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Sample records for bound protein grb2

  1. Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb 2 insights to identify novel inhibitors

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    Sandeep S

    2016-10-01

    Full Text Available Background: Human growth factor receptor bound protein-2 (Grb 2 involves in initiation of kinase signaling by Son of Sevenless (SOS and activates mitogen activated protein kinase pathway. Grb2 overexpress during cancerous condition hence it emerged as a potent target for various cancers. Material and Methods: Seven pharmacophores were developed from seven co-crystal structures of Grb2 and applied for common pharmacophore hypothesis. Two common pharmacophore hypothesis (CPH models were screened and hits were applied for docking and free energy [G] calculations. Results: Two leads were proposed from docking and G analysis. Energy of the system, RMSD, RMSF, hydrogen bonds and water bridges of lead1 was better than the co-crystal ligand during 50 ns molecular dynamics simulations. Discussion: Two leads are interacting with Src homology 2 (SH2 domain of Grb2 and blocking the function of Grb2.

  2. Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2

    DEFF Research Database (Denmark)

    VanderKuur, J; Allevato, G; Billestrup, Nils;

    1995-01-01

    Growth hormone (GH) has been shown to stimulate the mitogen-activated protein (MAP) kinases designated ERKs (extracellular signal regulated kinases) 1 and 2. One pathway by which ERKs 1 and 2 are activated by tyrosine kinases involves the Src homology (SH)-2 containing proteins SHC and Grb2. To...... phosphorylation of 66-, 52-, and 46-kDa SHC proteins in 3T3-F442A fibroblasts. GH also promoted binding of GHR and JAK2 to the SH2 domain of 46/52-kDa SHC protein fused to glutathione S-transferase (GST). Constitutively phosphorylated JAK2, from COS-7 cells transiently transfected with murine JAK2 cDNA, bound to...

  3. Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.

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    Ambarish Nag

    Full Text Available The linker for activation of T cells (LAT, the linker for activation of B cells (LAB, and the linker for activation of X cells (LAX form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate. We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate.

  4. Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated signaling and anaplastic large cell lymphoma growth.

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    Riera, Ludovica; Lasorsa, Elena; Ambrogio, Chiara; Surrenti, Nadia; Voena, Claudia; Chiarle, Roberto

    2010-08-20

    Most anaplastic large cell lymphomas (ALCL) express oncogenic fusion proteins derived from chromosomal translocations or inversions of the anaplastic lymphoma kinase (ALK) gene. Frequently ALCL carry the t(2;5) translocation, which fuses the ALK gene to the nucleophosmin (NPM1) gene. The transforming activity mediated by NPM-ALK fusion induces different pathways that control proliferation and survival of lymphoma cells. Grb2 is an adaptor protein thought to play an important role in ALK-mediated transformation, but its interaction with NPM-ALK, as well as its function in regulating ALCL signaling pathways and cell growth, has never been elucidated. Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. An intact SH3 domain at the C terminus of Grb2 was required for Tyr(160) phosphorylation. Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). Finally, shRNA knockdown experiments showed that Grb2 regulates primarily the NPM-ALK-mediated phosphorylation of SHP2 and plays a key role in ALCL cell growth.

  5. Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and associated with the adaptor protein Grb2

    DEFF Research Database (Denmark)

    Su, J; Batzer, A; Sap, J

    1994-01-01

    -phosphorylated and associated in vivo with the Grb2 protein. This association can be reproduced in stably and transiently transfected cells, as well as in vitro using recombinant Grb2 protein. Association requires the presence of an intact SH2 domain in Grb2, as well as tyrosine phosphorylation of R-PTP-alpha. This observation......Receptor tyrosine phosphatases (R-PTPases) have generated interest because of their suspected involvement in cellular signal transduction. The adaptor protein Grb2 has been implicated in coupling receptor tyrosine kinases to Ras. We report that a ubiquitous R-PTPase, R-PTP-alpha, is tyrosine...... links a receptor tyrosine phosphatase with a key component of a central cellular signalling pathway and provides a basis for addressing R-PTP-alpha function....

  6. Molecular cloning and characterization of growth factor receptor bound-protein in Clonorchis sinensis.

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    Xuelian Bai

    Full Text Available BACKGROUND: Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2 is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2 from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS: A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. CONCLUSION: Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths.

  7. Association between receptor protein-tyrosine phosphatase RPTPalpha and the Grb2 adaptor. Dual Src homology (SH) 2/SH3 domain requirement and functional consequences

    DEFF Research Database (Denmark)

    Su, J; Yang, L T; Sap, J

    1996-01-01

    Receptor protein-tyrosine phosphatase RPTPalpha is found associated in vivo with the adaptor protein Grb2. Formation of this complex, which contains no detectable levels of Sos, is known to depend on a C-terminal phosphorylated tyrosine residue (Tyr798) in RPTPalpha and on the Src homology (SH) 2...

  8. Grb2 Is Important for T Cell Development, Th Cell Differentiation, and Induction of Experimental Autoimmune Encephalomyelitis.

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    Radtke, Daniel; Lacher, Sonja M; Szumilas, Nadine; Sandrock, Lena; Ackermann, Jochen; Nitschke, Lars; Zinser, Elisabeth

    2016-04-01

    The small adaptor protein growth factor receptor-bound protein 2 (Grb2) modulates and integrates signals from receptors on cellular surfaces in inner signaling pathways. In murine T cells, Grb2 is crucial for amplification of TCR signaling. T cell-specific Grb2(fl/fl) Lckcre(tg) Grb2-deficient mice show reduced T cell numbers due to impaired negative and positive selection. In this study, we found that T cell numbers in Grb2(fl/fl) CD4cre(tg) mice were normal in the thymus and were only slightly affected in the periphery. Ex vivo analysis of CD4(+) Th cell populations revealed an increased amount of Th1 cells within the CD4(+) population of Grb2(fl/fl) CD4cre(tg) mice. Additionally, Grb2-deficient T cells showed a greater potential to differentiate into Th17 cells in vitro. To test whether these changes in Th cell differentiation potential rendered Grb2(fl/fl) CD4cre(tg) mice more prone to inflammatory diseases, we used the murine Th1 cell- and Th17 cell-driven model of experimental autoimmune encephalomyelitis (EAE). In contrast to our expectations, Grb2(fl/fl) CD4cre(tg) mice developed a milder form of EAE. The impaired EAE disease can be explained by the reduced proliferation rate of Grb2-deficient CD4(+) T cells upon stimulation with IL-2 or upon activation by allogeneic dendritic cells, because the activation of T cells by dendritic cells and the subsequent T cell proliferation are known to be crucial factors for the induction of EAE. In summary, Grb2-deficient T cells show defects in T cell development, increased Th1 and Th17 cell differentiation capacities, and impaired proliferation after activation by dendritic cells, which likely reduce the clinical symptoms of EAE.

  9. Inhibition of Grb2-mediated activation of MAPK signal transduction suppresses NOR1/CB1954-induced cytotoxicity in the HepG2 cell line.

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    Gui, Rong; Li, Dengqing; Qi, Guannan; Suhad, Ali; Nie, Xinmin

    2012-09-01

    The nitroreductase oxidored-nitro domain containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyngeal carcinoma (NPC). We have previously demonstrated that NOR1 overexpression is capable of converting the monofunctional alkylating agent 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) into a toxic form by reducing the 4-nitro group of CB1954. Toxic CB1954 is able to enhance cell killing in the NPC cell line CNE1; however, the underlying mechanisms remain unknown. Using cDNA microarrays and quantitative real-time PCR, we previously discovered that NOR1 increases the expression of growth factor receptor-bound protein 2 (Grb2) mRNA by 4.8-fold in the human hepatocellular carcinoma cell line HepG2. In the present study, we revealed that NOR1 increased Grb2 protein expression by 3-fold in HepG2 cells. Additionally, we demonstrated that NOR1 enhanced CB1954-induced cell killing in HepG2 cells, and cell cytotoxicity was inhibited with the tyrosine kinase inhibitor genistein, or by stable transfection of Grb2 small hairpin RNA (shRNA) pU6(+27)-shGrb2 to silence the expression of Grb2. Western blot analysis revealed that Grb2 downregulation may reduce the activity of the mitogen-activated protein kinase (MAPK). Inhibiting the activation of MAPK using the methyl ethyl ketone (MEK) inhibtor PD98059 suppressed CB1954-induced cell killing. These results suggested that the NOR1 gene enhances CB1954-mediated cell cytotoxicity through the upregulation of Grb2 expression and the activation of MAPK signal transduction in the HepG2 cell line. PMID:23741254

  10. Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.

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    Shounak Baksi

    Full Text Available Growth factor receptor protein binding protein 2 (Grb2 is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt, a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease (HD. We observed an elevated expression of Grb2 in neuronal cells in animal and cell models of HD. Grb2 overexpression was predominantly regulated by the transcription factor Forkhead Box D3 (Foxd3. Exogenous expression of Grb2 also reduced aggregation of mutant Htt in Neuro2A cells. Grb2 is also known to interact with Htt, depending on epidermal growth factor receptor (EGFR activation. Grb2- mutant Htt interaction in the contrary, took place in vesicular structures, independent of EGFR activation that eventually merged with autophagosomes and activated the autophagy machinery helping in autophagosome and lysosome fusion. Grb2, with its emerging dual role, holds promise for a survival mechanism for HD.

  11. Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner.

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    McDonald, Caleb B; El Hokayem, Jimmy; Zafar, Nawal; Balke, Jordan E; Bhat, Vikas; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Farooq, Amjad

    2013-02-01

    Allostery plays a key role in dictating the stoichiometry and thermodynamics of multi-protein complexes driving a plethora of cellular processes central to health and disease. Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in concert in lieu of a composite Sos1-Grb2-Gab1 ternary complex. Of particular interest is the observation that the binding of Sos1 to the nSH3 domain within Grb2 sterically blocks the binding of Gab1 to the cSH3 domain and vice versa in a mutually exclusive manner. Importantly, the formation of both the Grb2-Sos1 and Grb2-Gab1 binary complexes is governed by a stoichiometry of 2:1, whereby the respective SH3 domains within Grb2 homodimer bind to Sos1 and Gab1 via multivalent interactions. Collectively, our study sheds new light on the role of allostery in mediating cellular signaling machinery. PMID:23334917

  12. Quantification and kinetic analysis of Grb2-EGFR interaction on micro-patterned surfaces for the characterization of EGFR-modulating substances.

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    Peter Lanzerstorfer

    Full Text Available The identification of the epidermal growth factor receptor (EGFR as an oncogene has led to the development of several anticancer therapeutics directed against this receptor tyrosine kinase. However, drug resistance and low efficacy remain a severe challenge, and have led to a demand for novel systems for an efficient identification and characterization of new substances. Here we report on a technique which combines micro-patterned surfaces and total internal reflection fluorescence (TIRF microscopy (μ-patterning assay for the quantitative analysis of EGFR activity. It does not simply measure the phosphorylation of the receptor, but instead quantifies the interaction of the key signal transmitting protein Grb2 (growth factor receptor-bound protein 2 with the EGFR in a live cell context. It was possible to demonstrate an EGF dependent recruitment of Grb2 to the EGFR, which was significantly inhibited in the presence of clinically tested EGFR inhibitors, including small tyrosine kinase inhibitors and monoclonal antibodies targeting the EGF binding site. Importantly, in addition to its potential use as a screening tool, our experimental setup offers the possibility to provide insight into the molecular mechanisms of bait-prey interaction. Recruitment of the EGFR together with Grb2 to clathrin coated pits (CCPs was found to be a key feature in our assay. Application of bleaching experiments enabled calculation of the Grb2 exchange rate, which significantly changed upon stimulation or the presence of EGFR activity inhibiting drugs.

  13. Bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner.

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    McDonald, Caleb B; Bhat, Vikas; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Farooq, Amjad

    2012-06-01

    Although the growth factor receptor binder 2 (Grb2)-Grb2-associated binder (Gab)1 macromolecular complex mediates a multitude of cellular signaling cascades, the molecular basis of its assembly has hitherto remained largely elusive. Herein, using an array of biophysical techniques, we show that, whereas Grb2 exists in a monomer-dimer equilibrium, the proline-rich (PR) domain of Gab1 is a monomer in solution. Of particular interest is the observation that although the PR domain appears to be structurally disordered, it nonetheless adopts a more or less compact conformation reminiscent of natively folded globular proteins. Importantly, the structurally flexible conformation of the PR domain appears to facilitate the binding of Gab1 to Grb2 with a 1:2 stoichiometry. More specifically, the formation of the Grb2-Gab1 signaling complex is driven via a bivalent interaction through the binding of the C-terminal homology 3 (cSH3) domain within each monomer of Grb2 homodimer to two distinct RXXK motifs, herein designated G1 and G2, located within the PR domain of Gab1. Strikingly, in spite of the key role of bivalency in driving this macromolecular assembly, the cSH3 domains bind to the G1 and G2 motifs in an independent manner with zero cooperativity. Taken together, our findings shed new light on the physicochemical forces driving the assembly of a key macromolecular signaling complex that is relevant to cellular health and disease. PMID:22536782

  14. Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

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    Gesang, Luobu; Dan, Zeng; Gusang, Lamu

    2016-01-01

    The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.

  15. Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis.

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    Clark, Jo-Anna B J; Tully, Sara J; Dawn Marshall, H

    2014-12-01

    Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron-exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.

  16. Isolation of In Vivo SUMOylated Chromatin-Bound Proteins.

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    Bawa-Khalfe, Tasneem

    2016-01-01

    SUMO posttranslational modification directs gene transcription and epigenetic programming to support normal cell function. The dynamic nature of SUMO-modification makes it difficult to identify endogenous protein substrates. Isolation of chromatin-bound SUMO targets is exceptionally challenging, as conventional immunoprecipitation assays are inefficient at concentrating this protein population. This chapter describes a protocol that effectively precipitates chromatin-associated fractions of SUMOylated heterochromatin protein 1α in cultured cells. Techniques to enrich endogenous SUMO substrates at the chromatin are also demonstrated and discussed. This approach could be adapted to evaluate chromatin-bound SUMO targets in additional in vivo systems. PMID:27631808

  17. CBC bound proteins and RNA fate

    DEFF Research Database (Denmark)

    Giacometti, Simone

    2016-01-01

    ) complex (CBCN), were recently shown to target capped RNA either toward export or degradation, but the mechanisms by which they can discriminate between different RNA families and route them toward different metabolic pathways still remain unclear. A major question to be answered is how and when...... the different CBC subcomplexes are recruited to the RNP. Here, we used an individual nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP) approach to identify the transcriptome-wide targets for 5 different components of the CBCAP and CBCN complexes, and compared results to the previously......), while MTR4 is additionally present on mature RNAs. Although more experimental work is needed to fully support our model, we propose that CBCAP and CBCN bind overlapping sets of RNAs, indicating a competition between the proteins ZC3H18 and PHAX, and the lack of a strict RNA sorting mechanism. RNA fate...

  18. Grb2 Is a Negative Modulator of the Intrinsic Ras-GEF Activity of hSos1

    OpenAIRE

    Zarich, Natasha; Oliva, José Luis; Martínez, Natalia; Jorge, Rocío; Ballester, Alicia; Gutiérrez-Eisman, Silvia; García-Vargas, Susana; Rojas, José M

    2006-01-01

    hSos1 is a Ras guanine-nucleotide exchange factor. It was suggested that the carboxyl-terminal region of hSos1 down-regulates hSos1 functionality and that the intrinsic guanine-nucleotide exchange activity of this protein may be different before and after stimulation of tyrosine kinase receptors. Using different myristoylated hSos1 full-length and carboxyl-terminal truncated mutants, we show that Grb2 function accounts not only for recruitment of hSos1 to the plasma membrane but also for modu...

  19. Substrate-Bound Protein Gradients to Study Haptotaxis

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    Sebastien G. Ricoult

    2015-03-01

    Full Text Available Cells navigate in response to inhomogeneous distributions of extracellular guidance cues. The cellular and molecular mechanisms underlying migration in response to gradients of chemical cues have been investigated for over a century. Following the introduction of micropipettes and more recently microfluidics for gradient generation, much attention and effort was devoted to study cellular chemotaxis, which is defined as guidance by gradients of chemical cues in solution. Haptotaxis, directional migration in response to gradients of substrate-bound cues, has received comparatively less attention; however it is increasingly clear that in vivo many physiologically relevant guidance proteins – including many secreted cues – are bound to cellular surfaces or incorporated into extracellular matrix and likely function via a haptotactic mechanism. Here, we review the history of haptotaxis. We examine the importance of the reference surface, the surface in contact with the cell that is not covered by the cue, which forms a gradient opposing the gradient of the protein cue and must be considered in experimental designs and interpretation of results. We review and compare microfluidics, contact-printing, light patterning and 3D fabrication to pattern substrate-bound protein gradients in vitro, and focus on their application to study axon guidance. The range of methods to create substrate-bound gradients discussed herein make possible systematic analyses of haptotactic mechanisms. Furthermore, understanding the fundamental mechanisms underlying cell motility will inform bioengineering approaches to program cell navigation and recover lost function.

  20. Substrate-bound protein gradients to study haptotaxis.

    Science.gov (United States)

    Ricoult, Sébastien G; Kennedy, Timothy E; Juncker, David

    2015-01-01

    Cells navigate in response to inhomogeneous distributions of extracellular guidance cues. The cellular and molecular mechanisms underlying migration in response to gradients of chemical cues have been investigated for over a century. Following the introduction of micropipettes and more recently microfluidics for gradient generation, much attention and effort was devoted to study cellular chemotaxis, which is defined as guidance by gradients of chemical cues in solution. Haptotaxis, directional migration in response to gradients of substrate-bound cues, has received comparatively less attention; however, it is increasingly clear that in vivo many physiologically relevant guidance proteins - including many secreted cues - are bound to cellular surfaces or incorporated into extracellular matrix and likely function via a haptotactic mechanism. Here, we review the history of haptotaxis. We examine the importance of the reference surface, the surface in contact with the cell that is not covered by the cue, which forms a gradient opposing the gradient of the protein cue and must be considered in experimental designs and interpretation of results. We review and compare microfluidics, contact printing, light patterning, and 3D fabrication to pattern substrate-bound protein gradients in vitro. The range of methods to create substrate-bound gradients discussed herein makes possible systematic analyses of haptotactic mechanisms. Furthermore, understanding the fundamental mechanisms underlying cell motility will inform bioengineering approaches to program cell navigation and recover lost function.

  1. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia

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    Gillis, LC; Berry, DM; Minden, MD; McGlade, CJ; Barber, DL

    2016-01-01

    Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (B-ALL), are driven by the oncogenic BCR-ABL fusion protein. Animal modeling experiments utilizing retroviral transduction and subsequent bone marrow transplantation have demonstrated that BCR-ABL generates both myeloid and lymphoid disease in mice receiving whole bone marrow transduced with BCR-ABL. Y177 of BCR-ABL is critical to the development of myeloid disease, and phosphorylation of Y177 has been shown to induce GRB2 binding to BCR-ABL, followed by activation of the Ras and phosphoinositide 3 kinase signaling pathways. We show that the GRB2-related adapter protein, GADS, also associates with BCR-ABL, specifically through Y177 and demonstrate that BCR-ABL-driven lymphoid disease requires Gads. BCR-ABL transduction of Gads(−/−) bone marrow results in short latency myeloid disease within 3–4 weeks of transplant, while wild-type mice succumb to both a longer latency lymphoid and myeloid diseases. We report that GADS mediates a unique BCR-ABL complex with SLP-76 in BCR-ABL-positive cell lines and B-ALL patient samples. These data suggest that GADS mediates lymphoid disease downstream of BCR-ABL through the recruitment of specific signaling intermediates. PMID:23399893

  2. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    DEFF Research Database (Denmark)

    Huebner, K; Kastury, K; Druck, T;

    1994-01-01

    Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding "...

  3. Study of the SH3-donain GRB2-like 2 gene expression in laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    SHANG Chao; FU Wei-neng; GUO Yan; HUANG Dai-fa; SUN Kai-lai

    2007-01-01

    Background Laryngeal carcinoma is a common malignant tumor of the upper respiratory tract, and in 95% of cases the tumor is laryngeal squamous cell carcinoma (LSCC). The abnormity of SH3-domain GRB2-like 2 (SH3GL2) gene was found in LSCC. In order to clarify the relationship between SH3GL2 gene and LSCC, we evaluated the expression of the SH3GL2 gene in LSCC.Method Real-time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC.Results The result of real-time PCR showed that the expression level of SH3GL2 mRNA in LSCC tissue was apparently down-regulated; immunohistochemical analysis showed that SH3GL2 protein was mainly located in cytoplasm, the rate of positive cells and SH3GL2 protein expression level were fluctuated with the pathological classification of LSCC; the result of Western blotting showed that SH3GL2 protein was down-regulated significantly in LSCC samples, especially in metastatic lymph nodes.Conclusions These results suggest that SH3GL2 is a LSCC related gene and its expression level is fluctuated with the pathological classification which indicate that SH3GL2 participates in the development and progression of LSCC. And it may be considered as a novel tumor marker to find both a new anti-oncogene and relative factors of invasion and metastasis of laryngeal carcinoma.

  4. Computational structural analysis: multiple proteins bound to DNA.

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    Andrija Tomovic

    Full Text Available BACKGROUND: With increasing numbers of crystal structures of proteinratioDNA and proteinratioproteinratioDNA complexes publically available, it is now possible to extract sufficient structural, physical-chemical and thermodynamic parameters to make general observations and predictions about their interactions. In particular, the properties of macromolecular assemblies of multiple proteins bound to DNA have not previously been investigated in detail. METHODOLOGY/PRINCIPAL FINDINGS: We have performed computational structural analyses on macromolecular assemblies of multiple proteins bound to DNA using a variety of different computational tools: PISA; PROMOTIF; X3DNA; ReadOut; DDNA and DCOMPLEX. Additionally, we have developed and employed an algorithm for approximate collision detection and overlapping volume estimation of two macromolecules. An implementation of this algorithm is available at http://promoterplot.fmi.ch/Collision1/. The results obtained are compared with structural, physical-chemical and thermodynamic parameters from proteinratioprotein and single proteinratioDNA complexes. Many of interface properties of multiple proteinratioDNA complexes were found to be very similar to those observed in binary proteinratioDNA and proteinratioprotein complexes. However, the conformational change of the DNA upon protein binding is significantly higher when multiple proteins bind to it than is observed when single proteins bind. The water mediated contacts are less important (found in less quantity between the interfaces of components in ternary (proteinratioproteinratioDNA complexes than in those of binary complexes (proteinratioprotein and proteinratioDNA.The thermodynamic stability of ternary complexes is also higher than in the binary interactions. Greater specificity and affinity of multiple proteins binding to DNA in comparison with binary protein-DNA interactions were observed. However, protein-protein binding affinities are stronger in

  5. Construction of Grb2-SH2 genetic restructuring-slow virus carrier with Gateway system%用Gateway系统构建携带Grb2-SH2基因重组慢病毒载体

    Institute of Scientific and Technical Information of China (English)

    蔡忠良; 阴继凯; 韩腾龙; 张健; 鲁建国

    2012-01-01

    目的:构建携带Grb2-SH2基因重组慢病毒载体.方法:把Grb2-SH2基因从合成的工程载体PUC-57中导到入门载体pentr--3C中,再利用LR反应重组到目的载体plenti,通过酶切和测序分析对比验证Grb2-SH2基因后,将plenti- Grb2-SH2质粒利用慢病毒转染系统转染人胚胎肾上皮细胞株293T细胞获得携带Grb2-SH2慢病毒载体.结果:构建的重组质粒经酶切及测序和分析比对鉴定正确,目的基因片段大小约为500bp;该质粒与包装质粒共转染293T细胞获取的慢病毒,转染效率约为90%.结论:成功构建转载质粒plenti- Grb2-SH2及携带Grb2-SH2基因慢病毒载体.%Construct Grb2-SH2 genetic recombination slow virus carrier. Methods: Put the Grb2-SH2 genes into introductory carrier pentr-3 C from synthetic engineering carrier PUC-57, reuse LR reaction to recombinate into the purpose plenti carrier, after comparing and testing gene Grb2-SH2 through the enzyme cut and sequencing analysis and comparison ,use slow virus carrying system to transfect human embryonic renal epithelial cell lines 293 T cells acquring Grb2-SH2 slow virus carrier. Results: The restructuring plasmid proved to be correct by the enzyme cut and sequencing analysis and the purpose genetic fragments is about 500 bp; The efficiency of the plasmid and packaging plasmid transfect 293 T cells get slow is about 90%. Conclusion: Successful construction reproduced plasmid plenti-Grb2-SH2 and Grb2-SH2 gene slow virus carrier.

  6. Removal of the Protein-Bound Solutes Indican and P-Cresol Sulfate by Peritoneal Dialysis

    OpenAIRE

    Pham, Nhat M.; Recht, Natalie S.; Hostetter, Thomas H.; Meyer, Timothy W.

    2008-01-01

    Background and objectives: Protein-bound solutes are poorly cleared by peritoneal dialysis. We examined the hypothesis that plasma concentrations of bound solutes would therefore rise as residual renal function is lost.

  7. Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

    Science.gov (United States)

    Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

    1995-03-01

    Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context

  8. Dynamic nuclear polarization of membrane proteins: covalently bound spin-labels at protein–protein interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Wylie, Benjamin J. [Columbia University, Department of Chemistry (United States); Dzikovski, Boris G. [Cornell University, National Biomedical Center for Advanced ESR Technology, Department of Chemistry and Chemical Biology (United States); Pawsey, Shane; Caporini, Marc; Rosay, Melanie [Bruker BioSpin Corporation (United States); Freed, Jack H. [Cornell University, National Biomedical Center for Advanced ESR Technology, Department of Chemistry and Chemical Biology (United States); McDermott, Ann E., E-mail: aem5@columbia.edu [Columbia University, Department of Chemistry (United States)

    2015-04-15

    We demonstrate that dynamic nuclear polarization of membrane proteins in lipid bilayers may be achieved using a novel polarizing agent: pairs of spin labels covalently bound to a protein of interest interacting at an intermolecular interaction surface. For gramicidin A, nitroxide tags attached to the N-terminal intermolecular interface region become proximal only when bimolecular channels forms in the membrane. We obtained signal enhancements of sixfold for the dimeric protein. The enhancement effect was comparable to that of a doubly tagged sample of gramicidin C, with intramolecular spin pairs. This approach could be a powerful and selective means for signal enhancement in membrane proteins, and for recognizing intermolecular interfaces.

  9. Protein sequences bound to mineral surfaces persist into deep time

    DEFF Research Database (Denmark)

    Demarchi, Beatrice; Hall, Shaun; Roncal-Herrero, Teresa;

    2016-01-01

    Proteins persist longer in the fossil record than DNA, but the longevity, survival mechanisms and substrates remain contested. Here, we demonstrate the role of mineral binding in preserving the protein sequence in ostrich (Struthionidae) eggshell, including from the palaeontological sites of Laet...

  10. Protein sequences bound to mineral surfaces persist into deep time

    Science.gov (United States)

    Demarchi, Beatrice; Hall, Shaun; Roncal-Herrero, Teresa; Freeman, Colin L; Woolley, Jos; Crisp, Molly K; Wilson, Julie; Fotakis, Anna; Fischer, Roman; Kessler, Benedikt M; Rakownikow Jersie-Christensen, Rosa; Olsen, Jesper V; Haile, James; Thomas, Jessica; Marean, Curtis W; Parkington, John; Presslee, Samantha; Lee-Thorp, Julia; Ditchfield, Peter; Hamilton, Jacqueline F; Ward, Martyn W; Wang, Chunting Michelle; Shaw, Marvin D; Harrison, Terry; Domínguez-Rodrigo, Manuel; MacPhee, Ross DE; Kwekason, Amandus; Ecker, Michaela; Kolska Horwitz, Liora; Chazan, Michael; Kröger, Roland; Thomas-Oates, Jane; Harding, John H; Cappellini, Enrico; Penkman, Kirsty; Collins, Matthew J

    2016-01-01

    Proteins persist longer in the fossil record than DNA, but the longevity, survival mechanisms and substrates remain contested. Here, we demonstrate the role of mineral binding in preserving the protein sequence in ostrich (Struthionidae) eggshell, including from the palaeontological sites of Laetoli (3.8 Ma) and Olduvai Gorge (1.3 Ma) in Tanzania. By tracking protein diagenesis back in time we find consistent patterns of preservation, demonstrating authenticity of the surviving sequences. Molecular dynamics simulations of struthiocalcin-1 and -2, the dominant proteins within the eggshell, reveal that distinct domains bind to the mineral surface. It is the domain with the strongest calculated binding energy to the calcite surface that is selectively preserved. Thermal age calculations demonstrate that the Laetoli and Olduvai peptides are 50 times older than any previously authenticated sequence (equivalent to ~16 Ma at a constant 10°C). DOI: http://dx.doi.org/10.7554/eLife.17092.001 PMID:27668515

  11. Iron-sulfur Proteins Are the Major Source of Protein-bound Dinitrosyl Iron Complexes Formed in Escherichia coli Cells under Nitric Oxide Stress

    OpenAIRE

    Landry, Aaron P.; Duan, Xuewu; Huang, Hao; Ding, Huangen

    2011-01-01

    Protein-bound dinitrosyl iron complexes (DNICs) have been observed in prokaryotic and eukaryotic cells under nitric oxide (NO) stress. The identity of proteins that bind DNICs, however, still remains elusive. Here we demonstrate that iron-sulfur proteins are the major source of protein-bound DNICs formed in Escherichia coli cells under NO stress. Expression of recombinant iron-sulfur proteins, but not the proteins without iron-sulfur clusters, almost doubles the amount of protein-bound DNICs ...

  12. Superoxide dismutase activity of Cu-bound prion protein

    Science.gov (United States)

    Hodak, Miroslav; Lu, Wenchang; Bernholc, Jerry

    2009-03-01

    Misfolding of the prion protein, PrP, has been linked to a group of neurodegenerative diseases, including the mad cow disease in cattle and the Creutzfeldt-Jakob disease in humans. The normal function of PrP is still unknown, but it was found that the PrP can efficiently bind Cu(II) ions. Early experiments suggested that Cu-PrP complex possesses significant superoxide dismutase (SOD) activity, but later experiments failed to confirm it and at present this issue remains unresolved. Using a recently developed hybrid DFT/DFT method, which combines Kohn-Sham DFT for the solute and its first solvation shells with orbital-free DFT for the remainder of the solvent, we have investigated SOD activity of PrP. The PrP is capable of incorporating Cu(II) ions in several binding modes and our calculations find that each mode has a different SOD activity. The highest activity found is comparable to those of well-known SOD proteins, suggesting that the conflicting experimental results may be due to different bindings of Cu(II) in those experiments.

  13. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  14. Dimer model for Tau proteins bound in microtubule bundles

    Science.gov (United States)

    Hall, Natalie; Kluber, Alexander; Hayre, N. Robert; Singh, Rajiv; Cox, Daniel

    2013-03-01

    The microtubule associated protein tau is important in nucleating and maintaining microtubule spacing and structure in neuronal axons. Modification of tau is implicated as a later stage process in Alzheimer's disease, but little is known about the structure of tau in microtubule bundles. We present preliminary work on a proposed model for tau dimers in microtubule bundles (dimers are the minimal units since there is one microtubule binding domain per tau). First, a model of tau monomer was created and its characteristics explored using implicit solvent molecular dynamics simulation. Multiple simulations yield a partially collapsed form with separate positively/negatively charged clumps, but which are a factor of two smaller than required by observed microtubule spacing. We argue that this will elongate in dimer form to lower electrostatic energy at a cost of entropic ``spring'' energy. We will present preliminary results on steered molecular dynamics runs on tau dimers to estimate the actual force constant. Supported by US NSF Grant DMR 1207624.

  15. Preparation of iron bound succinylated milk protein concentrate and evaluation of its stability.

    Science.gov (United States)

    Shilpashree, B G; Arora, Sumit; Sharma, Vivek; Bajaj, Rajesh Kumar; Tomar, S K

    2016-04-01

    Major problems associated with the fortification of soluble iron salts include chemical reactivity and incompatibility with other components. Milk protein concentrate (MPC) are able to bind significant amount of iron due to the presence of both casein and whey protein. MPC in its native state possess very poor solubility, therefore, succinylated derivatives of MPC (succ. MPC) were also used for the preparation of protein-iron complex. Preparation of the complex involved centrifugation (to remove insoluble iron), ultrafiltration (to remove unbound iron) and lyophilisation (to attain in dry form). Iron binding ability of MPC enhanced significantly (P<0.05) upon succinylation. Stability of bound iron from both varieties of complexes was monitored under different conditions encountered during processing. Higher stability (P<0.05) of bound iron was observed in succ. MPC-iron complex than native protein complex. This method could be adopted for the production of stable iron enriched protein, an organic iron source.

  16. Identification of proteins bound to a thioaptamer probe on a proteomics array

    International Nuclear Information System (INIS)

    A rapid method to screen and identify unknown bound proteins to specific nucleic acid probes anchored on ProteinChip array surfaces from crude biological samples has been developed in this paper. It was demonstrated with screening specific binding proteins from LPS-stimulated mouse 70Z/3 pre-B cell nuclear extracts by direct coupling of thioaptamer XBY-S2 to the pre-activated ProteinChip array surfaces. With pre-fractionation of crude nuclear extracts by ion exchange method, specific 'on-chip' captured proteins have been obtained that were pure enough to do 'on-chip' digestion and the subsequent identification of the 'on-chip' bound proteins by microsequencing of the trypsin digested peptide fragments through tandem MS. Five mouse heterogeneous nuclear ribonucleoproteins (hnRNPs) A1, A2/B1, A3, A/B, and D0 were identified. To verify those bound hnRNPs, a novel thioaptamer/antibody sandwich assay provides highly sensitive and selective identification of proteins on ProteinChip arrays

  17. Computational Protein Design Using AND/OR Branch-and-Bound Search.

    Science.gov (United States)

    Zhou, Yichao; Wu, Yuexin; Zeng, Jianyang

    2016-06-01

    The computation of the global minimum energy conformation (GMEC) is an important and challenging topic in structure-based computational protein design. In this article, we propose a new protein design algorithm based on the AND/OR branch-and-bound (AOBB) search, a variant of the traditional branch-and-bound search algorithm, to solve this combinatorial optimization problem. By integrating with a powerful heuristic function, AOBB is able to fully exploit the graph structure of the underlying residue interaction network of a backbone template to significantly accelerate the design process. Tests on real protein data show that our new protein design algorithm is able to solve many problems that were previously unsolvable by the traditional exact search algorithms, and for the problems that can be solved with traditional provable algorithms, our new method can provide a large speedup by several orders of magnitude while still guaranteeing to find the global minimum energy conformation (GMEC) solution. PMID:27167301

  18. Proteomic Analysis to Identify Tightly-Bound Cell Wall Protein in Rice Calli

    OpenAIRE

    Cho, Won Kyong; Hyun, Tae Kyung; Kumar, Dhinesh; Rim, Yeonggil; Chen, Xiong Yan; Jo, Yeonhwa; Kim, Suwha; Lee, Keun Woo; Park, Zee-Yong; Lucas, William J.; Kim, Jae-Yean

    2015-01-01

    Rice is a model plant widely used for basic and applied research programs. Plant cell wall proteins play key roles in a broad range of biological processes. However, presently, knowledge on the rice cell wall proteome is rudimentary in nature. In the present study, the tightly-bound cell wall proteome of rice callus cultured cells using sequential extraction protocols was developed using mass spectrometry and bioinformatics methods, leading to the identification of 1568 candidate proteins. Ba...

  19. Structure of an Intrinsically Disordered Stress Protein Alone and Bound to a Membrane Surface.

    Science.gov (United States)

    Atkinson, John; Clarke, Matthew W; Warnica, Josephine M; Boddington, Kelly F; Graether, Steffen P

    2016-08-01

    Dehydrins are a group of intrinsically disordered proteins that protect plants from damage caused by drought, cold, and high salinity. Like other intrinsically disordered proteins, dehydrins can gain structure when bound to a ligand. Previous studies have shown that dehydrins are able to protect liposomes from cold damage, but the interactions that drive membrane binding and the detailed structure of the bound and unbound forms are not known. We use an ensemble-structure approach to generate models of a dehydrin known as K2 in the presence and absence of sodium dodecyl sulfate micelles, and we docked the bound structure to the micelle. The collection of residual dipolar coupling data, amide protection factors, and paramagnetic relaxation enhancement distances, in combination with chemical shifts and relaxation measurements, allows for determining plausible structures that are not otherwise visible in time-averaged structural data. The results show that in the bound structure, the conserved lysines are important for membrane binding, whereas the flanking hydrophobic residues play a lesser role. The unbound structure shows a high level of disorder and an extended structure. We propose that the structural differences between bound and unbound forms allow dehydrins to act as molecular shields in their unbound state and as membrane protectants in their bound state. Unlike α-synuclein, the significant gain of α-helicity in K2 at low concentrations of sodium dodecyl sulfate is not due to a decrease in the critical micelle concentration. The study provides structural insight into how a disordered protein can interact with a membrane surface. PMID:27508433

  20. Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy

    Directory of Open Access Journals (Sweden)

    Yasuyuki Goto, Takafumi Ando, Kazuko Nishio, Sayo Kawai, Yoshiko Ishida, Mariko Naito, Hidemi Goto, Nobuyuki Hamajima

    2007-01-01

    Full Text Available Background: Various single nucleotide polymorphisms (SNPs have explained the association between Helicobacter pylori (H. pylori and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1 polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2 and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. Methods: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345 was examined for 454 Japanese health checkup examinees (126 males and 328 females aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients (134 males and 68 females aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. Results: The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI: 0.08-0.71. Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40. Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90 relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66. Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. Conclusions: This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These findings require confirmation in much larger studies.

  1. Evidence against the involvement of ionically bound cell wall proteins in pea epicotyl growth

    Science.gov (United States)

    Melan, M. A.; Cosgrove, D. J.

    1988-01-01

    Ionically bound cell wall proteins were extracted from 7 day old etiolated pea (Pisum sativum L. cv Alaska) epicotyls with 3 molar LiCl. Polyclonal antiserum was raised in rabbits against the cell wall proteins. Growth assays showed that treatment of growing region segments (5-7 millimeters) of peas with either dialyzed serum, serum globulin fraction, affinity purified immunoglobulin, or papain-cleaved antibody fragments had no effect on growth. Immunofluorescence microscopy confirmed antibody binding to cell walls and penetration of the antibodies into the tissues. Western blot analysis, immunoassay results, and affinity chromatography utilizing Sepharose-bound antibodies confirmed recognition of the protein preparation by the antibodies. Experiments employing in vitro extension as a screening measure indicated no effect upon extension by antibodies, by 50 millimolar LiCl perfusion of the apoplast or by 3 molar LiCl extraction. Addition of cell wall protein to protease pretreated segments did not restore extension nor did addition of cell wall protein to untreated segments increase extension. It is concluded that, although evidence suggests that protein is responsible for the process of extension, the class(es) of proteins which are extracted from pea cell walls with 3 molar LiCl are probably not involved in this process.

  2. Multivalent binding and facilitated diffusion account for the formation of the Grb2-Sos1 signaling complex in a cooperative manner.

    Science.gov (United States)

    McDonald, Caleb B; Balke, Jordan E; Bhat, Vikas; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Farooq, Amjad

    2012-03-13

    Despite its key role in driving cellular growth and proliferation through receptor tyrosine kinase (RTK) signaling, the Grb2-Sos1 macromolecular interaction remains poorly understood in mechanistic terms. Herein, using an array of biophysical methods, we provide evidence that although the Grb2 adaptor can potentially bind to all four PXψPXR motifs (designated herein S1-S4) located within the Sos1 guanine nucleotide exchange factor, the formation of the Grb2-Sos1 signaling complex occurs with a 2:1 stoichiometry. Strikingly, such bivalent binding appears to be driven by the association of the Grb2 homodimer to only two of four potential PXψPXR motifs within Sos1 at any one time. Of particular interest is the observation that of a possible six pairwise combinations in which S1-S4 motifs may act in concert for the docking of the Grb2 homodimer through bivalent binding, only S1 and S3, S1 and S4, S2 and S4, and S3 and S4 do so, while pairwise combinations of sites S1 and S2 and sites S2 and S3 appear to afford only monovalent binding. This salient observation implicates the role of local physical constraints in fine-tuning the conformational heterogeneity of the Grb2-Sos1 signaling complex. Importantly, the presence of multiple binding sites within Sos1 appears to provide a physical route for Grb2 to hop in a flip-flop manner from one site to the next through facilitated diffusion, and such rapid exchange forms the basis of positive cooperativity driving the bivalent binding of Grb2 to Sos1 with high affinity. Collectively, our study sheds new light on the assembly of a key macromolecular signaling complex central to cellular machinery in health and disease. PMID:22360309

  3. Characterization of a major 31-kilodalton peptidoglycan-bound protein of Legionella pneumophila

    International Nuclear Information System (INIS)

    A 31-kilodalton (kDa) protein was solubilized from the peptidoglycan (PG) fraction of Legionella pneumophila after treatment with either N-acetylmuramidase from the fungus Chalaropsis sp. or with mutanolysin from Streptomyces globisporus. The protein exhibited a ladderlike banding pattern by autoradiography when radiolabeled [(35S]cysteine or [35S]methionine) PG material was extensively treated with hen lysozyme. The banding patterns ranging between 31 and 45 kDa and between 55 and 60 kDa resolved as a single 31-kDa protein when the material was subsequently treated with N-acetylmuramidase. Analysis of the purified 31-kDa protein for diaminopimelic acid by gas chromatography revealed 1 mol of diaminopimelic acid per mol of protein. When outer membrane PG material containing the major outer membrane porin protein was treated with N-acetylmuramidase or mutanolysin, both the 28.5-kDa major outer membrane protein and the 31-kDa protein were solubilized from the PG material under reducing conditions. In the absence of 2-mercaptoethanol, a high-molecular-mass complex (100 kDa) was resolved. The results of this study indicate that a 31-kDa PG-bound protein is a major component of the cell wall of L. pneumophila whose function may be to anchor the major outer membrane protein to PG. Finally, a survey of other Legionella species and other serogroups of L. pneumophila suggested that PG-bound proteins may be a common feature of this genus

  4. A Branch and Bound Algorithm for the Protein Folding Problem in the HP Lattice Model

    Institute of Scientific and Technical Information of China (English)

    Mao Chen; Wen-Qi Huang

    2005-01-01

    A branch and bound algorithm is proposed for the two-dimensional protein folding problem in the HP lattice model. In this algorithm, the benefit of each possible location of hydrophobic monomers is evaluated and only promising nodes are kept for further branching at each level. The proposed algorithm is compared with other well-known methods for 10 benchmark sequences with lengths ranging from 20 to 100 monomers. The results indicate that our method is a very efficient and promising tool for the protein folding problem.

  5. Appraisal of the Missing Proteins Based on the mRNAs Bound to Ribosomes.

    Science.gov (United States)

    Xu, Shaohang; Zhou, Ruo; Ren, Zhe; Zhou, Baojin; Lin, Zhilong; Hou, Guixue; Deng, Yamei; Zi, Jin; Lin, Liang; Wang, Quanhui; Liu, Xin; Xu, Xun; Wen, Bo; Liu, Siqi

    2015-12-01

    Considering the technical limitations of mass spectrometry in protein identification, the mRNAs bound to ribosomes (RNC-mRNA) are assumed to reflect the mRNAs participating in the translational process. The RNC-mRNA data are reasoned to be useful for appraising the missing proteins. A set of the multiomics data including free-mRNAs, RNC-mRNAs, and proteomes was acquired from three liver cancer cell lines. On the basis of the missing proteins in neXtProt (release 2014-09-19), the bioinformatics analysis was carried out in three phases: (1) finding how many neXtProt missing proteins have or do not have RNA-seq and/or MS/MS evidence, (2) analyzing specific physicochemical and biological properties of the missing proteins that lack both RNA-seq and MS/MS evidence, and (3) analyzing the combined properties of these missing proteins. Total of 1501 missing proteins were found by neither RNC-mRNA nor MS/MS in the three liver cancer cell lines. For these missing proteins, some are expected higher hydrophobicity, unsuitable detection, or sensory functions as properties at the protein level, while some are predicted to have nonexpressing chromatin structures on the corresponding gene level. With further integrated analysis, we could attribute 93% of them (1391/1501) to these causal factors, which result in the expression products scarcely detected by RNA-seq or MS/MS.

  6. Rep provides a second motor at the replisome to promote duplication of protein-bound DNA.

    Science.gov (United States)

    Guy, Colin P; Atkinson, John; Gupta, Milind K; Mahdi, Akeel A; Gwynn, Emma J; Rudolph, Christian J; Moon, Peter B; van Knippenberg, Ingeborg C; Cadman, Chris J; Dillingham, Mark S; Lloyd, Robert G; McGlynn, Peter

    2009-11-25

    Nucleoprotein complexes present challenges to genome stability by acting as potent blocks to replication. One attractive model of how such conflicts are resolved is direct targeting of blocked forks by helicases with the ability to displace the blocking protein-DNA complex. We show that Rep and UvrD each promote movement of E. coli replisomes blocked by nucleoprotein complexes in vitro, that such an activity is required to clear protein blocks (primarily transcription complexes) in vivo, and that a polarity of translocation opposite that of the replicative helicase is critical for this activity. However, these two helicases are not equivalent. Rep but not UvrD interacts physically and functionally with the replicative helicase. In contrast, UvrD likely provides a general means of protein-DNA complex turnover during replication, repair, and recombination. Rep and UvrD therefore provide two contrasting solutions as to how organisms may promote replication of protein-bound DNA. PMID:19941825

  7. Membrane-bound complement regulatory proteins as biomarkers and potential therapeutic targets for SLE.

    Science.gov (United States)

    Das, Nibhriti; Biswas, Bintili; Khera, Rohan

    2013-01-01

    For the last two decades, there had been remarkable advancement in understanding the role of complement regulatory proteins in autoimmune disorders and importance of complement inhibitors as therapeutics. Systemic lupus erythematosus is a prototype of systemic autoimmune disorders. The disease, though rare, is potentially fatal and afflicts women at their reproductive age. It is a complex disease with multiorgan involvement, and each patient presents with a different set of symptoms. The diagnosis is often difficult and is based on the diagnostic criteria set by the American Rheumatology Association. Presence of antinuclear antibodies and more specifically antidouble-stranded DNA indicates SLE. Since the disease is multifactorial and its phenotypes are highly heterogeneous, there is a need to identify multiple noninvasive biomarkers for SLE. Lack of validated biomarkers for SLE disease activity or response to treatment is a barrier to the efficient management of the disease, drug discovery, as well as development of new therapeutics. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins (CRPs) may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Case-controlled and followup studies carried out in our laboratory suggest an intimate relation between the level of DAF, MCP, CR1, and CD59 transcripts and the disease activity in SLE. Based on comparative evaluation of our data on these four membrane-bound complement regulatory proteins, we envisaged CR1 and MCP transcripts as putative noninvasive disease activity markers and the respective proteins as therapeutic targets for SLE. Following is a brief appraisal on membrane-bound complement regulatory proteins DAF, MCP, CR1, and CD59 as biomarkers and therapeutic targets for SLE. PMID:23402019

  8. Mineral and Protein-Bound Water and Latching Action Control Mechanical Behavior at Protein-Mineral Interfaces in Biological Nanocomposites

    Directory of Open Access Journals (Sweden)

    Pijush Ghosh

    2008-01-01

    Full Text Available The nacre structure consists of laminated interlocked mineral platelets separated by nanoscale organic layers. Here, the role of close proximity of mineral to the proteins on mechanical behavior of the protein is investigated through steered molecular dynamics simulations. Our simulations indicate that energy required for unfolding protein in the proximity of mineral aragonite is several times higher than that for isolated protein in the absence of the mineral. Here, we present details of specific mechanisms which result in higher energy for protein unfolding in the proximity of mineral. At the early stage of pulling, peaks in the load-displacement (LD plot at mineral proximity are quantitatively correlated to the interaction energy between atoms involved in the latching phenomenon of amino acid side chain to aragonite surface. Water plays an important role during mineral and protein interaction and water molecules closer to the mineral surface are highly oriented and remain rigidly attached as the protein strand is pulled. Also, the high magnitude of load for a given displacement originates from attractive interactions between the protein, protein-bound water, and mineral. This study provides an insight into mineral-protein interactions that are predominant in biological nanocomposites and also provides guidelines towards design of biomimetic nanocomposites.

  9. Bound water at protein-protein interfaces: partners, roles and hydrophobic bubbles as a conserved motif.

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    Mostafa H Ahmed

    Full Text Available BACKGROUND: There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. METHODOLOGY: A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. RESULTS: The water molecules were found to be involved in: a (bridging interactions with both proteins (21%, b favorable interactions with only one protein (53%, and c no interactions with either protein (26%. This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins' interaction (-0.46 kcal mol(-1, but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol(-1. Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å(2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or "hydrophobic bubbles". Such water molecules may have an important biological purpose in mediating protein-protein interactions.

  10. Measuring binding of protein to gel-bound ligands using magnetic levitation.

    Science.gov (United States)

    Shapiro, Nathan D; Mirica, Katherine A; Soh, Siowling; Phillips, Scott T; Taran, Olga; Mace, Charles R; Shevkoplyas, Sergey S; Whitesides, George M

    2012-03-28

    This paper describes the use of magnetic levitation (MagLev) to measure the association of proteins and ligands. The method starts with diamagnetic gel beads that are functionalized covalently with small molecules (putative ligands). Binding of protein to the ligands within the bead causes a change in the density of the bead. When these beads are suspended in a paramagnetic aqueous buffer and placed between the poles of two NbFeB magnets with like poles facing, the changes in the density of the bead on binding of protein result in changes in the levitation height of the bead that can be used to quantify the amount of protein bound. This paper uses a reaction-diffusion model to examine the physical principles that determine the values of rate and equilibrium constants measured by this system, using the well-defined model system of carbonic anhydrase and aryl sulfonamides. By tuning the experimental protocol, the method is capable of quantifying either the concentration of protein in a solution, or the binding affinities of a protein to several resin-bound small molecules simultaneously. Since this method requires no electricity and only a single piece of inexpensive equipment, it may find use in situations where portability and low cost are important, such as in bioanalysis in resource-limited settings, point-of-care diagnosis, veterinary medicine, and plant pathology. It still has several practical disadvantages. Most notably, the method requires relatively long assay times and cannot be applied to large proteins (>70 kDa), including antibodies. The design and synthesis of beads with improved characteristics (e.g., larger pore size) has the potential to resolve these problems. PMID:22364170

  11. Scanning a DNA molecule for bound proteins using hybrid magnetic and optical tweezers.

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    Marijn T J van Loenhout

    Full Text Available The functional state of the genome is determined by its interactions with proteins that bind, modify, and move along the DNA. To determine the positions and binding strength of proteins localized on DNA we have developed a combined magnetic and optical tweezers apparatus that allows for both sensitive and label-free detection. A DNA loop, that acts as a scanning probe, is created by looping an optically trapped DNA tether around a DNA molecule that is held with magnetic tweezers. Upon scanning the loop along the λ-DNA molecule, EcoRI proteins were detected with ~17 nm spatial resolution. An offset of 33 ± 5 nm for the detected protein positions was found between back and forwards scans, corresponding to the size of the DNA loop and in agreement with theoretical estimates. At higher applied stretching forces, the scanning loop was able to remove bound proteins from the DNA, showing that the method is in principle also capable of measuring the binding strength of proteins to DNA with a force resolution of 0.1 pN/[Formula: see text]. The use of magnetic tweezers in this assay allows the facile preparation of many single-molecule tethers, which can be scanned one after the other, while it also allows for direct control of the supercoiling state of the DNA molecule, making it uniquely suitable to address the effects of torque on protein-DNA interactions.

  12. Study of the protein-bound fraction of calcium, iron, magnesium and zinc in bovine milk

    Science.gov (United States)

    Silva, Fernando V.; Lopes, Gisele S.; Nóbrega, Joaquim A.; Souza, Gilberto B.; Nogueira, Ana Rita A.

    2001-10-01

    Two approaches were used to study the interaction of Ca, Fe, Mg and Zn with bovine milk proteins by inductively coupled plasma optical emission spectrometry (ICPOES). Selective separations in bovine milk samples were accomplished employing an acid protein precipitation using 100 g l -1 trichloroacetic acid (TCA), and an enzymatic protein hydrolysis using 50 g l -1 pepsin (PEP) solution, respectively. The results were compared with total mineral contents determined after microwave-assisted acid digestion. The results obtained by enzymatic and acid precipitation evidenced the different interaction forms of Ca, Fe, Mg and Zn in the system formed by milk components. Iron was not solubilized by the TCA treatment, but was recovered completely after the enzymatic treatment. Quantitative recoveries of Ca, Mg and Zn were obtained using both approaches, showing that these analytes were bound to milk compounds affected by either treatment. Calcium, Mg and Zn are mainly associated with colloidal calcium phosphate and Fe is bound to the backbone of the casein polypeptide chain, cleaved by pepsin enzyme. The proposed approaches could be used to assess the complexity of these chemical interactions.

  13. Protein-bound solute removal during extended multipass versus standard hemodialysis

    DEFF Research Database (Denmark)

    Eloot, Sunny; Van Biesen, Wim; Axelsen, Mette;

    2015-01-01

    BACKGROUND: Multipass hemodialysis (MPHD) is a recently described dialysis modality, involving the use of small volumes of dialysate which are repetitively recycled. Dialysis regimes of 8 hours for six days a week using this device result in an increased removal of small water soluble solutes...... and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well. METHODS: A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD...

  14. pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins.

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    Priyanka Prakash

    2015-10-01

    Full Text Available Probe-based or mixed solvent molecular dynamics simulation is a useful approach for the identification and characterization of druggable sites in drug targets. However, thus far the method has been applied only to soluble proteins. A major reason for this is the potential effect of the probe molecules on membrane structure. We have developed a technique to overcome this limitation that entails modification of force field parameters to reduce a few pairwise non-bonded interactions between selected atoms of the probe molecules and bilayer lipids. We used the resulting technique, termed pMD-membrane, to identify allosteric ligand binding sites on the G12D and G13D oncogenic mutants of the K-Ras protein bound to a negatively charged lipid bilayer. In addition, we show that differences in probe occupancy can be used to quantify changes in the accessibility of druggable sites due to conformational changes induced by membrane binding or mutation.

  15. Structure of Rotavirus Outer-Layer Protein VP7 Bound with a Neutralizing Fab

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Scott T.; Settembre, Ethan C.; Trask, Shane D.; Greenberg, Harry B.; Harrison, Stephen C.; Dormitzer, Philip R.; (Stanford-MED); (CH-Boston)

    2009-06-17

    Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca{sup 2+}) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca{sup 2+} sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.

  16. Crystallization, dehydration and preliminary X-ray analysis of excisionase (Xis) proteins cooperatively bound to DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sam, My D.; Abbani, Mohamad A.; Cascio, Duilio [Department of Chemistry and Biochemistry and the UCLA-DOE Center for Genomics and Proteomics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1570 (United States); Johnson, Reid C. [Department of Biological Chemistry, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-1737 (United States); Clubb, Robert T., E-mail: rclubb@mbi.ucla.edu [Department of Chemistry and Biochemistry and the UCLA-DOE Center for Genomics and Proteomics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1570 (United States)

    2006-08-01

    This paper describes the crystallization, dehydration and preliminary X-ray data analysis of a complex containing several bacteriophage lambda excisionase (Xis) proteins cooperatively bound to a 33-mer DNA duplex (Xis–DNA{sup X1-X2}). This paper describes the crystallization, dehydration and preliminary X-ray data analysis of a complex containing several bacteriophage lambda excisionase (Xis) [Bushman et al. (1984 ▶). Cell, 39, 699–706] proteins cooperatively bound to a 33-mer DNA duplex (Xis–DNA{sup X1-X2}). Xis is expected to recognize this regulatory element in a novel manner by cooperatively binding and distorting multiple head-to-tail orientated DNA-binding sites. Crystals of this complex belonged to space group P3{sub 1}21 or P3{sub 2}21, with unit-cell parameters a = b = 107.7, c = 73.5 Å, α = β = 90, γ = 120°. Based on the unit-cell parameters for the asymmetric unit, V{sub M} is 3.0 Å{sup 3} Da{sup −1}, which corresponds to a solvent content of ∼59%. The approaches used to crystallize the unusually long DNA fragment in the complex and the dehydration technique applied that dramatically improved the diffraction of the crystals from 10 to 2.6 Å are discussed.

  17. Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas

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    Matsutani Tomoo

    2012-10-01

    Full Text Available Abstract Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1 was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.

  18. Phosphorylation Regulates the Bound Structure of an Intrinsically Disordered Protein: The p53-TAZ2 Case.

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    Raúl Esteban Ithuralde

    Full Text Available Disordered regions and Intrinsically Disordered Proteins (IDPs are involved in critical cellular processes and may acquire a stable three-dimensional structure only upon binding to their partners. IDPs may follow a folding-after-binding process, known as induced folding, or a folding-before-binding process, known as conformational selection. The transcription factor p53 is involved in the regulation of cellular events that arise upon stress or DNA damage. The p53 domain structure is composed of an N-terminal transactivation domain (p53TAD, a DNA Binding Domain and a tetramerization domain. The activity of TAD is tightly regulated by interactions with cofactors, inhibitors and phosphorylation. To initiate transcription, p53TAD binds to the TAZ2 domain of CBP, a co-transcription factor, and undergoes a folding and binding process, as revealed by the recent NMR structure of the complex. The activity of p53 is regulated by phosphorylation at multiple sites on the TAD domain and recent studies have shown that modifications at three residues affect the binding towards TAZ2. However, we still do not know how these phosphorylations affect the structure of the bound state and, therefore, how they regulate the p53 function. In this work, we have used computational simulations to understand how phosphorylation affects the structure of the p53TAD:TAZ2 complex and regulates the recognition mechanism. Phosphorylation has been proposed to enhance binding by direct interaction with the folded protein or by changing the unbound conformation of IDPs, for example by pre-folding the protein favoring the recognition mechanism. Here, we show an interesting turn in the p53 case: phosphorylation mainly affects the bound structure of p53TAD, highlighting the complexity of IDP protein-protein interactions. Our results are in agreement with previous experimental studies, allowing a clear picture of how p53 is regulated by phosphorylation and giving new insights into how

  19. A photophysical study of two fluorogen-activating proteins bound to their cognate fluorogens

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotto, Tiziano [Los Alamos National Laboratory; Nguyen, Hau B [Los Alamos National Laboratory; Jung, Jaemyeong [Los Alamos National Laboratory; Bradbury, Andrew M [Los Alamos National Laboratory; Gnanakaran, S. [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory; Waldo, Geoffrey S [Los Alamos National Laboratory; Goodwin, Peter M [Los Alamos National Laboratory

    2010-12-14

    We are exploring the feasibility of using recently developed flu orogen-activating proteins (FAPs) as reporters for single-molecule imaging. FAPs are single-chain antibodies choosen to specifically bind small chromophoric molecules termed f1uorogens. Upon binding to its cognate FAP the fluorescence quantum yield of the fluorogen can increase substantially giving rise to a fluorescent complex. Based on the seminal work of Szent-Gyorgyi et al. (Nature Biotechnology, Volume 26, Number 2, pp 235-240, 2008) we have chosen to study two fluorogen-activating single-chain antibodies, HL 1.0.1-TOI and H6-MG bound to their cognate fluorogens, thiazole orange and malachite green derivatives, respectively. Here we use fluorescence correlation spectroscopy study the photophysics of these fluorescent complexes.

  20. Characterization of the yellow fever mosquito sterol carrier protein-2 like 3 gene and ligand-bound protein structure

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, David H.; Vyazunova, Irina; Lorch, Jeffery M.; Forest, Katrina T.; Lan, Que; (UW)

    2009-06-12

    The sterol carrier protein-2 like 3 gene (AeSCP-2L3), a new member of the SCP-2 protein family, is identified from the yellow fever mosquito, Aedes aegypti. The predicted molecular weight of AeSCP-2L3 is 13.4 kDa with a calculated pI of 4.98. AeSCP-2L3 transcription occurs in the larval feeding stages and the mRNA levels decrease in pupae and adults. The highest levels of AeSCP-2L3 gene expression are found in the body wall, and possibly originated in the fat body. This is the first report of a mosquito SCP-2-like protein with prominent expression in tissue other than the midgut. The X-ray protein crystal structure of AeSCP-2L3 reveals a bound C16 fatty acid whose acyl tail penetrates deeply into a hydrophobic cavity. Interestingly, the ligand-binding cavity is slightly larger than previously described for AeSCP-2 (Dyer et al. J Biol Chem 278:39085-39091, 2003) and AeSCP-2L2 (Dyer et al. J Lipid Res M700460-JLR200, 2007). There are also an additional 10 amino acids in SCP-2L3 that are not present in other characterized mosquito SCP-2s forming an extended loop between {beta}3 and {beta}4. Otherwise, the protein backbone is exceedingly similar to other SCP-2 and SCP-2-like proteins. In contrast to this observed high structural homology of members in the mosquito SCP2 family, the amino acid sequence identity between the members is less than 30%. The results from structural analysis imply that there have been evolutionary constraints that favor the SCP-2 C{alpha} backbone fold while the specificity of ligand binding can be altered.

  1. The influence of a Grb2 inhibitor on K562 cell growth%Grb2抑制剂对K562细胞生长增生的影响

    Institute of Scientific and Technical Information of China (English)

    叶韵斌; 陈强; 林建银; 刘枋; LIU wang-qing; Michel VIDAL; Christiane GARBAY

    2008-01-01

    Objective To analyze the effects of an inhibitor of the SH3 (Src homology) domains of Grb2 on the growth and proliferation of K562 cells. Methods The peptidimer [(VPPPVPPRRR)2-K], penetratin (RQIKIWFQNRRMKWKK) and peptidimer-c [poptidimer linked to penetratin: (VPPPVPPRRR)2-K-Aha-RQIKIWFQNRRMKWKK] were synthesized by solid-phase synthesis using Fmoc chemistry, and purified by high performance liquid chromatography (HPLC) on a C18 column. Purity was evaluated by HPLC, and the identity of the peptides was checked by electrospray mass spectroscopy (MS). A pull-down assay was used to observe the specific binding of peptidimer-c to the Grb2 of K562 cell lysates. The inhibition of peptidimer-c on K562 cell proliferation was evaluated by trypan blue exclusion assay, the cytostatic effect was tested by clonogenic assay, and the cytotoxicity was examined by WST-1 method. A further experiment was performed with clonogenic assay to analyze the co-effect of peptidimer-c respectively combined with Gleevec, Hydroxyurea and Cytarabine by Jing's method. Results The HPLC analysis showed only a simple peak, which means that the peptide is in high purity. MS analysis showed the peptides were coincided with the design. The molecular weight of peptidimer-c was of 4794.0 and that of the penetratin 2246.7. Pull-down assay demonstrated that the peptidimer-c, not the penetratin, could bind to Grb2 specifically. The trypan blue assay showed that the peptidimer-c could inhibit the proliferation of K562 significantly in a dose-dependent manner, even 3~6 h after the cells were exposed to the drug, and penetratin alone did not influence the cell proliferation. Gleevec inhibited the growth of K562 not only in a dose-dependent manner, but also in a time-dependent manner. WST-1 test showed the cytotoxieity of peptidimer-c or Gleevec on K562 cells, the IC50 of peptidimer-c was (17±2) μmol/L and the IC50 of Gleevec was (0.25±0.05) μmol/L. In the methylcellulose semi-solid medium system, the

  2. Thiols screened by the neocarzinostatin protein for preserving or detoxifying its bound enediyne antibiotic.

    Science.gov (United States)

    Chi, Hung-Wen; Huang, Chun-Chi; Chin, Der-Hang

    2012-05-14

    Neocarzinostatin is an antibiotic chromoprotein produced by Streptomyces carzinostaticus. Its enediyne-containing chromophore exhibits high DNA cleavage activity and belongs to one of the most potent categories of antitumor agents. The labile chromophore is readily inactivated by environmental thiols including the most abundant glutathione. How the microorganism preserves the secreted antibiotic and at the same time is immune to its toxicity are of interest. Site-directed mutagenesis studies of the neocarzinostatin protein have shown that residues D33 and D99 play primary and secondary roles, respectively, in preserving neocarzinostatin from acidic glutathione whereas D79 and other residues around the opening of the binding cleft have an insignificant effect. Biothiol analyses revealed that cells of S. carzinostaticus produced no glutathione, but instead neutral mycothiol, which is known to serve functions analogous to glutathione. Mycothiol was the only neutral-charged thiol produced by the organism; all other identified biothiols carried at least partial negative charges. When the bacteria were cultured under conditions that stimulated the biosynthesis of neocarzinostatin, the yield of mycothiol increased significantly, which suggests mycothiol-dependent cellular detoxification. Treating neocarzinostatin samples with the cell extract that retained active sulfhydryls led to efficient drug inactivation, which indicates that mycothiol is allowed to approach the protein-bound chromophore. The anionic side-chains of D33 and D99 in the neocarzinostatin protein played two critical roles in a single thiol-screening operation: Preserving the antibiotic for defense and survival by rejecting the ubiquitous glutathione through charge-charge repulsion in the outer-cell environment and detoxifying the toxin in the inner-cell body for self-resistance by accepting the cell-produced neutral mycothiol. PMID:22473745

  3. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

    Directory of Open Access Journals (Sweden)

    Christopher J. Petzold

    2013-10-01

    bone cofactor was identified as a lipid containing a ceramide phosphate, a single chained glycerol lipid and a linker. Tendon uses a different cofactor made up of two fatty acid chains linked directly to the phosphate yielding a molecule about half the size. Moreover, adding the tendon factor/cofactor to osteosarcoma cells causes them to stop growing, which is opposite to its role with tendon cells. Thus, the cofactor is cell type specific both in composition and in the triggered response. Further support of its proposed role came from frozen sections from 5 week old mice where an antibody to the factor stained strongly at the growing ends of the tendon as predicted. In conclusion, the molecule needed for cell density signaling is a small protein bound to a unique, tissue-specific phospholipid yielding a membrane associated but diffusible molecule. Signal transduction is postulated to occur by an increased ordering of the plasma membrane as the concentration of this protein/lipid increases with cell density.

  4. Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor.

    Science.gov (United States)

    Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

    2016-06-01

    Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure-function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met-p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc-Grb2-Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

  5. Studying repair of a single protein-bound nick in vivo using the Flp-nick system

    DEFF Research Database (Denmark)

    Nielsen, Ida; Andersen, Anni Hangaard; Bjergbæk, Lotte

    2012-01-01

    The Flp-nick system is a simple in vivo system developed for studying the cellular responses to a protein-bound nick at a single genomic site in the budding yeast Saccharomyces cerevisiae. The Flp-nick system takes advantage of a mutant Flp recombinase that can introduce a nick at a specific Flp ...

  6. Increased protein oxidation and loss of protein-bound sialic acid in hepatic tissues of D-galactose induced aged rats.

    Science.gov (United States)

    Cakatay, Ufuk; Aydın, Seval; Atukeren, Pınar; Yanar, Karolin; Sitar, Mustafa E; Dalo, Enis; Uslu, Ezel

    2013-07-01

    A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not been fully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original research focuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic aging rats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establish mimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonyl groups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialic acid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides) and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young control groups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA (Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our results demonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose- induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, which are pertinent to increased oxidative stress and altered redox homeostasis.

  7. Intraerythrocyte Non-Protein-Bound Iron in Children with Bronchopulmonary Pathology

    Directory of Open Access Journals (Sweden)

    E.M. Vasilyeva

    2014-12-01

    Full Text Available A total of 230 children having bronchopulmonary pathology (BPP were examined. Patients were divided into 4 groups according to their intraerythrocyte non-protein- bound iron (IE-NPBI levels. We investigated the relationship of the IE-NPBI level with parameters of respiratory function (RF tests, the severity of comorbidities, and level of other free intracellular ions, such as copper, zinc, and magnesium. The pronounced increase in IE-NPBI level was typical for patients with the connective tissue dysplasia, often accompanied by mitral valve prolapse, osteopenia, and mineral metabolism violation. The severe comorbid diagnoses were typical for patients with reduced levels of IE-NPBI (chronic cor pulmonale, tuberculosis infection. The largest number of comorbidities, aggravating the underlying disease, took place in the group of patients with a significant reduction in IE-NPBI level. A significant increase in IE-NPBI level, as well as a marked reduction of IE-NPBI level, was an unfavorable factor for the underlying disease. We found a correlation between IE-NPBI level and parameters of RF-test in patients with moderate increase in IE-NPBI level.

  8. Competition between bound and free peptides in an ELISA-based procedure that assays peptides derived from protein digests

    Directory of Open Access Journals (Sweden)

    Pace Umberto

    2006-05-01

    Full Text Available Abstract Background We describe an ELISA-based method that can be used to identify and quantitate proteins in biological samples. In this method, peptides in solution, derived from proteolytic digests of the sample, compete with substrate-attached synthetic peptides for antibodies, also in solution, generated against the chosen peptides. The peptides used for the ELISA are chosen on the basis of their being (i products of the proteolytic (e.g. tryptic digestion of the protein to be identified and (ii unique to the target protein, as far as one can know from the published sequences. Results In this paper we describe the competition assay and we define the optimal conditions for the most effective assay. We have performed an analysis of the kinetics of interaction between the four components of the assay: the plastic substratum to which the peptide is bound, the bound peptide itself, the competing added peptide, and the antibody that is specific for the peptide and we compare the results of theoretical simulations to the actual data in some model systems. Conclusion The data suggest that the peptides bind to the plastic substratum in more than one conformation and that, once bound, the peptide displays different affinities for the antibody, depending on how it has bound to the plate

  9. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo;

    2012-01-01

    ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell......-surface are possibly crucial in these contexts. We here investigated internalization and subsequent recycling or degradation of ADAM12 as a potentially important regulatory mechanism. Our results show that ADAM12 is constitutively internalized primarily via the clathrin-dependent pathway and is subsequently detected...... in both early and recycling endosomes. The protease activity of ADAM12 does not influence this internalization mechanism. Analysis of essential elements for internalization established that proline-rich regions in the cytoplasmic domain of ADAM12, previously shown to interact with Src-homology 3 domains...

  10. Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

    Science.gov (United States)

    Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2014-10-01

    Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

  11. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein.

    Science.gov (United States)

    Klumpp, Klaus; Lam, Angela M; Lukacs, Christine; Vogel, Robert; Ren, Suping; Espiritu, Christine; Baydo, Ruth; Atkins, Kateri; Abendroth, Jan; Liao, Guochun; Efimov, Andrey; Hartman, George; Flores, Osvaldo A

    2015-12-01

    The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target for antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of an antiviral compound bound to the HBV core protein. The compound NVR-010-001-E2 can induce assembly of the HBV core wild-type and Y132A mutant proteins and thermostabilize the proteins with a Tm increase of more than 10 °C. NVR-010-001-E2 binds at the dimer-dimer interface of the core proteins, forms a new interaction surface promoting protein-protein interaction, induces protein assembly, and increases stability. The impact of naturally occurring core protein mutations on antiviral activity correlates with NVR-010-001-E2 binding interactions determined by crystallography. The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein-protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties.

  12. Crystal Structures of SlyA Protein, a Master Virulence Regulator of Salmonella, in Free and DNA-bound States

    Energy Technology Data Exchange (ETDEWEB)

    Dolan, Kyle T.; Duguid, Erica M.; He, Chuan (UC)

    2011-11-17

    SlyA is a master virulence regulator that controls the transcription of numerous genes in Salmonella enterica. We present here crystal structures of SlyA by itself and bound to a high-affinity DNA operator sequence in the slyA gene. SlyA interacts with DNA through direct recognition of a guanine base by Arg-65, as well as interactions between conserved Arg-86 and the minor groove and a large network of non-base-specific contacts with the sugar phosphate backbone. Our structures, together with an unpublished structure of SlyA bound to the small molecule effector salicylate (Protein Data Bank code 3DEU), reveal that, unlike many other MarR family proteins, SlyA dissociates from DNA without large conformational changes when bound to this effector. We propose that SlyA and other MarR global regulators rely more on indirect readout of DNA sequence to exert control over many genes, in contrast to proteins (such as OhrR) that recognize a single operator.

  13. Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase.

    Science.gov (United States)

    Krishnan, Hari B; Chen, Ming-Hsuan

    2013-06-01

    Rice, the staple food of south and east Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16, 26, 33, and 56 kDa have been identified as allergens. Recently, it was documented that the 56 kDa rice allergen was responsible for rice-induced anaphylaxis. The 14-16 kDa allergens have been identified as α-amylase inhibitors; the 26 kDa protein has been identified as α-globulin; and the 33 kDa protein has been identified as glyoxalase I. However, the identity of the 56 kDa rice allergen has not yet been determined. In this study, we demonstrate that serum from patients allergic to maize shows IgE binding to a 56 kDa protein that was present in both maize and rice but not in the oil seeds soybean and peanut. The 56 kDa IgE-binding protein was abundant in the rice endosperm. We have purified this protein from rice endosperm and demonstrated its reactivity to IgE antibodies from the serum of maize-allergic patients. The purified protein was subjected to matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry analysis, resulting in identification of this rice allergen as granule-bound starch synthase, a product of the Waxy gene. Immunoblot analysis using protein extracts from a waxy mutant of rice revealed the absence of the 56 kDa IgE-binding protein. Our results demonstrate that the 56 kDa rice allergen is granule-bound starch synthase and raise the possibility of using waxy mutants of rice as a potential source of the hypoallergenic diet for patients sensitized to the 56 kDa rice allergen.

  14. Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

  15. Native SDS-PAGE: High Resolution Electrophoretic Separation of Proteins With Retention of Native Properties Including Bound Metal Ions

    Science.gov (United States)

    Nowakowski, Andrew B.; Wobig, William J.; Petering, David H.

    2014-01-01

    Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is commonly used to obtain high resolution separation of complex mixtures of proteins. The method initially denatures the proteins that will undergo electrophoresis. Although covalent structural features of resolved proteins can be determined with SDS-PAGE, functional properties are destroyed, including the presence of non-covalently bound metal ions. To address this shortcoming, blue-native (BN)-PAGE has been introduced. This method retains functional properties but at the cost of protein resolving power. To address the need for a high resolution PAGE method that results in the separation of native proteins, experiments tested the impact of changing the conditions of SDS-PAGE on the quality of protein separation and retention of functional properties. Removal of SDS and EDTA from the sample buffer together with omission of a heating step had no effect on the results of PAGE. Reduction of SDS in the running buffer from 0.1% to 0.0375% together with deletion of EDTA also made little impact on the quality of the electrophoretograms of fractions of pig kidney (LLC-PK1) cell proteome in comparison with that achieved with the SDS-PAGE method. The modified conditions were called native (N)SDS-PAGE. Retention of Zn2+ bound in proteomic samples increased from 26 to 98% upon shifting from standard to modified conditions. Moreover, seven of nine model enzymes, including four Zn2+ proteins that were subjected to NSDS-PAGE retained activity. All nine were active in BN-PAGE, whereas all underwent denaturation during SDS-PAGE. Metal retention after electrophoresis was additionally confirmed using laser ablation-inductively coupled plasma-mass spectrometry and in-gel Zn-protein staining using the fluorophore TSQ. PMID:24686569

  16. Effects of solution chemistry and aging time on prion protein adsorption and replication of soil-bound prions.

    Directory of Open Access Journals (Sweden)

    Samuel E Saunders

    Full Text Available Prion interactions with soil may play an important role in the transmission of chronic wasting disease (CWD and scrapie. Prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. We investigated HY TME prion protein (PrP(Sc adsorption to soil minerals in aqueous solutions of phosphate buffered saline (PBS, sodium chloride, calcium chloride, and deionized water using western blotting. The replication efficiency of bound prions following adsorption in these solutions was also evaluated by protein misfolding cyclic amplification (PMCA. Aging studies investigated PrP(Sc desorption and replication efficiency up to one year following adsorption in PBS or DI water. Results indicate that adsorption solution chemistry can affect subsequent prion replication or desorption ability, especially after incubation periods of 30 d or longer. Observed effects were minor over the short-term (7 d or less. Results of long-term aging experiments demonstrate that unbound prions or prions bound to a diverse range of soil surfaces can readily replicate after one year. Our results suggest that while prion-soil interactions can vary with solution chemistry, prions bound to soil could remain a risk for transmitting prion diseases after months in the environment.

  17. Effect of Protein Binding on the Pharmacological Activity of Highly Bound Antibiotics▿

    OpenAIRE

    Schmidt, Stephan; Röck, Katharina; Sahre, Martina; Burkhardt, Olaf; Brunner, Martin; Lobmeyer, Maximilian T.; Derendorf, Hartmut

    2008-01-01

    During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used ...

  18. High throughput identification of monoclonal antibodies to membrane bound and secreted proteins using yeast and phage display.

    Directory of Open Access Journals (Sweden)

    Lequn Zhao

    Full Text Available Antibodies are ubiquitous and essential reagents for biomedical research. Uses of antibodies include quantifying proteins, identifying the temporal and spatial pattern of expression in cells and tissue, and determining how proteins function under normal or pathological conditions. Specific antibodies are only available for a small portion of the proteome, limiting study of those proteins for which antibodies do not exist. The technologies to generate target-specific antibodies need to be improved to obtain high quality antibodies to the proteome at reasonable cost. Here we show that renewable, validated, and standardized monoclonal antibodies can be generated at high throughput, without the need for antigen production or animal immunizations. In this study, 60 protein domains from 24 selected secreted proteins were expressed on the surface of yeast and used for selection of phage antibodies, over 400 monoclonal antibodies were identified within 3 weeks. A subset of these antibodies was validated for binding to cancer cells that overexpress the target protein by flow cytometry or immunohistochemistry. This approach will be applicable to many of the membrane-bound and the secreted proteins, 20-40% of the proteome, accelerating the timeline for Ab generation while reducing the cost.

  19. Major membrane surface proteins of Mycoplasma hyopneumoniae selectively modified by covalently bound lipid

    International Nuclear Information System (INIS)

    Surface protein antigens of Mycoplasma hyopneumoniae were identified by direct antibody-surface binding or by radioimmunoprecipitation of surface 125I-labeled proteins with a series of monoclonal antibodies (MAbs). Radioimmunoprecipitation of TX-114-phase proteins from cells labeled with [35S] methionine, 14C-amino acids, or [3H] palmitic acid showed that proteins p65, p50, and p44 were abundant and (with one other hydrophobic protein, p60) were selectively labeled with lipid. Alkaline hydroxylamine treatment of labeled proteins indicated linkage of lipids by amide or stable O-linked ester bonds. Proteins p65, p50, and p44 were highly immunogenic in the natural host as measured by immunoblots of TX-114-phase proteins with antisera from swine inoculated with whole organisms. These proteins were antigenically and structurally unrelated, since hyperimmune mouse antibodies to individual gel-purified proteins were monospecific and gave distinct proteolytic epitope maps. Intraspecies size variants of one surface antigen of M. hyopneumoniae were revealed by a MAb to p70 (defined in strain J, ATCC 25934), which recognized a large p73 component on strain VPP11 (ATCC 25617). In addition, MAb to internal, aqueous-phase protein p82 of strain J failed to bind an analogous antigen in strain VPP11

  20. Concise and enantioselective synthesis of Fmoc-Pmp(But)2-OH and design of potent Pmp-containing Grb2-SH2 domain antagonists.

    Science.gov (United States)

    Li, Peng; Zhang, Manchao; Peach, Megan L; Liu, Hongpeng; Yang, Dajun; Roller, Peter P

    2003-08-21

    [reaction: see text] L-Phosphonomethylphenylalanine (L-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(Bu(t))(2)-OH was developed in order to incorporate the functionally significant L-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer.

  1. Protein-bound water molecule counting by resolution of (1)H spin-lattice relaxation mechanisms.

    OpenAIRE

    Kiihne, S; Bryant, R G

    2000-01-01

    Water proton spin-lattice relaxation is studied in dilute solutions of bovine serum albumin as a function of magnetic field strength, oxygen concentration, and solvent deuteration. In contrast to previous studies conducted at high protein concentrations, the observed relaxation dispersion is accurately Lorentzian with an effective correlation time of 41 +/- 3 ns when measured at low proton and low protein concentrations to minimize protein aggregation. Elimination of oxygen flattens the relax...

  2. Distribution between protein-bound and free forms of plasma cortisol in the gilt and fetal pig near term.

    Science.gov (United States)

    Kattesh, H G; Baumbach, G A; Gillespie, B B; Schneider, J F; Murai, J T

    1997-01-01

    Thirty-five time-dated pregnant gilts were used to document plasma levels of total and free cortisol, corticosteroid-binding globulin (CBG) binding capacity, and percent distribution of cortisol among protein-bound (CBG and albumin) and free forms in the fetal pig during the last 24 days of gestation. Plasma from fetal pigs on days 110-114 of gestation (gestation length 114 days) had significantly higher levels of total cortisol (p pigs located in the cervical region of the uterus had lower (p pig are directly related and highly similar to those of another precocious species, the sheep.

  3. Chromatin-bound NLS proteins recruit membrane vesicles and nucleoporins for nuclear envelope assembly via importin-α/β

    Institute of Scientific and Technical Information of China (English)

    Quanlong Lu; Zhigang Lu; Qinying Liu; Li Guo; He Ren; Jingyan Fu; Qing Jiang; Paul R Clarke; Chuanmao Zhang

    2012-01-01

    The mechanism for nuclear envelope (NE) assembly is not fully understood.Importin-β and the small GTPase Ran have been implicated in the spatial regulation of NE assembly process.Here we report that chromatin-bound NLS (nuclear localization sequence) proteins provide docking sites for the NE precursor membrane vesicles and nucleoporins via importin-α and -β during NE assembly in Xenopus egg extracts.We show that along with the fast recruitment of the abundant NLS proteins such as nucleoplasmin and histones to the demembranated sperm chromatin in the extracts,importin-α binds the chromatin NLS proteins rapidly.Meanwhile,importin-β binds cytoplasmic NE precursor membrane vesicles and nucleoporins.Through interacting with importin-α on the chromatin NLS proteins,importin-β targets the membrane vesicles and nucleoporins to the chromatin surface.Once encountering RanGTP on the chromatin generated by RCC1,importin-β preferentially binds Ran-GTP and releases the membrane vesicles and nucleoporins for NE assembly.NE assembly is disrupted by blocking the interaction between importin-α and NLS proteins with excess soluble NLS proteins or by depletion of importin-β from the extract.Our findings reveal a novel molecular mechanism for NE assembly in Xenopus egg extracts.

  4. The CDC25 protein of Saccharomyces cerevisiae promotes exchange of guanine nucleotides bound to ras.

    OpenAIRE

    Jones, S; Vignais, M L; Broach, J R

    1991-01-01

    The product of the CDC25 gene of Saccharomyces cerevisiae, in its capacity as an activator of the RAS/cyclic AMP pathway, is required for initiation of the cell cycle. In this report, we provide an identification of Cdc25p, the product of the CDC25 gene, and evidence that it promotes exchange of guanine nucleotides bound to Ras in vitro. Extracts of strains containing high levels of Cdc25p catalyze both removal of GDP from and the concurrent binding of GTP to Ras. This same activity is also o...

  5. Structural insights into a protein-bound iron-molybdenum cofactor precursor

    OpenAIRE

    Corbett, Mary C.; Hu, Yilin; Fay, Aaron W.; Ribbe, Markus W.; Hedman, Britt; Hodgson, Keith O.

    2006-01-01

    The iron-molybdenum cofactor (FeMoco) of the nitrogenase MoFe protein is a highly complex metallocluster that provides the catalytically essential site for biological nitrogen fixation. FeMoco is assembled outside the MoFe protein in a stepwise process requiring several components, including NifB-co, an iron- and sulfur-containing FeMoco precursor, and NifEN, an intermediary assembly protein on which NifB-co is presumably converted to FeMoco. Through the comparison of Azotobacter vinelandii s...

  6. Structure analysis of free and bound states of an RNA aptamer against ribosomal protein S8 from Bacillus anthracis.

    Science.gov (United States)

    Davlieva, Milya; Donarski, James; Wang, Jiachen; Shamoo, Yousif; Nikonowicz, Edward P

    2014-01-01

    Several protein-targeted RNA aptamers have been identified for a variety of applications and although the affinities of numerous protein-aptamer complexes have been determined, the structural details of these complexes have not been widely explored. We examined the structural accommodation of an RNA aptamer that binds bacterial r-protein S8. The core of the primary binding site for S8 on helix 21 of 16S rRNA contains a pair of conserved base triples that mold the sugar-phosphate backbone to S8. The aptamer, which does not contain the conserved sequence motif, is specific for the rRNA binding site of S8. The protein-free RNA aptamer adopts a helical structure with multiple non-canonical base pairs. Surprisingly, binding of S8 leads to a dramatic change in the RNA conformation that restores the signature S8 recognition fold through a novel combination of nucleobase interactions. Nucleotides within the non-canonical core rearrange to create a G-(G-C) triple and a U-(A-U)-U quartet. Although native-like S8-RNA interactions are present in the aptamer-S8 complex, the topology of the aptamer RNA differs from that of the helix 21-S8 complex. This is the first example of an RNA aptamer that adopts substantially different secondary structures in the free and protein-bound states and highlights the remarkable plasticity of RNA secondary structure.

  7. Structure-function studies of STAR family Quaking proteins bound to their in vivo RNA target sites

    Energy Technology Data Exchange (ETDEWEB)

    Teplova, Marianna; Hafner, Markus; Teplov, Dmitri; Essig, Katharina; Tuschl, Thomas; Patel, Dinshaw J. [MSKCC; (Rockefeller)

    2013-09-27

    Mammalian Quaking (QKI) and its Caenorhabditis elegans homolog, GLD-1 (defective in germ line development), are evolutionarily conserved RNA-binding proteins, which post-transcriptionally regulate target genes essential for developmental processes and myelination. We present X-ray structures of the STAR (signal transduction and activation of RNA) domain, composed of Qua1, K homology (KH), and Qua2 motifs of QKI and GLD-1 bound to high-affinity in vivo RNA targets containing YUAAY RNA recognition elements (RREs). The KH and Qua2 motifs of the STAR domain synergize to specifically interact with bases and sugar-phosphate backbones of the bound RRE. Qua1-mediated homodimerization generates a scaffold that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in many QKI-targeted transcripts. Structure-guided mutations reduced QKI RNA-binding affinity in vitro and in vivo, and expression of QKI mutants in human embryonic kidney cells (HEK293) significantly decreased the abundance of QKI target mRNAs. Overall, our studies define principles underlying RNA target selection by STAR homodimers and provide insights into the post-transcriptional regulatory function of mammalian QKI proteins.

  8. Purification of noncoding RNA and bound proteins using FLAG peptide-conjugated antisense-oligonucleotides.

    Science.gov (United States)

    Adachi, Shungo; Natsume, Tohru

    2015-01-01

    To understand the function of certain RNAs, including noncoding RNAs, it is important to identify the proteins that interact with the RNAs. Here we describe the method for purification of ribonucleoprotein (RNP) complexes composed of specific cellular RNAs by pull-down with FLAG peptide-conjugated antisense oligonucleotide (ASO). Using this method, we identified a novel protein component of U7 snRNP complex.

  9. Proteomics of loosely bound cell wall proteins of Arabidopsis thaliana cell suspension cultures: a critical analysis.

    OpenAIRE

    Borderies, Gisèle; Jamet, Elisabeth; Lafitte, Claude; Rossignol, Michel; Jauneau, Alain; Boudart, Georges; Monsarrat, Bernard; Esquerré-Tugayé, Marie-Thérèse; Boudet, Alain; Pont-Lezica, Rafael

    2003-01-01

    The complete sequencing of the Arabidopsis thaliana genome allows the use of the recently developed mass spectrometry techniques to identify the cell wall proteins (CWPs). Most proteomic approaches depend on the quality of sample preparation. Extraction of CWPs is particularly complex since the proteins may be free in the apoplast or are embedded in a polysaccharide matrix where they are retained by Van der Waals interactions, hydrogen bonds, hydrophobic or ionic interactions, or cross-linked...

  10. Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA

    OpenAIRE

    Guy, Colin P.; Atkinson, John; Gupta, Milind K.; Mahdi, Akeel A.; Gwynn, Emma J.; Rudolph, Christian J.; Moon, Peter B.; van Knippenberg, Ingeborg C.; Cadman, Chris J.; Dillingham, Mark S.; Lloyd, Robert G.; McGlynn, Peter

    2009-01-01

    Summary Nucleoprotein complexes present challenges to genome stability by acting as potent blocks to replication. One attractive model of how such conflicts are resolved is direct targeting of blocked forks by helicases with the ability to displace the blocking protein-DNA complex. We show that Rep and UvrD each promote movement of E. coli replisomes blocked by nucleoprotein complexes in vitro, that such an activity is required to clear protein blocks (primarily transcription complexes) in vi...

  11. A Polycomb complex remains bound through DNA replication in the absence of other eukaryotic proteins

    KAUST Repository

    Lengsfeld, Bettina M.

    2012-09-17

    Propagation of chromatin states through DNA replication is central to epigenetic regulation and can involve recruitment of chromatin proteins to replicating chromatin through interactions with replication fork components. Here we show using a fully reconstituted T7 bacteriophage system that eukaryotic proteins are not required to tether the Polycomb complex PRC1 to templates during DNA replication. Instead, DNA binding by PRC1 can withstand passage of a simple replication fork.

  12. Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain

    International Nuclear Information System (INIS)

    The three-dimensional structure of the N-terminal SH3 domain (residues 583-660) of murine Vav, which contains a tetra-proline sequence (Pro 607-Pro 610), was determined by NMR. The solution structure of the SH3 domain shows a typical SH3 fold, but it exists in two conformations due to cis-trans isomerization at the Gly614-Pro615 bond. The NMR structure of the P615G mutant, where Pro615 is replaced by glycine, reveals that the tetra-proline region is inserted into the RT-loop and binds to its own SH3 structure. The C-terminal SH3 domain of Grb2 specifically binds to the trans form of the N-terminal SH3 domain of Vav. The surface of Vav N-terminal SH3 which binds to Grb2 C-terminal SH3 was elucidated by chemical shift mapping experiments using NMR. The surface does not involve the tetra-proline region but involves the region comprising the n-src loop, the N-terminal and the C-terminal regions. This surface is located opposite to the tetra-proline containing region, consistent with that of our previous mutagenesis studies

  13. Single-stranded DNA bound to bacterial cold-shock proteins: preliminary crystallographic and Raman analysis.

    Science.gov (United States)

    Bienert, Ralf; Zeeb, Markus; Dostál, Lubomir; Feske, Anette; Magg, Christine; Max, Klaas; Welfle, Heinz; Balbach, Jochen; Heinemann, Udo

    2004-04-01

    The cold-shock response has been described for several bacterial species. It is characterized by distinct changes in intracellular protein patterns whereby a set of cold-shock-inducible proteins become abundant. The major cold-shock proteins of Bacillus subtilis (Bs-CspB) and Bacillus caldolyticus (Bc-Csp) are small oligonucleotide/oligosaccharide-binding (OB) fold proteins that have been described as binding single-stranded nucleic acids. Bs-CspB (Mr = 7365) and Bc-Csp (Mr = 7333) were crystallized in the presence of the deoxyhexanucleotide (dT)6. Crystals of (dT)6 with Bs-CspB grew in the orthorhombic space group C222(1), with unit-cell parameters a = 49.0, b = 53.2, c = 77.0 A. Crystals with Bc-Csp grew in the primitive orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 74.3, b = 64.9, c = 31.2 A. These crystals diffract to maximal resolutions of 1.78 and 1.29 A, respectively. The presence of protein and DNA in the crystals was demonstrated by Raman spectroscopy.

  14. Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

    Science.gov (United States)

    Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

    2011-07-13

    ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram.

  15. Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates

    Science.gov (United States)

    Liang, Zhili; Li, Lin; Qi, Haiping; Zhang, Xia; Xu, Zhenbo; Li, Bing

    2016-01-01

    Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs) in foods. Peptide-enriched drinks (PEDs) are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr). In this study we determined free-form pyrraline (Free-Pyr) and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH), soy protein hydrolysate (SPH) and collagen protein hydrolysate (CPH). A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE). The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD) of total pyrraline, whereas Free-Pyr was present in a small proportion (less than four percent) of total pyrraline. The results indicate that PED is an important extrinsic source of pyrraline, especially Pep-Pyr. As compared with CPH- and SPH-enriched drinks, WPH-enriched drinks contained high content of Pep-Pyr. The Pep-Pyr content is associated with the distribution of peptide lengths and the amino acid compositions of protein in PEDs. PMID:27384561

  16. Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates.

    Science.gov (United States)

    Liang, Zhili; Li, Lin; Qi, Haiping; Zhang, Xia; Xu, Zhenbo; Li, Bing

    2016-01-01

    Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs) in foods. Peptide-enriched drinks (PEDs) are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr). In this study we determined free-form pyrraline (Free-Pyr) and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH), soy protein hydrolysate (SPH) and collagen protein hydrolysate (CPH). A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE). The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD) of distribution of peptide lengths and the amino acid compositions of protein in PEDs. PMID:27384561

  17. The morphogenetic MreBCD proteins of Escherichia coli form an essential membrane-bound complex

    DEFF Research Database (Denmark)

    Kruse, Thomas; Bork-Jensen, Jette; Gerdes, Kenn

    2005-01-01

    MreB proteins of Escherichia coli, Bacillus subtilis and Caulobacter crescentus form actin-like cables lying beneath the cell surface. The cables are required to guide longitudinal cell wall synthesis and their absence leads to merodiploid spherical and inflated cells prone to cell lysis. In B...

  18. Elevated mercury bound to serum proteins in methylmercury poisoned rats after selenium treatment.

    Science.gov (United States)

    Li, Yunyun; Fan, Yuqin; Zhao, Jiating; Xu, Xiaohan; Jing, Hui; Shang, Lihai; Gao, Yuxi; Li, Bai; Li, Yu-Feng

    2016-10-01

    Methylmercury is a toxic pollutant and is generated by microbial methylation of elemental or inorganic mercury in the environment. Previous study found decreased hepatic MDA levels and urinary mercury levels in methylmercury poisoned rats after sodium selenite treatment. This study further found increased mercury levels in serum samples from methylmercury poisoned rats after selenium treatment. By using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, three Hg- binding protein fractions and two Se-binding protein fractions were identified with the molecular weight of approximately 21, 40, and 75 kDa and of 40 and 75 kDa, respectively. Elevated mercury level in the 75 kDa protein fraction was found binding with both Hg and Se, which may explain the decreased urinary Hg excretion in MeHg poisoned rats after Se treatment. MALDI-TOF-MS analysis of the serum found that the 75 kDa protein fractions were albumin binding with both Hg and Se and the 21 kDa fraction was Hg- binding metallothionein. PMID:27542163

  19. Chemically bound gold nanoparticle arrays on silicon: assembly, properties and SERS study of protein interactions.

    Science.gov (United States)

    Kaminska, Agnieszka; Inya-Agha, Obianuju; Forster, Robert J; Keyes, Tia E

    2008-07-28

    A highly reproducible and facile method for formation of ordered 2 dimensional arrays of CTAB protected 50 nm gold nanoparticles bonded to silicon wafers is described. The silicon wafers have been chemically modified with long-chain silanes terminated with thiol that penetrate the CTAB bilayer and chemically bind to the underlying gold nanoparticle. The silicon wafer provides a reproducibly smooth, chemically functionalizable and non-fluorescent substrate with a silicon phonon mode which may provide a convenient internal frequency and intensity calibration for vibrational spectroscopy. The CTAB bilayer provides a potentially biomimetic environment for analyte, yet allows a sufficiently small nanoparticle separation to achieve a significant electric field enhancement. The arrays have been characterized using SEM and Raman spectroscopy. These studies reveal that the reproducibility of the arrays is excellent both between batches (effect of temperature on the arrays was also investigated. The interaction of protein and amino acid with the nanoparticle arrays was investigated using Raman microscopy to investigate their potential in bio-SERS spectroscopy. Raman of phenylalanine and the protein bovine pancreatic trypsin inhibitor, BPTI were studied using 785 nm excitation, coincident with the surface plasmon absorbance of the array. The arrays exhibit SERS enhancements of the order of 2.6 x 10(4) for phenylalanine, the standard deviation on the relative intensity of the 1555 cm(-1) mode of phenylalanine is less than 10% for 100 randomly distributed locations across a single substrate and less than 20% between different substrates. Significantly, comparisons of the Raman spectra of the protein and phenylalanine in solution and immobilized on the nanoparticle arrays indicates that the protein is non-randomly orientated on the arrays. Selective SERS enhancements suggest that aromatic residues penetrate through the bilayer inducing conformational changes in the protein. PMID

  20. Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products.

    Science.gov (United States)

    Hegele, Jörg; Buetler, Timo; Delatour, Thierry

    2008-06-01

    Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N(epsilon)-fructoselysine (FL), N(epsilon)-carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34+/-3.81 nmol CML per micromol of free Lys (Lys(free)) and 81.5+/-87.8 nmol Pyr micromol(-1) Lys(free)(-1) vs. 3.72+/-1.29 nmol FL micromol(-1) Lys(free)(-1). In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47+/-0.08 nmol FL micromol(-1) of protein-bound Lys (Lys(p-b)), 0.04+/-0.03 nmol CML micromol(-1) Lys(p-b)(-1) and 0.06+/-0.02 nmol Pyr micromol(-1)Lys(p-b)(-1). It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products.

  1. Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products

    DEFF Research Database (Denmark)

    Morgan, Philip E; Dean, Roger T; Davies, Michael Jonathan

    2002-01-01

    products. In this study, we have examined the effect of glucose and carbonyl compounds (methylglyoxal, glyoxal, glycolaldehyde, and hydroxyacetone), and glycation products arising from reaction of these materials with model proteins, on the activity of three key cellular enzymes: glyceraldehyde-3-phosphate...... dehydrogenase (GAPDH), glutathione reductase, and lactate dehydrogenase, both in isolation and in cell lysates. In contrast to glucose (1M, both fresh and aged for 8 weeks), which had no effect, marked inhibition of all three enzymes was observed with methylglyoxal and glyoxal. GAPDH was also inhibited...... by glycolaldehyde and hydroxyacetone. Incubation of these enzymes with proteins that had been preglycated with methylglyoxal, but not glucose, also resulted in significant time- and concentration-dependent inhibition with both isolated enzymes and cell lysates. This inhibition was not metal ion, oxygen, superoxide...

  2. In planta modification of potato starch granule biogenesis by different granule-bound fusion proteins

    OpenAIRE

    Nazarian, F.

    2007-01-01

    Starch is composed of amylose and amylopectin and it is deposited in amyloplasts/choloroplasts as semi-crystalline granules. Many biosynthetic enzymes are involved in starch degradation and biosynthesis. Some microbial starch degrading enzymes have a Starch Binding Domain (SBD) which has affinity for the starch granules on its own. In our laboratory, expression of SBD alone or fused to other effector proteins has been demonstrated. In industry, starch is modified after harvesting by chemical,...

  3. Pressurized liquid extraction-assisted mussel cytosol preparation for the determination of metals bound to metallothionein-like proteins

    Energy Technology Data Exchange (ETDEWEB)

    Santiago-Rivas, Sandra; Moreda-Pineiro, Antonio [Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, University of Santiago de Compostela, Avenida das Ciencias s/n, 15782 Santiago de Compostela (Spain); Bermejo-Barrera, Pilar [Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, University of Santiago de Compostela, Avenida das Ciencias s/n, 15782 Santiago de Compostela (Spain)], E-mail: pbermejo@usc.es; Moreda-Pineiro, Jorge; Alonso-Rodriguez, Elia; Muniategui-Lorenzo, Soledad [Department of Analytical Chemistry, Faculty of Sciences, University of A Coruna, Campus da Zapateira s/n, 15071 A Coruna (Spain); Lopez-Mahia, Purificacion; Prada-Rodriguez, Dario [Department of Analytical Chemistry, Faculty of Sciences, University of A Coruna, Campus da Zapateira s/n, 15071 A Coruna (Spain); University Institute of Environment, University of A Coruna, Pazo de Longora, Lians, 15179 Oleiros (Spain)

    2007-11-05

    The possibilities of pressurized liquid extraction (PLE) have been novelty tested to assist the cytosol preparation from wet mussel soft tissue before the determination of metals bound to metallothionein-like proteins (MLPs). Results obtained after PLE were compared with those obtained after a classical blending procedure for mussel cytosolic preparation. Isoforms MLP-1 (retention time of 4.1 min) and MLP-2 (retention time of 7.4 min) were separated by anion exchange high-performance liquid chromatography (HPLC) and the concentrations of Ba, Cu, Mn, Sr and Zn bound to MLP isoforms were directly measured by inductively coupled plasma-atomic emission spectrometry (ICP-OES) as a multi-element detector. The optimized PLE-assisted mussel cytosol preparation has consisted of one extraction cycle at room temperature and 1500 psi for 2 min. Since separation between the solid mussel residue and the extract (cytosol) is performed by the PLE system, the cytosol preparation method is faster than conventional cytosol preparation methods by cutting/blending using Ultraturrax or Stomacher devices.

  4. Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes Created by Mutant EcoRII Methyltransferase.

    Directory of Open Access Journals (Sweden)

    Morgan L Henderson

    Full Text Available Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A in Escherichia coli leads to tightly bound DNA-protein complexes (TBCs, located sporadically on the chromosome rather than in tandem arrays. The mechanisms behind the lethality induced by such sporadic TBCs are not well studied, nor is it clear whether very tight binding but non-covalent complexes are processed in the same way as covalent DNA-protein crosslinks (DPCs. Using 2D gel electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication forks in vivo. Specific bubble molecules were detected as spots on the 2D gel, only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific EcoRII methylation site led to disappearance of the corresponding spot. We also performed a candidate gene screen for mutants that are hypersensitive to TBCs induced by M.EcoRII-C186A. We found several gene products necessary for protection against these TBCs that are known to also protect against DPCs induced with wild-type M.EcoRII (after 5-azacytidine incorporation: RecA, RecBC, RecG, RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA. In contrast, the RecFOR pathway and Rep helicase are needed for protection against TBCs but not DPCs induced by M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes release of tightly bound (but non-covalent blocking proteins, perhaps by licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our studies also argued against the involvement of several proteins that might be expected to protect against TBCs. We took the opportunity to directly compare the sensitivity of all tested mutants to two quinolone antibiotics, which target bacterial type II topoisomerases and induce a unique form of DPC. We uncovered rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained evidence against the involvement of a number of functions that might be expected to protect against quinolones.

  5. Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes Created by Mutant EcoRII Methyltransferase.

    Science.gov (United States)

    Henderson, Morgan L; Kreuzer, Kenneth N

    2015-01-01

    Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A) in Escherichia coli leads to tightly bound DNA-protein complexes (TBCs), located sporadically on the chromosome rather than in tandem arrays. The mechanisms behind the lethality induced by such sporadic TBCs are not well studied, nor is it clear whether very tight binding but non-covalent complexes are processed in the same way as covalent DNA-protein crosslinks (DPCs). Using 2D gel electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication forks in vivo. Specific bubble molecules were detected as spots on the 2D gel, only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific EcoRII methylation site led to disappearance of the corresponding spot. We also performed a candidate gene screen for mutants that are hypersensitive to TBCs induced by M.EcoRII-C186A. We found several gene products necessary for protection against these TBCs that are known to also protect against DPCs induced with wild-type M.EcoRII (after 5-azacytidine incorporation): RecA, RecBC, RecG, RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA). In contrast, the RecFOR pathway and Rep helicase are needed for protection against TBCs but not DPCs induced by M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes release of tightly bound (but non-covalent) blocking proteins, perhaps by licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our studies also argued against the involvement of several proteins that might be expected to protect against TBCs. We took the opportunity to directly compare the sensitivity of all tested mutants to two quinolone antibiotics, which target bacterial type II topoisomerases and induce a unique form of DPC. We uncovered rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained evidence against the involvement of a number of functions that might be expected to protect against quinolones. PMID:25993347

  6. Functional analysis of membrane-bound complement regulatory protein on T-cell immune response in ginbuna crucian carp.

    Science.gov (United States)

    Nur, Indriyani; Abdelkhalek, Nevien K; Motobe, Shiori; Nakamura, Ryota; Tsujikura, Masakazu; Somamoto, Tomonori; Nakao, Miki

    2016-02-01

    Complements have long been considered to be a pivotal component in innate immunity. Recent researches, however, highlight novel roles of complements in T-cell-mediated adaptive immunity. Membrane-bound complement regulatory protein CD46, a costimulatory protein for T cells, is a key molecule for T-cell immunomodulation. Teleost CD46-like molecule, termed Tecrem, has been newly identified in common carp and shown to function as a complement regulator. However, it remains unclear whether Tecrem is involved in T-cell immune response. We investigated Tecrem function related to T-cell responses in ginbuna crucian carp. Ginbuna Tecrem (gTecrem) proteins were detected by immunoprecipitation using anti-common carp Tecrem monoclonal antibody (mAb) and were ubiquitously expressed on blood cells including CD8α(+) and CD4(+) lymphocytes. gTecrem expression on leucocyte surface was enhanced after stimulation with the T-cell mitogen, phytohaemagglutinin (PHA). Coculture with the anti-Tecrem mAb significantly inhibited the proliferative activity of PHA-stimulated peripheral blood lymphocytes, suggesting that cross-linking of Tecrems on T-cells interferes with a signal transduction pathway for T-cell activation. These findings indicate that Tecrem may act as a T-cell moderator and imply that the complement system in teleost, as well as mammals, plays an important role for linking adaptive and innate immunity.

  7. Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR

    Energy Technology Data Exchange (ETDEWEB)

    Eddy, Matthew T. [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States); Su, Yongchao; Silvers, Robert; Andreas, Loren; Clark, Lindsay [Massachusetts Institute of Technology, Department of Chemistry (United States); Wagner, Gerhard [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Pintacuda, Guido; Emsley, Lyndon [Université de Lyon, Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (CNRS, ENS Lyon, UCB Lyon 1) (France); Griffin, Robert G., E-mail: rgg@mit.edu [Massachusetts Institute of Technology, Department of Chemistry (United States)

    2015-04-15

    The human voltage dependent anion channel 1 (VDAC) is a 32 kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction structures, a structural basis for the mechanism of its function is not yet fully understood. Biophysical studies suggest VDAC requires a lipid bilayer to achieve full function, motivating the need for atomic resolution structural information of VDAC in a membrane environment. Here we report an essential step toward that goal: extensive assignments of backbone and side chain resonances for VDAC in DMPC lipid bilayers via magic angle spinning nuclear magnetic resonance (MAS NMR). VDAC reconstituted into DMPC lipid bilayers spontaneously forms two-dimensional lipid crystals, showing remarkable spectral resolution (0.5–0.3 ppm for {sup 13}C line widths and <0.5 ppm {sup 15}N line widths at 750 MHz). In addition to the benefits of working in a lipid bilayer, several distinct advantages are observed with the lipid crystalline preparation. First, the strong signals and sharp line widths facilitated extensive NMR resonance assignments for an integral membrane β-barrel protein in lipid bilayers by MAS NMR. Second, a large number of residues in loop regions were readily observed and assigned, which can be challenging in detergent-solubilized membrane proteins where loop regions are often not detected due to line broadening from conformational exchange. Third, complete backbone and side chain chemical shift assignments could be obtained for the first 25 residues, which comprise the functionally important N-terminus. The reported assignments allow us to compare predicted torsion angles for VDAC prepared in DMPC 2D lipid crystals, DMPC liposomes, and LDAO-solubilized samples to address the possible effects of the membrane mimetic environment on the conformation of the protein. Concluding, we discuss the strengths and weaknesses of the

  8. Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR

    International Nuclear Information System (INIS)

    The human voltage dependent anion channel 1 (VDAC) is a 32 kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction structures, a structural basis for the mechanism of its function is not yet fully understood. Biophysical studies suggest VDAC requires a lipid bilayer to achieve full function, motivating the need for atomic resolution structural information of VDAC in a membrane environment. Here we report an essential step toward that goal: extensive assignments of backbone and side chain resonances for VDAC in DMPC lipid bilayers via magic angle spinning nuclear magnetic resonance (MAS NMR). VDAC reconstituted into DMPC lipid bilayers spontaneously forms two-dimensional lipid crystals, showing remarkable spectral resolution (0.5–0.3 ppm for 13C line widths and <0.5 ppm 15N line widths at 750 MHz). In addition to the benefits of working in a lipid bilayer, several distinct advantages are observed with the lipid crystalline preparation. First, the strong signals and sharp line widths facilitated extensive NMR resonance assignments for an integral membrane β-barrel protein in lipid bilayers by MAS NMR. Second, a large number of residues in loop regions were readily observed and assigned, which can be challenging in detergent-solubilized membrane proteins where loop regions are often not detected due to line broadening from conformational exchange. Third, complete backbone and side chain chemical shift assignments could be obtained for the first 25 residues, which comprise the functionally important N-terminus. The reported assignments allow us to compare predicted torsion angles for VDAC prepared in DMPC 2D lipid crystals, DMPC liposomes, and LDAO-solubilized samples to address the possible effects of the membrane mimetic environment on the conformation of the protein. Concluding, we discuss the strengths and weaknesses of the reported

  9. Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins

    OpenAIRE

    Zhou, Dapeng; Cantu, Carlos; Sagiv, Yuval; Schrantz, Nicolas; Kulkarni, Ashok B.; Qi, Xiaoyang; Mahuran, Don J.; Carlos R Morales; Grabowski, Gregory A.; Benlagha, Kamel; Savage, Paul; Bendelac, Albert; Teyton, Luc

    2003-01-01

    It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Vα14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the...

  10. Time-resolved FTIR spectroscopy for monitoring protein dynamics exemplified by functional studies of Ras protein bound to a lipid bilayer

    International Nuclear Information System (INIS)

    Graphical abstract: The first time resolved FTIR investigation of a GTPase reaction of a protein anchored at a single lipid bilayer. Display Omitted Highlights: ► FTIR difference spectroscopy monitors protein dynamics with atomic detail. ► ATR–FTIR allows the measurement of a monolayer sample. ► Membrane proteins can be investigated near physiological conditions. ► The hydrolysis reaction of Ras was investigated in this condition for the first time. - Abstract: Time-resolved Fourier transform infrared (FTIR) difference spectroscopy is a valuable tool for monitoring the dynamics of protein reactions and interactions. Absorbance changes can be monitored with time resolutions down to nanoseconds and followed for time periods that range over nine orders of magnitude. Membrane proteins bound to solid supported lipid bilayers can be investigated in near physiological conditions with the attenuated total reflection (ATR) technique. Here, we review the basics of time-resolved FTIR with a focus on Ras, a GTPase that is mutated in 25% of human tumors. We show the first time-resolved measurements of membrane anchored Ras and observed the switching between its activated and its inactivated state. We compared those measurements with measurements of the truncated Ras in solution. We found that both the kinetics and the functional groups involved were very similar. This suggested that the membrane did not have a major influence on the hydrolysis reaction.

  11. Studies of the molecular effects of a solid support upon lipid membranes and membrane bound proteins

    Science.gov (United States)

    Hartshorn, Christopher M.

    Often, membrane/protein systems are studied and/or utilized on solid supports. The underlying substrate in solid supported lipid bilayer assemblies causes large perturbations to the membrane, but the nature of these effects are not well understood. To gain an understanding, these effects were studied on two fronts: the effect upon the membrane by itself, and then the effects upon a membrane/protein system. First, all-atom molecular dynamics (MD) simulations of DLPC, DMPC, POPC, and DEPC on a hydroxylated nanocrystalline alpha-quartz (011) slab revealed a pronounced thinning effect in the lipid bilayers. It was shown that this thinning effect proceeded by one of two mechanisms: the first through a curling of the terminal methyl groups at the interface of the opposing leaflets, and the second through increased interdigitation of the alkyl chains. Also, with the introduction of the solid support, marked asymmetries in a number of structural properties were reported. These asymmetries included (a) the surface area per lipid, (b) the electron densities of the polar head groups, (c) the radial distributions of the choline groups, and (d) the average orientation of water surrounding the membranes. Next, the free energy perturbation method was used to begin calculating the change in free energy (DeltaGbinding) from a Gramicidin monomer to its dimeric state, which were simulated via MD of supported DLPC, DMPC, and DEPC bilayers. The most notable effect was an asymmetry of the calculated free energies relative to the bilayer side closest to the solid support. In all three systems, there was a large difference in free energy between the Gramicidin monomers that were close to the support and the monomers further from the support.

  12. Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates

    Directory of Open Access Journals (Sweden)

    Zhili Liang

    2016-07-01

    Full Text Available Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs in foods. Peptide-enriched drinks (PEDs are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr. In this study we determined free-form pyrraline (Free-Pyr and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH, soy protein hydrolysate (SPH and collagen protein hydrolysate (CPH. A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE. The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD of <5%. The limits of detection and quantification obtained were 30.4 and 70.3 ng/mL, respectively. Pep-Pyr was identified as the most abundant form (above 96 percent of total pyrraline, whereas Free-Pyr was present in a small proportion (less than four percent of total pyrraline. The results indicate that PED is an important extrinsic source of pyrraline, especially Pep-Pyr. As compared with CPH- and SPH-enriched drinks, WPH-enriched drinks contained high content of Pep-Pyr. The Pep-Pyr content is associated with the distribution of peptide lengths and the amino acid compositions of protein in PEDs.

  13. Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechol(amine)s

    DEFF Research Database (Denmark)

    Pattison, David I; Dean, Roger T; Davies, Michael Jonathan

    2002-01-01

    in the presence of molecular O(2) and redox-active metal ions (e.g. Fe(3+), Cu(2+), Cr(6+)), which are known to increase the rate of DOPA oxidation. The majority of oxidative damage appears to be mediated by reactive oxygen species (ROS) such as superoxide and HO(.) radicals, though other DOPA oxidation products......, including semiquinone radicals, quinones, and metal ion-DOPA complexes have also been implicated in some cases. Non-radical reactions of DOPA with suitable nucleophiles (e.g. thiol groups) can also result in modification of the target, with this process being particularly prevalent with proteins...

  14. Microanalysis characterization of bioactive protein-bound polysaccharides produced by Amanita ponderosa cultures.

    Science.gov (United States)

    Salvador, Cátia; Martins, M Rosário; Caldeira, A Teresa

    2015-02-01

    Different compounds of edible mushrooms are responsible for their bioactivity. The ability to synthesize polysaccharides, namely protein-polysaccharide (PPS) complexes, is related to the antioxidant capacity of these compounds and present great interest in preventing a number of diseases, including cancer, cardiovascular and auto-immune diseases, and accelerated aging. Amanita ponderosa are wild edible mushrooms that grow in Mediterranean "montado" areas [Portuguese name given to cork oak (Quercus suber) and holm oak (Quercus ilex) forests]. The aim of this study was to evaluate the production of PPS complexes obtained from A. ponderosa cultures using a new microanalytical approach to quickly and easily monitor the production process. Microanalysis using Fourier-transform infrared using attenuated total reflection and Raman spectroscopy of PPS samples showed spectra compatible with identification of this type of compound in culture extracts. PPS separated by size-exclusion chromatography showed seven main complexes. Molecular weights of the main PPS complexes isolated from cultures ranged between 1.5 and 20 kDa and did not present toxicity against Artemia salina, demonstrating the potential of A. ponderosa as a source of biologically active compounds with nutraceutical value. Application of this microanalytical approach to monitoring the production of PPS compounds can be successfully applied in biotechnological processes.

  15. TGF-β2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages.

    Science.gov (United States)

    Haidar, Malak; Whitworth, Jessie; Noé, Gaelle; Liu, Wang Qing; Vidal, Michel; Langsley, Gordon

    2015-10-29

    Theileria-infected macrophages display many features of cancer cells such as heightened invasive capacity; however, the tumor-like phenotype is reversible by killing the parasite. Moreover, virulent macrophages can be attenuated by multiple in vitro passages and so provide a powerful model to elucidate mechanisms related to transformed macrophage virulence. Here, we demonstrate that in two independent Theileria-transformed macrophage cell lines Grb2 expression is down-regulated concomitant with loss of tumor virulence. Using peptidimer-c to ablate SH2 and SH3 interactions of Grb2 we identify TGF-receptor II and the p85 subunit of PI3-K, as Grb2 partners in virulent macrophages. Ablation of Grb2 interactions reduces PI3-K recruitment to TGF-RII and decreases PIP3 production, and dampens JNK phosphorylation and AP-1-driven transcriptional activity down to levels characteristic of attenuated macrophages. Loss of TGF-R>PI3-K>JNK>AP-1 signaling negatively impacts on virulence traits such as reduced JAM-L/ITG4A and Fos-B/MMP9 expression that contribute to virulent macrophage adhesion and invasiveness.

  16. Does p-cresylglucuronide have the same impact on mortality as other protein-bound uremic toxins?

    Directory of Open Access Journals (Sweden)

    Sophie Liabeuf

    Full Text Available BACKGROUND: Uremic toxins are emerging as important, non-traditional cardiovascular risk factors in chronic kidney disease (CKD. P-cresol has been defined as a prototype protein-bound uremic toxin. Conjugation of p-cresol creates p-cresylsulfate (PCS as the main metabolite and p-cresylglucuronide (PCG, at a markedly lower concentration. The objective of the present study was to evaluate serum PCG levels, determine the latter's association with mortality and establish whether the various protein-bound uremic toxins (i.e. PCS, PCG and indoxylsulfate (IS differed in their ability to predict mortality. METHODOLOGY/PRINCIPAL FINDINGS: We studied 139 patients (mean ± SD age: 67±12; males: 60% at different CKD stages (34.5% at CKD stages 2-3, 33.5% at stage 4-5 and 32% at stage 5D. A recently developed high-performance liquid chromatography method was used to assay PCG concentrations. Total and free PCG levels increased with the severity of CKD. During the study period (mean duration: 779±185 days, 38 patients died. High free and total PCG levels were correlated with overall and cardiovascular mortality independently of well-known predictors of survival, such as age, vascular calcification, anemia, inflammation and (in predialysis patients the estimated glomerular filtration rate. In the same cohort, free PCS levels and free IS levels were both correlated with mortality. Furthermore, the respective predictive powers of three Cox multivariate models (free PCS+other risk factors, free IS+other risk factors and free PCS+other risk factors were quite similar--suggesting that an elevated PCG concentration has much the same impact on mortality as other uremic toxins (such as PCS or IS do. CONCLUSIONS: Although PCG is the minor metabolite of p-cresol, our study is the first to reveal its association with mortality. Furthermore, the free fraction of PCG appears to have much the same predictive power for mortality as PCS and IS do.

  17. Body composition, tissue deposition, and lysine utilization for protein deposition of barrows and gilts fed crystalline or protein-bound lysine.

    Science.gov (United States)

    Colina, J J; Miller, P S; Lewis, A J; Fischer, R L; Diedrichsen, R M

    2016-05-01

    An experiment with 2 trials (28 d/trial) was conducted to determine body composition, tissue deposition, and utilization of Lys for protein deposition (PD) of barrows and gilts fed -Lys·HCl (CLys) or protein-bound Lys in soybean meal (SBM). Thirty-two growing pigs (16 barrows and 16 gilts; average initial BW of 18.6 kg) were used in each of 2 trials. Four pigs (2 barrows and 2 gilts) were euthanized at the start of each trial to determine initial body composition. The remaining pigs were euthanized at the end of the trials to determine empty-body composition and deposition rates of water, protein, fat, ash, and AA. Pigs were randomly allotted to 1 of 7 dietary treatments. There were 2 replications per treatment in each trial for a total of 4 replications. Dietary treatments consisted of a corn-SBM basal diet (0.48% Lys) and diets containing 0.56%, 0.65%, and 0.74% standardized ileal digestible (SID) Lys that were achieved by adding Lys to the basal diet from either SBM or CLys. Pigs fed the CLys-supplemented diets at 0.65% SID Lys had more ( < 0.05) body water (663 vs. 624 g/kg) and less ( < 0.01) body protein (153 vs. 160 g/kg) than pigs fed the SBM-supplemented diets. Body fat content decreased ( < 0.01) as the dietary Lys increased similarly for pigs fed Lys from SBM and pigs fed CLys. Gilts had greater ( = 0.05) body Lys content in body protein than barrows (7.68 vs. 7.52 g/100 g). Empty-body ash contents were not different between pigs fed CLys or SBM-supplemented diets. Water deposition and PD increased linearly ( < 0.01) with dietary Lys and were least ( < 0.01) in pigs fed the basal diet but were similar when comparing pigs fed CLys and SBM-supplemented diets at the same dietary Lys concentration. Lysine deposition showed a linear increase ( < 0.01) with dietary Lys but was not different between pigs fed the 2 Lys sources at the same concentration. Barrows and gilts did not differ in tissue deposition rates. Overall, empty-body contents and deposition

  18. Structure of the red fluorescent protein from a lancelet (Branchiostoma lanceolatum): a novel GYG chromophore covalently bound to a nearby tyrosine

    OpenAIRE

    Pletnev, Vladimir Z.; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Souslova, Ekaterina A.; Fradkov, Arkady F.; Chudakov, Dmitry M.; Chepurnykh, Tatyana; Yampolsky, Ilia V.; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Sergei

    2013-01-01

    The crystal structure of the novel red emitting fluorescent protein from lancelet Branchiostoma lanceolatum (Chordata) revealed an unusual five residues cyclic unit comprising Gly58-Tyr59-Gly60 chromophore, the following Phe61 and Tyr62 covalently bound to chromophore Tyr59.

  19. The role of AST-120 and protein-bound uremic toxins in irritable bowel syndrome: a therapeutic perspective.

    Science.gov (United States)

    Mosińska, Paula; Storr, Martin; Fichna, Jakub

    2015-09-01

    AST-120 (kremezin) exhibits its favourable effects in reducing the levels of renal toxins by selective adsorption of low molecular weight substances from the intestinal lumen. So far, a vast majority of studies were focused on the role of AST-120 in the treatment of chronic kidney diseases and cardiovascular disorders, and positive therapeutic effects of the agent have already been confirmed in clinical conditions. Up to the present, there are only a few studies regarding the role of AST-120 in irritable bowel syndrome (IBS). Compelling data suggest the ability of the compound to adsorb protein-bound uremic toxins and mast cell derived mediators and to modulate the farnesoid X receptor, which is a bile acid sensor indispensable for maintaining homeostasis in the intestine. In this review we focus on the actions of AST-120 on intestinal permeability, reduction of visceral sensitivity and alteration of gut motility. We also discuss whether AST-120 can mitigate common IBS symptoms, such as abdominal pain, bloating and malfunction of the colonic transit and thus improve the quality of life of patients with IBS. PMID:26327918

  20. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition.

    Science.gov (United States)

    Gagnon, Matthieu G; Roy, Raktim N; Lomakin, Ivan B; Florin, Tanja; Mankin, Alexander S; Steitz, Thomas A

    2016-03-18

    With bacterial resistance becoming a serious threat to global public health, antimicrobial peptides (AMPs) have become a promising area of focus in antibiotic research. AMPs are derived from a diverse range of species, from prokaryotes to humans, with a mechanism of action that often involves disruption of the bacterial cell membrane. Proline-rich antimicrobial peptides (PrAMPs) are instead actively transported inside the bacterial cell where they bind and inactivate specific targets. Recently, it was reported that some PrAMPs, such as Bac71 -35, oncocins and apidaecins, bind and inactivate the bacterial ribosome. Here we report the crystal structures of Bac71 -35, Pyrrhocoricin, Metalnikowin and two oncocin derivatives, bound to the Thermus thermophilus 70S ribosome. Each of the PrAMPs blocks the peptide exit tunnel of the ribosome by simultaneously occupying three well characterized antibiotic-binding sites and interferes with the initiation step of translation, thereby revealing a common mechanism of action used by these PrAMPs to inactivate protein synthesis. Our study expands the repertoire of PrAMPs and provides a framework for designing new-generation therapeutics. PMID:26809677

  1. ER-bound protein tyrosine phosphatase PTP1B interacts with Src at the plasma membrane/substrate interface.

    Directory of Open Access Journals (Sweden)

    Melisa C Monteleone

    Full Text Available PTP1B is an endoplasmic reticulum (ER anchored enzyme whose access to substrates is partly dependent on the ER distribution and dynamics. One of these substrates, the protein tyrosine kinase Src, has been found in the cytosol, endosomes, and plasma membrane. Here we analyzed where PTP1B and Src physically interact in intact cells, by bimolecular fluorescence complementation (BiFC in combination with temporal and high resolution microscopy. We also determined the structural basis of this interaction. We found that BiFC signal is displayed as puncta scattered throughout the ER network, a feature that was enhanced when the substrate trapping mutant PTP1B-D181A was used. Time-lapse and co-localization analyses revealed that BiFC puncta did not correspond to vesicular carriers; instead they localized at the tip of dynamic ER tubules. BiFC puncta were retained in ventral membrane preparations after cell unroofing and were also detected within the evanescent field of total internal reflection fluorescent microscopy (TIRFM associated to the ventral membranes of whole cells. Furthermore, BiFC puncta often colocalized with dark spots seen by surface reflection interference contrast (SRIC. Removal of Src myristoylation and polybasic motifs abolished BiFC. In addition, PTP1B active site and negative regulatory tyrosine 529 on Src were primary determinants of BiFC occurrence, although the SH3 binding motif on PTP1B also played a role. Our results suggest that ER-bound PTP1B dynamically interacts with the negative regulatory site at the C-terminus of Src at random puncta in the plasma membrane/substrate interface, likely leading to Src activation and recruitment to adhesion complexes. We postulate that this functional ER/plasma membrane crosstalk could apply to a wide array of protein partners, opening an exciting field of research.

  2. Bounded Earthquakes

    OpenAIRE

    Saric, Dragomir

    2006-01-01

    We give a short proof of the fact that bounded earthquakes of the unit disk induce quasisymmetric maps of the unit circle. By a similar method, we show that symmetric maps are induced by bounded earthquakes with asymptotically trivial measures.

  3. Bound entanglement and entanglement bounds

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, Simeon [Physikalisch-Astronomische Fakultaet, Friedrich-Schiller-Univesitaet Jena (Germany)]|[Physikalisches Institut, Albert-Ludwigs-Universitaet Freiburg, Hermann-Herder-Strasse 3, D-79104 Freiburg (Germany); Melo, Fernando de; Mintert, Florian; Buchleitner, Andreas [Physikalisches Institut, Albert-Ludwigs-Universitaet Freiburg, Hermann-Herder-Strasse 3, D-79104 Freiburg (Germany)]|[Max-Planck-Institut fuer Physik komplexer Systeme, Noethnitzer Str.38, D-01187 Dresden (Germany); Bae, Joonwoo [School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-012 (Korea); Hiesmayr, Beatrix [Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Vienna (Austria)

    2008-07-01

    We investigate the separability of Bell-diagonal states of two qutrits. By using lower bounds to algebraically estimate concurrence, we find convex regions of bound entangled states. Some of these regions exactly coincide with the obtained results when employing optimal entanglement witnesses, what shows that the lower bound can serve as a precise detector of entanglement. Some hitherto unknown regions of bound entangled states were discovered with this approach, and delimited efficiently.

  4. Clinical experience of immunotherapy based on oleic acid bound to glycosylated vitamin d-binding protein in localised and metastatic adenocarcinoma of the pancreas

    OpenAIRE

    Lynda Thyer; Branca, Jacopo J. V.; Margit Taubmann

    2014-01-01

    Adenocarcinoma of the pancreas still carries a dramatically poor prognosis and the survival rate for this disease has not improved substantially in the past 40 years. Therefore, new treatment options are urgently needed and this need motivates oncologists to search for novel approaches such as immunotherapy. Here we report two clinical cases successfully treated with an integrative immunotherapeutic approach based on oleic acid bound to glycosylated vitamin D-binding protein (OA-GcMAF). Consi...

  5. A role for DNA-mediated charge transport in regulating p53: Oxidation of the DNA-bound protein from a distance

    OpenAIRE

    Augustyn, Katherine E.; Merino, Edward J.; Barton, Jacqueline K.

    2007-01-01

    Charge transport (CT) through the DNA base pairs provides a means to promote redox reactions at a remote site and potentially to effect signaling between molecules bound to DNA. Here we describe the oxidation of a cell-cycle regulatory protein, p53, from a distance through DNA-mediated CT. A consensus p53 binding site as well as three DNA promoters regulated by p53 were synthesized containing a tethered DNA photooxidant, anthraquinone. Photoinduced oxidation of the protein occurs from a dista...

  6. Crystal Structures of Apo and Metal-Bound Forms of the UreE Protein from Helicobacter pylori: Role of Multiple Metal Binding Sites

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Rong; Munger, Christine; Asinas, Abdalin; Benoit, Stephane L.; Miller, Erica; Matte, Allan; Maier, Robert J.; Cygler, Miroslaw (McGill); (Georgia); (Biotech Res.)

    2010-10-22

    The crystal structure of the urease maturation protein UreE from Helicobacter pylori has been determined in its apo form at 2.1 {angstrom} resolution, bound to Cu{sup 2+} at 2.7 {angstrom} resolution, and bound to Ni{sup 2+} at 3.1 {angstrom} resolution. Apo UreE forms dimers, while the metal-bound enzymes are arranged as tetramers that consist of a dimer of dimers associated around the metal ion through coordination by His102 residues from each subunit of the tetramer. Comparison of independent subunits from different crystal forms indicates changes in the relative arrangement of the N- and C-terminal domains in response to metal binding. The improved ability of engineered versions of UreE containing hexahistidine sequences at either the N-terminal or C-terminal end to provide Ni{sup 2+} for the final metal sink (urease) is eliminated in the H102A version. Therefore, the ability of the improved Ni{sup 2+}-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102.

  7. Measurement of homonuclear three-bond J(HNH{alpha}) coupling constants in unlabeled peptides complexed with labeled proteins: Application to a decapeptide inhibitor bound to the proteinase domain of the NS3 protein of hepatitis C virus (HCV)

    Energy Technology Data Exchange (ETDEWEB)

    Cicero, Daniel O.; Barbato, Gaetano; Koch, Uwe; Ingallinella, Paolo; Bianchi, Elisabetta; Sambucini, Sonia; Neddermann, Petra; De Francesco, Raffaele; Pessi, Antonello; Bazzo, Renzo

    2001-05-15

    A new isotope-filtered experiment has been designed to measure homonuclear three-bond J(H{sup N}H{sup {alpha}}) coupling constants of unlabeled peptides complexed with labeled proteins. The new experiment is based on the 3D HNHA pulse scheme, and belongs to the 'quantitative J-correlation' type. It has been applied to a decapeptide inhibitor bound to the proteinase domain of the NS3 protein of human hepatitis C virus (HCV)

  8. Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations

    Energy Technology Data Exchange (ETDEWEB)

    Moaddel, Ruin [Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825 (United States); Wainer, Irving W. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825 (United States)]. E-mail: Wainerir@grc.nia.nih.gov

    2006-03-30

    Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic support or on the surface of an activated glass capillary. The resulting chromatographic columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K {sub d} values) and non-linear chromatography can be used to assess the association (k {sub on}) and dissociation (k {sub off}) rate constants and the thermodynamics of the binding process. Membrane-based affinity columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein.

  9. Structure of a heterogeneous, glycosylated, lipid-bound, in vivo-grown protein crystal at atomic resolution from the viviparous cockroach Diploptera punctata.

    Science.gov (United States)

    Banerjee, Sanchari; Coussens, Nathan P; Gallat, François-Xavier; Sathyanarayanan, Nitish; Srikanth, Jandhyam; Yagi, Koichiro J; Gray, James S S; Tobe, Stephen S; Stay, Barbara; Chavas, Leonard M G; Ramaswamy, Subramanian

    2016-07-01

    Macromolecular crystals for X-ray diffraction studies are typically grown in vitro from pure and homogeneous samples; however, there are examples of protein crystals that have been identified in vivo. Recent developments in micro-crystallography techniques and the advent of X-ray free-electron lasers have allowed the determination of several protein structures from crystals grown in cellulo. Here, an atomic resolution (1.2 Å) crystal structure is reported of heterogeneous milk proteins grown inside a living organism in their functional niche. These in vivo-grown crystals were isolated from the midgut of an embryo within the only known viviparous cockroach, Diploptera punctata. The milk proteins crystallized in space group P1, and a structure was determined by anomalous dispersion from the native S atoms. The data revealed glycosylated proteins that adopt a lipocalin fold, bind lipids and organize to form a tightly packed crystalline lattice. A single crystal is estimated to contain more than three times the energy of an equivalent mass of dairy milk. This unique storage form of nourishment for developing embryos allows access to a constant supply of complete nutrients. Notably, the crystalline cockroach-milk proteins are highly heterogeneous with respect to amino-acid sequence, glycosylation and bound fatty-acid composition. These data present a unique example of protein heterogeneity within a single in vivo-grown crystal of a natural protein in its native environment at atomic resolution. PMID:27437115

  10. Bounding the $\

    CERN Document Server

    Gutiérrez-Rodríguez, A

    2003-01-01

    A bound on the nu /sup tau / magnetic moment is calculated through the reaction e/sup +/e/sup -/ to nu nu gamma at the Z/sub 1/-pole, and in the framework of a left-right symmetric model at LEP energies. We find that the bound is almost independent of the mixing angle phi of the model in the allowed experimental range for this parameter. (31 refs).

  11. Crystal structure of Helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center in a zinc or cadmium-bound form

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Hideshi, E-mail: h-yokoya@u-shizuoka-ken.ac.jp [School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Tsuruta, Osamu; Akao, Naoya; Fujii, Satoshi [School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Structures of a metal-bound Helicobacter pylori neutrophil-activating protein were determined. Black-Right-Pointing-Pointer Two zinc ions were tetrahedrally coordinated by ferroxidase center (FOC) residues. Black-Right-Pointing-Pointer Two cadmium ions were coordinated in a trigonal-bipyramidal and octahedral manner. Black-Right-Pointing-Pointer The second metal ion was more weakly coordinated than the first at the FOC. Black-Right-Pointing-Pointer A zinc ion was found in one negatively-charged pore suitable as an ion path. -- Abstract: Helicobacter pylori neutrophil-activating protein (HP-NAP) is a Dps-like iron storage protein forming a dodecameric shell, and promotes adhesion of neutrophils to endothelial cells. The crystal structure of HP-NAP in a Zn{sup 2+}- or Cd{sup 2+}-bound form reveals the binding of two zinc or two cadmium ions and their bridged water molecule at the ferroxidase center (FOC). The two zinc ions are coordinated in a tetrahedral manner to the conserved residues among HP-NAP and Dps proteins. The two cadmium ions are coordinated in a trigonal-bipyramidal and distorted octahedral manner. In both structures, the second ion is more weakly coordinated than the first. Another zinc ion is found inside of the negatively-charged threefold-related pore, which is suitable for metal ions to pass through.

  12. Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I.

    Science.gov (United States)

    Troise, Antonio Dario; Buonanno, Martina; Fiore, Alberto; Monti, Simona Maria; Fogliano, Vincenzo

    2016-12-01

    Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37°C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods. PMID:27374589

  13. Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I.

    Science.gov (United States)

    Troise, Antonio Dario; Buonanno, Martina; Fiore, Alberto; Monti, Simona Maria; Fogliano, Vincenzo

    2016-12-01

    Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37°C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods.

  14. Crystal Structure of Epiphyas Postvittana Takeout 1 With Bound Ubiquinone Supports a Role As Ligand Carriers for Takeout Proteins in Insects

    Energy Technology Data Exchange (ETDEWEB)

    Hamiaux, C.; Stanley, D.; Greenwood, D.R.; Baker, E.N.; Newcomb, R.D.

    2009-05-19

    Takeout (To) proteins are found exclusively in insects and have been proposed to have important roles in various aspects of their physiology and behavior. Limited sequence similarity with juvenile hormone-binding proteins (JHBPs), which specifically bind and transport juvenile hormones in Lepidoptera, suggested a role for To proteins in binding hydrophobic ligands. We present the first crystal structure of a To protein, EpTo1 from the light brown apple moth Epiphyas postvittana, solved in-house by the single-wavelength anomalous diffraction technique using sulfur anomalous dispersion, and refined to 1.3 {angstrom} resolution. EpTo1 adopts the unusual {alpha}/{beta}-wrap fold, seen only for JHBP and several mammalian lipid carrier proteins, a scaffold tailored for the binding and/or transport of hydrophobic ligands. EpTo1 has a 45 {angstrom} long, purely hydrophobic, internal tunnel that extends for the full length of the protein and accommodates a bound ligand. The latter was shown by mass spectrometry to be ubiquinone-8 and is probably derived from Escherichia coli. The structure provides the first direct experimental evidence that To proteins are ligand carriers; gives insights into the nature of endogenous ligand(s) of EpTo1; shows, by comparison with JHBP, a basis for different ligand specificities; and suggests a mechanism for the binding/release of ligands.

  15. PROTEIN TARGETING TO STARCH is required for localising GRANULE-BOUND STARCH SYNTHASE to starch granules and for normal amylose synthesis in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    David Seung

    2015-02-01

    Full Text Available The domestication of starch crops underpinned the development of human civilisation, yet we still do not fully understand how plants make starch. Starch is composed of glucose polymers that are branched (amylopectin or linear (amylose. The amount of amylose strongly influences the physico-chemical behaviour of starchy foods during cooking and of starch mixtures in non-food manufacturing processes. The GRANULE-BOUND STARCH SYNTHASE (GBSS is the glucosyltransferase specifically responsible for elongating amylose polymers and was the only protein known to be required for its biosynthesis. Here, we demonstrate that PROTEIN TARGETING TO STARCH (PTST is also specifically required for amylose synthesis in Arabidopsis. PTST is a plastidial protein possessing an N-terminal coiled coil domain and a C-terminal carbohydrate binding module (CBM. We discovered that Arabidopsis ptst mutants synthesise amylose-free starch and are phenotypically similar to mutants lacking GBSS. Analysis of granule-bound proteins showed a dramatic reduction of GBSS protein in ptst mutant starch granules. Pull-down assays with recombinant proteins in vitro, as well as immunoprecipitation assays in planta, revealed that GBSS physically interacts with PTST via a coiled coil. Furthermore, we show that the CBM domain of PTST, which mediates its interaction with starch granules, is also required for correct GBSS localisation. Fluorescently tagged Arabidopsis GBSS, expressed either in tobacco or Arabidopsis leaves, required the presence of Arabidopsis PTST to localise to starch granules. Mutation of the CBM of PTST caused GBSS to remain in the plastid stroma. PTST fulfils a previously unknown function in targeting GBSS to starch. This sheds new light on the importance of targeting biosynthetic enzymes to sub-cellular sites where their action is required. Importantly, PTST represents a promising new gene target for the biotechnological modification of starch composition, as it is

  16. Affinity chromatography—dependent selection (ACDS) of genomic DNA fragments bound specifically to bacterial synthesized Myc/Myn proteins

    Institute of Scientific and Technical Information of China (English)

    SHICAN; PEIWANG; 等

    1995-01-01

    This paper describes an approach to seek for mouse c-Myc/Myn proteins-bound specific sequences among genomic DNA.cDNA fragment of myn gene was obtained through RT-PCR technique from RNA of NIH3T3 cells.DNA fragments encoding BR/HLH/LZ structure of Myc and Myn proteins were cloned in frame into pGEX-2T vector respectively.Fusion GST-Myc and GST-Myn synthesized in E.coli hosts showed affinity to CACGTG E-box DNA and subsequently interacted with genomic fragments prepared through whole-genome-PCR.A PCR-assisted procedure which combines protein-DNA interaction and affinity chromatography was designed to enrich Myc/Myn bound DNA.At least two genomic DNA fragments obtained exhibit specifical binding capacity to Myc/Myn complex but not to GST alone.Significance of the work and of the technique itself as well asidentification of the DNAs are discussed.

  17. Orphan nuclear receptor Errγ induces C-reactive protein gene expression through induction of ER-bound Bzip transmembrane transcription factor CREBH.

    Directory of Open Access Journals (Sweden)

    Jagannath Misra

    Full Text Available The orphan nuclear receptor estrogen-related receptor-γ (ERRγ is a constitutively active transcription factor regulating genes involved in several important cellular processes, including hepatic glucose metabolism, alcohol metabolism, and the endoplasmic reticulum (ER stress response. cAMP responsive element-binding protein H (CREBH is an ER-bound bZIP family transcription factor that is activated upon ER stress and regulates genes encoding acute-phase proteins whose expression is increased in response to inflammation. Here, we report that ERRγ directly regulates CREBH gene expression in response to ER stress. ERRγ bound to the ERRγ response element (ERRE in the CREBH promoter. Overexpression of ERRγ by adenovirus significantly increased expression of CREBH as well as C-reactive protein (CRP, whereas either knockdown of ERRγ or inhibition of ERRγ by ERRγ specific inverse agonist, GSK5182, substantially inhibited ER stress-mediated induction of CREBH and CRP. The transcriptional coactivator PGC1α was required for ERRγ mediated induction of the CREBH gene as demonstrated by the chromatin immunoprecipitation (ChIP assay showing binding of both ERRγ and PGC1α on the CREBH promoter. The ChIP assay also revealed that histone H3 and H4 acetylation occurred at the ERRγ and PGC1α binding site. Moreover, chronic alcoholic hepatosteatosis, as well as the diabetic obese condition significantly increased CRP gene expression, and this increase was significantly attenuated by GSK5182 treatment. We suggest that orphan nuclear receptor ERRγ directly regulates the ER-bound transcription factor CREBH in response to ER stress and other metabolic conditions.

  18. The membrane bound LRR lipoprotein Slr, and the cell wall-anchored M1 protein from Streptococcus pyogenes both interact with type I collagen.

    Directory of Open Access Journals (Sweden)

    Marta Bober

    Full Text Available Streptococcus pyogenes is an important human pathogen and surface structures allow it to adhere to, colonize and invade the human host. Proteins containing leucine rich repeats (LRR have been identified in mammals, viruses, archaea and several bacterial species. The LRRs are often involved in protein-protein interaction, are typically 20-30 amino acids long and the defining feature of the LRR motif is an 11-residue sequence LxxLxLxxNxL (x being any amino acid. The streptococcal leucine rich (Slr protein is a hypothetical lipoprotein that has been shown to be involved in virulence, but at present no ligands for Slr have been identified. We could establish that Slr is a membrane attached horseshoe shaped lipoprotein by homology modeling, signal peptidase II inhibition, electron microscopy (of bacteria and purified protein and immunoblotting. Based on our previous knowledge of LRR proteins we hypothesized that Slr could mediate binding to collagen. We could show by surface plasmon resonance that recombinant Slr and purified M1 protein bind with high affinity to collagen I. Isogenic slr mutant strain (MB1 and emm1 mutant strain (MC25 had reduced binding to collagen type I as shown by slot blot and surface plasmon resonance. Electron microscopy using gold labeled Slr showed multiple binding sites to collagen I, both to the monomeric and the fibrillar structure, and most binding occurred in the overlap region of the collagen I fibril. In conclusion, we show that Slr is an abundant membrane bound lipoprotein that is co-expressed on the surface with M1, and that both these proteins are involved in recruiting collagen type I to the bacterial surface. This underlines the importance of S. pyogenes interaction with extracellular matrix molecules, especially since both Slr and M1 have been shown to be virulence factors.

  19. A Potential Protein-RNA Recognition Event Along the RISC-Loading Pathway from the Structure of A. aeolicus Argonaute with Externally Bound siRNA

    Energy Technology Data Exchange (ETDEWEB)

    Yuan,Y.; Pei, Y.; Chen, H.; Tuschl, T.; Patel, D.

    2006-01-01

    Argonaute proteins are key components of the RNA-induced silencing complex (RISC). They provide both architectural and catalytic functionalities associated with small interfering RNA (siRNA) guide strand recognition and subsequent guide strand-mediated cleavage of complementary mRNAs. We report on the 3.0 {angstrom} crystal structures of 22-mer and 26-mer siRNAs bound to Aquifex aeolicus Argonaute (Aa-Ago), where one 2 nt 3' overhang of the siRNA inserts into a cavity positioned on the outer surface of the PAZ-containing lobe of the bilobal Aa-Ago architecture. The first overhang nucleotide stacks over a tyrosine ring, while the second overhang nucleotide, together with the intervening sugar-phosphate backbone, inserts into a preformed surface cavity. Photochemical crosslinking studies on Aa-Ago with 5-iodoU-labeled single-stranded siRNA and siRNA duplex provide support for this externally bound siRNA-Aa-Ago complex. The structure and biochemical data together provide insights into a protein-RNA recognition event potentially associated with the RISC-loading pathway.

  20. A FRAP model to investigate reaction-diffusion of proteins within a bounded domain: a theoretical approach

    CERN Document Server

    Tsibidis, George D

    2008-01-01

    Temporally and spatially resolved measurements of protein transport inside cells provide important clues to the functional architecture and dynamics of biological systems. Fluorescence Recovery After Photobleaching (FRAP) technique has been used over the past three decades to measure the mobility of macromolecules and protein transport and interaction with immobile structures inside the cell nucleus. A theoretical model is presented that aims to describe protein transport inside the nucleus, a process which is influenced by the presence of a boundary (i.e. membrane). A set of reaction-diffusion equations is employed to model both the diffusion of proteins and their interaction with immobile binding sites. The proposed model has been designed to be applied to biological samples with a Confocal Laser Scanning Microscope (CLSM) equipped with the feature to bleach regions characterised by a scanning beam that has a radially Gaussian distributed profile. The proposed model leads to FRAP curves that depend on the o...

  1. Determination of steady-state protein breakdown rate in vivo by the disappearance of protein-bound tracer-labeled amino acids

    DEFF Research Database (Denmark)

    Holm, Lars; O'Rourke, Bruce; Ebenstein, David;

    2013-01-01

    A method to determine the rate of protein breakdown in individual proteins was developed and tested in rats and confirmed in humans, using administration of deuterium oxide and incorporation of the deuterium into alanine that was subsequently incorporated into body proteins. Measurement of the fr...... applicability of this protein-specific FBR approach is suitable for human in vivo experimentation. The labeling period of deuterium oxide administration is dependent on the turnover rate of the protein of interest.......A method to determine the rate of protein breakdown in individual proteins was developed and tested in rats and confirmed in humans, using administration of deuterium oxide and incorporation of the deuterium into alanine that was subsequently incorporated into body proteins. Measurement of the...... fractional breakdown rate of proteins was determined from the rate of disappearance of deuterated alanine from the proteins. The rate of disappearance of deuterated alanine from the proteins was calculated using an exponential decay, giving the fractional breakdown rate (FBR) of the proteins. The...

  2. Optimised purification and characterisation of lipid transfer protein 1 (LTP1) and its lipid-bound isoform LTP1b from barley malt.

    Science.gov (United States)

    Nieuwoudt, Melanie; Lombard, Nicolaas; Rautenbach, Marina

    2014-08-15

    In beer brewing, brewers worldwide strive to obtain product consistency in terms of flavour, colour and foam. Important proteins contributing to beer foam are lipid transfer proteins (LTPs), in particular LTP1 and its lipid-bound isoform LTP1b, which are known to transport lipids in vivo and prevent lipids from destabilising the beer foam. LTP1 and LTP1b were successfully purified using only five purification steps with a high purified protein yield (160 mg LTP1 and LTP1b from 200 g barley). Circular dichroism of LTP1 and LTP1b confirmed that both proteins are highly tolerant to high temperatures (>90 °C) and are pH stable, particularly at a neutral to a more basic pH. Only LTP1 exhibited antiyeast and thermo-stable lytic activity, while LTP1b was inactive, indicating that the fatty acid moiety compromised the antimicrobial activity of LTP1. This lack in antiyeast activity and the positive foam properties of LTP1b would benefit beer fermentation and quality.

  3. A Quantitative Approach to Evaluate the Impact of Fluorescent Labeling on Membrane-Bound HIV-Gag Assembly by Titration of Unlabeled Proteins.

    Science.gov (United States)

    Gunzenhäuser, Julia; Wyss, Romain; Manley, Suliana

    2014-01-01

    The assembly process of the human immunodeficiency virus 1 (HIV-1) is driven by the viral polyprotein Gag. Fluorescence imaging of Gag protein fusions is widely performed and has revealed important information on viral assembly. Gag fusion proteins are commonly co-transfected with an unlabeled form of Gag to prevent labeling artifacts such as morphological defects and decreased infectivity. Although viral assembly is widely studied on individual cells, the efficiency of the co-transfection rescue has never been tested at the single cell level. Here, we first develop a methodology to quantify levels of unlabeled to labeled Gag in single cells using a fluorescent reporter protein for unlabeled Gag and fluorescence correlation spectroscopy. Using super-resolution imaging based on photoactivated localization microscopy (PALM) combined with molecular counting we then study the nanoscale morphology of Gag clusters as a function of unlabeled to labeled Gag ratios in single cells. We show that for a given co-transfection ratio, individual cells express a wide range of protein ratios, necessitating a quantitative read-out for the expression of unlabeled Gag. Further, we show that monomerically labeled Gag assembles into membrane-bound clusters that are morphologically indistinguishable from mixtures of unlabeled and labeled Gag.

  4. A Quantitative Approach to Evaluate the Impact of Fluorescent Labeling on Membrane-Bound HIV-Gag Assembly by Titration of Unlabeled Proteins.

    Directory of Open Access Journals (Sweden)

    Julia Gunzenhäuser

    Full Text Available The assembly process of the human immunodeficiency virus 1 (HIV-1 is driven by the viral polyprotein Gag. Fluorescence imaging of Gag protein fusions is widely performed and has revealed important information on viral assembly. Gag fusion proteins are commonly co-transfected with an unlabeled form of Gag to prevent labeling artifacts such as morphological defects and decreased infectivity. Although viral assembly is widely studied on individual cells, the efficiency of the co-transfection rescue has never been tested at the single cell level. Here, we first develop a methodology to quantify levels of unlabeled to labeled Gag in single cells using a fluorescent reporter protein for unlabeled Gag and fluorescence correlation spectroscopy. Using super-resolution imaging based on photoactivated localization microscopy (PALM combined with molecular counting we then study the nanoscale morphology of Gag clusters as a function of unlabeled to labeled Gag ratios in single cells. We show that for a given co-transfection ratio, individual cells express a wide range of protein ratios, necessitating a quantitative read-out for the expression of unlabeled Gag. Further, we show that monomerically labeled Gag assembles into membrane-bound clusters that are morphologically indistinguishable from mixtures of unlabeled and labeled Gag.

  5. Optimised purification and characterisation of lipid transfer protein 1 (LTP1) and its lipid-bound isoform LTP1b from barley malt.

    Science.gov (United States)

    Nieuwoudt, Melanie; Lombard, Nicolaas; Rautenbach, Marina

    2014-08-15

    In beer brewing, brewers worldwide strive to obtain product consistency in terms of flavour, colour and foam. Important proteins contributing to beer foam are lipid transfer proteins (LTPs), in particular LTP1 and its lipid-bound isoform LTP1b, which are known to transport lipids in vivo and prevent lipids from destabilising the beer foam. LTP1 and LTP1b were successfully purified using only five purification steps with a high purified protein yield (160 mg LTP1 and LTP1b from 200 g barley). Circular dichroism of LTP1 and LTP1b confirmed that both proteins are highly tolerant to high temperatures (>90 °C) and are pH stable, particularly at a neutral to a more basic pH. Only LTP1 exhibited antiyeast and thermo-stable lytic activity, while LTP1b was inactive, indicating that the fatty acid moiety compromised the antimicrobial activity of LTP1. This lack in antiyeast activity and the positive foam properties of LTP1b would benefit beer fermentation and quality. PMID:24679818

  6. Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

    Science.gov (United States)

    Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

  7. Effects of Solution Chemistry and Aging Time on Prion Protein Adsorption and Replication of Soil-Bound Prions

    OpenAIRE

    Samuel E Saunders; Yuan, Qi; Bartz, Jason C.; Bartelt-Hunt, Shannon

    2011-01-01

    Prion interactions with soil may play an important role in the transmission of chronic wasting disease (CWD) and scrapie. Prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. We investigated HY TME prion protein (PrPSc) adsorption to soil minerals in aqueous solutions of phosphate buffered saline (PBS), sodium chloride, calcium chloride, and deionized water using ...

  8. Crystal structure of the E2 transactivation domain of human papillomavirus type 11 bound to a protein interaction inhibitor.

    Science.gov (United States)

    Wang, Yong; Coulombe, René; Cameron, Dale R; Thauvette, Louise; Massariol, Marie-Josée; Amon, Lynn M; Fink, Dominique; Titolo, Steve; Welchner, Ewald; Yoakim, Christiane; Archambault, Jacques; White, Peter W

    2004-02-20

    Interaction between the E2 protein and E1 helicase of human papillomaviruses (HPVs) is essential for the initiation of viral DNA replication. We recently described a series of small molecules that bind to the N-terminal transactivation domain (TAD) of HPV type 11 E2 and inhibits its interaction with E1 in vitro and in cellular assays. Here we report the crystal structures of both the HPV11 TAD and of a complex between this domain and an inhibitor, at 2.5- and 2.4-A resolution, respectively. The HPV11 TAD structure is very similar to that of the analogous domain of HPV16. Inhibitor binding caused no significant alteration of the protein backbone, but movements of several amino acid side chains at the binding site, in particular those of Tyr-19, His-32, Leu-94, and Glu-100, resulted in the formation of a deep hydrophobic pocket that accommodates the indandione moiety of the inhibitor. Mutational analysis provides functional evidence for specific interactions between Tyr-19 and E1 and between His-32 and the inhibitor. A second inhibitor molecule is also present at the binding pocket. Although evidence is presented that this second molecule makes only weak interactions with the protein and is likely an artifact of crystallization, its presence defines additional regions of the binding pocket that could be exploited to design more potent inhibitors. PMID:14634007

  9. Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE.

    Science.gov (United States)

    Das, Nibhriti

    2015-11-01

    Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA.

  10. A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts

    Directory of Open Access Journals (Sweden)

    Galperin Michael Y

    2005-06-01

    Full Text Available Abstract Background Analysis of complete microbial genomes showed that intracellular parasites and other microorganisms that inhabit stable ecological niches encode relatively primitive signaling systems, whereas environmental microorganisms typically have sophisticated systems of environmental sensing and signal transduction. Results This paper presents results of a comprehensive census of signal transduction proteins – histidine kinases, methyl-accepting chemotaxis receptors, Ser/Thr/Tyr protein kinases, adenylate and diguanylate cyclases and c-di-GMP phosphodiesterases – encoded in 167 bacterial and archaeal genomes, sequenced by the end of 2004. The data have been manually checked to avoid false-negative and false-positive hits that commonly arise during large-scale automated analyses and compared against other available resources. The census data show uneven distribution of most signaling proteins among bacterial and archaeal phyla. The total number of signal transduction proteins grows approximately as a square of genome size. While histidine kinases are found in representatives of all phyla and are distributed according to the power law, other signal transducers are abundant in certain phylogenetic groups but virtually absent in others. Conclusion The complexity of signaling systems differs even among closely related organisms. Still, it usually can be correlated with the phylogenetic position of the organism, its lifestyle, and typical environmental challenges it encounters. The number of encoded signal transducers (or their fraction in the total protein set can be used as a measure of the organism's ability to adapt to diverse conditions, the 'bacterial IQ', while the ratio of transmembrane receptors to intracellular sensors can be used to define whether the organism is an 'extrovert', actively sensing the environmental parameters, or an 'introvert', more concerned about its internal homeostasis. Some of the microorganisms with the

  11. OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins.

    Science.gov (United States)

    Holbrook, Lisa-Marie; Kwong, Lai-Shan; Metcalfe, Clive L; Fenouillet, Emmanuel; Jones, Ian M; Barclay, A Neil

    2016-01-01

    In vivo, enzymatic reduction of some protein disulfide bonds, allosteric disulfide bonds, provides an important level of structural and functional regulation. The free cysteine residues generated can be labeled by maleimide reagents, including biotin derivatives, allowing the reduced protein to be detected or purified. During the screening of monoclonal antibodies for those specific for the reduced forms of proteins, we isolated OX133, a unique antibody that recognizes polypeptide resident, N-ethylmaleimide (NEM)-modified cysteine residues in a sequence-independent manner. OX133 offers an alternative to biotin-maleimide reagents for labeling reduced/alkylated antigens and capturing reduced/alkylated proteins with the advantage that NEM-modified proteins are more easily detected in mass spectrometry, and may be more easily recovered than is the case following capture with biotin based reagents. PMID:26986548

  12. Enhancement of Antitumor Effect of Tegafur/Uracil (UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide, PSK, in Mouse Models

    Institute of Scientific and Technical Information of China (English)

    Ryoji Katoh; Mitsuru Ooshiro

    2007-01-01

    We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV)and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly.UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

  13. Reproducing the conformations of protein-bound ligands: a critical evaluation of several popular conformational searching tools.

    Science.gov (United States)

    Boström, J

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution (Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*\\GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed. PMID:12160095

  14. Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

    Directory of Open Access Journals (Sweden)

    Makio Saeki

    Full Text Available Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

  15. Reproducing the conformations of protein-bound ligands: a critical evaluation of several popular conformational searching tools.

    Science.gov (United States)

    Boström, J

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution (Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*\\GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed.

  16. Use of mass spectrometry techniques for the characterization of metal bound to proteins (metallomics) in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Ariza, J.L.; Garcia-Barrera, T.; Lorenzo, F.; Bernal, V.; Villegas, M.J.; Oliveira, V

    2004-10-25

    The need to determine the individual chemical species (speciation), especially when they are known to have a differential action and behavior in relation to toxicity, mobility, or bioavailability, is discussed. The analytical approaches for small mass metal species characterization, as well as sample treatment and storage, is now well established on the basis of chromatographic-atomic detector combinations. The description of a new scenario centered on endogenous and exogenous metallic species in biological systems, bioactive macromolecules, such as proteins, DNA restriction fragments, phytochelatins, metallothioneins and others is fulfilled. Many of these systems are not well known at present and require a new generation of analytical tools that substitute the traditional atomic detectors based in the use of photons (atomic absorption spectrometry (AAS), flame photoionization detector (FPD), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), atomic fluorescence spectroscopy (AFS)) by mass detectors (mass spectrometry (MS) and inductively coupled plasma-mass spectrometry (ICP-MS)) that characterize ions. The photonic analytical tool is now being substituted by the ionic paradigm. Many cases related to biological molecules involving proteins and multiprotein systems, in which metals frequently participate (metallomics) are described, and a generic metallomics analytical approach is proposed for the identification and quantification of metalloproteins, and other metallomacromolecules present in life systems, on the basis of three experimental focuses: (i) a separation technique - selectivity component; (ii) an element-high sensitivity detector--sensitivity component; and (iii) a molecule-specific detector, generally based on mass spectrometry-structural component. This multiplexed analytical approach brings together both elemental and molecular detectors for easy metalloproteins identification. Finally, the possibilities of the metallomics approach in

  17. Structure of the red fluorescent protein from a lancelet (Branchiostoma lanceolatum): a novel GYG chromophore covalently bound to a nearby tyrosine

    International Nuclear Information System (INIS)

    The crystal structure of the novel red emitting fluorescent protein from lancelet Branchiostoma lanceolatum (Chordata) revealed an unusual five residues cyclic unit comprising Gly58-Tyr59-Gly60 chromophore, the following Phe61 and Tyr62 covalently bound to chromophore Tyr59. A key property of proteins of the green fluorescent protein (GFP) family is their ability to form a chromophore group by post-translational modifications of internal amino acids, e.g. Ser65-Tyr66-Gly67 in GFP from the jellyfish Aequorea victoria (Cnidaria). Numerous structural studies have demonstrated that the green GFP-like chromophore represents the ‘core’ structure, which can be extended in red-shifted proteins owing to modifications of the protein backbone at the first chromophore-forming position. Here, the three-dimensional structures of green laGFP (λex/λem = 502/511 nm) and red laRFP (λex/λem ≃ 521/592 nm), which are fluorescent proteins (FPs) from the lancelet Branchiostoma lanceolatum (Chordata), were determined together with the structure of a red variant laRFP-ΔS83 (deletion of Ser83) with improved folding. Lancelet FPs are evolutionarily distant and share only ∼20% sequence identity with cnidarian FPs, which have been extensively characterized and widely used as genetically encoded probes. The structure of red-emitting laRFP revealed three exceptional features that have not been observed in wild-type fluorescent proteins from Cnidaria reported to date: (i) an unusual chromophore-forming sequence Gly58-Tyr59-Gly60, (ii) the presence of Gln211 at the position of the conserved catalytic Glu (Glu222 in Aequorea GFP), which proved to be crucial for chromophore formation, and (iii) the absence of modifications typical of known red chromophores and the presence of an extremely unusual covalent bond between the Tyr59 Cβ atom and the hydroxyl of the proximal Tyr62. The impact of this covalent bond on the red emission and the large Stokes shift (∼70 nm) of laRFP was verified

  18. Structure of the red fluorescent protein from a lancelet (Branchiostoma lanceolatum): a novel GYG chromophore covalently bound to a nearby tyrosine

    Energy Technology Data Exchange (ETDEWEB)

    Pletnev, Vladimir Z., E-mail: vzpletnev@gmail.com; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Souslova, Ekaterina A.; Fradkov, Arkady F.; Chudakov, Dmitry M.; Chepurnykh, Tatyana; Yampolsky, Ilia V. [Russian Academy of Sciences, Moscow (Russian Federation); Wlodawer, Alexander [National Cancer Institute, Frederick, MD 21702 (United States); Dauter, Zbigniew [National Cancer Institute, Argonne, IL 60439 (United States); Pletnev, Sergei, E-mail: vzpletnev@gmail.com [National Cancer Institute, Argonne, IL 60439 (United States); SAIC-Frederick, Argonne, IL 60439 (United States); Russian Academy of Sciences, Moscow (Russian Federation)

    2013-09-01

    The crystal structure of the novel red emitting fluorescent protein from lancelet Branchiostoma lanceolatum (Chordata) revealed an unusual five residues cyclic unit comprising Gly58-Tyr59-Gly60 chromophore, the following Phe61 and Tyr62 covalently bound to chromophore Tyr59. A key property of proteins of the green fluorescent protein (GFP) family is their ability to form a chromophore group by post-translational modifications of internal amino acids, e.g. Ser65-Tyr66-Gly67 in GFP from the jellyfish Aequorea victoria (Cnidaria). Numerous structural studies have demonstrated that the green GFP-like chromophore represents the ‘core’ structure, which can be extended in red-shifted proteins owing to modifications of the protein backbone at the first chromophore-forming position. Here, the three-dimensional structures of green laGFP (λ{sub ex}/λ{sub em} = 502/511 nm) and red laRFP (λ{sub ex}/λ{sub em} ≃ 521/592 nm), which are fluorescent proteins (FPs) from the lancelet Branchiostoma lanceolatum (Chordata), were determined together with the structure of a red variant laRFP-ΔS83 (deletion of Ser83) with improved folding. Lancelet FPs are evolutionarily distant and share only ∼20% sequence identity with cnidarian FPs, which have been extensively characterized and widely used as genetically encoded probes. The structure of red-emitting laRFP revealed three exceptional features that have not been observed in wild-type fluorescent proteins from Cnidaria reported to date: (i) an unusual chromophore-forming sequence Gly58-Tyr59-Gly60, (ii) the presence of Gln211 at the position of the conserved catalytic Glu (Glu222 in Aequorea GFP), which proved to be crucial for chromophore formation, and (iii) the absence of modifications typical of known red chromophores and the presence of an extremely unusual covalent bond between the Tyr59 C{sup β} atom and the hydroxyl of the proximal Tyr62. The impact of this covalent bond on the red emission and the large Stokes shift (

  19. Inhibitor-3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore-bound protein phosphatase-1.

    Science.gov (United States)

    Eiteneuer, Annika; Seiler, Jonas; Weith, Matthias; Beullens, Monique; Lesage, Bart; Krenn, Veronica; Musacchio, Andrea; Bollen, Mathieu; Meyer, Hemmo

    2014-11-18

    Faithful chromosome segregation during mitosis is tightly regulated by opposing activities of Aurora B kinase and protein phosphatase-1 (PP1). PP1 function at kinetochores has been linked to SDS22, but the exact localization of SDS22 and how it affects PP1 are controversial. Here, we confirm that SDS22 is required for PP1 activity, but show that SDS22 does not normally localize to kinetochores. Instead, SDS22 is kept in solution by formation of a ternary complex with PP1 and inhibitor-3 (I3). Depletion of I3 does not affect the amount of PP1 at kinetochores but causes quantitative association of SDS22 with PP1 on KNL1 at the kinetochore. Such accumulation of SDS22 at kinetochores interferes with PP1 activity and inhibits Aurora B threonine-232 dephosphorylation, which leads to increased Aurora B activity in metaphase and persistence in anaphase accompanied with segregation defects. We propose a model in which I3 regulates an SDS22-mediated PP1 activation step in solution that precedes SDS22 dissociation and transfer of PP1 to kinetochores, and which is required for PP1 to efficiently antagonize Aurora B. PMID:25298395

  20. A critical switch in the enzymatic properties of the Cid1 protein deciphered from its product-bound crystal structure.

    Science.gov (United States)

    Munoz-Tello, Paola; Gabus, Caroline; Thore, Stéphane

    2014-03-01

    The addition of uridine nucleotide by the poly(U) polymerase (PUP) enzymes has a demonstrated impact on various classes of RNAs such as microRNAs (miRNAs), histone-encoding RNAs and messenger RNAs. Cid1 protein is a member of the PUP family. We solved the crystal structure of Cid1 in complex with non-hydrolyzable UMPNPP and a short dinucleotide compound ApU. These structures revealed new residues involved in substrate/product stabilization. In particular, one of the three catalytic aspartate residues explains the RNA dependence of its PUP activity. Moreover, other residues such as residue N165 or the β-trapdoor are shown to be critical for Cid1 activity. We finally suggest that the length and sequence of Cid1 substrate RNA influence the balance between Cid1's processive and distributive activities. We propose that particular processes regulated by PUPs require the enzymes to switch between the two types of activity as shown for the miRNA biogenesis where PUPs can either promote DICER cleavage via short U-tail or trigger miRNA degradation by adding longer poly(U) tail. The enzymatic properties of these enzymes may be critical for determining their particular function in vivo. PMID:24322298

  1. Coordination Environment of Cu(II) Ions Bound to N-Terminal Peptide Fragments of Angiogenin Protein.

    Science.gov (United States)

    Magrì, Antonio; Munzone, Alessia; Peana, Massimiliano; Medici, Serenella; Zoroddu, Maria Antonietta; Hansson, Orjan; Satriano, Cristina; Rizzarelli, Enrico; La Mendola, Diego

    2016-08-01

    Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in patients affected by different types of cancers. The specific Ang cellular receptors have not been identified, but it is known that Ang-actin interaction induces changes both in the cell cytoskeleton and in the extracellular matrix. Most in vitro studies use the recombinant form (r-Ang) instead of the form that is normally present in vivo ("wild-type", wt-Ang). The first residue of r-Ang is a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological activity is influenced by copper ions. To elucidate the role of such a free amino group on the protein-copper binding, we scrutinized the copper(II) complexes with the peptide fragments Ang(1-17) and AcAng(1-17), which encompass the sequence 1-17 of angiogenin (QDNSRYTHFLTQHYDAK-NH₂), with free amino and acetylated N-terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the two peptides show a different metal coordination environment. Confocal microscopy imaging of neuroblastoma cells with the actin staining supports the spectroscopic results, with the finding of different responses in the cytoskeleton organization upon the interaction, in the presence or not of copper ions, with the free amino and the acetylated N-terminus peptides.

  2. Bounded Rationality

    Directory of Open Access Journals (Sweden)

    Ballester Pla, Coralio

    2012-03-01

    Full Text Available The observation of the actual behavior by economic decision makers in the lab and in the field justifies that bounded rationality has been a generally accepted assumption in many socio-economic models. The goal of this paper is to illustrate the difficulties involved in providing a correct definition of what a rational (or irrational agent is. In this paper we describe two frameworks that employ different approaches for analyzing bounded rationality. The first is a spatial segregation set-up that encompasses two optimization methodologies: backward induction and forward induction. The main result is that, even under the same state of knowledge, rational and non-rational agents may match their actions. The second framework elaborates on the relationship between irrationality and informational restrictions. We use the beauty contest (Nagel, 1995 as a device to explain this relationship.

    La observación del comportamiento de los agentes económicos tanto en el laboratorio como en la vida real justifica que la racionalidad acotada sea un supuesto aceptado en numerosos modelos socio-económicos. El objetivo de este artículo es ilustrar las dificultades que conlleva una correcta definición de qué es un agente racional (irracional. En este artículo se describen dos marcos que emplean diferentes metodologías para analizar la racionalidad acotada. El primero es un modelo de segregación espacial donde se contrastan dos metodologías de optimización: inducción hacia atrás y hacia adelante. El resultado principal es que, incluso con el mismo nivel de conocimiento, tanto agentes racionales como irracionales podrían coincidir en sus acciones. El segundo marco trabaja sobre la relación entre irracionalidad y restricción de información. Se utiliza el juego llamado “beauty contest” (Nagel 1995 como mecanismo para explicar dicha relación.

  3. Protein-bound Polysaccharide-K Inhibits Hedgehog Signaling Through Down-regulation of MAML3 and RBPJ Transcription Under Hypoxia, Suppressing the Malignant Phenotype in Pancreatic Cancer.

    Science.gov (United States)

    Yamasaki, Akio; Onishi, Hideya; Imaizumi, Akira; Kawamoto, Makoto; Fujimura, Akiko; Oyama, Yasuhiro; Katano, Mitsuo

    2016-08-01

    Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia. PSK reduced SMO, MAML3 and RBPJ expression in pancreatic cancer cells under hypoxia. PSK also blocked RBPJ-induced invasiveness under hypoxia by inhibiting matrix metalloproteinase expression. Lastly, we showed that PSK attenuated RBPJ-induced proliferation both in vitro and in vivo. These results suggest that PSK suppresses Hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, inhibiting the induction of a malignant phenotype in pancreatic cancer. Our results may lead to development of new treatments for refractory pancreatic cancer using PSK as a Hedgehog inhibitor. PMID:27466498

  4. Isolation of an inactive bovine heart cAMP-dependent protein kinase holoenzyme containing bound cAMP

    International Nuclear Information System (INIS)

    Bovine heart Type II cAMP-dependent protein kinase (PK) was purified to homogeneity as determined by SDS-PAGE. The purification steps were DEAE-cellulose, ammonium sulfate precipitation, phenyl-Sepharose, alumina C-γ, and HPLC-DEAE. The last step resolved two distinct peaks of cAMP dependent kinase activity (activity ratios = 0.05 - 0.10) eluting at approximately 250 (Peak 1) and 275 (Peak 2) mM NaCl. When subjected to HPLC-gel permeation they had the same Stoke's radii. Linear sucrose gradients gave S/sub 20,w/ values of 7.73 S and 7.25 S for Peaks 1 and 2, respectively. It was determined by integrating the areas of scanned SDS-PAGE bands that regulatory and catalytic subunits were present in equimolar amounts in both Peaks 1 and 2. The ratios of equilibrium [3H] cAMP binding to kinase activity for the two peaks were the same. cAMP was present in trace amounts in Peak 1 but in stoichiometric amounts in Peak 2 (between 25 and 75 % saturation of cAMP binding sites). Although SDS-PAGE analysis ruled out conversions by proteolysis or autophosphorylation-dephosphorylation, Peak 1 could be partially converted to Peak 2 by the addition of subsaturating amounts of cAMP, 3H] cAMP binding and in kinase activation (as indicated by a larger Hill coefficient) of Peak 2 relative to Peak 1 also supported the presence of cAMP in Peak 2. In conclusion, two forms of inactive PK have been isolated, one of which is a ternary complex of PK holoenzyme and cAMP. This complex could represent a cellular form of the enzyme which is primed for activation

  5. Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique.

    Science.gov (United States)

    Bhaskara, Srividya

    2016-01-01

    Histone deacetylases 1 and 2 (HDAC1,2) localize to the sites of DNA replication. In the previous study, using a selective inhibitor and a genetic knockdown system, we showed novel functions for HDAC1,2 in replication fork progression and nascent chromatin maintenance in mammalian cells. Additionally, we used a BrdU-ChIP-Slot-Western technique that combines chromatin immunoprecipitation (ChIP) of bromo-deoxyuridine (BrdU)-labeled DNA with slot blot and Western analyses to quantitatively measure proteins or histone modification associated with nascent DNA. Actively dividing cells were treated with HDAC1,2 selective inhibitor or transfected with siRNAs against Hdac1 and Hdac2 and then newly synthesized DNA was labeled with the thymidine analog bromodeoxyuridine (BrdU). The BrdU labeling was done at a time point when there was no significant cell cycle arrest or apoptosis due to the loss of HDAC1,2 functions. Following labeling of cells with BrdU, chromatin immunoprecipitation (ChIP) of histone acetylation marks or the chromatin-remodeler was performed with specific antibodies. BrdU-labeled input DNA and the immunoprecipitated (or ChIPed) DNA was then spotted onto a membrane using the slot blot technique and immobilized using UV. The amount of nascent DNA in each slot was then quantitatively assessed using Western analysis with an anti-BrdU antibody. The effect of loss of HDAC1,2 functions on the levels of newly synthesized DNA-associated histone acetylation marks and chromatin remodeler was then determined by normalizing the BrdU-ChIP signal obtained from the treated samples to the control samples. PMID:26863264

  6. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Directory of Open Access Journals (Sweden)

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  7. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography : application to non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    Herráez-Hernández, R; van de Merbel, N C; Brinkman, U A

    1995-01-01

    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of dr

  8. Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study.

    Science.gov (United States)

    Tao, Xia; Thijssen, Stephan; Kotanko, Peter; Ho, Chih-Hu; Henrie, Michael; Stroup, Eric; Handelman, Garry

    2016-03-22

    Protein-bound uraemic toxins (PBUTs) cause various deleterious effects in end-stage kidney disease patients, because their removal by conventional haemodialysis (HD) is severely limited by their low free fraction in plasma. Here we provide an experimental validation of the concept that the HD dialytic removal of PBUTs can be significantly increased by extracorporeal infusion of PBUT binding competitors. The binding properties of indoxyl sulfate (IS), indole-3-acetic acid (IAA) and hippuric acid (HIPA) and their binding competitors, ibuprofen (IBU), furosemide (FUR) and tryptophan (TRP) were studied in uraemic plasma. The effect of binding competitor infusion on fractional removal of PBUT was then quantified in an ex vivo single-pass HD model using uraemic human whole blood. The infusion of a combination of IBU and FUR increased the fractional removal of IS from 6.4 ± 0.1 to 18.3 ± 0.4%. IAA removal rose from 16.8 ± 0.3 to 34.5 ± 0.7%. TRP infusion increased the removal of IS and IAA to 10.5 ± 0.1% and 27.1 ± 0.3%, respectively. Moderate effects were observed on HIPA removal. Pre-dialyzer infusion of PBUT binding competitors into the blood stream can increase the HD removal of PBUTs. This approach can potentially be applied in current HD settings.

  9. [The Role of Membrane-Bound Heat Shock Proteins Hsp90 in Migration of Tumor Cells in vitro and Involvement of Cell Surface Heparan Sulfate Proteoglycans in Protein Binding to Plasma Membrane].

    Science.gov (United States)

    Snigireva, A V; Vrublevskaya, V V; Skarga, Y Y; Morenkov, O S

    2016-01-01

    Heat shock protein Hsp90, detected in the extracellular space and on the membrane of cells, plays an important role in cell motility, migration, invasion and metastasis of tumor cells. At present, the functional role and molecular mechanisms of Hsp90 binding to plasma membrane are not elucidated. Using isoform-specific antibodies against Hsp90, Hsp9α and Hsp90β, we showed that membrane-bound Hsp90α and Hsp90β play a significant role in migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Disorders of sulfonation of cell heparan sulfates, cleavage of cell heparan. sulfates by heparinase I/III as well as treatment of cells with heparin lead to an abrupt reduction in the expression level of Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. The results obtained demonstrate that two isoforms of membrane-bound Hsp90 are involved in migration of tumor cells in vitro and that cell surface heparan sulfate proteoglycans play a pivotal role in the "anchoring" of Hsp90α and Hsp90β to the plasma membrane.

  10. Effects of RING-SH2Grb², a chimeric protein containing the E3 ligase domain of Cbl, on the EGFR pathway.

    Science.gov (United States)

    Lee, Wei-Hao; Wang, Pei-Yu; Lin, Yu-Hung; Chou, He-Yen; Lee, Yen-Hsien; Lee, Chien-Kuo; Pai, Li-Mei

    2014-12-31

    The E3 ubiquitin-protein ligase Casitas B-lineage lymphoma protein (Cbl) negatively regulates epidermal growth factor receptor (EGFR) signaling pathway in many organisms, and has crucial roles in cell growth, development and human pathologies, including lung cancers. RING-SH2Grb² a chimeric protein of 215 amino acids containing the RING domain of Cbl that provides E3 ligase activity, and the SH2 domain of Grb2 that serves as an adaptor for EGFR. In this study, we demonstrated that RING-SH2Grb² could promote the ubiquitinylation and degradation of EGFR in a human non-small cell lung carcinoma cell line H1299. Moreover, we discovered that the RING-SH2Grb² chimera promoted the internalization of ligand-bound EGFR, inhibited the growth of H1299 cells, and significantly suppressed tumor growth in a xenograft mouse model. In summary, our results revealed a potential new cancer therapeutic approach for non-small cell lung cancer. PMID:25575524

  11. The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

    Energy Technology Data Exchange (ETDEWEB)

    Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Mariette, Christophe [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, 1 place de Verdun, 59045 Lille Cedex (France); Van Seuningen, Isabelle, E-mail: isabelle.vanseuningen@inserm.fr [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France)

    2011-09-23

    Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

  12. Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Junya [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Hirano, Hidemi [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Structural Biology Research Center, Graduate School of Science, Nagoya University (Japan); Matsuura, Yoshiyuki, E-mail: matsuura.yoshiyuki@d.mbox.nagoya-u.ac.jp [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Structural Biology Research Center, Graduate School of Science, Nagoya University (Japan)

    2015-07-31

    In Saccharomyces cerevisiae, the protein phosphatase Cdc14p is an antagonist of mitotic cyclin-dependent kinases and is a key regulator of late mitotic events such as chromosome segregation, spindle disassembly and cytokinesis. The activity of Cdc14p is controlled by cell-cycle dependent changes in its association with its competitive inhibitor Net1p (also known as Cfi1p) in the nucleolus. For most of the cell cycle up to metaphase, Cdc14p is sequestered in the nucleolus in an inactive state. During anaphase, Cdc14p is released from Net1p, spreads into the nucleus and cytoplasm, and dephosphorylates key mitotic targets. Although regulated nucleocytoplasmic shuttling of Cdc14p has been suggested to be important for exit from mitosis, the mechanism underlying Cdc14p nuclear trafficking remains poorly understood. Here we show that the C-terminal region (residues 517–551) of Cdc14p can function as a nuclear localization signal (NLS) in vivo and also binds to Kap121p (also known as Pse1p), an essential nuclear import carrier in yeast, in a Gsp1p-GTP-dependent manner in vitro. Moreover we report a crystal structure, at 2.4 Å resolution, of Kap121p bound to the C-terminal region of Cdc14p. The structure and structure-based mutational analyses suggest that either the last five residues at the extreme C-terminus of Cdc14p (residues 547–551; Gly-Ser-Ile-Lys-Lys) or adjacent residues with similar sequence (residues 540–544; Gly-Gly-Ile-Arg-Lys) can bind to the NLS-binding site of Kap121p, with two residues (Ile in the middle and Lys at the end of the five residues) of Cdc14p making key contributions to the binding specificity. Based on comparison with other structures of Kap121p-ligand complexes, we propose “IK-NLS” as an appropriate term to refer to the Kap121p-specific NLS. - Highlights: • The C-terminus of Cdc14p binds to Kap121p in a Gsp1p-GTP-dependent manner. • The crystal structure of Kap121p-Cdc14p complex is determined. • The structure reveals how

  13. Small-angle X-ray scattering analysis reveals the ATP-bound monomeric state of the ATPase domain from the homodimeric MutL endonuclease, a GHKL phosphotransferase superfamily protein.

    Science.gov (United States)

    Iino, Hitoshi; Hikima, Takaaki; Nishida, Yuya; Yamamoto, Masaki; Kuramitsu, Seiki; Fukui, Kenji

    2015-05-01

    DNA mismatch repair is an excision system that removes mismatched bases chiefly generated by replication errors. In this system, MutL endonucleases direct the excision reaction to the error-containing strand of the duplex by specifically incising the newly synthesized strand. Both bacterial homodimeric and eukaryotic heterodimeric MutL proteins belong to the GHKL ATPase/kinase superfamily that comprises the N-terminal ATPase and C-terminal dimerization regions. Generally, the GHKL proteins show large ATPase cycle-dependent conformational changes, including dimerization-coupled ATP binding of the N-terminal domain. Interestingly, the ATPase domain of human PMS2, a subunit of the MutL heterodimer, binds ATP without dimerization. The monomeric ATP-bound state of the domain has been thought to be characteristic of heterodimeric GHKL proteins. In this study, we characterized the ATP-bound state of the ATPase domain from the Aquifex aeolicus MutL endonuclease, which is a homodimeric GHKL protein unlike the eukaryotic MutL. Gel filtration, dynamic light scattering, and small-angle X-ray scattering analyses clearly showed that the domain binds ATP in a monomeric form despite its homodimeric nature. This indicates that the uncoupling of dimerization and ATP binding is a common feature among bacterial and eukaryotic MutL endonucleases, which we suggest is closely related to the molecular mechanisms underlying mismatch repair. PMID:25809295

  14. Scattering by bound nucleons

    International Nuclear Information System (INIS)

    Scattering of a particle by bound nucleons is discussed. Effects of nucleons that are bound in a nucleus are taken as a structure function. The way how to calculate the structure function is given. (author)

  15. Variance bounding Markov chains

    OpenAIRE

    Roberts, Gareth O.; Jeffrey S. Rosenthal

    2008-01-01

    We introduce a new property of Markov chains, called variance bounding. We prove that, for reversible chains at least, variance bounding is weaker than, but closely related to, geometric ergodicity. Furthermore, variance bounding is equivalent to the existence of usual central limit theorems for all L2 functionals. Also, variance bounding (unlike geometric ergodicity) is preserved under the Peskun order. We close with some applications to Metropolis–Hastings algorithms.

  16. Crystal Structure of the Redox-Active Cofactor Dibromothymoquinone Bound to Circadian Clock Protein KaiA and Structural Basis for Dibromothymoquinone's Ability to Prevent Stimulation of KaiC Phosphorylation by KaiA

    Energy Technology Data Exchange (ETDEWEB)

    Pattanayek, Rekha; Sidiqi, Said K.; Egli, Martin [Vanderbilt-MED

    2013-09-19

    KaiA protein that stimulates KaiC phosphorylation in the cyanobacterial circadian clock was recently shown to be destabilized by dibromothymoquinone (DBMIB), thus revealing KaiA as a sensor of the plastoquinone (PQ) redox state and suggesting an indirect control of the clock by light through PQ redox changes. Here we show using X-ray crystallography that several DBMIBs are bound to KaiA dimer. Some binding modes are consistent with oligomerization of N-terminal KaiA pseudoreceiver domains and/or reduced interdomain flexibility. DBMIB bound to the C-terminal KaiA (C-KaiA) domain and limited stimulation of KaiC kinase activity by C-KaiA in the presence of DBMIB demonstrate that the cofactor may weakly inhibit KaiA-KaiC binding.

  17. The Zea mays glycine-rich RNA-binding protein MA16 is bound to a ribonucleotide(s) by a stable linkage.

    Science.gov (United States)

    Freire, Miguel Angel

    2012-09-01

    Expression of the gene encoding the maize glycine-rich RNA-binding protein MA16 is developmentally regulated and it is involved in environmental stress responses. The MA16 protein shows a wide spectrum of RNA-binding activities. On the basis of in vivo labelling, where a [³²P]phosphate label was linked to the MA16 protein, Freire and Pages (Plant Mol Biol 29:797-807, 1995) suggested that the protein may be post-translationally modified by phosphorylation. However, further analysis showed that the [³²P]phosphate label was sensitive to different treatments, suggesting that modification distinct from protein phosphorylation might occur in the MA16 protein. Biochemical analysis revealed that this [³²P]phosphate labelling was resistant to phenol extraction and denaturing SDS-PAGE but sensitive to micrococcal nuclease, RNase A and RNase T1 treatments. The mobility of [³⁵S] labelled MA16 protein on SDS-PAGE did not significantly changed after the nuclease treatments suggesting that the [³²P]phosphate label associated to MA16 protein could be a ribonucleotide or a very short ribonucleotide chain. In addition, immunoprecipitation of labelled extracts showed that the ribonucleotide(s) linked to the MA16 protein was removed by phosphorolytic activity. This activity could be catalysed by a phosphate-dependent ribonuclease. The C-terminus of MA16 protein harbouring a glycine-rich domain was predicted to be an intrinsically disordered region.

  18. Brain-specific interaction of a 91-kDa membrane-bound protein with the cytoplasmic tail of the 300-kDa mannose 6-phosphate receptor

    DEFF Research Database (Denmark)

    Rosorius, O; Issinger, O G; Braulke, T

    1996-01-01

    in microsomal and synaptosomal fractions. Furthermore, the formation of cross-link complexes with membrane proteins appeared to be developmentally and regionally regulated in the brain and inhibited upon ATP hydrolysis. The data suggest the requirement of specific protein interactions for MPR 300...

  19. Physical Uncertainty Bounds (PUB)

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-19

    This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

  20. The DMM Bound

    DEFF Research Database (Denmark)

    Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

    2010-01-01

    ) resultant by means of mixed volume, as well as recent advances on aggregate root bounds for univariate polynomials, and are applicable to arbitrary positive dimensional systems. We improve upon Canny's gap theorem [7] by a factor of O(dn-1), where d bounds the degree of the polynomials, and n is the number...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

  1. Fluorescence competition assay for the assessment of green leaf volatiles and trans-β-farnesene bound to three odorant-binding proteins in the wheat aphid Sitobion avenae (Fabricius).

    Science.gov (United States)

    Zhong, Tao; Yin, Jiao; Deng, Sisi; Li, Kebin; Cao, Yazhong

    2012-06-01

    Odorant-binding proteins (OBPs) are important parts of insect olfactory systems, and sensitive olfaction is vital for phytophagous insects in host foraging. Electrophysiological studies are helpful in understanding olfactory sensing in Sitobion avenae (Hemiptera: Aphididae), but the functions of odorant-binding proteins in this insect are poorly understood. In this study, we used fluorescence competition assays to measure the binding specificities of SaveOBPs. The results showed that both SaveOBP2 and SaveOBP3 were superior to SaveOBP7 in binding green leaf volatiles. It was unexpected that SaveOBP7 bound trans-β-farnesene strongly, which was known as alarm pheromone of this species. Host volatiles were recognized much more easily by SaveOBP2, and the observed binding activity of SaveOBP2 equaled for tested green leaf volatiles. Our results imply that SaveOBP7 might play a more important role in aphid alarm pheromone discrimination.

  2. Identification of peptides from foot-and-mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA-1*0401 and SLA-2*0401.

    Science.gov (United States)

    Pedersen, L E; Harndahl, M; Nielsen, M; Patch, J R; Jungersen, G; Buus, S; Golde, W T

    2013-06-01

    Characterization of the peptide-binding specificity of swine leukocyte antigen (SLA) class I and II molecules is critical to the understanding of adaptive immune responses of swine toward infectious pathogens. Here, we describe the complete binding motif of the SLA-2*0401 molecule based on a positional scanning combinatorial peptide library approach. By combining this binding motif with data achieved by applying the NetMHCpan peptide prediction algorithm to both SLA-1*0401 and SLA-2*0401, we identified high-affinity binding peptides. A total of 727 different 9mer and 726 different 10mer peptides within the structural proteins of foot-and-mouth disease virus (FMDV), strain A24 were analyzed as candidate T-cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA-1*0401 and SLA-2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted FMDV peptides bound to SLA-2*0401, whereas five of the nine predicted FMDV peptides bound to SLA-1*0401. These methods provide the characterization of T-cell epitopes in response to pathogens in more detail. The development of such approaches to analyze vaccine performance will contribute to a more accelerated improvement of livestock vaccines by virtue of identifying and focusing analysis on bona fide T-cell epitopes.

  3. LB3D: a protein three-dimensional substructure search program based on the lower bound of a root mean square deviation value.

    Science.gov (United States)

    Terashi, Genki; Shibuya, Tetsuo; Takeda-Shitaka, Mayuko

    2012-05-01

    Searching for protein structure-function relationships using three-dimensional (3D) structural coordinates represents a fundamental approach for determining the function of proteins with unknown functions. Since protein structure databases are rapidly growing in size, the development of a fast search method to find similar protein substructures by comparison of protein 3D structures is essential. In this article, we present a novel protein 3D structure search method to find all substructures with root mean square deviations (RMSDs) to the query structure that are lower than a given threshold value. Our new algorithm runs in O(m + N/m(0.5)) time, after O(N log N) preprocessing, where N is the database size and m is the query length. The new method is 1.8-41.6 times faster than the practically best known O(N) algorithm, according to computational experiments using a huge database (i.e., >20,000,000 C-alpha coordinates).

  4. Purification of a NifEN protein complex that contains bound molybdenum and a FeMo-Co precursor from an Azotobacter vinelandii DeltanifHDK strain.

    Science.gov (United States)

    Soboh, Basem; Igarashi, Robert Y; Hernandez, Jose A; Rubio, Luis M

    2006-12-01

    The NifEN protein complex serves as a molecular scaffold where some of the steps for the assembly of the iron-molybdenum cofactor (FeMo-co) of nitrogenase take place. A His-tagged version of the NifEN complex has been previously purified and shown to carry two identical [4Fe-4S] clusters of unknown function and a [Fe-S]-containing FeMo-co precursor. We have improved the purification of the his-NifEN protein from a DeltanifHDK strain of Azotobacter vinelandii and have found that the amounts of iron and molybdenum within NifEN were significantly higher than those reported previously. In an in vitro FeMo-co synthesis system with purified components, the NifEN protein served as a source of both molybdenum and a [Fe-S]-containing FeMo-co precursor, showing significant FeMo-co synthesis activity in the absence of externally added molybdate. Thus, the NifEN scaffold protein, purified from DeltanifHDK background, contained the Nif-Bco-derived Fe-S cluster and molybdenum, although these FeMo-co constituents were present at different levels within the protein complex. PMID:17012743

  5. Graviton Mass Bounds

    CERN Document Server

    de Rham, Claudia; Tolley, Andrew J; Zhou, Shuang-Yong

    2016-01-01

    Recently, aLIGO has announced the first direct detections of gravitational waves, a direct manifestation of the propagating degrees of freedom of gravity. The detected signals GW150914 and GW151226 have been used to examine the basic properties of these gravitational degrees of freedom, particularly setting an upper bound on their mass. It is timely to review what the mass of these gravitational degrees of freedom means from the theoretical point of view, particularly taking into account the recent developments in constructing consistent massive gravity theories. Apart from the GW150914 mass bound, a few other observational bounds have been established from the effects of the Yukawa potential, modified dispersion relation and fifth force that are all induced when the fundamental gravitational degrees of freedom are massive. We review these different mass bounds and examine how they stand in the wake of recent theoretical developments and how they compare to the bound from GW150914.

  6. Primosomal Proteins DnaD and DnaB Are Recruited to Chromosomal Regions Bound by DnaA in Bacillus subtilis▿

    OpenAIRE

    Smits, Wiep Klaas; Merrikh, Houra; Bonilla, Carla Yaneth; Grossman, Alan D.

    2010-01-01

    The initiation of DNA replication requires the binding of the initiator protein, DnaA, to specific binding sites in the chromosomal origin of replication, oriC. DnaA also binds to many sites around the chromosome, outside oriC, and acts as a transcription factor at several of these. In low-G+C Gram-positive bacteria, the primosomal proteins DnaD and DnaB, in conjunction with loader ATPase DnaI, load the replicative helicase at oriC, and this depends on DnaA. DnaD and DnaB also are required to...

  7. Axial Ligation and Redox Changes at the Cobalt Ion in Cobalamin Bound to Corrinoid Iron-Sulfur Protein (CoFeSP or in Solution Characterized by XAS and DFT.

    Directory of Open Access Journals (Sweden)

    Peer Schrapers

    Full Text Available A cobalamin (Cbl cofactor in corrinoid iron-sulfur protein (CoFeSP is the primary methyl group donor and acceptor in biological carbon oxide conversion along the reductive acetyl-CoA pathway. Changes of the axial coordination of the cobalt ion within the corrin macrocycle upon redox transitions in aqua-, methyl-, and cyano-Cbl bound to CoFeSP or in solution were studied using X-ray absorption spectroscopy (XAS at the Co K-edge in combination with density functional theory (DFT calculations, supported by metal content and cobalt redox level quantification with further spectroscopic methods. Calculation of the highly variable pre-edge X-ray absorption features due to core-to-valence (ctv electronic transitions, XANES shape analysis, and cobalt-ligand bond lengths determination from EXAFS has yielded models for the molecular and electronic structures of the cobalt sites. This suggested the absence of a ligand at cobalt in CoFeSP in α-position where the dimethylbenzimidazole (dmb base of the cofactor is bound in Cbl in solution. As main species, (dmbCoIII(OH2, (dmbCoII(OH2, and (dmbCoIII(CH3 sites for solution Cbl and CoIII(OH2, CoII(OH2, and CoIII(CH3 sites in CoFeSP-Cbl were identified. Our data support binding of a serine residue from the reductive-activator protein (RACo of CoFeSP to the cobalt ion in the CoFeSP-RACo protein complex that stabilizes Co(II. The absence of an α-ligand at cobalt not only tunes the redox potential of the cobalamin cofactor into the physiological range, but is also important for CoFeSP reactivation.

  8. Developing a Biologically-Inspired Molecular Solar Energy Conversion Device: Reaction of Solution and Protein-Bound Cobalamins with Carbon Dioxide and Halo-Organic Compounds

    Science.gov (United States)

    Robertson, Wesley D.; Ennist, Nathan M.; Warncke, Kurt

    2009-11-01

    Our aim is to design and construct protein-based artificial photosynthetic systems that reduce carbon dioxide (CO2) and toxic halo-organic compounds within the robust and adaptable (βα)8 TIM-barrel protein structure. The EutB subunit of the adenosylcobalamin-dependent enzyme, ethanolamine ammonia-lyase (EAL), from Salmonella typhimurium, was selected as the protein template. The Co^I forms of the native cobalamin (Cbl) cofactor and a derivative, cobinamide (Cbi), possess relatively low redox potentials that are commensurate with reduction of CO2 and halo-organic compounds. Titanium^III citrate and pulsed laser-excited 5'-deazariboflavin (5'-DRF) were used to reduce Cbl or Cbi. UV/visible absorption spectroscopy was used to monitor the reaction kinetics of reduced Cbl and Cbi with CO2 and halo-organics, and 13C-NMR was used for product analysis. The results provide fundamental information for development of an organocobalt-based protein-catalytic device for stable fuels generation and toxic chemical remediation.

  9. PROTEIN TARGETING TO STARCH Is Required for Localising GRANULE-BOUND STARCH SYNTHASE to Starch Granules and for Normal Amylose Synthesis in Arabidopsis

    OpenAIRE

    Sedwick, Caitlin

    2015-01-01

    The mechanism by which plants make starch—a vital foodstuff for billions of humans—is poorly understood, with a clear role for just one enzyme, granular binding starch synthase. A new study identifies a protein needed to recruit this enzyme to the starch granule. Read the Research Article.

  10. Multicolor Bound Soliton Molecule

    CERN Document Server

    Luo, Rui; Lin, Qiang

    2015-01-01

    We show a new class of bound soliton molecule that exists in a parametrically driven nonlinear optical cavity with appropriate dispersion characteristics. The composed solitons exhibit distinctive colors but coincide in time and share a common phase, bound together via strong inter-soliton four-wave mixing and Cherenkov radiation. The multicolor bound soliton molecule shows intriguing spectral locking characteristics and remarkable capability of spectrum management to tailor soliton frequencies, which may open up a great avenue towards versatile generation and manipulation of multi-octave spanning phase-locked Kerr frequency combs, with great potential for applications in frequency metrology, optical frequency synthesis, and spectroscopy.

  11. Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1

    International Nuclear Information System (INIS)

    Crystallization of the human CHP2–NHE1 binding domain complex. Calcineurin homologous protein (CHP) is a Ca2+-binding protein that directly interacts with and regulates the activity of all plasma-membrane Na+/H+-exchanger (NHE) family members. In contrast to the ubiquitous isoform CHP1, CHP2 is highly expressed in cancer cells. To understand the regulatory mechanism of NHE1 by CHP2, the complex CHP2–NHE1 (amino acids 503–545) has been crystallized by the sitting-drop vapour-diffusion method using PEG 3350 as precipitant. The crystals diffract to 2.7 Å and belong to a tetragonal space group, with unit-cell parameters a = b = 49.96, c = 103.20 Å

  12. The Activation Domain of the Bovine Papillomavirus E2 Protein Mediates Association of DNA-Bound Dimers to form DNA Loops

    Science.gov (United States)

    Knight, Jonathan D.; Li, Rong; Botchan, Michael

    1991-04-01

    The E2 transactivator protein of bovine papillomavirus binds its specific DNA target sequence as a dimer. We have found that E2 dimers, performed in solution independent of DNA, exhibit substantial cooperativity of DNA binding as detected by both nitrocellulose filter retention and footprint analysis techniques. If the binding sites are widely spaced, E2 forms stable DNA loops visible by electron microscopy. When three widely separated binding sites reside on te DNA, E2 condenses the molecule into a bow-tie structure. This implies that each E2 dimer has at least two independent surfaces for multimerization. Two naturally occurring shorter forms of the protein, E2C and D8/E2, which function in vivo as repressors of transcription, do not form such loops. Thus, the looping function of E2 maps to the 161-amino acid activation domain. These results support the looping model of transcription activation by enhancers.

  13. GTP bound to chloroplast thylakoid membranes is required for light-induced, multienzyme degradation of the photosystem II D1 protein

    OpenAIRE

    Spetea, Cornelia; Hundal, Torill; Lohmann, Felix; Andersson, Bertil

    1999-01-01

    Even though light is the driving force in photosynthesis, it also can be harmful to plants. The water-splitting photosystem II is the main target for this light stress, leading to inactivation of photosynthetic electron transport and photooxidative damage to its reaction center. The plant survives through an intricate repair mechanism involving proteolytic degradation and replacement of the photodamaged reaction center D1 protein. Based on experiments with isolated chloroplast thylakoid membr...

  14. The activation domain of the bovine papillomavirus E2 protein mediates association of DNA-bound dimers to form DNA loops

    OpenAIRE

    Knight, J. D.; Li, R; Botchan, M

    1991-01-01

    The E2 transactivator protein of bovine papillomavirus binds its specific DNA target sequence as a dimer. We have found that E2 dimers, preformed in solution independent of DNA, exhibit substantial cooperativity of DNA binding as detected by both nitrocellulose filter retention and footprint analysis techniques. If the binding sites are widely spaced, E2 forms stable DNA loops visible by electron microscopy. When three widely separated binding sites reside on the DNA, E2 condenses the molecul...

  15. Crystallization and preliminary X-ray diffraction analysis of prion protein bound to the Fab fragment of the POM1 antibody

    International Nuclear Information System (INIS)

    The complex of MoPrP(120–232) and Fab POM1 has been crystallized (space group C2, unit-cell parameters a = 83.68, b = 106.9, c = 76.25 Å, β = 95.6°). Diffraction data to 2.30 Å resolution have been collected using synchrotron radiation. Prion diseases are neurodegenerative diseases that are characterized by the conversion of the cellular prion protein PrPc to the pathogenic isoform PrPsc. Several antibodies are known to interact with the cellular prion protein and to inhibit this transition. An antibody Fab fragment, Fab POM1, was produced that recognizes a structural motif of the C-terminal domain of mouse prion protein. To study the mechanism by which Fab POM1 recognizes and binds the prion molecule, the complex between Fab POM1 and the C-terminal domain of mouse prion (residues 120–232) was prepared and crystallized. Crystals of this binary complex belonged to the monoclinic space group C2, with unit-cell parameters a = 83.68, b = 106.9, c = 76.25 Å, β = 95.6°

  16. The flexible structure of the K24S28 region of Leucine-Rich Amelogenin Protein (LRAP) bound to apatites as a function of surface type, calcium, mutation, and ionic strength

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Junxia; Burton, Sarah D.; Xu, Yimin; Buchko, Garry W.; Shaw, Wendy J.

    2014-07-11

    Leucine-Rich Amelogenin Protein (LRAP) is a member of the amelogenin family of biomineralization proteins, proteins which play a critical role in enamel formation. Recent studies have revealed the structure and orientation of the N- and C-terminus of LRAP bound to hydroxyapatite (HAP), a surface used as an analog of enamel. The structure of one region, K24 to S28, was found to be sensitive to phosphorylation of S16, the only naturally observed site of serine phosphorylation in LRAP, suggesting that the residues from K24 to S28 may sit at a key region of structural flexibility and play a role in the protein’s function. In this work, we investigated the sensitivity of the structure and orientation of this region when bound to HAP as a function of several factors which may vary during enamel formation to influence structure: the ionic strength (0.05 M, 0.15 M, 0.2 M), the calcium concentration (0.07 mM and 0.4 mM), and the surface to which it is binding (HAP and carbonated apatite (CAP), a more direct mimic of enamel). A naturally occurring mutation found in amelogenin (T21I), was also investigated. The structure in the K24S28 region of the protein was found to be sensitive to these conditions, with the CAP surface and excess Ca2+ (8:1 [Ca2+]:[LRAP-K24S28(+P)]) resulting in a much tighter helix, while low ionic strength relaxed the helical structure. Higher ionic strength and the point mutation did not result in any structural change in this region. The distance of the backbone of K24 from the surface was most sensitive to excess Ca2+ and in the T21I-mutation. Collectively, these data suggest that the protein is able to accommodate structural changes while maintaining its interaction with the surface, and provides further evidence of the structural sensitivity of the K24 to S28 region, a sensitivity that may contribute to function in biomineralization. This research was supported by NIH-NIDCR Grant DE-015347. The research was performed at the Pacific Northwest

  17. Quaternionic bound states

    Energy Technology Data Exchange (ETDEWEB)

    De Leo, Stefano [Department of Applied Mathematics, University of Campinas, PO Box 6065, SP 13083-970, Campinas (Brazil); Ducati, Gisele C [Department of Mathematics, University of Parana PO Box 19081, PR 81531-970, Curitiba (Brazil)

    2005-04-15

    We study the bound-state solutions of vanishing angular momentum in a quaternionic spherical square-well potential of finite depth. As in standard quantum mechanics, such solutions occur for discrete values of energy. At first glance, it seems that the continuity conditions impose a very restrictive constraint on the energy eigenvalues and, consequently, no bound states were expected for energy values below the pure quaternionic potential. Nevertheless, a careful analysis shows that pure quaternionic potentials do not remove bound states. It is also interesting to compare these new solutions with the bound state solutions of the trial-complex potential. The study presented in this paper represents a preliminary step towards a full understanding of the role that quaternionic potentials could play in quantum mechanics. Of particular interest for the authors is the analysis of confined wave packets and tunnelling times in this new formulation of quantum theory.

  18. Bound or free: interaction of the C-terminal domain of Escherichia coli single-stranded DNA-binding protein (SSB) with the tetrameric core of SSB.

    Science.gov (United States)

    Su, Xun-Cheng; Wang, Yao; Yagi, Hiromasa; Shishmarev, Dmitry; Mason, Claire E; Smith, Paul J; Vandevenne, Marylène; Dixon, Nicholas E; Otting, Gottfried

    2014-04-01

    Single-stranded DNA (ssDNA)-binding protein (SSB) protects ssDNA from degradation and recruits other proteins for DNA replication and repair. Escherichia coli SSB is the prototypical eubacterial SSB in a family of tetrameric SSBs. It consists of a structurally well-defined ssDNA binding domain (OB-domain) and a disordered C-terminal domain (C-domain). The eight-residue C-terminal segment of SSB (C-peptide) mediates the binding of SSB to many different SSB-binding proteins. Previously published nuclear magnetic resonance (NMR) data of the monomeric state at pH 3.4 showed that the C-peptide binds to the OB-domain at a site that overlaps with the ssDNA binding site, but investigating the protein at neutral pH is difficult because of the high molecular mass and limited solubility of the tetramer. Here we show that the C-domain is highly mobile in the SSB tetramer at neutral pH and that binding of the C-peptide to the OB-domain is so weak that most of the C-peptides are unbound even in the absence of ssDNA. We address the problem of determining intramolecular binding affinities in the situation of fast exchange between two states, one of which cannot be observed by NMR and cannot be fully populated. The results were confirmed by electron paramagnetic resonance spectroscopy and microscale thermophoresis. The C-peptide-OB-domain interaction is shown to be driven primarily by electrostatic interactions, so that binding of 1 equiv of (dT)35 releases practically all C-peptides from the OB-domain tetramer. The interaction is much more sensitive to NaCl than to potassium glutamate, which is the usual osmolyte in E. coli. As the C-peptide is predominantly in the unbound state irrespective of the presence of ssDNA, long-range electrostatic effects from the C-peptide may contribute more to regulating the activity of SSB than any engagement of the C-peptide by the OB-domain.

  19. A possibility of a protein-bound water molecule as the ionizable group responsible for pKe at the alkaline side in human matrix metalloproteinase 7 activity.

    Science.gov (United States)

    Morishima, Aiko; Yasukawa, Kiyoshi; Inouye, Kuniyo

    2012-05-01

    Human matrix metalloproteinase 7 (MMP-7) activity exhibits broad bell-shaped pH profile with the acidic and alkaline pK(a) (pK(e1) and pK(e2)) values of about 4 and 10. The ionizable group for pK(e2) was assigned to Lys or Arg by thermodynamic analysis; however, no such residues are present in the active site. Hence, based on the crystal structure, we hypothesized that a water molecule bound to the main-chain nitrogen of Ala162 (W1) or the main-chain carbonyl oxygen of Pro217 (W2) is a candidate for the ionizable group for pK(e2) [Takeharu, H. et al. (2011) Biochim. Biophys. Acta 1814, 1940-1946]. In this study, we inspected this hypothesis. In the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu-Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-L-Ala-L-Arg-NH(2), all 19 variants, in which one of all Lys and Arg residues was replaced by Ala, retained activity, indicating that neither Lys nor Arg is the ionizable group. pK(e2) values of A162S, A162V and A162G were 9.6 ± 0.1, 9.5 ± 0.1 and 10.4 ± 0.2, respectively, different from that of wild-type MMP-7 (WT) (9.9 ± 0.1) by 0.3-0.5 pH unit, and those of P217S, P217V and P217G were 10.1 ± 0.1, 9.8 ± 0.1 and 9.7 ± 0.1, respectively, different from that of WT by 0.1-0.2 pH unit. These results suggest a possibility of W1 or W2 as the ionizable group for pK(e2).

  20. Staphylococcus aureus mutants lacking cell wall-bound protein A found in isolates from bacteraemia, MRSA infection and a healthy nasal carrier.

    Science.gov (United States)

    Sørum, Marit; Sangvik, Maria; Stegger, Marc; Olsen, Renate S; Johannessen, Mona; Skov, Robert; Sollid, Johanna U E

    2013-02-01

    Staphylococcus aureus is a major human pathogen and a multitude of virulence factors enables it to cause infections, from superficial lesions to life-threatening systemic conditions. Staphylococcal protein A (SpA) is a surface protein contributing to S. aureus pathogenesis by interfering with immune responses and activating inflammation. Seven isolates with frameshift mutations in the spa repeat region were investigated to determine whether these mutations lead to truncation and secretion of SpA into the extracellular environment. Five isolates originated from blood cultures, one from an MRSA infection and one from a persistent nasal carrier. Full-length spa genes from the seven isolates were sequenced, and Western blot experiments were performed to localize SpA. Three isolates had identical deviating 25-bp spa repeats, but all isolates displayed different repeat successions. The DNA sequence revealed that the frameshift mutations created premature stop codons in all seven isolates, resulting in truncated SpA of different lengths, however, all lacking the XC region with the C-terminal sorting signal. SpA was detected by Western blot in six of the seven isolates, mainly extracellularly. Our findings demonstrate that S. aureus isolates with truncated SpA, not anchored to the cell wall, can still be found in bacteraemia, infection and among carriers.

  1. The flexible structure of the K24S28 region of Leucine-Rich Amelogenin Protein (LRAP bound to apatites as a function of surface type, calcium, mutation, and ionic strength

    Directory of Open Access Journals (Sweden)

    Junxia eLu

    2014-07-01

    Full Text Available Leucine-Rich Amelogenin Protein (LRAP is a member of the amelogenin family of biomineralization proteins, proteins which play a critical role in enamel formation. Recent studies have revealed the structure and orientation of the N- and C-terminus of LRAP bound to hydroxyapatite (HAP, a surface used as an analog of enamel. The structure of one region, K24 to S28, was found to be sensitive to phosphorylation of S16, the only naturally observed site of serine phosphorylation in LRAP, suggesting that K24S28 may sit at a key region of structural flexibility and play a role in the protein’s function. In this work, we investigated the sensitivity of the structure and orientation of this region when bound to HAP as a function of several factors which may vary during enamel formation to influence structure: the ionic strength (0.05 M, 0.15 M, 0.2 M, the calcium concentration (0.07 mM and 0.4 mM, and the surface to which it is binding (HAP and carbonated apatite (CAP, a more direct mimic of enamel. A naturally occurring mutation found in amelogenin (T21I was also investigated. The structure in the K24S28 region of the protein was found to be sensitive to these conditions, with the CAP surface and excess Ca2+ (8:1 [Ca2+]:[LRAP-K24S28(+P] resulting in a tighter helix, while low ionic strength relaxed the helical structure. Higher ionic strength and the point mutation did not result in any structural change in this region. The distance of the backbone of K24 from the surface was most sensitive to excess Ca2+ and in the T21I-mutation. Collectively, these data suggest that phosphorylated LRAP is able to accommodate structural changes while maintaining its interaction with the surface, and provides further evidence of the structural sensitivity of the K24S28 region, a sensitivity that may contribute to function in biomineralization.

  2. Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin; Marmorstein, Ronen (UPENN)

    2008-04-02

    The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.

  3. Lectures on Bound states

    CERN Document Server

    Hoyer, Paul

    2016-01-01

    Even a first approximation of bound states requires contributions of all powers in the coupling. This means that the concept of "lowest order bound state" needs to be defined. In these lectures I discuss the "Born" (no loop, lowest order in $\\hbar$) approximation. Born level states are bound by gauge fields which satisfy the classical field equations. As a check of the method, Positronium states of any momentum are determined as eigenstates of the QED Hamiltonian, quantized at equal time. Analogously, states bound by a strong external field $A^\\mu(\\xv)$ are found as eigenstates of the Dirac Hamiltonian. Their Fock states have dynamically created $e^+e^-$ pairs, whose distribution is determined by the Dirac wave function. The linear potential of $D=1+1$ dimensions confines electrons but repels positrons. As a result, the mass spectrum is continuous and the wave functions have features of both bound states and plane waves. The classical solutions of Gauss' law are explored for hadrons in QCD. A non-vanishing bo...

  4. Bounding species distribution models

    Institute of Scientific and Technical Information of China (English)

    Thomas J. STOHLGREN; Catherine S. JARNEVICH; Wayne E. ESAIAS; Jeffrey T. MORISETTE

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern.Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development,yet there is no recommended best practice for “clamping” model extrapolations.We relied on two commonly used modeling approaches:classification and regression tree (CART) and maximum entropy (Maxent) models,and we tested a simple alteration of the model extrapolations,bounding extrapolations to the maximum and minimum values of primary environmental predictors,to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States.Findings suggest that multiple models of bounding,and the most conservative bounding of species distribution models,like those presented here,should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5):642-647,2011].

  5. Novel protein-inhibitor interactions in site 3 of Ca(2+)-bound S100B as discovered by X-ray crystallography.

    Science.gov (United States)

    Cavalier, Michael C; Melville, Zephan; Aligholizadeh, Ehson; Raman, E Prabhu; Yu, Wenbo; Fang, Lei; Alasady, Milad; Pierce, Adam D; Wilder, Paul T; MacKerell, Alexander D; Weber, David J

    2016-06-01

    Structure-based drug discovery is under way to identify and develop small-molecule S100B inhibitors (SBiXs). Such inhibitors have therapeutic potential for treating malignant melanoma, since high levels of S100B downregulate wild-type p53 tumor suppressor function in this cancer. Computational and X-ray crystallographic studies of two S100B-SBiX complexes are described, and both compounds (apomorphine hydrochloride and ethidium bromide) occupy an area of the S100B hydrophobic cleft which is termed site 3. These data also reveal novel protein-inhibitor interactions which can be used in future drug-design studies to improve SBiX affinity and specificity. Of particular interest, apomorphine hydrochloride showed S100B-dependent killing in melanoma cell assays, although the efficacy exceeds its affinity for S100B and implicates possible off-target contributions. Because there are no structural data available for compounds occupying site 3 alone, these studies contribute towards the structure-based approach to targeting S100B by including interactions with residues in site 3 of S100B. PMID:27303795

  6. Validation of EMP bounds

    Energy Technology Data Exchange (ETDEWEB)

    Warne, L.K.; Merewether, K.O.; Chen, K.C.; Jorgenson, R.E.; Morris, M.E.; Solberg, J.E.; Lewis, J.G. [Sandia National Labs., Albuquerque, NM (United States); Derr, W. [Derr Enterprises, Albuquerque, NM (United States)

    1996-07-01

    Test data on canonical weapon-like fixtures are used to validate previously developed analytical bounding results. The test fixtures were constructed to simulate (but be slightly worse than) weapon ports of entry but have known geometries (and electrical points of contact). The exterior of the test fixtures exhibited exterior resonant enhancement of the incident fields at the ports of entry with magnitudes equal to those of weapon geometries. The interior consisted of loaded transmission lines adjusted to maximize received energy or voltage but incorporating practical weapon geometrical constraints. New analytical results are also presented for bounding the energies associated with multiple bolt joints and for bounding the exterior resonant enhancement of the exciting fields.

  7. Information, Utility & Bounded Rationality

    CERN Document Server

    Ortega, Pedro A

    2011-01-01

    Perfectly rational decision-makers maximize expected utility, but crucially ignore the resource costs incurred when determining optimal actions. Here we employ an axiomatic framework for bounded rational decision-making based on a thermodynamic interpretation of resource costs as information costs. This leads to a variational "free utility" principle akin to thermodynamical free energy that trades off utility and information costs. We show that bounded optimal control solutions can be derived from this variational principle, which leads in general to stochastic policies. Furthermore, we show that risk-sensitive and robust (minimax) control schemes fall out naturally from this framework if the environment is considered as a bounded rational and perfectly rational opponent, respectively. When resource costs are ignored, the maximum expected utility principle is recovered.

  8. Are the SSB-Interacting Proteins RecO, RecG, PriA and the DnaB-Interacting Protein Rep Bound to Progressing Replication Forks in Escherichia coli?

    Directory of Open Access Journals (Sweden)

    Esma Bentchikou

    Full Text Available In all organisms several enzymes that are needed upon replication impediment are targeted to replication forks by interaction with a replication protein. In most cases these proteins interact with the polymerase clamp or with single-stranded DNA binding proteins (SSB. In Escherichia coli an accessory replicative helicase was also shown to interact with the DnaB replicative helicase. Here we have used cytological observation of Venus fluorescent fusion proteins expressed from their endogenous loci in live E. coli cells to determine whether DNA repair and replication restart proteins that interact with a replication protein travel with replication forks. A custom-made microscope that detects active replisome molecules provided that they are present in at least three copies was used. Neither the recombination proteins RecO and RecG, nor the replication accessory helicase Rep are detected specifically in replicating cells in our assay, indicating that either they are not present at progressing replication forks or they are present in less than three copies. The Venus-PriA fusion protein formed foci even in the absence of replication forks, which prevented us from reaching a conclusion.

  9. Are the SSB-Interacting Proteins RecO, RecG, PriA and the DnaB-Interacting Protein Rep Bound to Progressing Replication Forks in Escherichia coli?

    Science.gov (United States)

    Bentchikou, Esma; Chagneau, Carine; Long, Emilie; Matelot, Mélody; Allemand, Jean-François; Michel, Bénédicte

    2015-01-01

    In all organisms several enzymes that are needed upon replication impediment are targeted to replication forks by interaction with a replication protein. In most cases these proteins interact with the polymerase clamp or with single-stranded DNA binding proteins (SSB). In Escherichia coli an accessory replicative helicase was also shown to interact with the DnaB replicative helicase. Here we have used cytological observation of Venus fluorescent fusion proteins expressed from their endogenous loci in live E. coli cells to determine whether DNA repair and replication restart proteins that interact with a replication protein travel with replication forks. A custom-made microscope that detects active replisome molecules provided that they are present in at least three copies was used. Neither the recombination proteins RecO and RecG, nor the replication accessory helicase Rep are detected specifically in replicating cells in our assay, indicating that either they are not present at progressing replication forks or they are present in less than three copies. The Venus-PriA fusion protein formed foci even in the absence of replication forks, which prevented us from reaching a conclusion. PMID:26244508

  10. Bounded Tamper Resilience

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Faust, Sebastian; Mukherjee, Pratyay;

    2013-01-01

    a public tamper-proof common reference string. Finally, we explain how to boost bounded tampering and leakage resilience (as in 1. and 2. above) to continuous tampering and leakage resilience, in the so-called floppy model where each user has a personal hardware token (containing leak- and tamper...

  11. Towards Secure Distance Bounding

    OpenAIRE

    Boureanu, Ioana; Mitrokotsa, Aikaterini; Vaudenay, Serge

    2013-01-01

    Relay attacks (and, more generally, man-in-the-middle attacks) are a serious threat against many access control and payment schemes. In this work, we present distance-bounding protocols, how these can deter relay attacks, and the security models formalizing these protocols. We show several pitfalls making existing protocols insecure (or at least, vulnerable, in some cases). Then, we introduce the SKI protocol which enjoys resistance to all popular attack-models and features provable security....

  12. Maps of Bounded Rationality

    OpenAIRE

    Kahneman, Daniel

    2002-01-01

    The work cited by the Nobel committee was done jointly with the late Amos Tversky (1937-1996) during a long and unusually close collaboration. Together, we explored the psychology of intuitive beliefs and choices and examined their bounded rationality. This essay presents a current perspective on the three major topics of our joint work: heuristics of judgment, risky choice, and framing effects. In all three domains we studied intuitions - thoughts and preferences that come to mind quickly an...

  13. BOUNDING PYRAMIDS AND BOUNDING CONES FOR TRIANGULAR BEZIER SURFACES

    Institute of Scientific and Technical Information of China (English)

    Jian-song Deng; Fa-lai Chen; Li-li Wang

    2000-01-01

    This paper describes practical approaches on how to construct bounding pyramids and bounding cones for triangular Bézier surfaces. Examples are provided to illustrate the process of construction and comparison is made between various surface bounding volumes. Furthermore, as a starting point for the construction,we provide a way to compute hodographs of triangular Bézier surfaces and improve the algorithm for computing the bounding cone of a set of vectors.

  14. Universal bounds on current fluctuations

    Science.gov (United States)

    Pietzonka, Patrick; Barato, Andre C.; Seifert, Udo

    2016-05-01

    For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

  15. A bound on chaos

    CERN Document Server

    Maldacena, Juan; Stanford, Douglas

    2015-01-01

    We conjecture a sharp bound on the rate of growth of chaos in thermal quantum systems with a large number of degrees of freedom. Chaos can be diagnosed using an out-of-time-order correlation function closely related to the commutator of operators separated in time. We conjecture that the influence of chaos on this correlator can develop no faster than exponentially, with Lyapunov exponent $\\lambda_L \\le 2 \\pi k_B T/\\hbar$. We give a precise mathematical argument, based on plausible physical assumptions, establishing this conjecture.

  16. Regularity of Bound States

    DEFF Research Database (Denmark)

    Faupin, Jeremy; Møller, Jacob Schach; Skibsted, Erik

    2011-01-01

    We study regularity of bound states pertaining to embedded eigenvalues of a self-adjoint operator H, with respect to an auxiliary operator A that is conjugate to H in the sense of Mourre. We work within the framework of singular Mourre theory which enables us to deal with confined massless Pauli......–Fierz models, our primary example, and many-body AC-Stark Hamiltonians. In the simpler context of regular Mourre theory, our results boil down to an improvement of results obtained recently in [8, 9]....

  17. Blog life: Entropy Bound

    Science.gov (United States)

    Steinberg, Peter

    2008-06-01

    Who is the blog written by? Peter Steinberg is a nuclear physicist at the Brookhaven National Laboratory in New York, US. He is acting project manager of the PHOBOS experiment, which used Brookhaven's Relativistic Heavy Ion Collider (RHIC) to search for unusual events produced during collisions between gold nuclei. He is also involved with the PHENIX experiment, which seeks to discover a new state of matter known as the quark-gluon plasma. In addition to his own blog Entropy Bound, Steinberg is currently blogging on a website that was set up last year to publicize the involvement of US scientists with the Large Hadron Collider (LHC) at CERN.

  18. Novel Bounds on Marginal Probabilities

    OpenAIRE

    Mooij, Joris M.; Kappen, Hilbert J

    2008-01-01

    We derive two related novel bounds on single-variable marginal probability distributions in factor graphs with discrete variables. The first method propagates bounds over a subtree of the factor graph rooted in the variable, and the second method propagates bounds over the self-avoiding walk tree starting at the variable. By construction, both methods not only bound the exact marginal probability distribution of a variable, but also its approximate Belief Propagation marginal (``belief''). Th...

  19. Tight Bernoulli tail probability bounds

    OpenAIRE

    Dzindzalieta, Dainius

    2014-01-01

    The purpose of the dissertation is to prove universal tight bounds for deviation from the mean probability inequalities for functions of random variables. Universal bounds shows that they are uniform with respect to some class of distributions and quantity of variables and other parameters. The bounds are called tight, if we can construct a sequence of random variables, such that the upper bounds are achieved. Such inequalities are useful for example in insurance mathematics, for constructing...

  20. Error bounds for set inclusions

    Institute of Scientific and Technical Information of China (English)

    ZHENG; Xiyin(郑喜印)

    2003-01-01

    A variant of Robinson-Ursescu Theorem is given in normed spaces. Several error bound theorems for convex inclusions are proved and in particular a positive answer to Li and Singer's conjecture is given under weaker assumption than the assumption required in their conjecture. Perturbation error bounds are also studied. As applications, we study error bounds for convex inequality systems.

  1. Bounded Fixed-Point Iteration

    DEFF Research Database (Denmark)

    Nielson, Hanne Riis; Nielson, Flemming

    1992-01-01

    they obtain a quadratic bound. These bounds are shown to be tight. Specializing the case of strict and additive functions to functionals of a form that would correspond to iterative programs they show that a linear bound is tight. This is related to several analyses studied in the literature (including...

  2. Separable subgroups have bounded packing

    CERN Document Server

    Yang, Wen-yuan

    2010-01-01

    In this note, we prove that separable subgroups have bounded packing in ambient groups. The notion bounded packing was introduced by Hruska-Wise \\cite{HrWi} and in particular, our result confirms a conjecture in \\cite{HrWi} which states each subgroup of a virtually polycyclic group has the bounded packing property.

  3. Formation of "bound

    Science.gov (United States)

    Nowak, K.; Kästner, M.; Miltner, A.

    2009-04-01

    During degradation of organic pollutants in soil, metabolites, microbial biomass, CO2and "bound" residues ("non-extractable" residues in soil organic matter) are formed. Enhanced transformation of these contaminants into "bound" residues has been proposed as an alternative remediation method for polluted soils. However, this kind of residues may pose a potential risk for the environment due to their chemical structure and possible remobilization under different conditions. Therefore particular attention is given actually to "bound" residues. Part of these non-extractable residues may be "biogenic," because microorganisms use the carbon from the pollutant to form their biomass components (fatty acids, amino acids, amino sugars), which subsequently may be incorporated into soil organic matter. Furthermore, the CO2 originating from mineralization of xenobiotics, can be re-assimilated by microorganisms and also incorporated into "biogenic residue". The hazard posed by "bound" residues may be overestimated because they are "biogenic" (contain microbial fatty acids and amino acids). The knowledge about the pathways of "biogenic residue" formation is necessary for a proper assessment of the fate of tested pollutants and their turnover in the soil environment. Moreover, these data are needed to establish the realistic degradation rates of the contaminants in soil. The main objectives of this study are: to quantify the extent of "biogenic residue" (fatty acids, amino acids, amino sugars) formation during the degradation of a model pollutant (2,4-dichlorophenoxyacetic acid = 2,4-D) and during CO2 assimilation by microorganisms and to evaluate which components are mainly incorporated into "bound" residues. To investigate the extent of "biogenic residue" formation in soil during the degradation of 2,4-D, experiments with either 14C-U-ring and 13C6-2,4-D or carboxyl-14C 2,4-D were performed. The incubation experiments were performed according to OECD test guideline 307, in the

  4. Bounding approaches to system identification

    CERN Document Server

    Norton, John; Piet-Lahanier, Hélène; Walter, Éric

    1996-01-01

    In response to the growing interest in bounding error approaches, the editors of this volume offer the first collection of papers to describe advances in techniques and applications of bounding of the parameters, or state variables, of uncertain dynamical systems. Contributors explore the application of the bounding approach as an alternative to the probabilistic analysis of such systems, relating its importance to robust control-system design.

  5. Bounded Rationality in Transposition Processes

    DEFF Research Database (Denmark)

    Vollaard, Hans; Martinsen, Dorte Sindbjerg

    2014-01-01

    that concerns the organisation and financing of national healthcare systems. This article applies the perspective of bounded rationality to explain (irregularities in) the timely and correct transposition of EU directives. The cognitive and organisational constraints long posited by the bounded rationality...... perspective may affect the commonly employed explanatory factors of administrative capacities, misfit and the heterogeneity of preferences among veto players. To prevent retrospective rationalisation of the transposition process, this paper traces this process as it unfolded in Denmark and the Netherlands....... As bounded rationality is apparent in the transposition processes in these relatively well-organised countries, future transposition studies should devote greater consideration to the bounded rationality perspective....

  6. Bounds for Asian basket options

    Science.gov (United States)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  7. A Lower Bound on Concurrence

    Institute of Scientific and Technical Information of China (English)

    LIU Li-Guo; TIAN Cheng-Lin; CHEN Ping-Xing; YUAN Nai-Chang

    2009-01-01

    We derive an analytical lower bound on the concurrence for bipartite quantum systems with an improved computable cross norm or realignment criterion and an improved positive partial transpose criterion respectively.Furthermore we demonstrate that our bound is better than that obtained from the local uncertainty relations criterion with optimal local orthogonal observables which is known as one of the best estimations of concurrence.

  8. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  9. Bounded Model Checking of CTL

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Tao; Cong-Hua Zhou; Zhong Chen; Li-Fu Wang

    2007-01-01

    Bounded Model Checking has been recently introduced as an efficient verification method for reactive systems.This technique reduces model checking of linear temporal logic to propositional satisfiability.In this paper we first present how quantified Boolean decision procedures can replace BDDs.We introduce a bounded model checking procedure for temporal logic CTL* which reduces model checking to the satisfiability of quantified Boolean formulas.Our new technique avoids the space blow up of BDDs, and extends the concept of bounded model checking.

  10. Bound states in string nets

    CERN Document Server

    Schulz, M D; Vidal, J

    2016-01-01

    We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

  11. Curvature bounds for configuration spaces

    OpenAIRE

    Erbar, Matthias; Huesmann, Martin

    2014-01-01

    We show that the configuration space over a manifold M inherits many curvature properties of the manifold. For instance, we show that a lower Ricci curvature bound on M implies for the configuration space a lower Ricci curvature bound in the sense of Lott-Sturm-Villani, the Bochner inequality, gradient estimates and Wasserstein contraction. Moreover, we show that the heat flow on the configuration space, or the infinite independent particle process, can be identified as the gradient flow of t...

  12. Finite Domain Bounds Consistency Revisited

    OpenAIRE

    Choi, Chiu Wo; Harvey, Warwick; Lee, Jimmy Ho-Man; Stuckey, Peter J.

    2004-01-01

    A widely adopted approach to solving constraint satisfaction problems combines systematic tree search with constraint propagation for pruning the search space. Constraint propagation is performed by propagators implementing a certain notion of consistency. Bounds consistency is the method of choice for building propagators for arithmetic constraints and several global constraints in the finite integer domain. However, there has been some confusion in the definition of bounds consistency. In t...

  13. Entropy bounds for uncollapsed matter

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Gabriel; Visser, Matt, E-mail: Gabriel.Abreu@msor.vuw.ac.nz, E-mail: Matt.Visser@msor.vuw.ac.nz [School of Mathematics, Statistics and Operation Research Victoria University of Wellington Wellington (New Zealand)

    2011-09-22

    In any static spacetime the quasilocal Tolman mass contained within a volume can be reduced to a Gauss-like surface integral involving the flux of a suitably defined generalized surface gravity. By introducing some basic thermodynamics, and invoking the Unruh effect, one can then develop elementary bounds on the quasilocal entropy that are very similar in spirit to the holographic bound, and closely related to entanglement entropy.

  14. On a Generalization of Kingman's Bounds

    OpenAIRE

    Liu, Zhen; Nain, Philippe; Towsley, Don

    1994-01-01

    In this paper we develop a framework for computing upper and lower bounds of an exponential form for a class of single server queueing systems with non-renewal inputs. These bounds generalize Kingman's bounds for queues with renewal inputs.

  15. Structural Studies of Soybean Calmodulin Isoform 4 Bound to the Calmodulin-binding Domain of Tobacco Mitogen-activated Protein Kinase Phosphatase-1 Provide Insights into a Sequential Target Binding Mode*

    OpenAIRE

    Ishida, Hiroaki; Rainaldi, Mario; Vogel, Hans J.

    2009-01-01

    The calcium regulatory protein calmodulin (CaM) binds in a calcium-dependent manner to numerous target proteins. The calmodulin-binding domain (CaMBD) region of Nicotiana tabacum MAPK phosphatase has an amino acid sequence that does not resemble the CaMBD of any other known Ca2+-CaM-binding proteins. Using a unique fusion protein strategy, we have been able to obtain a high resolution solution structure of the complex of soybean Ca2+-CaM4 (SCaM4) and this CaMBD. Complete isotope labeling of b...

  16. Eta nuclear bound states revisited

    CERN Document Server

    Friedman, E; Mareš, J

    2013-01-01

    The strong energy dependence of the s-wave eta-N scattering amplitude at and below threshold, as evident in coupled-channels K-matrix fits and chiral models that incorporate the S11 N*(1535) resonance, is included self consistently in eta-nuclear bound state calculations. This approach, applied recently in calculations of kaonic atoms and Kbar-nuclear bound states, is found to impose stronger constraints than ever on the onset of eta-nuclear binding, with a minimum value of Re a_{eta N} approximately 0.9 fm required to accommodate an eta-4He bound state. Binding energies and widths of eta-nuclear states are calculated within several underlying eta-N models for nuclei across the periodic table, including eta-25Mg for which some evidence was proposed in a recent COSY experiment.

  17. Improved Range Searching Lower Bounds

    DEFF Research Database (Denmark)

    Larsen, Kasper Green; Nguyen, Huy L.

    2012-01-01

    range reporting problem. In approximate simplex range reporting, points that lie within a distance of ε ⋅ Diam(s) from the border of a query simplex s, are free to be included or excluded from the output, where ε ≥ 0 is an input parameter to the range searching problem. We prove our lower bounds......Table of Contents -------------------------------------------------------------------------------- In this paper we present a number of improved lower bounds for range searching in the pointer machine and the group model. In the pointer machine, we prove lower bounds for the approximate simplex...... by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...

  18. Simulation bounds for system availability

    International Nuclear Information System (INIS)

    System availability is a dominant factor in the practicality of nuclear power electrical generating plants. A proposed model for obtaining either lower bounds or interval estimates on availability uses observed data on ''n'' failure-to-repair cycles of the system to estimate the parameters in the time-to-failure and time-to-repair models. These estimates are then used in simulating failure/repair cycles of the system. The availability estimate is obtained for each of 5000 samples of ''n'' failure/repair cycles to form a distribution of estimates. Specific percentile points of those simulated distributions are selected as lower simulation bounds or simulation interval bounds for the system availability. The method is illustrated with operational data from two nuclear plants for which an exponential time-to-failure and a lognormal time-to-repair are assumed

  19. Energy bounds in designer gravity

    Science.gov (United States)

    Amsel, Aaron J.; Marolf, Donald

    2006-09-01

    We consider asymptotically anti-de Sitter gravity coupled to tachyonic scalar fields with mass at or slightly above the Breitenlohner-Freedman bound in d≥4 spacetime dimensions. The boundary conditions in these “designer gravity” theories are defined in terms of an arbitrary function W. We give a general argument that the Hamiltonian generators of asymptotic symmetries for such systems will be finite, and proceed to construct these generators using the covariant phase space method. The direct calculation confirms that the generators are finite and shows that they take the form of the pure gravity result plus additional contributions from the scalar fields. By comparing the generators to the spinor charge, we derive a lower bound on the gravitational energy when W has a global minimum and the Breitenlohner-Freedman bound is not saturated.

  20. Experimental activation of bound entanglement.

    Science.gov (United States)

    Kaneda, Fumihiro; Shimizu, Ryosuke; Ishizaka, Satoshi; Mitsumori, Yasuyoshi; Kosaka, Hideo; Edamatsu, Keiichi

    2012-07-27

    Entanglement is one of the essential resources in quantum information and communication technology (QICT). The entanglement thus far explored and applied to QICT has been pure and distillable entanglement. Yet, there is another type of entanglement, called "bound entanglement," which is not distillable by local operations and classical communication. We demonstrate the experimental "activation" of the bound entanglement held in the four-qubit Smolin state, unleashing its immanent entanglement in distillable form, with the help of auxiliary two-qubit entanglement and local operations and classical communication. We anticipate that it opens the way to a new class of QICT applications that utilize more general classes of entanglement than ever, including bound entanglement.

  1. Refining Castelnuovo-Halphen bounds

    CERN Document Server

    Di Gennaro, Vincenzo

    2011-01-01

    Fix integers $r,d,s,\\pi$ with $r\\geq 4$, $d\\gg s$, $r-1\\leq s \\leq 2r-4$, and $\\pi\\geq 0$. Refining classical results for the genus of a projective curve, we exhibit a sharp upper bound for the arithmetic genus $p_a(C)$ of an integral projective curve $C\\subset {\\mathbb{P}^r}$ of degree $d$, assuming that $C$ is not contained in any surface of degree $ \\pi$. Next we discuss other types of bound for $p_a(C)$, involving conditions on the entire Hilbert polynomial of the integral surfaces on which $C$ may lie.

  2. Variables Bounding Based Retiming Algorithm

    Institute of Scientific and Technical Information of China (English)

    宫宗伟; 林争辉; 陈后鹏

    2002-01-01

    Retiming is a technique for optimizing sequential circuits. In this paper, wediscuss this problem and propose an improved retiming algorithm based on variables bounding.Through the computation of the lower and upper bounds on variables, the algorithm can signi-ficantly reduce the number of constraints and speed up the execution of retiming. Furthermore,the elements of matrixes D and W are computed in a demand-driven way, which can reducethe capacity of memory. It is shown through the experimental results on ISCAS89 benchmarksthat our algorithm is very effective for large-scale sequential circuits.

  3. High-Resolution Solid-State NMR Spectroscopy of Membrane Bound Proteins and Peptides Aligned in Hydrated Lipids%水化磷脂层中蛋白质和多肽的高分辨固体核磁共振波谱学

    Institute of Scientific and Technical Information of China (English)

    傅日强

    2009-01-01

    有序样品的固体核磁共振(NMR)已快速发展成测定蛋白质和多肽在"仿真"水化磷脂层中高分辨结构的重要谱学方法. 由于与膜相连的蛋白质和多肽的结构、动力学和功能往往都和其周边自然环境密切相关, 因此人们把蛋白质和多肽有序排列于水化磷脂层中进行固体NMR测量, 从而获得与取向相关的各向异性自旋相互作用. 这些取向约束可作为结构参数重构蛋白质在水化磷脂层中的高分辨三维结构. 近十年来在样品制备, NMR探头和实验方法方面的显著发展, 极大地促进了有序样品的固体NMR的发展, 并使之成为测定与膜相连的蛋白质和多肽结构的有效方法. 该综述介绍有序样品的固体NMR谱学方法, 并总结此领域里的最新研究进展.%Solid-state nuclear magnetic resonance (NMR) of aligned samples has been rapidly emerged as a successful and important spectroscopic approach for high-resolution structural characterization of membrane-bound proteins and peptides in their "native-like" hydrated lipid bilayers. Because the structures, dynamics, and functions of membrane-bound proteins and peptides are highly associated with heterogeneous native environments, proteins and peptides are prepared for solid-state NMR measurements in the presence of either bilayers that are mechanically aligned on glass plates or magnetically aligned bicelles. Orientation dependent anisotropic spin nuclear interactions from these aligned proteins and peptides can be obtained. These orientational restraints can be assembled into high-resolution three-dimensional structures. Driven by significant advances in sample preparation protocols as well as NMR probes and other methodology developments in the past decade, the aligned sample NMR approach has been well developed and become an effective way for structural characterization of membrane-bound proteins and peptides. This review introduces high resolution solid-state NMR

  4. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing...

  5. Market Access through Bound Tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    WTO negotiations deal predominantly with bound - besides applied - tariff rates. But, how can reductions in tariffs ceilings, i.e. tariff rates that no exporter may ever actually be confronted with, generate market access? The answer to this question relates to the effects of tariff bindings on t...

  6. Market access through bound tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    2010-01-01

    WTO negotiations deal predominantly with bound - besides applied - tariff rates. But, how can reductions in tariffs ceilings, i.e. tariff rates that no exporter may ever actually be confronted with, generate market access? The answer to this question relates to the effects of tariff bindings on t...

  7. Unconditional lower bounds against advice

    NARCIS (Netherlands)

    H. Buhrman; L. Fortnow; R. Santhanam

    2009-01-01

    We show several unconditional lower bounds for exponential time classes against polynomial time classes with advice, including: (1) For any constant c, NEXP not in P^{NP[n^c]} (2) For any constant c, MAEXP not in MA/n^c (3) BPEXP not in BPP/n^{o(1)}. It was previously unknown even whether NEXP in NP

  8. Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

    OpenAIRE

    Veldhuis, J D; Johnson, M.L.; Faunt, L M; MERCADO, M.; Baumann, G

    1993-01-01

    The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of p...

  9. A Functional Calculus for Quotient Bounded Operators

    Directory of Open Access Journals (Sweden)

    Sorin Mirel Stoian

    2006-12-01

    Full Text Available If (X, P is a sequentially locally convex space, then a quotient bounded operator T beloging to QP is regular (in the sense of Waelbroeck if and only if it is a bounded element (in the sense of Allan of algebra QP. The classic functional calculus for bounded operators on Banach space is generalized for bounded elements of algebra QP.

  10. Rab proteins specify motorized vesicle transport

    NARCIS (Netherlands)

    Wanschers, B.F.J.

    2008-01-01

    Small GTPases of the Rab-family are key regulators of intracellular membrane traffic. These proteins constantly cycle between an 'active' GTP-bound and 'inactive' GDP-bound state. In their GTP-bound conformation Rab proteins can engage in complex formation with so called effector proteins. It is at

  11. Development of a rapid in vitro protein refolding assay which discriminates between peptide-bound and peptide-free forms of recombinant porcine major histocompatibility class I complex (SLA-I)

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Kristensen, B.; Ladekjaer-Mikkelsen, A.S.;

    2002-01-01

    The extracellular domains of swine leukocyte antigen class I (SLA-I, major histocompatibility complex protein class 1) were cloned and sequenced for two haplotypes (114 and H7) which do not share any alleles based on serological typing, and which are the most important in Danish farmed pigs....... The extracellular domain of SLA-I was connected to porcine beta2 microglobulin by glycine-rich linkers. The engineered sin.-le-chain proteins, consisting of fused SLA-I and beta2 microglobulin, were overexpressed as inclusion bodies in Escherichia coli. Also, variants were made of the single-chain proteins......, by linking them through glycine-rich linkers to peptides representing T-cell epitopes from classical swine fever virus (CSFV) and foot-and-mouth disease virus (FMDV). An in vitro refold assay was developed, using a monoclonal anti-SLA antibody (PT85A) to gauge refolding. The single best-defined, SLA...

  12. Physics with loosely bound nuclei

    Indian Academy of Sciences (India)

    Chhanda Samanta

    2001-08-01

    The essential aspect of contemporary physics is to understand properties of nucleonic matter that constitutes the world around us. Over the years research in nuclear physics has provided strong guidance in understanding the basic principles of nuclear interactions. But, the scenario of nuclear physics changed drastically as the new generation of accelerators started providing more and more rare isotopes, which are away from the line of stability. These weakly bound nuclei are found to exhibit new forms of nuclear matter and unprecedented exotic behaviour. The low breakup thresholds of these rare nuclei are posing new challenges to both theory and experiments. Fortunately, nature has provided a few loosely bound stable nuclei that have been studied thoroughly for decades. Attempts are being made to find a consistent picture for the unstable nuclei starting from their stable counterparts. Some significant differences in the structure and reaction mechanisms are found.

  13. Concentration Bounds for Stochastic Approximations

    CERN Document Server

    Frikha, Noufel

    2012-01-01

    We obtain non asymptotic concentration bounds for two kinds of stochastic approximations. We first consider the deviations between the expectation of a given function of the Euler scheme of some diffusion process at a fixed deterministic time and its empirical mean obtained by the Monte-Carlo procedure. We then give some estimates concerning the deviation between the value at a given time-step of a stochastic approximation algorithm and its target. Under suitable assumptions both concentration bounds turn out to be Gaussian. The key tool consists in exploiting accurately the concentration properties of the increments of the schemes. For the first case, as opposed to the previous work of Lemaire and Menozzi (EJP, 2010), we do not have any systematic bias in our estimates. Also, no specific non-degeneracy conditions are assumed.

  14. Entropy Bounds in Spherical Space

    CERN Document Server

    Brevik, I; Odintsov, S D; Brevik, Iver; Milton, Kimball A.; Odintsov, Sergei D.

    2002-01-01

    Exact calculations are given for the Casimir energy for various fields in $R\\times S^3$ geometry. The Green's function method naturally gives a result in a form convenient in the high-temperature limit, while the statistical mechanical approach gives a form appropriate for low temperatures. The equivalence of these two representations is demonstrated. Some discrepancies with previous work are noted. In no case, even for ${\\cal N}=4$ SUSY, is the ratio of entropy to energy found to be bounded.

  15. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Science.gov (United States)

    2013-03-26

    ... Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math Science... Upward Bound Math Science Annual Performance Report. OMB Control Number: 1840-NEW. Type of Review: New... under the regular Upward Bound (UB) and Upward Bound Math and Science (UBMS) Programs. The Department...

  16. Bounded Delay Packet Scheduling in a Bounded Buffer

    CERN Document Server

    Fung, Stanley P Y

    2009-01-01

    We study the problem of buffer management in QoS-enabled network switches in the bounded delay model where each packet is associated with a weight and a deadline. We consider the more realistic situation where the network switch has a finite buffer size. A 9.82-competitive algorithm is known for the case of multiple buffers (Azar and Levy, SWAT'06). Recently, for the case of a single buffer, a 3-competitive deterministic algorithm and a 2.618-competitive randomized algorithm was known (Li, INFOCOM'09). In this paper we give a simple deterministic 2-competitive algorithm for the case of a single buffer.

  17. Identification of peptides from foot‐and‐mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA‐1*0401 and SLA‐2*0401

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, M.; Nielsen, Morten;

    2013-01-01

    Characterization of the peptide‐binding specificity of swine leukocyte antigen (SLA) class I and II molecules is critical to the understanding of adaptive immune responses of swine toward infectious pathogens. Here, we describe the complete binding motif of the SLA‐2*0401 molecule based...... on a positional scanning combinatorial peptide library approach. By combining this binding motif with data achieved by applying the NetMHCpan peptide prediction algorithm to both SLA‐1*0401 and SLA‐2*0401, we identified high‐affinity binding peptides. A total of 727 different 9mer and 726 different 10mer peptides...... within the structural proteins of foot‐and‐mouth disease virus (FMDV), strain A24 were analyzed as candidate T‐cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA‐1*0401 and SLA‐2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted...

  18. Argonaute and Argonaute-Bound Small RNAs in Stem Cells

    Directory of Open Access Journals (Sweden)

    Lihong Zhai

    2016-02-01

    Full Text Available Small RNAs are essential for a variety of cellular functions. Argonaute (AGO proteins are associated with all of the different classes of small RNAs, and are indispensable in small RNA-mediated regulatory pathways. AGO proteins have been identified in various types of stem cells in diverse species from plants and animals. This review article highlights recent progress on how AGO proteins and AGO-bound small RNAs regulate the self-renewal and differentiation of distinct stem cell types, including pluripotent, germline, somatic, and cancer stem cells.

  19. Bound Polaron Pair Formation in Poly (phenylenevinylenes)

    Science.gov (United States)

    Rothberg, Lewis

    The following sections are included: * INTRODUCTION * PHOTOGENERATED YIELD OF SINGLET EXCITONS * AGGREGRATION EFFECTS ON EXCITED STATE PHOTO-GENERATION * ASSIGNMENT TO BOUND POLARON PAIRS AND DISCUSSION * PROBLEMS WITH THE BOUND POLARON PAIR PICTURE AND CONCLUSION * REFERENCES

  20. An Exponential Bound for Cox Regression☆

    Science.gov (United States)

    Kosorok, M. R.

    2012-01-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold. PMID:23565013

  1. An Exponential Bound for Cox Regression.

    Science.gov (United States)

    Goldberg, Y; Kosorok, M R

    2012-07-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold.

  2. Monotonicity of the quantum linear programming bound

    OpenAIRE

    Eric M. Rains

    1998-01-01

    The most powerful technique known at present for bounding the size of quantum codes of prescribed minimum distance is the quantum linear programming bound. Unlike the classical linear programming bound, it is not immediately obvious that if the quantum linear programming constraints are satisfiable for dimension K, that the constraints can be satisfied for all lower dimensions. We show that the quantum linear programming bound is indeed monotonic in this sense, and give an explicitly monotoni...

  3. Bound entangled states invariant under Ux

    Institute of Scientific and Technical Information of China (English)

    Wang Zhen; Wang Zhi-Xi

    2008-01-01

    This paper obtains an entangled condition for isotropic-like states by using an atomic map. It constructs a class of bound entangled states from the entangled condition and shows that the partial transposition of the state from the constructed bound entangled class is an edge bound entangled state by using range criterion.

  4. Bounded rationality and heterogeneous expectations in macroeconomics

    NARCIS (Netherlands)

    D. Massaro

    2012-01-01

    This thesis studies the effect of individual bounded rationality on aggregate macroeconomic dynamics. Boundedly rational agents are specified as using simple heuristics in their decision making. An important aspect of the type of bounded rationality described in this thesis is that the population of

  5. Upper Bounds on Numerical Approximation Errors

    DEFF Research Database (Denmark)

    Raahauge, Peter

    2004-01-01

    This paper suggests a method for determining rigorous upper bounds on approximationerrors of numerical solutions to infinite horizon dynamic programming models.Bounds are provided for approximations of the value function and the policyfunction as well as the derivatives of the value function...... to approximations of a standard (strictly concave)growth model.KEYWORDS: Numerical approximation errors, Bellman contractions, Error bounds...

  6. Counting Young Tableaux of Bounded Height

    Science.gov (United States)

    Bergeron, Francois; Gascon, Francis

    2000-03-01

    We show that formulas of Gessel, for the generating functions for Young standard tableaux of height bounded by k (see [2]), satisfy linear differential equations, with polynomial coefficients, equivalent to P-recurrences conjectured by Favreau, Krob and the first author (see [1]) for the number of bounded height tableaux and pairs of bounded height tableaux.

  7. Profiling epidermal growth factor receptor and heregulin receptor 3 heteromerization using receptor tyrosine kinase heteromer investigation technology.

    Directory of Open Access Journals (Sweden)

    Mohammed Akli Ayoub

    Full Text Available Heteromerization can play an important role in regulating the activation and/or signal transduction of most forms of receptors, including receptor tyrosine kinases (RTKs. The study of receptor heteromerization has evolved extensively with the emergence of resonance energy transfer based approaches such as bioluminescence resonance energy transfer (BRET. Here, we report an adaptation of our Receptor-Heteromer Investigation Technology (Receptor-HIT that has recently been published as the G protein-coupled receptor (GPCR Heteromer Identification Technology (GPCR-HIT. We now demonstrate the utility of this approach for investigating RTK heteromerization by examining the functional interaction between the epidermal growth factor (EGF receptor (EGFR; also known as erbB1/HER1 and heregulin (HRG receptor 3 (HER3; also known as erbB3 in live HEK293FT cells using recruitment of growth factor receptor-bound protein 2 (Grb2 to the activated receptors. We found that EGFR and HER3 heteromerize specifically as demonstrated by HRG inducing a BRET signal between EGFR/Rluc8 and Grb2/Venus only when HER3 was co-expressed. Similarly, EGF stimulation promoted a specific BRET signal between HER3/Rluc8 and Grb2/Venus only when EGFR was co-expressed. Both EGF and HRG effects on Grb2 interaction are dose-dependent, and specifically blocked by EGFR inhibitor AG-1478. Furthermore, truncation of HER3 to remove the putative Grb2 binding sites appears to abolish EGF-induced Grb2 recruitment to the EGFR-HER3 heteromer. Our results support the concept that EGFR interacts with Grb2 in both constitutive and EGF-dependent manners and this interaction is independent of HER3 co-expression. In contrast, HER3-Grb2 interaction requires the heteromerization between EGFR and HER3. These findings clearly indicate the importance of EGFR-HER3 heteromerization in HER3-mediated Grb2-dependent signaling pathways and supports the central role of HER3 in the diversity and regulation of HER

  8. Higgs mass bounds from the functional RG

    International Nuclear Information System (INIS)

    We investigate a Top-Yukawa toy model to study Higgs mass bounds in the framework of the functional renormalization group (RG). Starting the calculations with a quartic ultraviolet (UV) potential we get a finite range of values for the Higgs mass in the infrared for a given cutoff. The bounds appear in a natural way as a consequence of the RG flow. The lower mass bound is approached for a vanishing UV quartic coupling. Furthermore, we study the influence of higher-dimensional operators on the lower Higgs mass bound. We find that even seemingly RG irrelevant interactions can take a substantial influence on the lower bound for the Higgs mass.

  9. Capacity Bounds for Parallel Optical Wireless Channels

    KAUST Repository

    Chaaban, Anas

    2016-01-01

    A system consisting of parallel optical wireless channels with a total average intensity constraint is studied. Capacity upper and lower bounds for this system are derived. Under perfect channel-state information at the transmitter (CSIT), the bounds have to be optimized with respect to the power allocation over the parallel channels. The optimization of the lower bound is non-convex, however, the KKT conditions can be used to find a list of possible solutions one of which is optimal. The optimal solution can then be found by an exhaustive search algorithm, which is computationally expensive. To overcome this, we propose low-complexity power allocation algorithms which are nearly optimal. The optimized capacity lower bound nearly coincides with the capacity at high SNR. Without CSIT, our capacity bounds lead to upper and lower bounds on the outage probability. The outage probability bounds meet at high SNR. The system with average and peak intensity constraints is also discussed.

  10. Antibaryon-nucleus bound states

    CERN Document Server

    Hrtánková, J

    2014-01-01

    We calculated antibaryon ($\\bar{B}$ = $\\bar{p}$, $\\bar{\\Lambda}$, $\\bar{\\Sigma}$, $\\bar{\\Xi}$) bound states in selected nuclei within the relativistic mean-field (RMF) model. The G-parity motivated $\\bar{B}$-meson coupling constants were scaled to yield corresponding potentials consistent with available experimental data. Large polarization of the nuclear core caused by $\\bar{B}$ was confirmed. The $\\bar{p}$ annihilation in the nuclear medium was incorporated by including a phenomenological imaginary part of the optical potential. The calculations using a complex $\\bar{p}$-nucleus potential were performed fully self-consistently. The $\\bar{p}$ widths significantly decrease when the phase space reduction is considered for $\\bar{p}$ annihilation products, but they still remain sizeable for potentials consistent with $\\bar{p}$-atom data.

  11. Bound states in the continuum

    Science.gov (United States)

    Hsu, Chia Wei; Zhen, Bo; Stone, A. Douglas; Joannopoulos, John D.; Soljačić, Marin

    2016-09-01

    Bound states in the continuum (BICs) are waves that remain localized even though they coexist with a continuous spectrum of radiating waves that can carry energy away. Their very existence defies conventional wisdom. Although BICs were first proposed in quantum mechanics, they are a general wave phenomenon and have since been identified in electromagnetic waves, acoustic waves in air, water waves and elastic waves in solids. These states have been studied in a wide range of material systems, such as piezoelectric materials, dielectric photonic crystals, optical waveguides and fibres, quantum dots, graphene and topological insulators. In this Review, we describe recent developments in this field with an emphasis on the physical mechanisms that lead to BICs across seemingly very different materials and types of waves. We also discuss experimental realizations, existing applications and directions for future work.

  12. Performance Bounds of Quaternion Estimators.

    Science.gov (United States)

    Xia, Yili; Jahanchahi, Cyrus; Nitta, Tohru; Mandic, Danilo P

    2015-12-01

    The quaternion widely linear (WL) estimator has been recently introduced for optimal second-order modeling of the generality of quaternion data, both second-order circular (proper) and second-order noncircular (improper). Experimental evidence exists of its performance advantage over the conventional strictly linear (SL) as well as the semi-WL (SWL) estimators for improper data. However, rigorous theoretical and practical performance bounds are still missing in the literature, yet this is crucial for the development of quaternion valued learning systems for 3-D and 4-D data. To this end, based on the orthogonality principle, we introduce a rigorous closed-form solution to quantify the degree of performance benefits, in terms of the mean square error, obtained when using the WL models. The cases when the optimal WL estimation can simplify into the SWL or the SL estimation are also discussed. PMID:25643416

  13. Towards Bounded Infeasible Code Detection

    CERN Document Server

    Christ, Jürgen; Schäf, Martin

    2012-01-01

    A first step towards more reliable software is to execute each statement and each control-flow path in a method once. In this paper, we present a formal method to automatically compute test cases for this purpose based on the idea of a bounded infeasible code detection. The method first unwinds all loops in a program finitely often and then encodes all feasible executions of the loop-free programs in a logical formula. Helper variables are introduced such that a theorem prover can reconstruct the control-flow path of a feasible execution from a satisfying valuation of this formula. Based on this formula, we present one algorithm that computes a feasible path cover and one algorithm that computes a feasible statement cover. We show that the algorithms are complete for loop-free programs and that they can be implemented efficiently. We further provide a sound algorithm to compute procedure summaries which makes the method scalable to larger programs.

  14. Spectral computations for bounded operators

    CERN Document Server

    Ahues, Mario; Limaye, Balmohan

    2001-01-01

    Exact eigenvalues, eigenvectors, and principal vectors of operators with infinite dimensional ranges can rarely be found. Therefore, one must approximate such operators by finite rank operators, then solve the original eigenvalue problem approximately. Serving as both an outstanding text for graduate students and as a source of current results for research scientists, Spectral Computations for Bounded Operators addresses the issue of solving eigenvalue problems for operators on infinite dimensional spaces. From a review of classical spectral theory through concrete approximation techniques to finite dimensional situations that can be implemented on a computer, this volume illustrates the marriage of pure and applied mathematics. It contains a variety of recent developments, including a new type of approximation that encompasses a variety of approximation methods but is simple to verify in practice. It also suggests a new stopping criterion for the QR Method and outlines advances in both the iterative refineme...

  15. VORONOI DIAGRAMS WITHOUT BOUNDING BOXES

    Directory of Open Access Journals (Sweden)

    E. T. K. Sang

    2015-10-01

    Full Text Available We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010 and Nerbonne et al (2011.

  16. Information bounds for Gaussian copulas

    CERN Document Server

    Hoff, Peter D; Wellner, Jon A

    2011-01-01

    Often of primary interest in the analysis of multivariate data are the copula parameters describing the dependence among the variables, rather than the univariate marginal distributions. Since the ranks of a multivariate dataset are invariant to changes in the univariate marginal distributions, rank-based procedures are natural candidates as semiparametric estimators of copula parameters. Asymptotic information bounds for such estimators can be obtained from an asymptotic analysis of the rank likelihood, i.e. the probability of the multivariate ranks. In this article, we obtain limiting normal distributions of the rank likelihood for Gaussian copula models. Our results cover models with structured correlation matrices, such as exchangeable, autoregressive and circular correlation, as well as unstructured correlation matrices. For all Gaussian copula models, the limiting distribution of the rank likelihood ratio is shown to be equal to that of a parametric likelihood ratio for an appropriately chosen multivari...

  17. Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors

    Directory of Open Access Journals (Sweden)

    Erik Svensjö

    2014-01-01

    Full Text Available Inhibitors of serine peptidases (ISPs expressed by Leishmania major enhance intracellular parasitism in macrophages by targeting neutrophil elastase (NE, a serine protease that couples phagocytosis to the prooxidative TLR4/PKR pathway. Here we investigated the functional interplay between ISP-expressing L. major and the kallikrein-kinin system (KKS. Enzymatic assays showed that NE inhibitor or recombinant ISP-2 inhibited KKS activation in human plasma activated by dextran sulfate. Intravital microscopy in the hamster cheek pouch showed that topically applied L. major promastigotes (WT and Δisp2/3 mutants potently induced plasma leakage through the activation of bradykinin B2 receptors (B2R. Next, using mAbs against kininogen domains, we showed that these BK-precursor proteins are sequestered by L. major promastigotes, being expressed at higher % in the Δisp2/3 mutant population. Strikingly, analysis of the role of kinin pathway in the phagocytic uptake of L. major revealed that antagonists of B2R or B1R reversed the upregulated uptake of Δisp2/3 mutants without inhibiting macrophage internalization of WT L. major. Collectively, our results suggest that L. major ISP-2 fine-tunes macrophage phagocytosis by inhibiting the pericellular release of proinflammatory kinins from surface bound kininogens. Ongoing studies should clarify whether L. major ISP-2 subverts TLR4/PKR-dependent prooxidative responses of macrophages by preventing activation of G-protein coupled B2R/B1R.

  18. Ecotin-like ISP of L. major promastigotes fine-tunes macrophage phagocytosis by limiting the pericellular release of bradykinin from surface-bound kininogens: a survival strategy based on the silencing of proinflammatory G-protein coupled kinin B2 and B1 receptors.

    Science.gov (United States)

    Svensjö, Erik; Nogueira de Almeida, Larissa; Vellasco, Lucas; Juliano, Luiz; Scharfstein, Julio

    2014-01-01

    Inhibitors of serine peptidases (ISPs) expressed by Leishmania major enhance intracellular parasitism in macrophages by targeting neutrophil elastase (NE), a serine protease that couples phagocytosis to the prooxidative TLR4/PKR pathway. Here we investigated the functional interplay between ISP-expressing L. major and the kallikrein-kinin system (KKS). Enzymatic assays showed that NE inhibitor or recombinant ISP-2 inhibited KKS activation in human plasma activated by dextran sulfate. Intravital microscopy in the hamster cheek pouch showed that topically applied L. major promastigotes (WT and Δisp2/3 mutants) potently induced plasma leakage through the activation of bradykinin B2 receptors (B2R). Next, using mAbs against kininogen domains, we showed that these BK-precursor proteins are sequestered by L. major promastigotes, being expressed at higher % in the Δisp2/3 mutant population. Strikingly, analysis of the role of kinin pathway in the phagocytic uptake of L. major revealed that antagonists of B2R or B1R reversed the upregulated uptake of Δisp2/3 mutants without inhibiting macrophage internalization of WT L. major. Collectively, our results suggest that L. major ISP-2 fine-tunes macrophage phagocytosis by inhibiting the pericellular release of proinflammatory kinins from surface bound kininogens. Ongoing studies should clarify whether L. major ISP-2 subverts TLR4/PKR-dependent prooxidative responses of macrophages by preventing activation of G-protein coupled B2R/B1R. PMID:25294952

  19. Phospho-tyrosine dependent protein–protein interaction network

    Science.gov (United States)

    Grossmann, Arndt; Benlasfer, Nouhad; Birth, Petra; Hegele, Anna; Wachsmuth, Franziska; Apelt, Luise; Stelzl, Ulrich

    2015-01-01

    Post-translational protein modifications, such as tyrosine phosphorylation, regulate protein–protein interactions (PPIs) critical for signal processing and cellular phenotypes. We extended an established yeast two-hybrid system employing human protein kinases for the analyses of phospho-tyrosine (pY)-dependent PPIs in a direct experimental, large-scale approach. We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells. About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes. Network analysis revealed that pY-mediated recognition events are tied to a highly connected protein module dedicated to signaling and cell growth pathways related to cancer. Using binding assays, protein complementation and phenotypic readouts to characterize the pY-dependent interactions of TSPAN2 (tetraspanin 2) and GRB2 or PIK3R3 (p55γ), we exemplarily provide evidence that the two pY-dependent PPIs dictate cellular cancer phenotypes. PMID:25814554

  20. Generating substrate bound functional chemokine gradients in vitro

    DEFF Research Database (Denmark)

    Hjortø, Gertrud Malene; Hansen, Morten; Larsen, Niels Bent;

    2009-01-01

    Microcontact printing (mCP) is employed to generate discontinuous microscale gradients of active fractalkine, a chemokine expressed by endothelial cells near sites of inflammation where it is believed to form concentration gradients descending away from the inflamed area. In vivo, fractalkine...... is a transmembrane molecule extending its chemokine domain into the vascular lumen. Substrate bound in vitro gradients may thus closely resemble in vivo conditions. Direct mCP of sensitive proteins like fractalkine may cause partial protein denaturation and will not ensure correct orientation of the biologically...

  1. Bound anionic states of adenine

    Energy Technology Data Exchange (ETDEWEB)

    Haranczyk, Maciej; Gutowski, Maciej S; Li, Xiang; Bowen, Kit H

    2007-03-20

    Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases, are thought to be adiabatically unbound. Contrary to this expectation, we have demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the new-found anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The discovery of these valence anionic states of adenine was facilitated by the development of: (i) a new experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (ii) a new combinatorial/ quantum chemical approach for identification of the most stable tautomers of organic molecules. The computational portion of this work was supported by the: (i) Polish State Committee for Scientific Research (KBN) Grants: DS/8000-4-0140-7 (M.G.) and N204 127 31/2963 (M.H.), (ii) European Social Funds (EFS) ZPORR/2.22/II/2.6/ARP/U/2/05 (M.H.), and (iii) US DOE Office of Biological and Environmental Research, Low Dose Radiation Research Program (M.G.). M.H. holds the Foundation for Polish Science (FNP) award for young scientists. The calculations were performed at the Academic

  2. Comparative Proteome Bioinformatics: Identification of Phosphotyrosine Signaling Proteins in the Unicellular Protozoan Ciliate Tetrahymena

    DEFF Research Database (Denmark)

    Gammeltoft, Steen; Christensen, Søren Tvorup; Joachimiak, Marcin;

    2005-01-01

    Tetrahymena, bioinformatics, cilia, evolution, signaling, TtPTK1, PTK, Grb2, SH-PTP 2, Plcy, Src, PTP, PI3K, SH2, SH3, PH......Tetrahymena, bioinformatics, cilia, evolution, signaling, TtPTK1, PTK, Grb2, SH-PTP 2, Plcy, Src, PTP, PI3K, SH2, SH3, PH...

  3. Bounds on double-diffusive convection

    Science.gov (United States)

    Balmforth, Neil J.; Ghadge, Shilpa A.; Kettapun, Atichart; Mandre, Shreyas D.

    2006-12-01

    We consider double-diffusive convection between two parallel plates and compute bounds on the flux of the unstably stratified species using the background method. The bound on the heat flux for Rayleigh Bénard convection also serves as a bound on the double-diffusive problem (with the thermal Rayleigh number equal to that of the unstably stratified component). In order to incorporate a dependence of the bound on the stably stratified component, an additional constraint must be included, like that used by Joseph (Stability of Fluid Motion, 1976, Springer) to improve the energy stability analysis of this system. Our bound extends Joseph's result beyond his energy stability boundary. At large Rayleigh number, the bound is found to behave like R_T(1/2) for fixed ratio R_S/R_T, where R_T and R_S are the Rayleigh numbers of the unstably and stably stratified components, respectively.

  4. Instanton bound states in ABJM theory

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [DESY Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

    2013-06-15

    The partition function of the ABJM theory receives non-perturbative corrections due to instanton effects. We study these non-perturbative corrections, including bound states of worldsheet instantons and membrane instantons, in the Fermi-gas approach. We require that the total non-perturbative correction should be always finite for arbitrary Chern-Simons level. This finiteness is realized quite non-trivially because each bound state contribution naively diverges at some levels. The poles of each contribution should be canceled out in total. We use this pole cancellation mechanism to find unknown bound state corrections from known ones. We conjecture a general expression of the bound state contribution. Summing up all the bound state contributions, we find that the effect of bound states is simply incorporated into the worldsheet instanton correction by a redefinition of the chemical potential in the Fermi-gas system. Analytic expressions of the 3- and 4-membrane instanton corrections are also proposed.

  5. Process expression of bounded Petri nets

    Institute of Scientific and Technical Information of China (English)

    吴哲辉

    1996-01-01

    The concept of process expression of bounded Petri nets is presented.Moreover,an algorithm to find the process expression for a bounded Petri net is given.A process expression of a bounded Petri net is a regular expression whose every alphabet symbol represents a basic subprocess of the net.The regular set expressed by the regular expression is the set of all surjective processes of a bounded Petri net.A surjective process of a bounded Petri net is a process of this net in which every s-cut corresponds to a reachable marking of the net.Therefore,all surjective processes of a bounded Petri net can be obtained as long as its process expression and the basic subprocess represented by the alphabet symbols of the process expression are given.

  6. Bound beta-decay: BOB

    International Nuclear Information System (INIS)

    For many years exotic decay modes of the neutron have been investigated as possible doorways to the exploration of new physics. The bound beta-decay (BOB) of the neutron into a hydrogen atom and an anti-neutrino offers a very elegant method to study neutrino helicities. However, this rare decay has not yet been observed for the free neutron, owing to the challenge of measuring a decay involving only electrically neutral particles and with an estimated branching ratio of only a few 106 of the three-body decay mode. During the past few years scientists from the TUM E18 Group have developed a novel experimental scheme which addresses all necessary problems associated with the observation of this two-body neutron decay in a very coherent way. The BOB experiment shall be installed at a tangential beam tube of a powerful research reactor such as the SR6 at the FRMII in Garching or H6-H7 beam tube at ILL. This talk will provide insights and ideas on how such an experiment is to be performed.

  7. Neutron bound {beta}- decay- BOB

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, M.; Berger, M.; Emmerich, R.; Faestermann, T.; Gutsmiedl, E.; Hartmann, F.J.; Paul, S.; Ruschel, S.; Schoen, J.; Schott, W.; Schubert, U.; Trautner, A. [Physik-Department, TUM, 85748 Garching (Germany); Engels, R. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Fierlinger, P. [Excellence Cluster Universe, TUM, 85748 Garching (Germany); Hertenberger, R. [Sektion Physik, LMU, 85748 Garching (Germany); Roehrmoser, R. [FRM2, TUM, 85748 Garching (Germany); Udem, T. [Max-Planck-Institut fuer Quantenphysik, 85748 Garching (Germany)

    2011-07-01

    The bound neutron {beta}-decay(BOB) into a hydrogen atom and an electron antineutrino is investigated.The hyper-fine-state population of the monoenergetic hydrogen atoms (326.3 eV) yields the neutrino left-handed-ness or a possible right-handed admixture and possible small scalar and tensor contributions to the weak force. Preexperiments to measure the BOB H(2s) atoms have been done or are being set up using ionizer and RF discharge proton sources, a Wien filter, Cs and Ar cells, a spin filter, electric counter and accelerating fields, a double focusing magnet and a solar blind PM for the Lyman-{alpha} photons. In a first experiment, the charge exchange of the H(2s) atoms into H{sup -}, offering a selective method to discriminate these states against background, is investigated. In a second step the number of background H(2s) resulting from protons interacting with the walls of the experimental setup are determined. For this a quenching E field and a solar blind PM are used.

  8. Stable Bound Orbits around Black Rings

    Energy Technology Data Exchange (ETDEWEB)

    Igata, Takahisa; Ishihara, Hideki; Takamori, Yohsuke, E-mail: igata@sci.osaka-cu.ac.jp [Department of Mathematics and Physics, Graduate School of Science, Osaka City University, Osaka 558-8585 (Japan)

    2011-09-22

    We study stable bound orbits of a free particle around a black ring. Unlike the higher-dimensional black hole case, we find that there exist stable bound orbits in toroidal spiral shape near the ring axis and stable circular orbits on the axis. In addition, radii of stable bound orbits can be infinitely large if the ring thickness is less than a critical value.

  9. Bounded rationality and learning in market competition

    OpenAIRE

    Tuinstra, J.; Hommes, C.H.; Kopányi, D.

    2015-01-01

    This thesis promotes the use of bounded rationality in economic models. The assumption of perfect rationality often imposes high informational and computational burden on economic agents and predictions based on this assumption are not in line with observed behavior in some cases. Models of bounded rationality may better explain actual behavior in such situations. In the thesis we consider market models where firms are boundedly rational: they do not know the demand for their product and they...

  10. Spontaneous R-Parity violation bounds

    CERN Document Server

    Frank, M

    2001-01-01

    We investigate bounds from tree-level and one-loop processes in generic supersymmetric models with spontaneous R-parity breaking in the superpotential. We analyse the bounds from a general point of view. The bounds are applicable both for all models with spontaneous R-parity violation and for explicit bilinear R-parity violation based on general lepton-chargino and neutrino-neutralino mixings. We find constraints from semileptonic B, D and K decays, leptonic decays of the mu and tau, electric dipole moments, as well as bounds for the anomalous magnetic moment of the muon.

  11. Bound States of Double Flavor Hyperons

    CERN Document Server

    Froemel, F; Riska, D O

    2005-01-01

    Several realistic phenomenological nucleon-nucleon interaction models are employed to investigate the possibility of bound deuteron-like states of such heavy flavor hyperons and nucleons, for which the interaction between the light flavor quark components is expected to be the most significant interaction. The results indicate that deuteron-like bound states are likely to form between nucleons and the $\\Xi_c^{'}$ and $\\Xi_{cc}$ charm hyperons as well as between $\\Xi$ hyperons and double-charm hyperons. Bound states between two $\\Sigma_c$ hyperons are also likely. In the case of beauty hyperons the corresponding states are likely to be deeply bound.

  12. Bound states of heavy flavor hyperons

    Science.gov (United States)

    Frömel, F.; Juliá-Díaz, B.; Riska, D. O.

    2005-04-01

    Several realistic phenomenological nucleon-nucleon interaction models are employed to investigate the possibility of bound deuteron-like states of such heavy flavor hyperons and nucleons, for which the interaction between the light flavor quark components is expected to be the most significant interaction. The results indicate that deuteron-like bound states are likely to form between nucleons and the Ξc' and Ξ charm hyperons as well as between Ξ hyperons and double-charm hyperons. Bound states between two Σ hyperons are also likely. In the case of beauty hyperons the corresponding states are likely to be deeply bound.

  13. A violation of the covariant entropy bound?

    CERN Document Server

    Masoumi, Ali

    2014-01-01

    Several arguments suggest that the entropy density at high energy density $\\rho$ should be given by the expression $s=K\\sqrt{\\rho/G}$, where $K$ is a constant of order unity. On the other hand the covariant entropy bound requires that the entropy on a light sheet be bounded by $A/4G$, where $A$ is the area of the boundary of the sheet. We find that in a suitably chosen cosmological geometry, the above expression for $s$ violates the covariant entropy bound. We consider different possible explanations for this fact; in particular the possibility that entropy bounds should be defined in terms of volumes of regions rather than areas of surfaces.

  14. Distortion Bounds for Source Broadcast over Degraded Channel

    OpenAIRE

    Yu, Lei; Li, Houqiang; Li, Weiping

    2016-01-01

    The joint source-channel coding problem of sending a memoryless source over a memoryless degraded broadcast channel is considered here. We derive an inner bound and two outer bounds on the achievable distortion region. Moreover, when specialized to Gaussian source broadcast or binary source broadcast, the inner bound and outer bounds could recover the best known inner bound and outer bound. Besides, we also extend the inner bound and outer bounds to Wyner-Ziv source broadcast problem, i.e., s...

  15. Nanopore sensing of individual transcription factors bound to DNA

    Science.gov (United States)

    Squires, Allison; Atas, Evrim; Meller, Amit

    2015-06-01

    Transcription factor (TF)-DNA interactions are the primary control point in regulation of gene expression. Characterization of these interactions is essential for understanding genetic regulation of biological systems and developing novel therapies to treat cellular malfunctions. Solid-state nanopores are a highly versatile class of single-molecule sensors that can provide rich information about local properties of long charged biopolymers using the current blockage patterns generated during analyte translocation, and provide a novel platform for characterization of TF-DNA interactions. The DNA-binding domain of the TF Early Growth Response Protein 1 (EGR1), a prototypical zinc finger protein known as zif268, is used as a model system for this study. zif268 adopts two distinct bound conformations corresponding to specific and nonspecific binding, according to the local DNA sequence. Here we implement a solid-state nanopore platform for direct, label- and tether-free single-molecule detection of zif268 bound to DNA. We demonstrate detection of single zif268 TFs bound to DNA according to current blockage sublevels and duration of translocation through the nanopore. We further show that the nanopore can detect and discriminate both specific and nonspecific binding conformations of zif268 on DNA via the distinct current blockage patterns corresponding to each of these two known binding modes.

  16. On the range of completely bounded maps

    Directory of Open Access Journals (Sweden)

    Richard I. Loebl

    1978-01-01

    Full Text Available It is shown that if every bounded linear map from a C*-algebra α to a von Neumann algebra β is completely bounded, then either α is finite-dimensional or β⫅⊗Mn, where is a commutative von Neumann algebra and Mn is the algebra of n×n complex matrices.

  17. A Cosmological Upper Bound on Superpartner Masses

    CERN Document Server

    Hall, Lawrence J; Volansky, Tomer

    2013-01-01

    If some superpartners were in thermal equilibrium in the early universe, and if the lightest superpartner is a cosmologically stable gravitino, then there is a powerful upper bound on the scale of the superpartner masses. Typically the bound is below tens of TeV, often much lower, and has similar parametrics to the WIMP miracle.

  18. Bounds in the location-allocation problem

    DEFF Research Database (Denmark)

    Juel, Henrik

    1981-01-01

    Develops a family of stronger lower bounds on the objective function value of the location-allocation problem. Solution methods proposed to solve problems in location-allocation; Efforts to develop a more efficient bound solution procedure; Determination of the locations of the sources....

  19. No-arbitrage bounds for financial scenarios

    DEFF Research Database (Denmark)

    Geyer, Alois; Hanke, Michael; Weissensteiner, Alex

    2014-01-01

    We derive no-arbitrage bounds for expected excess returns to generate scenarios used in financial applications. The bounds allow to distinguish three regions: one where arbitrage opportunities will never exist, a second where arbitrage may be present, and a third, where arbitrage opportunities...

  20. Holographic Bound in Brans-Dicke Cosmology

    OpenAIRE

    Gong, Yungui

    1999-01-01

    We apply the holographic principle to the Brans-Dicke cosmology. We analyze the holographic bound in both the Jordan and Einstein frames. The holographic bound is satisfied for both the k=0 and k=-1 universe, but it is violated for the k=1 matter dominated universe.

  1. Consumer choice and revealed bounded rationality

    OpenAIRE

    Manzini, Paola; Mariotti, Marco

    2006-01-01

    We study two boundedly rational procedures in consumer behavior. We show that these procedures can be detected by conditions on observable demand data of the same type as standard revealed preference axioms. This provides the basis for a non-parametric analysis of boundedly rational consumer behavior mirroring the classical one for utility maximization.

  2. A Note on Geodesically Bounded -Trees

    Directory of Open Access Journals (Sweden)

    Kirk WA

    2010-01-01

    Full Text Available It is proved that a complete geodesically bounded -tree is the closed convex hull of the set of its extreme points. It is also noted that if is a closed convex geodesically bounded subset of a complete -tree and if a nonexpansive mapping satisfies then has a fixed point. The latter result fails if is only continuous.

  3. Optimal online bounded space multidimensional packing

    NARCIS (Netherlands)

    Epstein, L.; Stee, R. van

    2003-01-01

    We solve an open problem in the literature by providing an online algorithm for multidimensional bin packing that uses only bounded space. We show that it is optimal among bounded space algorithms for any dimension $d>1$. Its asymptotic performance ratio is $(Pi_{infty})^d$, where $Pi_{infty}approx1

  4. Quantum Lower Bounds by Entropy Numbers

    OpenAIRE

    Heinrich, Stefan

    2006-01-01

    We use entropy numbers in combination with the polynomial method to derive a new general lower bound for the n-th minimal error in the quantum setting of information-based complexity. As an application, we improve some lower bounds on quantum approximation of embeddings between finite dimensional L_p spaces and of Sobolev embeddings.

  5. Bound states of singlet quarks at LHC

    OpenAIRE

    Krasnikov, N. V.

    1996-01-01

    We discuss the discovery potential of the bound states of singlet quarks at LHC. We find that it is possible to discover bound states of singlet quarks at LHC with singlet quark masses up to 300 Gev for $e_{Q} = \\frac{2}{3}$ and up to 200 Gev for $e_{Q} = -\\frac{1}{3}$.

  6. Spatial coagulation with bounded coagulation rate

    CERN Document Server

    Bailleul, Ismael

    2010-01-01

    We prove that the spatial coagulation equation with bounded coagulation rate is well-posed for all times in a given class of kernels if the convection term of the underlying particle dynamics has divergence bounded above by a negative constant. Multiple coagulations, fragmentation and scattering are also considered.

  7. Polynomially Bounded Sequences and Polynomial Sequences

    Directory of Open Access Journals (Sweden)

    Okazaki Hiroyuki

    2015-09-01

    Full Text Available In this article, we formalize polynomially bounded sequences that plays an important role in computational complexity theory. Class P is a fundamental computational complexity class that contains all polynomial-time decision problems [11], [12]. It takes polynomially bounded amount of computation time to solve polynomial-time decision problems by the deterministic Turing machine. Moreover we formalize polynomial sequences [5].

  8. Mass Bounds for Flavour Mixing Bileptons

    CERN Document Server

    Tully, M B

    1999-01-01

    Mass bounds for doubly-charged bilepton gauge bosons are derived from constraints on fermion pair production at LEP and lepton-flavour violating charged lepton decays. The limit obtained of 700 GeV for the doubly-charged bilepton does not depend on the bilepton coupling being flavour-diagonal, unlike other bounds which have been given in the literature.

  9. Probing bound states of D-branes

    CERN Document Server

    Lifschytz, G

    1996-01-01

    A zero-brane is used to probe non-threshold BPS bound states of ($p$, $p+2$,$p+4$)-branes. At long distances the stringy calculation agrees with the supergravity calculations. The supergravity description is given, using the interpretation of the $D=8$ dyonic membrane as the bound state of a two-brane inside a four-brane. We investigate the short distance structure of these bound states, compute the phase shift of the scattered zero-brane and find the bound states characteristic size. It is found that there should be a supersymmetric solution of type IIa supergravity, describing a bound state of a zero-brane and two orthogonal two-brane, all inside a four-brane , with an additional unbound zero-brane. We comment on the relationship between $p$-branes and $(p-2)$-branes.

  10. Rigorous Bounds for Optimal Dynamical Decoupling

    CERN Document Server

    Uhrig, Götz S

    2010-01-01

    We present rigorous performance bounds for the optimal dynamical decoupling pulse sequence protecting a quantum bit (qubit) against pure dephasing. Our bounds apply under the assumption of instantaneous pulses and of bounded perturbing environment and qubit-environment Hamiltonians. We show that if the total sequence time is fixed the optimal sequence can be used to make the distance between the protected and unperturbed qubit states arbitrarily small in the number of applied pulses. If, on the other hand, the minimum pulse interval is fixed and the total sequence time is allowed to scale with the number of pulses, then longer sequences need not always be advantageous. The rigorous bound may serve as testbed for approximate treatments of optimal decoupling in bounded models of decoherence.

  11. Structural Bounds on the Dyadic Effect

    CERN Document Server

    Cinelli, Matteo; Iovanella, Antonio

    2016-01-01

    In this paper we consider the dyadic effect introduced in complex networks when nodes are distinguished by a binary characteristic. Under these circumstances two independent parameters, namely dyadicity and heterophilicity, are able to measure how much the assigned characteristic affects the network topology. All possible configurations can be represented in a phase diagram lying in a two-dimensional space that represents the feasible region of the dyadic effect, which is bound by two upper bounds on dyadicity and heterophilicity. Using some network's structural arguments, we are able to improve such upper bounds and introduce two new lower bounds, providing a reduction of the feasible region of the dyadic effect as well as constraining dyadicity and heterophilicity within a specific range. Some computational experiences show the bounds' effectiveness and their usefulness with regards to different classes of networks.

  12. Automatic analysis of distance bounding protocols

    CERN Document Server

    Malladi, Sreekanth; Kothapalli, Kishore

    2010-01-01

    Distance bounding protocols are used by nodes in wireless networks to calculate upper bounds on their distances to other nodes. However, dishonest nodes in the network can turn the calculations both illegitimate and inaccurate when they participate in protocol executions. It is important to analyze protocols for the possibility of such violations. Past efforts to analyze distance bounding protocols have only been manual. However, automated approaches are important since they are quite likely to find flaws that manual approaches cannot, as witnessed in literature for analysis pertaining to key establishment protocols. In this paper, we use the constraint solver tool to automatically analyze distance bounding protocols. We first formulate a new trace property called Secure Distance Bounding (SDB) that protocol executions must satisfy. We then classify the scenarios in which these protocols can operate considering the (dis)honesty of nodes and location of the attacker in the network. Finally, we extend the const...

  13. Coulomb bound states of strongly interacting photons

    CERN Document Server

    Maghrebi, M F; Bienias, P; Choi, S; Martin, I; Firstenberg, O; Lukin, M D; Büchler, H P; Gorshkov, A V

    2015-01-01

    We show that two photons coupled to Rydberg states via electromagnetically induced transparency can interact via an effective Coulomb potential. This interaction gives rise to a continuum of two-body bound states. Within the continuum, metastable bound states are distinguished in analogy with quasi-bound states tunneling through a potential barrier. We find multiple branches of metastable bound states whose energy spectrum is governed by the Coulomb potential, thus obtaining a photonic analogue of the hydrogen atom. Under certain conditions, the wavefunction resembles that of a diatomic molecule in which the two polaritons are separated by a finite "bond length." These states propagate with a negative group velocity in the medium, allowing for a simple preparation and detection scheme, before they slowly decay to pairs of bound Rydberg atoms.

  14. Acidity and hydrogen exchange dynamics of iron(II)-bound nitroxyl in aqueous solution.

    Science.gov (United States)

    Gao, Yin; Toubaei, Abouzar; Kong, Xianqi; Wu, Gang

    2014-10-20

    Nitroxyl-iron(II) (HNO-Fe(II)) complexes are often unstable in aqueous solution, thus making them very difficult to study. Consequently, many fundamental chemical properties of Fe(II)-bound HNO have remained unknown. Using a comprehensive multinuclear ((1)H, (15)N, (17)O) NMR approach, the acidity of the Fe(II)-bound HNO in [Fe(CN)5(HNO)](3-) was investigated and its pK(a) value was determined to be greater than 11. Additionally, HNO undergoes rapid hydrogen exchange with water in aqueous solution and this exchange process is catalyzed by both acid and base. The hydrogen exchange dynamics for the Fe(II)-bound HNO have been characterized and the obtained benchmark values, when combined with the literature data on proteins, reveal that the rate of hydrogen exchange for the Fe(II)-bound HNO in the interior of globin proteins is reduced by a factor of 10(6). PMID:25205463

  15. Identifying Zn-bound histidine residues in metalloproteins using hydrogen-deuterium exchange mass spectrometry.

    Science.gov (United States)

    Dong, Jia; Callahan, Katie L; Borotto, Nicholas B; Vachet, Richard W

    2014-01-01

    In this work, we have developed a method that uses hydrogen-deuterium exchange (HDX) of C2-hydrogens of histidines coupled with mass spectrometry (MS) to identify Zn-bound histidines in metalloproteins. This method relies on differences in HDX reaction rates of Zn-bound and Zn-free His residues. Using several model peptides and proteins, we find that all Zn-bound His residues have substantially lower HDX reaction rates in the presence of the metal. The vast majority of non-Zn-binding His residues undergo no significant changes in HDX reaction rates when their reactivity is compared in the presence and absence of Zn. Using this new approach, we then determined the Zn binding site of β-2-microglobulin, a protein associated with metal-induced amyloidosis. Together, these results suggest that HDX-MS of His C2-hydrogens is a promising new method for identifying Zn-bound histidines in metalloproteins.

  16. The Fitness Level Method with Tail Bounds

    OpenAIRE

    Witt, Carsten

    2013-01-01

    The fitness-level method, also called the method of f-based partitions, is an intuitive and widely used technique for the running time analysis of randomized search heuristics. It was originally defined to prove upper and lower bounds on the expected running time. Recently, upper tail bounds were added to the technique; however, these tail bounds only apply to running times that are at least twice as large as the expectation. We remove this restriction and supplement the fitness-level method ...

  17. Positivity bounds on double parton distributions

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, Markus; Kasemets, Tomas

    2013-03-15

    Double hard scattering in proton-proton collisions is described in terms of double parton distributions. We derive bounds on these distributions that follow from their interpretation as probability densities, taking into account all possible spin correlations between two partons in an unpolarized proton. These bounds constrain the size of the polarized distributions and can for instance be used to set upper limits on the effects of spin correlations in double hard scattering. We show that the bounds are stable under leading-order DGLAP evolution to higher scales.

  18. Vulnerable Derivatives and Good Deal Bounds

    DEFF Research Database (Denmark)

    Murgoci, Agatha

    2013-01-01

    a new restriction in the arbitrage free model by setting upper bounds on the Sharpe ratios (SRs) of the assets. The potential prices that are eliminated represent unreasonably good deals. The constraint on the SR translates into a constraint on the stochastic discount factor. Thus, tight pricing bounds...... can be obtained. We provide a link between the objective probability measure and the range of potential risk-neutral measures, which has an intuitive economic meaning. We also provide tight pricing bounds for European calls and show how to extend the call formula to pricing other financial products...

  19. Continuous bounded cohomology of locally compact groups

    CERN Document Server

    2001-01-01

    Recent research has repeatedly led to connections between important rigidity questions and bounded cohomology. However, the latter has remained by and large intractable. This monograph introduces the functorial study of the continuous bounded cohomology for topological groups, with coefficients in Banach modules. The powerful techniques of this more general theory have successfully solved a number of the original problems in bounded cohomology. As applications, one obtains, in particular, rigidity results for actions on the circle, for representations on complex hyperbolic spaces and on Teichmüller spaces. A special effort has been made to provide detailed proofs or references in quite some generality.

  20. Lightweight Distance Bounding Protocol against Relay Attacks

    Science.gov (United States)

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  1. Redshift-space limits of bound structures

    NARCIS (Netherlands)

    Duenner, Rolando; Reisenegger, Andreas; Meza, Andres; Araya, Pablo A.; Quintana, Hernan

    2007-01-01

    An exponentially expanding Universe, possibly governed by a cosmological constant, forces gravitationally bound structures to become more and more isolated, eventually becoming causally disconnected from each other and forming so-called 'island universes'. This new scenario reformulates the question

  2. Lower bounds on fluctuations for internal DLA

    CERN Document Server

    Asselah, Amine

    2011-01-01

    We consider internal diffusion limited aggregation in dimension larger than or equal to two. This is a random cluster growth model, where random walks start at the origin of the d-dimensional lattice, one at a time, and stop moving when reaching a site that is not occupied by previous walks. When n random walks are sent from the origin, we establish a lower bound for the inner and outer errors fluctuations of order square root of the logarithm of n. When dimension is larger or equal to three, this lower bound matches the upper bound recently obtained in independent works of \\cite{AG2} and \\cite{JLS2}. Also, we produce as a corollary of our proof of \\cite{AG2}, an upper bound for the fluctuation of the inner error in a specified direction.

  3. Redshift-space limits of bound structures

    CERN Document Server

    D"unner, R; Meza, A; Araya, P A; Quintana, H; D\\"unner, Rolando; Reisenegger, Andreas; Meza, Andr\\'es; Araya, Pablo A.; Quintana, Hern\\'an

    2006-01-01

    An exponentially expanding Universe, possibly governed by a cosmological constant, forces gravitationally bound structures to become more and more isolated, eventually becoming causally disconnected from each other and forming so-called "island universes". This new scenario reformulates the question about which will be the largest structures that will remain gravitationally bound, together with requiring a systematic tool that can be used to recognize the limits and mass of these structures from observational data, namely redshift surveys of galaxies. Here we present a method, based on the spherical collapse model and N-body simulations, by which we can estimate the limits of bound structures as observed in redshift space. The method is based on a theoretical criterion presented in a previous paper that determines the mean density contrast that a spherical shell must have in order to be marginally bound to the massive structure within it. Understanding the kinematics of the system, we translated the real-spac...

  4. Slot antenna as a bound charge oscillator.

    Science.gov (United States)

    Choe, Jong-Ho; Kang, Ji-Hun; Kim, Dai-Sik; Park, Q-Han

    2012-03-12

    We study the scattering properties of an optical slot antenna formed from a narrow rectangular hole in a metal film. We show that slot antennas can be modeled as bound charge oscillators mediating resonant light scattering. A simple closed-form expression for the scattering spectrum of a slot antenna is obtained that reveals the nature of a bound charge oscillator and also the effect of a substrate. We find that the spectral width of scattering resonance is dominated by a radiative damping caused by the Abraham-Lorentz force acting on a bound charge. The bound charge oscillator model provides not only an intuitive physical picture for the scattering of an optical slot antenna but also reasonable numerical agreements with rigorous calculations using the finite-difference time-domain method. PMID:22418535

  5. Bound phenolics in foods, a review.

    Science.gov (United States)

    Acosta-Estrada, Beatriz A; Gutiérrez-Uribe, Janet A; Serna-Saldívar, Sergio O

    2014-01-01

    Among phytochemicals, phenolic compounds have been extensively researched due to their diverse health benefits. Phenolic compounds occur mostly as soluble conjugates and insoluble forms, covalently bound to sugar moieties or cell wall structural components. Absorption mechanisms for bound phenolic compounds in the gastrointestinal tract greatly depend on the liberation of sugar moieties. Food processes such as fermentation, malting, thermoplastic extrusion or enzymatic, alkaline and acid hydrolyses occasionally assisted with microwave or ultrasound have potential to release phenolics associated to cell walls. Different kinds of wet chemistry methodologies to release and detect bound phenolic have been developed. These include harsh heat treatments, chemical modifications or biocatalysis. New protocols for processing and determining phenolics in food matrices must be devised in order to release bound phenolics and for quality control in the growing functional food industry.

  6. THE EIGENVALUE PERTURBATION BOUND FOR ARBITRARY MATRICES

    Institute of Scientific and Technical Information of China (English)

    Wen Li; Jian-xin Chen

    2006-01-01

    In this paper we present some new absolute and relative perturbation bounds for the eigenvalue for arbitrary matrices, which improves some recent results. The eigenvalue inclusion region is also discussed.

  7. Finite blocklength converse bounds for quantum channels

    OpenAIRE

    Matthews, William; Wehner, Stephanie

    2012-01-01

    We derive upper bounds on the rate of transmission of classical information over quantum channels by block codes with a given blocklength and error probability, for both entanglement-assisted and unassisted codes, in terms of a unifying framework of quantum hypothesis testing with restricted measurements. Our bounds do not depend on any special property of the channel (such as memorylessness) and generalise both a classical converse of Polyanskiy, Poor, and Verd\\'{u} as well as a quantum conv...

  8. New Spectral Features from Bound Dark Matter

    DEFF Research Database (Denmark)

    Catena, Riccardo; Kouvaris, Chris

    2016-01-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature we predict can provide the ultimate smoking gun for dark matter discovery for experiments...... with positive signal but unclear background. The new feature is universal, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section....

  9. Explicit bounds of complex exponential frames

    Directory of Open Access Journals (Sweden)

    Boivin André

    2006-01-01

    Full Text Available We discuss the stability of complex exponential frames in , . Specifically, we improve the -theorem and obtain explicit upper and lower bounds for some complex exponential frames perturbed along the real and imaginary axes, respectively. Two examples are given to show that the bounds are best possible. In addition, the growth of the entire functions of exponential type on the integer sequence is estimated.

  10. Mutually Unbiased Bases and Bound Entanglement

    OpenAIRE

    Hiesmayr, Beatrix C.; Löffler, Wolfgang

    2013-01-01

    In this contribution we relate two different key concepts: mutually unbiased bases (MUBs) and entanglement; in particular we focus on bound entanglement, i.e. highly mixed states which cannot be distilled by local operations and classical communications. For a certain class of states --for which the state-space forms a "magic" simplex-- we analyze the set of bound entangled states detected by the MUB criterion for different dimensions d and number of particles n. We find that the geometry is ...

  11. Lower Bound of Electrical Conductivity from Holography

    CERN Document Server

    Ge, Xian-Hui; Wu, Shao-Feng

    2015-01-01

    We propose a universal lower bound of dc electrical conductivity in rotational- and translational- symmetries breaking systems via the holographic duality. This bound predicts that BTZ-black brane can be easily used to realize linear temperature resistivity. We also construct an anisotropic black brane solution, which yields linear temperature for the in-plane resistivity and insulating behavior for the out-of-plane resistivity. Ultimately, we discuss its implications in experiments.

  12. Monotonically convergent algorithms for bounded quantum controls

    OpenAIRE

    Turinici, Gabriel

    2003-01-01

    International audience Most of the numerical simulations in quantum (bilinear) control have used one of the monotonically convergent algorithms of Krotov (introduced by Tannor et al. (Tannor et al., 1992)) or of Zhu & Rabitz (Zhu and Rabitz, 1998). Recently(Maday and Turinici, 2002), new schemes have been designed that enlarge the class of monotonic algorithms. Within this context, this paper presents a new algorithm that implements a search for a bounded control with given bounds. Numeric...

  13. Refined Error Bounds for Several Learning Algorithms

    OpenAIRE

    Hanneke, Steve

    2015-01-01

    This article studies the achievable guarantees on the error rates of certain learning algorithms, with particular focus on refining logarithmic factors. Many of the results are based on a general technique for obtaining bounds on the error rates of sample-consistent classifiers with monotonic error regions, in the realizable case. We prove bounds of this type expressed in terms of either the VC dimension or the sample compression size. This general technique also enables us to derive several ...

  14. New spectral features from bound dark matter

    Science.gov (United States)

    Catena, Riccardo; Kouvaris, Chris

    2016-07-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature that we predict can provide a complementary verification of dark matter discovery at experiments with positive signal but unclear background. The effect is generically expected, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section.

  15. The neural basis of bounded rational behavior

    OpenAIRE

    Coricelli, Giorgio; Nagel, Rosemarie

    2010-01-01

    Bounded rational behaviour is commonly observed in experimental games and in real life situations. Neuroeconomics can help to understand the mental processing underlying bounded rationality and out-of-equilibrium behaviour. Here we report results from recent studies on the neural basis of limited steps of reasoning in a competitive setting —the beauty contest game. We use functional magnetic resonance imaging (fMRI) to study the neural correlates of human mental processes in strategic games. ...

  16. New Spectral Features from Bound Dark Matter

    CERN Document Server

    Catena, Riccardo

    2016-01-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature we predict can provide the ultimate smoking gun for dark matter discovery for experiments with positive signal but unclear background. The new feature is universal, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section.

  17. A Minority Game with Bounded Recall.

    OpenAIRE

    Renault, Jérôme; Scarsini, Marco; Tomala, Tristan

    2007-01-01

    This paper studies a repeated minority game with public signals, symmetric bounded recall, and pure strategies. We investigate both public and private equilibria of the game with fixed recall size. We first show how public equilibria in such a repeated game can be represented as colored subgraphs of a de Bruijn graph. Then we prove that the set of public equilibrium payoffs with bounded recall converges to the set of uniform equilibrium payoffs as the size of the recall increases. We also sho...

  18. HiggsBounds: Confronting arbitrary Higgs sectors with exclusion bounds from LEP and the Tevatron

    Science.gov (United States)

    Bechtle, P.; Brein, O.; Heinemeyer, S.; Weiglein, G.; Williams, K. E.

    2010-01-01

    HiggsBounds is a computer code that tests theoretical predictions of models with arbitrary Higgs sectors against the exclusion bounds obtained from the Higgs searches at LEP and the Tevatron. The included experimental information comprises exclusion bounds at 95% C.L. on topological cross sections. In order to determine which search topology has the highest exclusion power, the program also includes, for each topology, information from the experiments on the expected exclusion bound, which would have been observed in case of a pure background distribution. Using the predictions of the desired model provided by the user as input, HiggsBounds determines the most sensitive channel and tests whether the considered parameter point is excluded at the 95% C.L. HiggsBounds is available as a Fortran 77 and Fortran 90 code. The code can be invoked as a command line version, a subroutine version and an online version. Examples of exclusion bounds obtained with HiggsBounds are discussed for the Standard Model, for a model with a fourth generation of quarks and leptons and for the Minimal Supersymmetric Standard Model with and without CP-violation. The experimental information on the exclusion bounds currently implemented in HiggsBounds will be updated as new results from the Higgs searches become available.

  19. Negative regulation of lymphocyte activation by the adaptor protein LAX.

    Science.gov (United States)

    Zhu, Minghua; Granillo, Olivia; Wen, Renren; Yang, Kaiyong; Dai, Xuezhi; Wang, Demin; Zhang, Weiguo

    2005-05-01

    The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of PI3K. LAX, however, is not capable of replacing LAT in the TCR signaling pathway. In this study we report that upon T or B cell activation, the LAX protein was up-regulated dramatically. Although disruption of the LAX gene by homologous recombination had no major impact on lymphocyte development, it caused a significant reduction in CD23 expression on mature B cells. Interestingly, naive LAX(-/-) mice had spontaneous germinal center formation. Compared with normal T and B cells, LAX(-/-) T and B cells were hyperresponsive and had enhanced calcium flux, protein tyrosine phosphorylation, MAPK and Akt activation, and cell survival upon engagement of the T or B AgRs. Our data demonstrate that LAX functions as a negative regulator in lymphocyte signaling.

  20. Markers of protein oxidation

    DEFF Research Database (Denmark)

    Headlam, Henrietta A; Davies, Michael Jonathan

    2004-01-01

    Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed...... of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio...... modulated by EDTA. This is ascribed to metal ion-protein interactions affecting the sites of initial oxidation. Hypochlorous acid gave low concentrations of released carbonyls, but high yields of protein-bound material. The peroxyl radical generator 2,2'-azobis(2-amidinopropane) hydrochloride...

  1. Bounds of Deviation for Branching Chains in Random Environments

    Institute of Scientific and Technical Information of China (English)

    Wei Gang WANG

    2011-01-01

    We consider non-extinct branching processes in general random environments. Under the condition of means and second moments of each generation being bounded, we give the upper bounds and lower bounds for some form deviations of the process.

  2. Interaction measurement of particles bound to a lipid membrane

    Science.gov (United States)

    Sarfati, Raphael; Dufresne, Eric

    2015-03-01

    The local shape and dynamics of the plasma membrane play important roles in many cellular processes. Local membrane deformations are often mediated by the adsorption of proteins (notably from the BAR family), and their subsequent self-assembly. The emerging hypothesis is that self-assembly arises from long-range interactions of individual proteins through the membrane's deformation field. We study these interactions in a model system of micron-sized colloidal particles adsorbed onto a lipid bilayer. We use fluorescent microscopy, optical tweezers and particle tracking to measure dissipative and conservative forces as a function of the separation between the particles. We find that particles are driven together with forces of order 100 fN and remain bound in a potential well with a stiffness of order 100 fN/micron.

  3. Heterologous expression and purification of membrane-bound pyrophosphatases

    DEFF Research Database (Denmark)

    Kellosalo, J.; Kajander, T.; Palmgren, Michael Broberg;

    2011-01-01

    to obtain structural information for drug design. We have tested the expression of eight integral membrane pyrophosphatases in Saccharomyces cerevisiae, six from bacterial and archaeal sources and two from protozoa. Two proteins originating from hyperthermophilic organisms were purified in dimeric......Membrane-bound pyrophosphatases (M-PPases) are enzymes that couple the hydrolysis of inorganic pyrophosphate to pumping of protons or sodium ions. In plants and bacteria they are important for relieving stress caused by low energy levels during anoxia, drought, nutrient deficiency, cold and low...... light intensity. While they are completely absent in mammalians, they are key players in the survival of disease-causing protozoans making these proteins attractive pharmacological targets. In this work, we aimed at the purification of M-PPases in amounts suitable for crystallization as a first step...

  4. A Bound on Equipartition of Energy

    CERN Document Server

    Masi, Nicolo'

    2011-01-01

    In this article I want to demonstrate that the time-scale constraints for a thermodynamic system imply the new concept of equipartition of energy bound (EEB) or, more generally, a thermodynamical bound for the partition of energy. This means that I theorize and discuss the possibility to put an upper limit to the equipartition factor for a gas of particles. This could be interpreted as a sort of transcription of the entropy bounds from quantum-holographic sector. The number 4.93, i.e. the EEB, obtained from a comparison between the Margolus-Levitin quantum theorem and the TTT bound for relaxation times by Hod, seems like a special value for the thermodynamics of particle systems. This bound has been related to the idea of an extremal statistics and independently traced in a statistical mechanics framework. In fact, I identified a type of fluid that is capable of reaching to saturate the limit value I obtained for the equipartition factor. This was done by analyzing the mathematical behavior of the distributio...

  5. Matroidal Degree-Bounded Minimum Spanning Trees

    CERN Document Server

    Zenklusen, Rico

    2011-01-01

    We consider the minimum spanning tree (MST) problem under the restriction that for every vertex v, the edges of the tree that are adjacent to v satisfy a given family of constraints. A famous example thereof is the classical degree-constrained MST problem, where for every vertex v, a simple upper bound on the degree is imposed. Iterative rounding/relaxation algorithms became the tool of choice for degree-bounded network design problems. A cornerstone for this development was the work of Singh and Lau, who showed for the degree-bounded MST problem how to find a spanning tree violating each degree bound by at most one unit and with cost at most the cost of an optimal solution that respects the degree bounds. However, current iterative rounding approaches face several limits when dealing with more general degree constraints. In particular, when several constraints are imposed on the edges adjacent to a vertex v, as for example when a partition of the edges adjacent to v is given and only a fixed number of elemen...

  6. Bounds for graph regularity and removal lemmas

    CERN Document Server

    Conlon, David

    2011-01-01

    We show, for any positive integer k, that there exists a graph in which any equitable partition of its vertices into k parts has at least ck^2/\\log^* k pairs of parts which are not \\epsilon-regular, where c,\\epsilon>0 are absolute constants. This bound is tight up to the constant c and addresses a question of Gowers on the number of irregular pairs in Szemer\\'edi's regularity lemma. In order to gain some control over irregular pairs, another regularity lemma, known as the strong regularity lemma, was developed by Alon, Fischer, Krivelevich, and Szegedy. For this lemma, we prove a lower bound of wowzer-type, which is one level higher in the Ackermann hierarchy than the tower function, on the number of parts in the strong regularity lemma, essentially matching the upper bound. On the other hand, for the induced graph removal lemma, the standard application of the strong regularity lemma, we find a different proof which yields a tower-type bound. We also discuss bounds on several related regularity lemmas, inclu...

  7. Introduction to QCD - a bound state perspective

    CERN Document Server

    Hoyer, Paul

    2011-01-01

    These lecture notes focus on the bound state sector of QCD. Motivated by data which suggests that the strong coupling \\alpha_s(Q) freezes at low Q, and by similarities between the spectra of hadrons and atoms, I discuss if and how QCD bound states may be treated perturbatively. I recall the basic principles of perturbative gauge theory bound states at lowest order in the \\hbar expansion. Born level amplitudes are insensitive to the i\\epsilon prescription of propagators, which allows to eliminate the Z-diagrams of relativistic, time-ordered Coulomb interactions. The Dirac wave function thus describes a single electron which propagates forward in time only, even though the bound state has any number of pair constituents when Feynman propagators are used. In the absence of an external potential, states that are bound by the Coulomb attraction of their constituents can be analogously described using only their valence degrees of freedom. The instantaneous A^0 field is determined by Gauss' law for each wave functi...

  8. Structural changes in emulsion-bound bovine beta-lactoglobulin affect its proteolysis and immunoreactivity.

    Science.gov (United States)

    Marengo, Mauro; Miriani, Matteo; Ferranti, Pasquale; Bonomi, Francesco; Iametti, Stefania; Barbiroli, Alberto

    2016-07-01

    Adsorption on the surface of sub-micrometric oil droplets resulted in significant changes in the tertiary structure of bovine beta-lactoglobulin (BLG), a whey protein broadly used as a food ingredient and a major food allergen. The adsorbed protein had increased sensitivity to trypsin, and increased immunoreactivity towards specific monoclonal antibodies. In spite of the extensive tryptic breakdown of emulsion-bound BLG, some sequence stretches in BLG became trypsin-insensitive upon absorption of the protein on the fat droplets. As a consequence - at contrast with free BLG - proteolysis of emulsion-bound BLG did not decrease the immunoreactivity of the protein, and some of the large peptides generated by trypsinolysis of emulsion-bound BLG were still recognizable by specific monoclonal antibodies. Structural changes occurring in emulsion-bound BLG and their consequences are discussed in comparison with those occurring when the tertiary structure of BLG is modified by lipophilic salts, by urea, or upon interaction with solid hydrophobic surfaces. Such a comparison highlights the relevance of situation-specific structural modifications, that in turn may affect physiologically relevant features of the protein. PMID:27085639

  9. Bounded divergence measures based on Bhattacharyya coefficient

    CERN Document Server

    Roman, Ahmed; Shastry, Mahesh C

    2012-01-01

    We introduce a new class of entropy based measure for calculating the distance between probability distributions. Our measure, called the bounded Bhattacharyya distance (BBD) is based on the Bhattacharyya distance, and is symmetric, positive semi-definite, and bounded. Unlike the Kullback-Leibler divergence, BBD does not require probability density functions to be absolutely continuous with respect to each other. We show that BBD belongs to the class of Csiszars f-divergences and derive certain relationship between BBD and well known measures such as Bhattacharyya, Hellinger and Jensen-Shannon divergence. Bounds on Bayesian error probability are established with BBD measure. The second derivative of BBD is proportional to the Fishers information. For distributions with vector valued parameters of the same family, the curvature matrix can be used to get the Rao's geodesic distance between parametric distributions.

  10. A Proof of the Conformal Collider Bounds

    CERN Document Server

    Hofman, Diego M; Meltzer, David; Poland, David; Rejon-Barrera, Fernando

    2016-01-01

    In this paper, we prove that the "conformal collider bounds" originally proposed by Hofman and Maldacena hold for any unitary parity-preserving conformal field theory (CFT) with a unique stress tensor in spacetime dimensions larger than 2. In particular this implies that the ratio of central charges for a unitary 4d CFT lies in the interval $\\frac{31}{18} \\geq \\frac{a}{c} \\geq \\frac{1}{3}$. For superconformal theories this is further reduced to $\\frac{3}{2} \\geq \\frac{a}{c} \\geq \\frac{1}{2}$. The proof relies only on CFT first principles - in particular, bootstrap methods - and thus constitutes the first complete field theory proof of these bounds. We further elaborate on similar bounds for non-conserved currents and relate them to results obtained recently from deep inelastic scattering.

  11. Bounds on Codes Based on Graph Theory

    CERN Document Server

    Rouayheb, Salim Y El; Soljanin, E; Sprintson, A

    2008-01-01

    Let $A_q(n,d)$ be the maximum order (maximum number of codewords) of a $q$-ary code of length $n$ and Hamming distance at least $d$. And let $A(n,d,w)$ that of a binary code of constant weight $w$. Building on results from algebraic graph theory and Erd\\H{o}s-ko-Rado like theorems in extremal combinatorics, we show how several known bounds on $A_q(n,d)$ and $A(n,d,w)$ can be easily obtained in a single framework. For instance, both the Hamming and Singleton bounds can derived as an application of a property relating the clique number and the independence number of vertex transitive graphs. Using the same techniques, we also derive some new bounds and present some additional applications.

  12. Bounded Gaps between Products of Special Primes

    Directory of Open Access Journals (Sweden)

    Ping Ngai Chung

    2014-03-01

    Full Text Available In their breakthrough paper in 2006, Goldston, Graham, Pintz and Yıldırım proved several results about bounded gaps between products of two distinct primes. Frank Thorne expanded on this result, proving bounded gaps in the set of square-free numbers with r prime factors for any r ≥ 2, all of which are in a given set of primes. His results yield applications to the divisibility of class numbers and the triviality of ranks of elliptic curves. In this paper, we relax the condition on the number of prime factors and prove an analogous result using a modified approach. We then revisit Thorne’s applications and give a better bound in each case.

  13. Lower bounds for designs in symmetric spaces

    CERN Document Server

    Eidelstein, Noa

    2010-01-01

    We prove lower bounds on designs in spaces with a large group of symmetries. These spaces include globally symmetric Riemannian spaces (of any rank) and commutative association schemes with 1-transitive group of symmetries. Our bounds are, in general, implicit, relying on estimates on the spectral behavior of certain symmetry-invariant linear operators. They reduce to the first linear programming bound for designs in globally symmetric Riemannian spaces of rank 1 or in distance regular graphs. The proofs are different though, coming from viewpoint of abstract harmonic analysis in symmetric spaces. As a dividend we obtain the following geometric fact: a design is large because a union of "spherical caps" around its points "covers" the whole space.

  14. Entropy Bounds, Holographic Principle and Uncertainty Relation

    Directory of Open Access Journals (Sweden)

    I. V. Volovich

    2001-06-01

    Full Text Available Abstract: A simple derivation of the bound on entropy is given and the holographic principle is discussed. We estimate the number of quantum states inside space region on the base of uncertainty relation. The result is compared with the Bekenstein formula for entropy bound, which was initially derived from the generalized second law of thermodynamics for black holes. The holographic principle states that the entropy inside a region is bounded by the area of the boundary of that region. This principle can be called the kinematical holographic principle. We argue that it can be derived from the dynamical holographic principle which states that the dynamics of a system in a region should be described by a system which lives on the boundary of the region. This last principle can be valid in general relativity because the ADM hamiltonian reduces to the surface term.

  15. Correlation Distance and Bounds for Mutual Information

    Directory of Open Access Journals (Sweden)

    Michael J. W. Hall

    2013-09-01

    Full Text Available The correlation distance quantifies the statistical independence of two classical or quantum systems, via the distance from their joint state to the product of the marginal states. Tight lower bounds are given for the mutual information between pairs of two-valued classical variables and quantum qubits, in terms of the corresponding classical and quantum correlation distances. These bounds are stronger than the Pinsker inequality (and refinements thereof for relative entropy. The classical lower bound may be used to quantify properties of statistical models that violate Bell inequalities. Partially entangled qubits can have lower mutual information than can any two-valued classical variables having the same correlation distance. The qubit correlation distance also provides a direct entanglement criterion, related to the spin covariance matrix. Connections of results with classically-correlated quantum states are briefly discussed.

  16. Bounded link prediction in very large networks

    Science.gov (United States)

    Cui, Wei; Pu, Cunlai; Xu, Zhongqi; Cai, Shimin; Yang, Jian; Michaelson, Andrew

    2016-09-01

    Evaluating link prediction methods is a hard task in very large complex networks due to the prohibitive computational cost. However, if we consider the lower bound of node pairs' similarity scores, this task can be greatly optimized. In this paper, we study CN index in the bounded link prediction framework, which is applicable to enormous heterogeneous networks. Specifically, we propose a fast algorithm based on the parallel computing scheme to obtain all node pairs with CN values larger than the lower bound. Furthermore, we propose a general measurement, called self-predictability, to quantify the performance of similarity indices in link prediction, which can also indicate the link predictability of networks with respect to given similarity indices.

  17. Bound water in Kevlar 49 fibers

    International Nuclear Information System (INIS)

    From elemental analyses, thermogravimetric-mass spectroscopy studies and re-evaluation of previous water diffusion studies in Kevlar 49 fibers it is concluded that these fibers can contain two types of sorbed moisture. The fibers can absorb up to approx. 6 wt % loosely bound water with an activation energy for outgassing by desorption of 6 kcal/mole. This loosely bound water is a direct result of the presence of Na2SO4 impurities and the perturbations they induce on the packing of the rod-like poly (p-phenylene terephthalamide) macromolecules. Kevlar 49 fibers also inherently contain up to 30 wt % additional water which is tightly bound within the crystal lattice. This water exhibits an activation energy for outgassing by diffusion of approx. 40 kcal/mole and is only evolved from the fiber in significant quantities at t > 3500C over a period of hours

  18. Structural deformation upon protein-protein interaction: A structural alphabet approach

    OpenAIRE

    Lecornet Hélène; Regad Leslie; Martin Juliette; Camproux Anne-Claude

    2008-01-01

    Abstract Background In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. Results In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backb...

  19. HiggsBounds: Confronting Arbitrary Higgs Sectors with Exclusion Bounds from LEP and the Tevatron

    CERN Document Server

    Bechtle, Philip; Heinemeyer, Sven; Weiglein, Georg; Williams, Karina E

    2008-01-01

    HiggsBounds is a computer code that tests theoretical predictions of models with arbitrary Higgs sectors against the exclusion bounds obtained from the Higgs searches at LEP and the Tevatron. The included experimental information comprises exclusion bounds at 95% C.L. on topological cross sections. In order to determine which search topology has the highest exclusion power, the program also includes, for each topology, information from the experiments on the expected exclusion bound, which would have been observed in case of a pure background distribution. Using the predictions of the desired model provided by the user as input, HiggsBounds determines the most sensitive channel and tests whether the considered parameter point is excluded at the 95% C.L. HiggsBounds is available as a Fortran 77 and Fortran 90 code. The code can be invoked as a command line version, a subroutine version and an online version. Examples of exclusion bounds obtained with HiggsBounds are discussed for a model with a fourth generati...

  20. Career Development and Personal Functioning Differences between Work-Bound and Non-Work Bound Students

    Science.gov (United States)

    Creed, Peter A.; Patton, Wendy; Hood, Michelle

    2010-01-01

    We surveyed 506 Australian high school students on career development (exploration, planning, job-knowledge, decision-making, indecision), personal functioning (well-being, self-esteem, life satisfaction, school satisfaction) and control variables (parent education, school achievement), and tested differences among work-bound, college-bound and…

  1. Proof of a quantum Bousso bound

    Science.gov (United States)

    Bousso, Raphael; Casini, Horacio; Fisher, Zachary; Maldacena, Juan

    2014-08-01

    We prove the generalized covariant entropy bound, ΔS≤(A-A')/4Gℏ, for light-sheets with initial area A and final area A'. The entropy ΔS is defined as a difference of von Neumann entropies of an arbitrary state and the vacuum, with both states restricted to the light-sheet under consideration. The proof applies to free fields, in the limit where gravitational backreaction is small. We do not assume the null energy condition. In regions where it is violated, we find that the bound is protected by the defining property of light-sheets: that their null generators are nowhere expanding.

  2. Proof of a Quantum Bousso Bound

    CERN Document Server

    Bousso, Raphael; Fisher, Zachary; Maldacena, Juan

    2014-01-01

    We prove the generalized Covariant Entropy Bound, $\\Delta S\\leq (A-A')/4G\\hbar$, for light-sheets with initial area $A$ and final area $A'$. The entropy $\\Delta S$ is defined as a difference of von Neumann entropies of an arbitrary state and the vacuum, with both states restricted to the light-sheet under consideration. The proof applies to free fields, in the limit where gravitational backreaction is small. We do not assume the null energy condition. In regions where it is violated, we find that the bound is protected by the defining property of light-sheets: that their null generators are nowhere expanding.

  3. Learning within bounds and dream sleep

    Science.gov (United States)

    Geszti, T.; Pazmandi, F.

    1987-12-01

    In a bounded-synapses version of Hopfield's model (1984) for neural networks the quasienergy of a given memory, which is approximately equal to the depth of the corresponding energy well is calculated exactly by treating the change of a synaptic strength on learning as a random walk within bounds. Attractors corresponding to stored memories are found to be considerably flattened before serious retrieval errors arise. This allows dream sleep to be interpreted as random recall and relearning of fresh strong memories, in order to stack them on top of weak incidental memory imprints of a day.

  4. Bounded distortion homeomorphisms on ultrametric spaces

    CERN Document Server

    Hughes, Bruce; Morón, Manuel A

    2010-01-01

    It is well-known that quasi-isometries between R-trees induce power quasi-symmetric homeomorphisms between their ultrametric end spaces. This paper investigates power quasi-symmetric homeomorphisms between bounded, complete, uniformly perfect, ultrametric spaces (i.e., those ultrametric spaces arising up to similarity as the end spaces of bushy trees). A bounded distortion property is found that characterizes power quasi-symmetric homeomorphisms between such ultrametric spaces that are also pseudo-doubling. Moreover, examples are given showing the extent to which the power quasi-symmetry of homeomorphisms is not captured by the quasiconformal and bi-H\\"older conditions for this class of ultrametric spaces.

  5. Subconvex bounds for compact toric integrals

    OpenAIRE

    Wu, Han

    2016-01-01

    We generalize our method for $\\GL_2 \\times \\GL_1$ to the subconvexity for $L$-functions appearing in Waldspurger's formulae, a special case for $\\GL_2 \\times \\GL_2$. In this sense, the case for $\\GL_2 \\times \\GL_1$ is regarded as the subconvexity for split toric integral. Both were sketched in Venkatesh's paper. Surprisingly enough, this bound survives from the best known bounds for $\\GL_2 \\times \\GL_1$ and for $\\GL_2 \\times \\GL_2$ with a large "probability". This is in some sense equivalent ...

  6. The Bounded L2 Curvature Conjecture

    OpenAIRE

    Klainerman, Sergiu; Rodnianski, Igor; Szeftel, Jeremie

    2012-01-01

    This is the main paper in a sequence in which we give a complete proof of the bounded $L^2$ curvature conjecture. More precisely we show that the time of existence of a classical solution to the Einstein-vacuum equations depends only on the $L^2$-norm of the curvature and a lower bound on the volume radius of the corresponding initial data set. We note that though the result is not optimal with respect to the standard scaling of the Einstein equations, it is nevertheless critical with respect...

  7. A lower bound on web services composition

    OpenAIRE

    Muscholl, Anca; Walukiewicz, Igor

    2008-01-01

    A web service is modeled here as a finite state machine. A composition problem for web services is to decide if a given web service can be constructed from a given set of web services; where the construction is understood as a simulation of the specification by a fully asynchronous product of the given services. We show an EXPTIME-lower bound for this problem, thus matching the known upper bound. Our result also applies to richer models of web services, such as the Roman model.

  8. Deeply bound kaonic states in nuclei

    Institute of Scientific and Technical Information of China (English)

    LI Yi-He; WU Shi-Shu

    2009-01-01

    Using a new phenomenological (K)N interaction which reproduces A(1405) as an I = 0 bound state of (K)N, we have investigated K- -3 He(T = 0) and K- -4 He(T = 1/2) within the framework of the Brueckner-Hartree-Fock(BHF) theory. Our calculations show that the above kaonic nuclear systems are both deeply bound. The binding energy BK- is 124.4 MeV(94.1 MeV) and the width Γ is 11.8 MeV(25.8 MeV) for K- -3 He(T = 0)(K- -4 He(T= 1/2)).

  9. Torons and D-Brane Bound States

    OpenAIRE

    Guralnik, Z.; Ramgoolam, S.

    1997-01-01

    We interpret instantons on a torus with twisted boundary conditions, in terms of bound states of branes. The interplay between the SU(N) and U(1) parts of the U(N) theory of N 4-branes allows the construction of a variety of bound states. The SU(N) and U(1) parts can contribute fractional amounts to the total instanton number which is integral. The geometry of non-self intersecting two-cycles in $T^4$ sheds some light on a number of properties of these solutions.

  10. Bound constrained quadratic programming via piecewise

    DEFF Research Database (Denmark)

    Madsen, Kaj; Nielsen, Hans Bruun; Pinar, M. C.

    1999-01-01

    We consider the strictly convex quadratic programming problem with bounded variables. A dual problem is derived using Lagrange duality. The dual problem is the minimization of an unconstrained, piecewise quadratic function. It involves a lower bound of lambda/sub 1/ , the smallest eigenvalue...... of a symmetric, positive definite matrix, and is solved by Newton iteration with line search. The paper describes the algorithm and its implementation including estimation of lambda/sub 1/ , how to get a good starting point for the iteration, and up- and downdating of Cholesky factorization. Results of extensive...

  11. Naturalness bounds on gauge mediated soft terms

    CERN Document Server

    Ciafaloni, P; Ciafaloni, Paolo; Strumia, Alessandro

    1996-01-01

    After a general discussion about the quantitative meaning of the naturalness upper bounds on the masses of supersymmetric particles, we compute these bounds in models with gauge-mediated soft terms. We find interesting upper limits on the right-handed slepton masses that, unless the messenger fields are very light, disfavor minimal models with large messenger content. Deep unphysical minima, that however turn out to be non dangerous, are usually present in such models. The mu-problem can be solved by adding a light singlet only at the price of a large amount of fine tuning that gives also rise to heavy sparticles and large tan\\beta.

  12. Violation of Energy Bounds in Designer Gravity

    OpenAIRE

    Hertog, Thomas

    2006-01-01

    We continue our study of the stability of designer gravity theories, where one considers anti-de Sitter gravity coupled to certain tachyonic scalars with boundary conditions defined by a smooth function W. It has recently been argued there is a lower bound on the conserved energy in terms of the global minimum of W, if the scalar potential arises from a superpotential P and the scalar reaches an extremum of P at infinity. We show, however, there are superpotentials for which these bounds do n...

  13. A new upper bound for 3-SAT

    CERN Document Server

    Díaz, J; Mitsche, D; Perez-Gimenez, X

    2008-01-01

    We show that a randomly chosen 3-CNF formula over n variables with clauses-to-variables ratio at least 4.4898 is, as n grows large, asymptotically almost surely unsatisfiable. The previous best such bound, due to Dubois in 1999, was 4.506. The first such bound, independently discovered by many groups of researchers since 1983, was 5.19. Several decreasing values between 5.19 and 4.506 were published in the years between. The probabilistic techniques we use for the proof are, we believe, of independent interest.

  14. Bounds on Integrals of the Wigner Function

    CERN Document Server

    Bracken, A J; Wood, J G

    1999-01-01

    The integral of the Wigner function over a subregion of the phase-space of a quantum system may be less than zero or greater than one. It is shown that for systems with one degree of freedom, the problem of determining the best possible upper and lower bounds on such an integral, over all possible states, reduces to the problem of finding the greatest and least eigenvalues of an hermitian operator corresponding to the subregion. The problem is solved exactly in the case of an arbitrary elliptical region. These bounds provide checks on experimentally measured quasiprobability distributions.

  15. Lower bounds for the strict invariance entropy

    International Nuclear Information System (INIS)

    In this paper, we present a new method for obtaining lower bounds of the strict invariance entropy by combining an approach from the theory of escape rates and geometric methods used in the dimension theory of dynamical systems. For uniformly expanding systems and for inhomogeneous bilinear systems we can describe the lower bounds in terms of uniform volume growth rates on subbundles of the tangent bundle. In particular, we obtain criteria for positive entropy. We also apply the estimates to bilinear systems on projective space

  16. Better-Reply Strategies with Bounded Recall

    OpenAIRE

    Andriy Zapechelnyuk

    2007-01-01

    A decision maker (an agent) is engaged in a repeated interaction with Nature. The objective of the agent is to guarantee to himself the long-run average payoff as large as the best-reply payoff to Nature?s empirical distribution of play, no matter what Nature does. An agent with perfect recall can achieve this objective by a simple better-reply strategy. In this paper we demonstrate that the relationship between perfect recall and bounded recall is not straightforward: An agent with bounded r...

  17. Tightly bound nucleotides of the energy-transducing ATPase, and their role in oxidative phosphorylation. I. The Paracoccus denitrificans system.

    Science.gov (United States)

    Harris, D A; John, P; Radda, G K

    1977-03-11

    1. The coupling ATPase of Paracoccus denitrificans can be removed from the membrane by washing coupled membrane fragments at low salt concentrations. 2. This ATPase resembles coupling ATPases of mitochondria, chloroplasts and other bacteria. It is a negatively charged protein of molecular weight about 300,000. An inhibitor protein in bound tightly to the ATPase in vivo, and can be destroyed by trypsin treatment. 3. ATP and ADP are found tightly bound to the coupling ATPase of P. denitrificans, both in its membrane-bound and isolated state. The ATP/ADP ratio on the enzyme is greater than one. 4. Under de-energised condtions, the bound nucleotides are not available to the suspending medium. When the membrane is energised however, the bound nucleotides can exchange with added nucleotides and incorporate 32Pi. 32Ppi is incorporated into the beta and gamma positions of the bound nucleotides, but beta-labelling probably does not occur on the coupling ATPase. 5. Uncouplers inhibit the exchange of the free nucleotides or 32Pi into the bound nucleotides, while venturicidin (an energy transfer inhibitor) and aurovertin stimulate the exchange. 6. The response of the bound nucleotides to energisation is consistent with their being involved directly in the mechanism of oxidative phosphorylation.

  18. Call packing bound for overflow loss systems

    NARCIS (Netherlands)

    N.M. van Dijk; E. van der Sluis

    2009-01-01

    Finite loss queues with overflow naturally arise in a variety of communications structures. For these systems, there is no simple analytic expression for the loss probability. This paper proves and promotes easily computable bounds based on the so-called call packing principle. Under call packing, a

  19. Call packing bounds for overflow queues

    NARCIS (Netherlands)

    N.M. van Dijk; E. van der Sluis

    2004-01-01

    Finite queueing loss systems are studied with overflow. For these systems there is no simple analytic expression for the loss probability or throughput. This paper aims to prove and promote easily computable bounds as based upon the so-called call packing principle. Under call packing a standard pro

  20. BOUNDS FOR THE ZEROS OF POLYNOMIALS

    Institute of Scientific and Technical Information of China (English)

    W. M. Shah; A.Liman

    2004-01-01

    Let P(z) =n∑j=0 ajzj be a polynomial of degree n. In this paper we prove a more general result which interalia improves upon the bounds of a class of polynomials. We also prove a result which includes some extensions and generalizations of Enestrom-Kakeya theorem.

  1. Optimal bounds for quantum bit commitment

    CERN Document Server

    Chailloux, André

    2011-01-01

    Bit commitment is a fundamental cryptographic primitive with numerous applications. Quantum information allows for bit commitment schemes in the information theoretic setting where no dishonest party can perfectly cheat. The previously best-known quantum protocol by Ambainis achieved a cheating probability of at most 3/4[Amb01]. On the other hand, Kitaev showed that no quantum protocol can have cheating probability less than 1/sqrt{2} [Kit03] (his lower bound on coin flipping can be easily extended to bit commitment). Closing this gap has since been an important and open question. In this paper, we provide the optimal bound for quantum bit commitment. We first show a lower bound of approximately 0.739, improving Kitaev's lower bound. We then present an optimal quantum bit commitment protocol which has cheating probability arbitrarily close to 0.739. More precisely, we show how to use any weak coin flipping protocol with cheating probability 1/2 + eps in order to achieve a quantum bit commitment protocol with ...

  2. Relativistic bound states at Born level

    CERN Document Server

    Hoyer, Paul

    2012-01-01

    Theoretical and phenomenological studies indicate that the QCD coupling \\alpha_s(Q^2) freezes in the infrared. Hadrons may then be described by a perturbative expansion around "Born" states bound only by a confining potential. A linear potential results from the QCD equations of motion when Gauss' law for A^0 is solved with F_{\\mu\

  3. Bounded Rationality of Generalized Abstract Fuzzy Economies

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2014-01-01

    Full Text Available By using a nonlinear scalarization technique, the bounded rationality model M for generalized abstract fuzzy economies in finite continuous spaces is established. Furthermore, by using the model M, some new theorems for structural stability and robustness to (λ,ϵ-equilibria of generalized abstract fuzzy economies are proved.

  4. A PSL Bounded Model Checking Method

    Institute of Scientific and Technical Information of China (English)

    YU Lei; ZHAO Zongtao

    2012-01-01

    SAT-based bounded model checking (BMC) is introduced as an important complementary technique to OBDD-based symbolic model checking, and is an efficient verification method for parallel and reactive systems. However, until now the properties verified by bounded model checking are very finite. Temporal logic PSL is a property specification language (IEEE-1850) describing parallel systems and is divided into two parts, i.e. the linear time logic FL and the branch time logic OBE. In this paper, the specification checked by BMC is extended to PSL and its algorithm is also proposed. Firstly, define the bounded semantics of PSL, and then reduce the bounded semantics into SAT by translating PSL specification formula and the state transition relation of the system to the propositional formula A and B, respectively. Finally, verify the satisfiability of the conjunction propositional formula of A and B. The algorithm results in the translation of the existential model checking of the temporal logic PSL into the satisfiability problem of propositional formula. An example of a queue controlling circuit is used to interpret detailedly the executing procedure of the algorithm.

  5. Assessment of Wellness in Upward Bound Students.

    Science.gov (United States)

    Owen, T. Ross

    1997-01-01

    A study investigated the validity and reliability of a new instrument for assessing the wellness lifestyles of Upward Bound students. Subjects were 42 students from five high schools using the program. The study examined 14 variables, including total scores, 10 subscales, and three demographic variables (age, race, gender), and concluded that the…

  6. Do $\\Xi\\Xi$ bound states exist?

    CERN Document Server

    Haidenbauer, J; Petschauer, S

    2014-01-01

    The existence of baryon-baryon bound states in the strangeness sector is examined in the framework of SU(3) chiral effective field theory. Specifically, the role of SU(3) symmetry breaking contact terms that arise at next-to-leading order in the employed Weinberg power counting scheme is explored. We focus on the 1S0 partial wave and on baryon-baryon channels with maximal isospin since in this case there are only two independent SU(3) symmetry breaking contact terms. At the same time, those are the channels where most of the bound states have been predicted in the past. Utilizing $pp$ phase shifts and $\\Sigma^+ p$ cross section data allows us to pin down one of the SU(3) symmetry breaking contact terms and a clear indication for the decrease of attraction when going from the NN system to strangeness S=-2 is found, which rules out a bound state for $\\Sigma\\Sigma$ with isospin I=2. Assuming that the trend observed for S=0 to S=-2 is not reversed when going to $\\Xi\\Sigma$ and $\\Xi\\Xi$ makes also bound states in ...

  7. $\\eta$-Helium Quasi-Bound States

    CERN Document Server

    Willis, N; Zghiche, A; Wilkin, C; Wurzinger, R; Bing, O; Boivin, M; Courtat, P; Gacougnolle, R; Hibou, F; Martin, J M; Plouin, F; Tatischeff, B; Yonnet, J

    1997-01-01

    The cross section and tensor analysing power t_20 of the d\\vec{d}->eta 4He reaction have been measured at six c.m. momenta, 10 eta 3He case, suggests strongly the existence of a quasi-bound state in the eta-4He system and optical model fits indicate that this probably also the case for eta-3He.

  8. Covariant Entropy Bound and Padmanabhan's Emergent Paradigm

    CERN Document Server

    Hadi, H; Darabi, F

    2016-01-01

    The covariant entropy conjecture is invariant under time reversal and consequently its origin must be statistical rather than thermodynamical. This may impose a fundamental constraint on the number of degrees of freedom in nature. Indeed, the covariant entropy bound imposes an upper entropy bound for any physical system. Considering a cosmological system, we show that Padmanabhan's emergent paradigm, which indicates that the emergence of cosmic space is due to the discrepancy between the surface and bulk degrees of freedom, leads to a lower entropy bound. The lower and upper entropy bounds may coincide on the apparent horizon for the radiation field and dark energy with the equations of state $\\omega=\\frac{1}{3}$ and $\\omega=-1$, respectively. Moreover, the maximal entropy inside the apparent horizon occurs when it is filled completely by the radiation field or dark energy. It turns out that for dark energy case (pure de Sitter space)\\ the holographic principle is satisfied in the sense that the number of deg...

  9. Exact bound states in volcano potentials

    Energy Technology Data Exchange (ETDEWEB)

    Koley, Ratna [Department of Physics and Centre for Theoretical Studies, Indian Institute of Technology, Kharagpur 721 302 (India)]. E-mail: ratna@cts.iitkgp.ernet.in; Kar, Sayan [Department of Physics and Centre for Theoretical Studies, Indian Institute of Technology, Kharagpur 721 302 (India)]. E-mail: sayan@cts.iitkgp.ernet.in

    2007-04-09

    Quantum mechanics in a one-parameter family of volcano potentials is investigated. After a discussion on their construction and classical mechanics, we obtain exact, normalizable bound states for specific values of the energy. The nature of the wave functions and probability densities, as well as some curious features of the solutions are highlighted.

  10. Exact bound states in volcano potentials

    CERN Document Server

    Koley, R; Kar, Sayan; Koley, Ratna

    2006-01-01

    Quantum mechanics in a one--parameter family of volcano potentials is investigated. After a discussion on their construction and classical mechanics, we obtain exact, normalisable bound states for specific values of the energy. The nature of the wave functions and probability densities, as well as some curious features of the solutions are highlighted.

  11. Lower bounds for polynomials using geometric programming

    CERN Document Server

    Ghasemi, Mehdi

    2011-01-01

    We make use of a result of Hurwitz and Reznick, and a consequence of this result due to Fidalgo and Kovacec, to determine a new sufficient condition for a polynomial $f\\in\\mathbb{R}[X_1,...,X_n]$ of even degree to be a sum of squares. This result generalizes a result of Lasserre and a result of Fidalgo and Kovacec, and it also generalizes the improvements of these results given in [6]. We apply this result to obtain a new lower bound $f_{gp}$ for $f$, and we explain how $f_{gp}$ can be computed using geometric programming. The lower bound $f_{gp}$ is generally not as good as the lower bound $f_{sos}$ introduced by Lasserre and Parrilo and Sturmfels, which is computed using semidefinite programming, but a run time comparison shows that, in practice, the computation of $f_{gp}$ is much faster. The computation is simplest when the highest degree term of $f$ has the form $\\sum_{i=1}^n a_iX_i^{2d}$, $a_i>0$, $i=1,...,n$. The lower bounds for $f$ established in [6] are obtained by evaluating the objective function ...

  12. Strengthened Chernoff-type variance bounds

    OpenAIRE

    Afendras, G.; Papadatos, N.

    2014-01-01

    Let $X$ be an absolutely continuous random variable from the integrated Pearson family and assume that $X$ has finite moments of any order. Using some properties of the associated orthonormal polynomial system, we provide a class of strengthened Chernoff-type variance bounds.

  13. A symmetric divergence measure and its bounds

    Directory of Open Access Journals (Sweden)

    K. C. Jain

    2011-12-01

    Full Text Available A new symmetric divergence measure is proposed which is useful in comparing two probability distributions. This non-parametric measure belongs to the Csiszar's $f$ divergence class. Its properties are studied and bounds are obtained in terms of some well known divergence measures. A numerical illustration based on the probability distribution is carried out.

  14. Improved lower bound for online strip packing

    NARCIS (Netherlands)

    Harren, Rolf; Kern, Walter

    2015-01-01

    We study the online strip packing problem and derive an improved lower bound of ρ ≥ 2.589... for the competitive ratio of this problem. The construction is based on modified “Brown-Baker-Katseff sequences” (Brown et al. in Acta Inform. 18:207–225, 1982) using only two types of rectangles. In additio

  15. On Quantum Capacity and its Bound

    OpenAIRE

    Ohya, Masanori; Volovich, Igor V.

    2004-01-01

    The quantum capacity of a pure quantum channel and that of classical-quantum-classical channel are discussed in detail based on the fully quantum mechanical mutual entropy. It is proved that the quantum capacity generalizes the so-called Holevo bound.

  16. A Characterization of Complete Bounded Domain

    Institute of Scientific and Technical Information of China (English)

    殷慰萍; 苏简兵; 赵振刚

    2002-01-01

    @@ 1 IntroductionThis paper is concerned with biholomorphic mappings between two bounded domains D and G both in Cn.Consequently,an important question is whether the domain D is biholomorphic to G? We give an answer for this question under a very weak condition.

  17. Improved bounds on the supremum of autoconvolutions

    OpenAIRE

    Matolcsi, Máté; Vinuesa, Carlos

    2009-01-01

    We give a slight improvement of the best known lower bound for the supremum of autoconvolutions of nonnegative functions supported in a compact interval. Also, by means of explicit examples we disprove a long standing natural conjecture of Schinzel and Schmidt concerning the extremal function for such autoconvolutions.

  18. On operators with bounded approximation property

    OpenAIRE

    Reinov, Oleg

    2013-01-01

    It is known that any separable Banach space with BAP is a complemented subspace of a Banach space with a basis. We show that every operator with bounded approximation property, acting from a separable Banach space, can be factored through a Banach space with a basis.

  19. Scattering theory methods for bound state problems

    International Nuclear Information System (INIS)

    For the analysis of the properties of a bound state system one may use in place of the Schroedinger equation the Lippmann-Schwinger (LS) equation for the wave function or the LS equation for the reactance operator. Use of the LS equation for the reactance operator constrains the solution to have correct asymptotic behaviour, so this approach would appear to be desirable when the bound state wave function is to be used to calculate particle transfer form factors. The Schroedinger equation based N-level analysis of the s-wave bound states of a square well is compared to the ones based on the LS equation. It is found that the LS equation methods work better than the Schroedinger equation method. The method that uses the LS equation for the wave function gives the best results for the wave functions while the method that uses the LS equation for the reactance operator gives the best results for the binding energies. The accuracy of the reactance operator based method is remarkably insensitive to changes in the oscillator constant used for the harmonic oscillator function basis set. It is also remarkably insensitive to the number of nodes in the bound state wave function. (Auth.)

  20. A Simple Condition for Bounded Displacement

    CERN Document Server

    Solomon, Yaar

    2011-01-01

    We study separated nets that correspond to substitution tilings of the Euclidean space. We give a simple condition, in terms of the eigenvalues and eigenspaces of the substitution matrix, to know whether the separated net is a bounded displacement of the integer lattice or not.

  1. Bound - states for truncated Coulomb potentials

    OpenAIRE

    Odeh, Maen; Mustafa, Omar

    2000-01-01

    The pseudoperturbative shifted - $l$ expansion technique PSLET is generalized for states with arbitrary number of nodal zeros. Bound- states energy eigenvalues for two truncated coulombic potentials are calculated using PSLET. In contrast with shifted large-N expansion technique, PSLET results compare excellently with those from direct numerical integration.

  2. Combined perturbation bounds: Ⅱ. Polar decompositions

    Institute of Scientific and Technical Information of China (English)

    Wen LI; Wei-wei SUN

    2007-01-01

    In this paper, we study the perturbation bounds for the polar decomposition A= QH where Q is unitary and H is Hermitian. The optimal (asymptotic) bounds obtained in previous works for the unitary factor, the Hermitian factor and singular values of A are σ2r||△Q||2F ≤ ||△A||2F,1/2||△H||2F ≤ ||△A||2F and ||△∑||2F ≤ ||△A||2F, respectively, where ∑ = diag(σ1, σ2,..., σr, 0,..., 0) is the singular value matrix of A and σr denotes the smallest nonzero singular value. Here we present some new combined (asymptotic)perturbation bounds σ2r ||△Q||2F+1/2||△H||2F≤ ||△A||2F and σ2r||△Q||2F+||△∑ ||2F ≤||△A||2F which are optimal for each factor. Some corresponding absolute perturbation bounds are also given.

  3. Properties of Excitons Bound to Ionized Donors

    DEFF Research Database (Denmark)

    Skettrup, Torben; Suffczynski, M.; Gorzkowski, W.

    1971-01-01

    Binding energies, interparticle distances, oscillator strengths, and exchange corrections are calculated for the three-particle complex corresponding to an exciton bound to an ionized donor. The results are given as functions of the mass ratio of the electron and hole. Binding of the complex is o...

  4. Monotonicity and bounds on Bessel functions

    Directory of Open Access Journals (Sweden)

    Larry Landau

    2000-07-01

    Full Text Available survey my recent results on monotonicity with respect to order of general Bessel functions, which follow from a new identity and lead to best possible uniform bounds. Application may be made to the "spreading of the wave packet" for a free quantum particle on a lattice and to estimates for perturbative expansions.

  5. Antioxidant activity of commercial buckwheat flours and their free and bound phenolic compositions

    Science.gov (United States)

    Buckwheat flours (Whole, Farinetta, Supreme, and Fancy) were investigated for their compositions, free and bound phenolic contents, antioxidant activities, and flavonoid contents using spectrophotometer and LC-ESI-IT- MS (LC-MS). Farinetta flour contained the highest oil, protein, and free and boun...

  6. Photoexcitation dynamics of nitric oxide bound ferric myoglobin probed by femtosecond IR spectroscopy

    Directory of Open Access Journals (Sweden)

    Park Jaehun

    2013-03-01

    Full Text Available Time-resolved vibrational spectra show that photolysis quantum yield of NO bound ferric myoglobin is smaller than 0.86, the deligated NO geminately rebinds with subnanosecond time scale, and the rebinding kinetics depends on protein conformation.

  7. Sharp Bounds for Symmetric and Asymmetric Diophantine Approximation

    Institute of Scientific and Technical Information of China (English)

    Cornelis KRAAIKAMP; Ionica SMEETS

    2011-01-01

    In 2004,Tong found bounds for the approximation quality of a regular continued fraction convergent to a rational number,expressed in bounds for both the previous and next approximation.The authors sharpen his results with a geometric method and give both sharp upper and lower bounds.The asymptotic frequencies that these bounds occur are also calculated.

  8. Generalized weights and bounds for error probability over erasure channels

    OpenAIRE

    Lemes, Leandro Cruvinel; Firer, Marcelo

    2014-01-01

    New upper and lower bounds for the error probability over an erasure channel are provided, making use of Wei's generalized weights, hierarchy and spectra. In many situations the upper and lower bounds coincide and this allows improvement of existing bounds. Results concerning MDS and AMDS codes are deduced from those bounds.

  9. Construction of bound entangled states based on permutation operators

    Science.gov (United States)

    Zhao, Hui; Guo, Sha; Jing, Naihuan; Fei, Shaoming

    2016-04-01

    We present a construction of new bound entangled states from given bound entangled states for arbitrary dimensional bipartite systems. One way to construct bound entangled states is to show that these states are positive partial transpose (PPT) and violate the range criterion at the same time. By applying certain operators to given bound entangled states or to one of the subsystems of the given bound entangled states, we obtain a set of new states which are both PPT and violate the range criterion. We show that the derived bound entangled states are not local unitary equivalent to the original bound entangled states by detail examples.

  10. Interaction of peptide-bound beads with lipopolysaccharide and lipoproteins.

    Science.gov (United States)

    Suzuki, Masatsugu M; Matsumoto, Megumi; Omi, Hiroyuki; Kobayashi, Tomomi; Nakamura, Akio; Kishi, Hiroko; Kobayashi, Sei; Takagi, Takashi

    2014-05-01

    We previously reported the generation of lipopolysaccharide (LPS)-binding peptides by phage display and chemical modification. Among them, a dodecapeptide designated Li5-025 (K'YSSSISSIRAC'; K' and C' denote d-lysine and d-cysteine, respectively) showed a high binding affinity for LPS and was resistant to protease digestion (Suzuki et al., 2010). In the current study, Li5-025-bound silica beads, hereafter referred to as P-beads, were generated and found to be devoid of LPS-neutralizing activity. Thus, LPS bound to the P-beads could be directly used in the Limulus amebocyte lysate (LAL) assay. P-beads bound LPS dissolved in solutions of ethanol, pH4, pH10, and 0.5M NaCl and LPS bound to the P-beads was quantitatively assayed. The sensitivity of this assay was observed to be approximately 0.1pg/mL LPS. P-beads bound LPS dissolved in antithrombin III (AT III) solution which is a strong inhibitor of activated factors C and B as well as the clotting enzyme in the LAL assay; the inhibitory effect of AT III was completely reversed upon washing the P-beads with 25% acetonitrile. This was employed as the first step for the detection of free LPS in plasma using the LAL assay. LPS added to human plasma at 0°C followed by application to the P-beads and subsequent washing with 25% acetonitrile resulted in low LPS activity as detected by the LAL assay. However, further washing of the P-beads with 0.1% Triton X100 in 25% acetonitrile resulted in high LPS activity. This is the first instance of quantitative detection of free LPS in plasma using the LAL assay, and the sensitivity of this method was observed to be 1pg/mL of LPS. The proteins eluted in the 0.1% Triton X-100 wash were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Two protein bands of 28kDa and 18kDa were predominantly observed. Mass spectrometry analysis revealed that the 28kDa and 18kDa bands corresponded to apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), respectively. Apo

  11. Generation of self-clusters of galectin-1 in the farnesyl-bound form

    Science.gov (United States)

    Yamaguchi, Kazumi; Niwa, Yusuke; Nakabayashi, Takakazu; Hiramatsu, Hirotsugu

    2016-09-01

    Ras protein is involved in a signal transduction cascade in cell growth, and cluster formation of H-Ras and human galectin-1 (Gal-1) complex is considered to be crucial to achieve its physiological roles. It is considered that the complex is formed through interactions between Gal-1 and the farnesyl group (farnesyl-dependent model), post-translationally modified to the C-terminal Cys, of H-Ras. We investigated the role of farnesyl-bound Gal-1 in the cluster formation by analyzing the structure and properties of Gal-1 bound to farnesyl thiosalicylic acid (FTS), a competitive inhibitor of the binding of H-Ras to Gal-1. Gal-1 exhibited self-cluster formation upon interaction with FTS, and small- and large-size clusters were formed depending on FTS concentration. The galactoside-binding pocket of Gal-1 in the FTS-bound form was found to play an important role in small-size cluster formation. Large-size clusters were likely formed by the interaction among the hydrophobic sites of Gal-1 in the FTS-bound form. The present results indicate that Gal-1 in the FTS-bound form has the ability to form self-clusters as well as intrinsic lectin activity. Relevance of the self-clustering of FTS-bound Gal-1 to the cluster formation of the H-Ras-Gal-1complex was discussed by taking account of the farnesyl-dependent model and another (Raf-dependent) model.

  12. ALTERED ENZYMATIC ACTIVITY OF LYSOZYMES BOUND TO VARIOUSLY SULFATED CHITOSANS

    Institute of Scientific and Technical Information of China (English)

    Hong-wei Wang; Lin Yuan; Tie-liang Zhao; He Huang; Hong Chen; Di Wu

    2012-01-01

    The purpose of this research is to investigate the effects of the variously sulfated chitosans on lysozyme activity and structure.It was shown that the specific enzymatic activity of lysozyme remained almost similar to the native protein after being bound to 6-O-sulfated chitosan (6S-chitosan) and 3,6-O-sulfated chitosan (3,6S-chitosan),but decreased greatly after being bound to 2-N-6-O-sulfated chitosan (2,6S-chitosan).Meanwhile,among these sulfated chitosans,2,6S-chitosan induced the greatest conformational change in lysozyme as indicated by the fluorescence spectra.These findings demonstrated that when sulfated chitosans of different structures bind to lysozyme,lysozyme undergoes conformational change of different magnitudes,which results in corresponding levels of lysozyme activity.Further study on the interaction of sulfated chitosans with lysozyme by surface plasmon resonance (SPR) suggested that their affinities might be determined by their molecular structures.

  13. Microbial starch binding domains are superior to granule bound starch synthase 1 for anchoring luciferase to potato starch granules

    NARCIS (Netherlands)

    Ji, Q.; Vincken, J.P.; Suurs, L.C.J.M.; Visser, R.G.F.

    2006-01-01

    Microbial starch-binding domains (SBD) and granule-bound starch synthase I (GBSSI) are proteins which are accumulated in potato starch granules. The efficiency of SBD and GBSSI for targeting active luciferase reporter proteins to granules during starch biosynthesis was compared. GBSSI or SBD sequenc

  14. Dynamics of Nonlinear Waves on Bounded Domains

    CERN Document Server

    Maliborski, Maciej

    2016-01-01

    This thesis is concerned with dynamics of conservative nonlinear waves on bounded domains. In general, there are two scenarios of evolution. Either the solution behaves in an oscillatory, quasiperiodic manner or the nonlinear effects cause the energy to concentrate on smaller scales leading to a turbulent behaviour. Which of these two possibilities occurs depends on a model and the initial conditions. In the quasiperiodic scenario there exist very special time-periodic solutions. They result for a delicate balance between dispersion and nonlinear interaction. The main body of this dissertation is concerned with construction (by means of perturbative and numerical methods) of time-periodic solutions for various nonlinear wave equations on bounded domains. While turbulence is mainly associated with hydrodynamics, recent research in General Relativity has also revealed turbulent phenomena. Numerical studies of a self-gravitating massless scalar field in spherical symmetry gave evidence that anti-de Sitter space ...

  15. Lower Bounds for Quantum Oblivious Transfer

    CERN Document Server

    Chailloux, André; Sikora, Jamie

    2010-01-01

    Oblivious transfer is a fundamental primitive in cryptography. While perfect information theoretic security is impossible, quantum oblivious transfer protocols can limit the dishonest players' cheating. Finding the optimal security parameters in such protocols is an important open question. In this paper we show that every 1-out-of-2 oblivious transfer protocol allows a dishonest party to cheat with probability bounded below by a constant strictly larger than 1/2. Alice's cheating is defined as her probability of guessing Bob's index, and Bob's cheating is defined as his probability of guessing both input bits of Alice. In our proof, we relate these cheating probabilities to the cheating probabilities of a coin flipping protocol and conclude by using Kitaev's coin flipping lower bound. Then, we present an oblivious transfer protocol with two messages and cheating probabilities at most 3/4. Last, we extend Kitaev's semidefinite programming formulation to more general primitives, where the security is against a...

  16. REE bound DNA in natural plant

    Institute of Scientific and Technical Information of China (English)

    王玉琦; 江平; 郭繁清; 张智勇; 孙景信; 许雷; 曹国印

    1999-01-01

    The binding of rare earth elements (REEs) with nucleic acids in the leaves of fern Dicranopteris dichotoma (DD) has been studied by molecular activation analysis (MAA). The REEs bound DNA (REE-DNA) was obtained from the leaves of DD. The CTAB-based procedure was modified for extraction of total DNA. The purity of DNA was examined by UV spectroscopy. The DNA obtained was separated and determined by agarose gel electrophoresis further. Meanwhile, the contents of eight rare earth elements (La, Ce, Nd, Sm, Eu,Tb, Yb and Lu) in REE-DNA were detected by instrumental neutron activation analysis (INAA). The results showed that REE-DNA with higher purity could be extracted from plant using this method. It was also found that REEs were bound firmly with DNA in the leaves of DD. The molecular weight (MW) of REE-DNA band was about 22 kb in agarose gel electrophoresis.

  17. A Metric Encoding for Bounded Model Checking

    Science.gov (United States)

    Pradella, Matteo; Morzenti, Angelo; San Pietro, Pierluigi

    In Bounded Model Checking, both the system model and the checked property are translated into a Boolean formula to be analyzed by a SAT-solver. We introduce a new encoding technique which is particularly optimized for managing quantitative future and past metric temporal operators, typically found in properties of hard real time systems. The encoding is simple and intuitive in principle, but it is made more complex by the presence, typical of the Bounded Model Checking technique, of backward and forward loops used to represent an ultimately periodic infinite domain by a finite structure. We report and comment on the new encoding technique and on an extensive set of experiments carried out to assess its feasibility and effectiveness.

  18. Tight Bounds for Distributed Functional Monitoring

    DEFF Research Database (Denmark)

    Woodruff, David P.; Zhang, Qin

    2011-01-01

    We resolve several fundamental questions in the area of distributed functional monitoring, initiated by Cormode, Muthukrishnan, and Yi (SODA, 2008). In this model there are $k$ sites each tracking their input and communicating with a central coordinator that continuously maintain an approximate...... output to a function $f$ computed over the union of the inputs. The goal is to minimize the communication. We show the randomized communication complexity of estimating the number of distinct elements up to a $1+\\eps$ factor is $\\Omega(k/\\eps^2)$, improving the previous $\\Omega(k + 1/\\eps^2)$ bound......} t))$ to $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{4/p} t))$, giving the first bound for estimating $F_0$ in $t$ passes of $\\Omega(1/(\\eps^2 t))$ bits of space that does not use the gap-hamming problem, and showing a distribution for the gap-hamming problem with high external information cost or super-polynomial...

  19. Bounds on bacterial cell growth rates

    CERN Document Server

    Landy, Jonathan

    2013-01-01

    Recent experiments have shown that rod-like bacteria in nutrient-rich media grow in length at an exponential rate. Here, I point out that it is the elongated shape of these bacteria that allows for this behavior. Further, I show that when a bacterium's growth is limited by some nutrient -- taken in by the cell through a diffusion-to-capture process -- its growth is suppressed: In three-dimensional geometries, the length $L$ is bounded by $\\log L \\lesssim t^{1/2}$, while in two dimensions the length is bounded by a power-law form. Fits of experimental growth curves to these predicted, sub-exponential forms could allow for direct measures of quantities relating to cellular metabolic rates.

  20. Probabilistically Bounded Staleness for Practical Partial Quorums

    CERN Document Server

    Bailis, Peter; Franklin, Michael J; Hellerstein, Joseph M; Stoica, Ion

    2012-01-01

    Data store replication results in a fundamental trade-off between operation latency and data consistency. In this paper, we examine this trade-off in the context of quorum-replicated data stores. Under partial, or non-strict quorum replication, a data store waits for responses from a subset of replicas before answering a query, without guaranteeing that read and write replica sets intersect. As deployed in practice, these configurations provide only basic eventual consistency guarantees, with no limit to the recency of data returned. However, anecdotally, partial quorums are often "good enough" for practitioners given their latency benefits. In this work, we explain why partial quorums are regularly acceptable in practice, analyzing both the staleness of data they return and the latency benefits they offer. We introduce Probabilistically Bounded Staleness (PBS) consistency, which provides expected bounds on staleness with respect to both versions and wall clock time. We derive a closed-form solution for versi...

  1. Mutual information rate and bounds for it.

    Directory of Open Access Journals (Sweden)

    Murilo S Baptista

    Full Text Available The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR, is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic networks or between two time series (not fully deterministic, and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators.

  2. Mutual information rate and bounds for it.

    Science.gov (United States)

    Baptista, Murilo S; Rubinger, Rero M; Viana, Emilson R; Sartorelli, José C; Parlitz, Ulrich; Grebogi, Celso

    2012-01-01

    The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two time series (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators. PMID:23112809

  3. Tsirelson's bound and supersymmetric entangled states

    CERN Document Server

    Borsten, L; Duff, M J

    2012-01-01

    In order to see whether superqubits are more nonlocal than ordinary qubits, we construct a class of two-superqubit entangled states as a nonlocal resource in the CHSH game. Since super Hilbert space amplitudes are Grassmann numbers, the result depends on how we extract real probabilities and we examine three choices of map: (1) DeWitt (2) Trigonometric (3) Modified Rogers. In cases (1) and (2) the winning probability reaches the Tsirelson bound p(win) = cos^2 pi/8 \\simeq 0.8536 of standard quantum mechanics. Case (3) crosses Tsirelson's bound with p(win) = 0.9265. Although all states used in the game involve probabilities lying between 0 and 1, case (3) permits other changes of basis inducing negative transition probabilities.

  4. Bounded link prediction for very large networks

    CERN Document Server

    Cui, Wei; Xu, Zhongqi

    2015-01-01

    Evaluation of link prediction methods is a hard task in very large complex networks because of the inhibitive computational cost. By setting a lower bound of the number of common neighbors (CN), we propose a new framework to efficiently and precisely evaluate the performances of CN-based similarity indices in link prediction for very large heterogeneous networks. Specifically, we propose a fast algorithm based on the parallel computing scheme to obtain all the node pairs with CN values larger than the lower bound. Furthermore, we propose a new measurement, called self-predictability, to quantify the performance of the CN-based similarity indices in link prediction, which on the other side can indicate the link predictability of a network.

  5. Reinforcement Learning with Bounded Information Loss

    Science.gov (United States)

    Peters, Jan; Mülling, Katharina; Seldin, Yevgeny; Altun, Yasemin

    2011-03-01

    Policy search is a successful approach to reinforcement learning. However, policy improvements often result in the loss of information. Hence, it has been marred by premature convergence and implausible solutions. As first suggested in the context of covariant or natural policy gradients, many of these problems may be addressed by constraining the information loss. In this paper, we continue this path of reasoning and suggest two reinforcement learning methods, i.e., a model-based and a model free algorithm that bound the loss in relative entropy while maximizing their return. The resulting methods differ significantly from previous policy gradient approaches and yields an exact update step. It works well on typical reinforcement learning benchmark problems as well as novel evaluations in robotics. We also show a Bayesian bound motivation of this new approach [8].

  6. Optimal Bounds in Parametric LTL Games

    Directory of Open Access Journals (Sweden)

    Martin Zimmermann

    2011-06-01

    Full Text Available We consider graph games of infinite duration with winning conditions in parameterized linear temporal logic, where the temporal operators are equipped with variables for time bounds. In model checking such specifications were introduced as "PLTL" by Alur et al. and (in a different version called "PROMPT-LTL" by Kupferman et al.. We present an algorithm to determine optimal variable valuations that allow a player to win a game. Furthermore, we show how to determine whether a player wins a game with respect to some, infinitely many, or all valuations. All our algorithms run in doubly-exponential time; so, adding bounded temporal operators does not increase the complexity compared to solving plain LTL games.

  7. A Holographic Bound on Cosmic Magnetic Fields

    CERN Document Server

    McInnes, Brett

    2015-01-01

    Magnetic fields large enough to be observable are ubiquitous in astrophysics, even at extremely large length scales. This has led to the suggestion that such fields are seeded at very early (inflationary) times, and subsequently amplified by various processes involving, for example, dynamo effects. Many such mechanisms give rise to extremely large magnetic fields at the end of inflationary reheating, and therefore also during the quark-gluon plasma epoch of the early universe. Such plasmas have a well-known holographic description. We show that holography imposes an upper bound on the intensity of magnetic fields (scaled by the squared temperature) in these circumstances, and that the values expected in some models of cosmic magnetism come close to attaining that bound.

  8. Bound States for Magic State Distillation

    CERN Document Server

    Campbell, Earl T

    2009-01-01

    Magic state distillation is an important primitive in fault-tolerant quantum computation. The magic states are pure non-stabilizer states which can be distilled from certain mixed non-stabilizer states via Clifford group operations alone. Due to the Gottesman-Knill theorem, convex mixtures of Pauli eigenstates are not expected to be magic state distillable, but it has been an open question whether all mixed states outside this octahedral set may be distilled. In this Letter we show that, when resources are finitely limited, non-distillable states exist outside the stabilizer octahedron. In analogy with the bound entangled states, which arise in entanglement theory, we call such states bound states for magic state distillation.

  9. Quantum Bound States Around Black Holes

    OpenAIRE

    Grain, J.; Barrau, A.

    2007-01-01

    Quantum mechanics around black holes has shown to be one of the most fascinating fields of theoretical physics. It involves both general relativity and particle physics, opening new eras to establish the principles of unified theories. In this article, we show that quantum bound states with no classical equivalent -- as it can easily be seen at the dominant monopolar order -- should be formed around black holes for massive scalar particles. We qualitatively investigate some important physical...

  10. Bounding symbolic powers via asymptotic multiplier ideals

    Directory of Open Access Journals (Sweden)

    Zach Teitler

    2009-04-01

    Full Text Available We revisit a bound on symbolic powers found by Ein-Lazarsfeld-Smith and subsequently improved by Takagi-Yoshida. We show that the original argument of [6] actually gives the same improvement. On the other hand, we show by examples that any further improvement based on the same technique appears unlikely. This is primarily an exposition; only some examples and remarks might be new.

  11. {bar K}-NUCLEAR Deeply Bound States?

    Science.gov (United States)

    Gal, Avraham

    Following the prediction by Akaishi and Yamazaki of relatively narrow {bar K}-nuclear states, deeply bound by over 100 MeV where the main decay channel {bar K} N -> π Σ is closed, several experimental signals in stopped K- reactions on light nuclei have been interpreted recently as due to such states. In this talk I review (i) the evidence from K--atom data for a deep bar K-nucleus potential, as attractive as V{bar K}(ρ 0) ˜ -(150 - 200) MeV at nuclear matter density, that could support such states; and (ii) the theoretical arguments for a shallow potential, V{bar K}(ρ 0) ˜ -(40 - 60) MeV. I then review a recent work by Mareš, Friedman and Gal in which {bar K}-nuclear bound states are generated dynamically across the periodic table, using a RMF Lagrangian that couples the {bar K} to the scalar and vector meson fields mediating the nuclear interactions. The reduced phase space available for {bar K} absorption from these bound states is taken into account by adding a density- and energy-dependent imaginary term, underlying the corresponding {bar K}-nuclear level widths, with a strength constrained by K--atom fits. Substantial polarization of the core nucleus is found for light nuclei, with central nuclear densities enhanced by almost a factor of two. The binding energies and widths calculated in this dynamical model differ appreciably from those calculated for a static nucleus. These calculations provide a lower limit of Γ {bar K} ˜ 50 ± 10 MeV on the width of nuclear bound states for {bar K} binding energy in the range B{bar K} = 100 - 200 MeV.

  12. Upper and lower bounds on quantum codes

    Science.gov (United States)

    Smith, Graeme Stewart Baird

    This thesis provides bounds on the performance of quantum error correcting codes when used for quantum communication and quantum key distribution. The first two chapters provide a bare-bones introduction to classical and quantum error correcting codes, respectively. The next four chapters present achievable rates for quantum codes in various scenarios. The final chapter is dedicated to an upper bound on the quantum channel capacity. Chapter 3 studies coding for adversarial noise using quantum list codes, showing there exist quantum codes with high rates and short lists. These can be used, together with a very short secret key, to communicate with high fidelity at noise levels for which perfect fidelity is, impossible. Chapter 4 explores the performance of a family of degenerate codes when used to communicate over Pauli channels, showing they can be used to communicate over almost any Pauli channel at rates that are impossible for a nondegenerate code and that exceed those of previously known degenerate codes. By studying the scaling of the optimal block length as a function of the channel's parameters, we develop a heuristic for designing even better codes. Chapter 5 describes an equivalence between a family of noisy preprocessing protocols for quantum key distribution and entanglement distillation protocols whose target state belongs to a class of private states called "twisted states." In Chapter 6, the codes of Chapter 4 are combined with the protocols of Chapter 5 to provide higher key rates for one-way quantum key distribution than were previously thought possible. Finally, Chapter 7 presents a new upper bound on the quantum channel capacity that is both additive and convex, and which can be interpreted as the capacity of the channel for communication given access to side channels from a class of zero capacity "cloning" channels. This "clone assisted capacity" is equal to the unassisted capacity for channels that are degradable, which we use to find new upper

  13. Locating dominating codes: Bounds and extremal cardinalities

    CERN Document Server

    Cáceres, José; Mora, Mercè; Pelayo, Ignacio M; Puertas, María Luz

    2012-01-01

    In this work, two types of codes such that they both dominate and locate the vertices of a graph are studied. Those codes might be sets of detectors in a network or processors controlling a system whose set of responses should determine a malfunctioning processor or an intruder. Here, we present our more significant contributions on \\lambda-codes and \\eta-codes concerning concerning bounds, extremal values and realization theorems.

  14. Dilation volumes of sets of bounded perimeter

    DEFF Research Database (Denmark)

    Kiderlen, Markus; Rataj, Jan

    This paper analyzes the first order behavior (that is, the right sided derivative) of the volume of the dilation A ⊕ tQ as t converges to zero. Here A and Q are subsets of n-dimensional Euclidean space, A has bounded perimeter and Q is compact. If Q consists of two points only, x and x+u, say, this...

  15. The lower bound on independence number

    Institute of Scientific and Technical Information of China (English)

    LI; Yusheng

    2002-01-01

    [1]Caro, Y., New Results on the Independence Number, Technical Report, Tel_Aviv: Tel_Aviv University, 1979.[2]Wei, V., A lower bound on the stability number of a simple graph, Bell Laboratories Technical Memorandum, 1981, 81_11217_11219.\\}[3]Alon, N., Spencer, J., The Probabilistic Method, New York: Wiley_Interscience, 1992.[4]Ajtai, M., Komls, J., Szemerédi E., A note on Ramsey numbers, J. Combin. Theory, Ser. A, 1980, 29: 354-360.[5]Shearer, J., A note on the independence number of triangle_free graphs, Discrete Math., 1983, 46: 83-87.[6]Kim, J., The Ramsey number R(3,t)has order of magnitude t\\+2/logt, Random Structures Algorithms, 1995, 7: 174-207.[7]Tardos, E., 1997 Fulkerson Prize, Notices of American Math. Soc., 1998, 45(8): 984.[8]Griggs, J., Lower bounds on the independence number in term of the degrees, J. Combin. Theory, Ser. B, 1983, 34: 22-29.[9]Li, Y., Rousseau, C., Fan_complete graph Ramsey numbers, J. Graph Theory, 1996, 23: 413-420.[10]Shearer, J., A note on the independence number of triangle_free graphs, II, J. Combin. Theory, Ser. B, 1991, 53: 300-307.[11]Li, Y., Rousseau, C., On book_complete Ramsey numbers, J. Combin. Theory, Ser. B, 1996, 68: 36-44.[12]Li, Y., Rousseau, C., Zang, W., Asymptotic upper bounds for Ramsey functions, Graphs Combin., 2001, 17: 123-128.[13]Caro, Y., Li, Y., Rousseau, C. et al., Asymptotic bounds for some bipartite graph: complete graph Ramsey numbers, Discrete Math., 2000, 220: 51-56.

  16. Moment Problems on Bounded and Unbounded Domains

    Directory of Open Access Journals (Sweden)

    Octav Olteanu

    2013-01-01

    Full Text Available Using approximation results, we characterize the existence of the solution for a two-dimensional moment problem in the first quadrant, in terms of quadratic forms, similar to the one-dimensional case. For the bounded domain case, one considers a space of complex analytic functions in a disk and a space of continuous functions on a compact interval. The latter result seems to give sufficient (and necessary conditions for the existence of a multiplicative solution.

  17. Singular integral on bounded strictly pseudoconvex domain

    Institute of Scientific and Technical Information of China (English)

    GONG Ding-dong

    2008-01-01

    Kytmanov and Myslivets gave a special Cauchy principal value of the singular integral on the bounded strictly pseudoconvex domain with smooth boundary. By means of this Cauchy integral principal value, the corresponding singular integral and a composition formula are obtained. This composition formula is quite different from usual ones in form. As an application, the corresponding singular integral equation and the system of singular integral equations are discussed as well.

  18. The type N Karlhede bound is sharp

    CERN Document Server

    Milson, Robert

    2007-01-01

    We present a family of four-dimensional Lorentzian manifolds whose invariant classification requires the seventh covariant derivative of the curvature tensor. The spacetimes in questions are null radiation, type N solutions on an anti-de Sitter background. The large order of the bound is due to the fact that these spacetimes are properly $CH_2$, i.e., curvature homogeneous of order 2 but non-homogeneous. This means that tetrad components of $R, \

  19. Closed form bound-state perturbation theory

    Directory of Open Access Journals (Sweden)

    Ollie J. Rose

    1980-01-01

    Full Text Available The perturbed Schrödinger eigenvalue problem for bound states is cast into integral form using Green's Functions. A systematic algorithm is developed and applied to the resulting equation giving rise to approximate solutions expressed as functions of the given perturbation parameter. As a by-product, convergence radii for the traditional Rayleigh-Schrödinger and Brillouin-Wigner perturbation theories emerge in a natural way.

  20. Bounded cascade clouds: albedo and effective thickness

    OpenAIRE

    Cahalan, R. F.

    2002-01-01

    If climate models produced clouds having liquid water amounts close to those observed, they would compute a mean albedo that is often much too large, due to the treatment of clouds as plane-parallel. An approximate lower-bound for this "plane-parallel albedo bias" may be obtained from a fractal model having a range of optical thicknesses similar to those observed in marine stratocumulus, since they are more nearly plane-parallel than most other cloud types. We review ...

  1. General smile asymptotics with bounded maturity

    OpenAIRE

    Francesco Caravenna; Jacopo Corbetta

    2014-01-01

    We provide explicit conditions on the distribution of risk-neutral log-returns which yield sharp asymptotic estimates on the implied volatility smile. We allow for a variety of asymptotic regimes, including both small maturity (with arbitrary strike) and extreme strike (with arbitrary bounded maturity), extending previous work of Benaim and Friz [Math. Finance 19 (2009), 1-12]. We present applications to popular models, including Carr-Wu finite moment logstable model, Merton's jump diffusion ...

  2. Weakly bound states in heterogeneous waveguides

    Science.gov (United States)

    Amore, Paolo; Fernández, Francisco M.; Hofmann, Christoph P.

    2016-07-01

    We study the spectrum of the Helmholtz equation in a two-dimensional infinite waveguide, containing a weak heterogeneity localized at an internal point, and obeying Dirichlet boundary conditions at its border. We use the variational theorem to derive the condition for which the lowest eigenvalue of the spectrum falls below the continuum threshold and a bound state appears, localized at the heterogeneity. We devise a rigorous perturbation scheme and derive the exact expression for the energy to third order in the heterogeneity.

  3. Better-Reply Dynamics with Bounded Recall

    OpenAIRE

    Andriy Zapechelnyuk

    2008-01-01

    A decision maker is engaged in a repeated interaction with Nature. The objective of the decision maker is to guarantee to himself the average payoff as large as the best-reply payoff to Nature's empirical distribution of play, no matter what Nature does. The decision maker with perfect recall can achieve this objective by a simple better-reply strategy. In this paper we demonstrate that the relationship between perfect recall and bounded recall is not straightforward: The decision maker with ...

  4. Organically bound tritium, OBT: Its true constitution

    International Nuclear Information System (INIS)

    Full text: Tritium, which is analytically determined to be non-exchangeable bound in tissue solids, is assumed to be bound to carbon. Furthermore, it follows that the biochemical passways by photosynthesis or enzymatic transfer reactions are retarded by the kinetic isotope effect leading to discrimination of tritium in biomolecules. In contrast, the logistic growth analysis of plants discloses a larger intrinsic growth rate of OBT than of OBH, resulting in tritium accumulation in biomolecules. Exchange experiments providing fractionation factors of 1.4 and 2 confirm this accumulation. In summary a larger part of the so called OBT is not carbon bound but consists of tritium positioned in hydrogen bridges of biopolymers which have been occupied during formation of the molecules and which became later inaccessible for exchange (so called buried hydrogens). Furthermore, there are experimental results indicating even rapid exchange during the in vivo state but inhibited in the in vitro state, which is commonly given in bio samples prepared for analysis. (author)

  5. Andreev-Majorana bound states in superfluids

    Energy Technology Data Exchange (ETDEWEB)

    Silaev, M. A., E-mail: msilaev@ipm.sci-nnov.ru; Volovik, G. E., E-mail: volovik@boojum.hut.fi [Aalto University, Low Temperature Laboratory (Finland)

    2014-12-15

    We consider Andreev-Majorana (AM) bound states with zero energy on surfaces, interfaces, and vortices in different phases of the p-wave superfluids. We discuss the chiral superfluid {sup 3}He-A and time reversal invariant phases: superfluid {sup 3}He-B, planar and polar phases. The AM zero modes are determined by topology in the bulk and disappear at the quantum phase transition from the topological to nontopological state of the superfluid. The topology demonstrates the interplay of dimensions. In particular, the zero-dimensional Weyl points in chiral superfluids (the Berry phase monopoles in momentum space) give rise to the one-dimensional Fermi arc of AM bound states on the surface and to the one-dimensional flat band of AM modes in the vortex core. The one-dimensional nodal line in the polar phase produces a two-dimensional flat band of AM modes on the surface. The interplay of dimensions also connects the AM states in superfluids with different dimensions. For example, the topological properties of the spectrum of bound states in three-dimensional {sup 3}He-B are connected to the properties of the spectrum in the two-dimensional planar phase (thin film)

  6. Of Models and Machines: Implementing Bounded Rationality.

    Science.gov (United States)

    Dick, Stephanie

    2015-09-01

    This essay explores the early history of Herbert Simon's principle of bounded rationality in the context of his Artificial Intelligence research in the mid 1950s. It focuses in particular on how Simon and his colleagues at the RAND Corporation translated a model of human reasoning into a computer program, the Logic Theory Machine. They were motivated by a belief that computers and minds were the same kind of thing--namely, information-processing systems. The Logic Theory Machine program was a model of how people solved problems in elementary mathematical logic. However, in making this model actually run on their 1950s computer, the JOHNNIAC, Simon and his colleagues had to navigate many obstacles and material constraints quite foreign to the human experience of logic. They crafted new tools and engaged in new practices that accommodated the affordances of their machine, rather than reflecting the character of human cognition and its bounds. The essay argues that tracking this implementation effort shows that "internal" cognitive practices and "external" tools and materials are not so easily separated as they are in Simon's principle of bounded rationality--the latter often shaping the dynamics of the former. PMID:26685521

  7. Nonlinear Instabilities in Shock-Bounded Slabs

    CERN Document Server

    Vishniac, E T

    1993-01-01

    (substantial changes to section 3.2, otherwise minor) We present an analysis of the hydrodynamic stability of a cold slab bounded by two accretion shocks. Previous numerical work has shown that when the Mach number of the shock is large the slab is unstable. Here we show that to linear order both the bending and breathing modes of such a slab are stable. However, nonlinear effects will tend to soften the restoring forces for bending modes, and when the slab displacement is comparable to its thickness this gives rise to a nonlinear instability. The growth rate of the instability, above this threshold but for small bending angles, is $\\sim c_sk (k\\eta)^{1/2}$, where $\\eta$ is the slab displacement. When the bending angle is large the slab will contain a local vorticity comparable to $c_s/L$, where $L$ is the slab thickness. We discuss the implications of this work for gravitational instabilities of slabs. Finally, we examine the cases of a decelerating slab bounded by a single shock and a stationary slab bounde...

  8. Production of recombinant cholesterol oxidase containing covalently bound FAD in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Molla Gianluca

    2010-04-01

    Full Text Available Abstract Background Cholesterol oxidase is an alcohol dehydrogenase/oxidase flavoprotein that catalyzes the dehydrogenation of C(3-OH of cholesterol. It has two major biotechnological applications, i.e. in the determination of serum (and food cholesterol levels and as biocatalyst providing valuable intermediates for industrial steroid drug production. Cholesterol oxidases of type I are those containing the FAD cofactor tightly but not covalently bound to the protein moiety, whereas type II members contain covalently bound FAD. This is the first report on the over-expression in Escherichia coli of type II cholesterol oxidase from Brevibacterium sterolicum (BCO. Results Design of the plasmid construct encoding the mature BCO, optimization of medium composition and identification of the best cultivation/induction conditions for growing and expressing the active protein in recombinant E. coli cells, concurred to achieve a valuable improvement: BCO volumetric productivity was increased from ~500 up to ~25000 U/L and its crude extract specific activity from 0.5 up to 7.0 U/mg protein. Interestingly, under optimal expression conditions, nearly 55% of the soluble recombinant BCO is produced as covalently FAD bound form, whereas the protein containing non-covalently bound FAD is preferentially accumulated in insoluble inclusion bodies. Conclusions Comparison of our results with those published on non-covalent (type I COs expressed in recombinant form (either in E. coli or Streptomyces spp., shows that the fully active type II BCO can be produced in E. coli at valuable expression levels. The improved over-production of the FAD-bound cholesterol oxidase will support its development as a novel biotool to be exploited in biotechnological applications.

  9. Ionically Bound Peroxidase from Peach Fruit

    Directory of Open Access Journals (Sweden)

    Neves Valdir Augusto

    2002-01-01

    Full Text Available Soluble, ionically bound peroxidase (POD and polyphenoloxidase (PPO were extracted from the pulp of peach fruit during ripening at 20°C. Ionically bound form was purified 6.1-fold by DEAE-cellulose and Sephadex G-100 chromatography. The purified enzyme showed only one peak of activity on Sephadex G-100 and PAGE revealed that the enzyme was purified by the procedures adopted. The purified enzyme showed a molecular weight of 29000 Da, maximum activity at pH 5.0 and at 40ºC. The calculated apparent activation energy (Ea for the reaction was10.04 kcal/mol. The enzyme was heat-labile in the temperature range of 60 to 75ºC with a fast inactivation at 75ºC. Measurement of residual activity showed a stabilizing effect of sucrose at various temperature/sugar concentrations (0, 10, 20 %, w/w, with an activation energy (Ea for inactivation increasing with sucrose concentration from 0 to 20% (w/w. The Km and Vmax values were 9.35 and 15.38 mM for 0-dianisidine and H2O2, respectively. The bound enzyme was inhibited competitively by ferulic, caffeic and protocatechuic acids with different values of Ki,. L-cysteine, p-coumaric and indolacetic acid and Fe++ also inhibited the enzyme but at a lower grade. N-ethylmaleimide and p-CMB were not effective to inhibit the enzyme demonstrating the non-essentiality of SH groups.

  10. Bound states -- from QED to QCD

    OpenAIRE

    Hoyer, Paul

    2014-01-01

    These lectures are divided into two parts. In Part 1 I discuss bound state topics at the level of a basic course in field theory: The derivation of the Schr\\"odinger and Dirac equations from the QED Lagrangian, by summing Feynman diagrams and in a Hamiltonian framework. Less well known topics include the equal-time wave function of Positronium in motion and the properties of the Dirac wave function for a linear potential. The presentation emphasizes physical aspects and provides the framework...

  11. Arsenic-bound excitons in diamond

    Science.gov (United States)

    Barjon, J.; Jomard, F.; Morata, S.

    2014-01-01

    A set of new excitonic recombinations is observed in arsenic-implanted diamond. It is composed of two groups of emissions at 5.355/5.361 eV and at 5.215/5.220/5.227 eV. They are respectively attributed to the no-phonon and transverse-optical phonon-assisted recombinations of excitons bound to neutral arsenic donors. From the Haynes rule, an ionization energy of 0.41 eV is deduced for arsenic in diamond, which shows that arsenic is a shallower donor than phosphorus (0.6 eV), in agreement with theory.

  12. Bound Alternative Direction Optimization for Image Deblurring

    Directory of Open Access Journals (Sweden)

    Xiangrong Zeng

    2014-01-01

    the ℓp regularizer by a novel majorizer and then, based on a variable splitting, to reformulate the bound unconstrained problem into a constrained one, which is then addressed via an augmented Lagrangian method. The proposed algorithm actually combines the reweighted ℓ1 minimization method and the alternating direction method of multiples (ADMM such that it succeeds in extending the application of ADMM to ℓp minimization problems. The conducted experimental studies demonstrate the superiority of the proposed algorithm for the synthesis ℓp minimization over the state-of-the-art algorithms for the synthesis ℓ1 minimization on image deblurring.

  13. Valuation models and Simon's bounded rationality

    Directory of Open Access Journals (Sweden)

    Alexandra Strommer de Farias Godoi

    2009-09-01

    Full Text Available This paper aims at reconciling the evidence that sophisticated valuation models are increasingly used by companies in their investment appraisal with the literature of bounded rationality, according to which objective optimization is impracticable in the real world because it would demand an immense level of sophistication of the analytical and computational processes of human beings. We show how normative valuation models should rather be viewed as forms of reality representation, frameworks according to which the real world is perceived, fragmented for a better understanding, and recomposed, providing an orderly method for undertaking a task as complex as the investment decision.

  14. Total-variation regularization with bound constraints

    Energy Technology Data Exchange (ETDEWEB)

    Chartrand, Rick [Los Alamos National Laboratory; Wohlberg, Brendt [Los Alamos National Laboratory

    2009-01-01

    We present a new algorithm for bound-constrained total-variation (TV) regularization that in comparison with its predecessors is simple, fast, and flexible. We use a splitting approach to decouple TV minimization from enforcing the constraints. Consequently, existing TV solvers can be employed with minimal alteration. This also makes the approach straightforward to generalize to any situation where TV can be applied. We consider deblurring of images with Gaussian or salt-and-pepper noise, as well as Abel inversion of radiographs with Poisson noise. We incorporate previous iterative reweighting algorithms to solve the TV portion.

  15. BOUND PERIODICAL HOLDINGS BATTELLE - NORTHWEST LIBRARY

    Energy Technology Data Exchange (ETDEWEB)

    None

    1967-05-01

    This report lists the bound periodicals in the Technical Library at the Pacific Northwest Laboratory, operated by Battelle Memorial Institute. It was prepared from a computer program and is arranged in two parts. Part one is an alphabetical list of journals by title; part two is an arrangement of the journals by subject. The list headings are self-explanatory, with the exception of the title code, which is necessary in the machine processing. The listing is complete through June, 1966 and updates an earlier publication issued in March, 1965.

  16. Bounds on entanglement in qudit subsystems

    OpenAIRE

    Kendon, Vivien M.; Zyczkowski, Karol; Munro, William J.

    2002-01-01

    The entanglement in a pure state of N qudits (d-dimensional distinguishable quantum particles) can be characterised by specifying how entangled its subsystems are. A generally mixed subsystem of m qudits is obtained by tracing over the other N-m qudits. We examine the entanglement in the space of mixed states of m qudits. We show that for a typical pure state of N qudits, its subsystems smaller than N/3 qudits will have a positive partial transpose and hence are separable or bound entangled. ...

  17. Topological edge states of bound photon pairs

    CERN Document Server

    Gorlach, Maxim A

    2016-01-01

    We predict the existence of interaction-driven edge states of bound two-photon quasiparticles in a dimer periodic array of nonlinear optical cavities. Energy spectrum of photon pairs is dramatically richer than in the noninteracting case or in a simple lattice, featuring collapse and revival of multiple edge and bulk modes as well as edge states in continuum. Despite the unexpected breakdown of the Zak phase technique and the edge mixing of internal and center-of-mass motion we link the edge state existence to the two-photon quantum walk graph connectivity, thus uncovering the topological nature of the many-body problem in complex lattices.

  18. Andreev bound states. Some quasiclassical reflections

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Y., E-mail: yiriolin@illinois.edu; Leggett, A. J. [University of Illinois at Urhana-Champaign, Dept. of Physics (United States)

    2014-12-15

    We discuss a very simple and essentially exactly solvable model problem which illustrates some nice features of Andreev bound states, namely, the trapping of a single Bogoliubov quasiparticle in a neutral s-wave BCS superfluid by a wide and shallow Zeeman trap. In the quasiclassical limit, the ground state is a doublet with a splitting which is proportional to the exponentially small amplitude for “normal” reflection by the edges of the trap. We comment briefly on a prima facie paradox concerning the continuity equation and conjecture a resolution to it.

  19. Improved bound on facial parity edge coloring

    OpenAIRE

    Lužar, Borut; Škrekovski, Riste

    2013-01-01

    A facial parity edge coloring of a 2-edge connected plane graph is an edge coloring where no two consecutive edges of a facial walk of any face receive the same color. Additionally, for every face f and every color c either no edge or an odd number of edges incident to f are colored by c. Czap, Jendrol', Kardo\\v{s} and Sotak showed that every 2-edge connected plane graph admits a facial parity edge coloring with at most 20 colors. We improve this bound to 16 colors.

  20. Landauer bound for analog computing systems.

    Science.gov (United States)

    Diamantini, M Cristina; Gammaitoni, Luca; Trugenberger, Carlo A

    2016-07-01

    By establishing a relation between information erasure and continuous phase transitions we generalize the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence, every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy. PMID:27575108

  1. Landauer bound for analog computing systems

    Science.gov (United States)

    Diamantini, M. Cristina; Gammaitoni, Luca; Trugenberger, Carlo A.

    2016-07-01

    By establishing a relation between information erasure and continuous phase transitions we generalize the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence, every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  2. Landauer Bound for Analog Computing Systems

    CERN Document Server

    Diamantini, M Cristina; Trugenberger, Carlo A

    2016-01-01

    By establishing a relation between information erasure and continuous phase transitions we generalise the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  3. A balance for Dark Matter bound states

    OpenAIRE

    Nozzoli, F.

    2016-01-01

    Massive particles with self interactions of the order of 0.2 barn/GeV are intriguing Dark Matter candidates from an astrophysical point of view. Direct detection searches for very massive particles, with relatively high cross sections with ordinary matter, cannot rule out $\\sigma/M > 0.01$ barn/GeV, due to atmosphere and material shielding. Here, the possibility of the existence of bound states with ordinary matter, for Dark Matter candidates with not negligible interactions, is considered. T...

  4. A Holographic Bound for D3-Brane

    CERN Document Server

    Momeni, Davood; Bahamonde, Sebastian; Myrzakul, Aizhan; Myrzakulov, Ratbay

    2016-01-01

    In this paper, we will calculate the holographic entanglement entropy, holographic complexity, and fidelity susceptibility for a D3-brane. It will be demonstrated that for a D3-brane the holographic complexity is always greater than or equal to than the fidelity susceptibility. Furthermore, we will also demonstrate that the holographic complexity is related to the holographic entanglement entropy for this system. Thus, we will obtain a holographic bound involving holographic complexity, holographic entanglement entropy and fidelity susceptibility of a D3-brane.

  5. Jackson's Theorem on Bounded Symmetric Domains

    Institute of Scientific and Technical Information of China (English)

    Ming Zhi WANG; Guang Bin REN

    2007-01-01

    Polynomial approximation is studied on bounded symmetric domain Ω in C n for holo-morphic function spaces X ,such as Bloch-type spaces,Bergman-type spaces,Hardy spaces,Ω algebra and Lipschitz space.We extend the classical Jackson ’s theorem to several complex variables:E k f,X ) ω (1 /k,f,X ),where E k f,X )is the deviation of the best approximation of f ∈X by polynomials of degree at mostk with respect to the X -metric and ω (1/k,f,X )is the corresponding modulus of continuity.

  6. Mass Bounds on a Very Light Neutralino

    CERN Document Server

    Dreiner, H K; Kittel, O; Langenfeld, U; Weber, A M; Weiglein, G

    2009-01-01

    Within the Minimal Supersymmetric Standard Model (MSSM) we systematically investigate the bounds on the mass of the lightest neutralino. We allow for non-universal gaugino masses and thus even consider massless neutralinos, while assuming in general that R-parity is conserved. Our main focus are laboratory constraints. We consider collider data, precision observables, and also rare meson decays to very light neutralinos. We then discuss the astrophysical and cosmological implications. We find that a massless neutralino is allowed by all existing experimental data and astrophysical and cosmological observations.

  7. Novel Bound States in Graphene with Impurities

    CERN Document Server

    Gupta, Kumar S

    2008-01-01

    We obtain a novel bound state spectrum of the low energy excitations near the Fermi points of graphene in the presence of a charge impurity. The effects of possible short range interactions induced by the impurity are modelled by suitable boundary conditions. The spectrum in the subcritical region of the effective Coulomb coupling is labelled by a parameter which characterizes the boundary conditions and determines the inequivalent quantizations of the system. In the supercritical region we obtain a renormalization group flow for the effective Coulomb coupling.

  8. Magnetic moment of a bound electron

    International Nuclear Information System (INIS)

    Theoretical predictions underlying determinations of the fine structure constant α and the electron-to-proton mass ratio me/mp are reviewed, with the emphasis on the bound electron magnetic anomaly g-2. The theory of the interaction of hydrogen-like ions with a magnetic field is discussed. The status of efforts aimed at the determination of O(α(Zα)5) and O(α2(Zα)5) corrections to the g factor is presented. The reevaluation of analogous corrections to the Lamb shift and the hyperfine splitting is summarized.

  9. Mass bounds on a very light neutralino

    Energy Technology Data Exchange (ETDEWEB)

    Dreiner, Herbi K. [Bonn Univ. (Germany). Bethe Center for Theoretical Physis and Physikalisches Institut; Heinemeyer, Sven [Instituto de Fisica de Cantabria (CSIC-UC), Santander (Spain); Kittel, Olaf [Granada Univ. (Spain). Dept. de Fisica Teorica y del Cosmos and CAFPE; Langenfeld, Ulrich [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Weber, Arne M. [Max-Planck-Institut fuer Physik, Muenchen (Germany). Werner-Heisenberg-Institut; Weiglein, Georg [Durham Univ. (United Kingdom). IPPP

    2008-12-15

    Within the Minimal Supersymmetric Standard Model (MSSM) we systematically investigate the bounds on the mass of the lightest neutralino. We allow for non-universal gaugino masses and thus even consider massless neutralinos, while assuming in general that R-parity is conserved. Our main focus are laboratory constraints. We consider collider data, precision observables, and also rare meson decays to very light neutralinos. We then discuss the astrophysical and cosmological implications. We find that a massless neutralino is allowed by all existing experimental data and astrophysical and cosmological observations. (orig.)

  10. Complexity Considerations, cSAT Lower Bound

    CERN Document Server

    Hofman, Radoslaw

    2007-01-01

    This article discusses completeness of Boolean Algebra as First Order Theory in Goedel's meaning. If Theory is complete then any possible transformation is equivalent to some transformation using axioms, predicates etc. defined for this theory. If formula is to be proved (or disproved) then it has to be reduced to axioms. If every transformation is deducible then also optimal transformation is deducible. If every transformation is exponential then optimal one is too, what allows to define lower bound for discussed problem to be exponential (outside P). Then we show algorithm for NDTM solving the same problem in O(n^c) (so problem is in NP), what proves that P \

  11. Spectral conditions for entanglement witnesses vs. bound entanglement

    OpenAIRE

    Chruściński, Dariusz; Kossakowski, Andrzej; Sarbicki, Gniewomir

    2009-01-01

    It is shown that entanglement witnesses constructed via the family of spectral conditions are decomposable, i.e. cannot be used to detect bound entanglement. It supports several observations that bound entanglement reveals highly non-spectral features.

  12. General lower bounds for resonances in one dimension

    Energy Technology Data Exchange (ETDEWEB)

    Harrell, E.M. II

    1982-09-01

    Lower bounds are derived for the magnitude of the imaginary parts of the resonance eigenvalues of a Schroedinger operator on the line, depending only on the support and bounds of V and on the real part of the resonance eigenvalue.

  13. Persistence of noncompact normally hyperbolic invariant manifolds in bounded geometry

    CERN Document Server

    Eldering, Jaap

    2012-01-01

    We prove a persistence result for noncompact normally hyperbolic invariant manifolds in Riemannian manifolds of bounded geometry. The bounded geometry of the ambient manifold is a crucial assumption in order to control the uniformity of all estimates throughout the proof.

  14. The factorization method and ground state energy bounds

    Science.gov (United States)

    Schmutz, M.

    1985-04-01

    We discuss the relationship between the factorization method and the Barnsley bound to the ground state energy. The latter method is extended in such a way that both lower and upper analytic bounds can be obtained.

  15. 与蛋白质调控DNA空穴迁移相关的具有负离解能特征的亚稳态氢键%Metastable Hydrogen-bonds Featuring Negative Dissociation Energies in Protein-bound DNA in Hole Migration

    Institute of Scientific and Technical Information of China (English)

    王梅; 王军; 步宇翔

    2015-01-01

    利用密度泛函理论方法研究了作为空穴迁移载体的蛋白质复合的DNA三聚体( Protonated arginine…guanine…cytosine, ArgH+-GC)的氢键性质.结果表明,空穴迁移通过该载体单元时此类氢键表现为亚稳态,且具有明显的负离解能.正常情况下ArgH+基团在大小沟均能与GC碱对形成氢键,且具有正的离解能.然而,当空穴转移至此将削弱氢键至亚稳态,使之具有一定的离解势垒和负的离解能.这种势垒抑制的负离解能现象意味着由于空穴俘获导致此三聚体结构单元在它的 ArgH+…N7/O6键区储存了一定的能量(约108.78 kJ/mol).该氢键离解通道受控于此键区两个相关组分之间的静电排斥和氢键吸引之间的平衡以及这两个相反作用随氢键距离不同的衰减速率.基于电子密度分布的拓扑性质以及键临界点的Laplacian数值分析澄清了此类特殊的能量现象主要源自通过高能氢键(ArgH+…N7/O6)连接的授受体间的静电排斥.进一步空穴俘获诱导的G→C质子转移可扩展负离解能区至ArgH+…N7/O6和Watson-Crick( WC)氢键区.另外, ArgH+结合到GC的大小沟增加其电离势,因此削弱其空穴传导能力,削弱程度取决于ArgH+与GC的距离.推而广之,在protonated lysine-GC和protonated histidine-GC体系也可观察到类似的现象.显然,此类性质可调的亚稳态氢键可调控DNA空穴迁移机理.此工作为理解蛋白质调控的DNA空穴迁移机理提供了重要的能量学信息.%We theoretically investigated the properties of hydrogen bonds in the protein-bound DNA trimer( protona-ted arginine…guanine…cytosine, ArgH+-GC) units as hole migration carriers using density functional theory calcula-tions. Results suggest these hydrogen bonds are metastable and feature considerable negative dissociation energies up-on hole migration through the ArgH+-GC units of the carriers. Normally, the ArgH+ group can H-bond with the gua-nine-cytosine( GC

  16. Lower Bound Bayesian Networks - An Efficient Inference of Lower Bounds on Probability Distributions in Bayesian Networks

    CERN Document Server

    Andrade, Daniel

    2012-01-01

    We present a new method to propagate lower bounds on conditional probability distributions in conventional Bayesian networks. Our method guarantees to provide outer approximations of the exact lower bounds. A key advantage is that we can use any available algorithms and tools for Bayesian networks in order to represent and infer lower bounds. This new method yields results that are provable exact for trees with binary variables, and results which are competitive to existing approximations in credal networks for all other network structures. Our method is not limited to a specific kind of network structure. Basically, it is also not restricted to a specific kind of inference, but we restrict our analysis to prognostic inference in this article. The computational complexity is superior to that of other existing approaches.

  17. Do Reuss and Voigt Bounds Really Bound in High-Pressure Rheology Experiments?

    Energy Technology Data Exchange (ETDEWEB)

    Chen,J.; Li, L.; Yu, T.; Long, H.; Weidner, D.; Wang, L.; Vaughan, M.

    2006-01-01

    Energy dispersive synchrotron x-ray diffraction is carried out to measure differential lattice strains in polycrystalline Fe{sub 2}SiO{sub 4} (fayalite) and MgO samples using a multi-element solid state detector during high-pressure deformation. The theory of elastic modeling with Reuss (iso-stress) and Voigt (iso-strain) bounds is used to evaluate the aggregate stress and weight parameter, {alpha} (0{le}{alpha}{le}1), of the two bounds. Results under the elastic assumption quantitatively demonstrate that a highly stressed sample in high-pressure experiments reasonably approximates to an iso-stress state. However, when the sample is plastically deformed, the Reuss and Voigt bounds are no longer valid ({alpha} becomes beyond 1). Instead, if plastic slip systems of the sample are known (e.g. in the case of MgO), the aggregate property can be modeled using a visco-plastic self-consistent theory.

  18. Do Reuss and Voigt bounds really bound in high-pressure rheology experiments?

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jiuhua; Li Li; Yu, Tony; Long Hongbo; Weidner, Donald; Wang Liping; Vaughan, Michael [Mineral Physics Institute and Department of Geosciences, Stony Brook University, Stony Brook, NY 11794-2100 (United States)

    2006-06-28

    Energy dispersive synchrotron x-ray diffraction is carried out to measure differential lattice strains in polycrystalline Fe{sub 2}SiO{sub 4} (fayalite) and MgO samples using a multi-element solid state detector during high-pressure deformation. The theory of elastic modelling with Reuss (iso-stress) and Voigt (iso-strain) bounds is used to evaluate the aggregate stress and weight parameter, {alpha} (0{<=}{alpha}{<=}1), of the two bounds. Results under the elastic assumption quantitatively demonstrate that a highly stressed sample in high-pressure experiments reasonably approximates to an iso-stress state. However, when the sample is plastically deformed, the Reuss and Voigt bounds are no longer valid ({alpha} becomes beyond 1). Instead, if plastic slip systems of the sample are known (e.g. in the case of MgO), the aggregate property can be modelled using a visco-plastic self-consistent theory.

  19. Do Reuss and Voigt bounds really bound in high-pressure rheology experiments?

    Science.gov (United States)

    Chen, Jiuhua; Li, Li; Yu, Tony; Long, Hongbo; Weidner, Donald; Wang, Liping; Vaughan, Michael

    2006-06-28

    Energy dispersive synchrotron x-ray diffraction is carried out to measure differential lattice strains in polycrystalline Fe(2)SiO(4) (fayalite) and MgO samples using a multi-element solid state detector during high-pressure deformation. The theory of elastic modelling with Reuss (iso-stress) and Voigt (iso-strain) bounds is used to evaluate the aggregate stress and weight parameter, α (0≤α≤1), of the two bounds. Results under the elastic assumption quantitatively demonstrate that a highly stressed sample in high-pressure experiments reasonably approximates to an iso-stress state. However, when the sample is plastically deformed, the Reuss and Voigt bounds are no longer valid (α becomes beyond 1). Instead, if plastic slip systems of the sample are known (e.g. in the case of MgO), the aggregate property can be modelled using a visco-plastic self-consistent theory. PMID:22611095

  20. Persistence-Based Branch Misprediction Bounds for WCET Analysis

    DEFF Research Database (Denmark)

    Puffitsch, Wolfgang

    2015-01-01

    Branch prediction is an important feature of pipelined processors to achieve high performance. However, it can lead to overly pessimistic worst-case execution time (WCET) bounds when being modeled too conservatively. This paper presents bounds on the number of branch mispredictions for local dyna...... linear programming formulations of the WCET problem. An evaluation on a number of benchmarks shows that with these bounds, dynamic branch prediction does not necessarily lead to higher WCET bounds than static prediction schemes....

  1. Asymptotic bound on binary self-orthogonal codes

    Institute of Scientific and Technical Information of China (English)

    DING Yang

    2009-01-01

    We present two constructions for binary self-orthogonal codes. It turns out that our constructions yield a constructive bound on binary self-orthogonal codes. In particular, when the in-formation rate R = 1/2, by our constructive lower bound, the relative minimum distance δ≈ 0.0595 (for GV bound, δ≈0.110). Moreover, we have proved that the binary self-orthogonal codes asymptotically achieve the Gilbert-Varshamov bound.

  2. Bounds for the connective constant of the hexagonal lattice

    Energy Technology Data Exchange (ETDEWEB)

    Alm, S E; Parviainen, R [Department of Mathematics, Uppsala University, Box 480, 75106 Uppsala (Sweden)

    2004-01-23

    We give improved bounds for the connective constant of the hexagonal lattice. The lower bound is found by using Kesten's method of irreducible bridges and by determining generating functions for bridges on one-dimensional lattices. The upper bound is obtained as the largest eigenvalue of a certain transfer matrix. Using a relation between the hexagonal and the (3.12{sup 2}) lattices, we also give bounds for the connective constant of the latter lattice.

  3. Asymptotic bound on binary self-orthogonal codes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    We present two constructions for binary self-orthogonal codes. It turns out that our constructions yield a constructive bound on binary self-orthogonal codes. In particular, when the in-formation rate R = 1/2, by our constructive lower bound, the relative minimum distance δ≈ 0.0595 (for GV bound, δ≈ 0.110). Moreover, we have proved that the binary self-orthogonal codes asymptotically achieve the Gilbert-Varshamov bound.

  4. Coordination of Copper to the Membrane-Bound Form of α-Synuclein

    Energy Technology Data Exchange (ETDEWEB)

    Dudzik, Christopher G.; Walter, Eric D.; Abrams, Benjamin S.; Jurica, Melissa S.; Millhauser, Glenn L.

    2013-01-01

    Aggregation of the 140 amino acid protein α-synuclein (α-syn) is linked to the development of Parkinson's disease (PD). α-Syn is a copper binding protein with potential function as a regulator of metal dependent redox activity. Epidemiological studies suggest that human exposure to excess copper increases the incidence of PD. α-Syn exists in both solution and membrane bound forms. Previous work evaluated the Cu2+ uptake for α-syn in solution and identified Met1-Asp2 and His50 as primary contributors to the coordination shell, with a dissociation constant of approximately 0.1 nM. When bound to the membrane bilayer, α-syn takes on a predominantly helical conformation, which spatially separates His50 from the protein N-terminus and is therefore incompatible with the copper coordination geometry of the solution state. Here we use circular dichroism and electron paramagnetic resonance (continuous wave and pulsed) to evaluate copper coordination to the membrane bound form of α-syn. In this molecular environment, Cu2+ binds exclusively to the protein N-terminus (Met1-Asp2) with no participation from His50. Copper does not alter the membrane bound α-syn conformation, or enhance the protein's release from the bilayer. The Cu2+ affinity is similar to that identified for solution α-syn suggesting that copper coordination is retained in the membrane. Consideration of these results suggests that copper exerts its greatest conformational affect on the solution form of α-syn and this species may therefore be precursor to PD arising from environmental copper exposure.

  5. Uniform bounds for expressions involving modified Bessel functions

    OpenAIRE

    Gaunt, Robert E.

    2013-01-01

    In this paper, we obtain uniform bounds for a number of expressions that involve derivatives and integrals of modified Bessel functions. These uniform bounds are motivated by the need to bound such expressions in the study of variance-gamma and product normal approximations via Stein's method.

  6. Bounds in the generalized Weber problem under locational uncertainty

    DEFF Research Database (Denmark)

    Juel, Henrik

    1981-01-01

    An existing analysis of the bounds on the Weber problem solution under uncertainty is incorrect. For the generalized problem with arbitrary measures of distance, we give easily computable ranges on the bounds and state the conditions under which the exact values of the bounds can be found...

  7. Almost Chebyshev set with respect to bounded subsets

    Institute of Scientific and Technical Information of China (English)

    李冲; 王兴华

    1997-01-01

    The uniqueness and existence of restricted Chebyshev center with respect to arbitrary subset are investigated. The concept of almost Chebyshev sets with respect to bounded subsets is introduced. It is proved that each closed subset in a reflexive locally uniformly convex (uniformly convex, respectively) Banach space is an almost Chebyshev subset with respect to compact convex subsets (bounded convex subsets and bounded subsets, respectively).

  8. Semiparametric bounds of mean and variance for exotic options

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Finding semiparametric bounds for option prices is a widely studied pricing technique.We obtain closed-form semiparametric bounds of the mean and variance for the pay-off of two exotic(Collar and Gap) call options given mean and variance information on the underlying asset price.Mathematically,we extended domination technique by quadratic functions to bound mean and variances.

  9. Semiparametric bounds of mean and variance for exotic options

    Institute of Scientific and Technical Information of China (English)

    LIU GuoQing; LI V.Wenbo

    2009-01-01

    Finding semiparametric bounds for option prices is a widely studied pricing technique. We obtain closed-form semiparametric bounds of the mean and variance for the pay-off of two exotic (Collar and Gap) call options given mean and variance information on the underlying asset price. Mathematically, we extended domination technique by quadratic functions to bound mean and variances.

  10. Upper bounds on the solution of coupled algebraic riccati equation

    Directory of Open Access Journals (Sweden)

    Czornik Adam

    2001-01-01

    Full Text Available Upper bounds for eigenvalues of a solution to continuous time coupled algebraic Riccati equation (CCARE and discrete time coupled algebraic Riccati equation (DCARE are developed as special cases of bounds for the unified coupled algebraic Riccati equation (UCARE. They include bounds of the maximal eigenvalues, the sums of the eigenvalues and the trace.

  11. Bounds on the capacity of constrained two-dimensional codes

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Justesen, Jørn

    2000-01-01

    Bounds on the capacity of constrained two-dimensional (2-D) codes are presented. The bounds of Calkin and Wilf apply to first-order symmetric constraints. The bounds are generalized in a weaker form to higher order and nonsymmetric constraints. Results are given for constraints specified by run...

  12. Bounded Rationality, Retaliation, and the Spread of Urban Violence

    Science.gov (United States)

    Jacobs, Bruce A.; Wright, Richard

    2010-01-01

    Drawing from in-depth interviews with 52 active street criminals, this article examines the grounded theoretic implications of bounded rationality for retaliatory street violence. The bounds on rationality that this article explores are anger, uncertainty, and time pressure. These bounds create imperfections in the retaliatory decision-making…

  13. Improved Space Bounds for Cache-Oblivious Range Reporting

    DEFF Research Database (Denmark)

    Afshani, Peyman; Zeh, Norbert

    2011-01-01

    We provide improved bounds on the size of cacheoblivious range reporting data structures that achieve the optimal query bound of O(logB N + K/B) block transfers. Our first main result is an O(N √ logN log logN)-space data structure that achieves this query bound for 3-d dominance reporting and 2-d...

  14. Upper bounds on the solution of coupled algebraic riccati equation

    OpenAIRE

    Czornik Adam; Świerniak Andrzej

    2001-01-01

    Upper bounds for eigenvalues of a solution to continuous time coupled algebraic Riccati equation (CCARE) and discrete time coupled algebraic Riccati equation (DCARE) are developed as special cases of bounds for the unified coupled algebraic Riccati equation (UCARE). They include bounds of the maximal eigenvalues, the sums of the eigenvalues and the trace.

  15. Revisiting the upper bounding process in a safe Branch and Bound algorithm

    CERN Document Server

    Goldsztejn, Alexandre; Michel, Claude; Rueher, Michel

    2008-01-01

    Finding feasible points for which the proof succeeds is a critical issue in safe Branch and Bound algorithms which handle continuous problems. In this paper, we introduce a new strategy to compute very accurate approximations of feasible points. This strategy takes advantage of the Newton method for under-constrained systems of equations and inequalities. More precisely, it exploits the optimal solution of a linear relaxation of the problem to compute efficiently a promising upper bound. First experiments on the Coconuts benchmarks demonstrate that this approach is very effective.

  16. A balance for Dark Matter bound states

    CERN Document Server

    Nozzoli, F

    2016-01-01

    Massive particles with self interactions of the order of 0.2 barn/GeV are intriguing Dark Matter candidates from an astrophysical point of view. Direct detection searches for very massive particles, with relatively high cross sections with ordinary matter, cannot rule out $\\sigma/M > 0.01$ barn/GeV, due to atmosphere and material shielding. Here, the possibility of the existence of bound states with ordinary matter, for Dark Matter candidates with not negligible interactions, is considered. The existence of bound states, with binding energy larger than $\\sim$1 meV, would offer the possibility to test in laboratory capture cross sections of the order of a barn (or larger). The signature of the detection of a mass increasing of cryogenic samples, due to the possible Dark Matter accumulation, would allow the investigation of Dark Matter particles with mass up to the GUT scale. A proof of concept for a possible detection set-up and the evaluation of some noise sources are described.

  17. Bound states -- from QED to QCD

    CERN Document Server

    Hoyer, Paul

    2014-01-01

    These lectures are divided into two parts. In Part 1 I discuss bound state topics at the level of a basic course in field theory: The derivation of the Schr\\"odinger and Dirac equations from the QED Lagrangian, by summing Feynman diagrams and in a Hamiltonian framework. Less well known topics include the equal-time wave function of Positronium in motion and the properties of the Dirac wave function for a linear potential. The presentation emphasizes physical aspects and provides the framework for Part 2, which discusses the derivation of relativistic bound states at Born level in QED and QCD. A central aspect is the maintenance of Poincar\\'e invariance. The transformation of the wave function under boosts is studied in detail in D=1+1 dimensions, and its generalization to D=3+1 is indicated. Solving Gauss' law for $A^0$ with a non-vanishing boundary condition leads to a linear potential for QCD mesons, and an analogous confining potential for baryons.

  18. Generalized bounds for convex multistage stochastic programs

    CERN Document Server

    Künzi, H; Fandel, G; Trockel, W; Basile, A; Drexl, A; Dawid, H; Inderfurth, K; Kürsten, W; Schittko, U

    2005-01-01

    This work was completed during my tenure as a scientific assistant and d- toral student at the Institute for Operations Research at the University of St. Gallen. During that time, I was involved in several industry projects in the field of power management, on the occasion of which I was repeatedly c- fronted with complex decision problems under uncertainty. Although usually hard to solve, I quickly learned to appreciate the benefit of stochastic progr- ming models and developed a strong interest in their theoretical properties. Motivated both by practical questions and theoretical concerns, I became p- ticularly interested in the art of finding tight bounds on the optimal value of a given model. The present work attempts to make a contribution to this important branch of stochastic optimization theory. In particular, it aims at extending some classical bounding methods to broader problem classes of practical relevance. This book was accepted as a doctoral thesis by the University of St. Gallen in June 2004.1...

  19. Search for a bound K− pp system

    Directory of Open Access Journals (Sweden)

    Camerini P.

    2010-04-01

    Full Text Available Data from the K− absorption reaction on 6,7Li, 9Be, 13C and 16O have recently been collected by FINUDA at the DAΦNE φ-factory (Laboratori Nazionali di Frascati-INFN, following an earlier lower statitics run on 12C and some other targets. FINUDA is a high acceptance magnetic spectrometer which performed a wide range of studies by detecting the charged particles and neutrons exiting the targets after the absorption event. In this paper it is discussed about the study of the A(K− , Λp reaction in the context of the search for deeply bound $ar{K}$ - nuclear states. The observation of a bump in the Λp invariant mass distribution is discussed in terms of a possible signature of a deeply bound K− pp kaonic cluster as well as of more conventional physics. An overview of the experimental situation in this field will be given.

  20. $\\bar K$-Nuclear Deeply Bound States?

    CERN Document Server

    Gal, A

    2006-01-01

    Following the prediction by Akaishi and Yamazaki of relatively narrow $\\bar K$-nuclear states, deeply bound by over 100 MeV where the main decay channel $\\bar K N \\to \\pi \\Sigma$ is closed, several experimental signals in stopped $K^-$ reactions on light nuclei have been interpreted recently as due to such states. In this talk I review (i) the evidence from $K^-$-atom data for a {\\it deep} $\\bar K$-nucleus potential, as attractive as $V_{\\bar K}(\\rho_0) \\sim -(150 - 200)$ MeV at nuclear matter density, that could support such states; and (ii) the theoretical arguments for a {\\it shallow} potential, $V_{\\bar K}(\\rho_0) \\sim -(40 - 60)$ MeV. I then review a recent work by Mare\\v{s}, Friedman and Gal in which $\\bar K$-nuclear bound states are generated dynamically across the periodic table, using a RMF Lagrangian that couples the $\\bar K$ to the scalar and vector meson fields mediating the nuclear interactions. Substantial polarization of the core nucleus is found for light nuclei, with central nuclear densities...