0 g/h) compared with other forages (6.6 g/h). Fecal N excretion rates were lowest for red clover (4.1 g/h), intermediate for alfalfa (5.8 g/h), and greatest for cows fed high- and low-tannin birdsfoot trefoil (6.4 g/h). The ratio of fecal N to urinary N was highest for high-tannin trefoil, lowest for alfalfa and red clover, and higher in excreta collected in morning than evening. Concentrations of neutral detergent fiber (NDF) in feces, of N in NDF (NDIN) and acid detergent fiber (ADIN), and relative amounts of NDIN and ADIN excreted in feces were significantly higher from cows fed high-tannin birdsfoot trefoil than the other silage types. Study results imply that collection of excreta for environmental studies needs to consider forage polyphenol and diurnal effects on chemistry of dairy excreta.

  11. Combining features in a graphical model to predict protein binding sites.

    Science.gov (United States)

    Wierschin, Torsten; Wang, Keyu; Welter, Marlon; Waack, Stephan; Stanke, Mario

    2015-05-01

    Large efforts have been made in classifying residues as binding sites in proteins using machine learning methods. The prediction task can be translated into the computational challenge of assigning each residue the label binding site or non-binding site. Observational data comes from various possibly highly correlated sources. It includes the structure of the protein but not the structure of the complex. The model class of conditional random fields (CRFs) has previously successfully been used for protein binding site prediction. Here, a new CRF-approach is presented that models the dependencies of residues using a general graphical structure defined as a neighborhood graph and thus our model makes fewer independence assumptions on the labels than sequential labeling approaches. A novel node feature "change in free energy" is introduced into the model, which is then denoted by ΔF-CRF. Parameters are trained with an online large-margin algorithm. Using the standard feature class relative accessible surface area alone, the general graph-structure CRF already achieves higher prediction accuracy than the linear chain CRF of Li et al. ΔF-CRF performs significantly better on a large range of false positive rates than the support-vector-machine-based program PresCont of Zellner et al. on a homodimer set containing 128 chains. ΔF-CRF has a broader scope than PresCont since it is not constrained to protein subgroups and requires no multiple sequence alignment. The improvement is attributed to the advantageous combination of the novel node feature with the standard feature and to the adopted parameter training method.

  12. Structural Perspectives on the Evolutionary Expansion of Unique Protein-Protein Binding Sites.

    Science.gov (United States)

    Goncearenco, Alexander; Shaytan, Alexey K; Shoemaker, Benjamin A; Panchenko, Anna R

    2015-09-15

    Structures of protein complexes provide atomistic insights into protein interactions. Human proteins represent a quarter of all structures in the Protein Data Bank; however, available protein complexes cover less than 10% of the human proteome. Although it is theoretically possible to infer interactions in human proteins based on structures of homologous protein complexes, it is still unclear to what extent protein interactions and binding sites are conserved, and whether protein complexes from remotely related species can be used to infer interactions and binding sites. We considered biological units of protein complexes and clustered protein-protein binding sites into similarity groups based on their structure and sequence, which allowed us to identify unique binding sites. We showed that the growth rate of the number of unique binding sites in the Protein Data Bank was much slower than the growth rate of the number of structural complexes. Next, we investigated the evolutionary roots of unique binding sites and identified the major phyletic branches with the largest expansion in the number of novel binding sites. We found that many binding sites could be traced to the universal common ancestor of all cellular organisms, whereas relatively few binding sites emerged at the major evolutionary branching points. We analyzed the physicochemical properties of unique binding sites and found that the most ancient sites were the largest in size, involved many salt bridges, and were the most compact and least planar. In contrast, binding sites that appeared more recently in the evolution of eukaryotes were characterized by a larger fraction of polar and aromatic residues, and were less compact and more planar, possibly due to their more transient nature and roles in signaling processes.

  13. Progressive dry-core-wet-rim hydration trend in a nested-ring topology of protein binding interfaces

    Directory of Open Access Journals (Sweden)

    Li Zhenhua

    2012-03-01

    Full Text Available Abstract Background Water is an integral part of protein complexes. It shapes protein binding sites by filling cavities and it bridges local contacts by hydrogen bonds. However, water molecules are usually not included in protein interface models in the past, and few distribution profiles of water molecules in protein binding interfaces are known. Results In this work, we use a tripartite protein-water-protein interface model and a nested-ring atom re-organization method to detect hydration trends and patterns from an interface data set which involves immobilized interfacial water molecules. This data set consists of 206 obligate interfaces, 160 non-obligate interfaces, and 522 crystal packing contacts. The two types of biological interfaces are found to be drier than the crystal packing interfaces in our data, agreeable to a hydration pattern reported earlier although the previous definition of immobilized water is pure distance-based. The biological interfaces in our data set are also found to be subject to stronger water exclusion in their formation. To study the overall hydration trend in protein binding interfaces, atoms at the same burial level in each tripartite protein-water-protein interface are organized into a ring. The rings of an interface are then ordered with the core atoms placed at the middle of the structure to form a nested-ring topology. We find that water molecules on the rings of an interface are generally configured in a dry-core-wet-rim pattern with a progressive level-wise solvation towards to the rim of the interface. This solvation trend becomes even sharper when counterexamples are separated. Conclusions Immobilized water molecules are regularly organized in protein binding interfaces and they should be carefully considered in the studies of protein hydration mechanisms.

  14. IN SILICO EVALUATION OF ANGIOTENSIN II RECEPTOR ANTAGONIST’S PLASMA PROTEIN BINDING USING COMPUTED MOLECULAR DESCRIPTORS

    Directory of Open Access Journals (Sweden)

    Jadranka Odović

    2014-03-01

    Full Text Available The discovery of new pharmacologically active substances and drugs modeling led to necessity of predicting drugs properties and its ADME data. Angiotensin II receptor antagonists are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system and today represent the most commonly prescribed anti-hypertensive drugs. The aim of this study was to compare different molecular properties of seven angiotensin II receptor antagonists / blockers (ARBs, (eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their plasma protein binding (PPB data. Several ARBs molecular descriptors were calculated using software package Molinspiration Depiction Software as well as Virtual Computational Chemistry Laboratory (electronic descriptor – PSA, constitutional parameter – Mw, geometric descriptor – Vol, lipophilicity descriptors - logP values, aqueous solubility data – logS. The correlations between all collected descriptors and plasma protein binding data obtained from relevant literature were established. In the simple linear regression poor correlations were obtained in relationships between PPB data and all calculated molecular descriptors. In the next stage of the study multiple linear regression (MLR was used for correlation of PPB data with two different descriptors as independent variables. The best correlation (R2=0.70 with P<0.05 was established between PPB data and molecular weight with addition of volume values as independent variables. The possible application of computed molecular descriptors in drugs protein binding evaluation can be of great importance in drug research.

  15. Plasma protein-binding parameters of prednisolone in immune disease patients receiving long-term prednisone therapy.

    Science.gov (United States)

    Wagner, J G; Wexler, D; Ağabeyoğlu, I T; Bergstrom, R F; Sakmar, E; Kay, D R

    1981-04-01

    Prednisone and prednisolone bind in plasma to albumin and transcortin. In am attempt to determine whether prednisone side effects and/or type of disease correlated with prednisolone plasma protein binding, multiple plasma samples from 17 patients (three asthma, eight SLE, three RA, two PSS, one PAN) receiving long-term prednisone therapy were monitored during an interval between two prednisone doses. Prednisolone plasma protein binding was nonlinear and exhibited large intrapatient and interpatient variability. For the group, mean association constants of the prednisolone-albumin complex and the prednisolone-transcortin complex were 2.3 X 10(3) M-1 and 2.9 X 10(7) M-1, with coefficients of variation of 82% and 127%, respectively. SLE patients tended to have lower mean prednisolone association constants for albumin and transcortin than did other patients. The presence of corticosteroid side effects did not correlate with prednisolone plasma protein-binding parameters. The wide range of prednisolone free fraction noted in plasma from patients who achieved comparable total prednisolone plasma concentrations implies that administration of a uniform prednisone dose will not lead to a predictable clinical response.

  16. Simultaneous determination of human plasma protein binding of bioactive flavonoids in Polygonum orientale by equilibrium dialysis combined with UPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    Yong Huang; Yong-Lin Wang; Hui Chen; Feng He; Zhi-Rong Zhang; Lin Zheng; Yue Liu; Yan-Yu Lan; Shang-Gao Liao; Yong-Jun Li

    2013-01-01

    A simple and selective ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) assay was developed for the determination of the human plasma protein binding of four bioactive flavonoids (such as orientin and vitexin) in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C18 column with a mobile phase composed of 0.1%formic acid in acetonitrile and 0.1%aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITY™TQD system was operated under the multiple reaction monitoring (MRM) mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations (r40.99) of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.

  17. Automatic generation of 3D motifs for classification of protein binding sites

    Directory of Open Access Journals (Sweden)

    Herzyk Pawel

    2007-08-01

    Full Text Available Abstract Background Since many of the new protein structures delivered by high-throughput processes do not have any known function, there is a need for structure-based prediction of protein function. Protein 3D structures can be clustered according to their fold or secondary structures to produce classes of some functional significance. A recent alternative has been to detect specific 3D motifs which are often associated to active sites. Unfortunately, there are very few known 3D motifs, which are usually the result of a manual process, compared to the number of sequential motifs already known. In this paper, we report a method to automatically generate 3D motifs of protein structure binding sites based on consensus atom positions and evaluate it on a set of adenine based ligands. Results Our new approach was validated by generating automatically 3D patterns for the main adenine based ligands, i.e. AMP, ADP and ATP. Out of the 18 detected patterns, only one, the ADP4 pattern, is not associated with well defined structural patterns. Moreover, most of the patterns could be classified as binding site 3D motifs. Literature research revealed that the ADP4 pattern actually corresponds to structural features which show complex evolutionary links between ligases and transferases. Therefore, all of the generated patterns prove to be meaningful. Each pattern was used to query all PDB proteins which bind either purine based or guanine based ligands, in order to evaluate the classification and annotation properties of the pattern. Overall, our 3D patterns matched 31% of proteins with adenine based ligands and 95.5% of them were classified correctly. Conclusion A new metric has been introduced allowing the classification of proteins according to the similarity of atomic environment of binding sites, and a methodology has been developed to automatically produce 3D patterns from that classification. A study of proteins binding adenine based ligands showed that

  18. Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes.

    Science.gov (United States)

    Afek, Ariel; Cohen, Hila; Barber-Zucker, Shiran; Gordân, Raluca; Lukatsky, David B

    2015-08-01

    in vitro TF-DNA preferences obtained from the universal protein binding microarrays (PBM) for ~90 eukaryotic TFs belonging to 22 different DNA-binding domain types. As a result of this new analysis, we conclude that nonconsensus protein-DNA binding is a widespread phenomenon that significantly affects protein-DNA binding preferences and need not require the presence of consensus (specific) TFBSs in order to achieve genome-wide TF-DNA binding specificity.

  19. Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes.

    Directory of Open Access Journals (Sweden)

    Ariel Afek

    2015-08-01

    -scale analysis using in vitro TF-DNA preferences obtained from the universal protein binding microarrays (PBM for ~90 eukaryotic TFs belonging to 22 different DNA-binding domain types. As a result of this new analysis, we conclude that nonconsensus protein-DNA binding is a widespread phenomenon that significantly affects protein-DNA binding preferences and need not require the presence of consensus (specific TFBSs in order to achieve genome-wide TF-DNA binding specificity.

  20. Equilibrium-phase MR angiography: Comparison of unspecific extracellular and protein-binding gadolinium-based contrast media with respect to image quality.

    Science.gov (United States)

    Erb-Eigner, Katharina; Taupitz, Matthias; Asbach, Patrick

    2016-01-01

    The purpose of this study was to compare contrast and image quality of whole-body equilibrium-phase high-spatial-resolution MR angiography using a non-protein-binding unspecific extracellular gadolinium-based contrast medium with that of two contrast media with different protein-binding properties. 45 patients were examined using either 15 mL of gadobutrol (non-protein-binding, n = 15), 32 mL of gadobenate dimeglumine (weakly protein binding, n = 15) or 11 mL gadofosveset trisodium (protein binding, n = 15) followed by equilibrium-phase high-spatial-resolution MR-angiography of four consecutive anatomic regions. The time elapsed between the contrast injection and the beginning of the equilibrium-phase image acquisition in the respective region was measured and was up to 21 min. Signal intensity was measured in two vessels per region and in muscle tissue. Relative contrast (RC) values were calculated. Vessel contrast, artifacts and image quality were rated by two radiologists in consensus on a five-point scale. Compared with gadobutrol, gadofosveset trisodium revealed significantly higher RC values only when acquired later than 15 min after bolus injection. Otherwise, no significant differences between the three contrast media were found regarding vascular contrast and image quality. Equilibrium-phase high-spatial-resolution MR-angiography using a weakly protein-binding or even non-protein-binding contrast medium is equivalent to using a stronger protein-binding contrast medium when image acquisition is within the first 15 min after contrast injection, and allows depiction of the vasculature with high contrast and image quality. The protein-binding contrast medium was superior for imaging only later than 15 min after contrast medium injection.

  1. Friendly competition.

    Science.gov (United States)

    Chambers, David W

    2006-01-01

    Competition that is characterized by rules, often informal, agreed among mutually accepted participants, and that gives the competitors a special, advantageous status with others is called friendly competition. Dentists have engaged in it deeply and it is good for the profession. Friendly competition offers the advantages of spillover of commonly useful information and technologies, stimulation of innovation, a united and convenient face to customers and suppliers, and standards that promote growth. Friendly competition increases the size of the pie, regardless of market share. Paradoxically, this is even true for the little guy in the shadow of the giant. If carried to extremes, unfriendly competition leads to destroying competitors, the confusion of multiple rules, and encouragement of disruptive change.

  2. Functional homology between the yeast regulatory proteins GAL4 and LAC9: LAC9-mediated transcriptional activation in Kluyveromyces lactis involves protein binding to a regulatory sequence homologous to the GAL4 protein-binding site.

    OpenAIRE

    Breunig, K D; Kuger, P

    1987-01-01

    As shown previously, the beta-galactosidase gene of Kluyveromyces lactis is transcriptionally regulated via an upstream activation site (UASL) which contains a sequence homologous to the GAL4 protein-binding site in Saccharomyces cerevisiae (M. Ruzzi, K.D. Breunig, A.G. Ficca, and C.P. Hollenberg, Mol. Cell. Biol. 7:991-997, 1987). Here we demonstrate that the region of homology specifically binds a K. lactis regulatory protein. The binding activity was detectable in protein extracts from wil...

  3. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability

    Science.gov (United States)

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores th...

  4. Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability

    Science.gov (United States)

    The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores th...

  5. 牡荆素血浆蛋白结合率的测定%Determination of plasma protein binding rate of vitexin

    Institute of Scientific and Technical Information of China (English)

    童成亮; 吴小英

    2012-01-01

    目的:建立血浆中牡荆素浓度的分析方法,测定牡荆素血浆蛋白结合率.方法:采用平衡透析法透析,利用HPLC测定血浆中牡荆素浓度,计算牡荆素与人血浆蛋白结合率,并比较大鼠和人血浆中牡荆素的血浆蛋白结合率.结果:在2 ~16 mg·L-1,药物浓度对血浆蛋白结合率无显著影响,但牡荆素在大鼠和人的血浆蛋白结合率存在显著性差异,牡荆素与人的血浆蛋白结合率高于与大鼠血浆蛋白结合率.结论:牡荆素与血浆蛋白具有较强的结合.%Objective: To establish an analytical method on vitexin concentration in plasma to determine the plasma protein binding rate of vitexin. Method: The equilibrium dialysis method and HPLC were adopted to determine vitexin concentration in plasma , calculate human plasma protein binding rate of vitexin and compare rat and human plasma protein binding rates of vitexin. Result: At 2-16 mg · L-1 , there was no significant difference in the plasma protein binding rate. But the human plasma protein binding rate of vitexin was higher than its rat plasma protein binding rate, indicating a significant difference in rat and human plasma protein binding rates of vitexin. Conclusion: Vitexin has a higher protein binding rate with both rat plasma and human plasma.

  6. Controlled Modulation of Serum Protein Binding and Biodistribution of Asymmetric Cyanine Dyes by Variation of the Number of Sulfonate Groups

    Directory of Open Access Journals (Sweden)

    Franziska M. Hamann

    2011-07-01

    Full Text Available To assess the suitability of asymmetric cyanine dyes for in vivo fluoro-optical molecular imaging, a comprehensive study on the influence of the number of negatively charged sulfonate groups governing the hydrophilicity of the DY-67x family of asymmetric cyanines was performed. Special attention was devoted to the plasma protein binding capacity and related pharmacokinetic properties. Four members of the DY-67x cyanine family composed of the same main chromophore, but substituted with a sequentially increasing number of sulfonate groups (n = 1−4; DY-675, DY-676, DY-677, DY-678, respectively, were incubated with plasma proteins dissolved in phosphate-buffered saline. Protein binding was assessed by absorption spectroscopy, gel electrophoresis, ultrafiltration, and dialysis. Distribution of dye in organs was studied by intraveneous injection of 62 nmol dye/kg body weight into mice (n = 12; up to 180 minutes postinjection using whole-body near-infrared fluorescence imaging. Spectroscopic studies, gel electrophoresis, and dialysis demonstrated reduced protein binding with increasing number of sulfonate groups. The bovine serum albumin binding constant of the most hydrophobic dye, DY-675, is 18 times higher than that of the most hydrophilic fluorophore, DY-678. In vivo biodistribution analysis underlined a considerable influence of dye hydrophilicity on biodistribution and excretion pathways, with the more hydrophobic dyes, DY-675 and DY-676, accumulating in the liver, followed by strong fluorescence signals in bile and gut owing to accumulation in feces and comparatively hydrophilic DY-678-COOH accumulating in the bladder. Our results demonstrate the possibility of selectively controlling dye-protein interactions and, thus, biodistribution and excretion pathways via proper choice of the fluorophore's substitution pattern. This underlines the importance of structure-property relationships for fluorescent labels. Moreover, our data could provide the

  7. Analysis of drug-protein binding using on-line immunoextraction and high-performance affinity microcolumns: Studies with normal and glycated human serum albumin.

    Science.gov (United States)

    Matsuda, Ryan; Jobe, Donald; Beyersdorf, Jared; Hage, David S

    2015-10-16

    A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research.

  8. Calculation of relative free energies for ligand-protein binding, solvation, and conformational transitions using the GROMOS software.

    Science.gov (United States)

    Riniker, Sereina; Christ, Clara D; Hansen, Halvor S; Hünenberger, Philippe H; Oostenbrink, Chris; Steiner, Denise; van Gunsteren, Wilfred F

    2011-11-24

    The calculation of the relative free energies of ligand-protein binding, of solvation for different compounds, and of different conformational states of a polypeptide is of considerable interest in the design or selection of potential enzyme inhibitors. Since such processes in aqueous solution generally comprise energetic and entropic contributions from many molecular configurations, adequate sampling of the relevant parts of configurational space is required and can be achieved through molecular dynamics simulations. Various techniques to obtain converged ensemble averages and their implementation in the GROMOS software for biomolecular simulation are discussed, and examples of their application to biomolecules in aqueous solution are given.

  9. High protein binding and cidal activity against penicillin-resistant S. pneumoniae: a cefditoren in vitro pharmacodynamic simulation.

    Directory of Open Access Journals (Sweden)

    David Sevillano

    Full Text Available BACKGROUND: Although protein binding is a reversible phenomenon, it is assumed that antibacterial activity is exclusively exerted by the free (unbound fraction of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: Activity of cefditoren, a highly protein bound 3(rd generation cephalosporin, over 24h after an oral 400 mg cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/cefditoren MICs; microg/ml: S1 (0.12/0.25, S2 (0.25/0.25, S3 and S4 (0.5/0.5, S5 (1/0.5 and S6 (4/0.5. A computerized pharmacodynamic simulation with media consisting in 75% human serum and 25% broth (mean albumin concentrations = 4.85+/-0.12 g/dL was performed. Protein binding was measured. The cumulative percentage of a 24h-period that drug concentrations exceeded the MIC for total (T > MIC and unbound concentrations (fT > MIC, expressed as percentage of the dosing interval, were determined. Protein binding was 87.1%. Bactericidal activity (> or = 99.9% initial inocula reduction was obtained against strains S1 and S2 at 24h (T > MIC = 77.6%, fT > MIC = 23.7%. With T > MIC of 61.6% (fT > MIC = 1.7%, reductions against S3 and S4 ranged from 90% to 97% at 12h and 24h; against S5, reduction was 45.1% at 12h and up to 85.0% at 24h; and against S6, reduction was 91.8% at 12h, but due to regrowth of 52.9% at 24h. Cefditoren physiological concentrations exerted antibacterial activity against strains exhibiting MICs of 0.25 and 0.5 microg/ml under protein binding conditions similar to those in humans. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that, from the pharmacodynamic perspective, the presence of physiological albumin concentrations may not preclude antipneumococcal activity of highly bound cephalosporins as cefditoren.

  10. The Majorana Demonstrator Radioassay Program

    CERN Document Server

    Abgrall, N; Avignone, F T; Back, H O; Barabash, A S; Bertrand, F E; Boswell, M; Bradley, A W; Brudanin, V; Busch, M; Buuck, M; Byram, D; Caldwell, A S; Chan, Y-D; Christofferson, C D; Chu, P -H; Cuesta, C; Detwiler, J A; Dunmore, J A; Efremenko, Yu; Ejiri, H; Elliott, S R; Finnerty, P; Galindo-Uribarri, A; Gehman, V M; Gilliss, T; Giovanetti, G K; Goett, J; Green, M P; Gruszko, J; Guinn, I S; Guiseppe, V E; Henning, R; Hoppe, E W; Howard, S; Howe, M A; Jasinski, B R; Johnson, R A; Keeter, K J; Kidd, M F; Kochetoi, O; Konovalov, S I; Kouzes, R T; LaFerriere, B D; Leon, J; Loach, J C; MacMullin, J; MacMullin, S; Martin, R D; Massarczyk, R; Meijer, S; Mertens, S; Miller, M L; Orrell, J L; OShaughnessy, C; Overman, N R; Poon, A W P; Pushkin, K; Radford, D C; Rager, J; Rielage, K; Robertson, R G H; Romero-Romero, E; Ronquest, M C; Schubert, A G; Shanks, B; Shirchenko, M; Snavely, K J; Snyder, N; Steele, D; Suriano, A M; Tedeschi, D; Trimble, J E; Varner, R L; Vasilyev, S; Vetter, K; Vorren, K; White, B R; Wilkerson, J F; Wiseman, C; Xu, W; Yakushev, E; Yu, C -H; Yumatov, V; Zhitnikov, I

    2016-01-01

    The MAJORANA collaboration is constructing the MAJORANA DEMONSTATOR at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope \

  11. Quantitative Analysis of Multivalent Ligand Presentation on Gold Glyconanoparticles and Their Effects on Protein Binding

    Science.gov (United States)

    Wang, Xin; Ramström, Olof; Yan, Mingdi

    2010-03-01

    Bio-functionalized nanomaterials, which combine functions of biological ligands and unique properties of nano-sized building blocks, have exhibited increased potential applications in biosensing, therapeutics, and diagnostics. Glyconanoparitcles carrying a monolayer of carbohydrate ligands on nanoparticles provide an excellent platform for sensitive protein recognitions. Using Au nanoparticles as the scaffold, multivalent interactions between glycan ligands and proteins have been demonstrated. However, quantitative analysis especially the binding affinity of the resulting glyconanoparticles is challenging to determine. Here we present a new characterization technique, based on fluorescent competition binding assays, for measuring dissociation constants for glyconanoparticles-protein interactions. Au nanoparticles coupled with a series of un-derivatized carbohydrates were prepared by a photocoupling chemistry. Dramatic binding affinity enhancement was observed due to the high ligand density on nanoparticles, which was highly relevant to ligand display, controlled by the linker type, chain length, ligand size and density.

  12. Molecular Weight, Protein Binding Affinity and Methane Mitigation of Condensed Tannins from Mangosteen-peel (Garcinia mangostana L).

    Science.gov (United States)

    Paengkoum, P; Phonmun, T; Liang, J B; Huang, X D; Tan, H Y; Jahromi, M F

    2015-10-01

    The objectives of this study were to determine the molecular weight of condensed tannins (CT) extracted from mangosteen (Garcinia mangostana L) peel, its protein binding affinity and effects on fermentation parameters including total gas, methane (CH4) and volatile fatty acids (VFA) production. The average molecular weight (Mw) of the purified CT was 2,081 Da with a protein binding affinity of 0.69 (the amount needed to bind half the maximum bovine serum albumin). In vitro gas production declined by 0.409, 0.121, and 0.311, respectively, while CH4 production decreased by 0.211, 0.353, and 0.549, respectively, with addition of 10, 20, and 30 mg CT/500 mg dry matter (DM) compared to the control (pmangosteen-peel on in vitro DM degradability (IVDMD) and in vitro N degradability was negative and linear (pmangosteen-peel is lower than those reported for Leucaena forages, however, the former has stronger negative effect on IVDMD. Therefore, the use of mangosteen-peel as protein source and CH4 mitigating agent in ruminant feed requires further investigations.

  13. Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments

    Science.gov (United States)

    Becker, Daniel; Kaczmarska, Zuzanna; Arkona, Christoph; Schulz, Robert; Tauber, Carolin; Wolber, Gerhard; Hilgenfeld, Rolf; Coll, Miquel; Rademann, Jörg

    2016-09-01

    Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme-inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.

  14. Why mammals more susceptible to the hepatotoxic microcystins than fish: evidences from plasma and albumin protein binding through equilibrium dialysis.

    Science.gov (United States)

    Zhang, Wei; Liang, Gaodao; Wu, Laiyan; Tuo, Xun; Wang, Wenjing; Chen, Jun; Xie, Ping

    2013-08-01

    To elucidate the interspecies variation of susceptibility to microcystins (MCs), fresh plasma and purified albumin from six kinds of mammals and fish were used in toxins-substances binding test. Protein contents in the test plasma were analyzed and the binding characteristics to MCs were compared. Two kinds of widely observed MCs, microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were tested and data were collected through the method of equilibrium dialysis. It was found that total plasma protein and albumin content in mammals were nearly two times and four times higher than that in fish, respectively. In the test range of 0-100 μg/mL, binding rates of fish plasma to MCs were considered significant lower (p mammals. And human plasma demonstrated the highest binding rate in mammals. In all the test species, plasma protein binding rates of MC-RR were significantly higher than MC-LR (p 0.05). From the view of protein binding, it is concluded that both the variation of plasma protein composition and albumin binding characteristic could influence the existing form of MCs in circulation, change MCs utilization, alter MCs half-life and further contribute to the difference of susceptibility between mammals and fish.

  15. Stability, protein binding and clearance studies of [99mTc]DTPA. Evaluation of a commercially available dry-kit

    DEFF Research Database (Denmark)

    Rehling, M

    1988-01-01

    [99mTc]DTPA has achieved widespread use for the measurement of glomerular filtration rate (GFR) with the single injection plasma clearance technique and for gamma-camera renography. However, the quality of the commercial preparations varies. The purpose of the present investigation was to study...... the quality of a commercial [99mTc]DTPA preparation (C.I.S., France) with reference to stability, protein binding and accuracy of the determined plasma clearance values as a measure of GFR. The stability of the preparations was studied by thin-layer chromatography, the in vitro protein binding by Sephadex.......7% and 1.1%, respectively. The plasma clearance of [99mTc]DTPA was on an average 3.7% higher than that of [51Cr]EDTA in 27 patients. It is concluded that the [99mTc]DTPA preparation is reliable for the measurement of GFR. The preparation is stable for at least six hours at room temperature...

  16. Layer-by-Layer Deposition with Polymers Containing Nitrilotriacetate, A Convenient Route to Fabricate Metal- and Protein-Binding Films.

    Science.gov (United States)

    Wijeratne, Salinda; Liu, Weijing; Dong, Jinlan; Ning, Wenjing; Ratnayake, Nishanka Dilini; Walker, Kevin D; Bruening, Merlin L

    2016-04-27

    This paper describes a convenient synthesis of nitrilotriacetate (NTA)-containing polymers and subsequent layer-by-layer adsorption of these polymers on flat surfaces and in membrane pores. The resulting films form NTA-metal-ion complexes and capture 2-3 mmol of metal ions per mL of film. Moreover, these coatings bind multilayers of polyhistidine-tagged proteins through association with NTA-metal-ion complexes. Inclusion of acrylic acid repeat units in NTA-containing copolymers promotes swelling to increase protein binding in films on Au-coated wafers. Adsorption of NTA-containing films in porous nylon membranes gives materials that capture ∼46 mg of His-tagged ubiquitin per mL. However, the binding capacity decreases with the protein molecular weight. Due to the high affinity of NTA for metal ions, the modified membranes show modest leaching of Ni(2+) in binding and rinsing buffers. Adsorption of NTA-containing polymers is a simple method to create metal- and protein-binding films and may, with future enhancement of stability, facilitate development of disposable membranes that rapidly purify tagged proteins.

  17. Drug-drug interactions related to altered absorption and plasma protein binding: theoretical and regulatory considerations, and an industry perspective.

    Science.gov (United States)

    Hochman, Jerome; Tang, Cuyue; Prueksaritanont, Thomayant

    2015-03-01

    Drug-drug interactions (DDIs) related to altered drug absorption and plasma protein binding have received much less attention from regulatory agencies relative to DDIs mediated via drug metabolizing enzymes and transporters. In this review, a number of theoretical bases and regulatory framework are presented for these DDI aspects. Also presented is an industry perspective on how to approach these issues in support of drug development. Overall, with the exception of highly permeable and highly soluble (BCS 1) drugs, DDIs related to drug-induced changes in gastrointestinal (GI) physiology can be substantial, thus warranting more attentions. For a better understanding of absorption-associated DDI potential in a clinical setting, mechanistic studies should be conducted based on holistic integration of the pharmaceutical profiles (e.g., pH-dependent solubility) and pharmacological properties (e.g., GI physiology and therapeutic margin) of drug candidates. Although majority of DDI events related to altered plasma protein binding are not expected to be of clinical significance, exceptions exist for a subset of compounds with certain pharmacokinetic and pharmacological properties. Knowledge of the identity of binding proteins and the binding extent in various clinical setting (including disease states) can be valuable in aiding clinical DDI data interpretations, and ensuring safe and effective use of new drugs.

  18. Study on the plasma protein binding rate of Schisandra lignans based on the LC-IT-TOF/MS technique with relative quantitative analysis.

    Science.gov (United States)

    Liang, Yan; Zhou, Yuan-Yuan; Liu, Yan-Na; Guan, Tian-Ye; Zheng, Xiao; Dai, Chen; Xing, Lu; Rao, Tai; Xie, Lin; Wang, Guang-Ji

    2013-07-01

    The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components, and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example. Firstly, the rat, dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract (SLE), and ultramicrofiltration was used to obtain the unbound ingredients. Secondly, thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS. Lastly, a relative exposure approach, which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE, was applied in order to overcome the absence of authentic standards. The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein, furthermore, the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time, which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity. This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.

  19. Case competitions

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram

    2009-01-01

    The paper presents and discusses a teaching project with case competitions for MA students of specialised translation at the Aarhus School of Business, Aarhus University. Drawing on a series of online questionnaires, the paper ascertains how the project was evaluated by the participating students...

  20. Case competitions

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram

    2009-01-01

    The paper presents and discusses a teaching project with case competitions for MA students of specialised translation at the Aarhus School of Business, Aarhus University. Drawing on a series of online questionnaires, the paper ascertains how the project was evaluated by the participating students...

  1. EDITORIAL: Physics competitions Physics competitions

    Science.gov (United States)

    Jordens, H.; Mathelitsch, L.

    2009-11-01

    1. Physics competitions: aims and realizations One aim of physics competitions is to increase the interest of young students, primarily at upper secondary level, to physics and natural sciences in general. A competition has motivational aspects known usually from sports events or games—comparing one's own ability with others, of course with the desire to be better and to win. If competitions reach nationwide and even international levels, additional stimulation is created. Competitions provide greatest attraction to possible winners, to the group of gifted people in a particular field. This implies that science contests are excellent tools for the promotion of talented students. Traditional teaching has been shown to have problems in supporting this group of students. Very often teachers are overstretched with the demands of teaching both low- and high-level students. Extracurricular activities are therefore a good chance to relieve the teacher, and to give talented students the opportunity for appropriate training and challenge. The competitions, however, have a broader impact and address more young people than one might guess from the statements above. Training courses and selection at school level give a larger group of students extra and, to some extent, complimentary education in physics. The degree of complexity of the tasks corresponds very often to the standards of the next level of education in the school system. Interestingly, many physics competitions have their origin in countries beyond the former Iron Curtain. They started as regional and national tournaments, were joined by neighbouring countries and have grown, in some cases, to events with participants from more than 80 countries. Although the features mentioned above are common to the different competitions, there are distinct differences between them [1]. The International Physics Olympiad (IPhO) is the oldest international physics competition for students at upper secondary level [2]. It dates

  2. Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum.

    Science.gov (United States)

    Buscher, Brigitte; Laakso, Sirpa; Mascher, Hermann; Pusecker, Klaus; Doig, Mira; Dillen, Lieve; Wagner-Redeker, Winfried; Pfeifer, Thomas; Delrat, Pascal; Timmerman, Philip

    2014-03-01

    Plasma protein binding (PPB) is an important parameter for a drug's efficacy and safety that needs to be investigated during each drug-development program. Even though regulatory guidance exists to study the extent of PPB before initiating clinical studies, there are no detailed instructions on how to perform and validate such studies. To explore how PPB studies involving bioanalysis are currently executed in the industry, the European Bioanalysis Forum (EBF) has conducted three surveys among their member companies: PPB studies in drug discovery (Part I); in vitro PPB studies in drug development (Part II); and in vivo PPB studies in drug development. This paper reflects the outcome of the three surveys, which, together with the team discussions, formed the basis of the EBF recommendation. The EBF recommends a tiered approach to the design of PPB studies and the bioanalysis of PPB samples: 'PPB screening' experiments in (early) drug discovery versus qualified/validated procedures in drug development.

  3. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao

    2003-01-01

    Short regularly spaced repeats (SRSRs) occur in multiple large clusters in archaeal chromosomes and as smaller clusters in some archaeal conjugative plasmids and bacterial chromosomes. The sequence, size, and spacing of the repeats are generally constant within a cluster but vary between clusters...... that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N...... terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also...

  4. Study of plasma protein binding activity of isometamidium and its impact on anthelmintic activity using trypanosoma induced calf model

    Directory of Open Access Journals (Sweden)

    Suprita Sinha

    Full Text Available Aim: The objective of present study was to determine Plasma Protein Binding (PPB activity and its effect on clinical efficacy of isometamidium after intramuscular administration in calves. The binding of drugs to plasma proteins is an important factor in controlling the availability and distribution of drugs. In general, PPB reduces the free fraction of drug available for therapeutic activity, since only the non-protein bound drug is pharmacologically active. Materials and Methods: Six calves were used for PPB study and eighteen for clinical efficacy. Isometamidium was administered @ 0.5mg/kg intramuscularly as a single dose for PPB study. Equilibrium dialysis technique was used to determine the PPB activity. For clinical efficacy, infection with Trypanosoma was induced in calves of two groups, untreated control and experimental group. Infection was confirmed after 28 days by mice inoculation test. Isometamidium @ 0.5mg/kg was administered to experimental group. Haematoobiochemical and mice inoculation tests were performed after 7 days of drug administration (Day 35. Result: The percentage of PPB activity of isometamidium was 86.71 ± 0.59 to 93.03 ± 0.63% against the concentration 9.76± 0.84 to 4.39 ± 0.20 g ml-1. Higher percentage of PPB activity (>86% suggests greater duration of safety by this drug. It was found that anthelmintic activity of isometamidium was substantially affected by higher PPB. Conclusion: It was concluded that isometamidium has greater plasma protein binding capacity which did not hamper clinical efficacy of drug. [Vet World 2013; 6(7.000: 444-448

  5. Modifications of nano-titania surface for in vitro evaluations of hemolysis, cytotoxicity, and nonspecific protein binding

    Science.gov (United States)

    Datta, Aparna; Dasgupta, Sayantan; Mukherjee, Siddhartha

    2017-04-01

    In the past decade, a variety of drug carriers based on mesoporous silica nanoparticles has been extensively reported. However, their biocompatibility still remains debatable, which motivated us to explore the porous nanostructures of other metal oxides, for example titanium dioxide (TiO2), as potential drug delivery vehicles. Herein, we report the in vitro hemolysis, cytotoxicity, and protein binding of TiO2 nanoparticles, synthesized by a sol-gel method. The surface of the TiO2 nanoparticles was modified with hydroxyl, amine, or thiol containing moieties to examine the influence of surface functional groups on the toxicity and protein binding aspects of the nanoparticles. Our study revealed the superior hemocompatibility of pristine, as well as functionalized TiO2 nanoparticles, compared to that of mesoporous silica, the present gold standard. Among the functional groups studied, aminosilane moieties on the TiO2 surface substantially reduced the degree of hemolysis (down to 5%). Further, cytotoxicity studies by MTT assay suggested that surface functional moieties play a crucial role in determining the biocompatibility of the nanoparticles. The presence of NH2- functional groups on the TiO2 nanoparticle surface enhanced the cell viability by almost 28% as compared to its native counterpart (at 100 μg/ml), which was in agreement with the hemolysis assay. Finally, nonspecific protein adsorption on functionalized TiO2 surfaces was examined using human serum albumin and it was found that negatively charged surface moieties, like -OH and -SH, could mitigate protein adsorption to a significant extent.

  6. Polymerization Degrees, Molecular Weights and Protein-Binding Affinities of Condensed Tannin Fractions from a Leucaena leucocephala Hybrid

    Directory of Open Access Journals (Sweden)

    Mookiah Saminathan

    2014-06-01

    Full Text Available Condensed tannins (CTs form insoluble complexes with proteins and are able to protect them from degradation, which could lead to rumen bypass proteins. Depending on their degrees of polymerization (DP and molecular weights, CT fractions vary in their capability to bind proteins. In this study, purified condensed tannins (CTs from a Leucaena leucocephala hybrid were fractionated into five different molecular weight fractions. The structures of the CT fractions were investigated using 13C-NMR. The DP of the CT fractions were determined using a modified vanillin assay and their molecular weights were determined using Q-TOF LC-MS. The protein-binding affinities of the respective CT fractions were determined using a protein precipitation assay. The DP of the five CT fractions (fractions F1–F5 measured by the vanillin assay in acetic acid ranged from 4.86 to 1.56. The 13C-NMR results showed that the CT fractions possessed monomer unit structural heterogeneity. The number-average molecular weights (Mn of the different fractions were 1265.8, 1028.6, 652.2, 562.2, and 469.6 for fractions F1, F2, F3, F4, and F5, respectively. The b values representing the CT quantities needed to bind half of the maximum precipitable bovine serum albumin increased with decreasing molecular weight—from fraction F1 to fraction F5 with values of 0.216, 0.295, 0.359, 0.425, and 0.460, respectively. This indicated that higher molecular weight fractions of CTs from L. leucocephala have higher protein-binding affinities than those with lower molecular weights.

  7. Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles.

    Science.gov (United States)

    Brender, Jeffrey R; Zhang, Yang

    2015-10-01

    The formation of protein-protein complexes is essential for proteins to perform their physiological functions in the cell. Mutations that prevent the proper formation of the correct complexes can have serious consequences for the associated cellular processes. Since experimental determination of protein-protein binding affinity remains difficult when performed on a large scale, computational methods for predicting the consequences of mutations on binding affinity are highly desirable. We show that a scoring function based on interface structure profiles collected from analogous protein-protein interactions in the PDB is a powerful predictor of protein binding affinity changes upon mutation. As a standalone feature, the differences between the interface profile score of the mutant and wild-type proteins has an accuracy equivalent to the best all-atom potentials, despite being two orders of magnitude faster once the profile has been constructed. Due to its unique sensitivity in collecting the evolutionary profiles of analogous binding interactions and the high speed of calculation, the interface profile score has additional advantages as a complementary feature to combine with physics-based potentials for improving the accuracy of composite scoring approaches. By incorporating the sequence-derived and residue-level coarse-grained potentials with the interface structure profile score, a composite model was constructed through the random forest training, which generates a Pearson correlation coefficient >0.8 between the predicted and observed binding free-energy changes upon mutation. This accuracy is comparable to, or outperforms in most cases, the current best methods, but does not require high-resolution full-atomic models of the mutant structures. The binding interface profiling approach should find useful application in human-disease mutation recognition and protein interface design studies.

  8. Polymerization degrees, molecular weights and protein-binding affinities of condensed tannin fractions from a Leucaena leucocephala hybrid.

    Science.gov (United States)

    Saminathan, Mookiah; Tan, Hui Yin; Sieo, Chin Chin; Abdullah, Norhani; Wong, Clemente Michael Vui Ling; Abdulmalek, Emilia; Ho, Yin Wan

    2014-06-12

    Condensed tannins (CTs) form insoluble complexes with proteins and are able to protect them from degradation, which could lead to rumen bypass proteins. Depending on their degrees of polymerization (DP) and molecular weights, CT fractions vary in their capability to bind proteins. In this study, purified condensed tannins (CTs) from a Leucaena leucocephala hybrid were fractionated into five different molecular weight fractions. The structures of the CT fractions were investigated using 13C-NMR. The DP of the CT fractions were determined using a modified vanillin assay and their molecular weights were determined using Q-TOF LC-MS. The protein-binding affinities of the respective CT fractions were determined using a protein precipitation assay. The DP of the five CT fractions (fractions F1-F5) measured by the vanillin assay in acetic acid ranged from 4.86 to 1.56. The 13C-NMR results showed that the CT fractions possessed monomer unit structural heterogeneity. The number-average molecular weights (Mn) of the different fractions were 1265.8, 1028.6, 652.2, 562.2, and 469.6 for fractions F1, F2, F3, F4, and F5, respectively. The b values representing the CT quantities needed to bind half of the maximum precipitable bovine serum albumin increased with decreasing molecular weight--from fraction F1 to fraction F5 with values of 0.216, 0.295, 0.359, 0.425, and 0.460, respectively. This indicated that higher molecular weight fractions of CTs from L. leucocephala have higher protein-binding affinities than those with lower molecular weights.

  9. EDITORIAL: Physics competitions Physics competitions

    Science.gov (United States)

    Jordens, H.; Mathelitsch, L.

    2010-07-01

    This editorial opens the second special section on physics competitions in European Journal of Physics. In the first section last year, we asked for feedback on the idea of such a section and on the content of the articles. We received no answer whatsoever, which can be interpreted in two ways: the section is not interesting enough to raise motivation for feedback, or the reader is satisfied. Having no indication which scenario is the correct one, we are optimistic and favour the second. The section at hand contains three articles. Again, as last year, the organizer of the annual Olympiad reports on tasks and outcomes of this competition. The Olympiad took place in Merida, Mexico, and was by far the largest event with 316 contestants from 68 countries. Again, the predominance of Asian/Chinese students was manifest, showing how serious the training is taken by both their authorities and students. Unfortunately, the winners of the last International Young Physicists' Tournament (IYPT), the team from Korea, did not accept the offer to report on their prize-winning contribution. We are thankful that two students from Austria, who achieved second place with their team, took over and reported on the task which they presented in the finals of the competition. It connects the fields of sport and physics and explains a special move in skateboarding. The third contribution introduces a different competition, 'International Conference of Young Scientists'. On one hand, as in the Olympiad, it addresses individuals, not teams. On the other, as in the IYPT, students have several months to prepare and also the quality of the presentation is an important element of the judgment. In fact, this competition comes closer to real scientific research compared to the other events. Finally and again, we hope that this section will serve several purposes: To show the competitions as a very important tool in the support of gifted students. To raise awareness amongst university teachers, and

  10. Optimal Competition : A Benchmark for Competition Policy

    NARCIS (Netherlands)

    Boone, J.

    2003-01-01

    This paper introduces optimal competition: the best form of competition in an industry that a competition authority can achieve under the information constraint that it cannot observe firms' effciency levels.We show that the optimal competition outcome in an industry becomes more competitive as more

  11. Logo competition

    CERN Multimedia

    Staff Association

    2013-01-01

    Award of the prizes The price ceremony for the Staff Association’s new logo competition which took place on Friday 1st March at 5 p.m. was a big success. The first prize, an Ezee Suisse electric bike, was won by Paulo Rios, from Portugal. In his absence, the bike was handed to his brother Vitor. The other five winners of the competition also received their prize: Go Sport vouchers. A peize draw was then organized to award 22 other participants with prizes offered by our commercial partners (Aquaparc, BCGE, L’Occitane, Passeport Gourmand, Sephora, Theater La Comédie de Genève), whom we would like to warmly thank. After all prices were distributed the evening continued with discussions around a friendly drink.

  12. The future of competitions

    DEFF Research Database (Denmark)

    Bates, Gary; Jensen, Boris Brorman; Miessen, Markus

    2010-01-01

    We wanted to explore the potential of the competition. The question we asked ourselves was if the competition can generate new, relevant and critical ideas within architecture? We organized an idea competition about the architectural competition....

  13. EDITORIAL: Physics competitions Physics competitions

    Science.gov (United States)

    Jordens, H.; Mathelitsch, L.

    2011-07-01

    International tests on competences, such as TIMSS or PISA, and knowledge of young students have revealed low average scores in many countries, often unexpectedly. One effective measure to increase the average standard of a population is to bring the last third of the group to a higher level. Therefore, many nations put some effort into this activity. This brings the danger that not enough attention is paid to students at the other end, those who are talented. Indeed, it is a very difficult task for a teacher to support the less able and at the same time challenge the gifted students, to lead them to the limits of their abilities and provide for a smooth transition to university study. Physics competitions have been proven to fulfil these last demands to a large degree, and therefore are an important additional and, to some extent, complementary tool for the promotion of talented students. This third special section on physics competitions in European Journal of Physics contains three papers, each dealing with a different form of science contest. The first continues the series of presentations of tasks performed at the International Young Physicists' Tournament, which was held in Vienna in 2011. First place went to the team from Singapore, and they have put their investigation on vertical oscillations of coupled magnets into written form (not required by the tournament, where an oral presentation and a defence and discussion are the central aspects). Their paper shows how rich in physics this problem is, and what level of solutions high-school students can already achieve. Sadly, those responsible for the organization of last year's International Physics Olympiad did not provide us with a report on this competition. This is unfortunate, since the Olympiad in Zagreb was very successful and, in particular, the experimental tasks were creative and demanding. Very similar to the aims and the execution of the Physics Olympiad is the International Olympiad on Astronomy

  14. Release and protein binding of components from resin based composites in native saliva and other extraction media.

    Science.gov (United States)

    Rothmund, Lena; Shehata, Mostafa; Van Landuyt, Kirsten L; Schweikl, Helmut; Carell, Thomas; Geurtsen, Werner; Hellwig, Elmar; Hickel, Reinhard; Reichl, Franz-Xaver; Högg, Christof

    2015-05-01

    Unpolymerized (co)monomers and additives can be released from resin based composites (RBCs) and can enter the human organism. In this study, the binding of ingredients from composites to salivary proteins and plasma proteins was investigated. The composites investigated were Admira(®) flow, Venus(®) Diamond flow, Filtek™ Supreme XTE flow, Tetric EvoCeram(®), Tetric EvoFlow(®). The samples (n=4) were polymerized according to the instructions of the manufacturer of RBCs. The samples were immersed into native saliva, protein-free saliva (artificial saliva), water and ethyl acetate, and incubated at 37°C for 24h or 72h. The eluates were analyzed by gas chromatography/mass spectrometry. To determine the binding to salivary proteins, the concentration of (co)monomers and additives detected in native saliva was compared to the concentration of (co)monomers and additives detected in protein-free saliva, water and ethyl acetate respectively. To assess the affinity of TEGDMA, EGDMA, DEGDMA, PMGDMA, BPA, and DCHP to human serum albumin (HSA) and human α1-acid glycoprotein (AGP), a plasma protein binding assay (ABNOVA, Transil XL PPB Prediction Kit TMP-0212-2096) was performed. The statistical significance (psaliva was significantly lower than the concentration released in protein-free saliva or water (Admira(®) flow: concentration of TEGDMA after 72h: 0.08 mmol/L (native saliva), 0.34 mmol/L (protein-free saliva), 0.39 mmol/L (water)). The concentrations of HEMA, EGDMA, DDDMA and CQ released in native saliva remained even below the detection limit, compared to the other extraction media. Protein binding of the tested methacrylates to HSA+AGP was 82-85%, the binding of DCHP was 96.6%, and the binding of BPA was 95.2%. Artificial saliva or water as extraction medium does not reflect the real physiological situation in the body. Salivary and plasma proteins may bind (co)monomers and additives and may thereby contribute to a lower bioavailability of leachables from RBCs

  15. Predicting protein-binding RNA nucleotides using the feature-based removal of data redundancy and the interaction propensity of nucleotide triplets.

    Science.gov (United States)

    Choi, Sungwook; Han, Kyungsook

    2013-11-01

    Several learning approaches have been used to predict RNA-binding amino acids in a protein sequence, but there has been little attempt to predict protein-binding nucleotides in an RNA sequence. One of the reasons is that the differences between nucleotides in their interaction propensity are much smaller than those between amino acids. Another reason is that RNA exhibits less diverse sequence patterns than protein. Therefore, predicting protein-binding RNA nucleotides is much harder than predicting RNA-binding amino acids. We developed a new method that removes data redundancy in a training set of sequences based on their features. The new method constructs a larger and more informative training set than the standard redundancy removal method based on sequence similarity, and the constructed dataset is guaranteed to be redundancy-free. We computed the interaction propensity (IP) of nucleotide triplets by applying a new definition of IP to an extensive dataset of protein-RNA complexes, and developed a support vector machine (SVM) model to predict protein binding sites in RNA sequences. In a 5-fold cross-validation with 812 RNA sequences, the SVM model predicted protein-binding nucleotides with an accuracy of 86.4%, an F-measure of 84.8%, and a Matthews correlation coefficient of 0.66. With an independent dataset of 56 RNA sequences that were not used in training, the resulting accuracy was 68.1% with an F-measure of 71.7% and a Matthews correlation coefficient of 0.35. To the best of our knowledge, this is the first attempt to predict protein-binding RNA nucleotides in a given RNA sequence from the sequence data alone. The SVM model and datasets are freely available for academics at http://bclab.inha.ac.kr/primer.

  16. Impact of hyperlipidemia on plasma protein binding and hepatic drug transporter and metabolic enzyme regulation in a rat model of gestational diabetes.

    Science.gov (United States)

    Anger, Gregory J; Piquette-Miller, Micheline

    2010-07-01

    It is currently unknown whether gestational diabetes mellitus (GDM), a prevalent obstetrical complication, compounds the changes in drug disposition that occur naturally in pregnancy. Hyperlipidemia occurs in GDM. Using a rat model of GDM, we determined whether excess lipids compete with drugs for plasma protein binding. Because lipids activate nuclear receptors that regulate drug transporters and metabolic enzymes, we used proteome analysis to determine whether hyperlipidemia indirectly leads to the dysregulation of these proteins in the liver. GDM was induced on gestational day 6 (GD6) via streptozotocin injection. Controls received either vehicle alone or streptozotocin with subsequent insulin treatment. Liver and plasma were collected on GD20. Glyburide and saquinavir protein binding was determined by ultrafiltration, and an established solvent method was used for plasma delipidation. Proteomics analysis was performed by using isobaric tags for relative and absolute quantitation methodology with membrane-enriched hepatic protein samples. Relative to controls, GDM rat plasma contained more cholesterol and triglycerides. Plasma protein binding of glyburide and saquinavir was decreased in GDM. Delipidation normalized protein binding in GDM plasma. Proteins linked to lipid metabolism were strongly affected in the GDM proteomics data set, with prohyperlipidemic and antihyperlipidemic changes observed, and formed networks that implicated several nuclear receptors. Up-regulation of drug transporters and metabolic enzymes was observed (e.g., multidrug resistance 1/2, CYP2A1, CYP2B9, and CYP2D3). In this study, GDM-induced hyperlipidemia decreased protein binding and was associated with drug transporter and metabolic enzyme up-regulation in the liver. Both of these findings could change drug disposition in affected pregnancies, compounding changes associated with pregnancy itself.

  17. Isolation and identification of proteins binding to the major breakpoint region(mbr) of bcl2 gene

    Institute of Scientific and Technical Information of China (English)

    Nan Yang; Yujie Sun; Changyan Ma

    2009-01-01

    Objective: We have previously found that mbr is a regulatory element of the bcl2 gene. The objective of this study is to isolate and identify the proteins binding to the 37 mbr in the 3 '-end of the mbr. Methods: Streptavidin magnetic particles were ligated to concatameric oligonucleofides of 37 mbr and incubated with the nuclear extracts of Jurkat cells. The DNA-binding proteins were eluted and then resolved by SDS-PAGE. After silver staining, the protein bands were excised and subjected to MALDI-TOF MS. Results: Several protein bands were detected after the isolation with magnetic particles, and Splicing factor, proline-and glutamine-rich(SFPQ), Poly(ADP-ribose)polymerase I(PARP), and promyelocytic leukemia protein(PML) were identified by MALDI-TOF MS. Conclusion: Several proteins were isolated and identified from the 37 mbr-protein complex. Results of this study establish a foundation for further study of the mechanisms by which mbr executes its regulatory function.

  18. Assessment of algorithms for inferring positional weight matrix motifs of transcription factor binding sites using protein binding microarray data.

    Directory of Open Access Journals (Sweden)

    Yaron Orenstein

    Full Text Available The new technology of protein binding microarrays (PBMs allows simultaneous measurement of the binding intensities of a transcription factor to tens of thousands of synthetic double-stranded DNA probes, covering all possible 10-mers. A key computational challenge is inferring the binding motif from these data. We present a systematic comparison of four methods developed specifically for reconstructing a binding site motif represented as a positional weight matrix from PBM data. The reconstructed motifs were evaluated in terms of three criteria: concordance with reference motifs from the literature and ability to predict in vivo and in vitro bindings. The evaluation encompassed over 200 transcription factors and some 300 assays. The results show a tradeoff between how the methods perform according to the different criteria, and a dichotomy of method types. Algorithms that construct motifs with low information content predict PBM probe ranking more faithfully, while methods that produce highly informative motifs match reference motifs better. Interestingly, in predicting high-affinity binding, all methods give far poorer results for in vivo assays compared to in vitro assays.

  19. Sugar-coated proteins: the importance of degree of polymerisation of oligo-galacturonic acid on protein binding and aggregation.

    Science.gov (United States)

    Xu, Amy Y; Melton, Laurence D; Ryan, Timothy M; Mata, Jitendra P; Jameson, Geoffrey B; Rekas, Agata; Williams, Martin A K; McGillivray, Duncan J

    2017-04-05

    We have simplified the structural heterogeneity of protein-polysaccharide binding by investigating protein binding to oligosaccharides. The interactions between bovine beta-lactoglobulin A (βLgA) and oligo-galacturonic acids (OGAs) with various numbers of sugar residues have been investigated with a range of biophysical techniques. We show that the βLgA-OGA interaction is critically dependent on the length of the oligosaccharide. Isothermal titration calorimetry results suggest that a minimum length of 7 or 8 sugar residues is required in order to exhibit appreciable exothermic interactions with βLgA - shorter oligosaccharides show no enthalpic interactions at any concentration ratio. When titrating βLgA into OGAs with more than 7-8 sugar residues the sample solution also became turbid with increasing amounts of βLgA, indicating the formation of macroscopic assemblies. Circular dichroism, thioflavin T fluorescence and small angle X-ray/neutron scattering experiments revealed two structural regimes during the titration. When OGAs were in excess, βLgA formed discrete assemblies upon OGA binding, and no subsequent aggregation was observed. However, when βLgA was present in excess, multi-scale structures were formed and this eventually led to the separation of the solution into two liquid-phases.

  20. The Electronic Behavior of Zinc-Finger Protein Binding Sites in the Context of the DNA Extended Ladder Model

    Science.gov (United States)

    Oiwa, Nestor; Cordeiro, Claudette; Heermann, Dieter

    2016-05-01

    Instead of ATCG letter alignments, typically used in bioinformatics, we propose a new alignment method using the probability distribution function of the bottom of the occupied molecular orbital (BOMO), highest occupied molecular orbital (HOMO) and lowest unoccupied orbital (LUMO). We apply the technique to transcription factors with Cys2His2 zinc fingers. These transcription factors search for binding sites, probing for the electronic patterns at the minor and major DNA groves. The eukaryotic Cys2His2 zinc finger proteins bind to DNA ubiquitously at highly conserved domains. They are responsible for gene regulation and the spatial organization of DNA. To study and understand these zinc finger DNA-protein interactions, we use the extended ladder in the DNA model proposed by Zhu, Rasmussen, Balatsky & Bishop (2007) te{Zhu-2007}. Considering one single spinless electron in each nucleotide π-orbital along a double DNA chain (dDNA), we find a typical pattern for the bottom of BOMO, HOMO and LUMO along the binding sites. We specifically looked at two members of zinc finger protein family: specificity protein 1 (SP1) and early grown response 1 transcription factors (EGR1). When the valence band is filled, we find electrons in the purines along the nucleotide sequence, compatible with the electric charges of the binding amino acids in SP1 and EGR1 zinc finger.

  1. Multivariate Analysis of Side Effects of Drug Molecules Based on Knowledge of Protein Bindings and ProteinProtein Interactions.

    Science.gov (United States)

    Hasegawa, Kiyoshi; Funatsu, Kimito

    2014-12-01

    Here, we examined the relationships between 969 side effects associated with 658 drugs and their 1368 human protein targets using our hybrid approaches. Firstly, L-shaped PLS (LPLS) was used to construct a multivariate model of side effects and protein bindings of drug molecules. LPLS is an extension of standard PLS regression, where, in addition to the response matrix Y and the regressor matrix X, an extra data matrix Z is constructed that summarizes the background information of X. X and Y are matrices comprising drugs-target proteins, and drugs-side effects, respectively. The Z matrix is the proteinprotein interaction data. From the loading plot of Y, we could identify two remarkable side effects (urinary incontinence and increased salivation) From the corresponding loading plot of X, the responsible protein targets causing each side effect could be estimated (sodium channels and gamma-aminobutyric acid (GABA) receptors). The loading plot of the Z matrix indicated that the GABA receptors interact with each other and they heavily influence the side effect of increased salivation. Secondly, Bayesian classifier methods were separately applied to the cases of the two side effects. That is, the Bayesian classifier method was used to classify drug molecules as binding or not binding to the responsible protein targets associated with each side effect. Using atom-coloring techniques, it was possible to estimate which fragments on the drug molecule might cause the specific side effects. This information is valuable for drug design to avoid specific side effects.

  2. Screening of hepatocyte proteins binding to NS5ABP37 protein by yeast-two hybrid system

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Qing-yong Ma; Xian-kui Meng; Kang Li; Jun Cheng

    2009-01-01

    Objective To investigate the biological function of NS5ABP37 and to look for proteins interacting with NS5ABP37 protein in hepatocytes. Methods We constructed bait plasmid expressing NS5ABP37 protein of hepatitis C virus (HCV) by cloning the gene of NS5ABP37 protein into pGBKT7, then the recombinant plasmid DNA was transformed into yeast AH109 (α type). The transformed yeast AH109 was mated with yeast Y187 (α type) containing liver cDNA library plasmid in 2×YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing X-α-gal for selection and screening. After extracting and sequencing of plasmids from positive (blue) colonies, we made a sequence analysis by bioinformatics. Results We screened twenty-five proteins binding to NS5ABP37, including Homo sapiens cyclin Ⅰ (CCNI) gene, Homo sapiens matrix metallopeptidase 25 (MMP25) and Homo sapiens talin 1. Conclusion The yeast-two hybrid system is an effective method for identifying hepatocyte proteins interacting with NS5ABP37 of HCV. And the biological function of NS5ABP37 may be associated with glycometabolism, lipid metabolism and apoptosis.

  3. Interactome-wide prediction of protein-protein binding sites reveals effects of protein sequence variation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Felipe Leal Valentim

    Full Text Available The specificity of protein-protein interactions is encoded in those parts of the sequence that compose the binding interface. Therefore, understanding how changes in protein sequence influence interaction specificity, and possibly the phenotype, requires knowing the location of binding sites in those sequences. However, large-scale detection of protein interfaces remains a challenge. Here, we present a sequence- and interactome-based approach to mine interaction motifs from the recently published Arabidopsis thaliana interactome. The resultant proteome-wide predictions are available via www.ab.wur.nl/sliderbio and set the stage for further investigations of protein-protein binding sites. To assess our method, we first show that, by using a priori information calculated from protein sequences, such as evolutionary conservation and residue surface accessibility, we improve the performance of interface prediction compared to using only interactome data. Next, we present evidence for the functional importance of the predicted sites, which are under stronger selective pressure than the rest of protein sequence. We also observe a tendency for compensatory mutations in the binding sites of interacting proteins. Subsequently, we interrogated the interactome data to formulate testable hypotheses for the molecular mechanisms underlying effects of protein sequence mutations. Examples include proteins relevant for various developmental processes. Finally, we observed, by analysing pairs of paralogs, a correlation between functional divergence and sequence divergence in interaction sites. This analysis suggests that large-scale prediction of binding sites can cast light on evolutionary processes that shape protein-protein interaction networks.

  4. Lunabotics Mining Competition

    Science.gov (United States)

    Mueller, Rob; Murphy, Gloria

    2010-01-01

    This slide presentation describes a competition to design a lunar robot (lunabot) that can be controlled either remotely or autonomously, isolated from the operator, and is designed to mine a lunar aggregate simulant. The competition is part of a systems engineering curriculum. The 2010 competition winners in five areas of the competition were acknowledged, and the 2011 competition was announced.

  5. Multinationals and Institutional Competitiveness

    DEFF Research Database (Denmark)

    Hull Kristensen, Peer; Morgan, Glenn

    This article discusses how institutional competitiveness and multinationals are mutually enriching concepts. Seen from the perspective of Multinationals, institutional competitiveness becomes expressed at two levels. At the level of corporate HQs institutional competitiveness proves itself...... competitiveness of Liberal Market Economies and Coordinated Markets Economies under the current competitive regime....

  6. Competitive spirit

    Science.gov (United States)

    2000-01-01

    Leicester University will host the 65 international teams of students who will assemble in July for this year's International Physics Olympiad . The last time the Olympiad came to the UK was in 1986 in London, and it was the notable enthusiasm of the Leicester Physics and Astronomy department which persuaded the Olympiad Committee to give them the chance of organizing the prestigious event. The students taking part from all over the world are studying physics at A-level or an equivalent standard and they will take part in an intellectual marathon of theoretical and practical examinations. Each national team comprises five students selected from three rounds of competition and the teams will receive an official welcome from the city, as well as opportunities to visit some of the important educational and cultural centres of the surrounding region. The finalists will also be able to test their skills and initiative at the Challenger Learning Centre, which forms part of Leicester's new National Space Science Centre. Specific information on the event can be found on the Olympiad-2000 website at www.star.le.ac.uk/IphO-2000 . The Rudolf Ortvay problem solving contest in physics, which takes place in November, is a tradition of Eötvös University in Budapest, Hungary. The competition was first opened to international participants in 1998, enabling students from universities around the world to show their knowledge, ingenuity, problem-solving skills and physical insight into problems that are far beyond routine level. The problems (30 - 35 each year) are chosen from different branches of theoretical as well as applied physics. They have varying levels of difficulty, and every contestant can send solutions for ten problems. The focus is not on school-level problem-solving routines but rather on the `physical' way of thinking, recognition of the heart of the problem and an appropriate choice of mathematics. The majority of the assigned problems are original, few having

  7. New ruthenium(II) arene complexes of anthracenyl-appended diazacycloalkanes: effect of ligand intercalation and hydrophobicity on DNA and protein binding and cleavage and cytotoxicity.

    Science.gov (United States)

    Ganeshpandian, Mani; Loganathan, Rangasamy; Suresh, Eringathodi; Riyasdeen, Anvarbatcha; Akbarsha, Mohammad Abdulkadher; Palaniandavar, Mallayan

    2014-01-21

    A series of half-sandwich Ru(II) arene complexes of the type [Ru(η(6)-arene)(L)Cl](PF6) 1-4, where arene is benzene (1, 2) or p-cymene (3, 4) and L is N-methylhomopiperazine (L1) or 1-(anthracen-10-ylmethyl)-4-methylhomopiperazine (L2), has been isolated and characterized by using spectral methods. The X-ray crystal structures of 2, 3 and 4 reveal that the compounds possess a pseudo-octahedral "piano-stool" structure equipped with the arene ligand as the seat and the bidentate ligand and the chloride ion as the legs of the stool. The DNA binding affinity determined using absorption spectral titrations with CT DNA and competitive DNA binding studies varies as 4 > 2 > 3 > 1, depending upon both the arene and diazacycloalkane ligands. Complexes 2 and 4 with higher DNA binding affinities show strong hypochromism (56%) and a large red-shift (2, 10; 4, 11 nm), which reveals that the anthracenyl moiety of the ligand is stacked into the DNA base pairs and that the arene ligand hydrophobicity also dictates the DNA binding affinity. In contrast, the monocationic complexes 1 and 3 are involved in electrostatic binding in the minor groove of DNA. The enhancement in viscosities of CT DNA upon binding to 2 and 4 are higher than those for 1 and 3 supporting the DNA binding modes of interaction inferred. All the complexes cleave DNA effectively even in the absence of an external agent and the cleavage ability is enhanced in the presence of an activator like H2O2. Tryptophan quenching measurements suggest that the protein binding affinity of the complexes varies as 4 > 2 > 3 > 1, which is the same as that for DNA binding and that the fluorescence quenching of BSA occurs through a static mechanism. The positive ΔH(0) and ΔS(0) values for BSA binding of complexes indicate that the interaction between the complexes and BSA is mainly hydrophobic in nature and the energy transfer efficiency has been analysed according to the Förster non-radiative energy transfer theory. The

  8. Novel Prostate Specific Antigen plastic antibody designed withcharged binding sites for an improved protein binding and itsapplication in a biosensor of potentiometric transduction

    OpenAIRE

    Rebelo, Tânia S. C. R.; Santos, C.; Costa-Rodrigues, J.; Fernandes, M. H.; Noronha, João P. C.; Sales, M. Goreti F.

    2014-01-01

    This work shows that the synthesis of protein plastic antibodies tailored with selected charged monomersaround the binding site enhances protein binding. These charged receptor sites are placed over a neutralpolymeric matrix, thus inducing a suitable orientation the protein reception to its site. This is confirmed bypreparing control materials with neutral monomers and also with non-imprinted template. This concepthas been applied here to Prostate Specific Antigen (PSA), the protein of choice...

  9. Productive and Unproductive Competition

    DEFF Research Database (Denmark)

    Guerra, Alice; Luppi, Barbara; Parisi, Francesco

    Conventional theories of competition classify contests as being either “productive,” when the competitive efforts generate a surplus for society, or “unproductive,” when competition generates no social surplus and merely distributes already existing resources. These two discrete categories...... of competition create a division of real-world situations into analytical categories that fails to recognize the entire spectrum of competitive activities. Taking the existing models of productive and unproductive competition as benchmark idealizations, this paper explores the relationship between the privately...... and socially optimal levels of competition in the full range of intermediate cases, as well as in the extremum cases of destructive and super-productive competition....

  10. RNA-protein binding motifs mining with a new hybrid deep learning based cross-domain knowledge integration approach.

    Science.gov (United States)

    Pan, Xiaoyong; Shen, Hong-Bin

    2017-02-28

    RNAs play key roles in cells through the interactions with proteins known as the RNA-binding proteins (RBP) and their binding motifs enable crucial understanding of the post-transcriptional regulation of RNAs. How the RBPs correctly recognize the target RNAs and why they bind specific positions is still far from clear. Machine learning-based algorithms are widely acknowledged to be capable of speeding up this process. Although many automatic tools have been developed to predict the RNA-protein binding sites from the rapidly growing multi-resource data, e.g. sequence, structure, their domain specific features and formats have posed significant computational challenges. One of current difficulties is that the cross-source shared common knowledge is at a higher abstraction level beyond the observed data, resulting in a low efficiency of direct integration of observed data across domains. The other difficulty is how to interpret the prediction results. Existing approaches tend to terminate after outputting the potential discrete binding sites on the sequences, but how to assemble them into the meaningful binding motifs is a topic worth of further investigation. In viewing of these challenges, we propose a deep learning-based framework (iDeep) by using a novel hybrid convolutional neural network and deep belief network to predict the RBP interaction sites and motifs on RNAs. This new protocol is featured by transforming the original observed data into a high-level abstraction feature space using multiple layers of learning blocks, where the shared representations across different domains are integrated. To validate our iDeep method, we performed experiments on 31 large-scale CLIP-seq datasets, and our results show that by integrating multiple sources of data, the average AUC can be improved by 8% compared to the best single-source-based predictor; and through cross-domain knowledge integration at an abstraction level, it outperforms the state-of-the-art predictors by 6

  11. Study on Plasma Protein Binding Rate of Hesperetin in Rats%橙皮素的大鼠血浆蛋白结合率研究

    Institute of Scientific and Technical Information of China (English)

    吴中杰; 张艳; 胡佳骅

    2015-01-01

    目的:研究橙皮素的大鼠血浆蛋白结合率。方法使用平衡透析法模拟橙皮素在体内与血浆蛋白结合的过程,采用高效液相色谱法(HPLC)测定低、中、高3个浓度(0.5,2.5和10μg/ml)的橙皮素在透析袋内血浆中和透析袋外缓冲液中的浓度,计算血浆蛋白结合率。结果低、中、高3个浓度的橙皮素在体外与大鼠血浆蛋白的平均结合率分别为83.5%,84.3%和83.9%,3个浓度之间的血浆蛋白结合率比较,差异无统计学意义( P ﹥0.05)。结论橙皮素具有较高的血浆蛋白结合率,为含橙皮苷药物的临床合理应用提供理论指导。%Objective To study the plasma protein binding rate of hesperetin in rats. Methods The equilibrium dialysis method was used to imitate the in vivo plasma protein binding process of hesperetin. HPLC was adopted to determine the percentages of hesperetin in the plasma of dialysis bag and in the buffer out of the dialysis bag at low,middle and high concentrations(0. 5,2. 5 and10 μg/ ml). Results The aver-age plasma protein binding rates were 83. 5% ,84. 3% and 83. 9% in vitro at the low,middle and high con-centrations of hesperetin. The difference in plasma protein binding rate was not significant among the three concentrations(P ﹥ 0. 05). Conclusion Hesperetin has very high plasma protein binding rate,which pro-vides the theoretic guidance for the clinical rational application of hesperidin drugs.

  12. COMPETITIVENESS AND SUPPORTING THE BUSINESS COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Mester Liana-Eugenia

    2014-12-01

    Full Text Available Competitiveness designates efficiency, productivity, success, adaptability, quality products, optimum costs. Competitiveness is a complex concept which defines the ability of a firm or country to cope with actual or potential competition companies or countries on a particular market, on the world market respectively and it is synonymous with economic efficiency; competitiveness reflects a certain state of the economic activity arising from a certain resource consumption in order to achieve economic goods. Supporting the national competitiveness and flexibility is aimed at a sustained increase in productivity relying on the diversification and the innovation of the domestic industrial base. The Global Competitiveness Report 2011-2012 ranks Romania as the 77th out of 142 assessed economies. Romania has access to a large market and free trade area, which makes it attractive for many foreign companies, but Romania needs a coherent economic policy that changes the approach used today - from the traditionalist design of restructuring following the resources and, therefore, related to the comparative advantage to finding solutions that stimulate the activities based on knowledge and information so that they allow the emphasis of the competitive advantages. This paper aims to identify the factors and reasons that gave rise to the level of competitiveness for some activities or fields of activities from the economy of Romania during the reporting period, as well as the possibilities that would lead to increasing and supporting the competitiveness of the national economy.

  13. Nicotinic stimulation modulates tyrosine hydroxylase mRNA half-life and protein binding to the 3'UTR in a manner that requires transcription.

    Science.gov (United States)

    Roe, David F; Craviso, Gale L; Waymire, Jack C

    2004-01-05

    Tyrosine hydroxylase (TH) expression increases in adrenal chromaffin cells treated with the nicotinic agonist, dimethylphenylpiperazinium (DMPP; 1 microM). We are using this response as a model of the changes in TH level that occur during increased cholinergic neural activity. Here we report a 4-fold increase in TH mRNA half-life in DMPP-treated cells chromaffin cells that is apparent when using a pulse-chase analysis to measure TH mRNA half-life. No increase is apparent using actinomycin D to measure half-life, indicating a requirement for ongoing transcription. Characterization of protein binding to the TH 3'UTR responsible for stabilization using labeled TH 3'UTR probes and electro-mobility shift assays shows the presence of two complexes both of which are increased by DMPP-treatment. The faster migrating complex (FMC) increases 2.5-fold and the slower migrating complex (SMC) increases 1.5-fold. Both changes are prevented by actinomycin D. Characterization of the protein binding to the TH UTR probes indicates SMC is disrupted by polyribonucleotides, poly (A) and poly (U), while binding to FMC is reduced by poly (CU). Separation of UV crosslinked RNA-protein complexes on SDS polyacrylamide gels shows FMC to contain a single protein whereas SMC contains three proteins. Northwesterns yielded similar results. Comparison of DMPP-induced protein binding with the poly C binding protein (PCBP) involved in hypoxia induced rat PC12 TH mRNA stability indicates none of the bovine UTR binding proteins are the PCBP. Thus, nicotinic stimulation produces a transcription-dependent increase in TH mRNA half-life that is mediated by previously unrecognized TH mRNA binding proteins.

  14. Physics Competitions in Hungary

    Science.gov (United States)

    Lugosi, ErzséBet SzéP, Jenö

    The following sections are included: * Description of Physics Competitions in Hungary * Training of the Hungarian Team before the International Physics Olympiad * Few Problems for the Hungarian National Physics Competition for 15 - 16 Year Old students * Problems for the Hungarian National Physics Competition in 1989 for 17 - 18 Year Old Students * Experimental Problems for the Competition of KöMAL for 15 - 18 Year Old Students * Problems for the Hungarian National Physics Competition in 1989 for 17 - 18 Year Old Students * solving this equation we obtain m = 18kg * The work done is 427 joule - 80 joule 347 joule * Experimental Problems for the Competition of KöMAL for 15 - 18 Pear Old Students

  15. Diversifying evolution of competitiveness.

    Science.gov (United States)

    Baldauf, Sebastian A; Engqvist, Leif; Weissing, Franz J

    2014-10-29

    In many species, individuals express phenotypic characteristics that enhance their competitiveness, that is, the ability to acquire resources in competition with others. Moreover, the degree of competitiveness varies considerably across individuals and in time. By means of an evolutionary model, we provide an explanation for this finding. We make the assumption that investment into competitiveness enhances the probability to acquire a high-quality resource, but at the same time reduces the ability of exploiting acquired resources with maximal efficiency. The model reveals that under a broad range of conditions competitiveness either converges to a polymorphic state, where individuals differing in competitive ability stably coexist, or is subject to perpetual transitions between periods of high and low competitiveness. The dynamics becomes even more complex if females can evolve preferences for (or against) competitive males. In extreme cases, such preferences can even drive the population to extinction.

  16. CORCEMA refinement of the bound ligand conformation within the protein binding pocket in reversibly forming weak complexes using STD-NMR intensities

    Science.gov (United States)

    Jayalakshmi, V.; Rama Krishna, N.

    2004-05-01

    We describe an intensity-restrained optimization procedure for refining approximate structures of ligands within the protein binding pockets using STD-NMR intensity data on reversibly forming weak complexes. In this approach, the global minimum for the bound-ligand conformation is obtained by a hybrid structure refinement method involving CORCEMA calculation of intensities and simulated annealing optimization of torsion angles of the bound ligand using STD-NMR intensities as experimental constraints and the NOE R-factor as the pseudo-energy function to be minimized. This method is illustrated using simulated STD data sets for typical carbohydrate and peptide ligands. Our procedure also allows for the optimization of side chain torsion angles of protein residues within the binding pocket. This procedure is useful in refining and improving initial models based on crystallography or computer docking or other algorithms to generate models for the bound ligand (e.g., a lead compound) within the protein binding pocket compatible with solution STD-NMR data. This method may facilitate structure-based drug design efforts.

  17. Simple and Rapid Hollow Fiber Liquid Phase Microextraction Followed by High Performance Liquid Chromatography Method for Determination of Drug-protein Binding

    Institute of Scientific and Technical Information of China (English)

    XI Guo-chen; HU Shuang; BAI Xiao-hong

    2011-01-01

    A method was established using hollow fiber-liquid phase microextraction(HF-LPME) followed by high performance liquid chromatography(HPLC) to determine the concentration of the free(unbound) drug in the solution of the drug and protein.Measurements of drug-protein binding ratios and free drug concentrations were then analyzed with the Klotz equation to determine the equilibrium binding constant and number of binding sites for drug-protein interaction.The optimized method allows one to perform the efficient extraction and separation of free drug from protein-bound drug,protein,and other interfering substances.This approach was used to characterize the binding of the anticholinergic drugs atropine sulfate and scopolamine hydrobromide to proteins in human plasma and bovine serum albumin(BSA).The results demonstrate the utility of HF-LPME method for measuring free drug concentrations in protein-drug mixtures and determining the protein binding parameters of a pharmacologically important class of drugs.

  18. Ireland's Competitiveness Challenge 2011

    OpenAIRE

    2012-01-01

    The NCC publishes two annual competitiveness reports. Ireland's Competitiveness Challenge focuses on the national competitiveness issues of most importance to the enterprise sector and identifies policy recommendations required to address these issues. The report focuses on pursuing policies to improve competitiveness, particularly those to reduce the cost base for enterprise, to enhance the performance of the entire education system, and to deliver meaningful public sector reform. Ireland's ...

  19. Supplementing managed competition.

    Science.gov (United States)

    Higgins, W

    President Clinton's proposal for health care reform calls for managed competition within global expenditure targets. However, it is unlikely that health plans will have sufficient leverage with providers to negotiate arrangements consistent with expenditure targets in nonurban areas. This paper describes a reimbursement system based on competitive prospective payment and capitation (CPPC) which can supplement managed competition in less populous areas or replace managed competition should that strategy prove unsuccessful. The CPPC system is capable of enforcing an expenditure target while encouraging the formation of capitated networks and creating strong incentives for efficiency. It is generally compatible with the Clinton administration's version of managed competition.

  20. Gender and Competition in Adolescence

    DEFF Research Database (Denmark)

    Dreber, Anna; Essen, Emma von; Ranehill, Eva

    2013-01-01

    We look at gender differences among adolescents in Sweden in preferences for competition, altruism and risk. For competitiveness, we explore two different tasks that differ in associated stereotypes. We find no gender difference in competitiveness when comparing performance under competition...

  1. Preclinical pharmacokinetics, tissue distribution and plasma protein binding of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP, an innovative potent anti-ischemic stroke agent

    Directory of Open Access Journals (Sweden)

    Xin Tian

    2016-08-01

    Full Text Available Sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H-isobenzofuranone (Br-NBP in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution and plasma protein binding of BZP and Br-NBP, a rapid, sensitive and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6 and 12 mg/kg; i.v. and beagle dogs (1, 2 and 4 mg/kg; i.v.gtt were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO rats was more than in normal rats (P<0.05. The plasma protein binding degree of BZP at three concentrations (8000, 20000 and 80000 ng/mL from rat, beagle dog and human plasma were 98.1~98.7%, 88.9~92.7% and 74.8%~83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

  2. Approximate kernel competitive learning.

    Science.gov (United States)

    Wu, Jian-Sheng; Zheng, Wei-Shi; Lai, Jian-Huang

    2015-03-01

    Kernel competitive learning has been successfully used to achieve robust clustering. However, kernel competitive learning (KCL) is not scalable for large scale data processing, because (1) it has to calculate and store the full kernel matrix that is too large to be calculated and kept in the memory and (2) it cannot be computed in parallel. In this paper we develop a framework of approximate kernel competitive learning for processing large scale dataset. The proposed framework consists of two parts. First, it derives an approximate kernel competitive learning (AKCL), which learns kernel competitive learning in a subspace via sampling. We provide solid theoretical analysis on why the proposed approximation modelling would work for kernel competitive learning, and furthermore, we show that the computational complexity of AKCL is largely reduced. Second, we propose a pseudo-parallelled approximate kernel competitive learning (PAKCL) based on a set-based kernel competitive learning strategy, which overcomes the obstacle of using parallel programming in kernel competitive learning and significantly accelerates the approximate kernel competitive learning for large scale clustering. The empirical evaluation on publicly available datasets shows that the proposed AKCL and PAKCL can perform comparably as KCL, with a large reduction on computational cost. Also, the proposed methods achieve more effective clustering performance in terms of clustering precision against related approximate clustering approaches.

  3. Identification of cellular proteins that interact with Newcastle Disease Virus and human Respiratory Syncytial Virus by a two-dimensional virus overlay protein binding assay (VOPBA).

    Science.gov (United States)

    Holguera, Javier; Villar, Enrique; Muñoz-Barroso, Isabel

    2014-10-13

    Although it is well documented that the initial attachment receptors for Newcastle Disease Virus (NDV) and Respiratory Syncytial Virus (RSV) are sialic acid-containing molecules and glycosaminoglycans respectively, the exact nature of the receptors for both viruses remains to be deciphered. Moreover, additional molecules at the host cell surface might be involved in the entry mechanism. With the aim of identifying the cellular proteins that interact with NDV and RSV at the cell surface, we performed a virus overlay protein binding assay (VOPBA). Cell membrane lysates were separated by two dimensional (2D) gel electrophoresis and electrotransferred to PVDF membranes, after which they were probed with high viral concentrations. NDV interacted with a Protein Disulfide Isomerase from chicken fibroblasts. In the case of RSV, we detected 15 reactive spots, which were identified as six different proteins, of which nucleolin was outstanding. We discuss the possible role of PDI and nucleolin in NDV and RSV entry, respectively.

  4. Synthesis, characterization of α-amino acid Schiff base derived Ru/Pt complexes: Induces cytotoxicity in HepG2 cell via protein binding and ROS generation

    Science.gov (United States)

    Alsalme, Ali; Laeeq, Sameen; Dwivedi, Sourabh; Khan, Mohd. Shahnawaz; Al Farhan, Khalid; Musarrat, Javed; Khan, Rais Ahmad

    2016-06-01

    We have synthesized two new complexes of platinum (1) and ruthenium (2) with α-amino acid, L-alanine, and 2,3-dihydroxybenzaldehyde derived Schiff base (L). The ligand and both complexes were characterized by using elemental analysis and several other spectroscopic techniques viz; IR, 1H, 13C NMR, EPR, and ESI-MS. Furthermore, the protein-binding ability of synthesized complexes was monitored by UV-visible, fluorescence and circular dichroism techniques with a model protein, human serum albumin (HSA). Both the PtL2 and RuL2 complexes displayed significant binding towards HSA. Also, in vitro cytotoxicity assay for both complexes was carried out on human hepatocellular carcinoma cancer (HepG2) cell line. The results showed concentration-dependent inhibition of cell viability. Moreover, the generation of reactive oxygen species was also evaluated, and results exhibited substantial role in cytotoxicity.

  5. Unusual mode of protein binding by a cytotoxic π-arene ruthenium(ii) piano-stool compound containing an O,S-chelating ligand.

    Science.gov (United States)

    Hildebrandt, Jana; Görls, Helmar; Häfner, Norman; Ferraro, Giarita; Dürst, Matthias; Runnebaum, Ingo B; Weigand, Wolfgang; Merlino, Antonello

    2016-08-02

    A new pseudo-octahedral π-arene ruthenium(ii) piano-stool compound, containing an O,S-bidentate ligand (compound 1) and showing significant cytotoxic activity in vitro, was synthesized and characterized. In solution stability and interaction with the model protein bovine pancreatic ribonuclease (RNase A) were investigated by using UV-Vis absorption spectroscopy. Its crystal structure and that of the adduct formed upon reaction with RNase A were obtained by X-ray crystallography. The comparison between the structure of purified compound 1 and that of the fragment bound to RNase A reveals an unusual mode of protein binding that includes ligand exchange and alteration of coordination sphere geometry.

  6. Application of hollow fiber-supported liquid-phase microextraction coupled with HPLC for the determination of guaifenesin enantiomer-protein binding.

    Science.gov (United States)

    Hatami, Mehdi; Farhadi, Khalil

    2012-07-01

    A hollow fiber liquid-phase microextraction technique coupled with high-performance liquid chromatography with fluorescence detection was employed for determination and evaluation of the binding characteristics of drugs to bovine serum albumin (BSA). Enantiomers of guaifenesin (an expectorant drug) were investigated as a model system. After optimization of some influencing parameters on microextraction, the proposed method was used for calculation of the target drug distribution coefficient between n-octanol and the buffer solution as well as study of drug-BSA binding in physiological conditions. The developed method shows a new, improved and simple procedure for determination of free drug concentration in biological fluids and the extent of drug-protein binding. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle

    DEFF Research Database (Denmark)

    Frøsig, Christian; Pehmøller, Christian; Birk, Jesper Bratz

    2010-01-01

    TBC1D1 is a Rab-GTPase activating protein involved in regulation of GLUT4 translocation in skeletal muscle. We here evaluated exercise-induced regulation of TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. In separate experiments healthy men performed all......-out cycle exercise lasting either 30 sec, 2 min or 20 min. After all exercise protocols, TBC1D1 Ser237 phosphorylation increased (~70 - 230%, Pprotein showed a similar pattern of regulation...... increasing 60 - 250% (Pprotein kinase (AMPK) induced both Ser237 phosphorylation and 14-3-3 binding properties on human TBC1D1 when evaluated in vitro. To further characterize the role of AMPK as an upstream kinase regulating TBC1D1, extensor digitorum longus...

  8. A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2016-04-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Influence of one- and two-dimensional gel electrophoresis procedure on metal-protein bindings examined by electrospray ionization mass spectrometry, inductively coupled plasma mass spectrometry, and ultrafiltration.

    Science.gov (United States)

    Schmidt, Anne-Christine; Störr, Bianca; Kummer, Nicolai-Alexeji

    2011-08-15

    Three independent methods, (i) electrospray ionization mass spectrometry (ESI-MS), (ii) carrying out the complete protein preparation procedure required for protein gel electrophoresis (GE) including extraction, precipitation, washing, and desalting with subsequent microwave digestion of the produced protein fractions for metal content quantification, and (iii) ultrafiltration for separating protein-bound and unbound metal fractions, were employed to elucidate the influences of protein sample preparation and GE running conditions on metal-protein bindings. A treatment of the protein solution with acetone instead of trichloroacetic acid or ammonium sulfate for precipitate formation led to a strongly enhanced metal binding capacity. The desalting step of the resolubilized protein sample caused a metal loss between 10 and 35%. The omission of some extraction buffer additives led to a diminished metal binding capacity of protein fractions obtained from the sample preparation procedure for GE, whereas a tenside addition to the protein solution inhibited metal-protein bindings. The binding stoichiometry of Cu and Zn-protein complexes determined by ESI-MS was influenced by the type of the metal salt which was applied to the protein solution. A higher pH value of the sample solution promoted the metal ion complexation by the proteins. Ultrafiltration experiments revealed a higher Cu- and Zn-binding capacity of the model protein lysozyme in both resolubilization buffers for 1D- and 2D-GE compared to the protein extraction buffer. Strongly diminished metal binding capacities of lysozyme were recorded in the running buffer of 1D-GE and in the gel staining solutions.

  10. The importance of protein binding for the in vitro-in vivo extrapolation (IVIVE)-example of ibuprofen, a highly protein-bound substance.

    Science.gov (United States)

    Mielke, H; Di Consiglio, E; Kreutz, R; Partosch, F; Testai, E; Gundert-Remy, U

    2017-04-01

    A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading to the same concentration-time profile as measured in cultured human hepatic cells (Truisi et al. in Toxicol Lett 233(2):172-186, 2015). We parameterized the PBHKM with data from an in vivo study. Tissue partition coefficients were calculated by an algorithm and also derived from the experimental in vitro data for the liver. The predicted concentration-time profile in plasma was in excellent agreement with human experimental data when the liver partition coefficient was calculated by the algorithm (3.01) demonstrating values in line with findings obtained from human postmortem tissues. The results were less adequate when the liver partition coefficient was based on the experimental in vitro data (11.1). The in vivo doses necessary to reach the in vitro concentrations in the liver cells were 3610 mg using the best fitting model with a liver partition coefficient of 3.01 compared to 2840 mg with the in vitro liver partition coefficient of 11.1. We found that this difference is possibly attributable to the difference between protein binding in vivo (99.9 %) and in vitro (nearly zero) as the partition coefficient is highly dependent on protein binding. Hence, the fraction freely diffusible in the liver tissue is several times higher in vitro than in vivo. In consequence, when extrapolating from in vitro to in vivo liver toxicity, it is important to consider non-intended in vitro/in vivo differences in the tissue concentration which may occur due to a low protein content of the medium.

  11. Heterogeneous logics of competition

    DEFF Research Database (Denmark)

    Mossin, Christiane

    2015-01-01

    The purpose of the article is to demonstrate that in order to understand competition as a socially organizing phenomenon, we should not examine competition in isolation, but as constellations of heterogeneous logics. More precisely, the article is based on two main theoretical points: (1) Logics...... of competition are only realized as particular forms of social organization by virtue of interplaying with other kinds of logics, like legal logics. (2) Competition logics enjoy a peculiar status in-between constructedness and givenness; although competition depends on laws and mechanisms of socialization, we...... still experience competition as an expression of spontaneous human activities. On the basis of these perspectives, a study of fundamental rights of EU law, springing from the principle of ‘free movement of people’, is conducted. The first part of the empirical analysis seeks to detect the presence...

  12. Competition in treasury auctions

    OpenAIRE

    Elsinger, Helmut; Schmidt-Dengler, Philipp; Zulehner, Christine

    2016-01-01

    We investigate the role of competition on the outcome of Austrian Treasury auctions. Austria's EU accession led to an increase in the number of banks participating in treasury auctions. We use structural estimates of bidders' private values to examine the effect of increased competition on auction performance: We find that increased competition reduced bidder surplus substantially, but less than reduced form estimates would suggest. A significant component of the surplus reduction is due to m...

  13. Intramural Gymnastics Competition.

    Science.gov (United States)

    Cornelius, William L.

    1981-01-01

    An intramural gymnastic competition, if properly organized, can foster student and community interest in gymnastics. Aspects of organization and essential preplanning include: directing, judging, scoring, and managing. (JN)

  14. Intramural Gymnastics Competition.

    Science.gov (United States)

    Cornelius, William L.

    1981-01-01

    An intramural gymnastic competition, if properly organized, can foster student and community interest in gymnastics. Aspects of organization and essential preplanning include: directing, judging, scoring, and managing. (JN)

  15. Maternal Competition in Women.

    Science.gov (United States)

    Linney, Catherine; Korologou-Linden, Laurel; Campbell, Anne

    2017-03-01

    We examined maternal competition, an unexplored form of competition between women. Given women's high investment in offspring and mothers' key role in shaping their reproductive, social, and cultural success as adults, we might expect to see maternal competition between women as well as mate competition. Predictions about the effect of maternal characteristics (age, relationship status, educational background, number of children, investment in the mothering role) and child variables (age, sex) were drawn from evolutionary theory and sociological research. Mothers of primary school children (in two samples: N = 210 and 169) completed a series of questionnaires. A novel nine-item measure of maternal competitive behavior (MCQ) and two subscales assessing Covert (MCQ-C) and Face-to-Face (MCQ-FF) forms of competition were developed using confirmatory factor analysis. Competitiveness (MCQ score) was predicted by maternal investment, single motherhood, fewer children, and (marginally) child's older age. The effect of single motherhood (but not other predictors) was partially mediated by greater maternal investment. In response to a scenario of their child underperforming relative to their peers, a mother's competitive distress was a positive function of the importance she ascribed to their success and her estimation of her child's ability. Her competitive distress was highly correlated with the distress she attributed to a female friend, hinting at bidirectional dyadic effects. Qualitative responses indicated that nonspecific bragging and boasting about academic achievements were the most common irritants. Although 40% of women were angered or annoyed by such comments, less than 5% endorsed a direct hostile response. Instead, competitive mothers were conversationally shunned and rejected as friends. We suggest that the interdependence of mothers based on reciprocal childcare has supported a culture of egalitarianism that is violated by explicit competitiveness.

  16. Platinum group metallodrug-protein binding studies by capillary electrophoresis - inductively coupled plasma-mass spectrometry: a further insight into the reactivity of a novel antitumor ruthenium(III) complex toward human serum proteins.

    Science.gov (United States)

    Polec-Pawlak, Kasia; Abramski, Jan K; Semenova, Olga; Hartinger, Christian G; Timerbaev, Andrei R; Keppler, Bernhard K; Jarosz, Maciej

    2006-03-01

    Biochemical speciation analysis has become a hot area of CE research due largely to growing emergence of inductively coupled plasma (ICP)-MS as a proper detection technique. A benefit of CE-ICP-MS coupling in species-selective analysis of anticancer metal-based drugs is the possibility of distinguishing the signals of the intact drug and its metabolites and hence of quantifying them independently. This advantage (over CE with UV-vis detection) was exploited here in order to gain better knowledge about the rate and degree of the transformation of indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019), a promising tumor-inhibiting agent that successfully finished phase I clinical studies, upon its binding toward individual serum transport proteins. At increasing the KP1019/protein molar ratio, the reaction rate expressed by an evolving peak of the protein adduct became faster, with the equilibrium state being reached after about 40 and 60 min of incubation at 37 degrees C for transferrin and albumin, respectively. The binding reaction was shown to obey the first-order character that enabled for reliable calculation of the corresponding rate constants as (28.7 +/- 1.5) x 10(-4) and (10.6 +/- 0.7) x 10(-4)/s, respectively. When incubated with a ten-fold excess of KP1019, albumin and transferrin bound, respectively, up to 8 and 10 equiv. of ruthenium (Ru). Relative affinity of KP1019 toward different proteins under simulated physiological conditions was also characterized in terms of the overall binding constants (5600 and 10 600/M, respectively). To emphasize the difference in the protein-binding behavior, a competitive interaction of KP1019 was followed by CE-ICP-MS at the actual molar ratio of proteins in blood, i.e. a ten-fold excess of albumin over transferrin. The fact that KP1019 binds to albumin stronger than to transferrin was manifested by finding almost all ruthenium (98-99%) in the albumin fraction.

  17. Competition: Was Kohn Right?

    Science.gov (United States)

    Shields, David Light; Bredemeier, Brenda Light

    2010-01-01

    Alfie Kohn made the case for competition being destructive to education. The truth may be that there are two separate ways to contest: true competition, which is a healthy desire to excel, and decompetition, which is the unhealthy desire merely to beat the opponent. Decompetition leads to the ills that Kohn enumerated. Educators should teach their…

  18. Competition, Ownership and Productivity

    DEFF Research Database (Denmark)

    Baghdasaryan, Delia; la Cour, Lisbeth

    2013-01-01

    Theoretical results support two concurrent views regarding the mediating role that ownership structure might play on the effect of competition on firm performance. According to one stream of literature, competition has a high, positive impact in companies that have an effective ownership structur...

  19. Competition in investment banking

    Directory of Open Access Journals (Sweden)

    Katrina Ellis

    2011-01-01

    Full Text Available We construct a comprehensive measure of overall investment banking competitiveness for follow-on offerings that aggregates the various dimensions of competition such as fees, pricing accuracy, analyst recommendations, distributional abilities, market making prowess, debt offering capabilities, and overall reputation. The measure allows us to incorporate trade-offs that investment banks may use in competing for new or established clients. We find that firms who switch to similar-quality underwriters enjoy more intense competition among investment banks which manifests in lower fees and more optimistic recommendations. Investment banks do compete vigorously for some clients, with the level of competition related to the likelihood of gaining or losing clients. Finally, investment banks not performing up to market norms are more likely to be dropped in the follow-on offering. In contrast, firms who seek a higher reputation underwriter face relatively non-competitive markets.

  20. Pharmacokinetics, protein binding and metabolic profile of 3H-icometasone enbutate following intravenous, oral and intratracheal administrations to Sprague-Dawley rats.

    Science.gov (United States)

    Duchêne, P; Giudicelli, M D; Neau, B; Gronfier, A; Firmin, Y; Villax, P; Saivin, S; Houin, G

    1998-04-01

    Absorption, distribution and excretion of 3H-icometasone enbutate (9 alpha-chloro-11 beta,17 alpha,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 17-butyrate, 21-acetate, CAS 103466-73-5 CL09) were studied in male and female Sprague-Dawley rats after a single dose administration by intravenous (1 mg/kg), oral and intratracheal (2 mg/kg) routes. The metabolic profile after the different routes and protein binding were also determined. Independent of the route, the radioactivity was mainly excreted in faeces. Less than 10% of the dose were excreted in urine. The majority of the administered doses was recovered within 24 h postdose, and the total recovery of the doses administered was obtained. After oral and intravenous administration to bile-duct cannulated rats, most of the radioactivity was excreted in the bile (80% of the administered dose) and some radioactivity was found in the faeces. It can thus be concluded that some intestinal secretion occurred. After oral administration, mean maximum blood concentrations were obtained about 0.75 h postdose. For the intratracheal route, the radioactive dose administered was too low to determine precise blood pharmacokinetic parameters. However, the distribution study results allowed us to conclude that the drug was absorbed first from the lungs and then from the gastrointestinal tract. Immediately after the intravenous injection, the liver, the kidneys, the small intestine and its contents and the carcass presented the highest levels of radioactivity. 168 h postdose, low radioactivity was still measurable in these organs. In other tissues, the radioactivity decreased reaching the limit of quantification 72 h postdose. After oral administration, the maximum concentrations were observed 1 h after administration in the liver, the small intestine and its contents. Then the radioactivity decreased in most of the tissues but a slight increase at 72 and/or 120 h postdose was noted in large intestine contents, carcass

  1. Study on plasma protein binding rate of naringin in rats%柚皮苷的大鼠血浆蛋白结合率研究

    Institute of Scientific and Technical Information of China (English)

    李季泓

    2015-01-01

    目的:研究柚皮苷的大鼠血浆蛋白结合率。方法使用平衡透析法模拟柚皮苷在体内与血浆蛋白结合的过程,并建立测定柚皮苷的高效液相色谱-质谱联用( HPLC-MS/MS)方法,测定低、中、高3个浓度(100、600、3600 ng/mL)的柚皮苷在透析袋内血浆中和透析袋外缓冲液中的浓度,计算血浆蛋白结合率。结果低、中、高3个浓度的柚皮苷在体外与大鼠的平均血浆蛋白结合率分别为91.5%、90.5%和96.3%,3个浓度之间的血浆蛋白结合率比较差异无统计学意义(P>0.05)。结论柚皮苷与大鼠血浆蛋白高度结合。%Objective To study the plasma protein binding rate of naringin in rats. Methods Under three dif-ferent concentrations (100,600 and 3 600 ng/mL),this paper used equilibrium dialysis method to imitate the binding process between naringin and the plasma protein of rats,and determined the concentration of naringin in and out of the dialysis membrane by high performance liquid chromatography-tandem mass spectrometry ( LC-MS/MS) method. The binding rate was calculated. Results Under the experimental concentrations,the plasma protein binding rates of naring-in in rats were 91. 5%,90. 5% and 96. 3% at low,middle and high concentrations,respectively. There was no signifi-cant difference among the three concentrations. Conclusion Naringin is highly bound to plasma proteins in rats.

  2. Competition Policy and Innovation

    DEFF Research Database (Denmark)

    Møllgaard, Peter; Lorentzen, Jo

    2005-01-01

    We briefly review the rationale behind technological alliances and provide a snapshot oftheir role in global competition, especially insofar as it is based around intellectual capital.They nicely illustrate the increased importance of horizontal agreements and thusestablish the relevance...... of the topic. We move on to discuss the organisation of industriesin a dynamic context and draw out consequences for competition policy. We concludewith an outlook on the underlying tensions between technology alliances, competitionpolicy, and industrial policy.JEL codes: L4, L5, O31Keywords: Competition...

  3. Competition in education

    DEFF Research Database (Denmark)

    Knudsen, Hanne; Christensen, Søren

    Competition in education has two functions: selection and motivation. How do these two functions correlate, contradict or co-exist? How has the educational system reflected on the relation between competition as motivational technology and as a technology for selection? The aim of this paper...... is to formulate the problem of competition in education as a relation between selection and motivation and provide an analytical strategy to grasp this problem. Our ambition is to theorize the problem and give empirical illustrations of how the connection between selection and motivation has been articulated...... in various educational institutions and programs....

  4. Competition from Isotopic Modelling

    Directory of Open Access Journals (Sweden)

    Virginie Fabre

    2011-01-01

    Full Text Available During later MOIS3, in Europe two populations were present, autochthonous Neanderthals and modern humans. Ecological competition between these two populations has often been evoked but never demonstrated. Our aim is to establish whether resource competition occurred. In this paper, in order to examine the possibility of ecological competition between these two populations, 599 isotopic data were subjected to rigorous statistical treatment and analysis through mixing models. The aim of this paper was to compare dietary strategies of Neanderthals and modern humans over time. Our conclusions suggest that Neanderthals and modern humans shared dietary habits in the particular environmental context of MOIS3 characterised in Europe by climatic deterioration. In this environmental context, the resource competition between Neanderthals and modern humans may have accelerated the disappearance of the Neanderthal population.

  5. Competition between Women.

    Science.gov (United States)

    Joseph, R.

    1985-01-01

    Examined competition and physical attractiveness among women. Results indicated that a large number of females are highly critical of other women, particularly attractive ones, and are highly concerned about their own appearance in relation to other women. (Author/BL)

  6. Heterogeneous logics of competition

    DEFF Research Database (Denmark)

    Mossin, Christiane

    2015-01-01

    The purpose of the article is to demonstrate that in order to understand competition as a socially organizing phenomenon, we should not examine competition in isolation, but as constellations of heterogeneous logics. More precisely, the article is based on two main theoretical points: (1) Logics...... still experience competition as an expression of spontaneous human activities. On the basis of these perspectives, a study of fundamental rights of EU law, springing from the principle of ‘free movement of people’, is conducted. The first part of the empirical analysis seeks to detect the presence...... of a presumed logic of competition within EU law, whereas the second part focuses on particular legal logics. In this respect, the so-called ‘real link criterion’ (determining the access to transnational social rights for certain groups of unemployed people) is given special attention. What is particularly...

  7. DMEPOS Competitive Bidding

    Data.gov (United States)

    U.S. Department of Health & Human Services — The DMEPOS Competitive Bidding Program was mandated by Congress through the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The statute...

  8. COMPETITIVENESS FOR SUSTAINABLE ECONOMIES

    Directory of Open Access Journals (Sweden)

    Nelu Eugen POPESCU

    2014-04-01

    Full Text Available The current economic environment puts pressure on all national economies which struggle to improve their competitiveness and innovativeness in a sustainable way. This article aims to present the current state of the competitiveness by reviewing the main literature and worldwide researches, in order to provide a brief overview of the determinants that drive productivity and economic success at global and national level, taking into consideration the entrepreneurial activity for a country’s competitiveness and economic growth. The paper identifies the ways in which efficiency driven countries can improve their policies and get a better return on their investments, underlining a set of competitiveness enhancing policies (measures that can be implemented by public and private institutions in order to strengthen the economic fundamentals of the economies.

  9. Competition and Cheating

    Science.gov (United States)

    ... Cheating Family Life Listen Español Text Size Email Print Share Competition and Cheating Page Content Article Body My son tends to cheat when he plays games. What should we do? Cheating is the result ...

  10. Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

    Science.gov (United States)

    Tang, Dao-quan; Li, Yin-jie; Li, Zheng; Bian, Ting-ting; Chen, Kai; Zheng, Xiao-xiao; Yu, Yan-yan; Jiang, Shui-shi

    2015-08-01

    In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.

  11. BayesPI - a new model to study protein-DNA interactions: a case study of condition-specific protein binding parameters for Yeast transcription factors

    Directory of Open Access Journals (Sweden)

    Morigen

    2009-10-01

    Full Text Available Abstract Background We have incorporated Bayesian model regularization with biophysical modeling of protein-DNA interactions, and of genome-wide nucleosome positioning to study protein-DNA interactions, using a high-throughput dataset. The newly developed method (BayesPI includes the estimation of a transcription factor (TF binding energy matrices, the computation of binding affinity of a TF target site and the corresponding chemical potential. Results The method was successfully tested on synthetic ChIP-chip datasets, real yeast ChIP-chip experiments. Subsequently, it was used to estimate condition-specific and species-specific protein-DNA interaction for several yeast TFs. Conclusion The results revealed that the modification of the protein binding parameters and the variation of the individual nucleotide affinity in either recognition or flanking sequences occurred under different stresses and in different species. The findings suggest that such modifications may be adaptive and play roles in the formation of the environment-specific binding patterns of yeast TFs and in the divergence of TF binding sites across the related yeast species.

  12. UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein–DNA interactions

    Science.gov (United States)

    Hume, Maxwell A.; Barrera, Luis A.; Gisselbrecht, Stephen S.; Bulyk, Martha L.

    2015-01-01

    The Universal PBM Resource for Oligonucleotide Binding Evaluation (UniPROBE) serves as a convenient source of information on published data generated using universal protein-binding microarray (PBM) technology, which provides in vitro data about the relative DNA-binding preferences of transcription factors for all possible sequence variants of a length k (‘k-mers’). The database displays important information about the proteins and displays their DNA-binding specificity data in terms of k-mers, position weight matrices and graphical sequence logos. This update to the database documents the growth of UniPROBE since the last update 4 years ago, and introduces a variety of new features and tools, including a new streamlined pipeline that facilitates data deposition by universal PBM data generators in the research community, a tool that generates putative nonbinding (i.e. negative control) DNA sequences for one or more proteins and novel motifs obtained by analyzing the PBM data using the BEEML-PBM algorithm for motif inference. The UniPROBE database is available at http://uniprobe.org. PMID:25378322

  13. A Comparison of LC-MS/MS and a Fully Integrated Autosampler/Solid-Phase Extraction System for the Analysis of Protein Binding Samples.

    Science.gov (United States)

    Amaral, Adam; Saran, Chitra; Amin, Jakal; Hatsis, Panos

    2016-07-01

    A new analysis approach was evaluated for measuring plasma protein binding (PPB) of small molecules using the Agilent RapidFire high-throughput system coupled with a Sciex API 4000 mass spectrometer (RF-MS/MS). Thirty-three proprietary and 12 literature compounds were subjected to rapid equilibrium dialysis (RED) and evaluated in parallel using RF-MS/MS at 16.4 s/sample and traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS) at 3.5 min/sample, thus making the RF-MS/MS analysis over 12 times faster than LC-MS/MS. The high-throughput analysis method that was developed demonstrated excellent correlation with the traditional LC-MS/MS analysis method with an r(2) value of 0.96. The RF-MS/MS analysis method was implemented to increase sample throughput, decrease turnaround time for PPB data, and decrease time burden on existing LC-MS/MS instruments. © 2016 Society for Laboratory Automation and Screening.

  14. Synthesis and Structure of a Ternary Copper(II) Complex with Mixed Ligands of Diethylenetriamine and Picrate: DNA/Protein-Binding Property and In Vitro Anticancer Activity Studies.

    Science.gov (United States)

    Shi, Ya-Ning; Zheng, Kang; Zhu, Ling; Li, Yan-Tuan; Wu, Zhi-Yong; Yan, Cui-Wei

    2015-05-01

    Based on the importance of the design and synthesis of transition metal complexes with noncovalent DNA/protein-binding abilities in the field of metallo pharmaceuticals, a new mononuclear ternary copper(II) complex with mixed ligands of diethylenetriamine (dien) and picrate anion (pic), identified as [Cu(dien)(pic)](pic), was synthesized and characterized by elemental analysis, molar conductivity measurement, infrared spectrum, electronic spectral studies, and single-crystal X-ray diffractometry. The structure analysis reveals that the copper(II) complex crystallizes in the monoclinic space group P21 /c, and the copper(II) ion has a distorted square pyramidal coordination geometry. A two-dimensional supramolecular structure is formed through hydrogen bonds. The DNA/bovine serum albumin (BSA)-binding properties of the complex are explored, indicating that the complex can interact with herring sperm DNA via intercalation mode and bind to BSA responsible for quenching of tryptophan fluorescence by static quenching mechanism. The in vitro anticancer activity shows that the copper(II) complex is active against the selected tumor cell lines.

  15. Regulation of CCL2 expression by an upstream TALE homeodomain protein-binding site that synergizes with the site created by the A-2578G SNP.

    Science.gov (United States)

    Page, Stephen H; Wright, Edward K; Gama, Lucio; Clements, Janice E

    2011-01-01

    CC Chemokine Ligand 2 (CCL2) is a potent chemoattractant produced by macrophages and activated astrocytes during periods of inflammation within the central nervous system. Increased CCL2 expression is correlated with disease progression and severity, as observed in pulmonary tuberculosis, HCV-related liver disease, and HIV-associated dementia. The CCL2 distal promoter contains an A/G polymorphism at position -2578 and the homozygous -2578 G/G genotype is associated with increased CCL2 production and inflammation. However, the mechanisms that contribute to the phenotypic differences in CCL2 expression are poorly understood. We previously demonstrated that the -2578 G polymorphism creates a TALE homeodomain protein binding site (TALE binding site) for PREP1/PBX2 transcription factors. In this study, we identified the presence of an additional TALE binding site 22 bp upstream of the site created by the -2578 G polymorphism and demonstrated the synergistic effects of the two sites on the activation of the CCL2 promoter. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated increased binding of the TALE proteins PREP1 and PBX2 to the -2578 G allele, and binding of IRF1 to both the A and G alleles. The presence of TALE binding sites that form inverted repeats within the -2578 G allele results in increased transcriptional activation of the CCL2 distal promoter while the presence of only the upstream TALE binding site within the -2578 A allele exerts repression of promoter activity.

  16. Gaining Relational Competitive Advantages

    DEFF Research Database (Denmark)

    Hu, Yimei; Zhang, Si; Li, Jizhen

    2015-01-01

    Establishing strategic technological partnerships (STPs) with foreign partners is an increasingly studied topic within the innovation management literature. Partnering firms can jointly create sources of relational competitive advantage. Chinese firms often lack research and development (R......&D) capabilities but are increasingly becoming preferred technological partners for transnational corporations. We investigate an STP between a Scandinavian and a Chinese firm and try to explore how to gain relational competitive advantage by focusing on its two essential stages: relational rent generation...

  17. FameLab competition

    CERN Multimedia

    2011-01-01

    Are you 18 to 35 years old and studying or working in science in Switzerland? Are you passionate about your job and keen on exciting public imagination with a vision of the 21st century of science? Then this competition is for you!   For more information, check out http://www.famelab.ch/ or http://famelab.org/ or write to info@famelab.ch. Read more about the Famelab competition in this Bulletin article.  

  18. World competitiveness and agriculture

    Directory of Open Access Journals (Sweden)

    J. van Zyl

    1997-07-01

    Full Text Available Against the background of a changing environment in which market factors and greater world trade and competitiveness are increasingly becoming the only criteria for success, a framework for the analysis of world competitiveness is initially developed. This is followed by a discussion on the growth of productivity in agriculture, as well as an exposition of the role of agricultural research. Thirdly, price factors and the terms of trade are discussed, followed by a summary of policy implications.

  19. COMPETITION AS MARKET MECHANISM

    Directory of Open Access Journals (Sweden)

    N. Ya. Kazhuro

    2015-01-01

    Full Text Available The essence of a competition as an objective law for development of the commodities production based on private ownership of the means of production and commodity exchange has been revealed in the paper. The paper presents an economic basis of market economy (private ownership which generates a corresponding production objective. Such purpose is a maximization of profit and a minimization of market subject expenses. Therefore, a struggle for the most favourable conditions on commodity production and sales is inevitable in such situation. The struggle is considered in the community with developed market economy as a competition.The competition is regarded not as an exogenic factor exerting its influence on market economic system from the outside, but as an objective phenomenon which is inherent to management market system in itself. Such treatment is substantiated by economic disintegration of individual commodity producers. Being an important engine of market economy, the competition does not establish its laws, and its role is to be an executive of data which are internally inherent in commodity production laws and firstly it concerns a profit maximization law which defines a purpose and guiding motif of economic entities in the given economy.The competition plays a contradictory role under conditions of market economy. On the one hand, it makes manufacturers constantly to aspire to expense reduction for the sake of profit increase. This has resulted in labour productivity increase, production cost decrease and a company receives an opportunity to reduce retail price for its products. Consequently, the competition acts as a potential factor for lowering of prices while increasing production efficiency. On the other hand, sellers have more freedom in price fixing under conditions of imperfect competition as they sell their products under the conditions of a monopolistic competition or an oligopoly. This is the main weakest point of the market

  20. Racial Discrimination and Competition

    OpenAIRE

    Ross Levine; Alexey Levkov; Yona Rubinstein

    2008-01-01

    This paper assesses the impact of competition on racial discrimination. The dismantling of inter- and intrastate bank restrictions by U.S. states from the mid-1970s to the mid-1990s reduced financial market imperfections, lowered entry barriers facing nonfinancial firms, and boosted the rate of new firm formation. We use bank deregulation to identify an exogenous intensification of competition in the nonfinancial sector, and evaluate its impact on the racial wage gap, which is that component ...

  1. Competitiveness in mass tourism

    OpenAIRE

    Claver Cortés, Enrique; Molina-Azorín, José F.; Pereira-Moliner, Jorge

    2007-01-01

    This paper offers an indepth analysis of a second-generation destination specializing in sun and sand mass tourism: Benidorm, Spain. Contrary to the view of many researchers, it is argued that such destinations need not inevitably decline and can in fact continue to be competitive. The persistence of this sun and sand mass tourism model is shown empirically through an analysis of its evolution and competitive situation. The paper offers suggestions about the strategies Benidorm hotels s...

  2. Competition and Offshoring

    OpenAIRE

    Jose Antonio Rodriguez-Lopez

    2012-01-01

    I present a model of offshoring decisions with heterogeneous firms, random adjustment costs, and endogenous markups. The model shows an inverted-U relationship between firm-level productivity and the probability of offshoring; hence, the most productive firms are less likely to offshore than some lower-productivity firms. A tougher competitive environment has two opposing effects on firm-level offshoring likelihood: a Schumpeterian effect--accounting for the negative effect of competition on ...

  3. Untangling healthcare competition.

    Science.gov (United States)

    Harris, I C; McDaniel, R R

    1993-11-01

    Traditional approaches to competition may be inappropriate for healthcare providers. Neoclassical economics makes the implicit assumption that a single actor embodies consumption, compensation, and benefit from a transaction. In healthcare, this assumption does not hold. Instead, such actions are accomplished by three separate actors--consumers (physicians), customers (third-party payers), and clients (patients). A hospital simultaneously competes in three arenas. Hospitals compete for physicians along a technological dimension. Competition for third-party payers takes on a financial dimension. Hospitals compete for patients along a marketing dimension. Because of the complex marketplace interactions among hospital, patient, physician, and third-party payer, the role of price in controlling behavior is difficult to establish. The dynamics underlying the hospital selection decision--that is, the decision maker's expectations of services and the convenience of accessing services--must also be considered. Healthcare managers must understand the interrelationships involved in the three-pronged competitive perspective for several reasons. This perspective clarifies the multiple facets of competition a hospital faces. It also disentangles the actions previously fulfilled by the traditional single buyer. It illuminates the critical skills underlying the competition for each audience. Finally, it defines the primary criterion each audience uses in sorting among hospitals. Recognition of the multifaceted nature of competition among healthcare providers will help demystify market behavior and thereby improve internal organizational communication systems, managers' ability to focus on appropriate activities, and the hospital's ability to adapt to changing market conditions.

  4. The prion protein binds thiamine.

    Science.gov (United States)

    Perez-Pineiro, Rolando; Bjorndahl, Trent C; Berjanskii, Mark V; Hau, David; Li, Li; Huang, Alan; Lee, Rose; Gibbs, Ebrima; Ladner, Carol; Dong, Ying Wei; Abera, Ashenafi; Cashman, Neil R; Wishart, David S

    2011-11-01

    Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 μM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data, in conjunction with computer-aided docking and molecular dynamics, were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.

  5. COMPETITION: CLASSICAL VERSUS NEOCLASSICAL VIEW

    OpenAIRE

    Mihaela Cornelia Sandu

    2013-01-01

    Competition is an important element from economical theory. Over time it has experienced several definitions and classifications much of them being contradictory. In this paper I will make a parallel between classical and neoclassical point of view according to competition. Keywords. Competition; neoclassical theory; classical theory; monopolistic; perfect competition.

  6. Political Failures and Intergovernmental Competition

    Directory of Open Access Journals (Sweden)

    Jean Hindriks

    2012-01-01

    Full Text Available In normative public economics, intergovernmental competition is usually viewed as harmful. Although empirical support for this position does not abound, market integration has intensified competition among developed countries. In this paper we argue that when assessing welfare effects of intergovernmental competition for various forms of political failures (the public choice critique, the outcome is ambiguous and competition can be welfare improving.

  7. Competitively tight graphs

    CERN Document Server

    Kim, Suh-Ryung; Park, Boram; Sano, Yoshio

    2011-01-01

    The competition graph of a digraph $D$ is a (simple undirected) graph which has the same vertex set as $D$ and has an edge between $x$ and $y$ if and only if there exists a vertex $v$ in $D$ such that $(x,v)$ and $(y,v)$ are arcs of $D$. For any graph $G$, $G$ together with sufficiently many isolated vertices is the competition graph of some acyclic digraph. The competition number $k(G)$ of $G$ is the smallest number of such isolated vertices. In general, it is hard to compute the competition number $k(G)$ for a graph $G$ and it has been one of the important research problems in the study of competition graphs. Opsut~[1982] suggested that the edge clique cover number $\\theta_E(G)$ should be closely related to $k(G)$ by showing $\\theta_E(G)-|V(G)|+2 \\leq k(G) \\leq \\theta_E(G)$. In this note, we study on these inequalities. We first show that for any positive integer $m$ satisfying $2 \\leq m \\leq |V(G)|$, there is a graph $G$ satisfying $k(G)=\\theta_E(G)-|V(G)|+m$ and characterize a graph $G$ satisfying $k(G)=\\...

  8. A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization.

    Science.gov (United States)

    Freeman, N L; Lila, T; Mintzer, K A; Chen, Z; Pahk, A J; Ren, R; Drubin, D G; Field, J

    1996-02-01

    Saccharomyces cerevisiae cyclase-associated protein (CAP or Srv2p) is multifunctional. The N-terminal third of CAP binds to adenylyl cyclase and has been implicated in adenylyl cyclase activation in vivo. The widely conserved C-terminal domain of CAP binds to monomeric actin and serves an important cytoskeletal regulatory function in vivo. In addition, all CAP homologs contain a centrally located proline-rich region which has no previously identified function. Recently, SH3 (Src homology 3) domains were shown to bind to proline-rich regions of proteins. Here we report that the proline-rich region of CAP is recognized by the SH3 domains of several proteins, including the yeast actin-associated protein Abp1p. Immunolocalization experiments demonstrate that CAP colocalizes with cortical actin-containing structures in vivo and that a region of CAP containing the SH3 domain binding site is required for this localization. We also demonstrate that the SH3 domain of yeast Abp1p and that of the yeast RAS protein guanine nucleotide exchange factor Cdc25p complex with adenylyl cyclase in vitro. Interestingly, the binding of the Cdc25p SH3 domain is not mediated by CAP and therefore may involve direct binding to adenylyl cyclase or to an unidentified protein which complexes with adenylyl cyclase. We also found that CAP homologous from Schizosaccharomyces pombe and humans bind SH3 domains. The human protein binds most strongly to the SH3 domain from the abl proto-oncogene. These observations identify CAP as an SH3 domain-binding protein and suggest that CAP mediates interactions between SH3 domain proteins and monomeric actin.

  9. iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets

    Directory of Open Access Journals (Sweden)

    Jianhua Jia

    2016-01-01

    Full Text Available Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1 the K-Nearest Neighbors Cleaning (KNNC and Inserting Hypothetical Training Samples (IHTS treatments to optimize the training dataset; (2 the ensemble voting approach to select the most relevant features; and (3 the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem’s essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor’s web server (http://www.jci-bioinfo.cn/iPPBS-Opt to get the desired results without the need to go through the complicated mathematical equations involved.

  10. Characterization of the Effect of Drug-Drug Interaction on Protein Binding in Concurrent Administration of Sulfamethoxazol and Diclofenac Sodium Using Bovine Serum Albumin

    Science.gov (United States)

    Hossain, Md Kamal; Khatun, Amina; Rahman, Mahmudur; Akter, Md Nahid; Chowdhury, Sadia Afreen; Alam, SM Mahbubul

    2016-01-01

    Purpose: This project was aimed to determine the effect of concurrent administration of sulfamethoxazole and diclofenac sodium. Methods: Equilibrium dialysis method was adopted to study different protein binding aspects of sulfamethoxazole and diclofenac sodium. Results: Sulfamethoxazole showed two types of association constants; high affinity constant 29.0±0.20×106 M-1 with lower number of binding sites of 0.7±1 and low affinity constant 1.13±0.20×106 M-1 with higher number of binding sites of 3.45±1 at pH 7.4 and 40 °C temperature. Diclofenac sodium showed high affinity constant 33.66±0.20×106 M-1 with lower number of binding sites of 1.01±1 and low affinity constant 1.72±0.20×106 M-1 with higher number of binding sites of 6.40±1 at the same condition. Site specific probe displacement data implied that site-I, warfarin sodium site, was the high affinity site, while site-II, diazepam site, was the low affinity site for these drugs. During concurrent administration, sulfamethoxazole increased the free concentration of diclofenac sodium from 17.5±0.14% to 70.0±0.014% in absence and from 22.5±0.07% to 83.0±0.014% in presence of site-I specific probe. Diclofenac sodium also increased the free concentration of sulfamethoxazole from 2.8±0.07% to 52.0±0.14% and from 8.5±0.014% to 64.4±0.07% in absence and presence of site-I specific probe respectively. Conclusion: The study revealed that the concurrent administration of sulfamethoxazole and diclofenac sodium may result drug concentration alteration in blood. PMID:28101466

  11. Business plan competition

    CERN Multimedia

    2007-01-01

    "Venture – Companies for tomorrow" is a business plan competition, which supports students and other junior entrepreneurs in developing their business plans. The sixth edition of the competition is now taking place. Venture 2008 highlights: - prize money totalling CHF 150’000; - possibility to optimize business ideas and business plans with the help of experienced coaches: around 200 coaches are available, with a wide range of backgrounds, entrepreneurs as well as venture capitalists; -\tpossibility to present business ideas and business plans to potential investors ("Investor Days" - 17 January and 7 May); - active involvement in the start-up community; -\tcontribution to potential independence. The competition consists of two phases: Phase I, Business idea, Deadline for submission of business idea: 5 December 2007 (online at http://www.venture.ch). Award Ceremony: 17 January 2008 Phase II, Business plan Deadline for submission of business plan: 2 April 2008 (online at...

  12. Marketing mix and competitiveness

    Directory of Open Access Journals (Sweden)

    Anđelković Slobodan

    2007-01-01

    Full Text Available Competitiveness cannot simply be viewed as a country's ability to export or generate trade surpluses, since these can be brought about at least temporarily by means of artificially lowering the exchange rate and/or compressing domestic expenditures, as has been done in recent years by many DC that have tried to adjust to diminished resource availability. Authors standpoint is that international competitiveness requires creating comparative advantage where it does not exist, and requires action on several levels including an emerging consensus on the importance of macroeconomic policy, role and accountability of the government as well as the imperative of developing and internalizing technology body of knowledge for achieving competitiveness. Particular attention is given to the role and impact of marketing instruments marketing mix.

  13. COMPETITIVENESS THROUGH ENVIRONMENTAL HEALTH

    Directory of Open Access Journals (Sweden)

    Dinu Cristina

    2010-12-01

    Full Text Available This millennium, confronted with a globalization of means leading as fast as possible at certain pursued aims, highlights the importance of competitiveness from the perspective of the continuous fight against limitation of resources. In this context, the machine of life evolution and economy has got an engine named competitiveness. The rules of circulation should focus on all livings to whom, from the perspective of survival and natural, human and social life accomplishment, the well- known concept of health may be attached. At the same time, competitiveness through environment health should try to reach the convergent performances which means that any form of superior knowledge and experience should always take into consideration environment health.

  14. Context Construction through Competition

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    This paper examines the relation between the evolution of statehood and institutionalised competition in the European context. The first half of the paper develops a historical-sociological view on the evolution of modern political power in the state form in Europe while the second half the paper...... reconstructs how the institutionalisation of competition as a specific type of policy tool which has been used by emerging modern states to establish its authority vis-à-vis competing claims to authority. It furthermore engages in an examination of corporatist and governance based attempts to respectively curb...... and expand the use of competition as a tool for organising social processes and the implications of the se attempts for the state of statehood....

  15. Architectural Competition and BIM

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke; Frandsen, Anne Kathrine; Øien, Turid Borgestrand

    2015-01-01

    put under pressure. Thus, the two central actors involved inarchitectural competitions, architects and building clients, are continually influenced by such developments, interpreting and adaptingto changes according to their interests and horizons. During a project reviewing Nordic research literature...... on architecturalcompetitions, a series of interviews was conducted with building clients as well as architects, focusing on the impact of the above-mentioned changes within the building sector on architectural competitions as an institution. In the interviews, ICT and notleast BIM was a recurring theme that both parties saw...

  16. Competition Fosters Trust

    DEFF Research Database (Denmark)

    Huck, Steffen; Lünser, Gabriele; Tyran, Jean-Robert Karl

    2012-01-01

    We study the effects of reputation and competition in a trust game. If trustees are anonymous, outcomes are poor: trustees are not trustworthy, and trustors do not trust. If trustees are identifiable and can, hence, build a reputation, efficiency quadruples but is still at only a third of the first...... best. Adding more information by granting trustors access to all trustees' complete history has, somewhat surprisingly, no effect. On the other hand, we find that competition, coupled with some minimal information, eliminates the trust problem almost completely...

  17. Competition and social cohesion

    Directory of Open Access Journals (Sweden)

    Mario Libertini

    2014-03-01

    Full Text Available "Competition" and "social cohesion" are both protected by E.U. and Italian laws. The author moves from the analysis of the meaning of these two concepts, in order to reflect on their compatibility and the way to conciliate them. The central problem - in the opinion of the Author - is to abandon the myth of spontaneous markets' order and to rebuild a political order able to maintain and support, as far as possible, the competitive market economy, but also to govern economic processes in critical moments and situations.

  18. Competition Policy and Innovation

    DEFF Research Database (Denmark)

    Møllgaard, Peter; Lorentzen, Jo

    2005-01-01

    We briefly review the rationale behind technological alliances and provide a snapshot oftheir role in global competition, especially insofar as it is based around intellectual capital.They nicely illustrate the increased importance of horizontal agreements and thusestablish the relevance of the t......We briefly review the rationale behind technological alliances and provide a snapshot oftheir role in global competition, especially insofar as it is based around intellectual capital.They nicely illustrate the increased importance of horizontal agreements and thusestablish the relevance...... policy, innovation, alliances, industrial policy...

  19. Competition Fosters Trust

    DEFF Research Database (Denmark)

    Huck, Steffen; Ruchala, Gabriele K.; Tyran, Jean-Robert

    but is still at only a third of the first best. Adding more information by granting buyers access to all sellers’ complete history has, somewhat surprisingly, no effect. On the other hand, we find that competition, coupled with some minimal information, eliminates the trust problem almost completely......We study the effects of reputation and competition in a stylized market for experience goods. If interaction is anonymous, such markets perform poorly: sellers are not trustworthy, and buyers do not trust sellers. If sellers are identifiable and can, hence, build a reputation, efficiency quadruples...

  20. Competition Law in Malaysia

    OpenAIRE

    Anand Raj; Cynthia Lian; Wen-Ly Chin

    2015-01-01

    There is still some way for Malaysia to go and the lack of merger control (for the foreseeable future) remains a significant shortcoming in the Malaysian competition law regime at this stage. Anand Raj, Cynthia Lian, & Wen-Ly Chin (Shearn Delamore & Co., Kuala Lumpur)

  1. Positioning for Competition.

    Science.gov (United States)

    Lapovsky, Lucie; Hubbell, Loren Loomis

    2000-01-01

    Analyzes results of the 1999 National Association of College and Business Officers tuition discounting survey and identifies trends. Finds colleges and universities are reactively responding to market pressures and proactively trying to analyze and position themselves ahead of the competition, often regional rather than national, for the…

  2. Competition in Individualized CAI.

    Science.gov (United States)

    Hativa, Nira; And Others

    1993-01-01

    Examines the effects of competition and cooperation on learning through computer-assisted instruction (CAI). A questionnaire was administered to 457 Israeli fourth graders who used two CAI arithmetic systems. The characteristics of the systems are discussed, and the results of the survey are correlated to students' gender and achievement levels.…

  3. Industrial location and competitiveness

    NARCIS (Netherlands)

    S. Brakman (Steven); J.H. Garretsen (Harry); J.G.M. van Marrewijk (Charles)

    2006-01-01

    textabstractThe interaction between the extent of location advantages and the intensity of firm competition relative to the size of the market jointly determines the location of industrial activity. Technology, factor endowments, geography, and scale economies are influential for determining locatio

  4. Explaining competitive reaction effects

    NARCIS (Netherlands)

    Leeflang, P.S.H.; Wittink, D.R.

    Changes in promotional expenditure decisions for a brand, as in other marketing decisions, should be based on the expected impact on purchase and consumption behavior as well as on the likely reactions by competitors. Purchase behavior may be predicted from estimated demand functions. Competitive

  5. Conflict exposure and competitiveness

    NARCIS (Netherlands)

    Cecchi, Francesco; Leuveld, Koen; Voors, Maarten

    2016-01-01

    We use data from a street football tournament and a series of lab-in-field experiments in postconflict Sierra Leone to examine the impact of exposure to conflict violence on competitive behavior. We find that football players who experienced more intense exposure to violence are more likely to get a

  6. Business Ideas Competition

    CERN Multimedia

    2003-01-01

    Business Ideas Competition "The Rainbow Seed Fund is a UK fund, which provides finance to support the commercialization of good ideas founded on scientific research; it is for the benefit of the UK industry in particular. To encourage ideas from CERN the Rainbow Seed Fund is running a business ideas competition.The winner of this competition will receive an immediate cash prize of GBP £1,000. In addition the Rainbow Seed Fund may well provide finance for market research, for protection of Intellectual Property Rights (IPR) and for prototyping to take the idea forward. Further awards of GBP £750 will be made for ideas which gain investment from the Fund.Candidates will only be required to prepare a 2-4-page summary of their business idea, and not a full business plan. Full details and an entry form are available at www.rainbowseedfund.com ." ALL Members of the Personnel seeking participation in the business ideas competition are asked to submit their ideas via the CERN TT Unit (Jean-Marie.Le Goff@cern.ch) th...

  7. Conflict exposure and competitiveness

    NARCIS (Netherlands)

    Cecchi, Francesco; Leuveld, Koen; Voors, Maarten

    2016-01-01

    We use data from a street football tournament and a series of lab-in-field experiments in postconflict Sierra Leone to examine the impact of exposure to conflict violence on competitive behavior. We find that football players who experienced more intense exposure to violence are more likely to get a

  8. Crop–weed competition

    DEFF Research Database (Denmark)

    Gallandt, Eric R.; Weiner, Jacob

    2015-01-01

    on crops. Longer term management of crop–weed competition can be achieved through crop rotations, specifically crop sequences that reduce the weed seed bank, and therefore seedling density, and prevent proliferation of perennial weeds. Key ConceptsKey Concepts * Plant growth requires sunlight, water...

  9. Context Construction Through Competition

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    2015-01-01

    This article examines the relationship between the evolution of statehood and competition in the European context. To begin with, a particular take on the evolution of modern political power in the state form in Europe is developed. Against this background, the article reconstructs how the instit......This article examines the relationship between the evolution of statehood and competition in the European context. To begin with, a particular take on the evolution of modern political power in the state form in Europe is developed. Against this background, the article reconstructs how...... the institutionalization of competition as a specific type of policy tool has been used by emerging modern states to establish their authority vis-à-vis competing claims to public authority in society. The article, furthermore, engages in an examination of (neo-)corporatist and governance-based attempts both to curb...... and to expand the use of competition as a tool for organizing social processes, and the implications of these attempts for the state of statehood....

  10. Explaining competitive reaction effects

    NARCIS (Netherlands)

    Leeflang, P.S.H.; Wittink, D.R.

    2001-01-01

    Changes in promotional expenditure decisions for a brand, as in other marketing decisions, should be based on the expected impact on purchase and consumption behavior as well as on the likely reactions by competitors. Purchase behavior may be predicted from estimated demand functions. Competitive re

  11. Mediterranean Way of Competitiveness

    Directory of Open Access Journals (Sweden)

    Art Kovacic

    2010-12-01

    Full Text Available The Mediterranean area have a special concept of competitiveness topic. Normally is that region not so industrial and knowledge based oriented as a North Europe.That countries can't reach the same development level as the north one. Lisbon's and Goethenburg's strategies create the main framework of development programme. Mediterranean programme is such a case. European internal market has forced the EU countries to increase competitiveness. The economic prosperity of countries is associated with their ability to generate or attract economic activities which are able to increase income by performing well on themarket. Financial crisis in the EU has changed the look on the competitiveness research. Economy in the main countries has to find way of recovery. Former giants of the financial world have found themselves suddenly facing bankruptcy.Inevitably, the crisis is also having an effect on households and businesses - economic growth has slowed sharply and in some EU countries unemployment has begun to increase for the first time in several years. Form that perspective we have to find the right solution of European competitiveness.

  12. 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…

  13. A Swimming Competition

    Institute of Scientific and Technical Information of China (English)

    邹成兵; 邓新华

    2004-01-01

    Last Sunday, there was a swimming competition in our school. It had been a short time since I learned how to swim. Mr. Zhang, our PE teacher, said I had a gift in swimming and that competing in the game would help build up my confidence and courage. With his encouragement,I signed up for the swimming race.

  14. Context Construction Through Competition

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    2015-01-01

    This article examines the relationship between the evolution of statehood and competition in the European context. To begin with, a particular take on the evolution of modern political power in the state form in Europe is developed. Against this background, the article reconstructs how the instit...

  15. Environmental structure and competitive scoring advantages in team competitions

    Science.gov (United States)

    Merritt, Sears; Clauset, Aaron

    2013-10-01

    In most professional sports, playing field structure is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact environmental heterogeneities can have on scoring dynamics or competitive advantages. Applying a novel generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between the structure within a competition and its scoring dynamics, while controlling the impact of chance. Despite wide structural variations, we observe a common three-phase pattern in the tempo of events. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. Surprisingly, the most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the design principles of balanced competition, and illustrate the potential of online game data for investigating social dynamics and competition.

  16. Environmental structure and competitive scoring advantages in team competitions.

    Science.gov (United States)

    Merritt, Sears; Clauset, Aaron

    2013-10-29

    In most professional sports, playing field structure is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact environmental heterogeneities can have on scoring dynamics or competitive advantages. Applying a novel generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between the structure within a competition and its scoring dynamics, while controlling the impact of chance. Despite wide structural variations, we observe a common three-phase pattern in the tempo of events. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. Surprisingly, the most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the design principles of balanced competition, and illustrate the potential of online game data for investigating social dynamics and competition.

  17. Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes.

    Science.gov (United States)

    Putta, Venkat Reddy; Chintakuntla, Nagamani; Mallepally, Rajender Reddy; Avudoddi, Srishailam; K, Nagasuryaprasad; Nancherla, Deepika; V V N, Yaswanth; R S, Prakasham; Surya, Satyanarayana Singh; Sirasani, Satyanarayana

    2016-01-01

    The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5-(methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1

  18. Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma.

    Science.gov (United States)

    Jin, Yin-Xiu; Tang, Yi-Hong; Zeng, Su

    2008-04-14

    A stereoselective reversed-phase high-performance liquid chromatography (HPLC) assay to determine the enantiomers of flurbiprofen, ketoprofen and etodolac in human plasma was developed. Chiral drug enantiomers were extracted from human plasma with liquid-liquid extraction. Then flurbiprofen and ketoprofen enantiomers reacted with the acylation reagent thionyl chloride and pre-column chiral derivatization reagent (S)-(-)-alpha-(1-naphthyl)ethylamine (S-NEA), and etodolac enantiomers reacted with S-NEA using 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBT) as coupling agents. The derivatized products were separated on an Agilent Zorbax C18 (4.6 mm x 250 mm, 5 microm) column with a mixture of acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (70:30, v/v) for flurbiprofen enantiomers, acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (60:40, v/v) for ketoprofen enantiomers and methonal-0.01 mol.L(-1) potassium dihydrogen phosphate buffer (pH 4.5) (88:12, v/v) for etodolac enantiomers as mobile phase. The flow of mobile phase was set at 0.8 mL.min(-1) and the detection wavelength of UV detector was set at 250 nm for flurbiprofen and ketoprofen enantiomers and 278 nm for etodolac enantiomers. The assay was linear from 0.5 to 50 microg.mL(-1) for each enantiomer. The inter- and intra-day precision (R.S.D.) was less than 10% and the average extraction recovery was more than 87% for each enantiomer. The limit of quantification for the method was 0.5 microg.mL(-1) (R.S.D.<10%, n=5). The method developed was used to study the drug-protein binding of flurbiprofen, ketoprofen and etodolac enantiomers in human plasma. The results showed that the stereoselective binding of etodolac enantiomer was observed and flurbiprofen and ketoprofen enantiomers were not.

  19. Development of validated HPLC-UV method for simultaneous determination of Metformin, Amlodipine, Glibenclamide and Atorvastatin in human plasma and application to protein binding studies

    Directory of Open Access Journals (Sweden)

    Pawan K. Porwal

    2017-06-01

    Full Text Available A simple, sensitive, fast, and economical HPLC method was developed and validated for simultaneous estimation of two fixed dose combinations frequently prescribed in diabetes (Metformin plus Glibenclamide and hypertension with dyslipidemia (Amlodipine plus Atorvastatin in Human plasma for the first time. The validated HPLC method was used to quantify the concentration of selected actives in ultrafiltrate. Optimum separation conditions were obtained with Water’s Novapack Phenyl (150 mm × 4.6 mm, i.d., 5.0 μm column with mobile phase consisting of 0.1% Phosphoric acid (pH 3.0 and acetonitrile (ACN in gradient mode with column oven temperature maintained at 30 °C and elution monitored by a UV detector at 227 nm. Protein precipitation was employed to extract the selected analyte form human plasma. The recoveries were more than 90% for all analytes in cold aqueous 10% trichloroacetic acid (TCA and acetonitrile. The optimized HPLC-UV was validated in the calibration range of 10–10,000 ng mL−1 for Metformin, 25–5000 ng mL−1 for amlodipine, 50–10,000 ng mL−1 for glibenclamide and 10–5000 ng mL−1 for atorvastatin. The mean relative error was least when weighing of 1/×2 was applied for calibration curve. The accuracy of samples for six replicate measurements at LLOQ level was within limit. The precision and accuracy of samples for six replicate measurements at LLOQ level was within limit. The validated method was applied for quantitation of selected analytes in ultrafiltrate from protein binding experiments. A four to five fold increase in unbound fraction was observed when spiked to human serum albumin. Further the unbound fraction of highly albumin bound drugs was increased nearly to double when incubated with Gly-HSA as compare to HSA.

  20. The Literature of Competitive Intelligence.

    Science.gov (United States)

    Walker, Thomas D.

    1994-01-01

    Describes competitive intelligence (CI) literature in terms of its location, quantity, authorship, length, and problems of bibliographic access. Highlights include subject access; competitive intelligence research; espionage and security; monographs; and journals. (21 references) (LRW)

  1. Endogeneous Risk in Monopolistic Competition

    OpenAIRE

    Vladislav Damjanovic

    2012-01-01

    We consider a model of financial intermediation with a monopolistic competition market structure. A non-monotonic relationship between the risk measured as a probability of default and the degree of competition is established.

  2. The Value of Competitive Contracting

    Science.gov (United States)

    2014-09-01

    Contract FAR authority citations (from GAO, 2010) A few other notable reasons why some agencies inhibit competition are the following: a. Lack of...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA JOINT APPLIED PROJECT THE VALUE OF COMPETITIVE CONTRACTING By: Pamela A...

  3. RECONSIDERING COMPETITIVE ADVANTAGES

    Directory of Open Access Journals (Sweden)

    Valentina Zaharia

    2011-12-01

    Full Text Available Development of the competitive advantage involves a considerable effort from any organization. In particular, those organizations involved in a strong competitive market require the development of strategies to allocate long-term strategic marketing resources, efficiently and with easily quantifiable results. Faced with a multitude of phenomena and processes sometimes contradictory on different markets of consumption, contemporarily marketing has the mission to develop as creative as possible the business strategy of the organizations, their capacity of interacting with customers and other categories of audience. Such concepts as strategic positioning, relational marketing, management of the relationship with the consumer, marketing integrated research, a.s.o. are only a few of the tools with the help of which the marketing managers will implement successful operational strategies. All these developments are creating a real new paradigm of Marketing aimed to better explain the new types of complex market relationship in which the 21st Century organization is .

  4. Competition in Soccer Leagues

    DEFF Research Database (Denmark)

    Hansen, Bodil Olai; Tvede, Mich

    In the present paper a model of competition between sports clubs in a sports league is presented. Clubs are endowed with initial players but at a cost clubs are able to sell their initial players and buy new players. The results are that: if the quality of players is one-dimensional, then equilib......In the present paper a model of competition between sports clubs in a sports league is presented. Clubs are endowed with initial players but at a cost clubs are able to sell their initial players and buy new players. The results are that: if the quality of players is one......-dimensional, then equilibria in pure strategies exist, and; if the quality of players is multi-dimensional, then there need not exist equilibria in pure strategies, but equilibria in mixed strategies exist. Equilibria in mixed strategies resemblance signings on deadline day in european soccer...

  5. Competitiveness in Road Transport

    DEFF Research Database (Denmark)

    Borgström, Benedikte; Gammelgaard, Britta; Bruun, Poul

    take into account logistics service supplier strategic management. We also contribute with better understanding of value creation in order to escape commoditization and differentiate services through relationships (customers and/or other hauliers). Practical implications concern hauliers’ strategy...... a competitive value proposition? We will illustrate the strategy-as-practice with two projects, and discuss implications in terms of capabilities needed to create an effective value proposition and hence competitiveness. The theoretical contribution is in theorizing haulier strategic development in which we...... in the market also encourage strategic development of some road hauliers into providers of unique services. Such road haulier strategic development contributes to efficiency and effectiveness in basically all business sectors of EU. Little research is available of such strategic and operational management...

  6. Competitive Advantage through Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Maier, Maximilian; Wimschneider, Christine

    2016-01-01

    to failure several times. Before the current situation of the company, it remains challenging in the future as well. Hence, the Nespresso story provides interesting space for discussion and learning about what innovation is, how innovation emerges, and under which circumstances innovation can serve...... as a source for competitive advantage. Research limitations/implications Especially given the current market situation, the case offers different starting points for discussion about innovation and long-term company success. Practical implications Especially before the current market situation, the case...... offers different starting points for discussion about innovation and the success of a company on the long term. The case is designed to give practitioners a better understanding on what an innovation as, and how competitive advantages can be linked to innovation. Originality/value This case of Nespresso...

  7. Political Competition and Polarization

    DEFF Research Database (Denmark)

    Schultz, Christian

    This paper considers political competition and the consequences of political polarization when parties are better informed about how the economy functions than voters are. Specifically, parties know the cost producing a public good, voters do not. An incumbent's choice of policy acts like a signal...... for costs before an upcoming election. It is shown that the more polarized the political parties the more distorted the incumbent's policy choice....

  8. Managed competition that works.

    Science.gov (United States)

    Caper, P

    1993-05-19

    President Clinton has advocated managed competition within a global budget as a long-term strategy for simultaneously controlling health care costs and expanding access to medical care to all Americans. This proposal is intended to show how these two seemingly conflicting goals can be simultaneously accomplished. Managed competition, as it has been conceptualized to date, is primarily a strategy for reforming the system of providing health services. To work, it must be joined with a strategy for reforming our system of financing and paying for those services and of limiting overall system capacity. "Managed Competition That Works" is a proposal that would create a single trust-funded national system of health insurance, implemented through a system of vouchers to individuals. Global budgeting would be accomplished through establishment of the voucher's value each year. The trust fund would pay health plans for all medical care by capitation, but health plans would be free to negotiate a variety of payment arrangements with physicians, hospitals, and other providers. All plans would be required to offer a standard package of benefits, but would have great flexibility in offering benefits beyond the scope of the standard package, if those benefits replace high-cost with lower-cost services or permit the plan to compete more effectively for market share. This proposal would establish firm but acceptable national budget limits; provide universal, comprehensive, and uniform insurance coverage; eliminate cost shifting; encourage competition; reward efficiency-improving innovation; greatly reduce the need for centralized micromanagement of medical care; and retain local determination and a somewhat reduced level of consumer choice. Although this proposal is written as a national plan, trust funds could be implemented at the state level, if problems associated with portability of benefits among states could be solved.

  9. Competition and dental services.

    Science.gov (United States)

    Grytten, J; Sørensen, R

    2000-07-01

    Dental services for adults are different from all other Norwegian health services in that they are provided by private producers (dentists) who have full freedom to establish a practice. They have had this freedom since the end of World War II. A further liberalization of the market for dental services occurred in November 1995, when the so-called normal tariff was repealed. The system changed from a fixed fee system to a deregulated fee system. In principle, the market for dental services for adults operates as a free competitive market, in which dentists must compete for a market share. The aim of this study was to study the short-term effects of competition. A comprehensive set of data on fees, practice characteristics, treatment profiles and factors that dentists take into account when determining fees was analysed. The main finding was that competition has a weak effect. No support was found for the theory that the level of fees is the result of monopolistic competition or monopoly. The results also provided some evidence against the inducement hypothesis. At this stage, it is interesting to notice that dentists do not seem to exploit the power they have to control the market. One explanation, which is consistent with the more recent literature, is that physicians' behaviour to a large extent is influenced by professional norms and caring concerns about their patients. Financial incentives are important, but these incentives are constrained by norms other than self-interest. The interpretation of the results should also take into account that the deregulation has operated for a short time and that dentists and patients may not yet have adjusted to changes in the characteristics of the market.

  10. Ukraine Agricultural Competitiveness

    OpenAIRE

    2008-01-01

    The agri-food sector is an important part of the Ukrainian economy. Agriculture could make an even larger contribution to economic growth and the vitality of rural areas in Ukraine than is currently the case. Ukraine has the agro-climatic potential to be a major player on world agricultural markets. Agricultural competitiveness in Ukraine also suffers from inadequate systems to test and do...

  11. Attention Competition with Advertisement

    OpenAIRE

    Cetin, Uzay; Bingol, Haluk O.

    2012-01-01

    In the new digital age, information is available in large quantities. Since information consumes primarily the attention of its recipients, the scarcity of attention is becoming the main limiting factor. In this study, we investigate the impact of advertisement pressure on a cultural market where consumers have a limited attention capacity. A model of competition for attention is developed and investigated analytically and by simulation. Advertisement is found to be much more effective when a...

  12. Competition: the answers

    CERN Multimedia

    Staff Association

    2016-01-01

    The correct answers to the Staff Association Competition are: How many women delegates are there currently in the Staff Council? -14 Who is the current President of the Staff Association? - Alessandro Raimondo Which year was the Nursery School established by the Staff Association at CERN?  -1965 How many CERN clubs are supported by the Staff Association? -44 What is the supreme representative body of the Staff Association ? -The Staff Council   The winners will be informed by email.

  13. APPROACHES ON THE COMPETITIVE INTELLIGENCE

    OpenAIRE

    Ioan PETRIŞOR; Natalia Ana STRĂIN (SILAŞ)

    2013-01-01

    Within this study, we approached the concept of "competitive intelligence" (CI), which we consider a key element for the success of a business, especially in the current period, characterized by numerous economic and financial turbulence. According to Society of Competitive Intelligence (SCIP), competitive intelligence is defined as a method of ethical and moral collection, analysis and dissemination of information regarding the competitive environment, opportunities, vulnerabilities, and int...

  14. Uniqueness is Important in Competition

    Institute of Scientific and Technical Information of China (English)

    FENG Ai-Xia; XV Xiu-Lian; HE Da-Ren

    2009-01-01

    We propose a quantitative network description on the function of uniqueness in a competition system. Two statistical parameters, competition ability and uniqueness are defined, and their relationship in ordinary cases is analytically discussed. The competition between Chinese regional universities is taken as an example. The empirical investigation results show that the uniqueness of a university is really important in competition. Also,uniqueness is very helpful in the promotion of the university overall quality.

  15. Competition, cooperation, and collective choice

    DEFF Research Database (Denmark)

    Markussen, Thomas; Reuben Paris, Ernesto Guillermo; Tyran, Jean-Robert Karl

    2014-01-01

    scheme fosters cooperation. Competition is popular, but the electoral outcome depends strongly on specific voting rules of institutional choice. If the majority decides, competition is almost always adopted. If likely losers from competition have veto power, it is often not, and substantial gains...

  16. Competition, cooperation, and collective choice

    DEFF Research Database (Denmark)

    Markussen, Thomas; Reuben Paris, Ernesto Guillermo; Tyran, Jean-Robert Karl

    scheme fosters cooperation. Competition is popular but the electoral outcome depends strongly on specific voting rules of institutional choice. If the majority decides, competition is almost always adopted. If likely losers from competition have veto power, it is often not, and substantial gains...

  17. Competitive Intelligence and Social Advantage.

    Science.gov (United States)

    Davenport, Elisabeth; Cronin, Blaise

    1994-01-01

    Presents an overview of issues concerning civilian competitive intelligence (CI). Topics discussed include competitive advantage in academic and research environments; public domain information and libraries; covert and overt competitive intelligence; data diversity; use of the Internet; cooperative intelligence; and implications for library and…

  18. Competitive Environments and Protective Behaviour

    NARCIS (Netherlands)

    Borm, P.E.M.; Estevez Fernandez, M.A.; Fiestras-Janeiro, G.

    2005-01-01

    The class of two-person competition games is introduced and analyzed.For any game in this class the set of Nash equilibria is convex, equilibrium strategies are exchangeable, and all Nash equilibria lead to the same payoff vector. Competition games are compared to other competitive environments such

  19. Competition policy and cartel size

    NARCIS (Netherlands)

    Bos, A.M.; Harrington Jr., J.E.

    2013-01-01

    This paper examines endogenous cartel formation in the presence of a competition authority. Competition policy makes the most inclusive stable cartels less inclusive. In particular, small firms that might have been cartel members in the absence of a competition authority are no longer members. Regar

  20. Competition policy and cartel size

    NARCIS (Netherlands)

    Bos, A.M.; Harrington Jr., J.E.

    2013-01-01

    This paper examines endogenous cartel formation in the presence of a competition authority. Competition policy makes the most inclusive stable cartels less inclusive. In particular, small firms that might have been cartel members in the absence of a competition authority are no longer members.

  1. Competitive Environments and Protective Behaviour

    NARCIS (Netherlands)

    Borm, P.E.M.; Estevez Fernandez, M.A.; Fiestras-Janeiro, G.

    2005-01-01

    The class of two-person competition games is introduced and analyzed.For any game in this class the set of Nash equilibria is convex, equilibrium strategies are exchangeable, and all Nash equilibria lead to the same payoff vector. Competition games are compared to other competitive environments such

  2. Environmental structure and competitive scoring advantages in team competitions

    CERN Document Server

    Merritt, Sears

    2013-01-01

    In most professional sports, the structure of the environment is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact structural heterogeneities can have on scoring dynamics and producing competitive advantages. Applying a generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between a competition's structure and its scoring dynamics. Despite wide structural variations, we find the same three-phase pattern in the tempo of events observed in many sports. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. The most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the principles of balanced competition, and illustrate the potential of online game data...

  3. Hospital survival in a competitive environment: the competitive constituency model.

    Science.gov (United States)

    Ehreth, J

    1993-01-01

    Organizational theory is extended to develop a method for administrators to assess hospital effectiveness in a competitive environment. First, the literature pertaining to organizational effectiveness and survival is synthesized to show the lack of consideration for the effects of competition. Second, the article integrates the effects of competition on organizational effectiveness through a competitive constituency model. A step-by-step procedure is proposed to apply the theory in an organizational setting. The model explicitly addresses differences in power relations between hospitals, their competition, and their stakeholders. The relative nature of effectiveness is explored by comparing the hospital to its competition using criteria developed through specific goals of stakeholders. The distinction between managerial and organizational effectiveness constructs is clarified. Finally, the practical application of this model is demonstrated by assessing the effectiveness of a hospital in the competitive environment of Seattle, Washington, where two hospitals have recently closed.

  4. Competition in a Business Network

    DEFF Research Database (Denmark)

    Ellegaard, Chris; Medlin, Christopher J

    Competition and cooperation stabilize and structure business networks. In business research there is little focus on network based competition between firms and on how firms compete to gain network position. We review a range of conceptualizations of competition and cooperation and work towards...... a meaning of network competition and network cooperation based on goal structures within activity structures inside a firm network context. We conclude by presenting a framework to understand how network competition and cooperation are played out. We complete the paper with the opportunities for future...... research and also managerial thinking about network strategy and implementation....

  5. Competition Advocacy: the Italian Experience

    Directory of Open Access Journals (Sweden)

    Salvatore Rebecchini

    2014-07-01

    Full Text Available Competition advocacy is considered, together with enforcement, the core business of an antitrust authority. Broadly speaking there are at least three main tasks regularly performed by most, if not all, antitrust agencies that are amenable to the advocacy function: addressing laws and regulations in order to remove unnecessary impediments to competition; engaging in sector enquiries to understand markets behavior and identify critical issues; explaining the benefits of open competitive markets to the public opinion. This article examines these three main tasks and outlines the challenges for competition agencies, with references to the experience of the Italian Competition Authority (ICA and the initiatives undertaken at international level.

  6. Competitive Manufacturing Dynamics

    DEFF Research Database (Denmark)

    Rymaszewska, Anna; Christensen, Irene; Karlsson, Christer

    The increasing complexity of business environments and the pressure for organizations on delivering new products faster while maintaining the superior quality of their products, has forced manufacturing organizations to rethink their operations. Managers responsible for manufacturing ramp-up need...... to constantly improve this process in terms of time to volume, according to predefined cost and quality measures. The importance of the success of this process can lead to a significant creation of competitive advantage. This paper addresses the challenges of the manufacturing ramp-up process in the context...

  7. Attention competition with advertisement

    Science.gov (United States)

    Cetin, Uzay; Bingol, Haluk O.

    2014-09-01

    In the new digital age, information is available in large quantities. Since information consumes primarily the attention of its recipients, the scarcity of attention is becoming the main limiting factor. In this study, we investigate the impact of advertisement pressure on a cultural market where consumers have a limited attention capacity. A model of competition for attention is developed and investigated analytically and by simulation. Advertisement is found to be much more effective when the attention capacity of agents is extremely scarce. We have observed that the market share of the advertised item improves if dummy items are introduced to the market while the strength of the advertisement is kept constant.

  8. Profit maximization mitigates competition

    DEFF Research Database (Denmark)

    Dierker, Egbert; Grodal, Birgit

    1996-01-01

    We consider oligopolistic markets in which the notion of shareholders' utility is well-defined and compare the Bertrand-Nash equilibria in case of utility maximization with those under the usual profit maximization hypothesis. Our main result states that profit maximization leads to less price...... competition than utility maximization. Since profit maximization tends to raise prices, it may be regarded as beneficial for the owners as a whole. Moreover, if profit maximization is a good proxy for utility maximization, then there is no need for a general equilibrium analysis that takes the distribution...... of profits among consumers fully into account and partial equilibrium analysis suffices...

  9. Attention competition with advertisement.

    Science.gov (United States)

    Cetin, Uzay; Bingol, Haluk O

    2014-09-01

    In the new digital age, information is available in large quantities. Since information consumes primarily the attention of its recipients, the scarcity of attention is becoming the main limiting factor. In this study, we investigate the impact of advertisement pressure on a cultural market where consumers have a limited attention capacity. A model of competition for attention is developed and investigated analytically and by simulation. Advertisement is found to be much more effective when the attention capacity of agents is extremely scarce. We have observed that the market share of the advertised item improves if dummy items are introduced to the market while the strength of the advertisement is kept constant.

  10. Competitive Manufacturing Dynamics

    DEFF Research Database (Denmark)

    Rymaszewska, Anna; Christensen, Irene; Karlsson, Christer

    The increasing complexity of business environments and the pressure for organizations on delivering new products faster while maintaining the superior quality of their products, has forced manufacturing organizations to rethink their operations. Managers responsible for manufacturing ramp-up need...... to constantly improve this process in terms of time to volume, according to predefined cost and quality measures. The importance of the success of this process can lead to a significant creation of competitive advantage. This paper addresses the challenges of the manufacturing ramp-up process in the context...... of lean improvements as well as organizational learning....

  11. Entrepreneurship and corporate competitiveness

    Directory of Open Access Journals (Sweden)

    Mihailović Božo

    2005-01-01

    Full Text Available Macroeconomics reforms are not enough for long-range stability. Transition enterprises in domestic economy hasn't prepare itself for the market economy. It has some specific characteristics which are analyzed in this paper. Entrepreneurship is the corner stone for enterprise development in the sense of achieving sustainable competitiveness in the contemporary globalized world economy. There are two possibilities to introduce it in transition enterprises: (a self-development (development by itself or evolution and (b create partnerships or alliance with some reputable competitor. In current situation, author proposal is for the second solution.

  12. Competitive Moves over Time

    DEFF Research Database (Denmark)

    Antero, Michelle; Hedman, Jonas; Henningsson, Stefan

    2014-01-01

    its viability to survive in the marketplace. The study begins with a review of sourcing literature to position the Red Queen theory within the sourcing literature. It subsequently applies the framework to a case study of SAP AG to illustrate how sourcing strategies changed over time in response...... the firm; (c) organizations are reflexive and over time develop competitive hysteresis which allows them to become stronger competitors. In the case of SAP AG, various sourcing arrangements were selected over its 40-year history to respond to technological and market changes....

  13. Determination of protein binding rates of celastrol in different species of plasma by HPLC%雷公藤红素在不同血浆中的蛋白结合率测定

    Institute of Scientific and Technical Information of China (English)

    袁菱; 陈彦; 周蕾; 郑丽燕; 曹伟

    2013-01-01

    OBJECTIVE To study the protein binding rate of celastrol in the plasma of rats, Beagle dogs and humans. METHODS Equilibrium dialysis method was carried out to determine the plasma protein binding rates in different species. HPLC was employed to determine the concentration of celastrol inside or outside of the dialysis membrane, and then protein binding rates were calculated. RESULTS The plasma protein binding rates of celastrol at low, middle and high concentrations in different species were as follows, the plasma protein binding rates were (78. 5 ± 1. 6) %, (77. 3 ± 2. 2) %, (76. 4 ± 2. 9) % in rats, (69.6±4.7)%, (71.1±3.4)%, (68. 0 ±2. 1)% in Beagle dogs, and (85. 6 ± 2. 7)%, (84.0±4. 7)%, (83.1±2.8)% in humans, respectively. CONCLUSION The protein binding rates of celastrol were of middle strength, which in rats, Beagle dogs and humans plasma were decreased in the following order: humans plasma>rats plasma>Beagle dogs plasma.%目的:研究雷公藤红素与大鼠、比格犬和人的血浆蛋白结合率.方法:采用血浆平衡透析法,以高效液相色谱法对透析内液与外液中雷公藤红素的含量进行测定,计算雷公藤红素与大鼠、比格犬和人的血浆蛋白结合率.结果:雷公藤红素低中高(0.25,0.5,1.0 μg·mL-1)3个浓度的大鼠血浆蛋白结合率分别为(78.5±1.6)%,(77.3±2.2)%,(76.4±2.9)%,比格犬血浆蛋白结合率分别为(69.6±4.7)%,(71.1±3.4)%,(68.0±2.1)%,人血浆蛋白结合率分别为(85.0±2.7)%,(84.0±4.7)%,(83.1±2.8)%.结论:雷公藤红素与血浆蛋白具有中等强度的结合,其中与人血浆中的蛋白结合较强,且人>大鼠>比格犬.

  14. Staphylococci in Competition1

    Science.gov (United States)

    Peterson, A. C.; Black, J. J.; Gunderson, M. F.

    1964-01-01

    Foods containing large amounts of carbohydrate have frequently been involved in staphylococcal food poisoning. Custard has been considered to be a highly favorable culture medium for staphylococci; however, it may be a selective medium rather than an ideal one. The influence of dextrose, lactose, and sucrose in varying amounts from 0.25 to 18%, and of starch, on the growth of staphylococci in mixed populations with saprophytes was determined. The inhibitory effect of the sugars was much greater on the saprophyte population than on the staphylococci. Of the three sugars, sucrose was most inhibitory to the saprophytes. It greatly decreased their lag periods as the concentration of sugar increased. Dextrose was the least inhibitory; in fact, 0.5% dextrose gave considerable stimulus to saprophyte growth. This sharply repressed staphylococcal growth. Lactose occupied an intermediate position. Rapid onset of the death phase of the staphylococci was observed in all increased sugar concentrations and seemed to be a pH effect rather than a result of competition. Sucrose exerted an inhibitory effect on the growth of saprophytes at and above room temperature. In the presence of 2.5% corn starch, staphylococcal growth in mixed cultures was slightly inhibited, while the death phase was sharply accelerated. Thus, carbohydrates exert their influence on staphylococcal growth in mixed cultures through their effect on the saprophytes by decreasing or increasing competition. PMID:14106944

  15. Competitive interactions of ligands and macromolecular crowders with maltose binding protein.

    Directory of Open Access Journals (Sweden)

    Andrew C Miklos

    Full Text Available Cellular signaling involves a cascade of recognition events occurring in a complex environment with high concentrations of proteins, polysaccharides, and other macromolecules. The influence of macromolecular crowders on protein binding affinity through hard-core repulsion is well studied, and possible contributions of protein-crowder soft attraction have been implicated recently. Here we present direct evidence for weak association of maltose binding protein (MBP with a polysaccharide crowder Ficoll, and that this association effectively competes with the binding of the natural ligand, maltose. Titration data over wide ranges of maltose and Ficoll concentrations fit well with a three-state competitive binding model. Broadening of MBP (1H-(15N TROSY spectra by the addition of Ficoll indicates weak protein-crowder association, and subsequent recovery of sharp NMR peaks upon addition of maltose indicates that the interactions of the crowder and the ligand with MBP are competitive. We hypothesize that, in the Escherichia coli periplasm, the competitive interactions of polysaccharides and maltose with MBP could allow MBP to shuttle between the peptidoglycan attached to the outer membrane and the ATP-binding cassette transporter in the inner membrane.

  16. Tax competition: A general review

    Directory of Open Access Journals (Sweden)

    Raičević Božidar B.

    2004-01-01

    Full Text Available Tax competition is increasingly attracting the attention of not only experts Although it is difficult to define precisely, grosso modo, it is actually a competition between states (jurisdictions in attracting capital (investors by tax instruments, especially tax incentives. The first recorded cases of tax competition emerged in 12th century (attracting wool weavers into regions of North Italy-Piemont. Today, tax competition has undreamt-of and very dynamic forms, both territorial and sectored. However, tax competition is accompanied not only by positive but also by rather strong negative effects. Positive effects worth mentioning are the following: 1. control of power, 2. innovations, and 3. incentives. However, negative effects, embodied in "unfair tax competition", provoke a range of unwanted and important distortions in international trade. All of them arise from requirements and wants of tax payers (especially companies to minimize or evade their tax obligations, on the one hand, as well as.

  17. PUBLIC EDUCATION AND ECONOMIC COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Gabriel-Andrei Donici

    2011-09-01

    Full Text Available There is a certain connection between education and economic competitiveness. The relation between these two concepts is easy to intuit. On the medium and long term investments in education generate astrong increase in a country’s level of economic competitiveness. Through education the human capital is formed, and it affects all economic fields. Therefore we can observe that human capital has a decisive influence on the economic competitiveness of a country.

  18. Exploring binding characteristics and the related competition of different protein-bound uremic toxins.

    Science.gov (United States)

    Deltombe, Olivier; de Loor, Henriette; Glorieux, Griet; Dhondt, Annemieke; Van Biesen, Wim; Meijers, Björn; Eloot, Sunny

    2017-08-01

    Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin. Copyright

  19. Offshoring and International Competitiveness

    DEFF Research Database (Denmark)

    Ørberg Jensen, Peter D.; Pedersen, Torben

    2012-01-01

    During the past decade, offshoring has become an established business practice. Yet it is still more common to offshore less advanced tasks compared with offshoring more advanced tasks, i.e., tasks closer to the core activities of the firm. The latter is a new phenomenon which raises many new...... of advanced offshoring, exploring what causes firms to offshore some of their more advanced tasks. Our findings indicate that while the lower cost of unskilled, labor-intensive processes is the main driver for firms that offshore less advanced tasks, the offshoring of advanced tasks is part of firms’ strategy...... to achieve international competitiveness through access to cross-border knowledge flows and foreign knowledge resources. Furthermore, offshoring of advanced manufacturing tasks seems to be more widespread and experience-based than the offshoring of advanced service tasks....

  20. Driving Competitiveness Through Servitization

    DEFF Research Database (Denmark)

    Avlonitis, Viktor; Frandsen, Thomas; Hsuan, Juliana

    countries and emerging economies. It is our hope that this booklet can assist managers to analyze and plan a servitization strategy. The text is brief and comprehensive to supplement a workshop, but can also be used separately as a quick guide on steps to follow for a manager when considering servitization......Servitization, or adding services to the manufactured product, has become a strategy for increasing financial margins, getting closer to the customer and prolonging product lives. This is especially applicable to Western hemisphere companies in their efforts to compete with companies from low cost...... for the company. This booklet is produced to serve as a documentation of a research project together with industry on how servitization can be a strategy to enhance the competitiveness of manufacturing firms....

  1. Sport competitions in Antique Chersoneses.

    Directory of Open Access Journals (Sweden)

    Moutiev A.V.

    2011-12-01

    Full Text Available It is examined the content of physical education in Chersoneses in the ancient period. It is shown the participation of citizens in the Chersoneses competitions at various levels. Stressed the importance of physical culture, sports, sports training, organizing and conducting athletic competitions. Show the direction of physical education of youth, training for local and Panhellenic competitions, military service. The role of the teacher of gymnastics in physical education students in public schools. It is noted that the study involved in Chersoneses pedagogical methods and techniques. It is established that the citizens of Chersoneses actively participated in Panhellenic competitions and they became the victors.

  2. Competitive advantage and corporate communications

    Directory of Open Access Journals (Sweden)

    Mitić Sanja

    2013-01-01

    Full Text Available Strategic importance of corporate communications and its role in the development of competitive advantage has attracted interest of numerous researchers in the fields of organization, management, marketing and public relations. Recent studies particularly emphasise the growing importance of soft factors, such as reputation in the development of competitive advantage. Concept of reputation is strongly connected with stakeholder theory, which stresses the importance of corporate communications for competitive advantage of firms. The paper focuses on competitive advantage and the link among strategy, reputation and corporate communications.

  3. Competition in the Mashup Ecosystem

    Directory of Open Access Journals (Sweden)

    Amanda Shiga

    2011-01-01

    Full Text Available Mashups combine data from multiple sources to create innovative web applications. Data providers gain compelling advantages in offering an open application programming interface (API, but face a competitive environment where growth occurs by virtue of developers' independent choices and where competitors are also complementors. This article explores the nature of competition within the mashup ecosystem by focusing on competitive actions taken by API providers and their link to mashup network structure. The resulting insights help entrants and incumbents refine their competitive strategies within this complex and unique environment.

  4. BUSINESS COMPETITORS AND COMPETITIVE ADVANTAGE

    Directory of Open Access Journals (Sweden)

    SUCIU TITUS

    2013-08-01

    Full Text Available The paper presents the concept of competition, both from the perspective of the economic sector –where it is characteristic for pure monopole, oligopoly, monopole competition and pure competition, as well asfrom the market’s point of view – where it determines the strategies, objectives, advantages and weaknesses of acompany. The main point of the paper is the criticism of the pure and perfect competition theory. Concluding,the author insists on innovation, especially on the model of open innovation.

  5. Mapping your competitive position.

    Science.gov (United States)

    D'Aveni, Richard A

    2007-11-01

    A price-benefit positioning map helps you see, through your customers' eyes, how your product compares with all its competitors in a market. You can draw such a map quickly and objectively, without having to resort to costly, time-consuming consumer surveys or subjective estimates of the excellence of your product and the shortcomings of all the others. Creating a positioning map involves three steps: First, define your market to include everything your customers might consider to be your product's competitors or substitutes. Second, track the price your customers actually pay (wholesale or retail? bundled or unbundled?) and identify what your customers see as your offering's primary benefit. This is done through regression analysis, determining which of the product's attributes (as described objectively by rating services, government agencies, R&D departments, and the like) explains most of the variance in its price. Third, draw the map by plotting on a graph the position of every product in the market you've selected according to its price and its level of primary benefit, and draw a line that runs through the middle of the points. What you get is a picture of the competitive landscape of your market, where all the products above the line command a price premium owing to some secondary benefit customers value, and all those below the line are positioned to earn market share through lower prices and reduced secondary benefits. Using examples as varied as Harley-Davidson motorcycles, Motorola cell phones, and the New York restaurant market, Tuck professor D'Aveni demonstrates some of the many ways the maps can be used: to locate unoccupied or less-crowded spaces in highly competitive markets, for instance, or to identify opportunities created through changes in the relationship between the primary benefit and prices. The maps even allow companies to anticipate--and counter-- rivals' strategies. R eprint RO711G

  6. Determination of protein binding rate of salicylic acid in plasma derived from different species via high-per-formance liquid chromatography%水杨酸在不同血浆中的蛋白结合率测定

    Institute of Scientific and Technical Information of China (English)

    张农山; 张立; 王培民

    2014-01-01

    Objective To investigate the protein binding ratio of salicylic acid in the plasma derived from rats, Beagle dogs and human. Methods Equilibrium dialysis was performed to determine the plasma protein binding rates in plasma derived from different species. High-performance liquid chromatography (HPLC) was employed to determine the concentration of salicylic acid inside or outside of the dialysis membrane, which allowed the calculation of protein binding rates. Results The plasma protein binding rates of salicylic acid at low, middle and high concentrations in different species were (91.1±1.4)%, (90.2±2.5)% and (90.7±3.1)% in rats, (82.5±2.1)%, (81.3±1.8)% and (83.1±2.3)%in Beagle dogs, and (96.5±2.7)%, (97.2±3.0)% and (96.4±1.6)% in humans, respectively. Conclusion The protein binding rates of salicylic acid are highest in human, followed by rats and Beagle dogs.%目的:研究水杨酸与大鼠、比格犬和人的血浆蛋白结合率。方法采用平衡透析法,以高效液相色谱法对透析内液与外液中水杨酸的含量进行测定,计算水杨酸与大鼠、比格犬和人的血浆蛋白结合率。结果水杨酸低、中、高(0.6,1,3μg/ml)3个浓度的大鼠血浆蛋白结合率分别为(91.1±1.4)%,(90.2±2.5)%,(90.7±3.1)%;比格犬血浆蛋白结合率分别为(82.5±2.1)%,(81.3±1.8)%,(83.1±2.3)%;人血浆蛋白结合率分别为(96.5±2.7)%,(97.2±3.0)%,(96.4±1.6)%。结论水杨酸与血浆蛋白具有高强度的结合,其中与人血浆中的蛋白结合较强,且人>大鼠>比格犬。

  7. Plasma protein binding characteristics of triptolide in several species%雷公藤内酯醇与不同种属血浆蛋白结合率的研究

    Institute of Scientific and Technical Information of China (English)

    刘萍霞; 王娟; 庄笑梅; 张玉杰; 张振清; 阮金秀

    2012-01-01

    目的 考察雷公藤内酯醇在不同种属的血浆蛋白结合率.方法 超滤法分离结合型药物和游离型药物,LC-MS/MS法测定药物的浓度.结果 雷公藤内酯醇在不同浓度下与大鼠血浆的蛋白结合率分别是(25.4±1.8)、(12.7±8.5)和(11.5.±3.2)ng/ml,与比格犬血浆的蛋白结合率分别是(16.1±2.2)、(28.6±0.3)和(25.0±1.2)ng/ml;与人血浆的蛋白结合率分别是(21.5±2.1)、(18.9±5.7)和(21.3±2.6) ng/ml.结论 雷公藤内酯醇在实验浓度范围内与大鼠、比格犬和人血浆中蛋白结合率均较低,相同浓度雷公藤内酯醇与不同种属血浆蛋白结合率,以犬血浆最高[(28.6±0.3)ng/ml],与大鼠[(25.4±1.8) ng/ml]、人血浆[(18.9±5.7) g/ml]相比均具有统计学差异(P<0.05),大鼠与人血浆之间无统计学差异.各种属血浆蛋白结合率与药物浓度无明显依赖关系.%Objective To study the regularity of the plasma protein binding rate of triptolide ( TP ) in several species. Methods Ultrafiltration was employed to determine the plasma protein binding rate of triptolide in several species. Results The plasma protein binding rate of TP was 25.4 ± 1. 8, 12. 7 ±8. 5 and 11. 5 ±3.2 ng/ml in rat, 16. 1 ±2.2, 28.6 ±0.3 and 25. 0 ± 1.2 ng/ml in Beagles and 21. 5 ±2.1, 18. 9 ±5. 7 and 21. 3 ±2. 6 ng/ml in humans, respectively. Conclusion TP has a lower plasma protein binding rate in several species and the highest binding rate is showed in the dog plasma at the same concentration of 40 ng/ml. There is statistic difference between dog, rat and human plasma ( P <0. 05 ). The protein binding rates are not proportionally dependent on plasma concentrations of TP.

  8. Determination of the protein binding rates of apigenin with different kinds of plasma by HPLC%高效液相色谱法测定芹菜素在不同血浆中的蛋白结合率

    Institute of Scientific and Technical Information of China (English)

    任非; 段坤峰; 吴宗耀; 王蓓; 杨静; 陈学军

    2012-01-01

    目的:建立测定芹菜素在大鼠血浆、人血浆和牛血清白蛋白(BSA)中蛋白结合率的方法,并计算不同介质中的的相关参数.方法:采用高效液相色谱(HPLC)测定不同介质中芹菜素的浓度,并结合平衡透析法测定蛋白结合率.结果:高、中、低浓度下,芹菜素的血浆蛋白结合率分别为:大鼠血浆:(99.4±3.8)%、(99.6±5.6)%、(99.5±4.5)%;人血浆:(96.3±7.2)%、(97.9±10.5)%、(97.8±9.7)%;牛血清白蛋白:(98.7±8.6)%、(99.6±9.4)%、(99.1±8.0)%.结论:本方法快速、简便、可靠,芹菜素与大鼠血浆、人血浆和牛血清白蛋白结合率很高,且与血药浓度无显著相关性.%OBJECTIVE To establish a method for determining the protein binding rates of apigenin in rat plasma, human plasma.bovine serum albumin (BSA).and to calculate the correlate related parameters of apigenin in different matrix. METHODS The concentrations of apigenin in different matrix were assayed by high performance liquid chromatography (HPl.C). The protein binding rates of apigenin in different matrix were determined by equilibrium dialysis method. RESULTS The protein binding rates of apigenin with rat plasma,human plasma and BSA were (99. 4 ± 3.8) %. (99. 6 ± 5. 6) %, (99. 5 ± 4. 5) %, respectively, when high concentration of apigenin was used;they were (96. 3 ± 7. 2)%, (97. 9 + 10. 5)%. (97. 8 ± 9. 7)% .respectively, when medium concentration of apigenin was used;and they were (98. 7 ± 8. 6)%, (99. 6 + 9. 4)%, (99. 1 +8.0)%, respectively,when low concentration of apigenin was used CONCLUSION The method was validated to be rapid.and reliable. The protein binding rates of apigenin with rat plasma, human plasma and BSA were very high. Moreover, the plasma protein binding rates were dose-independent.

  9. Higher Education, Employability and Competitiveness

    Science.gov (United States)

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  10. Airline competition at European airports

    NARCIS (Netherlands)

    K. Frenken; S. van Terwisga; T. Verburg; G. Burghouwt

    2004-01-01

    Hub-and-spoke networks of airlines create entry barriers at large hub airports. As a result, deregulation does not necessary lead to more competition. In this paper, airline competition at European airports in the 1990s is analysed. Results show important differences between airports, which are rela

  11. Higher Education, Employability and Competitiveness

    Science.gov (United States)

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  12. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph); M.M. de Weerdt (Mathijs)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff

  13. The Power Trading Agent Competition

    NARCIS (Netherlands)

    Ketter, W.; Collins, J.; Reddy, P.; Flath, C.; De Weerdt, M.M.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff contracts,

  14. How to use competitive intelligence.

    Science.gov (United States)

    MacStravic, R S

    1989-02-01

    Keeping tabs on the competition is a necessity, not a luxury, for organizations operating in today's health-care marketplace. This article, the second of two, explores various strategies for using competitive intelligence and suggests ways to ensure organization-wide commitment to gathering and using this information as part of an overall strategic plan.

  15. The need for competitive intelligence.

    Science.gov (United States)

    MacStravic, R S

    1989-01-01

    Often associated with marketing warfare, competitive intelligence has become an essential part of health-care organizations' strategic planning efforts. Without overstepping ethical boundaries, providers can gather a vast array of "intelligence" about their competition from public sources, from the marketplace and from competitors themselves.

  16. Competitive strategy a new era.

    Science.gov (United States)

    Zuckerman, Alan M

    2007-11-01

    By adopting five basic practices, your organization will be ready to advance to the next level of competitive fitness: Develop a reliable financial baseline. Insist on development of a competitive intelligence database system. Employ rigorous business planning. Advocate for focus and discipline. Really commit to competing.

  17. Competitive dimensions of human resources

    OpenAIRE

    Neykova Rumyana Mykolaivna; Prokopenko Olha Volodymyrіvna; Shcherbachenko Viktoriia Oleksiivna

    2015-01-01

    This article deals with the essence of human resources competitive dimensions. Their competitive priorities are analyzed in dynamic business environment, with an emphasis on the quality of human resources, their adaptive skills, communication skills and mobility. The attention is paid to the role behavior of personnel and the policies for its management in the context of cutting down management costs.

  18. Prediction of Competitive Microbial Growth.

    Science.gov (United States)

    Fujikawa, Hiroshi

    2016-01-01

     Prediction of competitive microbial growth is becoming important for microbial food safety. There would be two approaches to predict competitive microbial growth with mathematical models. The first approach is the development of a growth model for competitive microbes. Among several candidates for the competition model considered, the combination of the primary growth model of the new logistic (NL) model and the competition model of the Lotka-Vorttera (LV) model showed the best performance in predicting microbial competitive growth in the mixed culture of two species. This system further successfully predicted the growth of three competitive species in mixed culture. The second approach is the application of the secondary model especially for the parameter of the maximum cell population in the primary growth model. The combination of the NL model and a polynomial model for the maximum population successfully predicted Salmonella growth in raw ground beef. This system further successfully predicted Salmonella growth in beef at various initial concentrations and temperatures. The first approach requires microbial growth data in monoculture for analysis. The second approach to the prediction of competitive growth from the viewpoint of microbial food safety would be more suitable for practical application.

  19. Competitive dimensions of human resources

    Directory of Open Access Journals (Sweden)

    Neykova Rumyana Mykolaivna

    2015-02-01

    Full Text Available This article deals with the essence of human resources competitive dimensions. Their competitive priorities are analyzed in dynamic business environment, with an emphasis on the quality of human resources, their adaptive skills, communication skills and mobility. The attention is paid to the role behavior of personnel and the policies for its management in the context of cutting down management costs.

  20. Essays on competition in banking

    NARCIS (Netherlands)

    van Boxtel, A.A.

    2015-01-01

    This thesis consists of three chapters of a theoretical nature, all related to the topic of competition in the financial sector. The first chapter studies how competition for talented workers induces banks to set variable wage schemes, and how these wage schemes can lead to excessive risk. The secon

  1. MEASURING COMPETITIVENESS OF ECONOMIC ENTITIES

    Directory of Open Access Journals (Sweden)

    MUNGIU-PUPĂZAN MARIANA CLAUDIA

    2013-12-01

    Full Text Available A competitive structure of a national economy is influenced by the competitiveness of each of the actors made the national economy. In other words, to achieve competitive economic structure shall contribute all sectors of the national economy and hence all branches of the national economy, all organizations within each branch. Thus, the productive sectors of the economy contribute by increasing their competitiveness, GDP growth, added value, while other branches making a contribution through activity, increased quality of life (health, culture, social in training skilled labor (education to ensure effective functioning of the judiciary, protection of private property and citizen safety, lower crime rate (police, reducing the risk of political instability, increasing social cohesion, social disparities (richness and extreme poverty, and discrimination against women and minority groups. Human resources are probably the most important factor determining the competitiveness of an area. The ability of a country to move up the value chain is closely related to human resource capability. In understanding the competitive evaluation is important to assess not only in terms of education, improvement, skills and work experience, but also in terms of other attributes, more difficult to measure, as entrepreneurial relationships, creativity and risk tolerance. Secondly, we must accept that individual productivity is determined by external factors. Latent potential of the individual can develop when the person moves to another environment that provides better and more opportunities. Currently structural changes to remain competitive obtaining essential parameters of the Romanian economy to cope with competitive pressures of the single European market.

  2. The competition for supplier resources

    NARCIS (Netherlands)

    Pulles, Niels J.

    2014-01-01

    Suppliers can have a major influence on the overall competitiveness of a firm. When firms lack certain capabilities or resources within their own organization, collaborations with suppliers can help them to acquire these resources and capabilities externally and improve competitive advantage. Howeve

  3. A Survey of Robotic Competitions

    Directory of Open Access Journals (Sweden)

    Richard Balogh

    2008-11-01

    Full Text Available A survey of robotic competitions all over the world, their short history and present state is given. Contests are classified according to their difficulty and conditions. Typical competition categories, also with interesting robot constructions are described. Sense, advantages and disadvantages of contests are discussed, especially concerning educational purposes. At the same time, our experiences with organising the contest Istrobot are presented.

  4. DOE Collegiate Wind Competition (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J.

    2014-02-01

    This presentation for the January Stakeholder Engagement and Outreach webinar outlines the expanded need for workers in the wind industry and provides an overview of the DOE Wind Competition (to be held in May 2014) and the guiding principles of the competition.

  5. Modeling discrete competitive facility location

    CERN Document Server

    Karakitsiou, Athanasia

    2015-01-01

    This book presents an up-to-date review of modeling and optimization approaches for location problems along with a new bi-level programming methodology which captures the effect of competition of both producers and customers on facility location decisions. While many optimization approaches simplify location problems by assuming decision making in isolation, this monograph focuses on models which take into account the competitive environment in which such decisions are made. New insights in modeling, algorithmic and theoretical possibilities are opened by this approach and new applications are possible. Competition on equal term plus competition between market leader and followers are considered in this study, consequently bi-level optimization methodology is emphasized and further developed. This book provides insights regarding modeling complexity and algorithmic approaches to discrete competitive location problems. In traditional location modeling, assignment of customer demands to supply sources are made ...

  6. Finite land resources and competition

    DEFF Research Database (Denmark)

    Haberl, Helmut; Mbow, Cheikh; Deng, Xiangzheng

    2014-01-01

    Rising demand for land-based products (food, feed, fi ber, and bioenergy) as well as conservation of forests and carbon sinks create increasing competition for land. Landuse competition has many drivers, takes different forms, and can have many significant implications for ecosystems as well as s...... and energy systems, “ land architecture” (i.e., the significance of spatial confi gurations), and multiscale models to assess local-global connections and impacts.......Rising demand for land-based products (food, feed, fi ber, and bioenergy) as well as conservation of forests and carbon sinks create increasing competition for land. Landuse competition has many drivers, takes different forms, and can have many significant implications for ecosystems as well...... as societal well-being. This chapter discusses several emerging issues, including the effect of increased demand for nonprovisioning ecosystem services ( biodiversity conservation and carbon sequestration), urbanization, bioenergy, and teleconnections. Three major types of land-use competition are discerned...

  7. Evolutionary disarmament in interspecific competition.

    Science.gov (United States)

    Kisdi, E; Geritz, S A

    2001-12-22

    Competitive asymmetry, which is the advantage of having a larger body or stronger weaponry than a contestant, drives spectacular evolutionary arms races in intraspecific competition. Similar asymmetries are well documented in interspecific competition, yet they seldom lead to exaggerated traits. Here we demonstrate that two species with substantially different size may undergo parallel coevolution towards a smaller size under the same ecological conditions where a single species would exhibit an evolutionary arms race. We show that disarmament occurs for a wide range of parameters in an ecologically explicit model of competition for a single shared resource; disarmament also occurs in a simple Lotka-Volterra competition model. A key property of both models is the interplay between evolutionary dynamics and population density. The mechanism does not rely on very specific features of the model. Thus, evolutionary disarmament may be widespread and may help to explain the lack of interspecific arms races.

  8. EU Competition Policy Since 1990

    DEFF Research Database (Denmark)

    Bartalevich, Dzmitry

    2013-01-01

    reforms, carry out a comparative analysis between EU and U.S. competition policies, detect convergence or divergence, and account for the degree of convergence and for the relevant mechanisms triggering convergence. The main focus is on the analysis of anticartel enforcement policy, antimonopoly policy......In spite of the evidence of strong influence on the incorporation of policy provisions from the U.S. antitrust into the recent competition policy reforms in the European Union (EU), few considerable attempts have been made to analyze the influence of U.S. antitrust on EU competition policy...... in anticartel enforcement policies, antimonopoly regulation, and the regulation of mergers and acquisitions. The purpose of this article is to fill the gap by attempting to link EU competition policy with U.S. antitrust, provide a critical overview of the most important elements of European competition policy...

  9. Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy. A comparative study with C-terminal (109-141)- and N-terminal (1-86)-region-specific PTHrP radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Suehiro, Mitsuko; Murakami, Minoru; Fukuchi, Minoru (Hyogo Coll. of Medicine, Nishinomiya (Japan))

    1994-11-01

    We evaluated the circulating forms of immunoreactive parathyroid hormone-related protein(PTHrP) in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109-141) fragment of PTHrP (C-RAS) and for the N-terminal(1-86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C) of PTHrP was calculated to be about 1 : 14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) humoral hypercalcemia malignancy(HHM) patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1 : 70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r=0.86). The values also showed a close correlation with serum Ca; r=0.75 for C-RAS and r=0.81 for N-RAS. In addition, the correlation between the PTHrP reading obtained with the different RASs and serum Cr were: r=0.42 with C-RAS and r=0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP (109-141). In contrast, circulating concentrations of the PTHrP (1-86) fragment are very low, but detection of the PTHrP (1-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PHPrP (109-141) fragment with C-RAS. (author).

  10. COMPETITIVE PRODUCT ADVANTAGES

    Directory of Open Access Journals (Sweden)

    Adrian MICU

    2006-01-01

    Full Text Available Cost advantages may be either internal or external. Internal economics of scope, scale, or experience, and external economies of focus or logistical integration, enable a company to produce some products at a lower cost than the competition. The coordination of pricing with suppliers, although not actually economizing resources, can improve the efficiency of pricing by avoiding the incrementalization of a supplier's nonincremental fixed costs and profit. Any of these strategies can generate cost advantages that are, at least in the short run, sustainable. Even cost advantages that are not sustainable, however, can generate temporary savings that are often the key to building more sustainable cost or product advantages later.. Even when a product's physical attributes are not readily differentiable, opportunities to develop product advantages remain. The augmented product that customers buy is more than the particular product or service exchanged. It includes all sorts of ancillary services and intangible relationships that make buying thesame product from one company less difficult, less risky, or more pleasant than buying from a competitor. Superior augmentation of the same basic product can add substantial value in the eyes of consumers, leading them to pay willingly what are often considerable price premiums.

  11. From monopoly to competition

    Energy Technology Data Exchange (ETDEWEB)

    Carpentier, J-M.

    1997-12-31

    For nearly a century, electric utilities have been vertically integrated, having control over power generation, distribution and transmission. They virtually monopolized the markets which they served. In 1977, during the energy crisis, the electric utilities were challenged with the establishment of the US Federal Energy Regulatory Commission (FERC) and in 1978 by the Public Utility Regulatory Policies Act (PURPA). This independent agency, which was initially set up to promote new energy sources and cogeneration, was also a major player in regulating electric power transmission and wholesale trade. PURPA required that electric utilities buy their electricity from qualifying independent power producers. In 1996, FERC orders 888 and 889 were issued which opened up competition to a large degree. Traditional utilities were forced to unbundle their generating and transmission costs. Order 889 opened up information systems to show available transmission capacity on power grids. By setting up a division to take charge of its power transmission system, Hydro-Quebec hopes to gain full access to transmission setups and the wholesale electricity market in the US. 1 fig.

  12. Competitiveness of the region : content, factors, policies

    OpenAIRE

    2009-01-01

    The article describes a framework conception of regional competitiveness. The notion of regional competitiveness as well as approaches to the classification of competi-tiveness factors are considered in detail. The author elaborates a set of indicators of re-gional competitiveness. The article also dis-cusses three groups of factors which can influence the competitiveness of any region.

  13. Marketing Aspect of Banking Competition

    Directory of Open Access Journals (Sweden)

    Nieizviestna Olena V.

    2015-03-01

    Full Text Available The aim of the article is to study the need for application of marketing tools in order to improve competitiveness and competitive advantages of banks. By analyzing, systematizing and summarizing the scientific works of many scientists, the relationship between the competitiveness of the commercial bank and its share in the banking market has been discovered. In the process of studying the integration of the strategy of maximizing customer satisfaction in the practice of strategic competition in the banking market there was presented the author’s position regarding the need to take into account the structure of the customer loyalty, as it is it that helps to properly distribute the bank’s marketing efforts. It has been proved that the technology of bank marketing should not only include the systems of identifying customer needs, creation of new financial products, but also contribute to the formation of the multi-factor strategic model of competitive strategy of the bank competitive development. It has been proposed to use the SWOT-analysis in order to effectively manage the bank’s competitiveness.

  14. Determination of plasma protein binding rate of five components in Eucommia ulmoides extract%杜仲提取物中五个成分血浆蛋白结合率的测定

    Institute of Scientific and Technical Information of China (English)

    曹旭; 谢玉敏; 朱迪; 陈鹏程; 巩仔鹏; 王爱民

    2015-01-01

    目的:测定杜仲药材中5个成分的血浆蛋白结合率。方法采用平衡透析法测定血浆蛋白结合率,生物样本用甲醇沉淀蛋白进行处理,以葛根素为内标,利用超高效液相色谱-串联质谱仪测定血浆和缓冲溶液中的5个成分浓度。结果在所研究浓度范围内,京尼平苷酸、原儿茶酸、绿原酸、松脂醇二葡萄糖苷和松脂醇单葡萄糖苷的平均蛋白结合率分别为(25.77±2.68)%、(57.54±3.79)%、(53.91±3.00)%、(24.15±4.92)%、(49.78±3.61)%。结论京尼平苷酸和松脂醇二葡萄糖苷的蛋白结合率较低,原儿茶酸、绿原酸和松脂醇单葡萄糖苷则与大鼠血浆蛋白有中等强度的结合。%Aim To determine the plasma protein binding rate of five components of Eucommia ulmoides extract. Methods The equilibrium dialysis method was used to study the plasma protein binding rate. The plasma samples were extracted by protein precipitation with methanol. With the use of puerarin as the internal standard, UPLC-MS/MS was carried out to determine the concentration of the five compounds in and out of the dialysis membrane. Results The average plasma protein binding rates of five compounds on the area of the concentration which was determinate were as fol-lows, respectively: geniposidic acid was ( 25. 77 ± 2. 68 )%, protocatechuic acid was ( 57. 54 ± 3. 79)%, chlorogenic acid was (53. 91 ± 3. 00)%, pinoresinol diglucoside was (24. 15 ± 4. 92)%, and pinoresinol singleglucoside was (49. 78 ± 3. 61)%. Conclusions The results show that the binding percentage of geniposidic acid and pinoresinol diglucoside is relatively low, but the binding rate of the others with rat plasma protein is moderate.

  15. Competition for nutrient and light: stable coexistence, alternative stable states, or competitive exclusion?

    NARCIS (Netherlands)

    Passarge, J.; Hol, S.; Escher, M.; Huisman, J.

    2006-01-01

    Competition theory has put forward three contrasting hypotheses: Competition for nutrients and light may lead to (i) stable coexistence of species, (ii) alternative stable states, or (iii) competitive exclusion. This paper presents a detailed investigation of competition among phytoplankton species

  16. Competition for nutrients and light: Stable coexistence, alternative stable states or competitive exclusion?

    NARCIS (Netherlands)

    Passarge, J.; Hol, S.; Escher, M.; Huisman, J.

    2006-01-01

    Abstract. Competition theory has put forward three contrasting hypotheses: Competition for nutrients and light may lead to (i) stable coexistence of species, (ii) alternative stable states, or (iii) competitive exclusion. This paper presents a detailed investigation of competition among phytoplankto

  17. Romania's Competitiveness and Competitive Position in Global Context

    Directory of Open Access Journals (Sweden)

    Valentin NECULITA

    2012-08-01

    Full Text Available Competitiveness increase has become a primordial framework of the social and economic development strategies of most world countries (mainly the most developed ones over the last decades. The vigorous boost of the contemporary phenomenon of globalization, which has widened the global area of economies, sectors and firms confrontation, has laid an emphasis on their competitiveness importance for their favorable position in the international competition and has therefore force the status to take proper, broad and concerted measures to stimulate the determining factors of action and to take better advantage of their effects. The purpose of the paper is to determine whether an increase in competitiveness could reduce the disparities between regions. The E.U. Member States and regions need significant financial help to solve various structural problems and to achieve their potential of growth. Romania is no exception, one of the main problems being the low rate in attracting European funds.

  18. Testosterone, cortisol, and human competition.

    Science.gov (United States)

    Casto, Kathleen V; Edwards, David A

    2016-06-01

    Testosterone and cortisol figure prominently in the research literature having to do with human competition. In this review, we track the history of this literature, concentrating particularly on major theoretical and empirical contributions, and provide commentary on what we see as important unresolved issues. In men and women, athletic competition is typically associated with an increase in testosterone (T) and cortisol (C). Hormone changes in response to non-athletic competition are less predictable. Person (e.g., power motivation, mood, aggressiveness, social anxiety, sex, and baseline levels of T and C) and context (e.g., whether a competition is won or lost, the closeness of the competition, whether the outcome is perceived as being influenced by ability vs. chance, provocations) factors can influence hormone responses to competition. From early on, studies pointed to a positive relationship between T and dominance motivation/status striving. Recent research, however, suggests that this relationship only holds for individuals with low levels of C - this is the core idea of the dual-hormone hypothesis, and it is certain that the broadest applications of the hypothesis have not yet been realized. Individuals differ with respect to the extent to which they embrace competition, but the hormonal correlates of competitiveness remain largely unexplored. Although rapid increases in both T and C associated with competition are likely adaptive, we still know very little about the psychological benefits of these hormonal changes. Administration studies have and will continue to contribute to this inquiry. We close with a discussion of what, we think, are important methodological and mechanistic issues for future research.

  19. Synthesis, structure, DNA/protein binding, and cytotoxic activity of a rhodium(III) complex with 2,6-bis(2-benzimidazolyl)pyridine.

    Science.gov (United States)

    Esteghamat-Panah, Roya; Hadadzadeh, Hassan; Farrokhpour, Hossein; Simpson, Jim; Abdolmaleki, Amir; Abyar, Fatemeh

    2017-02-15

    A new mononuclear rhodium(III) complex, [Rh(bzimpy)Cl3] (bzimpy = 2,6-bis(2-benzimidazolyl)pyridine), was synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structure of the complex was confirmed by single-crystal X-ray crystallography. The interaction of the complex with fish sperm DNA (FS-DNA) was investigated by UV spectroscopy, emission titration, and viscosity measurement in order to evaluate the possible DNA-binding mode and to calculate the corresponding DNA-binding constant. The results reveal that the Rh(III) complex interacts with DNA through groove binding mode with a binding affinity on the order of 10(4). In addition, the binding of the Rh(III) complex to bovine serum albumin (BSA) was monitored by UV-Vis and fluorescence emission spectroscopy at different temperatures. The mechanism of the complex interaction was found to be static quenching. The thermodynamic parameters (ΔH, ΔS, and ΔG) obtained from the fluorescence spectroscopy data show that van der Waals interactions and hydrogen bonds play a major role in the binding of the Rh(III) complex to BSA. For the comparison of the DNA- and BSA-binding affinities of the free bzimpy ligand with its Rh(III) complex, the absorbance titration and fluorescence quenching experiments of the free bzimpy ligand with DNA and BSA were carried out. Competitive experiments using eosin Y and ibuprofen as site markers indicated that the complex was mainly located in the hydrophobic cavity of site I of the protein. These experimental results were confirmed by the results of molecular docking. Finally, the in vitro cytotoxicity properties of the Rh(III) complex against the MCF-7, K562, and HT-29 cell lines were evaluated and compared with those of the free ligand (bzimpy). It was found that the complexation process improved the anticancer activity significantly.

  20. Distributed Wind Competitiveness Improvement Project

    Energy Technology Data Exchange (ETDEWEB)

    2016-05-01

    The Competitiveness Improvement Project (CIP) is a periodic solicitation through the U.S. Department of Energy and its National Renewable Energy Laboratory. Manufacturers of small and medium wind turbines are awarded cost-shared grants via a competitive process to optimize their designs, develop advanced manufacturing processes, and perform turbine testing. The goals of the CIP are to make wind energy cost competitive with other distributed generation technology and increase the number of wind turbine designs certified to national testing standards. This fact sheet describes the CIP and funding awarded as part of the project.

  1. Distributional preferences and competitive behavior.

    Science.gov (United States)

    Balafoutas, Loukas; Kerschbamer, Rudolf; Sutter, Matthias

    2012-06-01

    We study experimentally the relationship between distributional preferences and competitive behavior. We find that spiteful subjects react strongest to competitive pressure and win in a tournament significantly more often than efficiency-minded and inequality averse subjects. However, when given the choice between a tournament and a piece rate scheme, efficiency-minded subjects choose the tournament most often, while spiteful and inequality averse subjects avoid it. When controlling for distributional preferences, risk attitudes and past performance, the gender gap in the willingness to compete is no longer significant, indicating that gender-related variables explain why twice as many men as women self-select into competition.

  2. Keynote address: Coal competitiveness and energy alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Broadbent, G. [IEA Coal Research, Clean Coal Centre, London (United Kingdom)

    2001-02-01

    The competitiveness of coal versus gas, nuclear and renewables for power generation is discussed. It is concluded that coal is competitive on existing plant but it needs to accelerate technology development faster than the competition to sustain its future.

  3. 5 CFR 351.402 - Competitive area.

    Science.gov (United States)

    2010-01-01

    ... effect less than 90 days prior to the effective date of a reduction in force, a description of the... Competition § 351.402 Competitive area. (a) Each agency shall establish competitive areas in which...

  4. Competition in natural populations of Daphnia

    NARCIS (Netherlands)

    Boersma, M.

    1995-01-01

    I investigated the competitive relationships between two species of Daphnia, D. galeata and D. cucullata, and their interspecific hybrid. The term hemispecific competition was introduced to describe competition between parental species and hybrids. In eutrophic Tjeukemeer both parental species were

  5. 2-O-[2-(Methylthio)ethyl]-Modified Oligonucleotide: An Analog of 2-O-[2-(Methoxy)ethyl]-Modified Oligonucleotide with Improved Protein Binding Properties and High Binding Affinity to Target RNA

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, T.P.; Manoharan, M.; Fraser, A.S.; Kawasaki, A.M.; Lesnik, E.; Sioufi, N.; Leeds, J.M.; Teplova, M.; Egli, M.

    2010-03-08

    A novel 2'-modification, 2'-O-[2-(methylthio)ethyl] or 2'-O-MTE, has been incorporated into oligonucleotides and evaluated for properties relevant to antisense activity. The results were compared with the previously characterized 2'-O-[2-(methoxy)ethyl] 2'-O-MOE modification. As expected, the 2'-O-MTE modified oligonucleotides exhibited improved binding to human serum albumin compared to the 2'-O-MOE modified oligonucleotides. The 2'-O-MTE oligonucleotides maintained high binding affinity to target RNA. Nuclease digestion of 2'-O-MTE oligonucleotides showed that they have limited resistance to exonuclease degradation. We analyzed the crystal structure of a decamer DNA duplex containing the 2'-O-MTE modifcation. Analysis of the crystal structure provides insight into the improved RNA binding affinity, protein binding affinity and limited resistance of 2'-O-MTE modified oligonucleotides to exonuclease degradation.

  6. Determination of human plasma protein binding rate of oridonin by ultrafiltration and high-performance liquid chromatography%超滤法测定冬凌草甲素的血浆蛋白结合率

    Institute of Scientific and Technical Information of China (English)

    陈莹; 蔡爽

    2013-01-01

    Objective To study the plasma protein binding rate of oridonin in human plasma,rat plasma and rabbit plasma to provide the basis for designing reasonable dosage regimen.Methods Ultraflitration method was used to imitate the binding rates of oridonin.High performance liquid chromatography (HPLC) was employed to determine the concentration of oridonin,and then on the basis of which protein binding rates were calculated.Results The plasma protein binding rate of oridonin at the concentration of 5.4,21.6 and 108.0 μg/mL with normal human plasma were 80.6%,78.3% and 76.2%,with rat plasma were 69.3%,67.5% and 68.1%,while with rabbit plasma were 65.2%,66.7% and 64.3%,respectively.Conclusion The ultraflitration-HPLC method is simple,rapid,reliable and can be usd to determine the drug concentration of oridonin properly.The results suggested that the protein binding rates of oridonin were of middle strength in binding to plasma protein of rabbits,rats and human and it is not proportionally dependent on plasma concentration of oridonin.%目的 测定冬凌草甲素在健康人血浆、大鼠血浆和家兔血浆中的蛋白结合率,为设计合理的给药方案提供依据.方法 采用超滤法结合高效液相色谱法(HPLC)对冬凌草甲素与大鼠、家兔和健康人血浆的蛋白结合率进行测定.结果 冬凌草甲素在覆盖临床给药范围的5.4,21.6和108.0 μg/mL下与健康人血浆的血浆蛋白结合率分别为80.6%,78.3%,76.2%,与大鼠的血浆蛋白结合率分别为69.3%,67.5%,68.1%,与家兔的血浆蛋白结合率分别为65.2%,66.7%,64.3%.覆盖临床给药浓度的3个浓度的冬凌草甲素在同种血浆中血浆蛋白结合率差异无统计学意义(P>0.05).结论 结果表明本法简便快速、灵敏度高、专属性好,能够满足测试生物样品的要求,超滤法结合高效液相色谱法可用于冬凌草甲素血浆蛋白结合率的检测.在本研究试验浓度范围内,

  7. Competitive Think Tanks in Europe

    DEFF Research Database (Denmark)

    Kelstrup, Jesper Dahl

    in opportunity structures that are mediated by historically constituted institutions in knowledge regimes. The paper distinguishes between four different strategies, the authoritative, the collaborative, the agenda-setting and the competitive strategy that are distinguished by the relations think tanks have...... to established institutions and power in public policy. On the basis of the hypothesis that more competitive think tanks have emerged due to lower opportunity costs, the paper investigates how ‘competitive’ think tank strategies have been used in Germany, Denmark, the EU-institutions in Brussels...... and in the United Kingdom from 2000 to 2012. The findings contradict the hypothesis that the competitive think tank strategy is the dominant or even a common strategy across the cases under investigation. The competitive strategy is particularly rare among EU and German think tanks. As such the paper challenges...

  8. FLEXIBLE BUDGET OF SPORT COMPETITIONS

    Directory of Open Access Journals (Sweden)

    Dragan Vukasović

    2009-11-01

    Full Text Available Manager of sport competition has right to decide and also to take responsibility for costs, income and financial results. From economic point of wiev flexible budget and planning cost calculations is top management base for analyzing success level of sport competition. Flexible budget is made before sport competition with few output level, where one is always from static plan-master plan. At the end of competition when we have results, we make report of plan executing and we also analyzing plan variances. Results of comparation between achieved and planning level of static budget can be acceptable if achieved level is approximate to budget level or if we analyzing results from gross or net income. Flexible budget become very important in case of world eco- nomic crises

  9. The Scientific Competitiveness of Nations

    CERN Document Server

    Cimini, Giulio; Labini, Francesco Sylos

    2014-01-01

    We use citation data of scientific articles produced by individual nations in different scientific domains to determine the structure and efficiency of national research systems. We characterize the scientific fitness of each nation$-$that is, the competitiveness of its research system$-$and the complexity of each scientific domain by means of a non-linear iterative algorithm able to assess quantitatively the advantage of scientific diversification. We find that technological leading nations, beyond having the largest production of scientific papers and the largest number of citations, do not specialize in a few scientific domains. Rather, they diversify as much as possible their research system. On the other side, less developed nations are competitive only in scientific domains where also many other nations are present. Diversification thus represents the key element that correlates with scientific and technological competitiveness. A remarkable implication of this structure of the scientific competition is...

  10. Competitive Strategy in Continuing Education.

    Science.gov (United States)

    Baden, Clifford

    1987-01-01

    Reviews strategic variables available to those planning continuing education marketing programs. Discusses generic competitive strategies: (1) overall cost leadership, (2) differentiation, and (3) specialization. Mentions several potential problems. (CH)

  11. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely......We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized....... In particular, imperfect competition on the product markets and the positive profits associated with it may have the effect that there is a cycle even if the labor supply curve is increasing in the real-wage rate. For competitive cycles is required not only a decreasing labor supply curve, but a wage elasticity...

  12. Competitive Strategy in Continuing Education.

    Science.gov (United States)

    Baden, Clifford

    1987-01-01

    Reviews strategic variables available to those planning continuing education marketing programs. Discusses generic competitive strategies: (1) overall cost leadership, (2) differentiation, and (3) specialization. Mentions several potential problems. (CH)

  13. Logistics systems optimization under competition

    DEFF Research Database (Denmark)

    Choi, Tsan Ming; Govindan, Kannan; Ma, Lijun

    2015-01-01

    Nowadays, optimization on logistics and supply chain systems is a crucial and critical issue in industrial and systems engineering. Important areas of logistics and supply chain systems include transportation control, inventory management, and facility location planning. Under a competitive market...

  14. The Third International Timetabling Competition

    NARCIS (Netherlands)

    Post, Gerhard; Di Gaspero, Luca; Kingston, Jeffrey H.; McCollum, Barry; Schaerf, Andrea; Kjenstad, D.; Riise, A.; Nordlander, T.E.; McCollum, B.; Burke, E.

    2012-01-01

    This paper is the organizers’ report on the Third International Timetabling Competition (ITC2011), run during the first half of 2012. Its participants tackled 35 instances of the high school timetabling problem, taken from schools in 10 countries.

  15. Knowledge Resources and Competitive Advantage

    Directory of Open Access Journals (Sweden)

    Doris Gomezelj Omerzel

    2011-12-01

    Full Text Available The paper discusses some definitions of knowledge as a potential sourceof competitive advantage. It reviews the literature pertaining to the assessmentof knowledge assets. According to the resource-based view,which links the competitive advantage of organizations with resourcesand capabilities that are firm-specific, and difficult to imitate or substitute,a firm’s competitive advantage is built on a set of strategicallyrelevant resources (Barney 1991; Grant 1991; Peteraf 1993. When firmshave access to similar resources, it is those companies that are able tomaximize the utilization of those resources that attain a competitiveadvantage. Among various strategic resources and capabilities that helpdetermine the extent of competitive advantages, a pivotal role is oftenassigned to knowledge – as both a resource in itself and an integratingfactor that makes other resources and capabilities effective – especiallyin complex and dynamic environments.

  16. Mixed ligand copper(II) dicarboxylate complexes: the role of co-ligand hydrophobicity in DNA binding, double-strand DNA cleavage, protein binding and cytotoxicity.

    Science.gov (United States)

    Loganathan, Rangasamy; Ramakrishnan, Sethu; Ganeshpandian, Mani; Bhuvanesh, Nattamai S P; Palaniandavar, Mallayan; Riyasdeen, Anvarbatcha; Akbarsha, Mohamad Abdulkadhar

    2015-06-14

    A few water soluble mixed ligand copper(ii) complexes of the type [Cu(bimda)(diimine)] , where bimda is N-benzyliminodiacetic acid and diimine is 2,2'-bipyridine (bpy, ) or 1,10-phenanthroline (phen, ) or 5,6-dimethyl-1,10-phenanthroline (5,6-dmp, ) or 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8-tmp, ) and dipyrido[3,2-d: 2',3'-f]quinoxaline (dpq, ), have been successfully isolated and characterized by elemental analysis and other spectral techniques. The coordination geometry around copper(ii) in is described as distorted square based pyramidal while that in is described as square pyramidal. Absorption spectral titrations and competitive DNA binding studies reveal that the intrinsic DNA binding affinity of the complexes depends upon the diimine co-ligand, dpq () > 3,4,7,8-tmp () > 5,6-dmp () > phen () > bpy (). The phen and dpq co-ligands are involved in the π-stacking interaction with DNA base pairs while the 3,4,7,8-tmp/5,6-dmp and bpy co-ligands are involved in respectively hydrophobic and surface mode of binding with DNA. The small enhancement in the relative viscosity of DNA upon binding to supports the DNA binding modes proposed. Interestingly, and are selective in exhibiting a positive induced CD band (ICD) upon binding to DNA suggesting that they induce B to A conformational change. In contrast, and show CD responses which reveal their involvement in strong DNA binding. The complexes are unique in displaying prominent double-strand DNA cleavage while effects only single-strand DNA cleavage, and their ability to cleave DNA in the absence of an activator varies as > > > > . Also, all the complexes exhibit oxidative double-strand DNA cleavage activity in the presence of ascorbic acid, which varies as > > > > . The ability of the complexes to bind and cleave the protein BSA varies in the order > > > > . Interestingly, and cleave the protein non-specifically in the presence of H2O2 as an activator suggesting that they can act also as chemical proteases

  17. Mice with a Mutation in the Mdm2 Gene That Interferes with MDM2/Ribosomal Protein Binding Develop a Defect in Erythropoiesis

    Science.gov (United States)

    Kamio, Takuya; Gu, Bai-wei; Olson, Timothy S.; Zhang, Yanping; Mason, Philip J.; Bessler, Monica

    2016-01-01

    MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming a negative feedback loop that is important in cell cycle control. It has recently become apparent that the ubiquitination of p53 by MDM2 can be inhibited when certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This inhibition, and the resulting increase in p53 levels has been proposed to be responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA) and in 5q- myelodysplastic syndrome (MDS). DBA and 5q- MDS are associated with inherited (DBA) or acquired (5q- MDS) haploinsufficiency of ribosomal proteins. A mutation in Mdm2 causing a C305F amino acid substitution blocks the binding of ribosomal proteins. Mice harboring this mutation (Mdm2C305F), retain a normal p53 response to DNA damage, but lack the p53 response to perturbations in ribosome biogenesis. While studying the interaction between RP haploinsufficiency and the Mdm2C305F mutation we noticed that Mdm2C305F homozygous mice had altered hematopoiesis. These mice developed a mild macrocytic anemia with reticulocytosis. In the bone marrow (BM), these mice showed a significant decrease in Ter119hi cells compared to wild type (WT) littermates, while no decrease in the number of mature erythroid cells (Ter119hiCD71low) was found in the spleen, which showed compensated bone marrow hematopoiesis. In methylcellulose cultures, BFU-E colonies from the mutant mice were slightly reduced in number and there was a significant reduction in CFU-E colony numbers in mutant mice compared with WT controls (p < 0.01). This erythropoietic defect was abrogated by concomitant p53 deficiency (Trp53ko/ko). Further investigation revealed that in Mdm2C305F animals, there was a decrease in Lin-Sca-1+c-Kit+ (LSK) cells, accompanied by significant decreases in multipotent progenitor (MPP) cells (p < 0.01). Competitive BM repopulation experiments showed

  18. Mice with a Mutation in the Mdm2 Gene That Interferes with MDM2/Ribosomal Protein Binding Develop a Defect in Erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Takuya Kamio

    Full Text Available MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming a negative feedback loop that is important in cell cycle control. It has recently become apparent that the ubiquitination of p53 by MDM2 can be inhibited when certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This inhibition, and the resulting increase in p53 levels has been proposed to be responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA and in 5q- myelodysplastic syndrome (MDS. DBA and 5q- MDS are associated with inherited (DBA or acquired (5q- MDS haploinsufficiency of ribosomal proteins. A mutation in Mdm2 causing a C305F amino acid substitution blocks the binding of ribosomal proteins. Mice harboring this mutation (Mdm2C305F, retain a normal p53 response to DNA damage, but lack the p53 response to perturbations in ribosome biogenesis. While studying the interaction between RP haploinsufficiency and the Mdm2C305F mutation we noticed that Mdm2C305F homozygous mice had altered hematopoiesis. These mice developed a mild macrocytic anemia with reticulocytosis. In the bone marrow (BM, these mice showed a significant decrease in Ter119hi cells compared to wild type (WT littermates, while no decrease in the number of mature erythroid cells (Ter119hiCD71low was found in the spleen, which showed compensated bone marrow hematopoiesis. In methylcellulose cultures, BFU-E colonies from the mutant mice were slightly reduced in number and there was a significant reduction in CFU-E colony numbers in mutant mice compared with WT controls (p < 0.01. This erythropoietic defect was abrogated by concomitant p53 deficiency (Trp53ko/ko. Further investigation revealed that in Mdm2C305F animals, there was a decrease in Lin-Sca-1+c-Kit+ (LSK cells, accompanied by significant decreases in multipotent progenitor (MPP cells (p < 0.01. Competitive BM repopulation experiments

  19. DXC'11 Industrial Track Competition Data

    Data.gov (United States)

    National Aeronautics and Space Administration — Competition data, including nominal and faulty scenarios, for Diagnostic Problem I of the Third International Diagnostic Competition. Three file formats are...

  20. An amusement park physics competition

    Science.gov (United States)

    Moll, Rachel F.

    2010-07-01

    Amusement park physics is a popular way to reinforce physics concepts and to motivate physics learners. This article describes a novel physics competition where students use simple tools to take amusement park ride measurements and use the data to answer challenging exam questions. Research into the impact of participating in the competition reveals positive effects such as the acquisition of experimentation skills and improved attitudes towards physics.

  1. NEW APPROACHES TO EXPORT COMPETITIVENESS

    OpenAIRE

    Alina Petronela NEGREA

    2015-01-01

    The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs) increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of import...

  2. Medical coverage of gymnastics competitions.

    Science.gov (United States)

    Hecht, Suzanne S; Burton, Monique S

    2009-01-01

    Medical coverage of gymnastics competitions can be a challenging task for the sports medicine physician and other medical personnel because of the complexity and aerial nature of the sport. A broad understanding of the six gymnastics disciplines, along with the type of competitions, injury epidemiology, and the common acute gymnastics injuries will help sports medicine professionals in planning and delivering optimal care to the injured or ill gymnast.

  3. Bank Mergers, Competition and Liquidity

    OpenAIRE

    Carletti, Elena; Hartmann, Philipp; Spagnolo, Giancarlo

    2004-01-01

    We model the impact of bank mergers on loan competition, reserve holdings and aggregate liquidity. A merger changes the distribution of liquidity shocks and creates an internal money market, leading to financial cost efficiencies and more precise estimates of liquidity needs. The merged banks may increase their reserve holdings through an internalization effect or decrease them because of a diversification effect. The merger also affects loan market competition, which in turn modifies the dis...

  4. LOGISTICS - SOURCE OF COMPETITIVE ADVANTAGE

    OpenAIRE

    Adriana SCRIOSTEANU; Popescu, Daniela

    2014-01-01

    This paper presents the logistics if source of competitive advantage. Logistics can offer a source of competitive advantage, such as a superior position compared to the competitors regarding cost reductions, service diversity and satisfaction of consumer requirements. The logistic activities generate cost and give value to the final product .Despite that the same logistic activity can be done in many ways, with different costs and performance , the evaluation of the activities and the links b...

  5. Competitiveness of Slovenian Cargo Shipping

    Directory of Open Access Journals (Sweden)

    Milojka Počuča

    2012-10-01

    Full Text Available The paper presents Slovenian cargo shipping, its system oforganisation, ownership, age and value stntcture. It shows theimportance of shipping in the Slovenian overseas trade and itsimpact on the state's balance of payments. The analysis of thecompetitiveness of shipping was made from the viewpoint ofoperation costs and in comparison with the competitiveness ofEU shippers. The paper concludes with a proposal of possiblesystemic solutions which improve the competitiveness of Slovenianshipping.

  6. COMPETITIVENESS TEXTILE CLUSTER PERU MEXICO

    OpenAIRE

    Gutiérrez Huby, Ana María; Facultad de Ciencias Contables, Universidad Nacional Mayor de San Marcos; Amador Murguía, María Eugenia; Universidad de Guadalajara

    2014-01-01

    This article is a summary of the research study entitled "A comparative study in Peru- Mexico textile cluster in determining competitive strategies" that was developed in 2010 by the author in collaboration with a team of researchers at the University of Guadalajara. This article basically presents the results in comparative terms of the competitive situation of the textile cluster, Peru and Mexico, "Gamarra" and "Zapotlanejo" respectively representing the textile industry in their countries,...

  7. Competitive advantage and corporate communications

    OpenAIRE

    Mitić Sanja; Ognjanov Galjina

    2013-01-01

    Strategic importance of corporate communications and its role in the development of competitive advantage has attracted interest of numerous researchers in the fields of organization, management, marketing and public relations. Recent studies particularly emphasise the growing importance of soft factors, such as reputation in the development of competitive advantage. Concept of reputation is strongly connected with stakeholder theory, which stresses the importance of corporate communications ...

  8. Heart rates during competitive orienteering.

    OpenAIRE

    Bird, S R; Bailey, R.; Lewis, J.

    1993-01-01

    This study investigated the heart rate profiles of 16 experienced, competitive orienteers (aged 15-62 years) during three competitive events. Each competitor was assessed over three different types of course which were classified as: fast run (FR), slow run (SR) and highly physical (HP). The results showed that all subjects recorded heart rates that were between 140 and 180 beats min-1 for the majority of each event (irrespective of age or course type). The heart rate data indicated that the ...

  9. Spatial competition between shopping centers

    OpenAIRE

    António Brandão; João Correia-da-Silva; Joana Pinho

    2010-01-01

    We study competition between two shopping centers (department stores or shopping malls) located at the extremes of a linear city. In contrast with the existing literature, we do not restrict consumers to make all their purchases at a single place. We obtain this condition as an equilibrium result. In the case of competition between a shopping mall and a department store, we find that the shops at the mall, taken together, obtain a lower profit than the department store. However, the shops at ...

  10. Yardstick Competition and Policy Innovation

    OpenAIRE

    Rincke, Johannes

    2005-01-01

    A simple model of yardstick competition between jurisdictions is presented. Governments of jurisdictions face the alternative to choose between an old and a new policy with stochastic payoffs. The new policy is superior to the old policy in one state of the world, and inferior in the other. Governments are either benevolent, serving the interest of the voter, or rent-seeking. An equilibrium with yardstick competition is shown to exist where bad governments having a good government in their ne...

  11. Immunological impact of Taekwondo competitions.

    Science.gov (United States)

    Lee, Y W; Shin, K W; Paik, I-Y; Jung, W M; Cho, S-Y; Choi, S T; Kim, H D; Kim, J Y

    2012-01-01

    Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (pTaekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes. © Georg Thieme Verlag KG Stuttgart · New York.

  12. COMPETITION IN ROMANIAN BANKING SECTOR

    Directory of Open Access Journals (Sweden)

    Capraru Bogdan

    2011-07-01

    Full Text Available Recent turmoil in the global financial system has impacted severely on the banking sector with many banks suffering large losses and necessitating the need to raise additional capital privately or through their respective national governments. In our study we investigate the impact of structural reforms performed throughout the European Union (EU accession process on competition and contestability of banking systems in Romania. The literature of the measurement of competition can be divided into two major approaches: structural and non-structural. The structural approach to the assessment of competition embraces the Structure-Conduct-Performance Hypothesis (SCP and the Efficient Structure Hypothesis (ESH. The structural approach, as the name suggests, assesses bank competition by examining measures of market structure such as concentration ratios (the share of assets held by the top 3 or 5 institutions or indices (e.g., the Herfindhal-Hirschman index and supposes that higher concentration in the banking market causes less competitive bank conduct and leads to higher bank profitability. The SCP model is originally developed by Bain (1956. The second approach, ESH, developed by Demsetz (1973 and Peltzmann (1977 suggests that the superior performance of the market leaders determines the market structure, implying that higher efficiency produces both higher concentration and greater profitability. The non-structural indicators of competition are mainly based on the measures of monopoly power developed by Lerner (1934. The Lerner Index suggests the mark-up of price over marginal cost. An alternative non-structural indicator of the degree of market competition is the Panzar and Rosse (1987 H-statistic. The H-statistic measures the extent to which changes in banking costs are reflected in changes in banking revenues. In order to examine the level of competition and market power of banks in Romania for period 2003 - 2009, we estimate the non

  13. COMPETITIVE INTELLIGENCE ANALYSIS - SCENARIOS METHOD

    Directory of Open Access Journals (Sweden)

    Ivan Valeriu

    2014-07-01

    Full Text Available Keeping a company in the top performing players in the relevant market depends not only on its ability to develop continually, sustainably and balanced, to the standards set by the customer and competition, but also on the ability to protect its strategic information and to know in advance the strategic information of the competition. In addition, given that economic markets, regardless of their profile, enable interconnection not only among domestic companies, but also between domestic companies and foreign companies, the issue of economic competition moves from the national economies to the field of interest of regional and international economic organizations. The stakes for each economic player is to keep ahead of the competition and to be always prepared to face market challenges. Therefore, it needs to know as early as possible, how to react to others’ strategy in terms of research, production and sales. If a competitor is planning to produce more and cheaper, then it must be prepared to counteract quickly this movement. Competitive intelligence helps to evaluate the capabilities of competitors in the market, legally and ethically, and to develop response strategies. One of the main goals of the competitive intelligence is to acknowledge the role of early warning and prevention of surprises that could have a major impact on the market share, reputation, turnover and profitability in the medium and long term of a company. This paper presents some aspects of competitive intelligence, mainly in terms of information analysis and intelligence generation. Presentation is theoretical and addresses a structured method of information analysis - scenarios method – in a version that combines several types of analysis in order to reveal some interconnecting aspects of the factors governing the activity of a company.

  14. GLOBAL COMPETITION AND ROMANIA’S NATIONAL COMPETITIVE ADVANTAGE

    Directory of Open Access Journals (Sweden)

    Pop Nicolae Alexandru

    2013-07-01

    Full Text Available Analyzing products and services around us it is clear that most of them are the result of production factors, labor and capital becoming more international and increasingly less and less national. We are witnessing the globalization of markets and production, to a large global integration and interdependence, increase personalization of production and services as a result of new communication systems interaction and flexible production processes. Markets will continue to homogenize and diversify at the same time, so it is important that as a global marketer one addresses a market segment defined by income, age, and consumption habits and not by membership of a nation. The most visible and polarized is the premium segment fighting for high income clients where brand value plays an important role. Instead identification of large segments of customers offers the advantages of scale economy in production and marketing for global enterprises. Consumer profile is the dominant global consumer requesting and accepting global products and services easily. In fact, what can force an economic alignment to achieve the best performance, rather than the global consumer. The research methodology used includes literature review, comparative analysis, synthesis of data based on bibliographic resources and official documents.The aim of the paper is to highlight current models that underlie the competitive advantage of nations and assess the competitive advantage of Romania in the context of the global market. A case study is used to offer an overview of competitive advantage of Antibiotice Iasi SA, a competitive player, in a global pharmaceutical market with strong global competition. Countries moderate companies’ achievements of global efficiency objectives due to the countries’ rivalry. Romania has to understand that it is in competition with other countries in order to fulfill economic, political and social objectives. The scope in the end is the well

  15. RECENT ADVANCES IN TERRITORIAL COMPETITION AND COMPETITIVENESS ANALYSIS

    Directory of Open Access Journals (Sweden)

    Daniela-Luminita Constantin

    2006-10-01

    Full Text Available This paper addresses the question of territorial competitiveness – at national and regional level – from the perspective of the most important research undertaken in the international arena in order to build-up competitiveness indicators able to reveal the complexity and dynamics of this phenomenon in the contemporary society. A special emphasis is put on studies developed by prestigious organisations and research centres such as World Economic Forum, International Institute for Management Development, Cambridge Econometrics, ECORYS-NEI and so on.

  16. Political Globalization and the Competition State

    DEFF Research Database (Denmark)

    Pedersen, Ove K.

    2013-01-01

    Introduction to the concept of Competition State and descriptition of slow change from traditional welfare state towards the present competition state.......Introduction to the concept of Competition State and descriptition of slow change from traditional welfare state towards the present competition state....

  17. 40 CFR 35.382 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.382 Section 35...)(3)) § 35.382 Competitive process. State Wetlands Development Grants are awarded on a competitive... established by EPA. After the competitive process is complete, the recipient can, at its discretion,...

  18. 40 CFR 35.603 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.603 Section 35... (section 104(b)(3)) § 35.603 Competitive process. EPA will award water quality cooperative agreement funds through a competitive process in accordance with national program guidance. After the competitive...

  19. 24 CFR 791.406 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Competition. 791.406 Section 791... Authority for Housing Assistance § 791.406 Competition. (a) All budget authority allocated pursuant to § 791.403(b)(2) shall be reserved and obligated pursuant to a competition. Any such competition shall...

  20. Political Globalization and the Competition State

    DEFF Research Database (Denmark)

    Pedersen, Ove K.

    2013-01-01

    Introduction to the concept of Competition State and descriptition of slow change from traditional welfare state towards the present competition state.......Introduction to the concept of Competition State and descriptition of slow change from traditional welfare state towards the present competition state....

  1. The Scientific Competitiveness of Nations.

    Science.gov (United States)

    Cimini, Giulio; Gabrielli, Andrea; Sylos Labini, Francesco

    2014-01-01

    We use citation data of scientific articles produced by individual nations in different scientific domains to determine the structure and efficiency of national research systems. We characterize the scientific fitness of each nation-that is, the competitiveness of its research system-and the complexity of each scientific domain by means of a non-linear iterative algorithm able to assess quantitatively the advantage of scientific diversification. We find that technological leading nations, beyond having the largest production of scientific papers and the largest number of citations, do not specialize in a few scientific domains. Rather, they diversify as much as possible their research system. On the other side, less developed nations are competitive only in scientific domains where also many other nations are present. Diversification thus represents the key element that correlates with scientific and technological competitiveness. A remarkable implication of this structure of the scientific competition is that the scientific domains playing the role of "markers" of national scientific competitiveness are those not necessarily of high technological requirements, but rather addressing the most "sophisticated" needs of the society.

  2. Interaction Enhanced Imperialist Competitive Algorithms

    Directory of Open Access Journals (Sweden)

    Meng-Shiou Li

    2012-10-01

    Full Text Available Imperialist Competitive Algorithm (ICA is a new population-based evolutionary algorithm. It divides its population of solutions into several sub-populations, and then searches for the optimal solution through two operations: assimilation and competition. The assimilation operation moves each non-best solution (called colony in a sub-population toward the best solution (called imperialist in the same sub-population. The competition operation removes a colony from the weakest sub-population and adds it to another sub-population. Previous work on ICA focuses mostly on improving the assimilation operation or replacing the assimilation operation with more powerful meta-heuristics, but none focuses on the improvement of the competition operation. Since the competition operation simply moves a colony (i.e., an inferior solution from one sub-population to another sub-population, it incurs weak interaction among these sub-populations. This work proposes Interaction Enhanced ICA that strengthens the interaction among the imperialists of all sub-populations. The performance of Interaction Enhanced ICA is validated on a set of benchmark functions for global optimization. The results indicate that the performance of Interaction Enhanced ICA is superior to that of ICA and its existing variants.

  3. TAX HARMONIZATION VERSUS FISCAL COMPETITION

    Directory of Open Access Journals (Sweden)

    Florin Alexandru MACSIM

    2016-12-01

    Full Text Available Recent years have brought into discussion once again subjects like tax harmonization and fiscal competition. Every time the European Union tends to take a step forward critics enter the scene and give contrary arguments to European integration. Through this article we have offered our readers a compelling view over the “battle” between tax harmonization and fiscal competition. While tax harmonization has key advantages as less costs regarding public revenues, leads to higher degree of integration and allows the usage of fiscal transfers between regions, fiscal competition is no less and presents key advantages as high reductions in tax rates and opens a large path for new investments, especially FDI. Choosing tax harmonization or fiscal competition depends on a multitude of variables, of circumstances, the decision of choosing one path or the other being ultimately influenced by the view of central and local authorities. Our analysis indicates that if we refer to a group of countries that are a part of a monetary union or that form a federation, tax harmonization seems to be the best path to choose. Moving the analysis to a group of regions that aren’t taking any kind of correlated actions or that have not signed any major treaties regarding monetary or fiscal policies, the optimal solution is fiscal competition.

  4. MICROECONOMIC ANALYSIS IN COMPETITION POLICY

    Directory of Open Access Journals (Sweden)

    Paul Prisecaru

    2013-11-01

    Full Text Available This paper presents some of the most important microeconomic tools used in assessing antitrust and merger cases by the competition authorities. By explaining the way that microeconomic concepts like “market power”, “critical loss” or “price elasticity of demand” are used by the modern competition policy, the microeconomics scholar can get a practical perspective on the way that these concepts fit into the more general concept of “competition policy”. Extensive economic research has shown what are the market forces and economic factors that determine how cartels, which are at the core of antitrust policy, are established and sustained over time. One of the most important of these factors is the markets exposure to innovation, especially disruptive innovation. In these markets, the paradox, from a competition policy perspective, can be considered the fact that collusion is one of the least important concerns, due to the specific elements that determine the nature of competition.Instead, the main anticompetitive risk in the markets exposed to intensive innovation is unilateral conduct by which dominant incumbents can exclude competitors.

  5. NEW APPROACHES TO EXPORT COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Alina Petronela NEGREA

    2015-04-01

    Full Text Available The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of imports of intermediate goods which are part of the export value. In this case, a simple analysis of the evolution of exports can distort the international competitive position of a country. The article suggests a new approach based on the value-added content of international trade measured by means of global value chain analysis.

  6. Corporate reputation and competitive advantage

    Directory of Open Access Journals (Sweden)

    Mitić Sanja

    2009-01-01

    Full Text Available As the international environment changes, a closer inspection of the competitiveness drivers that change along with it becomes necessary. The rules are changing - competition is getting tougher, stakeholders are multiplying and the role of companies as members of the society grows. Undoubtedly, intangible resources are the key factors of success on the market in the 21st century. A company that can create and improve intangible resources is one that will have a good business performance. This paper aims to describe the role of corporate reputation, as a valuable intangible resource, in gaining competitive advantage. The social relations and interpersonal relationships form the base of corporate reputation. The reputation encompasses all relevant aspects of corporate activity in communication with all stakeholders, both internal and external.

  7. Global Energy Forecasting Competition 2012

    DEFF Research Database (Denmark)

    Hong, Tao; Pinson, Pierre; Fan, Shu

    2014-01-01

    The Global Energy Forecasting Competition (GEFCom2012) attracted hundreds of participants worldwide, who contributed many novel ideas to the energy forecasting field. This paper introduces both tracks of GEFCom2012, hierarchical load forecasting and wind power forecasting, with details on the asp......The Global Energy Forecasting Competition (GEFCom2012) attracted hundreds of participants worldwide, who contributed many novel ideas to the energy forecasting field. This paper introduces both tracks of GEFCom2012, hierarchical load forecasting and wind power forecasting, with details...... on the aspects of the problem, the data, and a summary of the methods used by selected top entries. We also discuss the lessons learned from this competition from the organizers’ perspective. The complete data set, including the solution data, is published along with this paper, in an effort to establish...

  8. NEW APPROACHES TO EXPORT COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Alina Petronela NEGREA

    2015-04-01

    Full Text Available The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of imports of intermediate goods which are part of the export value. In this case, a simple analysis of the evolution of exports can distort the international competitive position of a country. The article suggests a new approach based on the value-added content of international trade measured by means of global value chain analysis.

  9. Game on: creating competitive advantages.

    Science.gov (United States)

    Riskind, Patricia; Foreman, M Shane

    2004-01-01

    Whether you are opening a new imaging center or trying to keep an existing center competitive, there are 3 critical factors: customer service, marketing, and a "what's next?" attitude. Customer service: Outstanding customer service is what sticks in the minds of referring physicians and patients. Not only does providing better service differentiate you from the competition, but it also boosts employee morale and motivates people to acquire new skills. Marketing: From the front office staff to the radiologists,promoting the center should be part of every employee's job description. Simply paying lip service to the concept of marketing will not cut it. A "what's next?" attitude: Complacency is a luxury that does not exist in today's competitive health care arena. Three facilities provide examples of how these factors applied to their success.

  10. Finite land resources and competition

    DEFF Research Database (Denmark)

    Haberl, Helmut; Mbow, Cheikh; Deng, Xiangzheng;

    2014-01-01

    : production versus production (e.g., food vs. fuel), production versus conservation (e.g., food production vs. conservation), and built-up environment versus production or conservation (e.g., food vs. urban). Sustainability impacts that result from land-use competition are analyzed and found to differ...... strongly between the different types of land-use competition. They are associated with important trade-offs and high uncertainty. Institutional aspects related to land-use competition are discussed using a conceptual model that distinguishes types of institutions (government, private, community) as well...... and energy systems, “ land architecture” (i.e., the significance of spatial confi gurations), and multiscale models to assess local-global connections and impacts....

  11. Intrasexual competition among males : Competitive towards men, prosocial towards women

    NARCIS (Netherlands)

    Buunk, Abraham P.; Massar, Karlijn

    In a study among 40 males and 56 females, participants engaged in a series of decomposed social games in which they had to divide resources between themselves and either a same-sex or an opposite sex other. As predicted on the basis of theorizing on sexual selection, males behaved more competitively

  12. Can NCLB Survive the Competitiveness Competition? Education Outlook. Number 2

    Science.gov (United States)

    Hess, Frederick M.; Rotherham, Andrew J.

    2007-01-01

    Some see the George W. Bush administration's American Competitiveness Initiative (ACI) as the perfect complement to the No Child Left Behind Act's (NCLB) equity focus. The authors believe, however, that the prospects for synergy of these two agendas are not bright. In this essay, the authors discuss the history behind NCLB and the ACI, and argue…

  13. Intrasexual competition among males : Competitive towards men, prosocial towards women

    NARCIS (Netherlands)

    Buunk, Abraham P.; Massar, Karlijn

    2012-01-01

    In a study among 40 males and 56 females, participants engaged in a series of decomposed social games in which they had to divide resources between themselves and either a same-sex or an opposite sex other. As predicted on the basis of theorizing on sexual selection, males behaved more competitively

  14. Competition in a Noncompetitive Environment.

    Science.gov (United States)

    1987-05-01

    different markets with di#erenit pctentad] levelb o# competition. Our behavior muSt certair:ly dl -pend upur. the type of marlet, we muit procure weapons...deal has been written about split buy techniques and problems. See Beltramo (1983), Boger and Liao (1985/87), Meeker (1984), Pelzer (1979), Sellers...Competition in the Procurement of Weapon Systems", JounAnaiQl!_8#1!1, Vol 4, Na 2 (Fall). Boger , D.C. and S.S. Liao (1985), "An Analysis oi Quantity

  15. Credit rating dynamics and competition

    DEFF Research Database (Denmark)

    Hirth, Stefan

    2014-01-01

    I analyze the market for credit ratings with competition between more than two rating agencies. How can honest rating behavior be achieved, and under which conditions can a new honest rating agency successfully invade a market with inflating incumbents? My model predicts cyclic dynamics if sophis......I analyze the market for credit ratings with competition between more than two rating agencies. How can honest rating behavior be achieved, and under which conditions can a new honest rating agency successfully invade a market with inflating incumbents? My model predicts cyclic dynamics...

  16. Magnitude Sensitive Competitive Neural Networks

    OpenAIRE

    Pelayo Campillos, Enrique; Buldain Pérez, David; Orrite Uruñuela, Carlos

    2014-01-01

    En esta Tesis se presentan un conjunto de redes neuronales llamadas Magnitude Sensitive Competitive Neural Networks (MSCNNs). Se trata de un conjunto de algoritmos de Competitive Learning que incluyen un término de magnitud como un factor de modulación de la distancia usada en la competición. Al igual que otros métodos competitivos, MSCNNs realizan la cuantización vectorial de los datos, pero el término de magnitud guía el entrenamiento de los centroides de modo que se representan con alto de...

  17. 超滤法测定丹酚酸A的血浆蛋白结合率%Determination of Plasma Protein Binding Rate of Salvianol Acid A by Ultrafiltration

    Institute of Scientific and Technical Information of China (English)

    陈豆; 涂星; 张英丰

    2013-01-01

    Objective: To establish a method for the determination of salvianolic acid A in the plasma samples, and then study the plasma protein binding rate of salvianolic acid A. This can provide a reference to the further study of salvianol acid A in its metabolism, pharmacokinetics and clinical treatment. Method: The ultrafiltration was employed to determine the plasma protein binding rate of salvianol acid A in BSA plasma samples, rat plasma samples, the New Zealand rabbit plasma samples and beagle dog plasma samples. The plasma concentrations of salvianol acid A were measured by RP-HPLC. Result: The calibration curve of salvianolic acid A was linear within the ranges of 0. 01 -2. 5 mg ·L-1 ( r = 0. 999 4) . The average plasma protein binding rates of salvianol acid A with BSA, rat plasma, the New Zealand rabbit plasma and beagle dog plasma were (99.79 ± 0. 02) % , (99. 79 ± 0. 03 ) % , (99. 73 ± 0. 06) % , (99. 81 ± 0. 03 ) % in the plasma concentrations of 5. 0, 50.0, 100.0 mg · L-1 respectively. Conclusion: The method has high sensitivity, good specificity and reproduction, with simple management thus fulfilling the requirement. Salvianol acid A shows a high binding power to plasma protein. , and this was independent of the investigated concentrations and the different species.%目的:建立血浆样品中丹酚酸A浓度的分析方法,并测定丹酚酸A的血浆蛋白结合率,为进一步展开丹酚酸A的代谢和药动学研究及指导临床用药提供参考.方法:采用超滤法和HPLC测定丹酚酸A在牛血清白蛋白(BSA),大鼠血浆,新西兰兔血浆和比格犬血浆中的蛋白结合率.结果:丹酚酸A在0.01~2.5 mg·L-1线性良好,标准曲线方程为Y =0.8073X+0.013 2(r =0.999 4).丹酚酸A与BSA,大鼠血浆,新西兰兔血浆和比格犬血浆在5.0,50.0,100.0 mg·L-1的含药血浆中其平均蛋白结合率分别为(99.79±0.02)%,(99.79±0.03)%,(99.73±0.06)%,(99.81±0.03)%.结论:所建立的方法灵敏度高,专属性

  18. Substitutional impact on biological activity of new water soluble Ni(II) complexes: Preparation, spectral characterization, X-ray crystallography, DNA/protein binding, antibacterial activity and in vitro cytotoxicity.

    Science.gov (United States)

    Umadevi, C; Kalaivani, P; Puschmann, H; Murugan, S; Mohan, P S; Prabhakaran, R

    2017-02-01

    A series of new water soluble nickel(II) complexes containing triphenylphosphine and 4-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized. Crystallographic investigations confirmed the structure of the complexes (1-4) having the general structure [Ni(4-Msal-Rtsc)(PPh3)] (Where R=H (1); CH3 (2); C2H5 (3); C6H5 (4)) which showed that thiosemicarbazone ligands coordinated to nickel(II) ion as ONS tridentate bibasic donor. DNA/BSA protein binding ability of the ligands and their new complexes were studied by taking calf-thymus DNA (CT-DNA) and Bovine serum albumin (BSA) through absorption and emission titrations. Ethidium bromide (EB) displacement study showed the intercalative binding trend of the complexes to DNA. From the albumin binding studies, the mechanism of quenching was found as static and the alterations in the secondary structure of BSA by the compounds were confirmed with synchronous spectral studies. The binding affinity of the complexes to CT-DNA and BSA has the order of [Ni(4-Msal-etsc)(PPh3)] (3) >[Ni(4-Msal-mtsc)(PPh3)] (2) >[Ni(4-Msal-tsc)(PPh3)] (1) >[Ni(4-Msal-ptsc)(PPh3)] (4). In vitro cytotoxicity of the complexes was tested on human lung cancer cells (A549), human cervical cancer cells (HeLa), human liver carcinoma cells (Hep G2). All the complexes exhibited significant activity against three cancer cells. Among them, complex 4 exhibited almost 2.5 fold activity than cisplatin in A549 and HepG2 cell lines. In HeLa cell line, the complexes exhibited significant activity which is less than cisplatin. While comparing the activity of the complexes in A549 and HepG2 cell lines it falls in the order 4>1>2>3>cisplatin. The results obtained from DNA, protein binding and cytotoxicity studies, it is concluded that the cytotoxicity of the complexes as determined by MTT assay were not unduly influenced by the complexes having different binding efficiency with DNA and protein. The complexes exhibited good spectrum

  19. Evidence for Bacterial Chemotaxis to Cyanobacteria from a Radioassay Technique

    Science.gov (United States)

    Kangatharalingam, N.; Wang, Lizhu; Priscu, John C.

    1991-01-01

    Lyngbya birgei and Aphanizomenon flos-aquae elicited a significant chemotactic attraction of Aeromonas hydrophila compared with controls lacking cyanobacteria. There was a positive exponential relationship between biomass (chlorophyll a) of L. birgei and A. flos-aquae and chemotactic attraction of A. hydrophila. The assay equipment was simple and reliable and could be used to study bacterial chemotaxis in other species in situ. Images PMID:16348544

  20. Radio-assay of Titanium samples for the LUX Experiment

    CERN Document Server

    Akerib, D S; Bedikian, S; Bernard, E; Bernstein, A; Bradley, A; Cahn, S B; Carmona-Benitez, M C; Carr, D; Chapman, J J; Chan, Y-D; Clark, K; Classen, T; Coffey, T; Dazeley, S; deViveiros, L; Dragowsky, M; Druszkiewicz, E; Faham, C H; Fiorucci, S; Gaitskell, R J; Gibson, K R; Hall, C; Hanhardt, M; Holbrook, B; Ihm, M; Jacobsen, R G; Kastens, L; Kazkaz, K; Lander, R; Larsen, N; Lee, C; Leonard, D; Lesko, K; Lyashenko, A; Malling, D C; Mannino, R; McKinsey, D; Mei, D; Mock, J; Morii, M; Nelson, H; Nikkel, J A; Pangilinan, M; Parker, P D; Phelps, P; Shutt, T; Skulski, W; Sorensen, P; Spaans, J; Stiegler, T; Svoboda, R; Smith, A; Sweany, M; Szydagis, M; Thomson, J; Tripathi, M; Verbus, J R; Walsh, N; Webb, R; White, J T; Wlasenko, M; Wolfs, F L H; Woods, M; Uvarov, S; Zhang, C

    2011-01-01

    We report on the screening of samples of titanium metal for their radio-purity. The screening process described in this work led to the selection of materials used in the construction of the cryostats for the Large Underground Xenon (LUX) dark matter experiment. Our measurements establish titanium as a highly desirable material for low background experiments searching for rare events. The sample with the lowest total long-lived activity was measured to contain <0.25 mBq/kg of U-238, <0.2 mBq/kg of Th-232, and <1.2 mBq/kg of K-40. Measurements of several samples also indicated the presence of short-lived (84 day half life) Sc-46, likely produced cosmogenically via muon initiated (n,p) reactions.

  1. Volumetric radioassay of lead bricks being considered for unrestricted release

    Energy Technology Data Exchange (ETDEWEB)

    Gehrke, R.J.; Losinski, S.J.; Seal, G.L.

    1995-01-01

    The hardware, software, and a protocol have been developed for the screening of lead bricks for free release or recycle from the Idaho National Engineering Laboratory. The procedure for measuring the background from a sampling of ``clean`` lead bricks and for deducing the decision limits (in pCi/g) have been developed. At the decision limit, a radioactive lead brick would be detected with 95% confidence if it were present. The total and peak efficiencies of a 2.54-cm diameter {times} 2.54-cm high NaI(Tl) scintillation detector for the counting geometry of the present study were measured with a mixed radionuclide standard and calculated with a Monte Carlo program, CYLTRAN. The deduced decision limit for the counting conditions of the present study were 0.0588 pCi/g by analyzing the entire spectrum and 0.256 pCi/g by analyzing the 661-keV peak region for a 900-second count.

  2. Competitive Liner Shipping Network Design

    DEFF Research Database (Denmark)

    Karsten, Christian Vad

    The goal of this thesis is to develop decision support tools, which can be used to optimize container shipping networks while supporting competitive transportation services. The competitiveness of container liner shipping is to a high degree determined by transportation times and number of transs......The goal of this thesis is to develop decision support tools, which can be used to optimize container shipping networks while supporting competitive transportation services. The competitiveness of container liner shipping is to a high degree determined by transportation times and number...... shipping company earnings.The operation of the route net constitute the majority of the total costs, so it is essential to achieve a good capacity utilization in a route plan with travel times that satisfy customer requirements. Most academic articles dealing with the design of container networks neither.......The contributions of this thesis cover modeling, methodology, and applications.The developed methods address operational (cargo routing), tactical (speed optimization and service selection), and strategic (network design) planning problems faced by liner shipping companies. Ultimately, the proposed methods help...

  3. Competition in a Social Structure

    Science.gov (United States)

    Legara, Erika Fille; Longjas, Anthony; Batac, Rene

    Complex adaptive agents develop strategies in the presence of competition. In modern human societies, there is an inherent sense of locality when describing inter-agent dynamics because of its network structure. One then wonders whether the traditional advertising schemes that are globally publicized and target random individuals are as effective in attracting a larger portion of the population as those that take advantage of local neighborhoods, such as "word-of-mouth" marketing schemes. Here, we demonstrate using a differential equation model that schemes targeting local cliques within the network are more successful at gaining a larger share of the population than those that target users randomly at a global scale (e.g., television commercials, print ads, etc.). This suggests that success in the competition is dependent not only on the number of individuals in the population but also on how they are connected in the network. We further show that the model is general in nature by considering examples of competition dynamics, particularly those of business competition and language death.

  4. The rd LAK data competition

    NARCIS (Netherlands)

    Drachsler, Hendrik; Dietze, Stefan; Herder, Eelco; d'Aquin, Mathieu; Taibi, Davide; Scheffel, Maren

    2017-01-01

    The LAK Data Challenge 2015 continues the research efforts of the previous data competitions in 2013 and 2014 by stimulating research on the evolving fields Learning Analytics (LA) and Educational Data Mining (EDM). Building on a series of activities of the LinkedUp project, the challenge aims to ge

  5. The Fetish of Global Competition

    DEFF Research Database (Denmark)

    Hartmann, Eva

    2014-01-01

    A number of scholars have criticised the methodological nationalism of the mainstream study of capitalist diversity for ignoring a global convergence trend triggered by global competition. This contribution agrees with this criticism but insists on the need to take the diversities into account...

  6. Review of submissions: competition impacts

    NARCIS (Netherlands)

    G. Burghouwt; W. de Wit

    2015-01-01

    The Airports Commission requested ITF/SEO to provide technical assistance with analysing responses that pertain to the previous work undertaken by the ITF/SEO. This report assesses the submissions by the stakeholders in relation to competition impacts and compares them with the ITF/SEO results and t

  7. Robotics Competitions and Science Classrooms

    Science.gov (United States)

    Benke, Gertraud

    2012-01-01

    This paper looks at the distinctions between science classrooms and the robotics competition described in the article "Examining the mediation of power in a collaborative community: engaging in informal science as authentic practice" written by Anton Puvirajah, Geeta Verma and Horace Webb. Using the framework of "productive disciplinary…

  8. Media Competition and Electoral Politics

    NARCIS (Netherlands)

    Piolatto, A.; Schuett, F.

    2013-01-01

    Abstract: We build a framework linking competition in the media market to political participation, media slant, and selection of politicians. Media outlets report on the ability of candidates running for office and compete for audience through their choice of slant. Citizens derive utility from foll

  9. Competition and Mergers among Nonprofits

    NARCIS (Netherlands)

    Prüfer, J.

    2007-01-01

    Should mergers among nonprofit organizations be regulated differently than mergers among for-profit firms? The relevant empirical literature is highly controversial, the theoretical literature is scarce. We analyze the question by modeling duopoly competition with quality-differentiated goods. We co

  10. Competition and Mergers among Nonprofits

    NARCIS (Netherlands)

    Prüfer, J.

    2007-01-01

    Should mergers among nonprofit organizations be regulated differently than mergers among for-profit firms? The relevant empirical literature is highly controversial, the theoretical literature is scarce. I analyze the question by modeling duopoly competition with quality-differentiated goods. I comp

  11. Multipolarity, multilateralism, and strategic competition

    NARCIS (Netherlands)

    van Hooft, P.

    2012-01-01

    This paper explores the clash between political and economic transnationalisation, multipolarity, and the return of traditional inter-state competition. In response, the coming global order will be the result of the interplay between both structural and domestic factors, namely the realignment of

  12. Competitive strategies in the NHS.

    Science.gov (United States)

    Coad, H; Kennedy, B

    1992-04-01

    The NHS has, of necessity since implementation of the NHS and Community Care Act 1990, strengthened its skills in business, marketing and other functions borrowed from industry and commerce. One area where, however, the NHS is currently weak is in competitive intelligence. Hazel Coad and Barbara Kennedy explain what this strategically important function is and how it can help financial viability.

  13. Competition for cores in remanufacturing

    NARCIS (Netherlands)

    Bulmus, Serra Caner; Zhu, Stuart X.; Teunter, Ruud

    2014-01-01

    We study competition between an original equipment manufacturer (OEM) and an independently operating remanufacturer (IO). Different from the existing literature, the OEM and IO compete not only for selling their products but also for collecting returned products (cores) through their acquisition pri

  14. An Amusement Park Physics Competition

    Science.gov (United States)

    Moll, Rachel F.

    2010-01-01

    Amusement park physics is a popular way to reinforce physics concepts and to motivate physics learners. This article describes a novel physics competition where students use simple tools to take amusement park ride measurements and use the data to answer challenging exam questions. Research into the impact of participating in the competition…

  15. Economic Competitiveness: A Campaign Primer

    Science.gov (United States)

    Fischer, Karin

    2008-01-01

    With the dollar's continued swoon and grim news on the job front, American economic competitiveness has become a central theme in the presidential election. Stumping in Ohio and Pennsylvania, old-line industrial states hit hard by the flight of manufacturing jobs, Democrats Hillary Rodham Clinton and Barack Obama have called for renegotiating the…

  16. Raising Economic Competitiveness with Education.

    Science.gov (United States)

    Silberman, Harry F.

    The current school reform movement has been plagued by three false assumptions. The first of these postulates that more academic requirements will strengthen the minds of students, improve their reasoning, prepare them for a rapidly changing economy, and make the U.S. economy more competitive. Although it is true that the workers of the future…

  17. Market competition and efficient cooperation

    NARCIS (Netherlands)

    Brandts, J.; Riedl, A.M.

    2016-01-01

    We use laboratory experiments to study the causal effects of favorable and unfavorable competitive market experience on cooperation in a subsequent social dilemma game. The issues we study are part of the broader topic of whether there are behavioral spillovers between different spheres of social

  18. Japanese Competitiveness and Japanese Management.

    Science.gov (United States)

    Minabe, Shigeo

    1986-01-01

    Analyzes and compares Japanese and American industrial policy and labor practices. Proposes that certain aspects of the Japanese system be adapted by American businesses for purpose of increasing international competitiveness. Proposes specific actions and plans for both the Japanese and American systems. (ML)

  19. Urban Competition and Urban Crisis

    DEFF Research Database (Denmark)

    Greve, Anni

    The essay gives a brief summery of Michel Foucault's 1978-1979 lectures which offers an important point of reference for a deeper understanding of the shift from liberal to neo-liberal ideas. Here he points out that neo-liberalism is an art of governemt that seeks to enforce competition. But his...

  20. Competition in spatial location models

    NARCIS (Netherlands)

    Webers, H.M.

    1996-01-01

    Models of spatial competition are designed and analyzed to describe the fact that space, by its very nature, is a source of market power. This field of research, lying at the interface of game theory and economics, has attracted much interest because location problems are related to many aspects of

  1. Cooperation and competition between relatives

    NARCIS (Netherlands)

    West, S.A.; Pen, I.R.; Griffin, A.S.

    2002-01-01

    Individuals are predicted to. behave more altruistically and less competitively toward their relatives, because they share a relatively high proportion of their genes (e.g., one-half for siblings and one-eighth for cousins). Consequently, by helping a relative reproduce, an individual passes its gen

  2. Competition in spatial location models

    NARCIS (Netherlands)

    Webers, H.M.

    1996-01-01

    Models of spatial competition are designed and analyzed to describe the fact that space, by its very nature, is a source of market power. This field of research, lying at the interface of game theory and economics, has attracted much interest because location problems are related to many aspects of

  3. EU environmental policy and competitiveness

    Directory of Open Access Journals (Sweden)

    Stojanović Boban

    2006-01-01

    Full Text Available Protection of the environment was not a specific importance to the Community although the Treaty of Rome expressly specified that "health, safety environmental protection" shall be based on "a high level of protection". In deciding upon a framework for a European environmental policy, the Community was also responding to increased public awareness of the problem and concerns about the state of the natural and man-made environment. During the past years, competitiveness concerns have dominated the EU policy debate, in the course of which a growing consensus is being developed on the importance of eco-innovations and resource efficiency for EU competitiveness and on the market opportunities they offer. There is an increasing evidence that environmental policy and eco-innovations can promote economic growth, as well as maintain and create jobs, contributing both to competitiveness and employment. Environmental constraints to rapid economic growth are increasingly recognized by countries, leading to a rising awareness of the need for sustainable development. Implementation of an environmental policy however, generates significant implications for competition among countries.

  4. Does market competition explain fairness?

    Science.gov (United States)

    Descioli, Peter

    2013-02-01

    The target article by Baumard et al. uses their previous model of bargaining with outside options to explain fairness and other features of human sociality. This theory implies that fairness judgments are determined by supply and demand but humans often perceive prices (divisions of surplus) in competitive markets to be unfair.

  5. Factors Affecting Traditional Markets Competitiveness

    Directory of Open Access Journals (Sweden)

    Hotnier Sipahutar

    2016-05-01

    Full Text Available Nowadays, traditional market is increasingly squeezed by the emergence of modern market that develops rapidly. The dominance shift in national retail is apparent when globalization can no longer be contained, let alone be banned. Middle class and small class (traditional market business retail seem to be in increasingly difficult condition to compete with upscale retail business (modern market. The purpose of this study is to analyze the factors influencing the competitiveness of traditional market and to develop policies to improve the competitiveness of traditional market. This study utilizes research strategy of case study in Bandung City, Serang City, and Surabaya City with qualitative descriptive approach. The study shows that the factors inhibiting the competitiveness of traditional market with modern stores are (1 Traditional market’s bad image, and (2 Traditional market’s sellers and managers are unprofessional. To improve the competitiveness of traditional market, this study recommends: (1 routine and regular maintenance of buildings and infrastructure of traditional market, (2 professionalism improvement of traditional market’s sellers and managers, and (3 the partiality of local government in traditional markets.

  6. Regional Competition in Maghreb Region

    Institute of Scientific and Technical Information of China (English)

    EL AMOURI ALLAL

    2016-01-01

    Great powers focus on cooperation instead of competition in their regions in order to maintain stability and develop the economy of their regions and the world in general. The United States for example created the North American Free Trade Agreement (NAFT

  7. THE COMPETITIVENESS OF TEXTILE INDUSTRY

    Directory of Open Access Journals (Sweden)

    PRUNEA ANA

    2014-05-01

    Full Text Available The role of this paper is to highlight the position of the European players in the textile market and the challenges to which they are subjected. In this paper are presented ways, taking the „diamond" model of M. Porter and are adapted to the situation of the textile market. These adaptations have outlined the main existing problems and the possible solutions that can ensure the long-term competitive advantage. Gaining a competitive advantage based on innovation, the development of production and outsourcing strategies using the "diamond" model of M. Porter, we can say that is one of the viable solutions for gaining competitive advantages necessary for proper European companies to face competition from countries outside Europe. As developing countries do not meet certain environmental standards or norms of European law, but in terms of product innovation and development of new materials, they do not have the necessity for technology. We conducted an analysis of the factors that play a key role in the production of textiles, representing how they are used in the favor of European companies such investments to be supplemented can be found in how these factors act on the total costs.

  8. Management of competitiveness enterprise in modern terms

    Directory of Open Access Journals (Sweden)

    Serhii Spivak

    2014-05-01

    Full Text Available This paper discusses methodological approaches to assess the competitiveness of industrial enterprises on the basis of indicators to measure the production, finance, marketing potential, determination of the complex index of competitiveness. The problems of furniture manufacturing enterprises. The basic shortcomings of the industry in today's environment. The analysis of the competitiveness of furniture products on the market. Factors that influence the level of production and the mechanism of improving the competitiveness of enterprise management systems, including the implementation of the following steps: a the adoption of a fundamental decision by management on the feasibility competitiveness management; b formation of working groups; c analysis of the competitiveness of the furniture company, which is determined based on the competitiveness of certain furniture company; d management functional competitive furniture company; е evaluating the effectiveness of multi-use and implement actions organizational and economic mechanism of competitive.

  9. Designing competitions for education in robotics

    DEFF Research Database (Denmark)

    Andersen, Nils Axel; Ravn, Ole

    2012-01-01

    The paper describes design considerations for making a robot competition. Topics as level of participants, learning objective, evaluation form, task design and competition rules are treated. It is shown that careful design considering these topics are necessary for a succesful outcome of a compet......The paper describes design considerations for making a robot competition. Topics as level of participants, learning objective, evaluation form, task design and competition rules are treated. It is shown that careful design considering these topics are necessary for a succesful outcome...... of a competition. The conclusions are based on examples from more than 15 years of experience with robotic competitions....

  10. Human Sperm Competition: A Comparative Evolutionary Analysis

    Directory of Open Access Journals (Sweden)

    Michael N. Pham

    2014-08-01

    Full Text Available Sperm competition occurs when a female copulates with two or more males within a sufficiently brief time period, resulting in sperm of the different males competing to fertilize ova. Sperm competition has been documented or inferred to occur across several species. We address the evidence for sperm competition in humans by reviewing literature indicating apparently convergent adaptations to sperm competition in humans and non-humans. We discuss future research directions, and conclude that the evidence for anatomical, biological, physiological, and behavioral adaptations to human sperm competition provides compelling evidence that sperm competition has been a recurrent feature of human evolutionary history.

  11. Design, Synthesis, Acaricidal/Insecticidal Activity, and Structure-Activity Relationship Studies of Novel Oxazolines Containing Sulfone/Sulfoxide Groups Based on the Sulfonylurea Receptor Protein-Binding Site.

    Science.gov (United States)

    Yu, Xiuling; Liu, Yuxiu; Li, Yongqiang; Wang, Qingmin

    2016-04-20

    Enormous compounds containing sulfone/sulfoxide groups have been used in a variety of fields, especially in drug and pesticide design. To search for novel environmentally benign and ecologically safe pesticides with unique modes of action, a series of 2,4-diphenyl-1,3-oxazolines containing sulfone/sulfoxide groups as chitin synthesis inhibitors (CSIs) were designed and synthesized on the basis of the sulfonylurea receptor protein-binding site for CSIs. Their structures were characterized by (1)H and (13)C nuclear magnetic resonance and high-resolution mass spectrometry. The acaricidal and insecticidal activities of the new compounds were evaluated. It was found that most of the target compounds displayed wonderful acaricidal activities against spider mite (Tetranychus cinnabarinus) larvae and eggs. Especially compounds I-4, II-3, and II-4 displayed higher activities than commercial etoxazole at a concentration of 2.5 mg L(-1). Some target compounds exhibited insecticidal activities against lepidopteran pests. The present work demonstrated that these compounds containing sulfone/sulfoxide groups could be considered as potential candidates for the development of novel acaricides in the future.

  12. Demolishing the Competition: The Longitudinal Link between Competitive Video Games, Competitive Gambling, and Aggression

    Science.gov (United States)

    Adachi, Paul J. C.; Willoughby, Teena

    2013-01-01

    The majority of research on the link between video games and aggression has focused on the violent content in games. In contrast, recent experimental research suggests that it is video game competition, not violence, that has the greatest effect on aggression in the short-term. However, no researchers have examined the long-term relationship…

  13. Report on global environmental competitiveness (2013)

    National Research Council Canada - National Science Library

    Li, Jianping

    2014-01-01

    This book explores the environmental competitiveness of 133 countries around the world, presenting an index evaluation system to facilitate a comparative analysis of environmental competitiveness on a global scale...

  14. Competition: a social marketer's friend or foe?

    Science.gov (United States)

    Wayman, Jennifer J Clay; Beall, Tom; Thackeray, Rosemary; Brown, Kelli R McCormack

    2007-04-01

    In public health social marketing, is there such a thing as "healthy competition," or is the term an oxymoron? The primary focus of this article is on a type of competition that may not often be considered by public health social marketers--competition from other marketing activities that exist in the marketplace in which your intervention is operating. This could also be termed "promotion" competition. The purpose of this article is to briefly review promotion competition and then review competitive factors that can impact a social marketing initiative's success, examine how to conduct a useful competitive analysis, and offer strategies for maximizing the benefits and minimizing the negative implications of competition on your efforts.

  15. SIAM 2007 Text Mining Competition dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Subject Area: Text Mining Description: This is the dataset used for the SIAM 2007 Text Mining competition. This competition focused on developing text mining...

  16. Interspecific Resource Competition Effects on Fisheres Revenue

    NARCIS (Netherlands)

    Wolfshaar, van de K.E.; Schellekens, T.; Poos, J.J.; Kooten, van T.

    2012-01-01

    In many fisheries multiple species are simultaneously caught while stock assessments and fishing quota are defined at species level. Yet species caught together often share habitat and resources, resulting in interspecific resource competition. The consequences of resource competition on population

  17. Developing Information Systems for Competitive Intelligence Support.

    Science.gov (United States)

    Hohhof, Bonnie

    1994-01-01

    Discusses issues connected with developing information systems for competitive intelligence support; defines the elements of an effective competitive information system; and summarizes issues affecting system design and implementation. Highlights include intelligence information; information needs; information sources; decision making; and…

  18. Competitive Intelligence and the Information Center.

    Science.gov (United States)

    Greene, H. Frances

    1988-01-01

    Examines the competitive intelligence approach to corporate information gathering, and discusses how it differs from the traditional library information center approach. Steps for developing a competitive intelligence system in the library information center are suggested. (33 references) (MES)

  19. Tax Competition Leading to Strict Environmental Policy

    OpenAIRE

    Withagen, Cees; Halsema, Alex

    2012-01-01

    We study tax competition when pollution matters. Most notably we present a dynamic setting, where the supply of capital is endogenous. It is shown that tax competition may involve stricter environmental policy than the cooperative outcome.

  20. Dimensions of Real-World Competition

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2014-01-01

    Mainstream economics consistently ignores the various socio-economic and environmental downsides of capitalist competition and instead lends legitimacy to the prevailing neoliberal discourse according to which merciless competition is unambiguously positive. In opposition to this one-dimensional ...

  1. Competitive pressures on income distribution in China

    NARCIS (Netherlands)

    Pan, H.

    1999-01-01

    to explore what perfect competition would do to income distribution in China. The research analyzes this question by determining personal income distribution under hypothetical, perfectly competitive conditions, where factors are rewarded according to their marginal productivities. Comparison with t

  2. DXC'09 Industrial Track Competition Data

    Data.gov (United States)

    National Aeronautics and Space Administration — Competition data, including nominal and faulty scenarios, for Industrial Track Tier 1 and Tier 2 of the First International Diagnostic Competition. Three file...

  3. The monopolistic competition revolution in retrospect

    NARCIS (Netherlands)

    L.J.H. Bettendorf (Leon); B.J. Heijdra (Ben)

    2003-01-01

    textabstractAvinash Dixit and Joseph Stiglitz revolutionized the modelling of imperfectly competitive markets and launched "the second monopolistic competition revolution". Experts in the areas of macroeconomics, international trade theory, economic geography, and international growth theory examine

  4. DXC'10 Industrial Track Competition Data

    Data.gov (United States)

    National Aeronautics and Space Administration — Competition data, including nominal and faulty scenarios, for Diagnostic Problems I and II of the Second International Diagnostic Competition. Three file formats are...

  5. The political economy of competition in telecommunication

    DEFF Research Database (Denmark)

    Henten, Anders; Skouby, Knud Erik

    1998-01-01

    Article dealing with the regulation of telecommunications and the establishment of a competitive regime.......Article dealing with the regulation of telecommunications and the establishment of a competitive regime....

  6. The monopolistic competition revolution in retrospect

    NARCIS (Netherlands)

    L.J.H. Bettendorf (Leon); B.J. Heijdra (Ben)

    2003-01-01

    textabstractAvinash Dixit and Joseph Stiglitz revolutionized the modelling of imperfectly competitive markets and launched "the second monopolistic competition revolution". Experts in the areas of macroeconomics, international trade theory, economic geography, and international growth theory examine

  7. Neanderthal extinction by competitive exclusion.

    Directory of Open Access Journals (Sweden)

    William E Banks

    Full Text Available BACKGROUND: Despite a long history of investigation, considerable debate revolves around whether Neanderthals became extinct because of climate change or competition with anatomically modern humans (AMH. METHODOLOGY/PRINCIPAL FINDINGS: We apply a new methodology integrating archaeological and chronological data with high-resolution paleoclimatic simulations to define eco-cultural niches associated with Neanderthal and AMH adaptive systems during alternating cold and mild phases of Marine Isotope Stage 3. Our results indicate that Neanderthals and AMH exploited similar niches, and may have continued to do so in the absence of contact. CONCLUSIONS/SIGNIFICANCE: The southerly contraction of Neanderthal range in southwestern Europe during Greenland Interstadial 8 was not due to climate change or a change in adaptation, but rather concurrent AMH geographic expansion appears to have produced competition that led to Neanderthal extinction.

  8. Institutional Competitiveness in Media Markets

    DEFF Research Database (Denmark)

    Lund, Anker Brink

    a social science / leadership perspective - not from the perspective of a journalist or from the ideologically critical perspective of the license payer. Thirdly, we consider competition in the media market as an institutional phenomenon that is not solely conditioned by economic considerations. We aim......This inaugural address is a welcome opportunity to call your attention to a new area of research that the International Center for Business and Politics has chosen as one of five areas of special interest. By referring to this area of focus as'institutional competition in the media market' we also...... signal an approach that will be free of much of the traditional dogma in Danish media research: First of all, we will consider the media as a market for opinion, goods and services - not primarily as a cultural discourse with a singular focus on public service. Secondly, we consider media activity from...

  9. Plan competitions reveal entrepreneurial talent

    Energy Technology Data Exchange (ETDEWEB)

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  10. BDS thin film damage competition

    Energy Technology Data Exchange (ETDEWEB)

    Stolz, C J; Thomas, M D; Griffin, A J

    2008-10-24

    A laser damage competition was held at the 2008 Boulder Damage Symposium in order to determine the current status of thin film laser resistance within the private, academic, and government sectors. This damage competition allows a direct comparison of the current state-of-the-art of high laser resistance coatings since they are all tested using the same damage test setup and the same protocol. A normal incidence high reflector multilayer coating was selected at a wavelength of 1064 nm. The substrates were provided by the submitters. A double blind test assured sample and submitter anonymity so only a summary of the results are presented here. In addition to the laser resistance results, details of deposition processes, coating materials, and layer count will also be shared.

  11. Feature Discovery by Competitive Learning.

    Science.gov (United States)

    1984-06-01

    McCulloch , W. S., & Pitts , W. (1943). A logical calculus of the ideas immanent in neural nets. Bid- letin of Mathematical Biophysics. 5. 115-137. Minsky, M...elevated to a status of p eat importance in those days because it was somehow uniquely sociated with the properties of animal brains. After McCulloch and... Pitts (1943) showed how neural-like networks or Rumelhart and Zipser 3 Competitive Learning could compute, the main problem then facing workers in this

  12. Green tax reform and competitiveness

    OpenAIRE

    Koskela, Erkki; Schöb, Ronnie; Sinn, Hans-Werner

    2000-01-01

    This paper develops a model of a small open economy that produces an export good with domestic labour and imported energy and is stuck in an unemployment situation resulting from an excessive fixed net-of-tax wage rate. We study a revenue-neutral green tax reform that substitutes energy for wage taxes. A moderate green tax reform will boost employment, improve welfare, and increase the economy's competitiveness. The driving force behind these results is the technological substitution process ...

  13. Competition in the sharing economy

    OpenAIRE

    Demary, Vera

    2015-01-01

    Sharing goods, services or knowledge is at the center of the so-called Sharing Economy. Businesses are usually based on online platforms that match demand and supply which is in many cases, but not always provided by individuals. Sharing Economy companies typically compete with traditional companies in many different markets. The main challenge of this type of competition currently is the application of the existing regulation. While incumbent firms adhere to this, Sharing Economy companies o...

  14. Competition and the Ratchet Effect

    OpenAIRE

    Charness, Gary; Kuhn, Peter; Villeval, Marie-Claire

    2011-01-01

    Working Paper GATE 2008-28; International audience; The 'ratchet effect' refers to a situation where a principal uses private information that is revealed by an agent's early actions to the agent's later disadvantage, in a context where binding multi-period contracts are not enforceable. In a simple, context-rich environment, we experimentally study the robustness of the ratchet effect to the introduction of ex post competition for principals or agents. While we do observe substantial and sig...

  15. Comparative serum protein binding of anthracycline derivatives.

    Science.gov (United States)

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P

    1996-01-01

    The binding of doxorubicin, iododoxorubicin, daunorubicin, epirubicin, pirarubicin, zorubicin, aclarubicin, and mitoxantrone to 600 microM human serum albumin and 50 microM alpha 1-acid glycoprotein was studied by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by high-performance liquid chromatography (HPLC) with fluorometric detection. Binding to albumin (600 microM) varied from 61% (daunorubicin) to 94% (iododoxorubicin). The binding to alpha 1-acid glycoprotein (50 microM) was more variable, ranging from 31% (epirubicin) to 64% (zorubicin), and was essentially related to the hydrophobicity of the derivatives. Simulations showed that the total serum binding varied over a broad range from 71% (doxorubicin) to 96% (iododoxorubicin). We recently reported that the binding to lipoproteins of a series of eight anthracycline analogues could be ascribed to chemicophysical determinants of lipophilicity [2]. The present study was conducted to evaluate in vitro the contribution of albumin and alpha 1-acid glycoprotein to the total serum binding of these drugs.

  16. Quantifying drug-protein binding in vivo.

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, B; Bench, G; Keating III, G; Palmblad, M; Vogel, J; Grant, P G; Hillegonds, D

    2004-02-17

    Accelerator mass spectrometry (AMS) provides precise quantitation of isotope labeled compounds that are bound to biological macromolecules such as DNA or proteins. The sensitivity is high enough to allow for sub-pharmacological (''micro-'') dosing to determine macromolecular targets without inducing toxicities or altering the system under study, whether it is healthy or diseased. We demonstrated an application of AMS in quantifying the physiologic effects of one dosed chemical compound upon the binding level of another compound in vivo at sub-toxic doses [4].We are using tissues left from this study to develop protocols for quantifying specific binding to isolated and identified proteins. We also developed a new technique to quantify nanogram to milligram amounts of isolated protein at precisions that are comparable to those for quantifying the bound compound by AMS.

  17. Characterizing the morphology of protein binding patches.

    Science.gov (United States)

    Malod-Dognin, Noël; Bansal, Achin; Cazals, Frédéric

    2012-12-01

    Let the patch of a partner in a protein complex be the collection of atoms accounting for the interaction. To improve our understanding of the structure-function relationship, we present a patch model decoupling the topological and geometric properties. While the geometry is classically encoded by the atomic positions, the topology is recorded in a graph encoding the relative position of concentric shells partitioning the interface atoms. The topological-geometric duality provides the basis of a generic dynamic programming-based algorithm comparing patches at the shell level, which may favor topological or geometric features. On the biological side, we address four questions, using 249 cocrystallized heterodimers organized in biological families. First, we dissect the morphology of binding patches and show that Nature enjoyed the topological and geometric degrees of freedom independently while retaining a finite set of qualitatively distinct topological signatures. Second, we argue that our shell-based comparison is effective to perform atomic-level comparisons and show that topological similarity is a less stringent than geometric similarity. We also use the topological versus geometric duality to exhibit topo-rigid patches, whose topology (but not geometry) remains stable upon docking. Third, we use our comparison algorithms to infer specificity-related information amidst a database of complexes. Finally, we exhibit a descriptor outperforming its contenders to predict the binding affinities of the affinity benchmark. The softwares developed with this article are availablefrom http://team.inria.fr/abs/vorpatch_compatch/.

  18. Customer Relationship Management - Competitiveness Improvement Tool

    OpenAIRE

    Jovan Zubovic; Ivana Domazet

    2007-01-01

    On the global market competitiveness of Serbian companies is at a very low level. According to Global Competitiveness Report 2007-2008 Serbia was ranked 91. Leading country is USA, whereas the UK had lost the second and fell to ninth position. The criteria on which Global Competitiveness Report ranks 131 world countries are creation of business strategies and a quality of business environment1. Competitiveness increase of local companies’ should be assessed through holistic concept which targ...

  19. Competitive Pressures and Transition to Entrepreneurship

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    This paper investigates whether the likelihood of entrepreneurial activity is associated with the competitive pressures for promotion within a firm. We argue that competitive pressures increase the relative attractiveness of entrepreneurship as a career option. We test our prediction using...... if they start working in organizational settings with strong competitive pressures. Furthermore, this competitive effect is more pronounced in firms that are entrepreneurially prominent, i.e. firms that spawn more entrepreneurial ventures, suggesting that combining different sources of incentives...

  20. Logistics capabilities for sustainable competitive advantage

    OpenAIRE

    Sandberg, Erik; Abrahamsson, Mats

    2011-01-01

    The purpose of this paper is to explore how sustainable competitive advantage is generated in two Swedish best practice companies that successfully exploit logistics as a source for competitive advantage. Using a theoretical framework based on the resource-based view of the firm, this research elaborates on the links between operational and dynamic logistics capabilities and sustainable competitive advantage. The findings conclude that a sustainable competitive advantage is based on a combina...

  1. JPRS Report Science & Technology Europe Economic Competitiveness.

    Science.gov (United States)

    1992-10-06

    many of them are now getting into the business of " competitive intelligence ." This practice, which is too often confused with industrial espionnage...information is a decisive factor in competitive- ness. Americans use the term competitive intelligence to describe a company’s capacity to unremittingly...had formerly practiced competitive intelligence "in a fairly makeshift fashion." Assigned to "organize the function," Bruno Martinet first strove to

  2. Renewing Team Competition for Himos-Safaris

    OpenAIRE

    Karttimo, Maiju

    2013-01-01

    The aim of this thesis was to develop Himos-Safaris’ product, Team competition, into a more functional and fresher product and bring new lift for it. The competition had become outdated because it had stayed too long the same. Also the duration in the old competition was often too short. The total outcome for this project was a new team competition and related material for the company. The theoretical background of the thesis consisted of three parts: Product development, Experience Touri...

  3. PARADIGMS REGARDING CONCERTED PRACTICES OF COMPETITION POLICY

    Directory of Open Access Journals (Sweden)

    Gabriela\tNEMŢOI

    2015-06-01

    Full Text Available The process of completing the single market requires the application of appropriate measures also in competition field. Rather, it is a truism that, once are removed the non-tariff barriers (physical, technical, fiscal of hindering trade, companies and governments will seek new ways to limit the restrictions so that competition laws to protect domestic industries. This study is a reflection on competitive practices regarding the theoretical and practical aspects in the phenomenon of economic competition.

  4. Assessing competition policy on economic development

    OpenAIRE

    Tilsa Oré

    2013-01-01

    Implementation of competition policies is one of the most recommended strategies to developing countries as a tool for achieving economic development. Using a panel dataset of over 100 countries and 7 years (from 2005-2011), I estimate the effect of competition on economic development, and also determine which of the comprehensive policy factors are the most relevant for increasing competition. A fixed effects instrumental variable approach is used. I find that competition intensity positivel...

  5. Competitiveness in the global economic crisis

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2009-05-01

    Full Text Available The first challenge is to analyze the concept of "competitiveness" given the fact that in the centre of the great economic analystes' concerns lays from some time the phenomenon of competitiveness, along with the generation of competitive advantage at the organization level and, moreover, at country level. The economic science will have to be rethought, meaning that competitiveness will have to adapt to the new prospects launched today by the global economic crisis.

  6. Global Markets and Time-Based Competition

    OpenAIRE

    Elisa Rancati

    2005-01-01

    Time becomes the benchmark that defines a company's strategic behaviour, extensively revamping the entire company by reinterpreting the time dimension in a different, extremely dynamic context. Marketing activities always presuppose time-based competition. From a marketing perspective, oriented to analysis of the competition, time-based competition can be defined as a strategy based on immediate response to the customer's needs. In the competitive conditions of over-supply, the time dimension...

  7. Revised article: Business Ideas Competition

    CERN Multimedia

    2003-01-01

    THIS ARTICLE REPLACES THAT PUBLISHED IN BULLETIN 27/2003, PAGE 8. "The Rainbow Seed Fund is a UK fund, which provides finance to support the commercialization of good ideas founded on scientific research; it is for the benefit of the UK industry in particular. To encourage ideas from CERN the Rainbow Seed Fund is running a business ideas competition. The winner of this competition will receive an immediate cash prize of GBP £1,000. In addition the Rainbow Seed Fund may well provide finance for market research, for protection of Intellectual Property Rights (IPR) and for prototyping to take the idea forward. Further awards of GBP £750 will be made for ideas which gain investment from the Fund. Candidates will only be required to prepare a 2-4-page summary of their business idea, and not a full business plan. Full details and an entry form are available at http://www.rainbowseedfund.com." ALL Members of the Personnel seeking participation in the business ideas competition are asked to submit their ideas via ...

  8. Kinetic competition during glass formation

    Energy Technology Data Exchange (ETDEWEB)

    Perepezko, J.H., E-mail: perepezk@engr.wisc.edu [University of Wisconsin-Madison, Department of Materials Science and Engineering, 1509 University Ave., Madison, WI 53706 (United States); Santhaweesuk, C.; Wang, J.Q. [University of Wisconsin-Madison, Department of Materials Science and Engineering, 1509 University Ave., Madison, WI 53706 (United States); Imhoff, S.D. [Los Alamos National Laboratory, Materials Science and Technology Div., Los Alamos, NM 87545 (United States)

    2014-12-05

    Highlights: • The kinetics of glass formation has been elucidated in an Fe and Au-base alloy. • A critical cooling rate range should be considered for glass formation. • Wedge casting, calorimetry and upquenching data are used to model TTT curves. - Abstract: For vitrification of an alloy melt during cooling there is a kinetic competition with the nucleation and growth of metastable and stable crystalline phases. Many of the measures of glass forming ability (GFA) attempt to capture some of the features of the kinetic competition, but the GFA metrics are static measures and the kinetic processes are dynamic in nature. In fact, the critical cooling rate for glass formation should be viewed in terms of a critical cooling rate range to acknowledge the stochastic nature of crystal nucleation behavior. Direct measurements of the critical cooling rate range confirm this behavior and also provide useful input for kinetics analysis. Usually kinetics analyses are based upon crystallization behavior that is measured either isothermally or upon heating to temperatures near the crystallization onset, T{sub x} and the results are extrapolated to much higher temperatures. This practice is based upon a number of assumptions about transport behavior in the undercooled liquid. With rapid up-quenching of amorphous samples, the high temperature crystallization behavior can be measured and used to refine the kinetics analysis and provide useful insight on the kinetic competition and glass forming ability.

  9. Competition Policy in an Open Economy

    NARCIS (Netherlands)

    J.F. François (Joseph); H. Horn

    1998-01-01

    textabstractWe examine the setting of national competition policy in a two-country setting, emphasizing the relationship of trade to the goals of competition policy (such as the degree and nature of competition). The issues we address involve the general equilibrium distributional effects of competi

  10. Iranian mathematics competitions 1973–2007

    CERN Document Server

    Yahaghi, Bamdad R

    2010-01-01

    A collection of problems from a competition for college students organised by the Iranian Mathematical Society. It compiles problems from these competitions between 1973 and 2007 and provides solutions to most of them. It is suitable for students of mathematics preparing for competitions and for advanced studies.

  11. 40 CFR 35.362 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.362 Section 35... 104(b)(3)) § 35.362 Competitive process. EPA will award Water Quality Cooperative Agreement funds through a competitive process in accordance with national program guidance....

  12. 40 CFR 35.342 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.342 Section 35...) § 35.342 Competitive process. EPA Regions award Pollution Prevention State Grants to State programs through a competitive process in accordance with EPA guidance. When evaluating State applications,...

  13. 40 CFR 35.613 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.613 Section 35... (section 104(b)(3)) § 35.613 Competitive process. Wetlands development grants are awarded on a competitive... process is complete, the recipient can, at its discretion, accept the award as a wetlands...

  14. 40 CFR 35.723 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.723 Section 35... Grants (pub.l. 105-276) § 35.723 Competitive process. EPA will award Tribal hazardous waste program... guidance. After the competitive process is complete, the recipient can, at its discretion, accept the...

  15. 40 CFR 35.712 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.712 Section 35... Monitoring (section 28) § 35.712 Competitive process. EPA will award Toxic Substances Control Act Compliance Monitoring grants to Tribes or Intertribal Consortia through a competitive process in accordance...

  16. 40 CFR 35.661 - Competitive process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competitive process. 35.661 Section 35... 6605) § 35.661 Competitive process. EPA Regions award Pollution Prevention Grant funds to Tribes and Intertribal Consortia through a competitive process in accordance with EPA guidance. When evaluating a...

  17. 13 CFR 313.8 - Competitive process.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Competitive process. 313.8 Section... § 313.8 Competitive process. (a) Applications for assistance to develop a Strategic Plan or for an implementation grant shall be reviewed by EDA in accord with a competitive process as set forth in the...

  18. 14 CFR 1260.143 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Competition. 1260.143 Section 1260.143..., Hospitals, and Other Non-Profit Organizations Procurement Standards § 1260.143 Competition. All procurement... competition. The recipient shall be alert to organizational conflicts of interest as well as...

  19. 48 CFR 13.104 - Promoting competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  20. 45 CFR 2400.2 - Annual competition.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Annual competition. 2400.2 Section 2400.2 Public... FELLOWSHIP PROGRAM REQUIREMENTS General § 2400.2 Annual competition. To achieve its principal purposes, the Foundation holds an annual national competition to select teachers in grades 7-12, college seniors,...

  1. 22 CFR 145.43 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Competition. 145.43 Section 145.43 Foreign... Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert to organizational conflicts of...

  2. 28 CFR 70.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Competition. 70.43 Section 70.43 Judicial... Post-Award Requirements Procurement Standards § 70.43 Competition. All procurement transactions must be conducted in a manner to provide, to the maximum extent practical, open and free competition. The...

  3. 7 CFR 3430.11 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Competition. 3430.11 Section 3430.11 Agriculture...-GENERAL AWARD ADMINISTRATIVE PROVISIONS Pre-award: Solicitation and Application § 3430.11 Competition. (a) Standards for competition. Except as provided in paragraph (b) of this section, CSREES will enter...

  4. 20 CFR 435.43 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Competition. 435.43 Section 435.43 Employees...-Award Requirements Procurement Standards § 435.43 Competition. All procurement transactions must be conducted in a manner to provide, to the maximum extent practical, open and free competition. The...

  5. 48 CFR 370.504 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Competition. 370.504... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.504 Competition. (a) Contracts awarded under the Buy Indian Act are subject to competition among Indians or Indian concerns...

  6. 22 CFR 518.43 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Competition. 518.43 Section 518.43 Foreign... Procurement Standards § 518.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert...

  7. 7 CFR 550.5 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Competition. 550.5 Section 550.5 Agriculture... Competition. REE agencies may enter into non-assistance cooperative agreements, as authorized by this part, without regard to any requirements for competition. (7 U.S.C. 3318(e))....

  8. 32 CFR 32.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Competition. 32.43 Section 32.43 National... NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 32.43 Competition. All... free competition. The recipient shall be alert to organizational conflicts of interest as well...

  9. 34 CFR 74.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Competition. 74.43 Section 74.43 Education Office of... Standards § 74.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert...

  10. 14 CFR 1274.504 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Competition. 1274.504 Section 1274.504... FIRMS Procurement Standards § 1274.504 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall...

  11. 48 CFR 34.005-1 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Competition. 34.005-1... OF CONTRACTING MAJOR SYSTEM ACQUISITION General 34.005-1 Competition. (a) The program manager shall, throughout the acquisition process, promote full and open competition and sustain effective...

  12. 24 CFR 84.43 - Competition.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Competition. 84.43 Section 84.43... NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 84.43 Competition. All... free competition. The recipient shall be alert to organizational conflicts of interest as well...

  13. 49 CFR 19.43 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Competition. 19.43 Section 19.43 Transportation... Requirements Procurement Standards § 19.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall...

  14. 29 CFR 95.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Competition. 95.43 Section 95.43 Labor Office of the... Standards § 95.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert...

  15. 10 CFR 600.143 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Competition. 600.143 Section 600.143 Energy DEPARTMENT OF... Nonprofit Organizations Post-Award Requirements § 600.143 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The...

  16. 2 CFR 215.43 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Competition. 215.43 Section 215.43 Grants... ORGANIZATIONS (OMB CIRCULAR A-110) Post Award Requirements Procurement Standards § 215.43 Competition. All... free competition. The recipient shall be alert to organizational conflicts of interest as well...

  17. 38 CFR 49.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Competition. 49.43... NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 49.43 Competition. All... free competition. The recipient shall be alert to organizational conflicts of interest as well...

  18. 7 CFR 3019.43 - Competition.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Competition. 3019.43 Section 3019.43 Agriculture... § 3019.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert to...

  19. 48 CFR 570.104 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Competition. 570.104... PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.104 Competition. Unless you use the simplified procedures in subpart 570.2, the competition requirements of FAR part 6 apply to acquisition...

  20. 48 CFR 9.206-3 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Competition. 9.206-3... CONTRACTOR QUALIFICATIONS Qualifications Requirements 9.206-3 Competition. (a) Presolicitation. If a... solicitation to ascertain whether the number of sources is adequate for competition. (See 9.204(a) for...

  1. 36 CFR 1210.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Competition. 1210.43 Section... Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert to organizational conflicts of...

  2. 40 CFR 30.43 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competition. 30.43 Section 30.43... NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 30.43 Competition. All... free competition. The recipient shall be alert to organizational conflicts of interest as well...

  3. 43 CFR 12.943 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Competition. 12.943 Section 12.943 Public....943 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent practical, open and free competition. The recipient shall be alert to...

  4. 40 CFR 35.936-3 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Competition. 35.936-3 Section 35.936-3... ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act § 35.936-3 Competition. EPA's policy is to encourage free and open competition appropriate to the type of project work to be performed....

  5. 41 CFR 105-72.503 - Competition.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Competition. 105-72.503... NON-PROFIT ORGANIZATIONS 72.50-Post-Award Requirements/Procurement Standards § 105-72.503 Competition... practical, open and free competition. The recipient shall be alert to organizational conflicts of...

  6. METHODOLOGY FOR DETERMINATION OF ENTERPRISE POTENTIAL COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    A. F. Zubritsky

    2010-01-01

    Full Text Available The paper considers economic principles on enterprise potential management and its competitiveness.  Elements of the enterprise economic potential that permit to select an efficient strategy of an organization behaviour are presented in the paper. The paper proposes a methodology for determination of enterprise potential competitiveness on the basis of the existing standard indices and various competitiveness levels.

  7. REGULATION AND ENFORCEMENT OF COMPETITION POLICY

    Directory of Open Access Journals (Sweden)

    Liviana Andreea Niminet

    2014-12-01

    Full Text Available Competition policy starts by shaping a legislative framework. This is aimed to establish boundaries for conducting competition and also sets limits of licit and illicit demarcation, for competitive and anticompetitive practices. The Romanian Competition Law has a divalent approach and it aims to provide specific behavioral conditions in order to stimulate and protect free-market competition, with the ultimate goal of developing a balanced, efficient and competitive economy. Our country’s Competition policy is based on punishing the behavior. There are three such types of anti-competitive behavior, namely: agreements between undertakings, abuse of dominant position and mergers and other concentrations between undertakings. Recent Practice proved that this “enforcement-conduct-punishment” structure is not necessary the best way to address competition and it is high time for authorities to switch both regulation and enforcement of competition from the “classical perspective” towards concepts like “competition advocacy” and “soft power” and give competition policy a new, reshaped face.

  8. Synergetic effect of benchmarking competitive advantages

    Directory of Open Access Journals (Sweden)

    N.P. Tkachova

    2011-12-01

    Full Text Available It is analyzed the essence of synergistic competitive benchmarking. The classification of types of synergies is developed. It is determined the sources of synergies in conducting benchmarking of competitive advantages. It is proposed methodological framework definition of synergy in the formation of competitive advantage.

  9. Synergetic effect of benchmarking competitive advantages

    OpenAIRE

    N.P. Tkachova; P.G. Pererva

    2011-01-01

    It is analyzed the essence of synergistic competitive benchmarking. The classification of types of synergies is developed. It is determined the sources of synergies in conducting benchmarking of competitive advantages. It is proposed methodological framework definition of synergy in the formation of competitive advantage.

  10. Independent competition authorities in the EU

    NARCIS (Netherlands)

    Gronden, Johan W.van de; Vries, S.A. de

    2006-01-01

    In most Member States competition law powers have been granted to a more or less independent competition authority. The idea is that the application and enforcement of competition law should not be influenced by political and volatile considerations. However, some recent cases, most notably in the

  11. Exploring the Competitive Effects of Charter Schools

    Science.gov (United States)

    Carpenter, Dick M., II; Medina, Paul M.

    2011-01-01

    Central to the debate over school choice has been the question of how public schools respond to market-based competition. Many choice advocates suggest that competition can spur public schools to become more effective and efficient, but the evidence regarding the effect of competition from charters is comparably sparse and mixed. This article…

  12. 48 CFR 570.203-2 - Competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Competition. 570.203-2... 570.203-2 Competition. (a) Solicit at least three sources to promote competition to the maximum extent practicable. If you have repeated requirements for space in the same market, and if practicable, invite...

  13. A new way to measure competition

    NARCIS (Netherlands)

    J. Boone

    2008-01-01

    This article introduces a new way to measure competition based on firms' profits. Within a general model, we derive conditions under which this measure is monotone in competition, where competition can be intensified both through a fall in entry barriers and through more aggressive interaction betwe

  14. A New Way to Measure Competition

    NARCIS (Netherlands)

    Boone, J.

    2004-01-01

    This paper introduces a new way to measure competition based on firms' profits.Within a general model, we derive conditions under which this measure is monotone in competition, where competition can be intensified both through a fall in entry barriers and through more aggressive interaction between

  15. Marketing research model of competitive environment

    Directory of Open Access Journals (Sweden)

    Krasilya Dmitriy

    2015-11-01

    Full Text Available To support its competitive advantages in current market conditions, each company needs to choose better ways of guaranteeing its favorable competitive position. In this regard, considerable interest lies in the structuring and algorithmization of marketing research processes that provide the information background of such choice. The article is devoted to modeling the process of marketing research of competitive environment.

  16. How Banking Competition changed over Time

    NARCIS (Netherlands)

    Bikker, J.A.; Spierdijk, L.

    2008-01-01

    This paper is the first detailed and world-wide investigation of the developments in banking competition during the past fiffteen years. Using the Panzar-Rosse approach, we establish significant changes over time in the competitiveness of the banking industry. The changes in competition over time ar

  17. Evolution of definition of competitiveness of products

    Directory of Open Access Journals (Sweden)

    I.A. Aleksandrov

    2010-12-01

    Full Text Available Investigational evolution of definition of competitiveness of products, certainly the stages of his development. Classification of existent approaches is improved in relation to the estimation of competitiveness of products, found out the sources of competitive edges from position of consumer cost, marginal utility, differentiation of products, demand and supply, key competense, marketing categories and ecological approach.

  18. Competitiveness and linking of emission trading systems

    Energy Technology Data Exchange (ETDEWEB)

    Hausotter, Tobias; Steuwer, Sibyl; Taenzler, Dennis [adelphi, Berlin (Germany)

    2011-01-15

    The establishment of emission trading systems raises concerns among industries regarding international competitive disadvantages for the industries under an emissions cap. This study aims to assess competitiveness exposure of industrial sectors and presents policy measures to address these concerns. Moreover, the study provides a comparison of different existing approaches to competitiveness concerns proposed by regional emission trading systems. (orig.)

  19. Perception of competition : A measurement of competition from the perspective of the firm

    OpenAIRE

    Kemp, R.G.M.; Hanemaaijer, J.

    2004-01-01

    In this report, we study competition from a cognitive psychology, marketing and strategic management perspective and hope to contribute to the notion of competition and competitive processes. In addition, we propose a new method to measure competition that is based on these more psychological insights.

  20. Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.

    Science.gov (United States)

    Kuhnz, W; Baumann, A; Staks, T; Dibbelt, L; Knuppen, R; Jütting, G

    1993-10-01

    The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively