De Novo Transcriptome Analysis Shows That SAV-3 Infection Upregulates Pattern Recognition Receptors of the Endosomal Toll-Like and RIG-I-Like Receptor Signaling Pathways in Macrophage/Dendritic Like TO-Cells

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Cheng Xu

2016-04-01

Full Text Available A fundamental step in cellular defense mechanisms is the recognition of “danger signals” made of conserved pathogen associated molecular patterns (PAMPs expressed by invading pathogens, by host cell germ line coded pattern recognition receptors (PRRs. In this study, we used RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGG to identify PRRs together with the network pathway of differentially expressed genes (DEGs that recognize salmonid alphavirus subtype 3 (SAV-3 infection in macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L headkidney leukocytes. Our findings show that recognition of SAV-3 in TO-cells was restricted to endosomal Toll-like receptors (TLRs 3 and 8 together with RIG-I-like receptors (RLRs and not the nucleotide-binding oligomerization domain-like receptors NOD-like receptor (NLRs genes. Among the RLRs, upregulated genes included the retinoic acid inducible gene I (RIG-I, melanoma differentiation association 5 (MDA5 and laboratory of genetics and physiology 2 (LGP2. The study points to possible involvement of the tripartite motif containing 25 (TRIM25 and mitochondrial antiviral signaling protein (MAVS in modulating RIG-I signaling being the first report that links these genes to the RLR pathway in SAV-3 infection in TO-cells. Downstream signaling suggests that both the TLR and RLR pathways use interferon (IFN regulatory factors (IRFs 3 and 7 to produce IFN-a2. The validity of RNA-seq data generated in this study was confirmed by quantitative real time qRT-PCR showing that genes up- or downregulated by RNA-seq were also up- or downregulated by RT-PCR. Overall, this study shows that de novo transcriptome assembly identify key receptors of the TLR and RLR sensors engaged in host pathogen interaction at cellular level. We envisage that data presented here can open a road map for future intervention strategies in SAV infection of salmon.

RIG-I self-oligomerization is either dispensable or very transient for signal transduction.

Directory of Open Access Journals (Sweden)

Jade Louber

Full Text Available Effective host defence against viruses depends on the rapid triggering of innate immunity through the induction of a type I interferon (IFN response. To this end, microbe-associated molecular patterns are detected by dedicated receptors. Among them, the RIG-I-like receptors RIG-I and MDA5 activate IFN gene expression upon sensing viral RNA in the cytoplasm. While MDA5 forms long filaments in vitro upon activation, RIG-I is believed to oligomerize after RNA binding in order to transduce a signal. Here, we show that in vitro binding of synthetic RNA mimicking that of Mononegavirales (Ebola, rabies and measles viruses leader sequences to purified RIG-I does not induce RIG-I oligomerization. Furthermore, in cells devoid of endogenous functional RIG-I-like receptors, after activation of exogenous Flag-RIG-I by a 62-mer-5'ppp-dsRNA or by polyinosinic:polycytidylic acid, a dsRNA analogue, or by measles virus infection, anti-Flag immunoprecipitation and specific elution with Flag peptide indicated a monomeric form of RIG-I. Accordingly, when using the Gaussia Luciferase-Based Protein Complementation Assay (PCA, a more sensitive in cellula assay, no RIG-I oligomerization could be detected upon RNA stimulation. Altogether our data indicate that the need for self-oligomerization of RIG-I for signal transduction is either dispensable or very transient.

The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection.

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Ramanathan, Anand; Devarkar, Swapnil C; Jiang, Fuguo; Miller, Matthew T; Khan, Abdul G; Marcotrigiano, Joseph; Patel, Smita S

2016-01-29

RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Toscana virus NSs protein inhibits the induction of type I interferon by interacting with RIG-I.

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Gori-Savellini, Gianni; Valentini, Melissa; Cusi, Maria Grazia

2013-06-01

Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-β) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92:71-79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-β promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-β promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response.

Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors.

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Bryant, A H; Menzies, G E; Scott, L M; Spencer-Harty, S; Davies, L B; Smith, R A; Jones, R H; Thornton, C A

2017-07-01

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, -7, -8 and -9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes. © 2017 British Society for Immunology.

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

International Nuclear Information System (INIS)

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-01-01

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

LIBRA: LIgand Binding site Recognition Application.

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Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

2015-12-15

In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma.

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Glas, Martin; Coch, Christoph; Trageser, Daniel; Dassler, Juliane; Simon, Matthias; Koch, Philipp; Mertens, Jerome; Quandel, Tamara; Gorris, Raphaela; Reinartz, Roman; Wieland, Anja; Von Lehe, Marec; Pusch, Annette; Roy, Kristin; Schlee, Martin; Neumann, Harald; Fimmers, Rolf; Herrlinger, Ulrich; Brüstle, Oliver; Hartmann, Gunther; Besch, Robert; Scheffler, Björn

2013-06-01

Cellular heterogeneity, for example, the intratumoral coexistence of cancer cells with and without stem cell characteristics, represents a potential root of therapeutic resistance and a significant challenge for modern drug development in glioblastoma (GBM). We propose here that activation of the innate immune system by stimulation of innate immune receptors involved in antiviral and antitumor responses can similarly target different malignant populations of glioma cells. We used short-term expanded patient-specific primary human GBM cells to study the stimulation of the cytosolic nucleic acid receptors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). Specifically, we analyzed cells from the tumor core versus "residual GBM cells" derived from the tumor resection margin as well as stem cell-enriched primary cultures versus specimens without stem cell properties. A portfolio of human, nontumor neural cells was used as a control for these studies. The expression of RIG-I and MDA5 could be induced in all of these cells. Receptor stimulation with their respective ligands, p(I:C) and 3pRNA, led to in vitro evidence for an effective activation of the innate immune system. Most intriguingly, all investigated cancer cell populations additionally responded with a pronounced induction of apoptotic signaling cascades revealing a second, direct mechanism of antitumor activity. By contrast, p(I:C) and 3pRNA induced only little toxicity in human nonmalignant neural cells. Granted that the challenge of effective central nervous system (CNS) delivery can be overcome, targeting of RIG-I and MDA5 could thus become a quintessential strategy to encounter heterogeneous cancers in the sophisticated environments of the brain. Copyright © 2013 AlphaMed Press.

<i>Toxoplasma gondiii> peptide ligands open the gate of the HLA class I binding groove

DEFF Research Database (Denmark)

McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany

2016-01-01

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infect...

Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.

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Chiang, Jessica J; Sparrer, Konstantin M J; van Gent, Michiel; Lässig, Charlotte; Huang, Teng; Osterrieder, Nikolaus; Hopfner, Karl-Peter; Gack, Michaela U

2018-01-01

The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.

DISTINCT ROLES OF β1 MIDAS, ADMIDAS AND LIMBS CATION-BINDING SITES IN LIGAND RECOGNITION BY INTEGRIN α2β1*

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Valdramidou, Dimitra; Humphries, Martin J.; Mould, A. Paul

2012-01-01

Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as α2β1, ligand recognition takes place exclusively at the α subunit I domain. However, activation of the αI domain depends on its interaction with a structurally similar domain in the β subunit known as the I-like or βI domain. The top face of the βI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS) and LIMBS (ligand-associated metal binding site). The role of these sites in controlling ligand binding to the αI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to α2β1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating mAb TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between αI and βI whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of βI. An activating mutation in the α2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca2+, Mg2+ and Mn2+ on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn2+ stimulates ligand binding, whereas the LIMBS is a stimulatory Ca2+-binding site, occupancy of which increases the affinity of Mg2+ for the MIDAS. PMID:18820259

Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and MDA5.

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Louber, Jade; Brunel, Joanna; Uchikawa, Emiko; Cusack, Stephen; Gerlier, Denis

2015-07-28

The cytoplasmic RIG-like receptors are responsible for the early detection of viruses and other intracellular microbes by activating the innate immune response mediated by type I interferons (IFNs). RIG-I and MDA5 detect virus-specific RNA motifs with short 5'-tri/diphosphorylated, blunt-end double-stranded RNA (dsRNA) and >0.5-2 kb long dsRNA as canonical agonists, respectively. However, in vitro, they can bind to many RNA species, while in cells there is an activation threshold. As SF2 helicase/ATPase family members, ATP hydrolysis is dependent on co-operative RNA and ATP binding. Whereas simultaneous ATP and cognate RNA binding is sufficient to activate RIG-I by releasing autoinhibition of the signaling domains, the physiological role of the ATPase activity of RIG-I and MDA5 remains controversial. A cross-analysis of a rationally designed panel of RNA binding and ATPase mutants and truncated receptors, using type I IFN promoter activation as readout, allows us to refine our understanding of the structure-function relationships of RIG-I and MDA5. RNA activation of RIG-I depends on multiple critical RNA binding sites in its helicase domain as confirmed by functional evidence using novel mutations. We found that RIG-I or MDA5 mutants with low ATP hydrolysis activity exhibit constitutive activity but this was fully reverted when associated with mutations preventing RNA binding to the helicase domain. We propose that the turnover kinetics of the ATPase domain enables the discrimination of self/non-self RNA by both RIG-I and MDA5. Non-cognate, possibly self, RNA binding would lead to fast ATP turnover and RNA disassociation and thus insufficient time for the caspase activation and recruitment domains (CARDs) to promote downstream signaling, whereas tighter cognate RNA binding provides a longer time window for downstream events to be engaged. The exquisite fine-tuning of RIG-I and MDA5 RNA-dependent ATPase activity coupled to CARD release allows a robust IFN response

Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1.

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Valdramidou, Dimitra; Humphries, Martin J; Mould, A Paul

2008-11-21

Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as alpha2beta1, ligand recognition takes place exclusively at the alpha subunit I domain. However, activation of the alphaI domain depends on its interaction with a structurally similar domain in the beta subunit known as the I-like or betaI domain. The top face of the betaI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS), and LIMBS (ligand-associated metal-binding site). The role of these sites in controlling ligand binding to the alphaI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to alpha2beta1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating monoclonal antibody TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between alphaI and betaI, whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of betaI. An activating mutation in the alpha2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca(2+), Mg(2+), and Mn(2+) on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn(2+) stimulates ligand binding, whereas the LIMBS is a stimulatory Ca(2+)-binding site, occupancy of which increases the affinity of Mg(2+) for the MIDAS.

Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss) ▿ †

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Chang, Mingxian; Collet, Bertrand; Nie, Pin; Lester, Katherine; Campbell, Scott; Secombes, Christopher J.; Zou, Jun

2011-01-01

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) comprise three homologues: RIG-I, melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). They activate the host interferon (IFN) system upon recognition of viral RNA pathogen-associated molecular patterns (PAMPs) in the cytoplasm. Bioinformatic analysis of the sequenced vertebrate genomes suggests that the cytosolic surveillance system is conserved in lower vertebrates, and recent functional studies have confirmed that RIG-I is important to fish antiviral immunity. In this study, we have identified MDA5 and LGP2 homologues from rainbow trout Oncorhynchus mykiss and an additional LGP2 variant with an incomplete C-terminal domain of RIG-I. Trout MDA5 and LGP2 were constitutively produced in fibroblast and macrophage cell lines and upregulated by poly(I:C), recombinant IFN, or infection by RNA viruses (viral hemorrhagic septicemia virus and salmon alphavirus) with a single-stranded positive or negative genome. Overexpression of MDA5 and LGP2 but not of the LGP2 variant resulted in significant accumulation of Mx transcripts in cultured cells, which correlated with a marked enhancement of protection against viral infection. These results demonstrate that both MDA5 and LGP2 are important RLRs in host surveillance against infection of both negative and positive viruses and that the LGP2 variant with a deletion of 54 amino acids at the C terminus acts as a negative regulator for LGP2-elicited antiviral signaling by competing for the viral RNA PAMPs. Interestingly, MDA5 expression was not affected by overexpressed LGP2 in transfected cells and vice versa, suggesting that they likely act in parallel as positive regulators for IFN production. PMID:21680521

Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance.

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Yang, Hui; Guo, He-Zhou; Li, Xian-Yang; Lin, Jian; Zhang, Wu; Zhao, Jun-Mei; Zhang, Hong-Xin; Chen, Sai-Juan; Chen, Zhu; Zhu, Jiang

2017-07-01

Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4 + T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I -/- CD4 + T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance. Mechanistically, apo-Rig-I physically associates with Stat3, thereby inhibiting Jak1's association with Stat3 while facilitating Shp2's association to inhibit p-Stat3 levels. Interestingly, inhibition of Stat3 ameliorates the Treg/Th17 imbalance and the colitis observed in Rig-I -/- mice. Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance. Copyright © 2017 by The American Association of Immunologists, Inc.

Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

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Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; De Biasi, Federico; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

2017-07-13

The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.

Recognition of mannose 6-phosphate ligands by dystrophic rat retinal pigment epithelium

International Nuclear Information System (INIS)

Tarnowski, B.; Shepherd, V.; McLaughlin, B.

1986-01-01

Retinal pigment epithelium (RPE) phagocytize discarded rod outer segments (ROS) during normal eye function. In the dystrophic rat, an animal model for retinitis pigmentosa in humans, ROS phagocytosis is defective. Dystrophic RPE can phagocytize particles other than ROS, suggesting that the defect may be in the RPE phagocytic recognition. They are currently investigating the recognition markers on RPE in dystrophic rats. In studies using ligand-coated latex beads, no uptake of mannose-coated beads was found in dystrophic rat RPE. They found that dystrophic RPE could specifically phagocytize phosphomannan-coated beads. Studies were begun to examine the presence and function of a phosphomannan receptor (PMR) on dystrophic RPE. α-Mannosidase, isolated from D. discoideum has been shown to be an efficient ligand for the PMR in fibroblasts and macrophages. It is also recognized by the macrophage mannose receptor. Dystrophic rat RPE and retina explants were placed in culture dishes (5-7/well). 125 I-Labelled α-mannosidase was added to each well in the presence or absence of 10 mM mannose 6-phosphate (M6P) or yeast mannan (lmg/ml). Explants were incubated at 37 0 for 2 hr., washed and bound 125 I-mannosidase quantitated. Approximately 2-3% of total counts added were bound to the RPE via a M6P-inhibitable recognition process. The binding to RPE was not blocked by mannan. No mannan or M6P-specific binding was found in retina explants. These results support the findings of specific uptake of phosphomannan-coated beads and demonstrate the presence of a specific PMR on dystrophic RPE phagocytic membranes

Cellular La protein shields nonsegmented negative-strand RNA viral leader RNA from RIG-I and enhances virus growth by diverse mechanisms.

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Bitko, Vira; Musiyenko, Alla; Bayfield, Mark A; Maraia, Richard J; Barik, Sailen

2008-08-01

The La antigen (SS-B) associates with a wide variety of cellular and viral RNAs to affect gene expression in multiple systems. We show that La is the major cellular protein found to be associated with the abundant 44-nucleotide viral leader RNA (leRNA) early after infection with respiratory syncytial virus (RSV), a nonsegmented negative-strand RNA virus. Consistent with this, La redistributes from the nucleus to the cytoplasm in RSV-infected cells. Upon RNA interference knockdown of La, leRNA is redirected to associate with the RNA-binding protein RIG-I, a known activator of interferon (IFN) gene expression, and this is accompanied by the early induction of IFN mRNA. These results suggest that La shields leRNA from RIG-I, abrogating the early viral activation of type I IFN. We mapped the leRNA binding function to RNA recognition motif 1 of La and showed that while wild-type La greatly enhanced RSV growth, a La mutant defective in RSV leRNA binding also did not support RSV growth. Comparative studies of RSV and Sendai virus and the use of IFN-negative Vero cells indicated that La supports the growth of nonsegmented negative-strand RNA viruses by both IFN suppression and a potentially novel IFN-independent mechanism.

Selective RNA targeting and regulated signaling by RIG-I is controlled by coordination of RNA and ATP binding.

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Fitzgerald, Megan E; Rawling, David C; Potapova, Olga; Ren, Xiaoming; Kohlway, Andrew; Pyle, Anna Marie

2017-02-17

RIG-I is an innate immune receptor that detects and responds to infection by deadly RNA viruses such as influenza, and Hepatitis C. In the cytoplasm, RIG-I is faced with a difficult challenge: it must sensitively detect viral RNA while ignoring the abundance of host RNA. It has been suggested that RIG-I has a ‘proof-reading’ mechanism for rejecting host RNA targets, and that disruptions of this selectivity filter give rise to autoimmune diseases. Here, we directly monitor RNA proof-reading by RIG-I and we show that it is controlled by a set of conserved amino acids that couple RNA and ATP binding to the protein (Motif III). Mutations of this motif directly modulate proof-reading by eliminating or enhancing selectivity for viral RNA, with major implications for autoimmune disease and cancer. More broadly, the results provide a physical explanation for the ATP-gated behavior of SF2 RNA helicases and receptor proteins.

Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETA and ETB.

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Lättig, Jens; Oksche, Alexander; Beyermann, Michael; Rosenthal, Walter; Krause, Gerd

2009-07-01

The molecular basis for recognition of peptide ligands endothelin-1, -2 and -3 in endothelin receptors is poorly understood. Especially the origin of ligand selectivity for ET(A) or ET(B) is not clearly resolved. We derived sequence-structure-function relationships of peptides and receptors from mutational data and homology modeling. Our major findings are the dissection of peptide ligands into four epitopes and the delineation of four complementary structural portions on receptor side explaining ligand recognition in both endothelin receptor subtypes. In addition, structural determinants for ligand selectivity could be described. As a result, we could improve the selectivity of BQ3020 about 10-fold by a single amino acid substitution, validating our hypothesis for ligand selectivity caused by different entrances to the receptors' transmembrane binding sites. A narrow tunnel shape in ET(A) is restrictive for a selected group of peptide ligands' N-termini, whereas a broad funnel-shaped entrance in ET(B) accepts a variety of different shapes and properties of ligands.

Measles Virus Suppresses RIG-I-like Receptor Activation in Dendritic Cells via DC-SIGN-Mediated Inhibition of PP1 Phosphatases

NARCIS (Netherlands)

Mesman, Annelies W.; Zijlstra-Willems, Esther M.; Kaptein, Tanja M.; de Swart, Rik L.; Davis, Meredith E.; Ludlow, Martin; Duprex, W. Paul; Gack, Michaela U.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.

2014-01-01

Dendritic cells (DCs) are targets of measles virus (MV) and play central roles in viral dissemination. However, DCs express the RIG-I-like receptors (RLRs) RIG-I and Mda5 that sense MV and induce type I interferon (IFN) production. Given the potency of this antiviral response, RLRs are tightly

Measles virus suppresses RIG-I-like receptor activation in dendritic cells via DC-SIGN-mediated inhibition of PP1 phosphatases

NARCIS (Netherlands)

A.W. Mesman (Annelies ); E.M. Zijlstra-Willems (Esther); T.M. Kaptein (Tanja); R.L. de Swart (Rik); M.E. Davis (Meredith); M. Ludlow (Martin); W.P. Duprex (Paul); M.U. Gack (Michaela); S.I. Gringhuis (Sonja); T.B.H. Geijtenbeek (Teunis)

2014-01-01

textabstractDendritic cells (DCs) are targets of measles virus (MV) and play central roles in viral dissemination. However, DCs express the RIG-I-like receptors (RLRs) RIG-I and Mda5 that sense MV and induce type I interferon (IFN) production. Given the potency of this antiviral response, RLRs are

One big rig, two valuable functions

Energy Technology Data Exchange (ETDEWEB)

Anon

2004-11-01

A hybrid coil tubing and conventional workover rig, tailor-made for conditions on Alaska's remote North Slope is described. The dual function rig, owned by BP Exploration, towers 142 feet above the barren Arctic tundra, and weighs between 1.5 and 2 million pounds, rests on eight enormous wheels that stand 11.5 feet tall and 3.5 feet wide, and is supported by 64 smaller tires in between. The rig includes the hybrid coiled tubing rig and a conventional workover rig; it exerts less than 100 pounds per square inch of pressure on the tender Arctic surface as it moves forward at a top speed of two miles per hour. It is considered by its developers as the next-step change in providing cost-effective access to reserves in the large, mature and remote oilfields such as those of Alaska's Prudhoe Bay. The rig is the product of cooperation between Schlumberger expertise in coiled tubing drilling and Nordic-Calista's know-how of jointed pipe operations and operating rigs in an Arctic environment. It is the first time in Prudhoe Bay, and probably in the world, that a coiled tubing unit was installed on a rig to do coiled-tubing sidetracks, i.e to drill a secondary wellbore away from the original wellbore. Since the first unit was commissioned in 1996, the rig has drilled 280 wells. Rig No. 2, much improved and commissioned in 2002, drilled about 30 wells to date. Unlike Rig No, 1, Rig No. 2 can change reels without a crane, and it has a hydraulic pipe skate that moves jointed pipe to and from the rig floor without human aid. The expectation is that using this rig it will be possible to do micro-hole exploration drilling on the North Slope (i.e. drilling a small surface hole with jointed pipe and then switch to coiled tubing), substantially cutting the cost of exploration.

Unique contributions of an arginine side chain to ligand recognition in a glutamate-gated chloride channel

DEFF Research Database (Denmark)

Lynagh, Timothy; Komnatnyy, Vitaly V; Pless, Stephan A

2017-01-01

Glutamate recognition by neurotransmitter receptors often relies on arginine (Arg) residues in the binding site, leading to the assumption that charge-charge interactions underlie ligand recognition. However, assessing the precise chemical contribution of Arg side chains to protein function......-gated chloride channel from the nematode Haemonchus contortus. Our data unveil a surprisingly small contribution of charge at a conserved arginine side chain previously suggested to form a salt bridge with the ligand, glutamate. Instead, our data show that Arg contributes crucially to ligand sensitivity via...

Human NKG2D-ligands: cell biology strategies to ensure immune recognition

Directory of Open Access Journals (Sweden)

Lola eFernández-Messina

2012-09-01

Full Text Available Immune recognition mediated by the activating receptor NKG2D plays an important role for the elimination of stressed cells, including tumours and virus-infected cells. On the other hand, the ligands for NKG2D can also be shed into the sera of cancer patients where they weaken the immune response by downmodulating the receptor on effector cells, mainly NK and T cells. Although both families of NKG2D-ligands, MICA/B and ULBPs, are related to MHC molecules and their expression is increased after stress, many differences are observed in terms of their biochemical properties and cell trafficking. In this paper, we summarise the variety of NKG2D-ligands and propose that selection pressure has driven evolution of diversity in their trafficking and shedding, but not receptor binding affinity. However, it is also possible to identify functional properties common to individual ULBP molecules and MICA/B alleles, but not generally conserved within the MIC or ULBP families. These characteristics likely represent examples of convergent evolution for efficient immune recognition, but are also attractive targets for pathogen immune evasion strategies. Categorization of NKG2D-ligands according to their biological features, rather than their genetic family, may help to achieve a better understanding of NKG2D-ligand association with disease.

Rig it right! Maya animation rigging concepts

CERN Document Server

O'Hailey, Tina

2013-01-01

Rigging a character can be a complicated undertaking. Move from a bi-pedal character to a quad- or poly-pedal and, well, things just got real. Where do you begin? Unlike all of those button-pushing manuals out there, Rig it Right! breaks down rigging so that you can achieve a fundamental understanding of the concept, allowing you to rig more intuitively in your own work. Veteran animation professor Tina O'Hailey will get you up and rigging in a matter of hours with step-by-step tutorials covering multiple animation control types, connection methods, interactive skinning, Blend

Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway.

Directory of Open Access Journals (Sweden)

Valéryane Dupuis-Maurin

Full Text Available Deregulated expression of oncogenes or transcription factors such as specificity protein 1 (Sp1 is observed in many human cancers and plays a role in tumor maintenance. Paradoxically in untransformed cells, Sp1 overexpression induces late apoptosis but the early intrinsic response is poorly characterized. In the present work, we studied increased Sp1 level consequences in untransformed cells and showed that it turns on an early innate immune transcriptome. Sp1 overexpression does not activate known cellular stress pathways such as DNA damage response or endoplasmic reticulum stress, but induces the activation of the OAS-RNase L pathway and the generation of small self-RNAs, leading to the upregulation of genes of the antiviral RIG-I pathway at the transcriptional and translational levels. Finally, Sp1-induced intrinsic innate immune response leads to the production of the chemokine CXCL4 and to the recruitment of inflammatory cells in vitro and in vivo. Altogether our results showed that increased Sp1 level in untransformed cells constitutes a novel danger signal sensed by the OAS-RNase L axis leading to the activation of the RIG-I pathway. These results suggested that the OAS-RNase L-RIG-I pathway may be activated in sterile condition in absence of pathogen.

RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA: a new antiviral pathway

Directory of Open Access Journals (Sweden)

Saurabh Chattopadhyay

2016-11-01

Full Text Available Abstract The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR and Nod-like receptors (NLR, and membrane bound Toll like receptors (TLR detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN and interferon stimulated genes (ISGs, which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death. The transcription factor IRF3 can mediate cellular antiviral responses by both inducing antiviral genes and triggering apoptosis through the activation of RIPA. The mechanism of IRF3 activation in RIPA is distinct from that of transcriptional activation; it requires linear polyubiquitination of specific lysine residues of IRF3. Using RIPA-active, but transcriptionally inactive, IRF3 mutants, it was shown that RIPA can prevent viral replication and pathogenesis in mice.

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

Directory of Open Access Journals (Sweden)

Seung Bum Park

Full Text Available Hepatitis C virus (HCV actively evades host interferon (IFN responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP and poly(IC. The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity.

Advancing rig design: latest rig technologies improving efficiency and safety

Energy Technology Data Exchange (ETDEWEB)

Greenaway, R.

1997-12-01

Recent advances in drilling rig technologies that improve the ways for finding oil and natural gas, and are also solving some safety and transportation problems, have been reviewed. The coiled tubing drilling rig developed by joint venture TransOcean Ensign Drilling Technology was one of the innovations described. It is able to run a three-and-a-quarter inch coiled tubing, the only system capable of doing this in a land-based application. Tesco Corporation`s new casing drilling rig, which is expected to lower the cost of moving the rig, and Brinkerhoff Drilling`s new generation modular (NGM)-rig, claimed to be the most mobile rig in North America, are other new developments worthy of note. Tesco`s casing drilling rig has the potential to reduce drilling costs by as much as 30 to 40 per cent, while the NGM-rig could reduce rig mobilization time by 50 to 80 per cent, and the number of wells drilled by the same rig could increase by 20 per cent, due to the NGM-rig`s versatility and flexibility.

A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition.

Science.gov (United States)

Liu, Jin; Xu, Congfeng; Hsu, Li-Chung; Luo, Yunping; Xiang, Rong; Chuang, Tsung-Hsien

2010-02-01

Toll-like receptors play important roles in regulating immunity against microbial infections. Toll-like receptor 8 (TLR8) belongs to a subfamily comprising TLR7, TLR8 and TLR9. Human TLR8 mediates anti-viral immunity by recognizing ssRNA viruses, and triggers potent anti-viral and antitumor immune responses upon ligation by synthetic small molecular weight ligands. Interestingly, distinct from human TLR8, mouse TLR8 was not responsive to ligand stimulation in the absence of polyT-oligodeoxynucleotides (polyT-ODN). The molecular basis for this distinct ligand recognition is still unclear. In the present study, we compared the activation of TLR8 from different species including mouse, rat, human, bovine, porcine, horse, sheep, and cat by ligand ligations. Only the TLR8s from the rodent species (i.e., mouse and rat TLR8s) failed to respond to ligand stimulation in the absence of polyT-ODN. Multiple sequence alignment analysis suggested that these two rodent TLR8s lack a five-amino-acid motif that is conserved in the non-rodent species with varied sequence. This small motif is located in an undefined region of the hTLR8 ectodomain, immediately following LRR-14. Deletion mutation analysis suggested that this motif is essential for the species-specific ligand recognition of hTLR8, whereas it is not required for self-dimerization and intracellular localization of this receptor. (c) 2009 Elsevier Ltd. All rights reserved.

Ligand recognition by RAR and RXR receptors: binding and selectivity.

Science.gov (United States)

Sussman, Fredy; de Lera, Angel R

2005-10-06

Fundamental biological functions, most notably embriogenesis, cell growth, cell differentiation, and cell apoptosis, are in part regulated by a complex genomic network that starts with the binding (and activation) of retinoids to their cognate receptors, members of the superfamily of nuclear receptors. We have studied ligand recognition of retinoic receptors (RXRalpha and RARgamma) using a molecular-mechanics-based docking method. The protocol used in this work is able to rank the affinity of pairs of ligands for a single retinoid receptor, the highest values corresponding to those that adapt better to the shape of the binding site and generate the optimal set of electrostatic and apolar interactions with the receptor. Moreover, our studies shed light onto some of the energetic contributions to retinoid receptor ligand selectivity. In this regard we show that there is a difference in polarity between the binding site regions that anchor the carboxylate in RAR and RXR, which translates itself into large differences in the energy of interaction of both receptors with the same ligand. We observe that the latter energy change is canceled off by the solvation energy penalty upon binding. This energy compensation is borne out as well by experiments that address the effect of site-directed mutagenesis on ligand binding to RARgamma. The hypothesis that the difference in binding site polarity might be exploited to build RXR-selective ligands is tested with some compounds having a thiazolidinedione anchoring group.

(125I)LSD labels 5-TCsub(IC) recognition sites in pig choriod plexus membranes. Comparison with (3H)mesulergine and (3H)5-HT binding

International Nuclear Information System (INIS)

Hoyer, D.; Srivatsa, S.; Pazos, A.; Engel, G.; Palacios, J.M.

1986-01-01

The mammalian choroid plexus is enriched in a newly described serotonin recognition site, the binding characteristics of ( 125 I)LSD, ( 3 H)mesulergine and ( 3 H)serotonin to pig choroid plexus membranes were compared. These ligands labelled with high affinity a similar number of sites. The binding profiles of the sites labelled with these radioligands are indistinguishable as illustrated by highly significant correlation parameters. These sites are very similar to those labelled by Nsub(I)-methyl-2-( 125 I)LSD in pig and rat choroid plexus membranes. The data demonstrate that these ligands label 5-HTsub(IC) recognition sites in the pig and rat choroid plexus membranes. (author)

Hoisting and Rigging (Formerly Hoisting and Rigging Manual)

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-06-01

This standard is intended as a reference document to be used by supervisors, line managers, safety personnel, equipment operators, and any other personnel responsible for safety of hoisting and rigging operations at DOE sites. It quotes or paraphrases the US OSHA and ANSI requirements. It also encompasses, under one cover,hoisting and rigging requirements, codes, standards, and regulations, eliminating the need to maintain extensive (and often incomplete) libraries of hoisting and rigging standards throughout DOE. The standard occasionally goes beyond the minimum general industry standards established by OSHA and ANSI, and also delineates the more stringent requirements necessary to accomplish the complex, diversified, critical, and often hazardous hoisting and rigging work found with the DOE complex.

Understanding Rig Rates

OpenAIRE

Petter Osmundsen; Knut Einar Rosendahl; Terje Skjerpen

2013-01-01

We examine the largest cost component in offshore development projects, drilling rates, which have been high over the last years. To our knowledge, rig rates have not been analysed empirically before in the economic literature. By econometric analysis we examine the effects on Gulf of Mexico rig rates of gas and oil prices, rig capacity utilization, contract length and lead time, and rig specific characteristics. Having access to a unique data set containing contract information, we are able ...

The art of rigging

CERN Document Server

Biddlecombe, George

1990-01-01

The best manual ever produced on rigging a sailing ship, based on extensively revised and updated 1848 edition prepared by Biddlecombe, Master in the Royal Navy. Complete definition of terms, on-shore operations, process of rigging ships, reeving the running rigging and bending sails, rigging brigs, yachts and small vessels, more. 17 plates.

Pathogen recognition in the innate immune response.

Science.gov (United States)

Kumar, Himanshu; Kawai, Taro; Akira, Shizuo

2009-04-28

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

Cytotoxicity of an 125I-labelled DNA ligand

International Nuclear Information System (INIS)

Karagiannis, T.C.; Lobachevsky, P.N.; Martin, R.F.

2000-01-01

The subcellular distribution and cytotoxicity of a DNA-binding ligand [ 125 I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125 I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125 I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging

Mechanistic pathways of recognition of a solvent-inaccessible cavity of protein by a ligand

Science.gov (United States)

Mondal, Jagannath; Pandit, Subhendu; Dandekar, Bhupendra; Vallurupalli, Pramodh

One of the puzzling questions in the realm of protein-ligand recognition is how a solvent-inaccessible hydrophobic cavity of a protein gets recognized by a ligand. We address the topic by simulating, for the first time, the complete binding process of benzene from aqueous media to the well-known buried cavity of L99A T4 Lysozyme at an atomistic resolution. Our multiple unbiased microsecond-long trajectories, which were completely blind to the location of target binding site, are able to unequivocally identify the kinetic pathways along which benzene molecule meanders across the solvent and protein and ultimately spontaneously recognizes the deeply buried cavity of L99A T4 Lysozyme at an accurate precision. Our simulation, combined with analysis based on markov state model and free energy calculation, reveals that there are more than one distinct ligand binding pathways. Intriguingly, each of the identified pathways involves the transient opening of a channel of the protein prior to ligand binding. The work will also decipher rich mechanistic details on unbinding kinetics of the ligand as obtained from enhanced sampling techniques.

Mobile Digital Recording: Adequacy of the iRig and iOS Device for Acoustic and Perceptual Analysis of Normal Voice.

Science.gov (United States)

Oliveira, Gisele; Fava, Gaetano; Baglione, Melody; Pimpinella, Michael

2017-03-01

To determine whether the iRig and iOS device recording system is comparable with a standard computer recording system for digital voice recording. Thirty-seven vocally healthy adults, between ages 20 and 62, with a mean age of 33.9 years, 13 males and 24 females, were recruited. Recordings were simultaneously digitalized in an iPad and iPhone using a unidirectional condenser microphone for smartphones/tablets (iRig Mic, IK Multimedia) and in a computer laptop (Dell-Inspiron) using a unidirectional condenser microphone (Samson-CL5) connected to a preamplifier with phantom power. Both microphones were lined up at an equal fixed distance from the subject's mouth. Speech tasks consisted of a sustained vowel "ah" at comfortable pitch/loudness, counting from 1 to 10, and a glissando "ah" from a low to a high note. The samples captured on the iOS devices were transferred via SoundCloud in WAV format, and analyzed using the Praat software. The acoustic parameters measured were mean, min, and max F0, SD F0, jitter local, jitter rap, jitter ppq5, jitter ddp, shimmer local, shimmer local-dB, shimmer apq3, shimmer apq5, shimmer apq11, shimmer dda, NHR, and HNR. There were no statistically significant differences for any parameter and speech task analyzed for both iOS devices as compared with the gold standard computer/preamp system (all P values > 0.050). In addition, there were no statistical differences in the perceptual identification of the recordings among devices (P device may provide reliable digital recording of normal voices. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Heterogeneity and dynamics of the ligand recognition mode in purine-sensing riboswitches.

Science.gov (United States)

Jain, Niyati; Zhao, Liang; Liu, John D; Xia, Tianbing

2010-05-04

High-resolution crystal structures and biophysical analyses of purine-sensing riboswitches have revealed that a network of hydrogen bonding interactions appear to be largey responsible for discrimination of cognate ligands against structurally related compounds. Here we report that by using femtosecond time-resolved fluorescence spectroscopy to capture the ultrafast decay dynamics of the 2-aminopurine base as the ligand, we have detected the presence of multiple conformations of the ligand within the binding pockets of one guanine-sensing and two adenine-sensing riboswitches. All three riboswitches have similar conformational distributions of the ligand-bound state. The known crystal structures represent the global minimum that accounts for 50-60% of the population, where there is no significant stacking interaction between the ligand and bases of the binding pocket, but the hydrogen-bonding cage collectively provides an electronic environment that promotes an ultrafast ( approximately 1 ps) charge transfer pathway. The ligand also samples multiple conformations in which it significantly stacks with either the adenine or the uracil bases of the A21-U75 and A52-U22 base pairs that form the ceiling and floor of the binding pocket, respectively, but favors the larger adenine bases. These alternative conformations with well-defined base stacking interactions are approximately 1-1.5 kcal/mol higher in DeltaG degrees than the global minimum and have distinct charge transfer dynamics within the picosecond to nanosecond time regime. Inside the pocket, the purine ligand undergoes dynamic motion on the low nanosecond time scale, sampling the multiple conformations based on time-resolved anisotropy decay dynamics. These results allowed a description of the energy landscape of the bound ligand with intricate details and demonstrated the elastic nature of the ligand recognition mode by the purine-sensing riboswitches, where there is a dynamic balance between hydrogen bonding

AHP 47: A RIG RGAD PO VISITS LHA SA

Directory of Open Access Journals (Sweden)

Pad ma skyid པདྨ་སྐྱིད།

2017-04-01

Full Text Available My name is Pad ma skyid. I was born in 1981 in Pan yag Community, 'Bo spa Township, Pad ma County, Mgo log Tibetan Autonomous Prefecture, Mtsho sngon (Qinghai Province. I have eight siblings. Growing up in a black yak-hair tent, we spent our days playing with lambs, foals, and calves. We told all sorts of stories when everyone was in bed - stories about King Ge sar, ghosts, marriages, and tricksters. It was a time for my whole family to relax and share. I heard many A rig rgad po stories from my parents, siblings, and guests. A rig rgad po became part of my childhood. These stories bring back many beautiful memories. ...

Consequences of Morphology on Molecularly Imprinted Polymer-Ligand Recognition

Directory of Open Access Journals (Sweden)

Annika M. Rosengren

2013-01-01

Full Text Available The relationship between molecularly imprinted polymer (MIP morphology and template-rebinding over a series of warfarin-imprinted methacrylic acid co(ethylene dimethacrylate polymers has been explored. Detailed investigations of the nature of template recognition revealed that an optimal template binding was obtained with polymers possessing a narrow population of pores (~3–4 nm in the mesopore size range. Importantly, the warfarin-polymer rebinding analyses suggest strategies for regulating ligand binding capacity and specificity through variation of the degree of cross-linking, where polymers prepared with a lower degree of cross-linking afford higher capacity though non-specific in character. In contrast, the co-existence of specific and non-specific binding was found in conjunction with higher degrees of cross-linking and resultant meso- and macropore size distributions.

Equipment available for automating rig operations

International Nuclear Information System (INIS)

McNair, W.L.

1990-01-01

Several manufacturers are producing automated rig equipment, from complete systems to individual functions for existing drilling rigs. Significant improvements in well site time, costs of operations, and improved drilling performance have led drilling contractors to install this equipment on their rigs. This paper details some of the equipment available for automating rigs

{open_quote}Nintendo Rig{close_quote} lets two men do work of three on traditional servicing rig

Energy Technology Data Exchange (ETDEWEB)

Rintoul, B.

1996-01-01

New well servicing rig saves costs and increases safety by using a robot derrickman. The rigs is called the Nintendo Rig, taking the name from the joystick that controls the robot on the racking board 25 feet above the ground. An automated tong/slip package permanently mounted on the front of the rig handles pipe and rods on the ground.

The mobile rig industry

International Nuclear Information System (INIS)

Karlsen, J.K.

1992-08-01

This study is part of the project ''A competitive Norway'', based on the theories and methods presented in the book ''The competitive advantage of nations'', by Michael E. Porter. The rig market may be segmented according to the type of service, the geographical market and the type of equipment. The focus of the report is exploration and appraisal drilling using jackup rigs and semi-submersible rigs in the Northwestern European market. Market shares of Norwegian, other European and US suppliers in the jackup and semi-submerisible market segments on the Norwegian continental shelf and the entire Northwestern market are presented. The main driving force behind the rig demand is the price of oil, but technological trends and changes in relative importance of the various geographical markets are also important. The industry is fairly fragmented on the supplier side, while the oil companies as customers have substantial bargaining power. There are high exit barriers because of the high capital intensity of the business. Combined with a highly volatile demand, this forces the industry through cycles of low capacity utilization and depressed rig day rates. 8 refs., 19 figs., 2 tabs

40th annual Reed rig census

International Nuclear Information System (INIS)

Fitts, R.L.; Stokes, T.A.

1992-01-01

This paper reports that declines characterize the 1992 rig census-in the number of available drilling rigs, in the number of active rigs, in rig utilization rate, in the number of rig owners and in industry optimism. The number of rotary rigs available for U.S. drilling fell by 255 units (11.3%) during the past 12 months, an attrition rate almost four times greater than in 1991. But despite the high attrition, only 59.7% of remaining rigs were working during the time the census was taken. Results of the 1992 census bring emphasis to an industry trend that became apparent in early 1991. The major oil companies, and many independents, continued their exodus form the U.S., and the remaining independents, which were hurt by low natural gas prices and unfavorable tax treatment of intangible drilling costs, were not able to pick u the drilling slack. Consequently, the past year has been disastrous for many U.S. drilling contractors, and the outlook for this industry segment remains bleak

Rig`s electricity to power top drive drilling system

Energy Technology Data Exchange (ETDEWEB)

Liderth, D.

1996-05-01

Permanent magnet brushless electric motors to supply torque to more space-efficient top drive drilling assemblies was the solution designed by Kaman Electromagnetic Corporation, working hand-in-hand with Calgary-based Tesco Drilling Technology, to remedy problems created by the bulkiness of standard hydraulic top drive systems. The biggest advantage of using electric over hydraulic top drive systems is the ability to tap into the rig`s existing power source, which lowers both cost and effort. A better power to weight ratio and reduced maintenance requirements are other desirable advantages.

39th annual Reed rig census

International Nuclear Information System (INIS)

Crowhurst, M.E.; Fitts, R.L.

1991-01-01

This paper reports on cutbacks in U.S. exploration and development drilling during the first half of 1991 which squeezed most of the optimism out of the drilling industry. Just how rough the year has been is underscored by the results of this year's rig census. The number of rotary rigs available for U.S. drilling declined by only 69 units (3%) during the past 12 months. But despite those withdrawals from competition, only 66% of the remaining rigs were working at the time the census was taken. Results of the 1991 census contrasted sharply with the stability and optimism that seemed apparent a year ago when 72% of the available rig fleet met the census definition of active. At that time, the mini-boom in horizontal drilling coupled with tax-credit- driven gas drilling led to a relatively high rig utilization rate and suggested that rig supply and demand might be close to an economically acceptable balance. However, it quickly became apparent in early 1991 that industry optimism was unjustified. Horizontal drilling began to drop and the lowest natural gas prices in 12 years triggered rapid declines in gas drilling. Although oil prices have been relatively stable and above $18 per bbl since January 1989, most major operators have concluded that a better return on investment can be had outside the U.S. and have drastically cut their domestic drilling budgets. These factors, combined with softened energy demand from the worldwide recession, further slowed U.S. drilling. The long awaited balance between rig supply and demand has seemingly slipped away. The 1991 Reed rig census describes an industry facing several more rough years. Details of this year's census include: The available U.S. fleet now stands at 2,251 rigs, down by 69 from the 2,320-unit total in 1990, and the lowest since 1976. Rigs meeting the census definition of active numbered 1,485, down 192 (11.4%) from the 1,677 active rigs counted a year earlier

Drilling rig mast

Energy Technology Data Exchange (ETDEWEB)

Bulgakov, E.S.; Barashkov, V.A.; Lebedev, A.I.; Panin, N.M.; Sirotkin, N.V.

1981-01-07

A drilling rig mast is proposed that contains a portal with a carrier shaft hinged to it and struts with stays. In order to decrease the time expended in the assembly and dessembly of the drilling rig, the portal is constructed from mobile and immobile parts that are connected together by a ball pivot; the immobile section of the portal has a T-shaped recess for directing the mobile section.

iNKT Cells and Their potential Lipid Ligands during Viral Infection

Directory of Open Access Journals (Sweden)

Anunya eOpasawatchai

2015-07-01

Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

Replacement team of mining drilling rigs

OpenAIRE

Hamodi, Hussan; Lundberg, Jan

2014-01-01

This paper presents a practical model to calculate the optimal replacement time (ORT) of drilling rigs used in underground mining. As a case study, cost data for drilling rig were collected over four years from a Swedish mine. The cost data include acquisition, operating, maintenance and downtime costs when using a redundant rig. A discount rate is used to determine the value of these costs over time. The study develops an optimisation model to identify the ORT of a mining drilling rig which ...

RigFit: a new approach to superimposing ligand molecules.

Science.gov (United States)

Lemmen, C; Hiller, C; Lengauer, T

1998-09-01

If structural knowledge of a receptor under consideration is lacking, drug design approaches focus on similarity or dissimilarity analysis of putative ligands. In this context the mutual ligand superposition is of utmost importance. Methods that are rapid enough to facilitate interactive usage, that allow to process sets of conformers and that enable database screening are of special interest here. The ability to superpose molecular fragments instead of entire molecules has proven to be helpful too. The RIGFIT approach meets these requirements and has several additional advantages. In three distinct test applications, we evaluated how closely we can approximate the observed relative orientation for a set of known crystal structures, we employed RIGFIT as a fragment placement procedure, and we performed a fragment-based database screening. The run time of RIGFIT can be traded off against its accuracy. To be competitive in accuracy with another state-of-the-art alignment tool, with which we compare our method explicitly, computing times of about 6 s per superposition on a common day workstation are required. If longer run times can be afforded the accuracy increases significantly. RIGFIT is part of the flexible superposition software FLEXS which can be accessed on the WWW [http:/(/)cartan.gmd.de/FlexS].

Investigation of ‘Head-to-Tail’-Connected Oligoaryl N,O-Ligands as Recognition Motifs for Cancer-Relevant G-Quadruplexes

Directory of Open Access Journals (Sweden)

Natalia Rizeq

2017-12-01

Full Text Available Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C–H activation of the formed oxazoles and their subsequent C–C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, ‘head-to-tail’-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22, the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes. Fluorescence titrations reveal excellent binding affinities of the 7-mer and 6-mer for a Na+-induced antiparallel 22AG G-quadruplex (KD = 0.6 × 10−7 M−1 and 0.8 × 10−7 M−1, respectively, and satisfactory (albeit lower affinities for the 22AG/K+ and Myc2345-Pu22/K+ G-quadruplexes. All ligands tested exhibit substantial selectivity for G-quadruplex versus duplex (ds26 DNA, as evidenced by competitive Förster resonance energy transfer (FRET melting assays. Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology transition of 22AG/K+ G-quadruplex.

Interrogating the Molecular Basis for Substrate Recognition in Serotonin and Dopamine Transporters with High-Affinity Substrate-Based Bivalent Ligands

DEFF Research Database (Denmark)

Andersen, Jacob; Ladefoged, Lucy Kate; Kristensen, Trine N. Bjerre

2016-01-01

insight into substrate recognition in SERT and DAT. An optimized bivalent ligand comprising two serotonin moieties binds SERT with 3,800-fold increased affinity compared to that of serotonin, suggesting that the human transporters have two distinct substrate binding sites. We show that the bivalent...... ligands are inhibitors of SERT and an experimentally validated docking model suggests that the bivalent compounds bind with one substrate moiety in the central binding site (the S1 site), whereas the other substrate moiety binds in a distinct binding site (the S2 site). A systematic study of nonconserved...

Hoisting and rigging manual: Uncontrolled document

Energy Technology Data Exchange (ETDEWEB)

NONE

1991-05-01

This document is a draft copy of a Hoisting and Rigging Manual for the Department of Energy. The manual is divided into ten chapters. The chapter titles follow: terminology and definitions; operator training and qualification; overhead and gantry cranes; mobile cranes; forklift trucks; hoists; hooks; wire rope, slings, and rigging accessories; construction hoisting and rigging equipment requirements; references.

A rigged market

International Nuclear Information System (INIS)

Thomas, M.

2000-01-01

The mobile rig market remains a unique sector of the global upstream oil and gas industry. Big oil is continuing to emerge blinking from the darkness of its recent cash-starved existence to bask in the glory of a resurgent oil price. But the rig sector is once again lagging behind the pace being set by operators as they open up their wallets for new or delayed exploration and production projects. This paper gives statistics on worldwide count and contracts

Development of irradiation rig in HTTR and dosimetry method. I-I type irradiation equipment

Energy Technology Data Exchange (ETDEWEB)

Shibata, Taiju; Kikuchi, Takayuki [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Miyamoto, Satoshi; Ogura, Kazutomo [Japan Atomic Power Co., Tokyo (Japan)

2002-12-01

The High Temperature Engineering Test Reactor (HTTR) is a graphite-moderated, helium gas-cooled test reactor with a maximum power of 30 MW. The HTTR aims not only to establish and upgrade the technological basis for the HTGRs but also to perform the innovative basic research on high temperature engineering with high temperature irradiation fields. It is planned that the HTTR is used to perform various engineering tests such as the safety demonstration test, high temperature test operation and irradiation test with large irradiation fields at high temperatures. This paper describes the design of the I-I type irradiation equipment developed as the first irradiation rig for the HTTR and does the planned dosimetry method at the first irradiation test. It was developed to perform in-pile creep test on a stainless steel with large standard size specimens in the HTTR. It can give great loads on the specimens stably and can control the irradiation temperature precisely. The in-core creep properties on the specimens are measured by newly developed differential transformers and the irradiation condition in the core is monitored by thermocouples and self-powered neutron detectors (SPNDs), continuously. The irradiated neutron fluence is assessed by neutron fluence monitors of small metallic wires after the irradiation. The obtained data at the first irradiation test can strongly be contributed to upgrade the technological basis for the HTGRs, since it is the first direct measurement of the in-core irradiation environments of the HTTR. (author)

Technology trends, energy prices affect worldwide rig activity

International Nuclear Information System (INIS)

Rappold, K.

1995-01-01

The major worldwide offshore rig markets have improved slightly this year, while the onshore markets generally lagged slightly. Offshore rig utilization rates have remained strong worldwide, with some areas reaching nearly 100%. Total worldwide offshore rig (jack ups, semisubmersible, drillships, submersibles, and barges) utilization was about 86%. Offshore drilling activity is driven primarily by oil and natural gas price expectations. Natural gas prices tend to drive North American offshore drilling activity, including the shallow waters in the Gulf of Mexico. International offshore drilling activity and deepwater projects in the Gulf of Mexico are more closely tied to oil prices. The paper discusses US rig count, directional drilling activity, jack up rig demand, semisubmersibles demand, rig replacement costs, and new construction

Rigged Hilbert spaces for chaotic dynamical systems

International Nuclear Information System (INIS)

Suchanecki, Z.; Antoniou, I.; Bandtlow, O.F.

1996-01-01

We consider the problem of rigging for the Koopman operators of the Renyi and the baker maps. We show that the rigged Hilbert space for the Renyi maps has some of the properties of a strict inductive limit and give a detailed description of the rigged Hilbert space for the baker maps. copyright 1996 American Institute of Physics

Learning Inverse Rig Mappings by Nonlinear Regression.

Science.gov (United States)

Holden, Daniel; Saito, Jun; Komura, Taku

2017-03-01

We present a framework to design inverse rig-functions-functions that map low level representations of a character's pose such as joint positions or surface geometry to the representation used by animators called the animation rig. Animators design scenes using an animation rig, a framework widely adopted in animation production which allows animators to design character poses and geometry via intuitive parameters and interfaces. Yet most state-of-the-art computer animation techniques control characters through raw, low level representations such as joint angles, joint positions, or vertex coordinates. This difference often stops the adoption of state-of-the-art techniques in animation production. Our framework solves this issue by learning a mapping between the low level representations of the pose and the animation rig. We use nonlinear regression techniques, learning from example animation sequences designed by the animators. When new motions are provided in the skeleton space, the learned mapping is used to estimate the rig controls that reproduce such a motion. We introduce two nonlinear functions for producing such a mapping: Gaussian process regression and feedforward neural networks. The appropriate solution depends on the nature of the rig and the amount of data available for training. We show our framework applied to various examples including articulated biped characters, quadruped characters, facial animation rigs, and deformable characters. With our system, animators have the freedom to apply any motion synthesis algorithm to arbitrary rigging and animation pipelines for immediate editing. This greatly improves the productivity of 3D animation, while retaining the flexibility and creativity of artistic input.

Endurance test on IR rig for RI production

International Nuclear Information System (INIS)

Chung, Heung June; Youn, Y. J.; Han, H. S.; Hong, S. B.; Cho, Y. G.; Ryu, J. S.

2000-12-01

This report presents the pressure drop, vibration and endurance test results for IR rig for RI production which were desigened and fabricated by KAERI. From the pressure drop test results, it is noted that the flow rate through the IR rig corresponding to the pressure drop of 200 kPa is measured to be about 3.12 kg/sec. Vibration frequency for the IR rig ranges from 13 to 17 Hz. RMS(Root Mean Square) displacement for the IR rig is less than 30 μm, and the maximum displacement is less than 110μm. These experimental results show that the design criteria of IR rig meet the HANARO limit conditions. Endurance test results show that the appreciable fretting wear for the IR rig does not occur, however tiny trace of wear between contact points is observed

Selectivity in ligand recognition of G-quadruplex loops.

Science.gov (United States)

Campbell, Nancy H; Patel, Manisha; Tofa, Amina B; Ghosh, Ragina; Parkinson, Gary N; Neidle, Stephen

2009-03-03

A series of disubstituted acridine ligands have been cocrystallized with a bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups of varying size. The crystal structures show that the diagonal loop in this quadruplex results in a large cavity for these groups, in contrast to the steric constraints imposed by propeller loops in human telomeric quadruplexes. We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds.

Endogenous ligands for C-type lectin receptors: the true regulators of immune homeostasis.

Science.gov (United States)

García-Vallejo, Juan J; van Kooyk, Yvette

2009-07-01

C-type lectin receptors (CLRs) have long been known as pattern-recognition receptors implicated in the recognition of pathogens by the innate immune system. However, evidence is accumulating that many CLRs are also able to recognize endogenous 'self' ligands and that this recognition event often plays an important role in immune homeostasis. In the present review, we focus on the human and mouse CLRs for which endogenous ligands have been described. Special attention is given to the signaling events initiated upon recognition of the self ligand and the regulation of glycosylation as a switch modulating CLR recognition, and therefore, immune homeostasis.

Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

Science.gov (United States)

Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

2015-01-23

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Speech Recognition for the iCub Platform

Directory of Open Access Journals (Sweden)

Bertrand Higy

2018-02-01

Full Text Available This paper describes open source software (available at https://github.com/robotology/natural-speech to build automatic speech recognition (ASR systems and run them within the YARP platform. The toolkit is designed (i to allow non-ASR experts to easily create their own ASR system and run it on iCub and (ii to build deep learning-based models specifically addressing the main challenges an ASR system faces in the context of verbal human–iCub interactions. The toolkit mostly consists of Python, C++ code and shell scripts integrated in YARP. As additional contribution, a second codebase (written in Matlab is provided for more expert ASR users who want to experiment with bio-inspired and developmental learning-inspired ASR systems. Specifically, we provide code for two distinct kinds of speech recognition: “articulatory” and “unsupervised” speech recognition. The first is largely inspired by influential neurobiological theories of speech perception which assume speech perception to be mediated by brain motor cortex activities. Our articulatory systems have been shown to outperform strong deep learning-based baselines. The second type of recognition systems, the “unsupervised” systems, do not use any supervised information (contrary to most ASR systems, including our articulatory systems. To some extent, they mimic an infant who has to discover the basic speech units of a language by herself. In addition, we provide resources consisting of pre-trained deep learning models for ASR, and a 2.5-h speech dataset of spoken commands, the VoCub dataset, which can be used to adapt an ASR system to the typical acoustic environments in which iCub operates.

Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG.

Science.gov (United States)

Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Wilde, Henry

2017-04-03

An increasing number of dog bite victims were being presented to public hospitals in Himachal Pradesh in 2014 amidst virtual non availability of any rabies immunoglobulin (RIG). Only a small quantity of equine rabies immunoglobulin (eRIG) was available from the government owned Central Research Institute (CRI) Kasauli. This available eRIG was used in 269 patients as an emergency response and only for local infiltration of severe bite wounds by suspected rabid dogs. This was followed by rabies vaccination, using the WHO approved intra-dermal Thai Red Cross Society vaccination schedule. A subgroup of 26 patients were later identified who had been severely bitten by laboratory confirmed rabid dogs. They were followed for more than one year and all were found to be alive.

ROLLER RIG TESTING AT THE CZECH TECHNICAL UNIVERSITY

Directory of Open Access Journals (Sweden)

J. Kalivoda

2016-08-01

Full Text Available Purpose. Although the advancements in computer simulation technology have paved way to provide very reliable simulation results, track tests still play an essential role during the process of development and homologation of any railway vehicle. On the other hand, track tests depend on weather conditions, are difficult to organize and are not suitable for testing vehicles in critical situations. On a roller rig, the tested vehicle is longitudinally fixed and a track is replaced by rotating rollers. Such device offer testing of railway vehicle running dynamics in safe and stable laboratory environment. The purpose of an article is to investigate and describe roller rig testing at the Czech technical university in Prague (CTU. Methodology. In the paper it is shown the history of development of the scaled CTU roller rig from the earlier stages until the current projects for which the CTU roller rig is utilized for. The current design of the experimental bogie, roller rig, sensors instrumentation and types of experiments conducted at the CTU roller rig are described in more detail. Findings. Although the differences in vehicle behaviour on a track and a scaled model on a roller rig are not negligible, scaled roller rig experiments are found as a relatively inexpensive way for verification and demonstration of computer simulations results. They are especially useful for verification of multibody system simulations (MBS of entirely new running gear concepts. Originality. The CTU roller rig is currently used for the experiments with active controlled wheelset guidance. According to simulations results published in many papers such systems offer, in principle, better performance compared to conventional passive vehicles. However, utilization and testing of active controlled wheelset guidance on vehicles is still rare. CTU roller rig serves as a tool to verify computer simulations and demonstrate benefits of active wheelset guidance. Practical value

Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation

NARCIS (Netherlands)

Feng, Qian; Langereis, Martijn A; Olagnier, David; Chiang, Cindy; van de Winkel, Roel; van Essen, Peter; Zoll, Jan; Hiscott, John; van Kuppeveld, Frank J M

2014-01-01

Upon viral infections, pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate an antiviral state associated with the production of type I interferons (IFNs) and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by

The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

Science.gov (United States)

Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

2017-07-25

Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

The Winfrith 9MW heat transfer rig

International Nuclear Information System (INIS)

Obertelli, J.D.

1976-01-01

The Winfrith 9MW Rig is used for studying heat transfer and flow resistance in a variety of test sections at system pressures up to 68 bar. The basic rig and its instrumentation are discussed together with the characteristics of the test section design. The rig has been used in studies involving the full scale simulation of Steam Generating Heavy Water (SGHW) fuel assemblies and the paper discusses the measurements made in this type of study. (author)

Rig supervisors

International Nuclear Information System (INIS)

Nordt, D.P.; Stone, M.S.

1992-01-01

This paper helps prepare the inexperienced rig supervisor to manage a drilling operation. It outlines operational-knowledge requirements and optimization concepts for improving drilling performance and lowering drilling costs. It gives guidelines on safety and environmental responsibilities, and provides recommendations on work tools, leadership, and communication

Experimental rigs for MHD studies

International Nuclear Information System (INIS)

Venkataramani, N.; Jayakumar, R.; Iyer, D.R.; Dixit, N.S.

1976-01-01

An MHD experimental rig is a miniature MHD installation consisting of basic equipments necessary for specific investigations. Some of the experimental rigs used in the investigations being carried out at the Bhabha Atomic Research Centre, Bombay (India) are dealt with. The experiments included diagnostics and evaluation of materials in seeded combustion plasmas and argon plasmas. The design specifications, schematics and some of the results of the investigations are also mentioned. (author)

THERMODYNAMICS OF PROTEIN-LIGAND INTERACTIONS AND THEIR ANALYSIS

Directory of Open Access Journals (Sweden)

Rummi Devi Saini

2017-11-01

Full Text Available Physiological processes are controlled mainly by intermolecular recognition mechanisms which involve protein–protein and protein–ligand interactions with a high specificity and affinity to form a specific complex. Proteins being an important class of macromolecules in biological systems, it is important to understand their actions through binding to other molecules of proteins or ligands. In fact, the binding of low molecular weight ligands to proteins plays a significant role in regulating biological processes such as cellular metabolism and signal transmission. Therefore knowledge of the protein–ligand interactions and the knowledge of the mechanisms involved in the protein-ligand recognition and binding are key in understanding biology at molecular level which will facilitate the discovery, design, and development of drugs. In this review, the mechanisms involved in protein–ligand binding, the binding kinetics, thermodynamic concepts and binding driving forces are discussed. Thermodynamic mechanisms involved in a few important protein-ligand binding are described. Various spectroscopic, non-spectroscopic and computational method for analysis of protein–ligand binding are also discussed.

29 CFR 1918.54 - Rigging gear.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Rigging gear. 1918.54 Section 1918.54 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Vessel's Cargo Handling Gear § 1918.54 Rigging gear. (a... other alternate device shall be provided to allow trimming of the gear and to prevent employees from...

A common minimal motif for the ligands of HLA-B*27 class I molecules.

Science.gov (United States)

Barriga, Alejandro; Lorente, Elena; Johnstone, Carolina; Mir, Carmen; del Val, Margarita; López, Daniel

2014-01-01

CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

A common minimal motif for the ligands of HLA-B*27 class I molecules.

Directory of Open Access Journals (Sweden)

Alejandro Barriga

Full Text Available CD8(+ T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

Endurance test of DUPIC irradiation test rig-003

Energy Technology Data Exchange (ETDEWEB)

Moon, J.S; Yang, M.S.; Lee, C.Y.; Ryu, J.S.; Jeon, H.G

2001-04-01

This report presents the pressure drop, vibration and endurance test results for DUPIC Irradiation Test Rig-003 which was design and fabricated by KAERI. From the pressure drop and vibration test results, it is verified that DUPIC Irradiation Test Rig-003 satisfied the limit conditions of HANARO. And, remarkable wear is not observed in DUPIC Irradiation Test Rig-003 during 40 endurance test days.

UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS

Directory of Open Access Journals (Sweden)

Penghua Wang

2013-04-01

Full Text Available RNA viruses are sensed by RIG-I-like receptors (RLRs, which signal through a mitochondria-associated adaptor molecule, MAVS, resulting in systemic antiviral immune responses. Although RLR signaling is essential for limiting RNA virus replication, it must be stringently controlled to prevent damage from inflammation. We demonstrate here that among all tested UBX-domain-containing protein family members, UBXN1 exhibits the strongest inhibitory effect on RNA-virus-induced type I interferon response. UBXN1 potently inhibits RLR- and MAVS-induced, but not TLR3-, TLR4-, or DNA-virus-induced innate immune responses. Depletion of UBXN1 enhances virus-induced innate immune responses, including those resulting from RNA viruses such as vesicular stomatitis, Sendai, West Nile, and dengue virus infection, repressing viral replication. Following viral infection, UBXN1 is induced, binds to MAVS, interferes with intracellular MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. These findings underscore a critical role of UBXN1 in the modulation of a major antiviral signaling pathway.

Field Demonstraton of Existing Microhole Coiled Tubing Rig (MCTR) Technology

Energy Technology Data Exchange (ETDEWEB)

Kent Perry; Samih Batarseh; Sheriff Gowelly; Thomas Hayes

2006-05-09

The performance of an advanced Microhole Coiled Tubing Rig (MCTR) has been measured in the field during the drilling of 25 test wells in the Niobrara formation of Western Kansas and Eastern Colorado. The coiled tubing (CT) rig designed, built and operated by Advanced Drilling Technologies (ADT), was documented in its performance by GTI staff in the course of drilling wells ranging in depth from 500 to nearly 3,000 feet. Access to well sites in the Niobrara for documenting CT rig performance was provided by Rosewood Resources of Arlington, VA. The ADT CT rig was selected for field performance evaluation because it is one of the most advanced commercial CT rig designs that demonstrate a high degree of process integration and ease of set-up and operation. Employing an information collection protocol, data was collected from the ADT CT rig during 25 drilling events that encompassed a wide range of depths and drilling conditions in the Niobrara. Information collected included time-function data, selected parametric information indicating CT rig operational conditions, staffing levels, and field observations of the CT rig in each phase of operation, from rig up to rig down. The data obtained in this field evaluation indicates that the ADT CT rig exhibited excellent performance in the drilling and completion of more than 25 wells in the Niobrara under varied drilling depths and formation conditions. In the majority of the 25 project well drilling events, ROP values ranged between 300 and 620 feet per hour. For all but the lowest 2 wells, ROP values averaged approximately 400 feet per hour, representing an excellent drilling capability. Most wells of depths between 500 and 2,000 feet were drilled at a total functional rig time of less than 16 hours; for wells as deep at 2,500 to 3,000 feet, the total rig time for the CT unit is usually well under one day. About 40-55 percent of the functional rig time is divided evenly between drilling and casing/cementing. The balance of

A new generation drilling rig: hydraulically powered and computer controlled

Energy Technology Data Exchange (ETDEWEB)

Laurent, M.; Angman, P.; Oveson, D. [Tesco Corp., Calgary, AB, (Canada)

1999-11-01

Development, testing and operation of a new generation of hydraulically powered and computer controlled drilling rig that incorporates a number of features that enhance functionality and productivity, is described. The rig features modular construction, a large heated common drilling machinery room, permanently-mounted draw works which, along with the permanently installed top drive, significantly reduces rig-up/rig-down time. Also featured are closed and open hydraulic systems and a unique hydraulic distribution manifold. All functions are controlled through a programmable logic controller (PLC), providing almost unlimited interlocks and calculations to increase rig safety and efficiency. Simplified diagnostic routines, remote monitoring and troubleshooting are also part of the system. To date, two rigs are in operation. Performance of both rigs has been rated as `very good`. Little or no operational problems have been experienced; downtime has averaged 0.61 per cent since August 1998 when the the first of the two rigs went into operation. The most important future application for this rig is for use with the casing drilling process which eliminates the need for drill pipe and tripping. It also reduces the drilling time lost due to unscheduled events such as reaming, fishing and taking kicks while tripping. 1 tab., 6 figs.

Advanced control strategies for a drill rig

International Nuclear Information System (INIS)

Banerjee, A.; Hiller, M.; Fink, B.

1996-01-01

The construction of tunnels is usually undertaken using a combination of blasting and drilling to achieve rock excavation. Easy handling and high accuracy, and thus greater efficiency, in drilling rigs is an essential ingredient of successful competition in the market place. This article describes a cartesian control concept used for a twin boom drill rig. This simplifies the handling of a drilling boom, reduces the duration of a working cycle and increases security. A remote control system has been added to the drill rig to support the operator working in complicated environments. (UK)

Body Language Advanced 3D Character Rigging

CERN Document Server

Allen, Eric; Fong, Jared; Sidwell, Adam G

2011-01-01

Whether you're a professional Character TD or just like to create 3D characters, this detailed guide reveals the techniques you need to create sophisticated 3D character rigs that range from basic to breathtaking. Packed with step-by-step instructions and full-color illustrations, Body Language walks you through rigging techniques for all the body parts to help you create realistic and believable movements in every character you design. You'll learn advanced rigging concepts that involve MEL scripting and advanced deformation techniques and even how to set up a character pipeline.

Gulf of Mexico rig activity up, international lags

International Nuclear Information System (INIS)

Rappold, K.

1994-01-01

Demand for jack up and semisubmersible rigs has improved in the Gulf of Mexico following a decline in activity earlier this year. International drilling activity, however, has shown slight declines in several regions. Relatively firm natural gas prices have helped buoy rig activity in North America. Rig day rates have not followed suit, mainly because of the influx of rigs from weaker international markets. Day rates in the US may not increase until international activity picks up and the world-wide drilling market tightens. Oil prices have hit almost $20/bbl, mainly because of the recent oil worker' strike in Nigeria and good demand. Natural gas prices in the US have hovered around $2.00/MMBTU, and many industry analysts expect gas prices to remain strong over the next few years. This paper gives data on drilling rig counts and crude oil and gas prices in the Gulf of Mexico and onshore

Customization creates more efficient, cleaner rigs

Energy Technology Data Exchange (ETDEWEB)

Budd, G.

2002-08-01

Technological advances in drilling equipment are essential to improving efficiency in the oilpatch; getting the technological upper hand on the competition is no less important for drilling equipment manufacturers than for actors in other sectors of the industry. While off-the-shelf uniformity that reduces unit cost has been the trend in fabricating field gas compression modules, custom manufacturing has become very popular in the rig manufacturing sector. Examples from Crown Energy Technologies and Tesco Corporation, both of Calgary, Aecon Industrial's Edmonton operations, PCL Industrial Construction Ltd of Nisku, and Toromont Process Systems of Houston and Calgary are described to illustrate the widespread demand for customized drilling rigs, including the growing preference for electric drives. Top drive systems, as opposed to rotary drives also have become very popular; six out of ten rigs are sold with electric top drives today compared with fewer than 10 rigs a decade ago. At the same time, Tesco has recently signed a deal with Conoco Inc to construct three revolutionary drilling rigs using Tesco's proprietary Casing Drilling Technology, which uses standard oilfield casing instead of drill pipe, allowing operators to simultaneously drill, case and evaluate oil and gas wells. Aecon and PCL Industrial Construction have had much demand for customized spools and modules particularly from the oil sands industry, while Toromont Process Systems is also expanding its Calgary facilities to meet the demand for its dual gas compression equipment used by power stations for gas compression and co-generation, natural gas refrigeration and specialty gas processing.

Deep water challenges for drilling rig design

Energy Technology Data Exchange (ETDEWEB)

Roth, M [Transocean Sedco Forex, Houston, TX (United States)

2001-07-01

Drilling rigs designed for deep water must meet specific design considerations for harsh environments. The early lessons for rig design came from experiences in the North Sea. Rig efficiency and safety considerations must include structural integrity, isolated/redundant ballast controls, triple redundant DP systems, enclosed heated work spaces, and automated equipment such as bridge cranes, pipe handling gear, offline capabilities, subsea tree handling, and computerized drill floors. All components must be designed to harmonize man and machine. Some challenges which are unique to Eastern Canada include frequent storms and fog, cold temperature, icebergs, rig ice, and difficult logistics. This power point presentation described station keeping and mooring issues in terms of dynamic positioning issues. The environmental influence on riser management during forced disconnects was also described. Design issues for connected deep water risers must insure elastic stability, and control deflected shape. The design must also keep stresses within acceptable limits. Codes and standards for stress limits, flex joints and tension were also presented. tabs., figs.

Innovative technology for a cost-effective land rig

Energy Technology Data Exchange (ETDEWEB)

Mehra, S.; Bryce, T.

1996-05-01

Sedco Forex has recently completed a new land drilling rig, currently deployed in Gabon, that integrates well construction activities with multiskilling to create cost savings across the board in drilling operations. Historically, operators have produced a comprehensive tender package specifying strictly the type and size of individual rig components and the number of personnel required to drill. In this case, the drilling contractor provides a fit-for-purpose rig, consistent with field location, well profile, operator`s priorities, and local constraints.

Innovative technology for a cost-effective land rig

International Nuclear Information System (INIS)

Mehra, S.; Bryce, T.

1996-01-01

Sedco Forex has recently completed a new land drilling rig, currently deployed in Gabon, that integrates well construction activities with multiskilling to create cost savings across the board in drilling operations. Historically, operators have produced a comprehensive tender package specifying strictly the type and size of individual rig components and the number of personnel required to drill. In this case, the drilling contractor provides a fit-for-purpose rig, consistent with field location, well profile, operator's priorities, and local constraints

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

Evolution of Recognition of Ligands from Gram-Positive Bacteria: Similarities and Differences in the TLR2-Mediated Response between Mammalian Vertebrates and Teleost Fish

NARCIS (Netherlands)

Ribeiro, Carla M. S.; Hermsen, Trudi; Taverne-Thiele, Anja J.; Savelkoul, Huub F. J.; Wiegertjes, Geert F.

2010-01-01

We investigated the role of the TLR2 receptor in the recognition of ligands from Gram-positive bacteria in fish. Comparative sequence analysis showed a highly conserved Toll/IL-1 receptor domain. Although the leucine-rich repeat domain was less conserved, the position of the critical peptidoglycan

Computer gaming comes to service rig training

Energy Technology Data Exchange (ETDEWEB)

Mowers, J.

2007-05-15

This article addressed the challenge of providing service rig workers with a good understanding of the tasks and risks involved in the job before they even step out into the field. The product, SimuLynx was presented. SimuLynx is based on video and gaming technology to immerse the user in the service rig work environment with other crew members. The user tries to perform the different steps of a junior floorhand's job while a coach gives directions. The article discussed how the system works. For example, when faced with a task, the user chooses from several options. The coach informs the virtual junior floorhand if the decision was right or wrong. He will also give warnings and let the user realize the consequences of a wrong action. The benefits of the system were also presented. For example, instead of 30 days of on-the-job training, an employee may only need several days after going through the program. Other benefits that were reviewed included reduced accident risk-levels for new workers; higher rig efficiency; and, lower training costs. In addition, a potential recruit can decide if the job is right for him before signing up for an expensive course or starting off with a service rig company. As well, the rig company can decide if someone is suitable before hiring that person. 3 figs.

Enterovirus 2Apro targets MDA5 and MAVS in infected cells

NARCIS (Netherlands)

Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

2014-01-01

RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress

Enterovirus 2Apro targets MDA5 and MAVS in infected cells

NARCIS (Netherlands)

Feng, Qian; Langereis, Martijn A; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M

2014-01-01

UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses

Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene- like receptors, which synergize to induce type I interferon production

DEFF Research Database (Denmark)

Rasmussen, Simon B; Jensen, Søren B; Nielsen, Christoffer

2009-01-01

The innate antiviral response is initiated by pattern recognition receptors, which recognize viral pathogen-associated molecular patterns. Here we show that retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in cooperation with Toll-like receptor (TLR) 9 is required for expression of type I...... interferons (IFNs) after infection with herpes simplex virus (HSV). Our work also identified RNase L as a critical component in IFN induction. Moreover, we found that TLR9 and RLRs activate distinct, as well as overlapping, intracellular signalling pathways. Thus, RLRs are important for recognition of HSV...

Ligand Electron Density Shape Recognition Using 3D Zernike Descriptors

Science.gov (United States)

Gunasekaran, Prasad; Grandison, Scott; Cowtan, Kevin; Mak, Lora; Lawson, David M.; Morris, Richard J.

We present a novel approach to crystallographic ligand density interpretation based on Zernike shape descriptors. Electron density for a bound ligand is expanded in an orthogonal polynomial series (3D Zernike polynomials) and the coefficients from this expansion are employed to construct rotation-invariant descriptors. These descriptors can be compared highly efficiently against large databases of descriptors computed from other molecules. In this manuscript we describe this process and show initial results from an electron density interpretation study on a dataset containing over a hundred OMIT maps. We could identify the correct ligand as the first hit in about 30 % of the cases, within the top five in a further 30 % of the cases, and giving rise to an 80 % probability of getting the correct ligand within the top ten matches. In all but a few examples, the top hit was highly similar to the correct ligand in both shape and chemistry. Further extensions and intrinsic limitations of the method are discussed.

Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

International Nuclear Information System (INIS)

Poór, Miklós; Li, Yin; Matisz, Gergely; Kiss, László; Kunsági-Máté, Sándor; Kőszegi, Tamás

2014-01-01

Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin

Crystal Structures and Physical Properties of Ag(I) Coordination Polymers with Unsymmetrical Dipyridyl Ligand

International Nuclear Information System (INIS)

Lee, Eunji; Ryu, Hyunsoo; Park, Kimin

2013-01-01

Three Ag(I) coordination polymers with the formula [Ag(L)]·(X)·(DMSO) n (X = ClO 4 (1), BF 4 (2), and PF 6 (3), and L = dipyridyl ligand) were prepared and characterized fully their structures. All three compounds are isostructures and stable 2-D honeycomb type coordination polymers, in which 1-D zigzag chains with -(Ag-L)- motif are linked by the argentophilic interactions and the π···π stacking interactions between pyridine rings. The investigation on photophysical properties of all compounds shows that the nature of emission can be attributed to the metal-to-ligand charge transfer as well as the formation of the polymeric structures with restriction of the flexibility of the free ligand. Based on the present solid state results, further investigation on the development and characterization of new coordination polymers using flexible unsymmetrical ligand is in progress. During last two decades, silver coordination polymers based on dipyridyl type ligands have attracted particular interest because of the various intriguing architectures caused by a variety of coordination geometry of Ag(I) ion as well as their potential applications as functional materials

Microchemical synthesis of the serotonin receptor ligand, 125I-LSD

International Nuclear Information System (INIS)

Hartig, P.R.; Krohn, A.M.; Hirschman, S.A.

1985-01-01

The synthesis and properties of 2-[ 125 I]-lysergic acid diethylamide, the first 125 I-labeled serotonin receptor ligand, are described. A novel microsynthesis apparatus was developed for this synthesis. The apparatus employs a micromanipulator and glass micro tools to handle microliter to nanoliter volumes on a microscope stage. This apparatus should be generally useful for the synthesis of radioligands and other compounds when limited amounts of material must be handled in small volumes

The role of the rigged Hilbert space in quantum mechanics

International Nuclear Information System (INIS)

Madrid, Rafael de la

2005-01-01

There is compelling evidence that, when a continuous spectrum is present, the natural mathematical setting for quantum mechanics is the rigged Hilbert space rather than just the Hilbert space. In particular, Dirac's braket formalism is fully implemented by the rigged Hilbert space rather than just by the Hilbert space. In this paper, we provide a pedestrian introduction to the role the rigged Hilbert space plays in quantum mechanics, by way of a simple, exactly solvable example. The procedure will be constructive and based on a recent publication. We also provide a thorough discussion on the physical significance of the rigged Hilbert space

21. century drilling rigs -- Tesco introduces new modular design

Energy Technology Data Exchange (ETDEWEB)

Anon.

1998-10-01

Development of a modular, hydraulic, self-elevating drilling rig, dubbed the `21. century drilling rig` was announced by the Tesco Corporation. The rig equipment is housed in 8 by 20 by 8.5 feet high sea containers that can be handled by a 20-ton oilfield picker. These containers, weighing about 15,000 to 20,000 pounds on average, eliminate the need for heavy and bulky standard oilfield skid buildings, besides avoiding costly over-width and over-weight permits. The containers can be easily shipped around the world at a fraction of the cost of shipping standard oilfield skid buildings. Time for shipping on land is comparable to conventional rigs, but with the added advantage of smaller and lighter loads, promising fewer transportation problems during spring breakup. Tesco also designed and built an 85-foot long, triple-axle, 24-wheel catwalk trailer to transport the top drive, drawworks and double telescoping mast as one unit. Another novel characteristic of this unit is that the hydraulic system is capable of selectable distribution of power to the main functions such as the top drive, drawworks, or mud pump, similar to the electric SCR rig. The rig also features a computerized control system managed by programmable logic controllers. The split crown and split block to facilitate wireline work, are other innovative features worthy of note.

Statistikeren skiftede spor som 49-årig

DEFF Research Database (Denmark)

Sølund, Sune; Rootzén, Helle

2010-01-01

En uddannelse til coach har ændret Helle Rototzens liv. Som 49-årig forlod hun et forskerliv på deltid til fordel for en karriere som DTU's eneste kvindelige institutdirektør.......En uddannelse til coach har ændret Helle Rototzens liv. Som 49-årig forlod hun et forskerliv på deltid til fordel for en karriere som DTU's eneste kvindelige institutdirektør....

Minimal disturbance : Ensign's ADR-1000-CT rig aimed at CBM market

International Nuclear Information System (INIS)

Roche, P.

2005-01-01

Ensign Resource Services Group Inc. has recently designed a light, mobile rig aimed at Western Canada's coalbed methane (CBM) market. With a 1000 metre depth rating, the automated ADR-1000-CT rig can drill with either jointed pipe or 3 and a half-inch coil. Tractor units are used to move the rig to avoid the extra traffic generated by third-party trucks. The rig's self-levelling capability creates less environmental disturbance. Each component works on sites with as much as 2 metres difference in elevation, which reduces the need for earth-moving equipment. As drilling moves closer to farms and acreages, minimal environmental disturbance is crucial to the CBM industry. The rig won a 2005 Alberta government award for innovations in workplace health and safety as the design eliminates many of the tasks where injuries occur on conventional rigs. On conventional rigs, drill-strings are suspended from a travelling block which is suspended from the crown of a large, heavy derrick. With the ADR, hydraulic cylinders bear the weight of the drill string, and the derrick serves mainly to guide the top drive. When drilling only with jointed pipe, the coiled-tubing reel is a separate load so that drilling crews don't have to transport it around on programs requiring only jointed pipe. If coil is needed, the reel can be trucked to the site and plugged in to the rest of the rig. Tubing is expected to last 3 times as long as on a regular coiled-tubing rig, as the reel is positioned directly over the rotary table. The rigs have been used for various drilling projects and have performed satisfactorily with high penetration rates due to their large mud pumps. It was concluded that the ADR-1000-CT rig's hydraulic self-levelling capability and agility are helpful features when drilling in a minimal disturbance environment. 3 figs

A study of natural circulation cooling using a flow visualization rig

International Nuclear Information System (INIS)

Bowman, W.C.; Ferch, R.L.; Omar, A.M.

1985-01-01

A flow visualization rig has been built at Monserco Limited to provide visual insight into the thermalhydraulic phenomena which occur during single phase and two phase thermosyphoning in a figure-of-eight heat transport loop. Tests performed with the rig have provided design information for the scaling and instrumentation of a high pressure rig being investigated for simulating CANDU reactor conditions during natural circulation cooling. A videotape was produced, for viewing at this presentation, to show important thermalhydraulic features of the thermosyphoning process. The rig is a standard figure-of-eight loop with two steam generators and three heated channels per pass. An elevated surge tank open to atmosphere was used for pressure control. Two variable speed pumps provided forced circulation for warming up the rig, and for establishing the desired initial conditions for testing. Test rig power could be varied between 0 and 15 kW

LWR primary coolant pipe rupture test rig

International Nuclear Information System (INIS)

Yoshitoshi, Shyoji

1978-01-01

The rupture test rig for primary coolant pipes is constructed in the Japan Atomic Energy Research Institute to verify the reliability of the primary coolant pipes for both PWRs and BWRs. The planned test items consisted of reaction force test, restraint test, whip test, jet test and continuous release test. A pressure vessel of about 4 m 3 volume, a circulating pump, a pressurizer, a heater, an air cooler and the related instrumentation and control system are included in this test rig. The coolant test condition is 160 kg/cm 2 g, 325 deg C for PWR test, and 70 kg/cm 2 g, saturated water and steam for BWR test, 100 ton of test load for the ruptured pipe bore of 8B Schedule 160, and 20 lit/min. discharge during 20 h for continuous release of coolant. The maximum pit internal pressure was estimated for various pipe diameters and time under the PWR and BWR conditions. The spark rupturing device was adopted for the rupture mechanics in this test rig. The computer PANAFACOM U-300 is used for the data processing. This test rig is expected to operate in 1978 effectively for the improvement of reliability of LWR primary coolant pipes. (Nakai, Y.)

Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach

Directory of Open Access Journals (Sweden)

Fantucci Piercarlo

2010-03-01

Full Text Available Abstract Background GPR17 is a hybrid G-protein-coupled receptor (GPCR activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes (cysteinyl-LTs, and involved in brain damage and repair. Its exploitment as a target for novel neuro-reparative strategies depends on the elucidation of the molecular determinants driving binding of purinergic and leukotrienic ligands. Here, we applied docking and molecular dynamics simulations (MD to analyse the binding and the forced unbinding of two GPR17 ligands (the endogenous purinergic agonist UDP and the leukotriene receptor antagonist pranlukast from both the wild-type (WT receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I to Ile. Results MD suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and extracellular loop (EL 2. The driving interaction involves R255 and the UDP phosphate moiety. To support this hypothesis, steered MD experiments showed that the energy required to unbind UDP is higher for the WT receptor than for R255I. Three potential binding sites for pranlukast where instead found and analysed. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the WT receptor and the R255I receptor were found for the unbinding of pranlukast. Conclusions These data thus suggest that, in contrast to which has been hypothesized for nucleotides, the lack of the R255 residue doesn't affect the binding of pranlukast a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17.

Solvent effect on thermodynamics of Ag(I) coordination to tripodal polypyridine ligands

DEFF Research Database (Denmark)

Del Piero, Silvia; Melchior, Andrea; Menotti, Davide

2009-01-01

  An investigation on the thermodynamics of complex formation between Ag(I) ion and different tripodal ligands (tris[(2-pyridyl)methyl]amine) (TPA) and 6,6'-bis[bis(2-pyridylmethyl)aminomethyl]-2,2'-bipyridine (BTPA) has been carried out in the aprotic solvents dimethylsulfoxide (DMSO) and dimeth......  An investigation on the thermodynamics of complex formation between Ag(I) ion and different tripodal ligands (tris[(2-pyridyl)methyl]amine) (TPA) and 6,6'-bis[bis(2-pyridylmethyl)aminomethyl]-2,2'-bipyridine (BTPA) has been carried out in the aprotic solvents dimethylsulfoxide (DMSO......)ethyl)amine  (Me3TREN) as a result of  combination of structural rigidity of TPA and lower s-donor ability of pyridinic moieties with respect to primary and secondary amines. The same trend is found if the stability of Ag(I) complex with TPA is compared with that of tris(2-(dimethylamino)ethyl)amine  (ME6TREN...... is largely influenced by the different solvational properties of the solvents towards Ag(I) ion rather than by the significative difference in the dielectric constants. Udgivelsesdato: Oktober...

Crystal Structures of Mouse CD1d-IGb3 Complex And Its Cognate Valpha14 T Cell Receptor Suggest a Model for Dual Recognition of Foreign And Self Glycolipids

Energy Technology Data Exchange (ETDEWEB)

Zajonc, D.M.; Saveage, P.B.; Bendelac, A.; Wilson, I.A.; Teyton, L.

2009-05-28

The semi-invariant Valpha14Jalpha18 T cell receptor (TCR) is expressed by regulatory NKT cells and has the unique ability to recognize chemically diverse ligands presented by CD1d. The crystal structure of CD1d complexed to a natural, endogenous ligand, isoglobotrihexosylceramide (iGb3), illustrates the extent of this diversity when compared to the binding of potent, exogenous ligands, such as alpha-galactosylceramide (alpha-GalCer). A single mode of recognition for these two classes of ligands would then appear problematic for a single T cell receptor. However, the Valpha14 TCR adopts two different conformations in the crystal where, in one configuration, the presence of a larger cavity between the two CDR3 regions could accommodate iGb3 and, in the other, a smaller cavity fits alpha-GalCer more snugly. Alternatively, the extended iGb3 headgroup could be 'squashed' upon docking of the TCR and accommodated between the CD1 and TCR surfaces. Thus, the same TCR may adopt alternative modes of recognition for these foreign and self-ligands for NKT cell activation.

Argentina's YPF outlines plan for sale of rigs

International Nuclear Information System (INIS)

Anon.

1992-01-01

This paper reports that state owned Yacimientos Petroliferos Fiscales (YPF) has unveiled the schedule it plans to follow to privatize oil and gas contract drilling in Argentine. YPF proposes to exit the drilling business by selling state owned drilling rigs, drill pipe, and accessories in a series of auctions beginning next month and lasting through first quarter 1993. YPF intends to open bids Dec. 16 for a completion unit and 30 drilling rigs, several working under contract. Bids will be opened during first quarter 1993 for new and used YPF drill pipe and collars, spare equipment and accessories, and an inventory of fishing tools said to be one of the largest in South America. Winners are to be notified immediately after each auction. YPF plans to hand over by Feb. 1, 1993, the rigs sold in December. Companies buying YPF drilling assets in first quarter 1993, the rigs sold in December. Companies buying YPF drilling assets in first quarter 1993 are to assume ownership by Mar. 24, 1993

Essays on bid rigging

NARCIS (Netherlands)

Seres, Gyula

2016-01-01

Manipulating prices in auctions raises antitrust concerns. Collusion lowers the revenue of the auctioneer and creates information rents. Bid rigging is a prevalent phenomenon and the affected market is enormous. Public procurement amounts to between 10 and 25 percent of national GDP in

The development of fuel pins and material specimens mixed loading irradiation test rig in the experimental fast reactor Joyo. The development of the fuel-material hybrid rig

International Nuclear Information System (INIS)

Oyamatsu, Yasuko; Someya, Hiroyuki

2013-02-01

In the experimental fast reactor Joyo, there were many tests using the irradiation rigs that it was possible to be set irradiation conditions for each compartment independently. In case of no alternative fuel element to irradiate after unloading the irradiated compartments, the irradiation test was restarted with the dummy compartment which the fuel elements was not mounted. If the material specimens are mounted in this space, it is possible to use the irradiation space effectively. For these reasons, the irradiation rig (hybrid rig) is developed that is consolidated with material specimens compartment and fuel elements compartment. Fuel elements and material specimens differ greatly with heat generation, so that the most important issue in developing of hybrid rig is being able to distribute appropriately the coolant flow which satisfies irradiation conditions. The following is described by this report. (1) It was confirmed that the flow distribution of loading the same irradiation rig with the compartment from which a flow demand differs could be satisfied. (2) It was confirmed that temperature setting range of hybrid rig could be equivalent to that of irradiation condition. (3) By standardizing the coolant entrance structure of the compartment lower part, the prospect which can perform easily recombination of the compartment from which a type differs between irradiation rigs was acquired. (author)

Crystal structures of a manganese(I and a rhenium(I complex of a bipyridine ligand with a non-coordinating benzoic acid moiety

Directory of Open Access Journals (Sweden)

Sheri Lense

2018-05-01

Full Text Available The structures of two facially coordinated Group VII metal complexes are reported, namely: fac-bromido[2-(2,2′-bipyridin-6-ylbenzoic acid-κ2N,N′]tricarbonylmanganese(I tetrahydrofuran monosolvate, [MnBr(C17H12N2O2(CO3]·C4H8O, I, and fac-[2-(2,2′-bipyridin-6-ylbenzoic acid-κ2N,N′]tricarbonylchloridorhenium(I tetrahydrofuran monosolvate, [ReCl(C17H12N2O2(CO3]·C4H8O, II. In both complexes, the metal ion is coordinated by three carbonyl ligands, a halide ion, and a 2-(2,2′-bipyridin-6-ylbenzoic acid ligand, in a distorted octahedral geometry. In manganese complex I, the tetrahydrofuran (THF solvent molecule could not be refined due to disorder. The benzoic acid fragment is also disordered over two positions, such that the carboxylic acid group is either positioned near to the bromide ligand or to the axial carbonyl ligand. In the crystal of I, the complex molecules are linked by a pair of C—H...Br hydrogen bonds, forming inversion dimers that stack up the a-axis direction. In the rhenium complex II, there is hydrogen bonding between the benzoic acid moiety and a disordered co-crystallized THF molecule. In the crystal, the molecules are linked by C—H...Cl hydrogen bonds, forming layers parallel to (100 separated by layers of THF solvent molecules.

RIG-I Helicase-Independent Pathway in Sendai Virus-Activated Dendritic Cells Is Critical for Preventing Lung Metastasis of AT6.3 Prostate Cancer

Directory of Open Access Journals (Sweden)

Tomonori Kato

2010-11-01

Full Text Available We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV, and proposed a new concept, “immunostimulatory virotherapy,” for cancer immunotherapy. However, there has been little information on the efficacies of thismethod: 1 inmore clinically relevant situations including metastatic diseases, 2 on other tumor types and other animal species, and 3 on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP-activated bone marrow-derived DCs (rSeV/dF-GFP-DC, consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I (rSeV/dF-RIGIC-DC, an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies.

Lapland longspur mortality at an oil well drilling rig site, Laramie County, Wyoming

Science.gov (United States)

Ramirez, Pedro; Dickerson, Kimberly K.; Lindstrom, Jim; Meteyer, Carol U.; Darrah, Scott

2015-01-01

Two hundred fifty-one Lapland longspur (Calcarius lapponicus) carcasses were recovered around an oil well drilling rig in Laramie County, Wyoming, USA, on December 13–14, 2010, apparent victims of a winter storm and “light entrapment” from the lights on the drilling rig during foggy conditions. We found Lapland longspur carcasses distributed around the drilling rig from 33 m to 171 m. Investigators did not find evidence of bird carcasses on the drilling rig deck or equipment immediately adjacent to the drilling rig. We ruled out chemical toxins and disease as a cause of mortality. Weather conditions, the circular depositional pattern of carcasses around the drilling rig, and bird necropsy results led investigators to conclude that the Lapland longspur mortality was the result of the migrating birds entering the area illuminated by the drilling rig lights in freezing fog and the birds repeatedly circling the drilling rig until they fell to the ground in exhaustion and dying from subsequent trauma. Further research is needed to understand how to most effectively adjust lighting of onshore drilling rigs to reduce the potential for avian light entrapment. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Professional development of new rig supervisors a must

International Nuclear Information System (INIS)

Nordt, D.P.; Stone, M.S.

1992-01-01

This paper reports that because the number of drilling personnel has dropped dramatically over the last decade, many operators now face a shortage of competent rig supervisors. To be effective, the rig supervisor must develop a knowledge of drilling operations, apply optimization techniques to improve drilling performance, demand safe work practices, and protect the environment. Petroleum engineering degree programs and industry training programs can teach the rig supervisor specific technical and management skills; however, traditionally, the supervisor trainee shadows an experienced company man to learn how to direct a drilling operation. The success of this method depends not only on the skills and learning capabilities of the trainee but also on the trainer's time, motivation, knowledge, and ability to teach the skills necessary to direct drilling activities

Drilling rig

Energy Technology Data Exchange (ETDEWEB)

Galiopa, A A; Yegorov, E K

1981-01-04

A drilling rig is proposed which contains a tower, lifter in the form of n infinite chain, and mobile rotator with holding device connected to the chain, and pipe holder. In order to accelerate the auxiliary operations to move the drilling string and unloaded rotator, the rotator is equipped with a clamp with means for transverse connection of it to both branches of the chain, while the pipe holders equipped with a clamp with means of connecting it to one of the branches of the chain.

Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

Energy Technology Data Exchange (ETDEWEB)

Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary); Li, Yin; Matisz, Gergely [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kiss, László [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary)

2014-01-15

Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin.

Flow Rate Measurement in Multiphase Flow Rig: Radiotracer and Conventional

International Nuclear Information System (INIS)

Nazrul Hizam Yusoff; Noraishah Othman; Nurliyana Abdullah; Amirul Syafiq Mohd Yunos; Rasif Mohd Zain; Roslan Yahya

2015-01-01

Applications of radiotracer technology are prevalent throughout oil refineries worldwide, and this industry is one of the main users and beneficiaries of the technology. Radioactive tracers have been used to a great extent in many applications i.e. flow rate measurement, RTD, plant integrity evaluation and enhancing oil production in oil fields. Chemical and petrochemical plants are generally continuously operating and technically complex where the radiotracer techniques are very competitive and largely applied for troubleshooting inspection and process analysis. Flow rate measurement is a typical application of radiotracers. For flow measurements, tracer data are important, rather than the RTD models. Research is going on in refining the existing methods for single phase flow measurement, and in developing new methods for multiphase flow without sampling. The tracer techniques for single phase flow measurements are recognized as ISO standards. This paper presents technical aspect of laboratory experiments, which have been carried out using Molybdenum-99 - Mo99 (radiotracer) to study and determine the flow rate of liquid in multiphase flow rig. The multiphase flow rig consists of 58.7 m long and 20 cm diameter pipeline that can accommodate about 0.296 m 3 of liquid. Tap water was used as liquid flow in pipeline and conventional flow meters were also installed at the flow rig. The flow rate results; radiotracer and conventional flow meter were compared. The total count method was applied for radiotracer technique and showed the comparable results with conventional flow meter. (author)

Hot corrosion testing of Ni-based alloys and coatings in a modified Dean rig

Science.gov (United States)

Steward, Jason Reid

Gas turbine blades are designed to withstand a variety of harsh operating conditions. Although material and coating improvements are constantly administered to increase the mean time before turbine refurbishment or replacement, hot corrosion is still considered as the major life-limiting factor in many industrial and marine gas turbines. A modified Dean rig was designed and manufactured at Tennessee Technological University to simulate the accelerated hot corrosion conditions and to conduct screening tests on the new coatings on Ni-based superalloys. Uncoated Ni-based superalloys, Rene 142 and Rene 80, were tested in the modified Dean rig to establish a testing procedure for Type I hot corrosion. The influence of surface treatments on the hot corrosion resistance was then investigated. It was found that grit-blasted specimens showed inferior hot corrosion resistance than that of the polished counterpart. The Dean rig was also used to test model MCrAlY alloys, pack cementation NiAl coatings, and electro-codeposited MCrAlY coatings. Furthermore, the hot corrosion attack on the coated-specimens were also assessed using a statistical analysis approach.

Challenges associated with pre-border management of biofouling on oil rigs.

Science.gov (United States)

Hopkins, Grant A; Forrest, Barrie M

2010-11-01

The potential for oil rigs to transport diverse, reef-like communities around the globe makes them high risk vectors for the inadvertent spread of non-indigenous species (NIS). This paper describes two case studies where a suite of pre-border management approaches was applied to semi-submersible drilling rigs. In the first case study, a drilling rig was defouled in-water prior to departure from New Zealand to Australia. Risk mitigation measures were successful in reducing biosecurity risks to the recipient region, but they resulted in the unintentional introduction of the non-indigenous brown mussel (Perna perna) to New Zealand when the rig was defouled in-water by divers. In the second case study, lessons learned from this high-profile incursion resulted in a more structured approach to pre-border management, and this serves as a useful template for future rig transfers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Study in flow rig by using radiotracer

International Nuclear Information System (INIS)

Widatalla, R. K.

2012-06-01

Application of radioisotope technology have proved itself to be effective techniques for troubleshooting and optimizing industrial process in petrochemical industry In this study gamma scanning technique has been employed for better understanding of malfunctions by using the flow rig system. The scanning were carried out using 9 9mT C gamma radiation source with activity of 1 mCi and quantity of 5 ml to measure the flow rate for the water flow rig The experiment was repeated by reducing the data interval time to get more precise result. The investigations were also carried out using 5 ml of 9 9mT C with activity of 0.3 mCi for measuring the Residence Time Distribution (RTD) inside the flow rig tank which enables calculating the effective volume for the operating tank and its dead volume. The results proved that the technique is sensitive, reliable and can be adopted to investigate industrial reactors. (Author)

A constructive presentation of rigged Hilbert spaces

International Nuclear Information System (INIS)

Celeghini, Enrico

2015-01-01

We construct a rigged Hilbert space for the square integrable functions on the line L2(R) adding to the generators of the Weyl-Heisenberg algebra a new discrete operator, related to the degree of the Hermite polynomials. All together, continuous and discrete operators, constitute the generators of the projective algebra io(2). L 2 (R) and the vector space of the line R are shown to be isomorphic representations of such an algebra and, as both these representations are irreducible, all operators defined on the rigged Hilbert spaces L 2 (R) or R are shown to belong to the universal enveloping algebra of io(2). The procedure can be extended to orthogonal and pseudo-orthogonal spaces of arbitrary dimension by tensorialization.Circumventing all formal problems the paper proposes a kind of toy model, well defined from a mathematical point of view, of rigged Hilbert spaces where, in contrast with the Hilbert spaces, operators with different cardinality are allowed. (paper)

Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

Science.gov (United States)

Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

2008-01-01

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287

Nanoparticle-based receptors mimic protein-ligand recognition

OpenAIRE

Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; Biasi, Federico De; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

2017-01-01

Summary The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the...

Operating experience of a sodium rig following the ingress of oil

Energy Technology Data Exchange (ETDEWEB)

Bell, A C; Mehew, R D; Robertson, C M [UKAEA, Dounreay, Thurso, Caithness, Scotland (United Kingdom)

1980-05-01

The experience of operating the Small Water Leak Rig at Dounreay in the two years following the ingress into the sodium of silicone oil from the pump is reported. The carbon penetration into the rig pipework has been monitored and has been found to agree with a diffusion model. The predictions based on this model have enabled an operating strategy to be determined to allow continued operation of the rig. (author)

Operating experience of a sodium rig following the ingress of oil

International Nuclear Information System (INIS)

Bell, A.C.; Mehew, R.D.; Robertson, C.M.

1980-01-01

The experience of operating the Small Water Leak Rig at Dounreay in the two years following the ingress into the sodium of silicone oil from the pump is reported. The carbon penetration into the rig pipework has been monitored and has been found to agree with a diffusion model. The predictions based on this model have enabled an operating strategy to be determined to allow continued operation of the rig. (author)

Synthesis of 123I-labelled analogues of imidazobenzodiazepine receptor ligands

International Nuclear Information System (INIS)

Katsifis, A.G.; Mattner, F.; McPhee, M.E.; Ridley, D.D.

1999-01-01

Reaction of bromo- or iodo-substituted isatoic anhydrides with N-methylglycine, L-proline or D-proline afforded bromo- or iodo-substituted 1,4-benzodiazepinediones which on condensation with ethyl or t-butyl isocyanoacetates gave ethyl or t-butyl bromo- or iodo-imidazobenzodiazepine carboxylates. These aryl halides were converted into the corresponding tributylstannanes with bis(tributyltin) in the presence of (triphenylphosphine)palladium(0), and the stannanes were treated with sodium ( 123 I)iodide in the presence of chloramine-T to give the required 123 I-labelled analogues of the imidazobenzodiazepine receptor ligands flumazenil and bretazenil. Copyright (1999) CSIRO Australia

Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

DEFF Research Database (Denmark)

Sainudiin, Raazesh; Wong, Wendy Shuk Wan; Yogeeswaran, Krithika

2005-01-01

:transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous...... Bayes approach is used to identify sites that may be important for ligand recognition in these proteins....

Advantages and limitations of remotely operated sea floor drill rigs

Science.gov (United States)

Freudenthal, T.; Smith, D. J.; Wefer, G.

2009-04-01

A variety of research targets in marine sciences including the investigation of gas hydrates, slope stability, alteration of oceanic crust, ore formation and palaeoclimate can be addressed by shallow drilling. However, drill ships are mostly used for deep drillings, both because the effort of building up a drill string from a drill ship to the deep sea floor is tremendous and control on drill bit pressure from a movable platform and a vibrating drill string is poor especially in the upper hundred meters. During the last decade a variety of remotely operated drill rigs have been developed, that are deployed on the sea bed and operated from standard research vessels. These developments include the BMS (Bentic Multicoring System, developed by Williamson and Associates, operated by the Japanese Mining Agency), the PROD (Portable Remotely Operated Drill, developed and operated by Benthic Geotech), the Rockdrill 2 (developed and operated by the British geological Survey) and the MeBo (German abbreviation for sea floor drill rig, developed and operated by Marum, University of Bremen). These drill rigs reach drilling depths between 15 and 100 m. For shallow drillings remotely operated drill rigs are a cost effective alternative to the services of drill ships and have the major advantage that the drilling operations are performed from a stable platform independent of any ship movements due to waves, wind or currents. Sea floor drill rigs can be deployed both in shallow waters and the deep sea. A careful site survey is required before deploying the sea floor drill rig. Slope gradient, small scale topography and soil strength are important factors when planning the deployment. The choice of drill bits and core catcher depend on the expected geology. The required drill tools are stored on one or two magazines on the drill rig. The MeBo is the only remotely operated drill rig world wide that can use wire line coring technique. This method is much faster than conventional

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

Directory of Open Access Journals (Sweden)

Stéphanie Pérot

Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

Science.gov (United States)

Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

2013-01-01

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

Computers make rig life extension an option

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-10-01

The worldwide semisubmersible drilling rig fleet is approaching retirement. But replacement is not an attractive option even though dayrates are reaching record highs. In 1991, Schlumberger Sedco Forex managers decided that an alternative might exist if regulators and insurers could be convinced to extend rig life expectancy through restoration. Sedco Forex chose their No. 704 semisubmersible, an 18-year North Sea veteran, to test their process. The first step was to determine what required restoration, meaning fatigue life analysis of each weld on the huge vessel. If inspected, the task would be unacceptably time-consuming and of questionable accuracy. Instead a suite of computer programs modeled the stress seen by each weld, statistically estimated the sea states seen by the rig throughout its North Sea service and calibrated a beam-element model on which to run their computer simulations. The elastic stiffness of the structure and detailed stress analysis of each weld was performed with ANSYS, a commercially available finite-element analysis program. The use of computer codes to evaluate service life extension is described.

Developmental test report, assessment of XT-70E percussion drill rig operation in tank farms

International Nuclear Information System (INIS)

Dougherty, L.F.

1996-01-01

The following report documents the testing of the XT-70E percussion drill rig for use in the 241-SX Tank Farm. The test is necessary to support evaluation of the safety and authorization level of the proposed activity of installing up to three new drywells in the 241- SX Tank Farm. The proposed activity plans to install drywells by percussion drilling 7 inch O.D./6 inch I.D. pipe in close proximity of underground storage tanks and associated equipment. The load transmitted from the drill rig's percussion hammer through the ground to the tank structure and equipment is not known and therefore testing is required to ensure the activity is safe and authorized

The laboratory test rig with miniature jet engine to research aviation fuels combustion process

Directory of Open Access Journals (Sweden)

Gawron Bartosz

2015-12-01

Full Text Available This article presents laboratory test rig with a miniature turbojet engine (MiniJETRig – Miniature Jet Engine Test Rig, that was built in the Air Force Institute of Technology. The test rig has been developed for research and development works aimed at modelling and investigating processes and phenomena occurring in full scale jet engines. In the article construction of a test rig is described, with a brief discussion on the functionality of each of its main components. Additionally examples of measurement results obtained during the realization of the initial tests have been included, presenting the capabilities of the test rig.

IT that works on the rig floor : computers on drilling rigs need to be certified and built with features that can handle the environment

Energy Technology Data Exchange (ETDEWEB)

Balsaver, N.

2010-07-15

This article discussed the design challenges faced in developing hazardous-location computers for rig-floor use and other recently introduced products from Laversab. Rig-floor computers must not only be certified as Zone-1 or Zone-2 compliant but must also have features that make them work dependably in an extreme environment, including a wide operating temperature range, an ability to withstand severe vibration, immunity to salt fog, a viewable display in bright daylight, networking capability, USB and serial interfaces, and touch screens. Size and weight has been a major obstacle, but recent innovations have made Zone-1 computers intrinsically safe (IS), making them much smaller and lighter. Wireless networking eliminates the need for installing copper and fibre-optic cabling, but the wireless interface must be strong enough to overcome the many obstructions that are typically present on oil rigs. The computer models described, including a Driller's Display designed to be IS for Zone-1 applications and a Directional MWD Surface System designed for Zone-2 applications, provide solutions to the challenges of a working rig-floor environment. 3 figs.

A Universal Rig for Supporting Large Hammer Drills: Reduced Injury Risk and Improved Productivity.

Science.gov (United States)

Rempel, David; Barr, Alan

2015-10-01

Drilling holes into concrete with heavy hammer and rock drills is one of the most physically demanding tasks performed in commercial construction and poses risks for musculoskeletal disorders, noise induced hearing loss, hand arm vibration syndrome and silicosis. The aim of this study was to (1) use a participatory process to develop a rig to support pneumatic rock drills or large electric hammer drills in order to reduce the health risks and (2) evaluate the usability of the rig. Seven prototype rigs for supporting large hammer drills were developed and modified with feedback from commercial contractors and construction workers. The final design was evaluated by laborers and electricians (N=29) who performed their usual concrete drilling with the usual method and the new rig. Subjective regional fatigue was significantly less in the neck, shoulders, hands and arms, and lower back) when using the universal rig compared to the usual manual method. Usability ratings for the rig were significantly better than the usual method on stability, control, drilling, accuracy, and vibration. Drilling time was reduced by approximately 50% with the rig. Commercial construction contractors, laborers and electricians who use large hammer drills for drilling many holes should consider using such a rig to prevent musculoskeletal disorders, fatigue, and silicosis.

Systematic Introduction of Aromatic Rings to Diphosphine Ligands for Emission Color Tuning of Dinuclear Copper(I) Iodide Complexes.

Science.gov (United States)

Okano, Yuka; Ohara, Hiroki; Kobayashi, Atsushi; Yoshida, Masaki; Kato, Masako

2016-06-06

We have newly synthesized two solution-stable luminescent dinuclear copper(I) complexes, [Cu2(μ-I)2(dpppy)2] (Cu-py) and [Cu2(μ-I)2(dpppyz)2] (Cu-pyz), where dpppy = 2,3-bis(diphenylphosphino)pyridine and dpppyz = 2,3-bis(diphenylphosphino)pyrazine, using chelating diphosphine ligands composed of N-heteroaromatic rings. X-ray analysis clearly indicates that the molecular structures of Cu-py and Cu-pyz are almost identical with that of the parent complex, [Cu2(μ-I)2(dppb)2] [Cu-bz; dppb = 2,3-bis(diphenylphosphino)benzene]. Complexes Cu-py and Cu-pyz exhibit luminescence [emission quantum yield (Φem) = 0.48 and 0.02, respectively] in the solid state at 298 K. A wide emission color tuning, from 497 to 638 nm (energy = 0.55 eV, with an emission color ranging from green to reddish-orange), was achieved in the solid state by the introduction of pyridinic N atoms into the bridging phenyl group between the two diphenylphosphine groups. Density functional theory calculations suggest that the emission could originate from the effective combination of the metal-to-ligand charge-transfer excited state with the halide-to-ligand charge-transfer excited state. Thus, the emission color change is due to stabilization of the π* levels of the central aryl group in the diphosphine ligand. Furthermore, these copper(I) complexes exhibit thermally activated delayed fluorescence at 298 K because of the small singlet-triplet energy difference (ΔE = 523 and 564 cm(-1) for Cu-py and Cu-pyz, respectively). The stability of these complexes in chloroform, due to the rigid bonds between the diphosphine ligands and the Cu(I) ions, enables the preparation of emissive poly(methyl methacrylate) films by the solution-doping technique.

Endurance test for IR rig for RI production assembly (test procedure)

International Nuclear Information System (INIS)

Chung, Heung June; Ryu, Jeong Soo

2000-08-01

This test procedure details the test loop, test method, and test procedure for pressure drop, vibration and endurance test of IR Rig for RI production. From the pressure drop test, the hydraulic design requirements of the capsule are verified. HANARO limit condition is checked and the compatibility with HANARO core is verified. From flow induced vibration test vibration frequency and displacement are investigated. The wear of IR Rig is investigated through endurance test, and these data are used to evaluate the expected wear at maximum resident time of the IR Rig for RI production

PANP is a novel O-glycosylated PILR{alpha} ligand expressed in neural tissues

Energy Technology Data Exchange (ETDEWEB)

Kogure, Amane [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Shiratori, Ikuo [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Wang, Jing [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Lanier, Lewis L. [Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 (United States); Arase, Hisashi, E-mail: arase@biken.osaka-u.ac.jp [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); JST CREST, Saitama 332-0012 (Japan)

2011-02-18

Research highlights: {yields} A Novel molecule, PANP, was identified to be a PILR{alpha} ligand. {yields} Sialylated O-glycan structures on PANP were required for PILR{alpha} recognition. {yields} Transcription of PANP was mainly observed in neural tissues. {yields} PANP seems to be involved in immune regulation as a ligand for PILR{alpha}. -- Abstract: PILR{alpha} is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR{alpha} to its ligand CD99 is involved in immune regulation; however, whether there are other PILR{alpha} ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR{alpha}. Transcription of PANP was mainly observed in neural tissues. PILR{alpha}-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR{alpha} reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR{alpha}.

Two novel mixed-ligand complexes containing organosulfonate ligands.

Science.gov (United States)

Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

2008-07-01

The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

The connection between metal ion affinity and ligand affinity in integrin I domains

DEFF Research Database (Denmark)

Vorup-Jensen, Thomas; Waldron, TT; Astrof, N

2007-01-01

Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes withi...

The economics and related factors involved in the replacement of land drilling rigs

International Nuclear Information System (INIS)

Holm, D.W.

1992-01-01

The principal purpose of this paper is to evaluate the construction cost of a medium depth land rig made from all NEW components and the resulting effect on drilling contractor economics. This evaluation will include an inventory of the proposed NEW rig, with a comparison of the costs of a similar rig built in 1981-1982, and a similar rig built from existing UNUSED equipment in manufacturer's current inventory. The paper discusses the problems encountered in obtaining quotations for NEW equipment from manufacturers, the current attitudes of equipment manufacturers, the potential for problems from the use of existing UNUSED equipment in manufacturers inventory, and finally the possible effect on the day rates needed to justify the construction of NEW land rigs. Probable reasons for the attitudes of the manufacturing industry and alternatives for the drilling contractor will be reviewed

Meso-Helical Ag(I) Coordination Polymer Based on a Pyridylimidazole Ligand

International Nuclear Information System (INIS)

Kang, Youngjin; Kim, Jinho; Lee, Eunji; Park, Ki-Min; Moon, Suk-Hee

2016-01-01

In the fields of material science and metallosupramolecular chemistry, coordination polymers with various helical types have been extensively explored because of their charming structures, and their potential applications in material chemistry. Among them, meso-helical coordination polymers consisting of achiral 1D strands, which are generally constructed by a crystallographic inversion symmetry, are relatively rare. The coordination polymer 1 exhibits a rare one-dimensional meso-helical chain topology constructed by its internal inversion symmetry. The skeleton of this meso-helical chain is preserved up to 300°C. The complexation of silver(I) ion to the free pyim ligand give rise to the enhanced photoluminescence intensity and slightly blue-shifted emission maximum, originated from intraligand (IL) π[BOND]π* transition and rigidochromic effect. Further exploration of complexation of this ligand with other transition metal ions is currently in progress

A power recirculating test rig for ball screw endurance tests

Directory of Open Access Journals (Sweden)

Giberti Hermes

2016-01-01

Full Text Available A conceptual design of an innovative test rig for endurance tests of ball screws is presented in this paper. The test rig layout is based on the power recirculating principle and it also allows to overtake the main critical issues of the ball screw endurance tests. Among these there are the high power required to make the test, the lengthy duration of the same and the high loads between the screw and the frame that holds it. The article describes the test rig designed scheme, the kinematic expedients to be adopted in order to obtain the required performance and functionality and the sizing procedure to choose the actuation system.

Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis.

NARCIS (Netherlands)

Roelofs, M.F.; Boelens, W.C.; Joosten, L.A.B.; Abdollahi-Roodsaz, S.; Geurts, J.; Wunderink, L.U.; Schreurs, B.W.; Berg, W.B. van den; Radstake, T.R.D.J.

2006-01-01

Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in

Deprotonation induced ligand-to-metal electron transfer: Synthesis of a mixed-valence Rh(-I,I) dinuclear compound and its reaction with dioxygen

NARCIS (Netherlands)

Tejel, C.; Ciriano, M.A.; del Río, M.P.; van den Bruele, F.J.; Hetterscheid, D.G.H.; Tsichlis i Spithas, N.; de Bruin, B.

2008-01-01

Treatment of bis(2-picolyl)amine (bpa) with [{Rh(nbd)(mu-OMe))(2)] leads to unexpected and unique redox asymmetric dinuclear Rh-I, Rh+I complex [{Rh(ndb)}(2)(bpa-2H)] (2) with a pi-coordinating imine bound to a tetrahedral low valent rhodate(-I). Mono-oxygenation of the deprotonated bpa ligand in 2

MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

Directory of Open Access Journals (Sweden)

Qian Feng

2012-11-01

Full Text Available RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C, a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.

Saving money on rig refurbishments through foreign trade zones or duty-drawback

International Nuclear Information System (INIS)

Ward, R.J. Jr.

1997-01-01

The recent boom in day rates for rigs capable of drilling in deep water and harsh environments has created a frenzy of rig refurbishment activity in shipyards located in US Gulf states. In most instances, the destination for the rigs upon completion is the US Outer Continental Shelf (USOCS) in the Gulf of Mexico. The problem faced by contractors/operators planning to use US shipyards is that this circumstance has caused difficulty in shielding rigs and their foreign-sourced components from US Customs duties. Under US Customs law, a bona fide exportation requires severance from US commerce and joining to the commerce of some foreign country or, in the case of a vessel supply, a qualifying international voyage. The USOCS does not qualify as an exportation, nor do movements to drilling sites located on it qualify as an international voyage. Described here are two possible solutions to this economic dilemma and an example of how the foreign trade zone solution was applied by Global marine in its plans for upgrading some of its semisubmersible drilling rigs for deepwater USOCS work

TITAN - a 9 MW, 179 bar pressurised water rig

International Nuclear Information System (INIS)

Mogford, D.J.; Lee, D.H.

1987-02-01

The report describes the TITAN rig built at Winfrith for thermal hydraulic experiments with water at up to 179 bar pressure. A power supply of 9 MW is available. The report describes three typical experiments that show the versatility of the rig. The first is a 25 rod pressurized water reactor fuel bundle critical heat flux experiment, the second is a parallel channel evaporator test and the third is a model jet pump test. (author)

Speeding up : new Atlas Copco rig meant to cut non-drilling time

Energy Technology Data Exchange (ETDEWEB)

Roche, P.

2009-06-15

Automation has significantly reduced the time needed to drill shallow to medium-depth wells. The time it takes for a drill to reach the production zone is decreasing because newly developed hydraulic systems are able to maintain a constant pace. However, a great deal of time is still consumed by demobilization, transportation and setting up to drill the next well. Atlas Copco Drilling Solutions, a Swedish-based global maker of industrial equipment such as mining and mineral exploration rigs, designed a new Predator drilling system that consists of a mobile rig, a substructure and a pipe-handling skate. The Predator drilling system reduces non-drilling time and the associated costs. This article described the design of this new drilling system with particular reference to how it combines the mobile rig, the substructure and the pipe-handling skate into a three-load package. In order to reduce rig weight and improve mobility, the system is designed so that the table, master bushing, hydraulic slips and iron roughneck are part of the substructure that travel together. The rig has a working hook load capacity of 200,000 pounds, translating into a nominal depth capacity of 8,000 to 10,000 feet. The article also described the mounting of the rig, maneuverability, hydraulic control, and pipe-handling safety. Its various components were also described. 1 ref., 1 fig.

Dual Recognition of Human Telomeric G-quadruplex by Neomycin-anthraquinone Conjugate

Science.gov (United States)

Ranjan, Nihar; Davis, Erik; Xue, Liang

2013-01-01

The authors report the recognition of a G-quadruplex formed by four repeat human telomeric DNA with aminosugar intercalator conjugates. The recognition of G-quadruplex through dual binding mode ligands significantly increased the affinity of ligands for G-quadruplex. One such example is a neomycin-anthraquinone 2 which exhibited nanomolar affinity for the quadruplex, and the affinity of 2 is nearly 1000 fold higher for human telomeric G-quadruplex DNA than its constituent units, neomycin and anthraquinone. PMID:23698792

Robotics Test Rig

International Nuclear Information System (INIS)

Schuurmans, P.

2007-01-01

The experimental Accelerator Driven System XT-ADS is being developed within the European 6th framework programme EUROTRANS using the MYRRHA DRAFT-2 as starting point. The aim for the XT-ADS is to demonstrate the feasibility of the ADS concept at reasonable power levels and to serve as a high performance, multi-purpose experimental irradiation device. One of the fundamental design options that has been taken is to do all maintenance and in-service inspection and repair duties by remote handling. Outside the XT-ADS vessel in a controlled though radio-active environment, remote handling concepts as those already in use at e.g. the Joint European Torus (JET) can be used. Extrapolation to remote handling inside the lead-bismuth eutectic filled main vessel of the XT-ADS is in principle feasible as was shown in a 2003 study performed by Oxford Technologies ltd for the case of MYRRHA. Nevertheless, it is clear that all critical remote handling components need to be qualified for use in liquid LBE. Thus, as a first step, a proof of principle (POP) experimental test rig is require. The principal goal of this work is to identify the critical technological issues that must be resolved to allow operation of remote handling manipulators inside the LBE filled main vessel of the XT-ADS and to propose a concept design and specification catalogue for a proof of principle test rig that is able to experimentally verify the main aspects of manipulator design

Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells.

Directory of Open Access Journals (Sweden)

Elena Lorente

Full Text Available The transporter associated with antigen processing (TAP translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.

Silver(I) and copper(I) complexes with the closo-decaborate anion B10H102- as a ligand

International Nuclear Information System (INIS)

Malinina, E.A.; Zhizhin, K.Yu.; Polyakova, I.N.; Lisovskij, M.V.; Kuznetsov, N.T.

2002-01-01

Studying the process of silver(I) and copper(I) complexing with closo-borate anion B 10 H 10 2- it is determined that the last can to play a role of intraspherical ligand forming stable coordination compounds of two types: Cat[MB 10 H 10 ] and [M 2 B 10 H 10 ] (M=Ag(I), Cu(I)). In these compounds the bond metal-boron skeleton is realized by means of formation of three-center bonds M-H-B. Structure of the complexes Cs[AgB 10 H 10 ] and [(C 2 H 5 ) 3 NH][AgB 10 H 10 ] and possible mechanism of their formation are discussed [ru

Testing of elastomer seals using small-size rigs

International Nuclear Information System (INIS)

Leeks, C.W.E.; Dunford, B.; Barnfield, J.H.; Gray, I.L.S.

1997-01-01

This paper looks at the use of small size seal leakage test rigs to demonstrate the compliance of full size container seals against the IAEA Transport Regulation's limits for activity release for normal transport and accident conditions. The detailed requirements of the regulations are discussed and it is concluded that an appropriate test programme to meet these requirements using only small size test rigs, can normally be set up and carried out on a relatively short time scale. It is important that any small test rigs should be designed to represent the relevant features of the seal arrangement and the overall test programme should cover all of the conditions, specified by the regulations, for the type, classification and contents of the container under consideration. The parameters of elastomer O-rings, which affect their sealing ability, are considered and those which are amenable to small scale testing or have to be modelled at full size are identified. Generally, the seals used in leakage tests have to be modelled with a full size cross-section but can have a reduced peripheral length. (Author)

Automatic X-ray television rig for high-speed radiography of polycrystals

International Nuclear Information System (INIS)

Bezbakh, V.D.; Garasim, Yu.A.; Oshkaderov, S.P.; Pet'kov, V.V.

1993-01-01

The high-speed radiography method is used for studying the phase and structural transformation in metals and alloys during rapid changes in temperature. In order to improve the effectiveness of this method the Institute of Metal Physics, Ukrainian Academy of Sciences, has developed an automatic rig for high-speed radiography of polycrystalline materials using a television method for recording the x-ray diffraction patterns. The rig, described here, consists of an x-ray block, a vacuum chamber, a device for programmed electro-contact heating of specimens, a system for imaging and scanning x-ray diffraction patterns, and a system for collecting and analyzing the data. Focusing is carried out by the Zeeman-Bolin method. The new rig helps to significantly reduce the recording time and ensures adequate quality and reliability of the recorded diffraction image over a wide range of temperatures. Data using the rig is presented for high-speed radiography for cooling a specimen of G20 steel. 4 refs., 4 figs

Experimental Analysis of Mast Lifting and Bending Forces on Vibration Patterns Before and After Pinion Reinstallation in an OH-58 Transmission Test Rig

Science.gov (United States)

Huff, Edward M.; Lewicki, David G.; Tumer, Irem Y.; Decker, Harry; Barszez, Eric; Zakrajsek, James J.; Norvig, Peter (Technical Monitor)

2000-01-01

As part of a collaborative research program between NASA Ames Research Center (ARC), NASA Glenn Research Center (GRC), and the US Army Laboratory, a series of experiments is being performed in GRC's 500 HP OH-58 Transmission Test Rig facility and ARC's AH-I Cobra and OH-58c helicopters. The findings reported in this paper were drawn from Phase-I of a two-phase test-rig experiment, and are focused on the vibration response of an undamaged pinion gear operating in the transmission test rig. To simulate actual flight conditions, the transmission system was run at three torque levels, as well as two mast lifting and two mast bending levels. The test rig was also subjected to disassembly and reassembly of the main pinion housing to simulate the effect of maintenance operations. An analysis of variance based on the total power of the spectral distribution indicates the relative effect of each experimental factor, including Wong interactions with torque. Reinstallation of the main pinion assembly is shown to introduce changes in the vibration signature, suggesting the possibility of a strong effect of maintenance on HUMS design and use. Based on these results, further research will be conducted to compare these vibration responses with actual OH58c helicopter transmission vibration patterns.

Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.

Directory of Open Access Journals (Sweden)

Gediminas Matulis

2010-06-01

Full Text Available Invariant Natural Killer T cells (iNKT are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.

PNNL Hoisting and Rigging Manual

Energy Technology Data Exchange (ETDEWEB)

Haynie, Todd O.; Fullmer, Michael W.

2008-12-29

This manual describes the safe and cost effective operation, inspection, maintenance, and repair requirements for cranes, hoists, fork trucks, slings, rigging hardware, and hoisting equipment. It is intended to be a user's guide to requirements, codes, laws, regulations, standards, and practices that apply to Pacific Northwest National Laboratory (PNNL) and its subcontractors.

Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in the Prostate-Specific G-Protein Coupled Receptor (PSGR).

Science.gov (United States)

Wolf, Steffen; Jovancevic, Nikolina; Gelis, Lian; Pietsch, Sebastian; Hatt, Hanns; Gerwert, Klaus

2017-11-22

We analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor with a known chemically near identic antagonist/agonist pair, α- and β-ionone. Using a combined theoretical and experimental approach, we propose that this receptor is activated by a ligand-induced rearrangement of a protein-internal hydrogen bond network. Surprisingly, this rearrangement is not induced by interaction of the ligand with the network, but by dynamic van der Waals contacts of the ligand with the involved amino acid side chains, altering their conformations and intraprotein connectivity. Ligand recognition in this GPCR is therefore highly stereo selective, but seemingly lacks any ligand recognition via polar contacts. A putative olfactory receptor-based drug design scheme will have to take this unique mode of protein/ligand action into account.

A Dynamic Behavior of the Nuclear Test Rig with Coolant using the Fluid-Structural interaction Analysis

Energy Technology Data Exchange (ETDEWEB)

Yang, Tae-Ho; Hong, Jintae; Ahn, Sung-Ho; Joung, Chang-Young; Jang, Seo-Yun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Yeon, Kon-Whi [Chungnam National University, Daejeon (Korea, Republic of)

2016-10-15

In this paper, the dynamic behavior of the test rig in the coolant flow simulator is evaluated by using the 2-way fluid-structural interaction analysis. The maximum value and location of the deformation and equivalent stress in the test rig is confirmed. The fluid-structural interaction analysis is applied to perform the fluid and structural analysis A fluid-structure interaction analysis is used to simulate the relationship between the deformation and hydraulic pressure. There are two types of fluid-structural interaction analysis. One is a 1-way direction analysis in which the hydraulic pressure is calculated by a CFD and transmitted to the surface of the structure, and a structural analysis is then performed. The other is a 2-way direction analysis that is performed by changing the data between the deformation of the structural and pressure of the coolant water for every time step. The location of the maximum deformation of the test rig is the bottom parts of the test rig. It is expected that the equivalent stress of the test rig is occurred. The maximum equivalent stress in the test rig under the circulation of the coolant is 90.1 MPa. The location of the maximum stress in the test rig is the connect part between the fuel rod and flow divider. A safety factor on the test rig is 3, approximately. The deformation motion of the test rig at the bottom part of the test rig is caused about the fluid-induced vibration. A test on the fluid-induced vibration of the test rig will be performed and compared with results of the analysis in further paper.

Technical and economic evaluation of selected compact drill rigs for drilling 10,000 foot geothermal production wells

Energy Technology Data Exchange (ETDEWEB)

Huttrer, G.W. [Geothermal Management Company, Inc., Frisco, CO (United States)

1997-11-01

This report summarizes the investigation and evaluation of several {open_quotes}compact{close_quotes} drill rigs which could be used for drilling geothermal production wells. Use of these smaller rigs would save money by reducing mobilization costs, fuel consumption, crew sizes, and environmental impact. Advantages and disadvantages of currently-manufactured rigs are identified, and desirable characteristics for the {open_quotes}ideal{close_quotes} compact rig are defined. The report includes a detailed cost estimate of a specific rig, and an evaluation of the cost/benefit ratio of using this rig. Industry contacts for further information are given.

Cellular uptake, nuclear localization and cytotoxicity of 125I-labelled DNA minor groove binding ligands in K562, human erythroleukaemia cells

International Nuclear Information System (INIS)

Karagiannis, T.C.; Lobachevsky, P.N.; Martin, R.F.

2000-01-01

Full text: Iodine-125 decays by orbital electron capture and internal conversion resulting in the emission of numerous Auger electrons which produce a highly localised radiochemical damage in the immediate vicinity of the site of decay. Given the requirement to deliver 125 I to the nuclear DNA, a minor groove binding bibenzimidazole, 125 I-iodoHoechst 33258 was investigated. It has been noted that this analogue may be prone to de-iodination in vitro and in vivo, given the presence of an orthoiodophenol moiety which is analogous to that in thyroxins. Therefore, an 125 I -iodoHoechst analogue without the hydroxyl group was also studied. The 125 I -iodoHoechst 33258 analogue was prepared by direct iodination of Hoechst 33258 and 125 I iodoHoechst was prepared by demetallation of a trimethylstannyl precursor. DNA binding studies indicated that both iodo-analogues bind to calf thymus DNA, K D = 89 ± 30nM, n = 0.018 bp - 1 for iodoHoechst 33258 and K D = 121 ± 31nM, n = 0.024 bp -1 for iodoHoechst. Similarly, nuclear localization following incubation with 5μM of either ligand at 37 deg C was observed in K562 cells by fluorescence microscopy. Flow cytometry was used to investigate the kinetics of drug uptake and efflux in K562 cells. The results indicated that when 10 6 cells were incubated with 5μM ligand at 37 deg C, the uptake reached a plateau at approximately 43 minutes for iodoHoechst 33258 and approximately 52 minutes for iodoHoechst. Ligand efflux results indicated two-phase kinetics. The initial phase which involves 50-60% of drug was characterised by a half-life time (t 1/2 ) of 55.4 minutes for efflux of iodoHoechst 33258 and a t 1/2 of 10.3 minutes for efflux of iodoHoechst, at 37 deg C. Furthermore, the results suggested that the DNA binding sites in a 10 6 cell/ml suspension were saturated by incubation with 3μM iodoHoechst 33258 and 5μM iodoHoechst. In the initial cytotoxicity experiments using 125 I-iodoHoechst 33258, K562 cells were incubated for 1

Pseudomonas Evades Immune Recognition of Flagellin in Both Mammals and Plants

Science.gov (United States)

Bardoel, Bart W.; van der Ent, Sjoerd; Pel, Michiel J. C.; Tommassen, Jan; Pieterse, Corné M. J.; van Kessel, Kok P. M.; van Strijp, Jos A. G.

2011-01-01

The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5) in mammals and flagellin-sensitive 2 (FLS2) in plants. Activation of these immune systems via flagellin leads eventually to elimination of the bacterium from the host. In order to prevent immune activation and thus favor survival in the host, bacteria secrete many proteins that hamper such recognition. In our search for Toll like receptor (TLR) antagonists, we screened bacterial supernatants and identified alkaline protease (AprA) of Pseudomonas aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL-8 production and NF-κB activation. AprA effectively degrades the TLR5 ligand monomeric flagellin, while polymeric flagellin (involved in bacterial motility) and TLR5 itself resist degradation. The natural occurring alkaline protease inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P. aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5 signaling, because they fail to degrade excess monomeric flagellin in their environment. Interestingly, AprA also prevents flagellin-mediated immune responses (such as growth inhibition and callose deposition) in Arabidopsis thaliana plants. This was due to decreased activation of the receptor FLS2 and clearly demonstrated by delayed stomatal closure with live bacteria in plants. Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes recognition by the innate immune systems of both mammals and plants. PMID:21901099

BURNER RIG TESTING OF A500 C/SiC

Science.gov (United States)

2018-03-17

AFRL-RX-WP-TR-2018-0071 BURNER RIG TESTING OF A500® C /SiC Larry P. Zawada Universal Technology Corporation Jennifer Pierce UDRI...TITLE AND SUBTITLE BURNER RIG TESTING OF A500® C /SiC 5a. CONTRACT NUMBER In-House 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62102F 6...test program characterized the durability behavior of A500® C /SiC ceramic matrix composite material at room and elevated temperature. Specimens were

Design and Checkout of a High Speed Research Nozzle Evaluation Rig

Science.gov (United States)

Castner, Raymond S.; Wolter, John D.

1997-01-01

The High Flow Jet Exit Rig (HFJER) was designed to provide simulated mixed flow turbojet engine exhaust for one- seventh scale models of advanced High Speed Research test nozzles. The new rig was designed to be used at NASA Lewis Research Center in the Nozzle Acoustic Test Rig and the 8x6 Supersonic Wind Tunnel. Capabilities were also designed to collect nozzle thrust measurement, aerodynamic measurements, and acoustic measurements when installed at the Nozzle Acoustic Test Rig. Simulated engine exhaust can be supplied from a high pressure air source at 33 pounds of air per second at 530 degrees Rankine and nozzle pressure ratios of 4.0. In addition, a combustion unit was designed from a J-58 aircraft engine burner to provide 20 pounds of air per second at 2000 degrees Rankine, also at nozzle pressure ratios of 4.0. These airflow capacities were designed to test High Speed Research nozzles with exhaust areas from eighteen square inches to twenty-two square inches. Nozzle inlet flow measurement is available through pressure and temperature sensors installed in the rig. Research instrumentation on High Speed Research nozzles is available with a maximum of 200 individual pressure and 100 individual temperature measurements. Checkout testing was performed in May 1997 with a 22 square inch ASME long radius flow nozzle. Checkout test results will be summarized and compared to the stated design goals.

Luminescence properties of copper(I), zinc(II) and cadmium(II) coordination compounds with picoline ligands

Energy Technology Data Exchange (ETDEWEB)

Małecki, Jan Grzegorz, E-mail: gmalecki@us.edu.pl; Maroń, Anna

2017-06-15

Mononuclear coordination compounds of copper(I) – [Cu(PPh{sub 3}){sub 2}(picoline)(NO{sub 3})], zinc(II) – [ZnCl{sub 2}(picoline){sub 2}] (picoline=3– and 4–methylpyridine) and polymeric cadmium(II) – [CdCl{sub 2}(β-picoline){sub 2}]{sub n} were prepared and their luminescence properties in solid state and acetonitrile solutions were determined. Single crystal X-ray crystallography revealed distorted tetrahedral geometry around the central ions of the compounds. The compounds exhibit green photoluminescence in solid state and in acetonitrile solutions. The emission of copper(I) compounds originated from metal-to-ligand charge transfer state combined with nitrato-to-picoline charge transfer state i.e. ({sup 1}(M+X)LCT). The presence of nitrato ligand in the coordination sphere of copper(I) compounds quenches the emission. Luminescence of zinc(II) and cadmium(II) compounds results from chloride-to-picoline charge transfer state and the quantum efficiency in the case of the polymeric Cd(II) compound reaches 39%. The photoluminescence quantum yields of the mononuclear zinc(II) compounds vary from 10 to 16% depending on the conditions (solid state, solution). - Graphical abstract: Coordination compounds of copper(I), zinc(II) and polymeric cadmium(II) with picoline ligands were prepared and their luminescence properties in solid state and acetonitrile solutions were determined. The compounds exhibit green photoluminescence in solid state and in acetonitrile solutions. Emission of copper(I) compounds originated from {sup 1}(M+X)LCT state. Luminescence of zinc(II) and cadmium(II) compounds results from chloride-to-picoline charge transfer state and the quantum efficiency in the case of the polymeric Cd(II) compound reaches 39%. The photoluminescence quantum yields of the mononuclear zinc(II) compounds vary from 10 to 16% depending on the conditions (solid state, solution).

MHC-I Ligand Discovery Using Targeted Database Searches of Mass Spectrometry Data: Implications for T-Cell Immunotherapies

DEFF Research Database (Denmark)

Murphy, J. Patrick; Konda, Prathyusha; Kowalewski, Daniel J.

2017-01-01

Class I major histocompatibility complex (MHC-I)-bound peptide ligands dictate the activation and specificity of CD8+ T cells and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these MHC-I pept...

Jet Exit Rig Six Component Force Balance

Science.gov (United States)

Castner, Raymond; Wolter, John; Woike, Mark; Booth, Dennis

2012-01-01

A new six axis air balance was delivered to the NASA Glenn Research Center. This air balance has an axial force capability of 800 pounds, primary airflow of 10 pounds per second, and a secondary airflow of 3 pounds per second. Its primary use was for the NASA Glenn Jet Exit Rig, a wind tunnel model used to test both low-speed, and high-speed nozzle concepts in a wind tunnel. This report outlines the installation of the balance in the Jet Exit Rig, and the results from an ASME calibration nozzle with an exit area of 8 square-inches. The results demonstrated the stability of the force balance for axial measurements and the repeatability of measurements better than 0.20 percent.

Structural insight into the recognition of complement C3 activation products by integrin receptors

DEFF Research Database (Denmark)

Bajic, Goran

2015-01-01

fragment C3a called anaphylatoxin. Complement leads to opsonization as the proteolytic fragment C3b becomes covalently linked to the activator surface through a reactive thioester. Self-surfaces are protected by complement regulators, whereas complement activation vividly amplifies on pathogens...... and their clearance by dendritic cells is mediated by αMβ2. The central molecule in my project, αMβ2 integrin, recognizes many diverse ligands including iC3b, but the molecular basis for such recognition was lacking. During my PhD I have obtained a major breakthrough in the dissection of iC3b interaction with αMβ2. I...

Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

Directory of Open Access Journals (Sweden)

Chriselle D. Braganza

2018-01-01

Full Text Available The macrophage inducible C-type lectin (Mincle is a pattern recognition receptor able to recognize both damage-associated and pathogen-associated molecular patterns, and in this respect, there has been much interest in determining the scope of ligands that bind Mincle and how structural modifications to these ligands influence ensuing immune responses. In this review, we will present Mincle ligands of known chemical structure, with a focus on ligands that have been synthetically prepared, such as trehalose glycolipids, glycerol-based ligands, and 6-acylated glucose and mannose derivatives. The ability of the different classes of ligands to influence the innate, and consequently, the adaptive, immune response will be described, and where appropriate, structure–activity relationships within each class of Mincle ligands will be presented.

The evaluation of secondary system oxygen-scavenging chemicals using a water-circulating rig

Energy Technology Data Exchange (ETDEWEB)

Collins, M.W. [Nuclear Dept., HMS Sultan (United Kingdom)

2002-07-01

To assess the efficiency, mode of action and possible by-products of chemical dosing agents, e.g. oxygen scavengers, a circulating water rig was constructed. The rig uses a demineralized water supply as a source of make-up water to fill a recirculating loop of approx. 10 litres volume. The rig pipework is made of polythene with standard off-the shelf pipe fittings and connectors. The following parameters can be measured within the rig: pH and conductivity measured by in-line monitor, dissolved oxygen level, temperature. The system has already been used for some preliminary testing. The following oxygen scavengers have been used for tests: ascorbic acid (vitamin C), N,N-diethyl-hydroxylamine (DEHA), Hydroquinone, hydrazine hydrate and anhydrous sodium sulfite. (authors)

The evaluation of secondary system oxygen-scavenging chemicals using a water-circulating rig

International Nuclear Information System (INIS)

Collins, M.W.

2002-01-01

To assess the efficiency, mode of action and possible by-products of chemical dosing agents, e.g. oxygen scavengers, a circulating water rig was constructed. The rig uses a demineralized water supply as a source of make-up water to fill a recirculating loop of approx. 10 litres volume. The rig pipework is made of polythene with standard off-the shelf pipe fittings and connectors. The following parameters can be measured within the rig: pH and conductivity measured by in-line monitor, dissolved oxygen level, temperature. The system has already been used for some preliminary testing. The following oxygen scavengers have been used for tests: ascorbic acid (vitamin C), N,N-diethyl-hydroxylamine (DEHA), Hydroquinone, hydrazine hydrate and anhydrous sodium sulfite. (authors)

Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes.

Science.gov (United States)

Raschka, Sebastian; Wolf, Alex J; Bemister-Buffington, Joseph; Kuhn, Leslie A

2018-04-01

Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes

Science.gov (United States)

Raschka, Sebastian; Wolf, Alex J.; Bemister-Buffington, Joseph; Kuhn, Leslie A.

2018-02-01

Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

Stochastic programming of drilling rigs supplies; Programacao estocastica de suprimentos de sondas

Energy Technology Data Exchange (ETDEWEB)

Vieira, Bruno Ferreira; Ferreira Filho, Virgilio Jose Martins [Coordenacao dos Programas de Pos-Graduacao de Engenharia (COPPE/UFRJ), RJ (Brazil)

2012-07-01

The goal of this work is to use techniques of stochastic programming to reduce logistic costs regarding offshore drilling rigs. This theme is of great interest to Brazilian oil industry since there is an increasing number of wells that need to be perforated so that Brazilian oil production can reach its expected growth over the next ten years (PETROBRAS in particular has an ambitious strategy in this respect). Proper treatment of the uncertainties involved in the deliveries of supplies to offshore drilling rigs is essential, namely, these uncertainties need to be included in the models used in logistic models. Delays in the deliveries of products such as chemicals, perforation fluids and tubes may force drilling rigs to stop their operations what highly increases costs. The daily hiring rates of drilling rigs represent the highest cost in the perforation and completion of a well. (author)

123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects

International Nuclear Information System (INIS)

Baeken, C.; D'haenen, H.; Flamen, P.; Bossuyt, A.; Mertens, J.; Terriere, D.; Chavatte, K.; Boumon, R.

1998-01-01

5-HT 2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT 2A receptors, 123 iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide ( 123 I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123 I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT 2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42%±7% was found. These results are in agreement with in vitro and positron emission tomography findings of a decline in 5-HT 2A receptor binding with age. The findings confirm the suitability of 123 I-5-I-R91150 for SPET imaging of 5-HT 2A receptors, and highlight the necessity for age-matched controls in clinical studies. (orig.)

Substantial Fatigue Similarity of a New Small-Scale Test Rig to Actual Wheel-Rail System

NARCIS (Netherlands)

Naeimi, M.; Li, Z.; Petrov, R.H.; Dollevoet, R.P.B.J.; Sietsma, J.; Wu, J.

2014-01-01

The substantial similarity of fatigue mechanism in a new test rig for rolling contact fatigue (RCF) has been investigated. A new reduced-scale test rig is designed to perform controlled RCF tests in wheel-rail materials. The fatigue mechanism of the rig is evaluated in this study using a combined

Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.

Science.gov (United States)

Spinello, A; Barone, G; Grunenberg, J

2016-01-28

In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial role in the molecular recognition process by G4-DNA. Depending on the proton concentration, different nitrogen atoms of the N-methyl-piperazine might (or might not) be protonated. This fact was considered in our simulation in terms of a case by case analysis, since the process of molecular recognition is determined by possible donor or acceptor positions. The results of our simulations show that the electrostatic interactions between the ND ligands and the G4 receptor are maximized in the case of the protonation of the terminal nitrogen atoms, forming compact ND G4 complexes inside the grooves. The influence of different protonation states in terms of the ability to form hydrogen bonds with the sugar-phosphate backbone, as well as the importance of mediated vs. direct hydrogen bonding, was analyzed in detail by MD and relaxed force constant (compliance constant) simulations.

Work over rig itinerary optimization; Otimizacao do itinerario de sondas de intervencao

Energy Technology Data Exchange (ETDEWEB)

Paiva, Ronaldo Oliveira de

1997-07-01

The costs of work over and the loss of revenue in wells waiting work over rigs are very high. This work proposes methods to prioritize these wells in order to minimize the total cost. To determine the work over sequence it is necessary to compare the rig expense with the wells losses. For calculating the wells losses, it is necessary to analyze the monetary influence of the well shutdown in the production curves. In this work, this analysis is made by using a numerical reservoir simulator. Simplified calculation procedures are also presented. The priority of the wells is based on the reduction of the total cost, which consists of the rig costs plus the revenue losses due to work over waiting. There are many algorithms able to determine the ideal rig path. Simple and intuitive algorithms are implemented and compared. The Simulated Annealing algorithm is recommended. This algorithm was implemented to optimize work over rig routes in a brazilian production region. Optimization of the work over sequence carried out in that region in 1996 identified a potential economy of 15% in the production losses, equivalent to 4.000m{sup 3}/year of oil (25.000 b bl/year). (author)

Development of TIG Welding System for a Nuclear Fuel Test Rig

Energy Technology Data Exchange (ETDEWEB)

Joung, Changyoung; Ahn, Sungho; Hong, Jintae; Kim, Kahye [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

The welding process is one of the most important among the instrumentation processes of the nuclear fuel test rig and rods. To manufacture the nuclear fuel test rig, a precision welding system needs to be fabricated to develop various welding technologies of the fuel test rig and rods jointing the various sensors and end caps on a fuel cladding tube, which is charged with fuel pellets and component parts. Thus, we designed and fabricated the precision welding system consisting of an orbital TIG welder, a low-pressure chamber, and a high-pressure chamber. Using this system, the performance tests were performed with the round and seal spot welds for each welding condition. This paper describes not only the contents for the fabrication of precision TIG welding system but also some results from weld tests using the low-pressure and high-pressure chambers to verify the performance of this system. The TIG welding system was developed to manufacture the nuclear fuel test rig and rods. It has been configured to be able to weld the nuclear fuel test rigs and rods by applying the TIG welder using a low-pressure chamber and a high-pressure chamber. The performance tests using this system were performed with the round and seal spot welds for the welding conditions. The soundness of the orbital TIG welding system was confirmed through performance tests in the low-pressure and high-pressure chambers.

Development of TIG Welding System for a Nuclear Fuel Test Rig

International Nuclear Information System (INIS)

Joung, Changyoung; Ahn, Sungho; Hong, Jintae; Kim, Kahye

2013-01-01

The welding process is one of the most important among the instrumentation processes of the nuclear fuel test rig and rods. To manufacture the nuclear fuel test rig, a precision welding system needs to be fabricated to develop various welding technologies of the fuel test rig and rods jointing the various sensors and end caps on a fuel cladding tube, which is charged with fuel pellets and component parts. Thus, we designed and fabricated the precision welding system consisting of an orbital TIG welder, a low-pressure chamber, and a high-pressure chamber. Using this system, the performance tests were performed with the round and seal spot welds for each welding condition. This paper describes not only the contents for the fabrication of precision TIG welding system but also some results from weld tests using the low-pressure and high-pressure chambers to verify the performance of this system. The TIG welding system was developed to manufacture the nuclear fuel test rig and rods. It has been configured to be able to weld the nuclear fuel test rigs and rods by applying the TIG welder using a low-pressure chamber and a high-pressure chamber. The performance tests using this system were performed with the round and seal spot welds for the welding conditions. The soundness of the orbital TIG welding system was confirmed through performance tests in the low-pressure and high-pressure chambers

Natural Cytotoxicity Receptors: Pattern Recognition and Involvement of Carbohydrates

Directory of Open Access Journals (Sweden)

Angel Porgador

2005-01-01

Full Text Available Natural cytotoxicity receptors (NCRs, expressed by natural killer (NK cells, trigger NK lysis of tumor and virus-infected cells on interaction with cell-surface ligands of these target cells. We have determined that viral hemagglutinins expressed on the surface of virus-infected cells are involved in the recognition by the NCRs, NKp44 and NKp46. Recognition of tumor cells by the NCRs NKp30 and NKp46 involves heparan sulfate epitopes expressed on the tumor cell membrane. Our studies provide new evidence for the identity of the ligands for NCRs and indicate that a broader definition should be applied to pathological patterns recognized by innate immune receptors. Since nonmicrobial endogenous carbohydrate structures contribute significantly to this recognition, there is an imperative need to develop appropriate tools for the facile sequencing of carbohydrate moieties.

Re-rigging Othering: Subversive Infantilisation in Contemporary Bosnian-Herzegovinian Prose

Directory of Open Access Journals (Sweden)

Fedja Borčak

2014-12-01

Full Text Available In this article I put forward the concept of subversive infantilisation to designate a phenomenon in contemporary Bosnian literature, which by using a certain kind of childish outlook on the world undermines paternalistic and balkanist Western discourse on Bosnia and Herzegovina. By analysing primarily the portrayal of the role of mass media in a few literary texts, principally books by Nenad Veličkovié and Miljenko Jergovié, I highlight the way in which these texts 're-rig' and by means of irony and exaggeration illuminate the problematic logic inherent in the subject position from which one represents the other. Textual characteristics of subversive infantilisation are contextualised further and seen as a discursive continuation of experiences of the 1990s war in Bosnia and Herzegovina.

Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system)

International Nuclear Information System (INIS)

Sardi, A.; Workman, M.; Mojzisik, C.; Hinkle, G.; Nieroda, C.; Martin, E.W. Jr.

1989-01-01

Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences

Computer aided extractor design for the RIG 10 high intensity ion source

International Nuclear Information System (INIS)

Tanzer, F.; Haeuser, J.; Eppel, D.

1980-01-01

The paper discusses recent progress of the rf-ion source RIG 10, and describes a computer code for the simulation of the ion trajectories. The RIG 10 is designed for current densities of some 300 mA/cm 2 , and will be used for the production of neutral. (orig.)

Dose dependent activation of retinoic acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Jingzhou Hu

Full Text Available The retinoic-acid-inducible gene (RIG-like receptor (RLR family proteins are major pathogen reorganization receptors (PRR responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC. RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5'-triphosphate RNA (3p-RNA induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell survival, whereas higher level of RIG-I activation leads to apoptosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.

This immortal coil? New CT rigs duel against singles

Energy Technology Data Exchange (ETDEWEB)

Creighton, J.

1998-12-01

New competition to conventional single rigs that have changed little in the last four decades face new competition from next-generation coiled tubing (CT) units which have multi-function capabilities, ranging from driving onto leases, drilling and setting surface case to cementing. Several of these new units are ready to challenge the conventional single rigs. Their ability to perform at high penetration rates (up to twice what single rigs can do) is expected to significantly cut drill time, with corresponding cost savings for both contractors and operators. Serval Corporation and Fleet Coiled Services are just two of the drilling service companies that have launched new shallow grass roots coiled tubing drilling units recently, gambling that the new technology will win over conventional methods hands down. Some major companies, like Fracmaster Ltd. and NOWSCO Well Service Ltd., have targeted the re-entry and horizontal markets, a much more difficult technical challenge, sinking billions of dollars of research and development money into advancing the most technically difficult applications of coil technology.

A new crystal form of human tear lipocalin reveals high flexibility in the loop region and induced fit in the ligand cavity

International Nuclear Information System (INIS)

Breustedt, Daniel A.; Chatwell, Lorenz; Skerra, Arne

2009-01-01

The crystal structure of tear lipocalin determined in space group P2 1 revealed large structural deviations from the previously solved X-ray structure in space group C2, especially in the loop region and adjoining parts of the β-barrel which give rise to the ligand-binding site. These findings illustrate a novel mechanism for promiscuity in ligand recognition by the lipocalin protein family. Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been crystallized in space group P2 1 with four protein molecules in the asymmetric unit and its X-ray structure has been solved at 2.6 Å resolution. TLC is a member of the lipocalin family that binds ligands with diverse chemical structures, such as fatty acids, phospholipids and cholesterol as well as microbial siderophores and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC crystallized in space group C2 revealed a rather large bifurcated ligand pocket and a partially disordered loop region at the entrace to the cavity. Analysis of the P2 1 crystal form uncovered major conformational changes (i) in β-strands B, C and D, (ii) in loops 1, 2 and 4 at the open end of the β-barrel and (iii) in the extended C-terminal segment, which is attached to the β-barrel via a disulfide bridge. The structural comparison indicates high conformational plasticity of the loop region as well as of deeper parts of the ligand pocket, thus allowing adaptation to ligands that differ vastly in size and shape. This illustrates a mechanism for promiscuity in ligand recognition which may also be relevant for some other physiologically important members of the lipocalin protein family

Synthesis and optical resolution of a Cu(I) double-stranded helicate with ketimine-bridged tris(bipyridine) ligands.

Science.gov (United States)

Furusho, Yoshio; Goto, Hidetoshi; Itomi, Ken; Katagiri, Hiroshi; Miyagawa, Toyoharu; Yashima, Eiji

2011-09-21

A tetranuclear Cu(I) double-stranded helicate was synthesized from ketimine-bridged tris(bipyridine) ligands and Cu(I) ions, and the racemate was successfully resolved by diastereomeric salt formation using an optically pure phosphate anion followed by anion exchange with NaPF(6) without racemization.

Pseudomonas evades immune recognition of flagellin in both mammals and plants.

Directory of Open Access Journals (Sweden)

Bart W Bardoel

2011-08-01

Full Text Available The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5 in mammals and flagellin-sensitive 2 (FLS2 in plants. Activation of these immune systems via flagellin leads eventually to elimination of the bacterium from the host. In order to prevent immune activation and thus favor survival in the host, bacteria secrete many proteins that hamper such recognition. In our search for Toll like receptor (TLR antagonists, we screened bacterial supernatants and identified alkaline protease (AprA of Pseudomonas aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL-8 production and NF-κB activation. AprA effectively degrades the TLR5 ligand monomeric flagellin, while polymeric flagellin (involved in bacterial motility and TLR5 itself resist degradation. The natural occurring alkaline protease inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P. aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5 signaling, because they fail to degrade excess monomeric flagellin in their environment. Interestingly, AprA also prevents flagellin-mediated immune responses (such as growth inhibition and callose deposition in Arabidopsis thaliana plants. This was due to decreased activation of the receptor FLS2 and clearly demonstrated by delayed stomatal closure with live bacteria in plants. Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes recognition by the innate immune systems of both mammals and plants.

Manganese(I-Based CORMs with 5-Substituted 3-(2-PyridylPyrazole Ligands

Directory of Open Access Journals (Sweden)

Ralf Mede

2017-01-01

Full Text Available The reaction of [(OC5MnBr] with substituted 3-(2-pyridylpyrazoles 2-PyPzRH (1a-l in methanol or diethyl ether yields the yellow to orange manganese(I complexes [(OC3Mn(Br(2-PyPzRH] (2a-l, the substituents R being phenyl (a, 1-naphthyl (b, 2-anthracenyl (c, 1-pyrenyl (d, 4-bromophenyl (e, 3-bromophenyl (f, duryl (g, 2-pyridyl (h, 2-furanyl (i, 2-thienyl (j, ferrocenyl (k, and 1-adamantyl (l. The carbonyl ligands are arranged facially, leading to three chemically different CO ligands due to different trans-positioned Lewis donors. The diversity of the substituent R demonstrates that this photoCORM backbone can easily be varied with a negligible influence on the central (OC3MnBr fragment, because the structural parameters and the spectroscopic data of this unit are very similar for all these derivatives. Even the ferrocenyl complex 2k shows a redox potential for the ferrocenyl subunit which is identical to the value of the free 5-ferrocenyl-3-(2-pyridylpyrazole (1k. The ease of variation of the starting 5-substituted 3-(2-pyridylpyrazoles offers a modular system to attach diverse substituents at the periphery of the photoCORM complex.

Thermodynamic fingerprints of ligand binding to human telomeric G-quadruplexes

OpenAIRE

Bon?ina, Matja?; Podlipnik, ?rtomir; Piantanida, Ivo; Eilmes, Julita; Teulade-Fichou, Marie-Paule; Vesnaver, Gorazd; Lah, Jurij

2015-01-01

Thermodynamic studies of ligand binding to human telomere (ht) DNA quadruplexes, as a rule, neglect the involvement of various ht-DNA conformations in the binding process. Therefore, the thermodynamic driving forces and the mechanisms of ht-DNA G-quadruplex-ligand recognition remain poorly understood. In this work we characterize thermodynamically and structurally binding of netropsin (Net), dibenzotetraaza[14]annulene derivatives (DP77, DP78), cationic porphyrin (TMPyP4) and two bisquinolini...

The A2iA French handwriting recognition system at the Rimes-ICDAR2011 competition

Science.gov (United States)

Menasri, Farès; Louradour, Jérôme; Bianne-Bernard, Anne-Laure; Kermorvant, Christopher

2012-01-01

This paper describes the system for the recognition of French handwriting submitted by A2iA to the competition organized at ICDAR2011 using the Rimes database. This system is composed of several recognizers based on three different recognition technologies, combined using a novel combination method. A framework multi-word recognition based on weighted finite state transducers is presented, using an explicit word segmentation, a combination of isolated word recognizers and a language model. The system was tested both for isolated word recognition and for multi-word line recognition and submitted to the RIMES-ICDAR2011 competition. This system outperformed all previously proposed systems on these tasks.

Investigating the Structure and Reactivity of Azolyl-Based Copper(I)–NHC Complexes: The Role of the Anionic Ligand

KAUST Repository

Trose, Michael; Nahra, Fady; Poater, Albert; Cordes, David B.; Slawin, Alexandra M. Z.; Cavallo, Luigi; Cazin, Catherine S. J.

2017-01-01

A family of copper(I)–NHC azolyl complexes was synthesized and deployed in the hydrosilylation of dicyclo-hexylketone to probe the role of the anionic ligand on catalytic performance. The azolyl ligand is shown to have a crucial role in catalytic activity without the need for additives, and this at very low catalyst loading.

Investigating the Structure and Reactivity of Azolyl-Based Copper(I)–NHC Complexes: The Role of the Anionic Ligand

KAUST Repository

Trose, Michael

2017-11-01

A family of copper(I)–NHC azolyl complexes was synthesized and deployed in the hydrosilylation of dicyclo-hexylketone to probe the role of the anionic ligand on catalytic performance. The azolyl ligand is shown to have a crucial role in catalytic activity without the need for additives, and this at very low catalyst loading.

Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors

Energy Technology Data Exchange (ETDEWEB)

Yao, Yongneng; Harrison, Chris B.; Freddolino, Peter L.; Schulten, Klaus; Mayer, Mark L. (UIUC); (NIH)

2008-10-27

NR3 subtype glutamate receptors have a unique developmental expression profile, but are the least well-characterized members of the NMDA receptor gene family, which have key roles in synaptic plasticity and brain development. Using ligand binding assays, crystallographic analysis, and all atom MD simulations, we investigate mechanisms underlying the binding by NR3A and NR3B of glycine and D-serine, which are candidate neurotransmitters for NMDA receptors containing NR3 subunits. The ligand binding domains of both NR3 subunits adopt a similar extent of domain closure as found in the corresponding NR1 complexes, but have a unique loop 1 structure distinct from that in all other glutamate receptor ion channels. Within their ligand binding pockets, NR3A and NR3B have strikingly different hydrogen bonding networks and solvent structures from those found in NR1, and fail to undergo a conformational rearrangement observed in NR1 upon binding the partial agonist ACPC. MD simulations revealed numerous interdomain contacts, which stabilize the agonist-bound closed-cleft conformation, and a novel twisting motion for the loop 1 helix that is unique in NR3 subunits.

Solid-state thermolysis of a fac-rhenium(I) carbonyl complex with a redox non-innocent pincer ligand.

Science.gov (United States)

Jurca, Titel; Chen, Wen-Ching; Michel, Sheila; Korobkov, Ilia; Ong, Tiow-Gan; Richeson, Darrin S

2013-03-25

The development of rhenium(I) chemistry has been restricted by the limited structural and electronic variability of the common pseudo-octahedral products fac-[ReX(CO)3L2] (L2 = α-diimine). We address this constraint by first preparing the bidentate bis(imino)pyridine complexes [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)3X] (X = Cl 2, Br 3), which were characterized by spectroscopic and X-ray crystallographic means, and then converting these species into tridentate pincer ligand compounds, [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2X] (X = Cl 4, Br 5). This transformation was performed in the solid-state by controlled heating of 2 or 3 above 200 °C in a tube furnace under a flow of nitrogen gas, giving excellent yields (≥95 %). Compounds 4 and 5 define a new coordination environment for rhenium(I) carbonyl chemistry where the metal center is supported by a planar, tridentate pincer-coordinated bis(imino)pyridine ligand. The basic photophysical features of these compounds show significant elaboration in both number and intensity of the d-π* transitions observed in the UV/Vis spec tra relative to the bidentate starting materials, and these spectra were analyzed using time-dependent DFT computations. The redox nature of the bis(imino)pyridine ligand in compounds 2 and 4 was examined by electrochemical analysis, which showed two ligand reduction events and demonstrated that the ligand reduction shifts to a more positive potential when going from bidentate 2 to tridentate 4 (+160 mV for the first reduction step and +90 mV for the second). These observations indicate an increase in electrostatic stabilization of the reduced ligand in the tridentate conformation. Elaboration on this synthetic methodology documented its generality through the preparation of the pseudo-octahedral rhenium(I) triflate complex [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2OTf] (7, 93 % yield). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modelling and simulation of dynamic wheel-rail interaction using a roller rig

International Nuclear Information System (INIS)

Anyakwo, A; Pislaru, C; Ball, A; Gu, F

2012-01-01

The interaction between the wheel and rail greatly influences the dynamic response of railway vehicles on the track. A roller rig facility can be used to study and monitor real time parameters that influence wheel-rail interaction such as wear, adhesion, friction and corrugation without actual field tests being carried out. This paper presents the development of the mathematical models for full scale roller rig and 1/5 scale roller rig and the wear prediction model based on KTH wear function. The simulated critical speed for the 1/5 scale roller rig is about one-fifth of the critical speed for the full scale model so the simulated results compare well with the theory related to wheel-rail contact and dynamics. Also the differences between the simulated rolling radii for the full scale model with and without wear function are analysed. This paper presents the initial stage of a large scale research project where the influence of wear on the wheel-rail performance will be studied in more depth.

RIG-1 expression is associated with sexual malfunctions of female type 2 diabetic patients

Directory of Open Access Journals (Sweden)

Batool Hajebrahimi

2017-03-01

Full Text Available Introduction: The patients with type 2 diabetes (T2D suffer from the malfunctions of the sexual behaviors, and several mechanisms have been proposed to describe these disorders. The innate immunity may be involved in the malfunctions of T2D patients. Melanoma differentiation-associated protein 5 (MDA5 and retinoic acid (RA-inducible gene 1 (RIG-1, as the innate immunity receptors, are the responsible molecules for the activation of some intracellular signaling pathways and the induction of inflammation. Thus, this study aimed to examine the molecules which may participate in the induction/stimulation of sexual malfunctions in the female T2D patients. Methods: Sexual functions were evaluated in 41 female T2D patients using the Female Sexual Function Index (FSFI questionnaire. Real-time polymerase chain reaction (PCR technique was used to quantify MDA5 and RIG-1 mRNA levels. Results: Results showed that increased RIG-1 mRNA levels were significantly associated with the bad orgasm in the female T2D patients compared to the female patients with good orgasm. Expression of RIG-1 and MDA5 levels were not associated with other sexual functions’ criteria. Conclusion: The findings of this study demonstrated that bad orgasm is associated with the increased RIG-1 expression. Consequently, the correlation between inflammation and bad orgasm in a RIG-1 dependent manner is suggested.

Wythenshawe boiler rig. Thirty years of support to the UK nuclear power industry

International Nuclear Information System (INIS)

Rudge, Andy; Woolsey, Ian S.; Moore, Andrew

2010-01-01

The Wythenshawe Boiler Rig in Manchester, UK, recently celebrated thirty years of operation in support of the UK nuclear power industry. The Boiler Rig, owned by EDF Energy and operated on EDF Energy's behalf by Serco plc, is a full scale once-through boiler test facility for the investigation of chemistry and corrosion related topics. This paper presents an overview of the design and operation of the Boiler Rig together with some of the technical highlights from its thirty years of operation, many of which have relevance to power plant operations beyond those plants for which the work was performed. (orig.)

Stress-life relation of the rolling-contact fatigue spin rig

Science.gov (United States)

Butler, Robert H; Carter, Thomas L

1957-01-01

The rolling-contact fatigue spin rig was used to test groups of SAE 52100 9.16-inch-diameter balls lubricated with a mineral oil at 600,000-, 675,000-, and 750,000-psi maximum Hertz stress. Cylinders of AISI M-1 vacuum and commercial melts and MV-1 (AISI M-50) were used as race specimens. Stress-life exponents produced agree closely with values accepted in industry. The type of failure obtained in the spin rig was similar to the subsurface fatigue spells found in bearings.

Azido, triazolyl, and alkynyl complexes of gold(I): syntheses, structures, and ligand effects.

Science.gov (United States)

Robilotto, Thomas J; Deligonul, Nihal; Updegraff, James B; Gray, Thomas G

2013-08-19

Gold(I) triazolyl complexes are prepared in [3 + 2] cycloaddition reactions of (tertiary phosphine)gold(I) azides with terminal alkynes. Seven such triazolyl complexes, not previously prepared, are described. Reducible functional groups are accommodated. In addition, two new (N-heterocyclic carbene)gold(I) azides and two new gold(I) alkynyls are described. Eight complexes are crystallographically authenticated; aurophilic interactions appear in one structure only. The packing diagrams of gold(I) triazolyls all show intermolecular hydrogen bonding between N-1 of one molecule and N-3 of a neighbor. This hydrogen bonding permeates the crystal lattice. Density-functional theory calculations of (triphenylphosphine)gold(I) triazolyls and the corresponding alkynyls indicate that the triazolyl is a stronger trans-influencer than is the alkynyl, but the alkynyl is more electron-releasing. These results suggest that trans-influences in two-coordinate gold(I) complexes can be more than a simple matter of ligand donicity.

Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

International Nuclear Information System (INIS)

Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

Enantioselective recognition of an isomeric ligand by a biomolecule: mechanistic insights into static and dynamic enantiomeric behavior and structural flexibility.

Science.gov (United States)

Peng, Wei; Ding, Fei

2017-10-24

Chirality is a ubiquitous basic attribute of nature, which inseparably relates to the life activity of living organisms. However, enantiomeric differences have still failed to arouse enough attention during the biological evaluation and practical application of chiral substances, and this poses a large threat to human health. In the current study, we explore the enantioselective biorecognition of a chiral compound by an asymmetric biomolecule, and then decipher the molecular basis of such a biological phenomenon on the static and, in particular, the dynamic scale. In light of the wet experiments, in silico docking results revealed that the orientation of the latter part of the optical isomer structures in the recognition domain can be greatly affected by the chiral carbon center in a model ligand molecule, and this event may induce large disparities between the static chiral bioreaction modes and noncovalent interactions (especially hydrogen bonding). Dynamic stereoselective biorecognition assays indicated that the conformational stability of the protein-(S)-diclofop system is clearly greater than the protein-(R)-diclofop adduct; and moreover, the conformational alterations of the diclofop enantiomers in the dynamic process will directly influence the conformational flexibility of the key residues found in the biorecognition region. These points enable the changing trends of biopolymer structural flexibility and free energy to exhibit significant distinctions when proteins sterically recognize the (R)-/(S)-stereoisomers. The outcomes of the energy decomposition further showed that the van der Waals' energy has roughly the same contribution to the chiral recognition biosystems, whereas the contribution of electrostatic energy to the protein-(R)-diclofop complex is notably smaller than to the protein-(S)-diclofop bioconjugate. This proves that differences in the noncovalent bonds would have a serious impact on the stereoselective biorecognition between a

Characteristic molecular vibrations of adenosine receptor ligands.

Science.gov (United States)

Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

2015-02-13

Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A Built for Purpose Micro-Hole Coiled Tubing Rig (MCTR)

Energy Technology Data Exchange (ETDEWEB)

Bart Patton

2007-09-30

This report will serve as the final report on the work performed from the contract period October 2005 thru April 2007. The project 'A Built for Purpose Microhole Coiled Tubing Rig (MCTR)' purpose was to upgrade an existing state-of-the-art Coiled Tubing Drilling Rig to a Microhole Coiled Tubing Rig (MCTR) capable of meeting the specifications and tasks of the Department of Energy. The individual tasks outlined to meet the Department of Energy's specifications are: (1) Concept and development of lubricator and tool deployment system; (2) Concept and development of process control and data acquisition; (3) Concept and development of safety and efficiency improvements; and (4) Final unit integration and testing. The end result of the MCTR upgrade has produced a unit capable of meeting the following requirements: (1) Capable of handling 1-inch through 2-3/8-inch coiled tubing (Currently dressed for 2-3/8-inch coiled tubing and capable of running up to 3-1/2-inch coiled tubing); (2) Capable of drilling and casing surface, intermediate, production and liner hole intervals; (3) Capable of drilling with coiled tubing and has all controls and installation piping for a top drive; (4) Rig is capable of running 7-5/8-inch range 2 casing; and (5) Capable of drilling 5,000 ft true vertical depth (TVD) and 6,000 ft true measured depth (TMD).

Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.

Science.gov (United States)

Zeng, Yi; Wang, Ping-Han; Zhang, Mao; Du, Jun-Rong

2016-02-01

The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury. Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury. Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls. The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.

Structural variability in Cu(I) and Ag(I) coordination polymers with a flexible dithione ligand: Synthesis, crystal structure, microbiological and theoretical studies

Energy Technology Data Exchange (ETDEWEB)

Beheshti, Azizolla, E-mail: a.beheshti@scu.ac.ir [Department of Chemistry, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz (Iran, Islamic Republic of); Nozarian, Kimia; Babadi, Susan Soleymani; Noorizadeh, Siamak [Department of Chemistry, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz (Iran, Islamic Republic of); Motamedi, Hossein [Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz (Iran, Islamic Republic of); Mayer, Peter [LMU München Department Chemie, Butenandtstr 5-13, D-81377 München (Germany); Bruno, Giuseppe [Dipartimento di Chimica Inorganica, Università di Messina, Vill. S. Agata, Salita Sperone 31, 98166 Messina (Italy); Rudbari, Hadi Amiri [Faculty of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of)

2017-05-15

Two new compounds namely [Cu(SCN)(µ-L)]{sub n} (1) and ([Ag (µ{sub 2}-L)](ClO{sub 4})){sub n} (2) have been synthesized at room temperature by one-pot reactions between the 1,1-(1,4-butanediyl)bis(1,3-dihydro-3-methyl-1H-imidazole- 2-thione) (L) and appropriate copper(I) and silver(I) salts. These polymers have been characterized by single crystal X-ray diffraction, XRPD, TGA, elemental analysis, infrared spectroscopy, antibacterial activity and scanning probe microscopy studies. In the crystal structure of 1, copper atoms have a distorted trigonal planar geometry with a CuS{sub 2}N coordination environment. Each of the ligands in the structure of 1 acting as a bidentate S-bridging ligand to form a 1D chain structure. Additionally, the adjacent 1D chains are interconnected by the intermolecular C-H…S interactions to create a 2D network structure. In contrast to 1, in the cationic 3D structure of 2 each of the silver atoms exhibits an AgS{sub 4} tetrahedral geometry with 4-membered Ag{sub 2}S{sub 2} rings. In the structure of 2, the flexible ligand adopts two different conformations; gauche-anti-gauche and anti-anti-anti. The antibacterial studies of these polymers showed that polymer 2 is more potent antibacterial agent than 1. Scanning probe microscopy (SPM) study of the treated bacteria was carried out to investigate the structural changes cause by the interactions between the polymers and target bacteria. Theoretical study of polymer 1 investigated by the DFT calculations indicates that observed transitions at 266 nm and 302 nm in the UV–vis spectrum could be attributed to the π→π* and MLCT transitions, respectively. - Graphical abstract: Two new Cu(I) and Ag(I) coordination polymers have been have been synthesized by one-pot reactions. Copper complex has a 2D non-covalent structure, but silver compound is a 3D coordination compound. These compounds have effective antibacterial activity. - Highlights: • Cu(I) and Ag(I) based coordination polymers

General Linker Diversification Approach to Bivalent Ligand Assembly: Generation of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.

Science.gov (United States)

Fei, Xiang; Zavorka, Megan E; Malik, Guillaume; Connelly, Christopher M; MacDonald, Richard G; Berkowitz, David B

2017-08-18

A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition.

Metalloradical Reactivity of RuI and Ru0 Stabilized by an Indole-Based Tripodal Tetraphosphine Ligand

NARCIS (Netherlands)

van de Watering, F.F.; van der Vlugt, J.I.; Dzik, W.I.; de Bruin, B.; Reek, J.N.H.

2017-01-01

The tripodal, tetradentate tris(1-(diphenylphosphanyl)-3-methyl-1H-indol-2-yl)phosphane PP3-ligand 1 stabilizes Ru in the RuII, RuI, and Ru0 oxidation states. The octahedral [(PP3)RuII(Cl)2] ( 2 ), distorted trigonal bipyramidal [(PP3)RuI(Cl)] ( 3 ), and trigonal bipyramidal [(PP3)Ru0(N2)] ( 4 )

Bycatch in 36 and 40 mm PA Turkish twin rigged beam trawl codends

African Journals Online (AJOL)

The Turkish twin rigged beam trawl which has two identical nets rigged side by side on the same beam targets mainly the Parapenaeus longirostris, although some bycatch fish species have also become target species. Thus, landings of the shrimp beam trawling fleet also include some commercially valuable fishes.

Magnetic ligand fishing as a targeting tool for HPLC-HRMS-SPE-NMR: α-glucosidase inhibitory ligands and alkylresorcinol glycosides from <i>Eugenia catharinaei>

DEFF Research Database (Denmark)

Wubshet, Sileshi Gizachew; Brighente, Inês M. C.; Moaddel, Ruin

2015-01-01

A bioanalytical platform combining magnetic ligand fishing for α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for structural identification of α-glucosidase inhibitory ligands, both directly from crude plant extracts, is presented. Magnetic beads with N-terminus-coupled α-glucosidase we...

Freon Rig design for performing to heat transfer experiments for nuclear reactors fuel bundles

International Nuclear Information System (INIS)

Flores, L.F.V.

1981-01-01

The main features of a Freon Rig design for performing to heat transfer experiments for PWR and BWR fuel bundles, are presented. The project is based on a Freon Rig pressurized at 30 bar with a flow rate up to 80 m 3 /h. The maximum power fed to test sections is of about 420 KW D.C. The rig was designed to use scaling techniques wich would enable a fluid of low latente heat to be used in place of water, thereby reducing the cost of testes. (Author) [pt

Analytical developments for screening of lanthanides/ligands interactions

International Nuclear Information System (INIS)

Varenne, F.

2012-01-01

This work investigates the potential of hyphenated capillary electrophoresis and inductively coupled mass spectrometry to classify different ligands according to their europium binding affinity in a hydro-organic medium. On the one hand, this method enables to evaluate the affinity of phosphorus-containing ligands in less than two hours and using less than 15 ng of ligand. On the other hand, complexation constants could be determined. The results are in excellent agreement with the values obtained by spectrophotometric titrations.Moreover, a library of copolymers for solid/liquid extraction of europium is investigated. The extraction protocol enables to classify copolymers according to their europium affinity in a hydro-organic medium. This screening requires 60 mg of copolymers. For the most promising recognition properties and selectivity La 3+ /Eu 3+ /Lu 3+ are evaluated. (author)

Transfer of the human NKG2D ligands UL16 binding proteins (ULBP) 1-3 is related to lytic granule release and leads to ligand retransfer and killing of ULBP-recipient natural killer cells.

Science.gov (United States)

López-Cobo, Sheila; Romera-Cárdenas, Gema; García-Cuesta, Eva M; Reyburn, Hugh T; Valés-Gómez, Mar

2015-09-01

After immune interactions, membrane fragments can be transferred between cells. This fast transfer of molecules is transient and shows selectivity for certain proteins; however, the constraints underlying acquisition of a protein are unknown. To characterize the mechanism and functional consequences of this process in natural killer (NK) cells, we have compared the transfer of different NKG2D ligands. We show that human NKG2D ligands can be acquired by NK cells with different efficiencies. The main findings are that NKG2D ligand transfer is related to immune activation and receptor-ligand interaction and that NK cells acquire these proteins during interactions with target cells that lead to degranulation. Our results further demonstrate that NK cells that have acquired NKG2D ligands can stimulate activation of autologous NK cells. Surprisingly, NK cells can also re-transfer the acquired molecule to autologous effector cells during this immune recognition that leads to their death. These data demonstrate that transfer of molecules occurs as a consequence of immune recognition and imply that this process might play a role in homeostatic tuning-down of the immune response or be used as marker of interaction. © 2015 John Wiley & Sons Ltd.

Graphical symbol recognition

OpenAIRE

K.C. , Santosh; Wendling , Laurent

2015-01-01

International audience; The chapter focuses on one of the key issues in document image processing i.e., graphical symbol recognition. Graphical symbol recognition is a sub-field of a larger research domain: pattern recognition. The chapter covers several approaches (i.e., statistical, structural and syntactic) and specially designed symbol recognition techniques inspired by real-world industrial problems. It, in general, contains research problems, state-of-the-art methods that convey basic s...

Rig automation: where it's been and where it's going

Energy Technology Data Exchange (ETDEWEB)

Rinaldi, R.

1982-06-01

For over 30 years dreamers, tinkerers and engineers have attempted to automate various drilling functions. Now this effort is paying off, and a partially automated rig is no longer a curiosity. Fully automated and computerized rigs are on the way. For the contractor this means higher productivity, but more maintenance and training responsibilities.

The Winfrith horizontal impact rig

International Nuclear Information System (INIS)

Barr, P.

1985-12-01

The Horizontal Impact Rig has been designed to allow studies of the impact of radioactive material transport containers and their associated transport vehicles and impact limiters, using large scale models, and to allow physically large missiles to be projected for studying the impact behaviour of metal and concrete structures. It provides an adequately rigid support structure for impact experiments with targets of large dimensions. Details of its design, instrumentation, performance prediction and construction are given. (U.K.)

Development of a low cost test rig for standalone WECS subject to electrical faults.

Science.gov (United States)

Himani; Dahiya, Ratna

2016-11-01

In this paper, a contribution to the development of low-cost wind turbine (WT) test rig for stator fault diagnosis of wind turbine generator is proposed. The test rig is developed using a 2.5kW, 1750 RPM DC motor coupled to a 1.5kW, 1500 RPM self-excited induction generator interfaced with a WT mathematical model in LabVIEW. The performance of the test rig is benchmarked with already proven wind turbine test rigs. In order to detect the stator faults using non-stationary signals in self-excited induction generator, an online fault diagnostic technique of DWT-based multi-resolution analysis is proposed. It has been experimentally proven that for varying wind conditions wavelet decomposition allows good differentiation between faulty and healthy conditions leading to an effective diagnostic procedure for wind turbine condition monitoring. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

TECHNICAL FEATURES OF RIGGED YACHT BY CATEGORIES AND CLASSES

Directory of Open Access Journals (Sweden)

Svitlana Yeroshkina

2016-06-01

Full Text Available The article is directed on the deeply meaningful scientific study and structural analysis of the technical features of the rigged world modern yachts to pass sailing regattas in different navigation areas. The complete classification of sailing boats in it’s world classes was done for olympic, international, national regattas. It was done the technical indicators of yachting racing classes. The economic analysis material selection sails for yachts are directed of different types of races. In it’s scientific article is made economic calculation of operating cost of the boat and it was done the analysis of cost saving yachts in european / ukrainian marinas.Key words: yachting, rigged yacht, racing, classes of yachts. JEL: L 92

Crystallization of protein–ligand complexes

International Nuclear Information System (INIS)

Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

2007-01-01

Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

Eigenfunction expansions and scattering theory in rigged Hilbert spaces

Energy Technology Data Exchange (ETDEWEB)

Gomez-Cubillo, F [Dpt. de Analisis Matematico, Universidad de Valladolid. Facultad de Ciencias, 47011 Valladolid (Spain)], E-mail: fgcubill@am.uva.es

2008-08-15

The work reviews some mathematical aspects of spectral properties, eigenfunction expansions and scattering theory in rigged Hilbert spaces, laying emphasis on Lippmann-Schwinger equations and Schroedinger operators.

Research on control system of truck-mounted rig for coalbed methane

Directory of Open Access Journals (Sweden)

Wang Hejian

2018-01-01

Full Text Available The coal-bed methane (CBM as a kind energy is clean and efficient, also it can become a security risk in mining process if it could not get out of the coal seam. In view of the current large-scale exploitation of coal-bed methane resources, the development of drilling rig for CBM drilling is needed. The parameters and structures were introduced in the paper. The rig uses a highly integrated approach that integrates the required functions on the chassis of the vehicle to meet the needs of rapid installation and transportation. Drilling control system uses hydraulic control and electro-hydraulic control dual control mode, can achieve short-range and remote control operations. The control system include security circuits and electric control system. Through the field trial, it is shown that the rig can meet the construction of the majority of coalbed methane drilling in the country and the performance is stable and the operation is simple.

Crystal structure of a mixed-ligand silver(I complex of the non-steroidal anti-inflammatory drug diclofenac and pyrimidine

Directory of Open Access Journals (Sweden)

Sevim Hamamci Alisir

2016-10-01

Full Text Available In the title mixed-ligand silver(I coordination polymeric complex with the non-steroidal anti-inflammatory drug diclofenac (C14H11Cl2NO2 (diclH and pyrimidine (pym, namely poly[{μ2-2-[2-(2,6-dichloroanilinophenyl]acetato-κ2O:O′}(μ2-pyrimidine-κ2N1:N3silver(I], [Ag(C14H10Cl2NO2(C4H4N2]n or [Ag(μ-dicl(μ-pym]n, the very distorted tetrahedral AgN2O2 coordination centres comprise two N-atom donors from bridging pym ligands [Ag—N = 2.381 (3 and 2.412 (3 Å] and two carboxylate O-atom donors from dicl ligands [Ag—O = 2.279 (2 and 2.280 (2 Å], which bridge Ag atoms, giving a centrosymmetric dinuclear units with a short Ag...Ag separation [2.8931 (5 Å]. Within the units are short intraligand C—Cl...π(pym interactions [3.6409 (15 Å]. The units are linked through the bridging N atoms of the pym ligand into a two-dimensional sheet–polymer structure lying parallel to (100 and stabilized by inter-ring π–π interactions between the pym ligands [Cg...Cg = 3.4199 (17 Å]. Additional inter-unit C—H...O and C—H...Cg hydrogen-bonding interactions between the sheets give an overall three-dimensional structure.

Ligand identification using electron-density map correlations

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2007-01-01

An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

A calibration rig for multi-component internal strain gauge balance using the new design-of-experiment (DOE) approach

Science.gov (United States)

Nouri, N. M.; Mostafapour, K.; Kamran, M.

2018-02-01

In a closed water-tunnel circuit, the multi-component strain gauge force and moment sensor (also known as balance) are generally used to measure hydrodynamic forces and moments acting on scaled models. These balances are periodically calibrated by static loading. Their performance and accuracy depend significantly on the rig and the method of calibration. In this research, a new calibration rig was designed and constructed to calibrate multi-component internal strain gauge balances. The calibration rig has six degrees of freedom and six different component-loading structures that can be applied separately and synchronously. The system was designed based on the applicability of formal experimental design techniques, using gravity for balance loading and balance positioning and alignment relative to gravity. To evaluate the calibration rig, a six-component internal balance developed by Iran University of Science and Technology was calibrated using response surface methodology. According to the results, calibration rig met all design criteria. This rig provides the means by which various methods of formal experimental design techniques can be implemented. The simplicity of the rig saves time and money in the design of experiments and in balance calibration while simultaneously increasing the accuracy of these activities.

Development of a test rig and its application for validation and reliability testing of safety-critical software

Energy Technology Data Exchange (ETDEWEB)

Thai, N D; McDonald, A M [Atomic Energy of Canada Ltd., Mississauga, ON (Canada)

1996-12-31

This paper describes a versatile test rig developed by AECL for functional testing of safety-critical software used in the process trip computers of the Wolsong CANDU stations. The description covers the hardware and software aspects of the test rig, the test language and its interpreter, and other major testing software utilities such as the test oracle, sampler and profiler. The paper also discusses the application of the rig in the final stages of testing of the process trip computer software, namely validation and reliability tests. It shows how random test cases are generated, test scripts prepared and automatically run on the test rig. The versatility of the rig is further demonstrated in other types of testing such as sub-system tests, verification of the test oracle, testing of newly-developed test script, self-test and calibration. (author). 5 tabs., 10 figs.

Development of a test rig and its application for validation and reliability testing of safety-critical software

International Nuclear Information System (INIS)

Thai, N.D.; McDonald, A.M.

1995-01-01

This paper describes a versatile test rig developed by AECL for functional testing of safety-critical software used in the process trip computers of the Wolsong CANDU stations. The description covers the hardware and software aspects of the test rig, the test language and its interpreter, and other major testing software utilities such as the test oracle, sampler and profiler. The paper also discusses the application of the rig in the final stages of testing of the process trip computer software, namely validation and reliability tests. It shows how random test cases are generated, test scripts prepared and automatically run on the test rig. The versatility of the rig is further demonstrated in other types of testing such as sub-system tests, verification of the test oracle, testing of newly-developed test script, self-test and calibration. (author). 5 tabs., 10 figs

Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Directory of Open Access Journals (Sweden)

Wojciech Służewski

2011-10-01

Full Text Available Pattern recognition receptors (PRRs constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs and RIG-1-like helicase receptors (RLR in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 helicase showed the most marked expression. In hepatitis B, TLR1, 3, 9, NOD1 and NALP expression were the most conspicuous. Expression PRRs in liver from hepatitis of unknown origin was much lower. It was also the case in cytospins from human hepatoma cell line. Several correlations between PRRs expression and clinical findings in patients could be shown by statistical exploration. In conclusion, this data suggests some role for PRRs in the pathogenesis of chronic viral hepatitis. (<i>Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 410–416i>

The Hydraulic Test Report for Non-instrumented Irradiation Test Rig of DUO-Cooled Annular Pellet

International Nuclear Information System (INIS)

Kim, Dae Ho; Lee, Kang Hee; Shin, Chang Hwan; Yang, Yong Sik; Kim, Sun Ki; Bang, Je Geon; Song, Kun Woo

2007-08-01

This report presents the results of pressure drop test and vibration test for non-instrumented rig of Advanced PWR DUO-Fuel Annular Pellet which were designed and fabricated by KAERI. From the pressure drop test results, it is noted that the flow velocity across the non-instrumented rig of Advanced PWR DUO-Fuel Annular Pellet corresponding to the pressure drop of 200 kPa is measured to be about 8.30 kg/sec. Vibration frequency results for the non-instrumented rig at the pump spin frequency ranges from 19.0 to 32.0 Hz, RMS(Root Mean Square) displacement for the non-instrumented rig of Advanced PWR DUO-Fuel Annular Pellet is less than 7.25 m, and the maximum displacement is less than 31.27 μm. This test was performed at the FIVPET facility

iFER: facial expression recognition using automatically selected geometric eye and eyebrow features

Science.gov (United States)

Oztel, Ismail; Yolcu, Gozde; Oz, Cemil; Kazan, Serap; Bunyak, Filiz

2018-03-01

Facial expressions have an important role in interpersonal communications and estimation of emotional states or intentions. Automatic recognition of facial expressions has led to many practical applications and became one of the important topics in computer vision. We present a facial expression recognition system that relies on geometry-based features extracted from eye and eyebrow regions of the face. The proposed system detects keypoints on frontal face images and forms a feature set using geometric relationships among groups of detected keypoints. Obtained feature set is refined and reduced using the sequential forward selection (SFS) algorithm and fed to a support vector machine classifier to recognize five facial expression classes. The proposed system, iFER (eye-eyebrow only facial expression recognition), is robust to lower face occlusions that may be caused by beards, mustaches, scarves, etc. and lower face motion during speech production. Preliminary experiments on benchmark datasets produced promising results outperforming previous facial expression recognition studies using partial face features, and comparable results to studies using whole face information, only slightly lower by ˜ 2.5 % compared to the best whole face facial recognition system while using only ˜ 1 / 3 of the facial region.

Entropy in molecular recognition by proteins.

Science.gov (United States)

Caro, José A; Harpole, Kyle W; Kasinath, Vignesh; Lim, Jackwee; Granja, Jeffrey; Valentine, Kathleen G; Sharp, Kim A; Wand, A Joshua

2017-06-20

Molecular recognition by proteins is fundamental to molecular biology. Dissection of the thermodynamic energy terms governing protein-ligand interactions has proven difficult, with determination of entropic contributions being particularly elusive. NMR relaxation measurements have suggested that changes in protein conformational entropy can be quantitatively obtained through a dynamical proxy, but the generality of this relationship has not been shown. Twenty-eight protein-ligand complexes are used to show a quantitative relationship between measures of fast side-chain motion and the underlying conformational entropy. We find that the contribution of conformational entropy can range from favorable to unfavorable, which demonstrates the potential of this thermodynamic variable to modulate protein-ligand interactions. For about one-quarter of these complexes, the absence of conformational entropy would render the resulting affinity biologically meaningless. The dynamical proxy for conformational entropy or "entropy meter" also allows for refinement of the contributions of solvent entropy and the loss in rotational-translational entropy accompanying formation of high-affinity complexes. Furthermore, structure-based application of the approach can also provide insight into long-lived specific water-protein interactions that escape the generic treatments of solvent entropy based simply on changes in accessible surface area. These results provide a comprehensive and unified view of the general role of entropy in high-affinity molecular recognition by proteins.

A reciprocating pin-on-plate test-rig for studying friction materials for holding brakes

DEFF Research Database (Denmark)

Poulios, Konstantinos; Drago, Nicola; Klit, Peder

2014-01-01

-on-plate test-rig for studying the evolution of wear by monitoring the pin height reduction using Eddy-current proximity sensors is presented. Moreover, a new mechanism for recording the friction force is suggested. Apart from the design of the test-rig, friction force and wear rate measurements for two...

Resonances, scattering theory and rigged Hilbert spaces

International Nuclear Information System (INIS)

Parravicini, G.; Gorini, V.; Sudarshan, E.C.G.

1979-01-01

The problem of decaying states and resonances is examined within the framework of scattering theory in a rigged Hilbert space formalism. The stationary free, in, and out eigenvectors of formal scattering theory, which have a rigorous setting in rigged Hilbert space, are considered to be analytic functions of the energy eigenvalue. The value of these analytic functions at any point of regularity, real or complex, is an eigenvector with eigenvalue equal to the position of the point. The poles of the eigenvector families give origin to other eigenvectors of the Hamiltonian; the singularities of the out eigenvector family are the same as those of the continued S matrix, so that resonances are seen as eigenvectors of the Hamiltonian with eigenvalue equal to their location in the complex energy plane. Cauchy theorem then provides for expansions in terms of complete sets of eigenvectors with complex eigenvalues of the Hamiltonian. Applying such expansions to the survival amplitude of a decaying state, one finds that resonances give discrete contributions with purely exponential time behavior; the background is of course present, but explicitly separated. The resolvent of the Hamiltonian, restricted to the nuclear space appearing in the rigged Hilbert space, can be continued across the absolutely continuous spectrum; the singularities of the continuation are the same as those of the out eigenvectors. The free, in and out eigenvectors with complex eigenvalues and those corresponding to resonances can be approximated by physical vectors in the Hilbert space, as plane waves can. The need for having some further physical information in addition to the specification of the total Hamiltonian is apparent in the proposed framework. The formalism is applied to the Lee-Friedrichs model. 48 references

Injury Rates on New and Old Technology Oil and Gas Rigs Operated by the Largest United States Onshore Drilling Contractor

Science.gov (United States)

Blackley, David J.; Retzer, Kyla D.; Hubler, Warren G.; Hill, Ryan D.; Laney, A. Scott

2015-01-01

Background Occupational fatality rates among oil and gas extraction industry and specifically among drilling contractor workers are high compared to the U.S. all-industry average. There is scant literature focused on non-fatal injuries among drilling contractors, some of which have introduced engineering controls to improve rig efficiency and reduce injury risk. Methods We compared injury rates on new and old technology rigs operated by the largest U.S. drilling contractor during 2003–2012, stratifying by job type and grouping outcomes by injury severity and body part affected. Results Six hundred seventy-one injuries were recorded over 77.4 million person-hours. The rate on new rigs was 66% of that on old rigs. Roughnecks had lower injury rates on new rigs, largely through reduced limb injury rates. New rigs had lower rates in each non-fatal injury severity category. Conclusions For this company, new technology rigs appear to provide a safer environment for roughnecks. Future studies could include data from additional companies. PMID:25164118

Injury rates on new and old technology oil and gas rigs operated by the largest United States onshore drilling contractor.

Science.gov (United States)

Blackley, David J; Retzer, Kyla D; Hubler, Warren G; Hill, Ryan D; Laney, A Scott

2014-10-01

Occupational fatality rates among oil and gas extraction industry and specifically among drilling contractor workers are high compared to the U.S. all-industry average. There is scant literature focused on non-fatal injuries among drilling contractors, some of which have introduced engineering controls to improve rig efficiency and reduce injury risk. We compared injury rates on new and old technology rigs operated by the largest U.S. drilling contractor during 2003-2012, stratifying by job type and grouping outcomes by injury severity and body part affected. Six hundred seventy-one injuries were recorded over 77.4 million person-hours. The rate on new rigs was 66% of that on old rigs. Roughnecks had lower injury rates on new rigs, largely through reduced limb injury rates. New rigs had lower rates in each non-fatal injury severity category. For this company, new technology rigs appear to provide a safer environment for roughnecks. Future studies could include data from additional companies. © 2014 Wiley Periodicals, Inc.

The Design and Manufacturing Report of Plug Type Non-Instrumented Rig for Irradiation Test in HANARO OR Hole

Energy Technology Data Exchange (ETDEWEB)

Kim, Dae Ho; Bang, Je Geon; Lim, Ik Sung; Kim, Sun Ki; Yang, Yong Sik; Song, Kun Woo

2008-09-15

This project is developed the plug type non-instrumented irradiation test rig of the advanced nuclear fuel in HANARO for pursuit advanced performance in High Performance Fuel Technology Development as a part Nuclear Mid and Long-term R and D Program. This irradiation rig was confirmed the integrity and HANARO core compatibility by the optimum design and the thermal hydraulic out-pile test in FIVPET. The characteristic of plug type non-instrument rig is to possible irradiation test of variable in-pile condition and reduced the wastes for reusable as function. This plug type non-instrumented rig was satisfied the quality assurance requirements and written out the end of manufacturing report. This plug type non-instrumented rig is adopt to the irradiation test for nuclear fuel irradiation test in HANARO OR hole.

Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

Directory of Open Access Journals (Sweden)

Qin Lan

2011-12-01

Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

Local gene regulation details a recognition code within the LacI transcriptional factor family.

Directory of Open Access Journals (Sweden)

Francisco M Camas

2010-11-01

Full Text Available The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs and nucleotides (NTs. This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs. We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations--determined by two AAs of the TFs and two NTs in the binding sites--that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications.

Estimation of kinetic and thermodynamic ligand-binding parameters using computational strategies.

Science.gov (United States)

Deganutti, Giuseppe; Moro, Stefano

2017-04-01

Kinetic and thermodynamic ligand-protein binding parameters are gaining growing importance as key information to consider in drug discovery. The determination of the molecular structures, using particularly x-ray and NMR techniques, is crucial for understanding how a ligand recognizes its target in the final binding complex. However, for a better understanding of the recognition processes, experimental studies of ligand-protein interactions are needed. Even though several techniques can be used to investigate both thermodynamic and kinetic profiles for a ligand-protein complex, these procedures are very often laborious, time consuming and expensive. In the last 10 years, computational approaches have enormous potential in providing insights into each of the above effects and in parsing their contributions to the changes in both kinetic and thermodynamic binding parameters. The main purpose of this review is to summarize the state of the art of computational strategies for estimating the kinetic and thermodynamic parameters of a ligand-protein binding.

Mach 0.3 Burner Rig Facility at the NASA Glenn Materials Research Laboratory

Science.gov (United States)

Fox, Dennis S.; Miller, Robert A.; Zhu, Dongming; Perez, Michael; Cuy, Michael D.; Robinson, R. Craig

2011-01-01

This Technical Memorandum presents the current capabilities of the state-of-the-art Mach 0.3 Burner Rig Facility. It is used for materials research including oxidation, corrosion, erosion and impact. Consisting of seven computer controlled jet-fueled combustors in individual test cells, these relatively small rigs burn just 2 to 3 gal of jet fuel per hour. The rigs are used as an efficient means of subjecting potential aircraft engine/airframe advanced materials to the high temperatures, high velocities and thermal cycling closely approximating actual operating environments. Materials of various geometries and compositions can be evaluated at temperatures from 700 to 2400 F. Tests are conducted not only on bare superalloys and ceramics, but also to study the behavior and durability of protective coatings applied to those materials.

Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations.

Science.gov (United States)

Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O

2013-10-28

End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring

Variations of structures and solid-state conductivity of isomeric silver(I) coordination polymers having linear and V-shaped thiophene-centered ditriazole ligands

International Nuclear Information System (INIS)

Hu, Bin; Geng, Jiao; Zhang, Lie; Huang, Wei

2014-01-01

A pair of new linear and V-shaped acceptor–donor–acceptor (A−D−A) thiophene-centered ditriazole structural isomers, i.e., 2,5-di(1H-1,2,4-triazol-1-yl)thiophene (L 1 ) and 3,4-di(1H-1,2,4-triazol-1-yl)thiophene (L 2 ), has been synthesized and characterized. They are used as μ 2 -bridging ligands to prepare a pair of silver(I) coordination polymers formulated as [Ag(L 1 )(NO 3 )] n (1) and [Ag(L 2 )(NO 3 )] n (2), which are also structural isomers at the supramolecular level. X-ray single-crystal diffraction analyses for 1 and 2 reveal that they exhibit the same one-dimensional (1D) coordination polymers but different structural architectures because of the distinguishable shape and configuration of isomeric ligands (L 1 and L 2 ) and the alterations of the coordination numbers. More interestingly, compared with the free ligands, 1D silver(I) polymeric isomers 1 and 2 show significant enhancement of solid-state conductivity to different extents (1.42×10 4 and 2.17×10 3 times), where 6.96 times' enhancement of solid-state conductivity from 1 to 2 has been observed. The formation of Ag–N coordinative bonds and the configurational discrepancy of L 1 and L 2 are believed to play important roles in facilitating the electron transport between molecules, which can also be supported by Density Function Theory calculations of their band gaps. - Graphical abstract: A pair of linear and V-shaped isomeric thiophene-centered ditriazole ligands (L 1 ) and L 2 are used to prepare a pair of silver(I) polymeric isomers (1 and 2), where significant enhancement of solid-state conductivity to different extents are observed originating from the distinguishable shape and configuration of isomeric ligands. - Highlights: • A pair of linear and V-shaped thiophene-centered ditriazole structural isomers is prepared. • They are used as µ 2 -bridging ligands to prepare a pair of silver(I) polymeric isomers. • Significant enhancement of solid-state conductivity is observed

Test Rig for Valves of Digital Displacement Machines

DEFF Research Database (Denmark)

Nørgård, Christian; Christensen, Jeppe Haals; Bech, Michael Møller

2017-01-01

A test rig for the valves of digital displacement machines has been developed at Aalborg University. It is composed of a commercial radial piston machine, which has been modified to facilitate Digital Displacement operation for a single piston. Prototype valves have been optimized, designed and m...

Design and Demonstration of a Test-Rig for Static Performance-Studies of Permanent Magnet Couplings

DEFF Research Database (Denmark)

Högberg, Stig; Jensen, Bogi Bech; Bendixen, Flemming Buus

2013-01-01

The design and construction of an easy-to-use test-rig for permanent magnet couplings is presented. Static torque of permanent magnet couplings as a function of angular displacement is measured of permanent magnet couplings through an semi-automated test system. The test-rig is capable of measuring...

A novel test rig to investigate under-platform damper dynamics

Science.gov (United States)

Botto, Daniele; Umer, Muhammad

2018-02-01

In the field of turbomachinery, vibration amplitude is often reduced by dissipating the kinetic energy of the blades with devices that utilize dry friction. Under-platform dampers, for example, are often placed in the underside of two consecutive turbine blades. Dampers are kept in contact with the under-platform of the respective blades by means of the centrifugal force. If the damper is well designed, vibration of blades instigate a relative motion between the under-platform and the damper. A friction force, that is a non-conservative force, arises in the contact and partly dissipates the vibration energy. Several contact models are available in the literature to simulate the contact between the damper and the under-platform. However, the actual dynamics of the blade-damper interaction have not fully understood yet. Several test rigs have been previously developed to experimentally investigate the performance of under-platform dampers. The majority of these experimental setups aim to evaluate the overall damper efficiency in terms of reduction in response amplitude of the blade for a given exciting force that simulates the aerodynamic loads. Unfortunately, the experimental data acquired on the blade dynamics do not provide enough information to understand the damper dynamics. Therefore, the uncertainty on the damper behavior remains a big issue. In this work, a novel experimental test rig has been developed to extensively investigate the damper dynamic behavior. A single replaceable blade is clamped in the rig with a specific clamping device. With this device the blade root is pressed against a groove machined in the test rig. The pushing force is controllable and measurable, to better simulate the actual centrifugal load acting on the blade. Two dampers, one on each side of the blade, are in contact with the blade under-platforms and with platforms on force measuring supports. These supports have been specifically designed to measure the contact forces on the

Cloning of low dose radiation induced gene RIG1 by RACE based on non-cloned cDNA library

International Nuclear Information System (INIS)

Luo Ying; Sui Jianli; Tie Yi; Zhang Yuanping; Zhou Pingkun; Sun Zhixian

2001-01-01

Objective: To obtain full-length cDNA of radiation induced new gene RIG1 based on its EST fragment. Methods: Based on non-cloned cDNA library, enhanced nested RACE PCR and biotin-avidin labelled probe for magnetic bead purification was used to obtain full-length cDNA of RIG1. Results: About 1 kb of 3' end of RIG1 gene was successfully cloned by this set of methods and cloning of RIG1 5' end is proceeding well. Conclusion: The result is consistent with the design of experiment. This set of protocol is useful for cloning of full-length gene based on EST fragment

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

Science.gov (United States)

Martínez, Isidoro; Oliveros, Juan C.; Cuesta, Isabel; de la Barrera, Jorge; Ausina, Vicente; Casals, Cristina; de Lorenzo, Alba; García, Ernesto; García-Fojeda, Belén; Garmendia, Junkal; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortín, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos-Sevillano, Elisa; Regueiro, Verónica; Rodriguez-Frandsen, Ariel; Solís, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.

2017-01-01

Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here. PMID:28298903

Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems

DEFF Research Database (Denmark)

Rasmussen, Simon Brandtoft; Sørensen, Louise Nørgaard; Malmgaard, Lene

2007-01-01

Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes...... simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-alpha/beta) response is derived from several cell types and induced independently of TLR9...

A Study on the Dynamic Analysis of the Nuclear Fuel Test Rig Using 1-Way Fluid-Structure Coupled Analysis

International Nuclear Information System (INIS)

Yang, Tae-Ho; Hong, Jin-Tae; Ahn, Sung-Ho; Joung, Chang-Young; Heo, Sung-Ho; Jang, Seo-Yun

2015-01-01

1-way fluid-structure coupled analysis is used to estimate the dynamic characteristic of the fuel test rig. the motion at the bottom of the test rig is confirmed. The maximum deformation of the test rig is 0.11 mm. The structural integrity of the test rig is performed by using the comparison with the Von-mises stress of the analysis and yield stress of the material. It is evaluated that the motion at the bottom of the test rig is able to cause other structural problem. Using the 2-way fluid-structural coupled analysis, the structural integrity of the test rig will be performed in further paper. The cooling water with specific flow rate was flowed in the nuclear fuel test rig. The structural integrity of the test rig was affected by the vibration. The fluid-induced vibration test had to be performed to obtain the amplitude of the vibration on the structure. Various test systems was developed. Flow-induced vibration and pressure drop experimental tester was developed in Korea Atomic Energy Research Institute. The vibration test with high fluid flow rate was difficult by the tester. To generate the nuclear fuel test environment, coolant flow simulation system was developed. The scaled nuclear fuel test was able to be performed by the simulation system. The mock-up model of the test rig was used in the simulation system. The mock-up model in the simulation system was manufactured with scaled down full model. In this paper, the fluid induced vibration characteristic of the full model in the nuclear fuel test is studied. The hydraulic pressure on the velocity of the fluid was calculated. The static structure analysis was performed by using the pressure. The structural integrity was assessed using the results of the analysis

Complete Vision-Based Traffic Sign Recognition Supported by an I2V Communication System

Directory of Open Access Journals (Sweden)

Miguel Gavilán

2012-01-01

Full Text Available This paper presents a complete traffic sign recognition system based on vision sensor onboard a moving vehicle which detects and recognizes up to one hundred of the most important road signs, including circular and triangular signs. A restricted Hough transform is used as detection method from the information extracted in contour images, while the proposed recognition system is based on Support Vector Machines (SVM. A novel solution to the problem of discarding detected signs that do not pertain to the host road is proposed. For that purpose infrastructure-to-vehicle (I2V communication and a stereo vision sensor are used. Furthermore, the outputs provided by the vision sensor and the data supplied by the CAN Bus and a GPS sensor are combined to obtain the global position of the detected traffic signs, which is used to identify a traffic sign in the I2V communication. This paper presents plenty of tests in real driving conditions, both day and night, in which an average detection rate over 95% and an average recognition rate around 93% were obtained with an average runtime of 35 ms that allows real-time performance.

Complete vision-based traffic sign recognition supported by an I2V communication system.

Science.gov (United States)

García-Garrido, Miguel A; Ocaña, Manuel; Llorca, David F; Arroyo, Estefanía; Pozuelo, Jorge; Gavilán, Miguel

2012-01-01

This paper presents a complete traffic sign recognition system based on vision sensor onboard a moving vehicle which detects and recognizes up to one hundred of the most important road signs, including circular and triangular signs. A restricted Hough transform is used as detection method from the information extracted in contour images, while the proposed recognition system is based on Support Vector Machines (SVM). A novel solution to the problem of discarding detected signs that do not pertain to the host road is proposed. For that purpose infrastructure-to-vehicle (I2V) communication and a stereo vision sensor are used. Furthermore, the outputs provided by the vision sensor and the data supplied by the CAN Bus and a GPS sensor are combined to obtain the global position of the detected traffic signs, which is used to identify a traffic sign in the I2V communication. This paper presents plenty of tests in real driving conditions, both day and night, in which an average detection rate over 95% and an average recognition rate around 93% were obtained with an average runtime of 35 ms that allows real-time performance.

The CC chemokine receptor 5 regulates olfactory and social recognition in mice.

Science.gov (United States)

Kalkonde, Y V; Shelton, R; Villarreal, M; Sigala, J; Mishra, P K; Ahuja, S S; Barea-Rodriguez, E; Moretti, P; Ahuja, S K

2011-12-01

Chemokines are chemotactic cytokines that regulate cell migration and are thought to play an important role in a broad range of inflammatory diseases. The availability of chemokine receptor blockers makes them an important therapeutic target. In vitro, chemokines are shown to modulate neurotransmission. However, it is not very clear if chemokines play a role in behavior and cognition. Here we evaluated the role of CC chemokine receptor 5 (CCR5) in various behavioral tasks in mice using Wt (Ccr5⁺/⁺) and Ccr5-null (Ccr5⁻/⁻)mice. Ccr5⁻/⁻ mice showed enhanced social recognition. Administration of CC chemokine ligand 3 (CCL3), one of the CCR5-ligands, impaired social recognition. Since the social recognition task is dependent on the sense of olfaction, we tested olfactory recognition for social and non-social scents in these mice. Ccr5⁻/⁻ mice had enhanced olfactory recognition for both these scents indicating that enhanced performance in social recognition task could be due to enhanced olfactory recognition in these mice. Spatial memory and aversive memory were comparable in Wt and Ccr5⁻/⁻ mice. Collectively, these results suggest that chemokines/chemokine receptors might play an important role in olfactory recognition tasks in mice and to our knowledge represents the first direct demonstration of an in vivo role of CCR5 in modulating social behavior in mice. These studies are important as CCR5 blockers are undergoing clinical trials and can potentially modulate behavior. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

CONCENTRIC TUBE-FOULING RIG FOR INVESTIGATION OF FOULING DEPOSIT FORMATION FROM PASTEURISER OF VISCOUS FOOD LIQUID

Directory of Open Access Journals (Sweden)

N. I. KHALID

2013-02-01

Full Text Available This paper reports the work on developing concentric tube-fouling rig, a new fouling deposit monitoring device. This device can detect and quantify the level of fouling deposit formation. It can also functioning as sampler for fouling deposit study, which can be attached at any food processing equipment. The design is initiated with conceptual design. The rig is designed with inner diameter of 7 cm and with tube length of 37 cm. A spiral insert with 34.5 cm length and with 5.4 cm diameter is fitted inside the tube to ensure the fluid flows around the tube. In this work, the rig is attached to the lab-scale concentric tube-pasteurizer to test its effectiveness and to collect a fouling sample after pasteurization of pink guava puree. Temperature changes are recorded during the pasteurization and the data is used to plot the heat transfer profile. Thickness of the fouling deposit is also measured. The trends for thickness, heat resistance profile and heat transfer profile for concentric tube-fouling rig matched the trends obtained from lab-scale concentric tube-pasteurizer very well. The findings from this work have shown a good potential of this rig however there is a limitation with spiral insert, which is discussed in this paper.

Simultaneous topography and recognition imaging: physical aspects and optimal imaging conditions

International Nuclear Information System (INIS)

Preiner, Johannes; Ebner, Andreas; Zhu Rong; Hinterdorfer, Peter; Chtcheglova, Lilia

2009-01-01

Simultaneous topography and recognition imaging (TREC) allows for the investigation of receptor distributions on natural biological surfaces under physiological conditions. Based on atomic force microscopy (AFM) in combination with a cantilever tip carrying a ligand molecule, it enables us to sense topography and recognition of receptor molecules simultaneously with nanometre accuracy. In this study we introduce optimized handling conditions and investigate the physical properties of the cantilever-tip-sample ensemble, which is essential for the interpretation of the experimental data gained from this technique. In contrast to conventional AFM methods, TREC is based on a more sophisticated feedback loop, which enables us to discriminate topographical contributions from recognition events in the AFM cantilever motion. The features of this feedback loop were investigated through a detailed analysis of the topography and recognition data obtained on a model protein system. Single avidin molecules immobilized on a mica substrate were imaged with an AFM tip functionalized with a biotinylated IgG. A simple procedure for adjusting the optimal amplitude for TREC imaging is described by exploiting the sharp localization of the TREC signal within a small range of oscillation amplitudes. This procedure can also be used for proving the specificity of the detected receptor-ligand interactions. For understanding and eliminating topographical crosstalk in the recognition images we developed a simple theoretical model, which nicely explains its origin and its dependence on the excitation frequency.

Aptamer-Based Molecular Recognition of Lysergamine, Metergoline and Small Ergot Alkaloids

Directory of Open Access Journals (Sweden)

Johan Robbens

2012-12-01

Full Text Available Ergot alkaloids are mycotoxins produced by fungi of the genus Claviceps, which infect cereal crops and grasses. The uptake of ergot alkaloid contaminated cereal products can be lethal to humans and animals. For food safety assessment, analytical techniques are currently used to determine the presence of ergot alkaloids in food and feed samples. However, the number of samples which can be analyzed is limited, due to the cost of the equipment and the need for skilled personnel. In order to compensate for the lack of rapid tests for the detection of ergot alkaloids, the aim of this study was to develop a specific recognition element for ergot alkaloids, which could be further applied to produce a colorimetric reaction in the presence of these toxins. As recognition elements, single-stranded DNA ligands were selected by using an iterative selection procedure named SELEX, i.e., Systematic Evolution of Ligands by EXponential enrichment. After several selection cycles, the resulting aptamers were cloned and sequenced. A surface plasmon resonance analysis enabled determination of the dissociation constants of the complexes of aptamers and lysergamine. Dissociation constants in the nanomolar range were obtained with three selected aptamers. One of the selected aptamers, having a dissociation constant of 44 nM, was linked to gold nanoparticles and it was possible to produce a colorimetric reaction in the presence of lysergamine. This system could also be applied to small ergot alkaloids in an ergot contaminated flour sample.

Electronic temperature control and measurements reactor fuel rig circuits

Energy Technology Data Exchange (ETDEWEB)

Glowacki, S W

1980-01-01

The electronic circuits of two digital temperature meters developed for the thermocouple of Ni-NiCr type are described. The output thermocouple signal as converted by means of voltage-to-freguency converter. The frequency is measured by a digital scaler controled by quartz generator signals. One of the described meter is coupled with digital temperature controler which drives the power stage of the reactor rig heater. The internal rig temperature is measured by the thermocouple providing the input signal to the mentioned voltage-to-frequency converter, that means the circuits work in the negative feedback loop. The converter frequency-to-voltage ratio is automatically adjusted to match to thermocouple sensitivity changes in the course of the temperature variations. The accuracy of measuring system is of order of +- 1degC for thermocouple temperature changes from 523 K up to 973 K (50degC up to 700degC).

Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

International Nuclear Information System (INIS)

Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H.

1990-01-01

To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the α-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor

The Thermal-hydraulic Performance Test Report for the Non-instrumented Irradiation Test Rig of Annular Fuel

Energy Technology Data Exchange (ETDEWEB)

Kim, Dae Ho; Lee, Kang Hee; Shin, Chang Hwan

2008-09-15

This report presents the results of pressure drop test, vibration test and endurance test for the non-instrumented rig using the irradiation test in HANARO of the double cooled annular fuel which were designed and fabricated by KAERI. From the out-pile thermal hydraulic tests, corresponding to the pressure drop of 200 kPa is measured to be about 9.72 kg/sec. Vibration frequency for the non-instrumented rig ranges from 5.0 to 10.7 kg/s. RMS(Root Mean Square) displacement for non-instrumented rig is less than 11.73 m, and the maximum displacement is less than 54.87m. The flow rate for endurance test were 10.5 kg/s, which was 110% of 9.72 kg/s. And the endurance test was carried out for 3 days. The test results found not to the wear and satisfied to the limits of pressure drop, flow rate, vibration and wear in the non-instrumented rig. This test was performed at the FIVPET facility.

Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor

DEFF Research Database (Denmark)

Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars

2005-01-01

of the ligand. Each isolated fragment of IF was tested for the binding to the specific receptor cubilin in the presence or absence of Cbl. Neither apo nor holo forms of IF(20) and IF(30) were recognized by the receptor. When two fragments were mixed and incubated with Cbl, they associated into a stable complex......; however, efficient retention of the ligand required the presence of both fragments. Detailed schemes of the interaction of Cbl with IF(50) and with IF(30) and IF(20) are presented, where the sequential attachment of Cbl to the IF(20) and IF(30) domains plays the key role in recognition and retention......, IF(30+20).Cbl, which bound to cubilin as well as the noncleaved IF(50).Cbl complex. We suggest that formation of the cubilin recognition site on IF is caused by assembly of two distant domains, which allows the saturated protein to be recognized by the receptor. The obtained parameters for ligand...

Collisions damage assessment of ships and jack-up rigs

DEFF Research Database (Denmark)

Zhang, Shengming; Pedersen, P. Terndrup; Ocakli, Hasan

2015-01-01

Ship collision with offshore installations is one of the key concerns in design and assess of platforms performance and safety. This paper presents an analysis on collision energy and structural damage in ship and offshore platform collisions for various collision scenarios. The platform or rig...

The method of rigged spaces in singular perturbation theory of self-adjoint operators

CERN Document Server

Koshmanenko, Volodymyr; Koshmanenko, Nataliia

2016-01-01

This monograph presents the newly developed method of rigged Hilbert spaces as a modern approach in singular perturbation theory. A key notion of this approach is the Lax-Berezansky triple of Hilbert spaces embedded one into another, which specifies the well-known Gelfand topological triple. All kinds of singular interactions described by potentials supported on small sets (like the Dirac δ-potentials, fractals, singular measures, high degree super-singular expressions) admit a rigorous treatment only in terms of the equipped spaces and their scales. The main idea of the method is to use singular perturbations to change inner products in the starting rigged space, and the construction of the perturbed operator by the Berezansky canonical isomorphism (which connects the positive and negative spaces from a new rigged triplet). The approach combines three powerful tools of functional analysis based on the Birman-Krein-Vishik theory of self-adjoint extensions of symmetric operators, the theory of singular quadra...

Micro-pyrolysis of technical lignins in a new modular rig and product analysis by GC-MS/FID and GC x GC-TOFMS/FID

NARCIS (Netherlands)

Windt, Michael; Meier, Dietrich; Marsman, Jan Henk; Heeres, Hero Jan; de Koning, Sjaak

A new offline-pyrolysis rig has been designed to allow multifunctional experiments for preparative and analytical purposes. The system conditions can be set and monitored, e.g. temperature, its gradients and heat flux. Some special features include ( I) high heating rates up to 120 degrees C/s with

Test rig overview for validation and reliability testing of shutdown system software

International Nuclear Information System (INIS)

Zhao, M.; McDonald, A.; Dick, P.

2007-01-01

The test rig for Validation and Reliability Testing of shutdown system software has been upgraded from the AECL Windows-based test rig previously used for CANDU6 stations. It includes a Virtual Trip Computer, which is a software simulation of the functional specification of the trip computer, and a real-time trip computer simulator in a separate chassis, which is used during the preparation of trip computer test cases before the actual trip computers are available. This allows preparation work for Validation and Reliability Testing to be performed in advance of delivery of actual trip computers to maintain a project schedule. (author)

Performance Analysis of Retrofitted Tribo-Corrosion Test Rig for Monitoring In Situ Oil Conditions

Directory of Open Access Journals (Sweden)

Arpith Siddaiah

2017-09-01

Full Text Available Oils and lubricants, once extracted after use from a mechanical system, can hardly be reused, and should be refurbished or replaced in most applications. New methods of in situ oil and lubricant efficiency monitoring systems have been introduced for a wide variety of mechanical systems, such as automobiles, aerospace aircrafts, ships, offshore wind turbines, and deep sea oil drilling rigs. These methods utilize electronic sensors to monitor the “byproduct effects” in a mechanical system that are not indicative of the actual remaining lifecycle and reliability of the oils. A reliable oil monitoring system should be able to monitor the wear rate and the corrosion rate of the tribo-pairs due to the inclusion of contaminants. The current study addresses this technological gap, and presents a novel design of a tribo-corrosion test rig for oils used in a dynamic system. A pin-on-disk tribometer test rig retrofitted with a three electrode-potentiostat corrosion monitoring system was used to analyze the corrosion and wear rate of a steel tribo-pair in industrial grade transmission oil. The effectiveness of the retrofitted test rig was analyzed by introducing various concentrations of contaminants in an oil medium that usually leads to a corrosive working environment. The results indicate that the retrofitted test rig can effectively monitor the in situ tribological performance of the oil in a controlled dynamic corrosive environment. It is a useful method to understand the wear–corrosion synergies for further experimental work, and to develop accurate predictive lifecycle assessment and prognostic models. The application of this system is expected to have economic benefits and help reduce the ecological oil waste footprint.

Performance Analysis of Retrofitted Tribo-Corrosion Test Rig for Monitoring In Situ Oil Conditions.

Science.gov (United States)

Siddaiah, Arpith; Khan, Zulfiqar Ahmad; Ramachandran, Rahul; Menezes, Pradeep L

2017-09-28

Oils and lubricants, once extracted after use from a mechanical system, can hardly be reused, and should be refurbished or replaced in most applications. New methods of in situ oil and lubricant efficiency monitoring systems have been introduced for a wide variety of mechanical systems, such as automobiles, aerospace aircrafts, ships, offshore wind turbines, and deep sea oil drilling rigs. These methods utilize electronic sensors to monitor the "byproduct effects" in a mechanical system that are not indicative of the actual remaining lifecycle and reliability of the oils. A reliable oil monitoring system should be able to monitor the wear rate and the corrosion rate of the tribo-pairs due to the inclusion of contaminants. The current study addresses this technological gap, and presents a novel design of a tribo-corrosion test rig for oils used in a dynamic system. A pin-on-disk tribometer test rig retrofitted with a three electrode-potentiostat corrosion monitoring system was used to analyze the corrosion and wear rate of a steel tribo-pair in industrial grade transmission oil. The effectiveness of the retrofitted test rig was analyzed by introducing various concentrations of contaminants in an oil medium that usually leads to a corrosive working environment. The results indicate that the retrofitted test rig can effectively monitor the in situ tribological performance of the oil in a controlled dynamic corrosive environment. It is a useful method to understand the wear-corrosion synergies for further experimental work, and to develop accurate predictive lifecycle assessment and prognostic models. The application of this system is expected to have economic benefits and help reduce the ecological oil waste footprint.

78 FR 70326 - Rigging Equipment for Material Handling; Extension of the Office of Management and Budget's (OMB...

Science.gov (United States)

2013-11-25

...] Rigging Equipment for Material Handling; Extension of the Office of Management and Budget's (OMB) Approval... on Rigging Equipment for Material Handling (29 CFR 1926.251). These paragraphs require affixing... automated or other technological information collection and transmission techniques. III. Proposed Actions...

Joint test rig for tests and calibration of different methods of two-phase mass flow measurement

International Nuclear Information System (INIS)

John, H.; Erbacher, F.; Wanner, E.

1975-01-01

On behalf of the Federal Ministry of Research and Technology, the Institute of Reactor Components (IRB) has begun building a test rig which will be used for testing and calibrating the methods of measuring non-steady state two-phase mass flows developed by various research agencies. The test rig is designed for the generation of steam-water mixtures of any mixing ratio and a maximum pressure of 160 data. Depending on the mixing ratio, the mass flow will reach a maximum level of 10 to 20 t/h. The conceptual design phase of the test rig has largely been finished, the component ordering phase has begun. (orig.) [de

Residue preference mapping of ligand fragments in the Protein Data Bank.

Science.gov (United States)

Wang, Lirong; Xie, Zhaojun; Wipf, Peter; Xie, Xiang-Qun

2011-04-25

The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71 798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

Substrate Recognition in the <i>Escherichia coli i>Ammonia Channel AmtB: A QM/MM Investigation

DEFF Research Database (Denmark)

Nygaard, Thomas Pedersen; Alfonso-Prieto, M.; Peters, Günther H.J.

2010-01-01

understood. The present computational study addresses the importance of intermolecular interactions with respect to substrate recruitment and recognition by means of ab initio QM/MM simulations. On the basis of calculations with substrates NH3, NH4+, Na+, and K+ positioned at the periplasmic binding site (Am......1) and NH3 and NH4+ at intraluminal binding sites (Am1a/b), we conclude that D160 is the single most important residue for substrate recruitment, whereas cation-pi interactions to W148 and F107 are found to be less important. Regarding substrate recruitment and recognition, we find that only NH4......+ and K+ reach the Am1 site. However, NH4+ has the largest affinity for this site due to its better dehydration compensation, while charge stabilization effects favor the binding of NH4+ over NH3 (i.e., if NH3 would enter the Am1 site, it is likely to be protonated). Therefore, we conclude that the Am1...

Molecular mechanism of ligand recognition by membrane transport protein, Mhp1

Science.gov (United States)

Simmons, Katie J; Jackson, Scott M; Brueckner, Florian; Patching, Simon G; Beckstein, Oliver; Ivanova, Ekaterina; Geng, Tian; Weyand, Simone; Drew, David; Lanigan, Joseph; Sharples, David J; Sansom, Mark SP; Iwata, So; Fishwick, Colin WG; Johnson, A Peter; Cameron, Alexander D; Henderson, Peter JF

2014-01-01

The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. PMID:24952894

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Science.gov (United States)

Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun

2017-10-19

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

Science.gov (United States)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Cytotoxic effects of 125I-labeled PBZr ligand PK 11195 in prostatic tumor cells: therapeutic implications

International Nuclear Information System (INIS)

Alenfall, J.; Kant, R.; Batra, S.

1998-01-01

The effect of [ 125 I]PK 11195 was examined in human prostatic tumor cells (DU 145) in culture and compared with Na[ 125 I] and non-radioactive PK 11195. [ 125 I]PK 11195 was clearly cytocidal. The data for dose-related cell survival with [ 125 I]PK 11195 showed a linear relationship. Na[ 125 I] or non-labeled PK 11195 at similar concentrations did not lead to any cell killing. The uptake of [ 125 I]PK 11195 and [ 3 H]PK 11195 in cells was very similar. Fragmentation of DNA measured by agarose gel electrophoresis showed that exposure of DU 145 cells to [ 125 I]PK 11195 for 1, 4 or 24 h caused no fragmentation. These results indicate that nuclear DNA is not the prime binding site for [ 125 I]PK 11195, which is consistent with the presence of specific peripheral benzodiazepine receptors (PBZr) in the mitochondria. The cell killing effect of [ 125 I]PK 11195 suggests the use of PBZr ligand for radiotherapy

The silver(I nitrate complex of the ligand N-(pyridin-2-ylmethylpyrazine-2-carboxamide: a metal–organic framework (MOF structure

Directory of Open Access Journals (Sweden)

Dilovan S. Cati

2017-04-01

Full Text Available The reaction of silver(I nitrate with the mono-substituted pyrazine carboxamide ligand, N-(pyridin-2-ylmethylpyrazine-2-carboxamide (L, led to the formation of the title compound with a metal–organic framework (MOF structure, [Ag(C11H10N4O(NO3]n, poly[μ-nitrato-[μ-N-(pyridin-2-ylmethyl-κNpyrazine-2-carboxamide-κN4]silver(I]. The silver(I atom is coordinated by a pyrazine N atom, a pyridine N atom, and two O atoms of two symmetry-related nitrate anions. It has a fourfold N2O2 coordination sphere, which can be described as distorted trigonal–pyramidal. The ligands are bridged by the silver atoms forming –Ag–L–Ag–L– zigzag chains along the a-axis direction. The chains are arranged in pairs related by a twofold screw axis. They are linked via the nitrate anions, which bridge the silver(I atoms in a μ2 fashion, forming the MOF structure. Within the framework there are N—H...O and C—H...O hydrogen bonds present.

Real-Time Ligand Binding Pocket Database Search Using Local Surface Descriptors

Science.gov (United States)

Chikhi, Rayan; Sael, Lee; Kihara, Daisuke

2010-01-01

Due to the increasing number of structures of unknown function accumulated by ongoing structural genomics projects, there is an urgent need for computational methods for characterizing protein tertiary structures. As functions of many of these proteins are not easily predicted by conventional sequence database searches, a legitimate strategy is to utilize structure information in function characterization. Of a particular interest is prediction of ligand binding to a protein, as ligand molecule recognition is a major part of molecular function of proteins. Predicting whether a ligand molecule binds a protein is a complex problem due to the physical nature of protein-ligand interactions and the flexibility of both binding sites and ligand molecules. However, geometric and physicochemical complementarity is observed between the ligand and its binding site in many cases. Therefore, ligand molecules which bind to a local surface site in a protein can be predicted by finding similar local pockets of known binding ligands in the structure database. Here, we present two representations of ligand binding pockets and utilize them for ligand binding prediction by pocket shape comparison. These representations are based on mapping of surface properties of binding pockets, which are compactly described either by the two dimensional pseudo-Zernike moments or the 3D Zernike descriptors. These compact representations allow a fast real-time pocket searching against a database. Thorough benchmark study employing two different datasets show that our representations are competitive with the other existing methods. Limitations and potentials of the shape-based methods as well as possible improvements are discussed. PMID:20455259

Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

DEFF Research Database (Denmark)

Rognan, D; Engberg, J; Stryhn, A

2000-01-01

-peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

Science.gov (United States)

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-01-01

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

Accelerated Bearing Life-time Test Rig Development for Low Speed Data Acquisition

Directory of Open Access Journals (Sweden)

Andreas Klausen

2017-07-01

Full Text Available Condition monitoring plays an important role in rotating machinery to ensure reliability of the equipment, and to detect fault conditions at an early stage. Although health monitoring methodologies have been thoroughly developed for rotating machinery, low-speed conditions often pose a challenge due to the low signal-to-noise ratio. To this aim, sophisticated algorithms that reduce noise and highlight the bearing faults are necessary to accurately diagnose machines undergoing this condition. In the development phase, sensor data from a healthy and damaged bearing rotating at low-speed is required to verify the performance of such algorithms. A test rig for performing accelerated life-time testing of small rolling element bearings is designed to collect necessary sensor data. Heavy loads at high-speed conditions are applied to the test bearing to wear it out fast. Sensor data is collected in intervals during the test to capture the degeneration features. The main objective of this paper is to provide a detailed overview for the development and analysis of this test rig. A case study with experimental vibration data is also presented to illustrate the efficacy of the developed test rig.

Substrate coated with receptor and labelled ligand for assays

International Nuclear Information System (INIS)

1980-01-01

Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

Science.gov (United States)

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Urate is a ligand for the transcriptional regulator PecS.

Science.gov (United States)

Perera, Inoka C; Grove, Anne

2010-09-24

PecS is a member of the MarR (multiple antibiotic resistance regulator) family, which has been shown in Erwinia to regulate the expression of virulence genes. MarR homologs typically bind a small molecule ligand, resulting in attenuated DNA binding. For PecS, the natural ligand has not been identified. We have previously shown that urate is a ligand for the Deinococcus radiodurans-encoded MarR homolog HucR (hypothetical uricase regulator) and identified residues responsible for ligand binding. We show here that all four residues involved in urate binding and propagation of conformational changes to DNA recognition helices are conserved in PecS homologs, suggesting that urate is the ligand for PecS. Consistent with this prediction, Agrobacterium tumefaciens PecS specifically binds urate, and urate attenuates DNA binding in vitro. PecS binds two operator sites in the intergenic region between the divergent pecS gene and pecM genes, one of which features two partially overlapping repeats to which PecS binds as a dimer on opposite faces of the duplex. Notably, urate dissociates PecS from cognate DNA, allowing transcription of both genes in vivo. Taken together, our data show that urate is a ligand for PecS and suggest that urate serves a novel function in signaling the colonization of a host plant. Copyright © 2010 Elsevier Ltd. All rights reserved.

Design and construction of a point-contact spectroscopy rig with lateral scanning capability

Energy Technology Data Exchange (ETDEWEB)

Tortello, M. [Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Torino 10129 (Italy); Park, W. K., E-mail: wkpark@illinois.edu; Ascencio, C. O.; Saraf, P.; Greene, L. H. [Department of Physics and Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States)

2016-06-15

The design and realization of a cryogenic rig for point-contact spectroscopy measurements in the needle-anvil configuration is presented. Thanks to the use of two piezoelectric nano-positioners, the tip can move along the vertical (z) and horizontal (x) direction and thus the rig is suitable to probe different regions of a sample in situ. Moreover, it can also form double point-contacts on different facets of a single crystal for achieving, e.g., an interferometer configuration for phase-sensitive measurements. For the later purpose, the sample holder can also host a Helmholtz coil for applying a small transverse magnetic field to the junction. A semi-rigid coaxial cable can be easily added for studying the behavior of Josephson junctions under microwave irradiation. The rig can be detached from the probe and thus used with different cryostats. The performance of this new probe has been tested in a Quantum Design PPMS system by conducting point-contact Andreev reflection measurements on Nb thin films over large areas as a function of temperature and magnetic field.

Analysis of the HIV-2 protease's adaptation to various ligands: characterization of backbone asymmetry using a structural alphabet.

Science.gov (United States)

Triki, Dhoha; Cano Contreras, Mario Enrique; Flatters, Delphine; Visseaux, Benoit; Descamps, Diane; Camproux, Anne-Claude; Regad, Leslie

2018-01-15

The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands. We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. On average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting different backbone local conformations in the two monomers. This asymmetry was observed all along its structure, particularly in the elbow and flap regions. We first differentiated structural asymmetry conserved in most PR2 structures from the one specific to some PR2. Then, we explored the origin of the detected asymmetry in PR2. We localized asymmetry that could be induced by PR2's flexibility, allowing transition from the semi-open to closed conformations and the asymmetry potentially induced by ligand binding. This latter could be important for the PR2's adaptation to diverse ligands. Our results highlighted some differences between asymmetry of PR2 bound to darunavir and amprenavir that could explain their differences of affinity. This knowledge is critical for a better description of PR2's recognition and adaptation to various ligands and for a better understanding of the resistance of PR2 to most PR2 inhibitors, a major antiretroviral class.

Ficolins and FIBCD1: Soluble and membrane bound pattern recognition molecules with acetyl group selectivity

DEFF Research Database (Denmark)

Thomsen, Theresa; Schlosser, Anders; Holmskov, Uffe

2011-01-01

as pattern recognition molecules. Ficolins are soluble oligomeric proteins composed of trimeric collagen-like regions linked to fibrinogen-related domains (FReDs) that have the ability to sense molecular patterns on both pathogens and apoptotic cell surfaces and activate the complement system. The ficolins......D-containing molecules, and discusses structural resemblance but also diversity in recognition of acetylated ligands....

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I).

Science.gov (United States)

Hanna, Jill R; Allan, Christopher; Lawrence, Charlotte; Meyer, Odile; Wilson, Neil D; Hulme, Alison N

2017-05-14

The CuAAC 'click' reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible 'turn-on' catalytic sensors for the detection of ligand-bound copper(I).

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I

Directory of Open Access Journals (Sweden)

Jill R. Hanna

2017-05-01

Full Text Available The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I. This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I.

Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels

DEFF Research Database (Denmark)

Lynagh, Timothy; Beech, Robin N.; Lalande, Maryline J.

2015-01-01

that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream......Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed......, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling....

The electronic temperature control and measurements reactor fuel rig circuits

International Nuclear Information System (INIS)

Glowacki, S.W.

1980-01-01

The electronic circuits of two digital temperature meters developed for the thermocouple of Ni-NiCr type are described. The output thermocouple signal as converted by means of voltage-to-freguency converter. The frequency is measured by a digital scaler controled by quartz generator signals. One of the described meter is coupled with digital temperature controler which drives the power stage of the reactor rig heater. The internal rig temperature is measured by the thermocouple providing the input signal to the mentioned voltage-to-frequency converter, that means the circuits work in the negative feedback loop. The converter frequency-to-voltage ratio is automatically adjusted to match to thermocouple sensitivity changes in the course of the temperature variations. The accuracy of measuring system is of order of +- 1degC for thermocouple temperature changes from 523 K up to 973 K (50degC up to 700degC). (author)

Lifting devices with minimum effort for testing, maintenance and repair at the example of a lifting rig for core internals

Energy Technology Data Exchange (ETDEWEB)

Pache, Martin [Westinghouse Electric Germany GmbH (Germany); Wiesendanger, Robert [Kernkraftwerk Beznau, NOK (Switzerland)

2008-07-01

Beznau is a Westinghouse built nuclear power plant in the Aargau area Switzerland. It consists of two PWR units, each providing 365 MWe net capacity. The units were set into operation in 1969 and 1972, respectively, and hold an unlimited license for operation, provided they continue to fulfill current legal and security requirements. Beznau's previous lifting rigs for core internals required a high effort in testing and maintenance. Moreover, a damage to one of the rigs nearly resulted in the inoperability of the rig. However, no element of the load chain was affected, so there was no danger of a crash, but it could have caused an extended outage. Hence, it was decided to replace the lifting rigs with a state-of-the-art functional design that reflects modern requirements on maintenance and testing. Although the plant was built to ASME standards and codes, the new lifting rigs have been designed to German KTA code for lifting devices (KTA 3902 / 3903 for equipment with increased requirements, as per section 4.3 of KTA 3902). Given KTA's demands on periodic testing, one main requirement on the new design was to minimize the testing effort for the new rigs. (orig.)

TLR3 Ligand Poly(I:C Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

Directory of Open Access Journals (Sweden)

Mojca Frank-Bertoncelj

2018-01-01

Full Text Available Extracellular vesicles (EV can modulate the responses of cells to toll-like receptor (TLR ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C, a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C-stimulated U937 cells [Poly(I:C EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C EV contain or associate with Poly(I:C and at least partially protect Poly(I:C from RNAse III degradation. Poly(I:C EV shuttle Poly(I:C to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C. Poly(I:C EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C. These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C and may reflect the route of Poly(I:C delivery via EV or the fine-tuning of Poly(I:C actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the

An Evaluation of Project iRead: A Program Created to Improve Sight Word Recognition

Science.gov (United States)

Marshall, Theresa Meade

2014-01-01

This program evaluation was undertaken to examine the relationship between participation in Project iRead and student gains in word recognition, fluency, and comprehension as measured by the Phonological Awareness Literacy Screening (PALS) Test. Linear regressions compared the 2012-13 PALS results from 5,140 first and second grade students at…

Improving mixing efficiency in a closed circuit water flow rig for ...

African Journals Online (AJOL)

. ... pulse velocity method, indicating that the flow meters functioned correctly. The modified rig with scaled-up mixing techniques could serve as platform for training in evaluating mixing vessels and flow meters in industrial process plants.

Radioiodinated ligands for dopamine receptors

International Nuclear Information System (INIS)

Kung, H.F.

1994-01-01

The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

Conformational isomerism in mixed-ligand complexes of 2,2'-bipyridine and triphenylphosphine with copper(I) halides

International Nuclear Information System (INIS)

Barron, P.F.; Engelhardt, L.M.; Healy, P.C.; Kildea, J.D.; White, A.H.

1988-01-01

Mixed-ligand complexes of triphenylphosphine and 2,2'-bipyridine and copper(I) halides have been synthesized. The 31 P NMR spectra of the complexes were measured and are reported along with data for complete structural characterization of the complexes. The results indicate a novel dichotomy of conformational isomers to be present in the chloride lattice. The Cu-P bond length was found to not vary with different halides. 8 refs., 4 figs., 6 tabs

Pattern activation/recognition theory of mind.

Science.gov (United States)

du Castel, Bertrand

2015-01-01

In his 2012 book How to Create a Mind, Ray Kurzweil defines a "Pattern Recognition Theory of Mind" that states that the brain uses millions of pattern recognizers, plus modules to check, organize, and augment them. In this article, I further the theory to go beyond pattern recognition and include also pattern activation, thus encompassing both sensory and motor functions. In addition, I treat checking, organizing, and augmentation as patterns of patterns instead of separate modules, therefore handling them the same as patterns in general. Henceforth I put forward a unified theory I call "Pattern Activation/Recognition Theory of Mind." While the original theory was based on hierarchical hidden Markov models, this evolution is based on their precursor: stochastic grammars. I demonstrate that a class of self-describing stochastic grammars allows for unifying pattern activation, recognition, organization, consistency checking, metaphor, and learning, into a single theory that expresses patterns throughout. I have implemented the model as a probabilistic programming language specialized in activation/recognition grammatical and neural operations. I use this prototype to compute and present diagrams for each stochastic grammar and corresponding neural circuit. I then discuss the theory as it relates to artificial network developments, common coding, neural reuse, and unity of mind, concluding by proposing potential paths to validation.

Recognition of an Independent Self-Consciousness

DEFF Research Database (Denmark)

Bjerre, Henrik Jøker

2009-01-01

Hegel's concept in the Phenomenology of the Spirit of the "recognition of an independent self-consciousness" is investigated as a point of separation for contemporary philosophy of recognition. I claim that multiculturalism and the theories of recognition (such as Axel Honneth's) based on empiric...... psychology neglect or deny crucial metaphysical aspects of the Hegelian legacy. Instead, I seek to point at an additional, "spiritual", level of recognition, based on the concept of the subject in Lacanian psychoanalysis....

Index method for analyzing cost effectiveness of drilling rigs

Energy Technology Data Exchange (ETDEWEB)

Batura, N P; Bocharov, V V

1978-01-01

The method for a complete analysis of the factors determining cost effectiveness of a drilling rig fleet is examined. The system of calculating production indexes from statistical reports is relatively simple and is not difficult to use for production organizations. The analytical results may be used to develop actual measures used to increase cost effectiveness of drilling operations.

Radiobiology with DNA ligands

International Nuclear Information System (INIS)

Weinreich, R.; Argentini, M.; Guenther, I.; Koziorowski, J.; Larsson, B.; Nievergelt-Egido, M.C.; Salt, C.; Wyer, L.; Dos Santos, D.F.; Hansen, H.J.

1997-01-01

The paper deals with the following topics: labelling of DNA ligands and other tumour-affinic compounds with 4.15-d 124 I, radiotoxicity of Hoechst 33258 and 33342 and of iodinated Hoechst 33258 in cell cultures, preparation of 76 Br-, 123 I-, and 221 At-labelled 5-halo-2'-deoxyuridine, chemical syntheses of boron derivatives of Hoechst 33258.III., Gadolinium neutron capture therapy

Automated ligand fitting by core-fragment fitting and extension into density

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Klei, Herbert; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2006-01-01

An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c )exp(iϕ c ) difference density from macromolecular structures in the Protein Data Bank. A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 Å) from the Protein Data Bank (PDB) into (F o − F c )exp(iϕ c ) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 Å (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10–100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58–73% over all resolution ranges tested

Development of a remote data acquisition and graphic display system for the sodium rigs

International Nuclear Information System (INIS)

Rajendran, A.; Sylvia, J.I.; Swaminathan, K.

1992-01-01

This paper describes the development of a Remote Data Acquisition System for Sodium Rigs. Seven data loggers, an alarm monitor and a PLC are geographically distributed in two sodium rigs over a distance of 500 m. A serial data highway based on RS485 transceivers has been constructed to remotely acquire data from these stations. The field stations are connected to the data highway in a multi drop fashion. A PC/AT computer on the same bus remotely acquires and monitors the data from the field stations. (author). 3 refs., 2 figs

Test Rig Design and Presentation for a Hydraulic Yaw System

DEFF Research Database (Denmark)

Stubkier, Søren; Pedersen, Henrik C.; Andersen, Torben Ole

2013-01-01

The design and development of a hydraulic yaw system for multi MWturbines is presented and the concept explained. As part of the development of the new concept a full scale test rig for a 5 MW wind turbine has been designed and constructed. The test rig is presented along with its unique design...... features. The design process is outlined to give insight in the design criteria driving the design. Loads and yaw demands are based on the IEC 61400-1 standard for wind turbine design, and the loads for this examination are extrapolated from the FAST aero elastic design software. The concepts are based...... on a 5 MW offshore turbine. After the system presentation, measurement results are presented to verify the behavior of the system. The loads to the system are applied by torque controlled electrical servo drives, which can add a load of up to 3 MNm to the system. This gives an exact picture of the system...

Superior serum half life of albumin tagged TNF ligands

International Nuclear Information System (INIS)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

2010-01-01

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

Cerebral kinetics of the dopamine D{sub 2} receptor ligand [{sup 123}I]IBZM in mice

Energy Technology Data Exchange (ETDEWEB)

Meyer, Philipp T. [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Department of Nuclear Medicine, University Hospital Aachen, 52074 Aachen (Germany)], E-mail: pmeyer@ukaachen.de; Salber, Dagmar [C. and O. Vogt Institute of Brain Research, University Hospital Duesseldorf, 40225 Duesseldorf (Germany); Schiefer, Johannes [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Cremer, Markus [Institute of Neurosciences and Biophysics, Research Center Juelich, 52425 Juelich (Germany); Schaefer, Wolfgang M. [Department of Nuclear Medicine, University Hospital Aachen, 52074 Aachen (Germany); Kosinski, Christoph M. [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Langen, Karl-Josef [Institute of Neurosciences and Biophysics, Research Center Juelich, 52425 Juelich (Germany)

2008-05-15

Introduction: In vivo small animal imaging of the dopaminergic system is of great interest for basic and applied neurosciences, especially in transgenic mice. Small animal SPECT is particularly attractive because of its superior spatial resolution and tracer availability. We investigated the kinetics of the commercial dopamine D{sub 2} receptor (DZR) ligand [{sup 123}I]IBZM in mice as a prerequisite for an appropriate design of translational SPECT imaging between mice and humans. Methods: Cerebral kinetics of [{sup 123}I]IBZM under isoflurane anaesthesia were assessed by autoradiography in mice sacrificed at 30, 60, 120 and 200 min after iv injection. To explore the possible effects of isoflurane anaesthesia, an additional mice group was only anaesthetized for 20 min before being sacrificed at 140 min (putative time of single-scan SPECT analysis). Results: Maximum [{sup 123}I]IBZM uptake in the striatum (D{sub 2}R-rich; 10.5{+-}2.7 %ID/g) and cerebellum (D{sub 2}R-devoid; 2.4{+-}0.7 %ID/g) was observed at 30 min after injection. Thereafter, [{sup 123}I]IBZM uptake decreased slowly in striatum and rapidly in the cerebellum (200 min: 5.3{+-}1.9 and 0.4{+-}0.2 %ID/g, respectively). The striatum-to-cerebellum (S/C) [{sup 123}I]IBZM uptake ratio increased from 4.6{+-}1.2 at 30 min to 11.6{+-}2.6 at 120 min. The S/C ratio at 200 min was highly variable (17.8{+-}10.1), possibly indicating pseudo-equilibration in some animals. In mice, which were only anaesthetized between 120 and 140 min, a higher S/C ratio of 17.0{+-}5.1 was observed. Conclusions: The present study suggests that [{sup 123}I]IBZM is a suitable ligand for D{sub 2}R-SPECT in mice. Although a single-scan analysis may be a pragmatic semi-quantitative approach, tracer kinetic analyses on dynamic SPECT data should be pursued. The interfering effects of isoflurane anaesthesia need to be considered.

Oxidation of a Silica-Containing Material in a Mach 0.3 Burner Rig

Science.gov (United States)

Nguyen, QuynhGiao N.; Cuy, Michael D.; Gray, Hugh R. (Technical Monitor)

2002-01-01

A primarily silica-containing material with traces of organic compounds, as well as aluminum and calcium additions, was exposed to a Mach 0.3 burner rig at atmospheric pressure using jet fuel. The sample was exposed for 5 continuous hours at 1370 C. Post exposure x-ray diffraction analyses indicate formation of cristobalite, quartz, NiO and Spinel (Al(Ni)CR2O4). The rig hardware is composed of a nickel-based superalloy with traces of Fe. These elements are indicated in the energy dispersive spectroscopy (EDS) results. This material was studied as a candidate for high temperature applications under an engine technology program.

Ligand recognition and domain structure of Vps10p, a vacuolar protein sorting receptor in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Jørgensen, M U; Emr, S D; Winther, Jakob R.

1999-01-01

Vp10p is a receptor that sorts several different vacuolar proteins by cycling between a late Golgi compartment and the endosome. The cytoplasmic tail of Vps10p is necessary for the recycling, whereas the lumenal domain is predicted to interact with the soluble ligands. We have studied ligand bind...

C-H and H-H Bond Activation via Ligand Dearomatization/Rearomatization of a PN3P-Rhodium(I) Complex

KAUST Repository

Huang, Kuo-Wei; Wang, Yuan; Zheng, Bin; Pan, Yupeng; Pan, Chengling; He, Lipeng

2015-01-01

A neutral complex PN3P-Rh(I)Cl (2) was prepared from a reaction of the PN3P pincer ligand (1) with [Rh(COD)Cl]2 (COD = 1,5-cyclooctadiene). Upon treatment with a suitable base, H–H and Csp2–H activation reactions can be achieved through

C-H and H-H Bond Activation via Ligand Dearomatization/Rearomatization of a PN3P-Rhodium(I) Complex

KAUST Repository

Huang, Kuo-Wei

2015-04-13

A neutral complex PN3P-Rh(I)Cl (2) was prepared from a reaction of the PN3P pincer ligand (1) with [Rh(COD)Cl]2 (COD = 1,5-cyclooctadiene). Upon treatment with a suitable base, H–H and Csp2–H activation reactions can be achieved through the deprotonation/reprotonation of one of the N–H arms and dearomatization/rearomatization of the central pyridine ring with the oxidation state of Rh remaining I.

Threshold Assessment of Gear Diagnostic Tools on Flight and Test Rig Data

Science.gov (United States)

Dempsey, Paula J.; Mosher, Marianne; Huff, Edward M.

2003-01-01

A method for defining thresholds for vibration-based algorithms that provides the minimum number of false alarms while maintaining sensitivity to gear damage was developed. This analysis focused on two vibration based gear damage detection algorithms, FM4 and MSA. This method was developed using vibration data collected during surface fatigue tests performed in a spur gearbox rig. The thresholds were defined based on damage progression during tests with damage. The thresholds false alarm rates were then evaluated on spur gear tests without damage. Next, the same thresholds were applied to flight data from an OH-58 helicopter transmission. Results showed that thresholds defined in test rigs can be used to define thresholds in flight to correctly classify the transmission operation as normal.

Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.

Directory of Open Access Journals (Sweden)

Anne Månsson Kvarnhammar

Full Text Available BACKGROUND: Pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs, NOD-like receptors (NLRs and RIG-I-like receptors (RLRs, recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs. METHODS: Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. RESULTS: HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C, LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C, down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. CONCLUSION: Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.

Preclinical pharmacological study on I-ADAM as a serotonin transporter ligand

International Nuclear Information System (INIS)

Wu Chunying; Lu Chunxiong; Jiang Quanfu; Zou Meifen; Chen Zhengping; Wang Songpei; Li Xiaomin; Zhang Tongxing; Zhu Junqing; Lin Xiangtong

2004-01-01

Objective: To evaluate the new ligand: I-2-( (22( (dimethylamino) methyl) phenyl) thio)-5- iodophenylamine (ADAM) as a serotonin imaging agent. Methods: Biological evaluations were performed in rats and mice. Results: Biodistribution studies in rats showed that the initial uptake of 131 I-ADAM in the brain was high (1.087%ID/organ at 2 min postinjection), and consistently displayed the highest binding (between 60-240 min postinjection) in hypothalamus, a region with the highest density of serotonin transporter (SERT). The specific binding [(TPCB)-1] of 131 I-ADAM in hypothalamus was 2.94, 3.03 and 3.09 at 60, 120 and 240 min postinjection, respectively. The (TPCB)-1 was significantly blocked by pretreatment with Paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug, Ketanserin, showed no blocking effect. The rat brain autoradiography and analysis showed that there was high 131 I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94 ± 0.39 to 1.30 ± 0.56 by pretreatment with Paroxetine at 60 min postinjection. Blood clearance kinetics was studied in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation was: C=3.6147·e -0.0725t + 1.0413 e -0.0028t . The thyroid uptake was 0.009 and 1.421% ID/organ at 2 min and 120 min postinjection, respectively, suggesting that in vivo deiodination maybe the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to human beings, assuming a body-weight of 50 kg. Conclusion: These data suggest that 131 I-ADAM may be useful for SPECT imaging of SERT binding sits in the brain. (authors)

125I-BH-8-MeO-N-PAT, a new ligand for studying 5-HT1A receptors in the central nervous system

International Nuclear Information System (INIS)

Ponchant, M.; Beaucourt, J.P.; Vanhove, A.

1988-01-01

Specific radioactive ligands are needed for studying the pharmacological properties and the regional distribution of the different classes of 5-HT 1 receptors within the central nervous system. We describe here the synthesis and some characteristics of the first iodinated specific ligand of 5-HT 1A receptors. Like its parent compound, the agonist 8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT, [ 125 I]-BH-8-MeO-N-PAT, exhibits a high affinity and excellent selectivity for 5-HT 1A sites. Its high specific radioactivity makes this ligand a useful tool for studying 5-HT 1A receptors in membranes and sections of the rat brain [fr

Evaluation of wheel/rail contact mechanics : roller rig concept design review.

Science.gov (United States)

2014-07-01

A need exists for a new test rig design with advanced sensing technologies that will allow the railroad industry and regulatory : agencies to better understand the wheel-rail contact dynamics and mechanics, especially as it pertains to high-speed rai...

A theoretical investigation on the neutral Cu(I) phosphorescent complexes with azole-based and phosphine mixed ligand

Science.gov (United States)

Ding, Xiao-Li; Shen, Lu; Zou, Lu-Yi; Ma, Ming-Shuo; Ren, Ai-Min

2018-04-01

A theoretical study on a series of neutral heteroleptic Cu(I) complexes with different azole-pyridine-based N^N ligands has been presented to get insight into the effect of various nitrogen atoms in the azole ring on photophysical properties. The results reveal that the highest occupied molecular orbital (HOMO) levels and the emission wavelengths of these complexes are mainly governed by the nitrogen atom number in azole ring. With the increasing number of nitrogen atom , the electron density distribution of HOMO gradually extend from the N^N ligand to the whole molecule, meanwhile, the improved contribution from Cu(d) orbits in HOMO results in an effective mixing of various charge transfermodes, and hence, the fast radiative decay(kr) and the slow non-radiative decay rate(knr) are achieved. The photoluminescence quantum yield (PLQY) show an apparent dependence on the nitrogen atom number in the five-membered nitrogen heterocycles. However, the increasing number of nitrogen atoms is not necessary for increasing PLQY. The complex 3 with 1,2,4-triazole-pyridine-based N^N ligands is considered to be a potential emitter with high phosphorescence efficiency. Finally, we hope that our investigations will contribute to systematical understanding and guiding for material molecular engineering.

Collagen Type I as a Ligand for Receptor-Mediated Signaling

Directory of Open Access Journals (Sweden)

Iris Boraschi-Diaz

2017-05-01

Full Text Available Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general

DEFF Research Database (Denmark)

Gustavsen, Marte W; Viken, Marte K; Celius, Elisabeth G

2014-01-01

Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated the associ......Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated...

Conformational changes and allosteric communications in human serum albumin due to ligand binding.

Science.gov (United States)

Ahalawat, Navjeet; Murarka, Rajesh K

2015-01-01

It is well recognized that knowledge of structure alone is not sufficient to understand the fundamental mechanism of biomolecular recognition. Information of dynamics is necessary to describe motions involving relevant conformational states of functional importance. We carried out principal component analysis (PCA) of structural ensemble, derived from 84 crystal structures of human serum albumin (HSA) with different ligands and/or different conditions, to identify the functionally important collective motions, and compared with the motions along the low-frequency modes obtained from normal mode analysis of the elastic network model (ENM) of unliganded HSA. Significant overlap is observed in the collective motions derived from PCA and ENM. PCA and ENM analysis revealed that ligand selects the most favored conformation from accessible equilibrium structures of unliganded HSA. Further, we analyzed dynamic network obtained from molecular dynamics simulations of unliganded HSA and fatty acids- bound HSA. Our results show that fatty acids-bound HSA has more robust community network with several routes to communicate among different parts of the protein. Critical nodes (residues) identified from dynamic network analysis are in good agreement with allosteric residues obtained from sequence-based statistical coupling analysis method. This work underscores the importance of intrinsic structural dynamics of proteins in ligand recognition and can be utilized for the development of novel drugs with optimum activity.

Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

DEFF Research Database (Denmark)

Jensen, Helle; Andresen, Lars; Nielsen, Jens

2011-01-01

Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection ...

New design head pendulum test rig for window airbag development; Neu entwickelte Kopfpendel-Testanlage fuer die Window-Airbag -Auslegung

Energy Technology Data Exchange (ETDEWEB)

Grundheber, C. [Adam Opel AG, Ruesselsheim (Germany); Lindstromberg, M. [Siemens Restraint Systems, Alzenau (Germany)

2001-07-01

Comparisons between vehicle crash tests and pendulum tests demonstrate good correlation. The head pendulum rig presents a faster, more economical alternative to the usual sled facilities. This is above all due to the simpler test set-up, which only considers the body parts relevant to the window airbag development, i.e. dummy head, neck and shoulder. The tuning of the system to new baseline values can also be carried out very quickly, by specific adjustments to the spring-damper arrangement. (orig.)

Study on aero-dynamic characteristics of the sloop rig (continued); Sloop ring no kuriki tokusei no ichikaiseki (zoku)

Energy Technology Data Exchange (ETDEWEB)

Shinkai, A.; Iyoda, H. [Kyushu University, Fukuoka (Japan). Faculty of Engineering

1997-09-04

A numerical simulation method was formerly provided for analyzing aero-dynamic characteristics of sloop rig by the vortex distribution method. For this method, aero-dynamic characteristics of the sloop rib were formulated by treating air flow around sail as a two-dimensional problem and by assuming sail as a membrane. The sloop rig is a yacht for more than two persons, which is the most popular form of rig. A main sail and a jib sheet are fixed on a mast. In this study, the method developed based on the panel method was introduced for analyzing the effects of jib sheet which can control the jib trim angle. Generality of the present aero-dynamic characteristics was enhanced, and problems of the analysis method were extracted through the numerical simulation of a yacht with sloop rig. Influence of the position of fairleader on the aero-dynamic characteristics was qualitatively grasped by considering the effects of jib sheet and by trimming the elevation into ideal one. 6 refs., 11 figs.

Correcting binding parameters for interacting ligand-lattice systems

Science.gov (United States)

Hervy, Jordan; Bicout, Dominique J.

2017-07-01

Binding of ligands to macromolecules is central to many functional and regulatory biological processes. Key parameters characterizing ligand-macromolecule interactions are the stoichiometry, inducing the number of ligands per macromolecule binding site, and the dissociation constant, quantifying the ligand-binding site affinity. Both these parameters can be obtained from analyses of classical saturation experiments using the standard binding equation that offers the great advantage of mathematical simplicity but becomes an approximation for situations of interest when a ligand binds and covers more than one single binding site on the macromolecule. Using the framework of car-parking problem with latticelike macromolecules where each ligand can cover simultaneously several consecutive binding sites, we showed that employing the standard analysis leads to underestimation of binding parameters, i.e., ligands appear larger than they actually are and their affinity is also greater than it is. Therefore, we have derived expressions allowing to determine the ligand size and true binding parameters (stoichiometry and dissociation constant) as a function of apparent binding parameters retrieved from standard saturation experiments.

Computational Approaches to the Chemical Equilibrium Constant in Protein-ligand Binding.

Science.gov (United States)

Montalvo-Acosta, Joel José; Cecchini, Marco

2016-12-01

The physiological role played by protein-ligand recognition has motivated the development of several computational approaches to the ligand binding affinity. Some of them, termed rigorous, have a strong theoretical foundation but involve too much computation to be generally useful. Some others alleviate the computational burden by introducing strong approximations and/or empirical calibrations, which also limit their general use. Most importantly, there is no straightforward correlation between the predictive power and the level of approximation introduced. Here, we present a general framework for the quantitative interpretation of protein-ligand binding based on statistical mechanics. Within this framework, we re-derive self-consistently the fundamental equations of some popular approaches to the binding constant and pinpoint the inherent approximations. Our analysis represents a first step towards the development of variants with optimum accuracy/efficiency ratio for each stage of the drug discovery pipeline. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Essential role of conformational selection in ligand binding.

Science.gov (United States)

Vogt, Austin D; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

2014-02-01

Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and

Identification of the ligand-binding subunit of the human 5-hydroxytryptamine1A receptor with N-(p-azido-m-[125I] iodophenethyl)spiperone, a high affinity radioiodinated photoaffinity probe

International Nuclear Information System (INIS)

Raymond, J.R.; Fargin, A.; Lohse, M.J.; Regan, J.W.; Senogles, S.E.; Lefkowitz, R.J.; Caron, M.G.

1989-01-01

The ligand-binding subunit of the human 5-hydroxytryptamine1A (5-HT1A) receptor transiently expressed in COS-7 cells and of the native human 5-HT1A receptor derived from hippocampus and frontal cortex were identified by photoaffinity labeling with N-(p-azido-m-[125I]iodophenethyl)spiperone [( 125I]N3-NAPS), previously characterized as a high affinity radioiodinated D2-dopamine receptor probe. The identity of the ligand-binding subunit was confirmed by immunoprecipitation with an antipeptide rabbit antiserum, JWR21, raised against a synthetic peptide derived from the predicted amino acid sequence of the putative third intracellular loop of the human 5-HT1A receptor. In transiently transfected COS-7 cells expressing 14 +/- 3 pmol/mg of protein human 5-HT1A receptors, a single broad 75-kDa band was photoaffinity labeled by [125I]N3-NAPS. This band displayed the expected pharmacology of the 5-HT1A receptor, as evidenced by the ability of a series of competing ligands to block [125I]N3-NAPS photoincorporation. Moreover, antiserum JWR21 specifically and quantitatively immunoprecipitated the 75-kDa photoaffinity-labeled band from a soluble extract of the transfected COS-7 cell membranes, further confirming its identity. Finally, utilizing a combination of photoaffinity labeling and immunoprecipitation, the native ligand-binding subunit of 62-64 kDa was identified in human hippocampus and frontal cortex. The availability of the high specific activity, high affinity, photoaffinity ligand [125I]N3-NAPS and of a potent immunoprecipitating antiserum (JWR21) should greatly facilitate the biochemical characterization of the human 5-HT1A receptor

Development of Induction Brazing System for Sealing Instrumentation Feed through Part of Nuclear Fuel Test Rig

Energy Technology Data Exchange (ETDEWEB)

Hong, Jintae; Kim, Kahye; Heo, Sungho; Ahn, Sungho; Joung, Changyoung; Son, Kwangjae; Jung, Yangil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-12-15

To test the performance of nuclear fuels, coolant needs to be circulated through the test rig installed in the test loop. Because the pressure and temperature of the coolant is 15.5 MPa and 300 .deg. C respectively, coolant sealing is one of the most important processes in fabricating a nuclear fuel test rig. In particular, 15 instrumentation cables installed in a test rig pass through the pressure boundary, and brazing is generally applied as a sealing method. In this study, an induction brazing system has been developed using a high frequency induction heater including a vacuum chamber. For application in the nuclear field, BNi2 should be used as a paste, and optimal process variables for Ni brazing have been found by several case studies. The performance and soundness of the brazed components has been verified by a tensile test, cross section test, and sealing performance test.

A role for carbohydrate recognition in mammalian sperm-egg binding

International Nuclear Information System (INIS)

Clark, Gary F.

2014-01-01

Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented

A role for carbohydrate recognition in mammalian sperm-egg binding

Energy Technology Data Exchange (ETDEWEB)

Clark, Gary F., E-mail: clarkgf@health.missouri.edu

2014-08-01

Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented.

Contrasting roles for TLR ligands in HIV-1 pathogenesis.

Directory of Open Access Journals (Sweden)

Beda Brichacek

2010-09-01

Full Text Available The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs. Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs 5 and 9, we examined their effect on human immunodeficiency virus (HIV-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist treatment enhanced replication of CC chemokine receptor 5 (CCR 5-tropic and CXC chemokine receptor 4 (CXCR4-tropic HIV-1, treatment with oligodeoxynucleotide (ODN M362 (TLR9 agonist suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

Designer ligands. Part 14. Novel Mn(lI), Ni(II) and Zn(II) complexes of benzamide- and biphenyl-derived ligands

CSIR Research Space (South Africa)

Wellington, Kevin W

2009-01-01

Full Text Available . Results and Discussion The ligands 1a-c (Scheme 1) were prepared by treating benzoic acid with carbonyl diimidazole (CDI)13 in dimethylformamide (DMF), followed by the respective primary amines, histamine, 2- (2-aminoethyl)benzimidazole and 2...-(2-aminoethyl)pyridine. [Histamine had to be released from its dihydrochloride salt by treatment with sodium methoxide, while 2-(2- aminoethyl)benzimidazole was prepared from 1,2-diaminobenzene and β-alanine.16] The synthesis of the biphenyl-derived ligand 2...

Tractor accelerated test on test rig

Directory of Open Access Journals (Sweden)

M. Mattetti

2013-09-01

Full Text Available The experimental tests performed to validate a tractor prototype before its production, need a substantial financial and time commitment. The tests could be reduced using accelerated tests able to reproduce on the structural part of the tractor, the same damage produced on the tractor during real life in a reduced time. These tests were usually performed reproducing a particular harsh condition a defined number of times, as for example using a bumpy road on track to carry out the test in any weather condition. Using these procedures the loads applied on the tractor structure are different with respect to those obtained during the real use, with the risk to apply loads hard to find in reality. Recently it has been demonstrated how, using the methodologies designed for cars, it is possible to also expedite the structural tests for tractors. In particular, automotive proving grounds were recently successfully used with tractors to perform accelerated structural tests able to reproduce the real use of the machine with an acceleration factor higher than that obtained with the traditional methods. However, the acceleration factor obtained with a tractor on proving grounds is in any case reduced due to the reduced speed of the tractors with respect to cars. In this context, the goal of the paper is to show the development of a methodology to perform an accelerated structural test on a medium power tractor using a 4 post test rig. In particular, several proving ground testing conditions have been performed to measure the loads on the tractor. The loads obtained were then edited to remove the not damaging portion of signals, and finally the loads obtained were reproduced in a 4 post test rig. The methodology proposed could be a valid alternative to the use of a proving ground to reproduce accelerated structural tests on tractors.

Complete Genome Sequence of the Campylobacter ureolyticus Clinical Isolate RIGS 9880

DEFF Research Database (Denmark)

Miller, William G; Yee, Emma; On, Stephen L W

2015-01-01

The emerging pathogen Campylobacter ureolyticus has been isolated from human and animal genital infections, human periodontal disease, domestic and food animals, and from cases of human gastroenteritis. We report the whole-genome sequence of the human clinical isolate RIGS 9880, which is the first...

Measurement techniques for AGR circulators in a full-density rig

International Nuclear Information System (INIS)

Watson, I.; Wilson, R.R.

1977-01-01

Safety and reliability are the most important factors of a nuclear power plant. This applies in particular to the circulators used to drive the high-density CO 2 around the reactor core and boiler circuits. Under operating conditions, very high sound-pressure levels are generated which could excite components and cause possible fatigue failures. Failures of this type were experienced on the original axial blowers for the Hinkley 'A' Magnox reactor and, following this, a stringent test plan was specified for the AGR circulators. The present paper describes some of the techniques used to measure strain, sound and vibration on circulators in a full-density rig. This rig reproduces the actual reactor working conditions of 300 0 C and 4.1 MN m -2 with gas velocities up to 120 m s -1 . Under these conditions sound-pressure levels of up to 172 dB are generated. This programme of circulator testing has continued for the past 10 years. During this period many obstacles and difficulties were encountered. Some of these problems, together with the solutions found, are discussed. (author)

π-Cation Interactions in Molecular Recognition: Perspectives on Pharmaceuticals and Pesticides.

Science.gov (United States)

Liang, Zhibin; Li, Qing X

2018-04-04

The π-cation interaction that differs from the cation-π interaction is a valuable concept in molecular design of pharmaceuticals and pesticides. In this Perspective we present an up-to-date review (from 1995 to 2017) on bioactive molecules involving π-cation interactions with the recognition site, and categorize into systems of inhibitor-enzyme, ligand-receptor, ligand-transporter, and hapten-antibody. The concept of π-cation interactions offers use of π systems in a small molecule to enhance the binding affinity, specificity, selectivity, lipophilicity, bioavailability, and metabolic stability, which are physiochemical features desired for drugs and pesticides.

The influence of chemicals on water quality in a high pressure separation rig

Energy Technology Data Exchange (ETDEWEB)

Johnsen, Einar E.; Hemmingsen, Paal V.; Mediaas, Heidi; Svarstad, May Britt E.; Westvik, Arild

2006-03-15

In the research laboratory of Statoil at Rotvoll, Trondheim, a high pressure experimental rig used for separation and foaming studies has been developed. There have been several studies to ensure that the high pressure separation rig produces reliable and consistent results with regard to the water-in-oil and oil-in-water contents. The results are consistent with available field data and, just as important, consistent when changing variables like temperature, pressure drop and water cut. The results are also consistent when changing hydrodynamic variables like flow velocity and mixing point (using different choke valves) and when using oil with and without gas saturation. At equal experimental conditions, the high pressure separation rig is able to differentiate between separation characteristics of oil and water from different fields and from different wells at the same field. The high pressure separation and foam rig can be used from -10 deg C to 175 deg C and at pressures up to 200 bar. Crude oil and water are studied under relevant process conditions with respect to temperature, pressure, shear, water cut and separation time. In the present work the influence of chemicals on the oil and water quality has been studied. Chemicals have been mixed into the oil and/or water beforehand or added in situ (on-stream; simulated well stream). The amount of oil in the water after a given residence time in the separation cell has been measured. The results from the high pressure rig show that some demulsifiers, with their primary purpose of giving less water in oil, also have influence on the water quality. Improvement of water quality has been observed as well as no effect or aggravation. The experimental results have been compared to results from bottle tests at the field. The results from the bottle tests and from the laboratory are not corresponding, and only a full-scale field test can tell which of them are the correct results, if any. (Experience from corresponding

Bio-specific recognition and applications: from molecular to colloidal scales

International Nuclear Information System (INIS)

Baudry, Jean; Bertrand, Emanuel; Lequeux, Nicolas; Bibette, Jerome

2004-01-01

Biomolecules have the well-known ability to build reversible complexes. Indeed, antigens and antibodies or adhesion molecules are able to recognize one another with a strong affinity and a very high specificity. This paper first reviews the various techniques and related results about binding and unbinding, at the scale of a unique ligand/receptor couple. One important biotechnological application arising from these recognition phenomena concerns immuno-diagnosis, which is essentially based on the formation of these specific complexes. We show how the physics of colloids associated with the growing scientific background concerning molecular recognition helps in rationalizing and inventing new diagnostic strategies. Finally the concept of colloidal self-assembling systems as biosensors is presented as directly impacting the most important questions related to molecular recognition and their biotechnological implications. (topical review)

Testing of a new morphing trailing edge flap system on a novel outdoor rotating test rig

DEFF Research Database (Denmark)

Aagaard Madsen, Helge; Barlas, Athanasios; Løgstrup Andersen, Tom

2015-01-01

The morphing trailing edge system or flap system, CRTEF, has been developed over the last 10 years at DTU Wind Energy. After a promising wind tunnel test of the system in 2009 the INDUFLAP project has been carried out from 2011-2014 to transfer the technology from laboratory to industrial...... manufacturing and application. To narrow the gap between wind tunnel testing and full scale prototype testing we developed the rotating test rig. The overall objectives with the rotating test rig are: 1) to test the flap system in a realistic rotating environment with a realistic g-loading; 2) to measure...... the flap performance in real turbulent inflow and 3) to test the flap system in a realistic size and Reynolds number when comparing with full scale applications.. The rotating test rig consists of a 2.2m blade section attached to a 10m boom and mounted on a 100kW turbine platform. It was installed in June...

The Hydraulic Test Procedure for Non-instrumented Irradiation Test Rig of Annular Fuel

Energy Technology Data Exchange (ETDEWEB)

Kim, Dae Ho; Lee, Kang Hee; Shin, Chang Hwan; Park, Chan Kook

2008-08-15

This report presents the procedure of pressure drop test, vibration test and endurance test for the non-instrumented rig using the irradiation test in HANARO of advanced PWR annular fuel which were designed and fabricated by KAERI. From the out-pile thermal hydraulic tests, confirm the flow rate at the 200 kPa pressure drop and measure the RMS displacement at this time. And the endurance test is confirmed the wear and the integrity of the non-instrumented rig at the 110% design flow rate. This out-pile test perform the Flow-Induced Vibration and Pressure Drop Experimental Tester(FIVPET) facility. The instruments in FIVPET facility was calibrated in KAERI and the pump and the thermocouple were certified by manufacturer.

A REAL TIME DECISION SUPPORT SYSTEM FOR THE ADJUSTMENT OF SAILBOAT RIGGING

Directory of Open Access Journals (Sweden)

Inmaculada Ortigosa

2016-01-01

Full Text Available The operational complexity and performance requirements of modern racing yachts demand the use of advanced applications, such as a decision support system (DSS able to assist crew members during navigation. In this article, the authors describe a near-time computational solver as the main piece of a DSS which analyses and monitors the behaviour of sails and rigging. The solver is made up of two different interconnected tools: an iterative Fluid-Structure Interaction algorithm and an advanced Wireless Sensor Network to monitor rigging. The real-time DSS quantifies crew manoeuvres in physical terms, which are reproduced by a simulation program. It can be used in the design phase of sailing yachts and as an aid for real-time boat performance optimisation and accident prevention. This novel DSS is a useful tool for navigation, especially in races.

Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

Science.gov (United States)

Zhao, Li-Hua; Zhou, X Edward; Yi, Wei; Wu, Zhongshan; Liu, Yue; Kang, Yanyong; Hou, Li; de Waal, Parker W; Li, Suling; Jiang, Yi; Scaffidi, Adrian; Flematti, Gavin R; Smith, Steven M; Lam, Vinh Q; Griffin, Patrick R; Wang, Yonghong; Li, Jiayang; Melcher, Karsten; Xu, H Eric

2015-01-01

Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. PMID:26470846

A universal suspension test rig for electrohydraulic active and passive automotive suspension system

Directory of Open Access Journals (Sweden)

Mahmoud Omar

2017-12-01

Full Text Available A fully active electro-hydraulic and passive automotive quarter car suspensions with their experimental test-rigs are designed and implemented. Investigation of the active performance compared against the passive is performed experimentally and numerically utilizing SIMULINK's Simscape library. Both systems are modeled as single-degree-of-freedom in order to simplify the validation process. Economic considerations were considered during the rig's implementation. The rig consists of two identical platforms fixed side by side allowing testing two independent suspensions simultaneously. Position sensors for sprung and unsprung masses on both platforms are installed. The road input is introduced by a cam and a roller follower mechanism driven by 1.12 kW single phase induction motor with speed reduction assembly. The active hydraulic cylinder was the most viable choice due to its high power-to-weight ratio. The active control is of the proportional-integral-differential (PID type. Though this technique is quite simple and not new, yet the emphasis of this paper is the engineering, design and implementation of the experimental setup and controller. A successful validation process is performed. Ride comfort significantly improved with active suspension, as shown by the results; 24.8% sprung mass vibration attenuation is achieved. The details of the developed system with the analytical and experimental results are presented. Keywords: Active suspension, Passive suspension, Servo, Hydraulic, Control, PID

Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis?

Science.gov (United States)

Yu, Li; Wang, Liantang; Chen, Shangwu

2012-03-01

Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis.

Protein-Templated Fragment Ligations-From Molecular Recognition to Drug Discovery.

Science.gov (United States)

Jaegle, Mike; Wong, Ee Lin; Tauber, Carolin; Nawrotzky, Eric; Arkona, Christoph; Rademann, Jörg

2017-06-19

Protein-templated fragment ligation is a novel concept to support drug discovery and can help to improve the efficacy of protein ligands. Protein-templated fragment ligations are chemical reactions between small molecules ("fragments") utilizing a protein's surface as a reaction vessel to catalyze the formation of a protein ligand with increased binding affinity. The approach exploits the molecular recognition of reactive small-molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations. In this way, chemical synthesis and bioassay are integrated in one single step. This Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein-templated ligation products. The chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flap testing on the rotating test rig in the INDUFLAP project

DEFF Research Database (Denmark)

Barlas, Athanasios; Aagaard Madsen, Helge; Enevoldsen, Karen

Tests of a prototype Controllable Rubber Trailing Edge Flap (CRTEF) are performed on the rotating test rig at the Risø campus of DTU. The general description and objectives are presented, along with an overview of sensors on the setup and the test cases. The post-processing of data is discussed...

Pharmaceutical research at the AAEC Part I: Ligand synthesis and biological studies

Energy Technology Data Exchange (ETDEWEB)

Wilson, J G [Australian Atomic Energy Commission Research Establishment, Lucas Heights

1982-09-01

Work on the synthesis of ligands capable of forming chelate complexes with technetium-99m as part of a search for tumour-localising radiopharmaceuticals is described. An account of the biological evaluation of a range of these compounds, in particular, benzimidazoles, sulphanilamides and acridines, and of the investigation of certain biochemical and biological properties affecting the clinical application of both ligands and radiopharmaceuticals is given. Interactions between therapeutic drugs and diagnostic radiopharmaceuticals are considered. The toxicological evaluation of a prospective hepatobiliary imaging agent, dimethyl-BIMIDA, is described.

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

Science.gov (United States)

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

Validation of RELAP5 model of experimental test rig simulating the natural convection in MTR research reactors

Energy Technology Data Exchange (ETDEWEB)

Khedr, A.; Abdel-Latif, Salwa H. [Nuclear and Radiological Regulatory Authority, Cairo (Egypt); Abdel-Hadi, Eed A. [Benha Univ., Cairo (Egypt). Shobra Faculty of Engineering; D' Auria, F. [Pisa Univ. (Italy)

2016-03-15

In an attempt to understand the built-up of natural circulation in MTR pool type upward flow research reactors after loss of power, an experimental test rig was built to simulate the loop of natural circulation in MTR reactors. The test rig consisting of two vertically oriented branches, in one of them the core is simulated by two rectangular, electrically heated, parallel channels. The other branch simulates the part of the return pipe that participates in the development of core natural circulation. In the first phase of the work, many experimental runs at different conditions of channel's power and branch's initial temperatures are performed. The channel's coolant and surface temperatures were measured. The measurements and their interpretation were published by the first three authors. In the present work the thermal hydraulic behavior of the test rig is complemented by theoretical analysis using RELAP5 Mod 3.3 system code. The analysis consisting of two parts; in the first part RELAP5 model is validated against the measured values and in the second part some of the other not measured hydraulic parameters are predicted and analyzed. The test rig is typically nodalized and an input dick is prepared. In spite of the low pressure of the test rig, the results show that RELAP5 qualitatively predicts the thermal hydraulic behaviour and the accompanied phenomenon of flow inversion of such facilities. Quantitatively, there is a difference between the predicted and measured values especially the channel's surface temperature. This difference may be return to the uncertainties in initial conditions of experimental runs, the position of the thermocouples which buried inside the heat structure, and the heat transfer package in RELAP5.

A compact internal drum test rig for measurements of rolling contact forces between a single tread block and a substrate

NARCIS (Netherlands)

Lundberg, O.E.; Kari, L.; Lopez Arteaga, I.

2017-01-01

A novel test rig design is presented which enables detailed studies of the three force components generated in the impact and release phase of rolling contact between a tyre tread block and a substrate. The design of the compact internal drum test rig provides realistic impact and release angles for

Designer ligands. Part 15. Synthesis and characterisation of novel Mn(lI), Ni(II) and Zn(II) complexes of 1,10-phenanthroline-derived ligands

CSIR Research Space (South Africa)

Wellington, Kevin W

2009-01-01

Full Text Available Series of manganese(II), nickel(II) and zinc(II) complexes have been prepared using 1,10-phenanthroline-derived ligands, and their coordination geometries have been assigned using infrared data. It is apparent that, depending on the ligand...

Isolation and characterization of the human homologue of rig and its pseudogenes: The functional gene has features characteristic of housekeeping genes

International Nuclear Information System (INIS)

Shiga, Kiyoto; Yamamoto, Hiroshi; Okamoto, Hiroshi

1990-01-01

Rig (rat insulinoma gene) was first isolated from a cDNA library of rat insulinomas and has been found to be activated in various human tumors such as insulinomas, esophageal cancers, and colon cancers. Here the authors isolated the human homologue of rig from a genomic DNA library constructed from a human esophageal carcinoma and determined its complete nucleotide sequence. The gene is composed of about 3,000 nucleotides and divided into four exons separated by three introns: exon 3 encodes the nuclear location signal and the DNA-binding domain of the RIG protein. The transcription initiation site was located at -46 base pairs upstream from the first ATG codon. The 5'-flanking region of the gene has no apparent TATA-box or CAAT-box sequence. However, two GC boxes are found at -189 and -30 base pairs upstream from the transcription initiation site and five GC boxes are also found in introns 1 and 2. The gene is bounded in the 5' region by CpG islands, regions of DNA with a high GC content and a high frequency of CpG dinucleotides relative to the bulk genome. Furthermore, the human genome contains at least six copies of RIG pseudogenes, and four of them have the characteristics of processed pseudogenes. From these results together with the finding that RIG is expressed in a wide variety of tissues and cells, they speculate that RIG belongs to the class of housekeeping genes, whose products are necessary for the growth of all cell types

Multispectroscopic DNA-Binding studies and antimicrobial evaluation of new mixed-ligand Silver(I) complex and nanocomplex: A comparative study

Science.gov (United States)

Movahedi, Elaheh; Rezvani, Ali Reza

2018-05-01

A novel mixed-ligand Ag(I) complex, , has been synthesized and characterized by the elemental analysis, IR spectroscopy and 1HNMR. In the formula, dian and phen are N-(4,5-diazafluoren-9-ylidene)aniline and 1,10-phenanthroline, respectively. This complex also has been prepared at nano size by sonochemical technique and characterized by the FTIR and scanning electron microscopy (SEM). To evaluate the biological preferences of the Ag(I) complex and nanocomplex and verify the relationships between the structure and biological function, in vitro DNA binding and antibacterial experiments have been carried out. DNA-complex interaction has been pursued by electronic absorption titration, luminescence titration, competitive binding experiment, effect of ionic strength, thermodynamic studies, viscometric evaluation and circular dichroism spectroscopy in the physiological pH. Each compound displays significant binding trend to the CT-DNA. The mode of binding to the CT-DNA probably is a moderate intercalation mode with the partial insertion of the planar ligands between the base stacks of double-stranded DNA. The relative viscosities and circular dichroism spectra of the CT-DNA with the complex solutions, confirm the intense interactions of the Ag(I) complex and nanocomplex with DNA. An in vitro antibacterial test of the complex and nanocomplex on a series of the Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis) and the Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) shows a remarkable antibacterial feature of the Ag(I) complex. The MIC values (minimum inhibitory concentration) of the compounds compare with silver nitrate and silver sulfadiazine. The bacterial inhibitions of the Ag(I) complex and nanocomplex are agreed to their DNA binding affinities.

Investigating the binding behaviour of two avidin-based testosterone binders using molecular recognition force spectroscopy.

Science.gov (United States)

Rangl, Martina; Leitner, Michael; Riihimäki, Tiina; Lehtonen, Soili; Hytönen, Vesa P; Gruber, Hermann J; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

2014-02-01

Molecular recognition force spectroscopy, a biosensing atomic force microscopy technique allows to characterise the dissociation of ligand-receptor complexes at the molecular level. Here, we used molecular recognition force spectroscopy to study the binding capability of recently developed testosterone binders. The two avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both testosterone and biotin but differ in their binding behaviour towards these ligands. To explore the ligand binding and dissociation energy landscape of these proteins, we tethered biotin or testosterone to the atomic force microscopy probe while the testosterone-binding protein was immobilized on the surface. Repeated formation and rupture of the ligand-receptor complex at different pulling velocities allowed determination of the loading rate dependence of the complex-rupturing force. In this way, we obtained the molecular dissociation rate (k(off)) and energy landscape distances (x(β)) of the four possible complexes: sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It was found that the kinetic off-rates for both proteins and both ligands are similar. In contrast, the x(β) values, as well as the probability of complex formations, varied considerably. In addition, competitive binding experiments with biotin and testosterone in solution differ significantly for the two testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2. Unravelling the binding behaviour of the investigated testosterone-binding proteins is expected to improve their usability for possible sensing applications. Copyright © 2014 John Wiley & Sons, Ltd.

I know my neighbour: individual recognition in Octopus vulgaris.

Science.gov (United States)

Tricarico, Elena; Borrelli, Luciana; Gherardi, Francesca; Fiorito, Graziano

2011-04-13

Little is known about individual recognition (IR) in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies) and field observations (octopuses of neighbouring dens display little agonism between each other). To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions. The experimental design was composed of 3 phases: Phase 1 (acclimatization): 12 "sight-allowed" (and 12 "isolated") pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque) partition to allow (and block) the vision of the conspecific; Phase 2 (cohabitation): members of each pair (both sight-allowed and isolated) were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test): each pair (both sight-allowed and isolated) was subject to a switch of an octopus to form pairs composed of either familiar ("sham switches") or unfamiliar conspecifics ("real switches"). Longer latencies (i.e. the time elapsed from the first interaction) and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition. Octopuses appear able to recognise conspecifics and to remember the individual previously met for at least one day. To the best of our knowledge, this is the first experimental study showing the occurrence of a form of IR in cephalopods. Future studies should clarify whether this is a "true" IR.

I know my neighbour: individual recognition in Octopus vulgaris.

Directory of Open Access Journals (Sweden)

Elena Tricarico

2011-04-01

Full Text Available Little is known about individual recognition (IR in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies and field observations (octopuses of neighbouring dens display little agonism between each other. To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions.The experimental design was composed of 3 phases: Phase 1 (acclimatization: 12 "sight-allowed" (and 12 "isolated" pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque partition to allow (and block the vision of the conspecific; Phase 2 (cohabitation: members of each pair (both sight-allowed and isolated were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test: each pair (both sight-allowed and isolated was subject to a switch of an octopus to form pairs composed of either familiar ("sham switches" or unfamiliar conspecifics ("real switches". Longer latencies (i.e. the time elapsed from the first interaction and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition.Octopuses appear able to recognise conspecifics and to remember the individual previously met for at least one day. To the best of our knowledge, this is the first experimental study showing the occurrence of a form of IR in cephalopods. Future studies should clarify whether this is a "true" IR.

Out-of-pile burnout experiments in a full-scale simulation of an irradiation rig in a HIFAR hollow fuel element facility

International Nuclear Information System (INIS)

Chapman, A.G.; Hargreaves, N.D.

1986-06-01

Flow measurement and burnout experiments were performed in an out-of-pile test rig which simulates the conditions of UO 2 irradiation rig in a hollow fuel element facility of the HIFAR reactor. One per cent of the coolant flow in the fuel element passed through the irradiation rig. A burnout heat flux of 90 W cm -2 was observed at the surface of an electrically-heated, dummy irradiation can. When the coolant flow rate in the irradiation rig was increased by a factor of 2.5, the burnout heat flux rose by 30 per cent to 117 W cm -2 . A simple modification to the supporting frame for the cans improved the burnout heat flux by 3 per cent at 1 per cent of the coolant flow, but enhanced it by 17 per cent at 2.5 per cent of the coolant flow. Of ten burnout events observed, eight were located upstream of the end of the heated length of the can. The burnout results form a self-consistent, credible set of data and provide a rational basis for the establishment of maximum permissible operating heat fluxes in irradiation rigs of the type simulated. Recommendations are made for the practical application of the results

Development and operation of the Above Dome Inspection Rig (ADIR)

International Nuclear Information System (INIS)

Dickson, R.P.; Moorby, J.

1984-01-01

Hinkley Point 'B' is developing its remote inspection equipment in order to be able to inspect reactor internals adequately without manned vessel entry. The Above Dome Inspection Rig has been built to allow a number of inspection systems to be introduced and operated within the reactor. The ability to introduce, use and remove inspection equipment without the necessity to lift the rig from the reactor is a vital feature in the speed achieved in completing inspections quickly. Television was selected for the A.D.M. because it has significant advantages in terms of operational convenience. However the quality of image obtained in terms of information available compares unfavourably with photography. The sharpness of a photographic image is largely dictated by the chemical structure of the emulsion, whereas video is limited by the picture line structure and bandwidth. The need for a photographic system for in reactor use is therefore essential for high definition inspection requirements. The first inspection system that has been developed for the ADIR is the Telefilm camera. It consists of a Hasselblad photographic camera using an Insight television camera looking through its viewfinder. The characteristics of television and photography have been combined. (author)

Cell-specific targeting by heterobivalent ligands.

Science.gov (United States)

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

Unstable quantum states and rigged Hilbert spaces

International Nuclear Information System (INIS)

Gorini, V.; Parravicini, G.

1978-10-01

Rigged Hilbert space techniques are applied to the quantum mechanical treatment of unstable states in nonrelativistic scattering theory. A method is discussed which is based on representations of decay amplitudes in terms of expansions over complete sets of generalized eigenvectors of the interacting Hamiltonian, corresponding to complex eigenvalues. These expansions contain both a discrete and a continuum contribution. The former corresponds to eigenvalues located at the second sheet poles of the S matrix, and yields the exponential terms in the survival amplitude. The latter arises from generalized eigenvectors associated to complex eigenvalues on background contours in the complex plane, and gives the corrections to the exponential law. 27 references

Hydraulic lifter for an underwater drilling rig

Energy Technology Data Exchange (ETDEWEB)

Garan' ko, Yu L

1981-01-15

A hydraulic lifter is suggested for an underwater drilling rig. It includes a base, hydraulic cylinders for lifting the drilling pipes connected to the clamp holder and hydraulic distributor. In order to simplify the design of the device, the base is made with a hollow chamber connected to the rod cavities and through the hydraulic distributor to the cavities of the hydraulic cylinders for lifting the drilling pipes. The hydraulic distributor is connected to the hydrosphere through the supply valve with control in time or by remote control. The base is equipped with reverse valves whose outlets are on the support surface of the base.

Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages

International Nuclear Information System (INIS)

Schlepper-Schaefer, J.; Huelsmann, D.; Djovkar, A.; Meyer, H.E.; Herbertz, L.; Kolb, H.; Kolb-Bachofen, V.

1986-01-01

The intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues is rat liver was followed. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au 5 ), 17 nm (Au 17 ), 50 nm (Au 50 ) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au 5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc

Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

Science.gov (United States)

Singer, M S; Shepherd, G M

1994-06-02

Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

Thermodynamic fingerprints of ligand binding to human telomeric G-quadruplexes.

Science.gov (United States)

Bončina, Matjaž; Podlipnik, Črtomir; Piantanida, Ivo; Eilmes, Julita; Teulade-Fichou, Marie-Paule; Vesnaver, Gorazd; Lah, Jurij

2015-12-02

Thermodynamic studies of ligand binding to human telomere (ht) DNA quadruplexes, as a rule, neglect the involvement of various ht-DNA conformations in the binding process. Therefore, the thermodynamic driving forces and the mechanisms of ht-DNA G-quadruplex-ligand recognition remain poorly understood. In this work we characterize thermodynamically and structurally binding of netropsin (Net), dibenzotetraaza[14]annulene derivatives (DP77, DP78), cationic porphyrin (TMPyP4) and two bisquinolinium ligands (Phen-DC3, 360A-Br) to the ht-DNA fragment (Tel22) AGGG(TTAGGG)3 using isothermal titration calorimetry, CD and fluorescence spectroscopy, gel electrophoresis and molecular modeling. By global thermodynamic analysis of experimental data we show that the driving forces characterized by contributions of specific interactions, changes in solvation and conformation differ significantly for binding of ligands with low quadruplex selectivity over duplexes (Net, DP77, DP78, TMPyP4; KTel22 ≈ KdsDNA). These contributions are in accordance with the observed structural features (changes) and suggest that upon binding Net, DP77, DP78 and TMPyP4 select hybrid-1 and/or hybrid-2 conformation while Phen-DC3 and 360A-Br induce the transition of hybrid-1 and hybrid-2 to the structure with characteristics of antiparallel or hybrid-3 type conformation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bystander protein protects potential vaccine-targeting ligands against intestinal proteolysis.

Science.gov (United States)

Reuter, Fabian; Bade, Steffen; Hirst, Timothy R; Frey, Andreas

2009-07-20

Endowing mucosal vaccines with ligands that target antigen to mucosal lymphoid tissues may improve immunization efficacy provided that the ligands withstand the proteolytic environment of the gastro-intestinal tract until they reach their destination. Our aim was to investigate whether and how three renowned ligands - Ulex europaeus agglutinin I and the B subunits of cholera toxin and E. coli heat-labile enterotoxin - master this challenge. We assessed the digestive power of natural murine intestinal fluid (natIF) using assays for trypsin, chymotrypsin and pancreatic elastase along with a test for nonspecific proteolysis. The natIF was compared with simulated murine intestinal fluid (simIF) that resembled the trypsin, chymotrypsin and elastase activities of its natural counterpart but lacked or contained albumins as additional protease substrates. The ligands were exposed to the digestive fluids and degradation was determined. The studies revealed that (i) the three pancreatic endoproteases constitute only one third of the total protease activity of natIF and (ii) the ligands resist proteolysis in natIF and protein-enriched simIF over 3 h but (iii) are partially destroyed in simIF that lacks additional protease substrate. We assume that the proteins of natIF are preferred substrates for the intestinal proteases and thus can protect vaccine-targeting ligands from destruction.

Recognition

DEFF Research Database (Denmark)

Gimmler, Antje

2017-01-01

In this article, I shall examine the cognitive, heuristic and theoretical functions of the concept of recognition. To evaluate both the explanatory power and the limitations of a sociological concept, the theory construction must be analysed and its actual productivity for sociological theory mus...

Rig Technician: Apprenticeship Course Outline. Apprenticeship and Industry Training. 5211.1

Science.gov (United States)

Alberta Advanced Education and Technology, 2011

2011-01-01

The graduate of the Rig Technician apprenticeship program is a certified journeyperson who will be able to: (1) take responsibility for personal safety and the safety of others; (2) supervise, coach and train apprentices and floor hands; (3) perform the duties of a motorhand, derrickhand or driller; and (4) perform assigned tasks in accordance…

Structural basis for AMPA receptor activation and ligand selectivity

DEFF Research Database (Denmark)

Hogner, A; Kastrup, Jette Sandholm Jensen; Jin, R

2002-01-01

Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology...... with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent...

Going deep : new generation of giant rigs extends drillers' reach

International Nuclear Information System (INIS)

Laverty Wilson, K.

2001-01-01

The Eirik Roude, an offshore super rig, arrived in Halifax Harbour from Florida in the summer 2001 for a retrofit before it is sent to work in the rugged environment offshore of Nova Scotia. The drilling platform is a joint venture between PanCanadian Petroleum and Ocean Rig. Is is the most technologically advanced and sophisticated deep water drilling platform in the world and can operate in 3,000 metre deep water for 365 days of the year. It is a fifth-generation semi-submersible rig. It floats on long legs that lower the centre of gravity below surface turbulence to provide a stable work platform even during Atlantic storms. The 110 metre long rig has three mud systems that store 593 cubic metres in mud pits, 1,260 cubic metres in pontoons, and can carry 26,140 barrels of fuel oil, 4,070 barrels of potable water and 13,210 barrels of drilling water. PanCanadian has provided $2 million to the Nova Scotia Community College to teach an appropriate curriculum for the required workforce. It is expected that 120 local workers will be recruited. PanCanadian plans to drill 3 or 4 offshore wells annually for the next 5 years. It is estimated that 700-800 workers will be on site at the peak of the retrofit. In addition, Marathon Oil has contracted the Smedvig-owned West Navion for Nova Scotia work. This vessel is designed to work in depths of up to 2,500 metres and can be upgraded to reach 3,000 metres. Its' dual handling capacity makes it suitable to do drilling and well completion simultaneously, thereby reducing the halts in operations and increasing the drilling efficiency. East Coast governments and trade associations are also committed to make the most of the offshore oil and gas revival, including the development of a petrochemical market. Their goal is to build a world class energy sector while protecting the environment and optimizing the financial, economic and social benefits to Nova Scotians. The Nova Scotia Benefits program requires that oil companies

Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins

DEFF Research Database (Denmark)

Rognan, D; Lauemoller, S L; Holm, A

1999-01-01

A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein...... coordinates of the MHC-bound peptide have first been determined with an accuracy of about 1-1.5 A. Furthermore, it may be easily recalibrated for any protein-ligand complex.......) and of a series of 16 peptides to H-2K(k). Predictions were more accurate for HLA-A2-binding peptides as the training set had been built from experimentally determined structures. The average error in predicting the binding free energy of the test peptides was 3.1 kJ/mol. For the homology model-derived equation...

Sampling protein motion and solvent effect during ligand binding

Science.gov (United States)

Limongelli, Vittorio; Marinelli, Luciana; Cosconati, Sandro; La Motta, Concettina; Sartini, Stefania; Mugnaini, Laura; Da Settimo, Federico; Novellino, Ettore; Parrinello, Michele

2012-01-01

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one. PMID:22238423

Master i Industriel Informationsteknologi

DEFF Research Database (Denmark)

Knudsen, Morten

2000-01-01

Målgruppen for denne åbne Masteruddannelse, som udbydes af Aalborg Universitet i samarbejde med IT-Vest, er personer, som dagligt arbejder med teknisk IT, og som har en videregående uddannelse på bachelorniveau. Uddannelsen, som er 3- årig på ½ tid, startede September 1998, og det samlede optag d...

Master i Industriel Informationsteknologi

DEFF Research Database (Denmark)

Knudsen, Morten

2001-01-01

Målgruppen for denne åbne Masteruddannelse, som udbydes af Aalborg Universitet i samarbejde med IT-Vest, er personer, som dagligt arbejder med teknisk IT, og som har en videregående uddannelse på bachelorniveau. Uddannelsen, som er 3- årig på ½ tid, startede September 1998, og det samlede optag d...

A drilling rig tower

Energy Technology Data Exchange (ETDEWEB)

Mironov, A.A.; Barashkov, V.A.; Bulgakov, E.S.; Kuldoshin, I.P.; Lebedev, A.I.; Papin, N.M.; Rebrik, B.M.; Sirotkin, N.V.

1981-05-23

Presentation is made of a drilling rig tower, comprising a gantry, a support shaft with a bracing strut and drawings out, and turn buckles. In order to increase the reliability of the tower in operation, to decrease the over all dimensions in a transport position, and to decrease the amount of time taken to transfer the tower from an operational position into a transportable one, and vice versa, the tower is equipped with a rotary frame made in the form of a triangular prism, whose lateral edges are connected by hinges: the first one with the lower part of the support shaft, the second with the gantry, and the third one to the upper part of the support shaft by means of the drawings out. The large boundary of the rotary frame is connected by a hinge to the support shaft by means of a bracing strut, which is equipped with a slide block connected to it by a hinge, and the rotary frame has a guide for the slide block reinforced to it on the large boundary. Besides this, the lateral edge of the rotary frame is connected to the gantry by means of turn buckles.

I Know My Neighbour: Individual Recognition in Octopus vulgaris

Science.gov (United States)

Tricarico, Elena; Borrelli, Luciana; Gherardi, Francesca; Fiorito, Graziano

2011-01-01

Background Little is known about individual recognition (IR) in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies) and field observations (octopuses of neighbouring dens display little agonism between each other). To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions. Methodology/Principal Findings The experimental design was composed of 3 phases: Phase 1 (acclimatization): 12 “sight-allowed” (and 12 “isolated”) pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque) partition to allow (and block) the vision of the conspecific; Phase 2 (cohabitation): members of each pair (both sight-allowed and isolated) were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test): each pair (both sight-allowed and isolated) was subject to a switch of an octopus to form pairs composed of either familiar (“sham switches”) or unfamiliar conspecifics (“real switches”). Longer latencies (i.e. the time elapsed from the first interaction) and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition. Conclusions Octopuses appear able to recognise conspecifics and to remember the individual previously met for at least one day. To the best of our knowledge, this is the first experimental study showing the occurrence of a form of IR in cephalopods. Future studies should clarify whether this is a “true” IR. PMID:21533257

Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.

Directory of Open Access Journals (Sweden)

Benno Wölk

Full Text Available Fine mapping of human cytotoxic T lymphocyte (CTL responses against hepatitis C virus (HCV is based on external loading of target cells with synthetic peptides which are either derived from prediction algorithms or from overlapping peptide libraries. These strategies do not address putative host and viral mechanisms which may alter processing as well as presentation of CTL epitopes. Therefore, the aim of this proof-of-concept study was to identify naturally processed HCV-derived major histocompatibility complex (MHC class I ligands. To this end, continuous human cell lines were engineered to inducibly express HCV proteins and to constitutively express high levels of functional HLA-A2. These cell lines were recognized in an HLA-A2-restricted manner by HCV-specific CTLs. Ligands eluted from HLA-A2 molecules isolated from large-scale cultures of these cell lines were separated by high performance liquid chromatography and further analyzed by electrospray ionization quadrupole time of flight mass spectrometry (MS/tandem MS. These analyses allowed the identification of two HLA-A2-restricted epitopes derived from HCV nonstructural proteins (NS 3 and 5B (NS3₁₄₀₆₋₁₄₁₅ and NS5B₂₅₉₄₋₂₆₀₂. In conclusion, we describe a general strategy that may be useful to investigate HCV pathogenesis and may contribute to the development of preventive and therapeutic vaccines in the future.

Indoor navigation by image recognition

Science.gov (United States)

Choi, Io Teng; Leong, Chi Chong; Hong, Ka Wo; Pun, Chi-Man

2017-07-01

With the progress of smartphones hardware, it is simple on smartphone using image recognition technique such as face detection. In addition, indoor navigation system development is much slower than outdoor navigation system. Hence, this research proves a usage of image recognition technique for navigation in indoor environment. In this paper, we introduced an indoor navigation application that uses the indoor environment features to locate user's location and a route calculating algorithm to generate an appropriate path for user. The application is implemented on Android smartphone rather than iPhone. Yet, the application design can also be applied on iOS because the design is implemented without using special features only for Android. We found that digital navigation system provides better and clearer location information than paper map. Also, the indoor environment is ideal for Image recognition processing. Hence, the results motivate us to design an indoor navigation system using image recognition.

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

Science.gov (United States)

Keegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Philip O; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M; Bloom, Barry R; Belisle, John T; Fortune, Sarah; Dedon, Peter C; Pellegrini, Matteo; Modlin, Robert L

2018-05-01

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. Copyright © 2018 by The American Association of Immunologists, Inc.

The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.

Directory of Open Access Journals (Sweden)

Xiliang Zheng

2015-04-01

Full Text Available We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity, the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics.

A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

Science.gov (United States)

Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

2017-07-01

Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

Match Rigging and the Career Concerns of Referees

DEFF Research Database (Denmark)

Severgnini, Battista; Boeri, Tito

2011-01-01

This paper contributes to the literature on career concerns and corruption by drawing on extensive information on the performance of referees and records from Calciopoli, a judicial inquiry carried out in 2006 on corruption in the Italian football league. Unlike previous studies, we can analyse...... in detail the assignment of the referees to the most important matches, which is an important step in their career. Moreover, we can relate this choice to the performance of referees in previous matches and the evaluations they received in this context. We find that referees involved in match rigging were...

Finite element calculation of fields around the end region of a turbine generator test rig

Energy Technology Data Exchange (ETDEWEB)

Eastham, J.F.; Rodger, D.; Lai, H.C.; Nouri, H. (Univ. of Bath (United Kingdom))

1993-03-01

Under transient conditions, most often caused by faults in the power system, unbalanced load is presented to a turbine generator. This gives rise to airgap fields which do not travel at the speed of the rotor, and cause induced currents which occur in the solid steel surface. This can cause high local heating. The current path is generally in the axial direction of the machine but the distribution in the end region is not so well known. Here, comparisons are drawn between the use of surface impedance elements and volume elements when modeling a test rig using the MEGA package. The test rig is representative of a turbine generator. The work is supported by practical measurements.

Interaction of In(I) and Tl(I) cations with 2,6-diaryl pyridine ligands: cation encapsulation within a very weakly interacting N/arene host environment.

Science.gov (United States)

Mansaray, Hassanatu B; Tang, Christina Y; Vidovic, Dragoslav; Thompson, Amber L; Aldridge, Simon

2012-12-03

The interaction of 2,6-dimesitylpyridine with Tl(I) and In(I) cations has been investigated with a view to developing tractable molecular M(I) compounds which are soluble in organic media. In stark contrast to isosteric and isoelectronic terphenyl systems, complexes featuring the [(2,6-Mes(2)py)M](+) fragment feature very weak metal-ligand interactions in the solid state, as revealed by M-N distances of the order of 2.45 Å (M = In) and 2.64 Å (M = Tl). While additional weak π interactions are observed with arene solvate molecules in these systems, the related 2:1 complex [(2,6-Mes(2)py)(2)In][BAr(f)(4)] features an In(I) center wholly encapsulated by the bulky Mes(2)py donors, and even longer In-N distances [2.586(6) and 2.662(5) Å]. These contacts are about 0.5 Å greater than the sum of the respective covalent radii (2.13 Å) and provide evidence for an effectively "naked" In(I) cation stabilized to a minor extent by orbital interactions.

@TOME-2: a new pipeline for comparative modeling of protein–ligand complexes

Science.gov (United States)

Pons, Jean-Luc; Labesse, Gilles

2009-01-01

@TOME 2.0 is new web pipeline dedicated to protein structure modeling and small ligand docking based on comparative analyses. @TOME 2.0 allows fold recognition, template selection, structural alignment editing, structure comparisons, 3D-model building and evaluation. These tasks are routinely used in sequence analyses for structure prediction. In our pipeline the necessary software is efficiently interconnected in an original manner to accelerate all the processes. Furthermore, we have also connected comparative docking of small ligands that is performed using protein–protein superposition. The input is a simple protein sequence in one-letter code with no comment. The resulting 3D model, protein–ligand complexes and structural alignments can be visualized through dedicated Web interfaces or can be downloaded for further studies. These original features will aid in the functional annotation of proteins and the selection of templates for molecular modeling and virtual screening. Several examples are described to highlight some of the new functionalities provided by this pipeline. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/AT2/ PMID:19443448

@TOME-2: a new pipeline for comparative modeling of protein-ligand complexes.

Science.gov (United States)

Pons, Jean-Luc; Labesse, Gilles

2009-07-01

@TOME 2.0 is new web pipeline dedicated to protein structure modeling and small ligand docking based on comparative analyses. @TOME 2.0 allows fold recognition, template selection, structural alignment editing, structure comparisons, 3D-model building and evaluation. These tasks are routinely used in sequence analyses for structure prediction. In our pipeline the necessary software is efficiently interconnected in an original manner to accelerate all the processes. Furthermore, we have also connected comparative docking of small ligands that is performed using protein-protein superposition. The input is a simple protein sequence in one-letter code with no comment. The resulting 3D model, protein-ligand complexes and structural alignments can be visualized through dedicated Web interfaces or can be downloaded for further studies. These original features will aid in the functional annotation of proteins and the selection of templates for molecular modeling and virtual screening. Several examples are described to highlight some of the new functionalities provided by this pipeline. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/AT2/

A study of the modes of advancement of multiple drilling rigs and the influence of the inertial effects on the efficiency of the towers

Energy Technology Data Exchange (ETDEWEB)

Karapetyan, K.V.

1979-01-01

Studied in a mathematical model with the use of experimental data obtained through a method of measurement filming is the process of advancement of a drilling rig and the inertial actions on the drilling equipment are determined. It is shown that the tower type rigs, the VM-41 may be safely advanced along with the package of drilling stands. For mast rigs, suitable for conditions of multiple drilling, the creation of special drive mechanisms with high travel smoothness is recommended.

An in situ thermo-mechanical rig for lattice strain measurement during creep using neutron diffraction

Science.gov (United States)

Wang, Y. Q.; Kabra, S.; Zhang, S. Y.; Truman, C. E.; Smith, D. J.

2018-05-01

A long-term high-temperature testing stress rig has been designed and fabricated for performing in situ neutron diffraction tests at the ENGIN-X beamline, ISIS facility in the UK. It is capable of subjecting metals to high temperatures up to 800 °C and uniaxial loading under different boundary conditions including constant load, constant strain, and elastic follow-up, each with minimum of external control. Samples are held horizontally between grips and connected to a rigid rig frame, a soft aluminium bar, and a stepper motor with forces up to 20 kN. A new three zone split electrical resistance furnace which generates a stable and uniform heat atmosphere over 200 mm length was used to heat the samples. An 8 mm diameter port at 45° to the centre of the furnace was made in order to allow the neutron beam through the furnace to illuminate the sample. The entire instrument is mounted on the positioner at ENGIN-X and has the potential ability to operate continuously while being moved in and out of the neutron diffraction beam. The performance of the rig has been demonstrated by tracking the evolution of lattice strains in type 316H stainless steel under elastic follow-up control at 550 °C.

Analysis of rig test data for an axial/centrifugal compressor in the 12 kg/sec

Science.gov (United States)

Owen, A. K.

1994-01-01

Extensive testing was done on a T55-L-712 turboshaft engine compressor in a compressor test rig at TEXTRON/Lycoming. These rig tests will be followed by a series of engine tests to occur at the NASA Lewis Research Center beginning in the last quarter of 1993. The goals of the rig testing were: (1) map the steady state compressor operation from 20 percent to 100 percent design speed, (2) quantify the effects of compressor bleed on the operation of the compressor, and (3) explore and measure the operation of the compressor in the flow ranges 'beyond' the normal compressor stall line. Instrumentation consisted of 497 steady state pressure sensors, 153 temperature sensors and 34 high response transducers for transient analysis in the pre- and post-stall operating regime. These measurements allow for generation of detailed stage characteristics as well as overall mapping. Transient data is being analyzed for the existence of modal disturbances at the front face of the compression system ('stall precursors'). This paper presents some preliminary results of the ongoing analysis and a description of the current and future program plans. It will primarily address the unsteady events at the front face of the compression system that occur as the system transitions from steady state to unsteady (stall/surge) operation.

Demonstration of various rotor instabilities (exhibit of Bently Rotor Dynamics Research Corporation Laborator rigs at symposium on instability in rotaing machinery)

Science.gov (United States)

Muszynska, A.

1985-01-01

The operation of rotor rigs used to demonstrate various instability phenomena occurring in rotating machines is described. The instability phenomena demonstrated included oil whirl/whip antiswirl, rub, loose rotating parts, water-lubricated bearing instabilities, and cracked shaft. The rotor rigs were also used to show corrective measures for preventing instabilities. Vibrational response data from the rigs were taken with modern, computerized instrumentation. The rotor nonsynchronous perturbation rig demonstrated modal identification techniques for rotor/bearing systems. Computer-aided data acquisition and presentation, using the dynamic stiffness method, makes it possible to identify rotor and bearing parameters for low modes. The shaft mode demonstrator presented the amplified modal shape line of the shaft excited by inertia forces of unbalance (synchronous perturbation). The first three bending modes of the shaft can be demonstrated. The user-friendly software, Orbits, presented a simulation of rotor precessional motion that is characteristic of various instability phenomena. The data presentation demonstration used data measured on a turbine driven compressor train as an example of how computer aided data acquisition and presentation assists in identifying rotating machine malfunctions.

Design and commission of an experimental test rig to apply a full-scale pressure load on composite sandwich panels representative of an aircraft secondary structure

International Nuclear Information System (INIS)

Crump, D A; Dulieu-Barton, J M; Savage, J

2010-01-01

This paper describes the design of a test rig, which is used to apply a representative pressure load to a full-scale composite sandwich secondary aircraft structure. A generic panel was designed with features to represent those in the composite sandwich secondary aircraft structure. To provide full-field strain data from the panels, the test rig was designed for use with optical measurement techniques such as thermoelastic stress analysis (TSA) and digital image correlation (DIC). TSA requires a cyclic load to be applied to a structure for the measurement of the strain state; therefore, the test rig has been designed to be mounted on a standard servo-hydraulic test machine. As both TSA and DIC require an uninterrupted view of the surface of the test panel, an important consideration in the design is facilitating the optical access for the two techniques. To aid the test rig design a finite element (FE) model was produced. The model provides information on the deflections that must be accommodated by the test rig, and ensures that the stress and strain levels developed in the panel when loaded in the test rig would be sufficient for measurement using TSA and DIC. Finally, initial tests using the test rig have shown it to be capable of achieving the required pressure and maintaining a cyclic load. It was also demonstrated that both TSA and DIC data can be collected from the panels under load, which are used to validate the stress and deflection derived from the FE model

Is having similar eye movement patterns during face learning and recognition beneficial for recognition performance? Evidence from hidden Markov modeling.

Science.gov (United States)

Chuk, Tim; Chan, Antoni B; Hsiao, Janet H

2017-12-01

The hidden Markov model (HMM)-based approach for eye movement analysis is able to reflect individual differences in both spatial and temporal aspects of eye movements. Here we used this approach to understand the relationship between eye movements during face learning and recognition, and its association with recognition performance. We discovered holistic (i.e., mainly looking at the face center) and analytic (i.e., specifically looking at the two eyes in addition to the face center) patterns during both learning and recognition. Although for both learning and recognition, participants who adopted analytic patterns had better recognition performance than those with holistic patterns, a significant positive correlation between the likelihood of participants' patterns being classified as analytic and their recognition performance was only observed during recognition. Significantly more participants adopted holistic patterns during learning than recognition. Interestingly, about 40% of the participants used different patterns between learning and recognition, and among them 90% switched their patterns from holistic at learning to analytic at recognition. In contrast to the scan path theory, which posits that eye movements during learning have to be recapitulated during recognition for the recognition to be successful, participants who used the same or different patterns during learning and recognition did not differ in recognition performance. The similarity between their learning and recognition eye movement patterns also did not correlate with their recognition performance. These findings suggested that perceptuomotor memory elicited by eye movement patterns during learning does not play an important role in recognition. In contrast, the retrieval of diagnostic information for recognition, such as the eyes for face recognition, is a better predictor for recognition performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ergonomic exposure on a drilling rig

DEFF Research Database (Denmark)

Jensen, Carsten; Jensen, Chris

. In a relatively old study on American drilling rigs it was indicated that lower back problems was a frequent cause of absence (Clemmer et al. 1991). Most of the incidents causing lower back injuries were associated with heavy lifting or pushing/pulling objects by roustabouts, floorhands, derrickmen and welders......, but for some of the most frequent problems, such as musculoskeletal problems, it is difficult to determine whether the causes are work‐related or not. As manual handling (lifting, pushing, etc.) in awkward body postures increase the risk of developing musculoskeletal disorders, it should be expected that work......‐related health problems contribute to sickness absence in the offshore industry, if these working postures are common. However, also work‐related psychosocial factors, personal factors and other factors may contribute to the development of lower back disorders, which often have a multifactorial background...

The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls

Directory of Open Access Journals (Sweden)

Bio DS

2013-05-01

Full Text Available Danielle Soares Bio,1 Márcio Gerhardt Soeiro-de-Souza,1 Maria Concepción Garcia Otaduy,2 Rodrigo Machado-Vieira,3 Ricardo Alberto Moreno11Mood Disorders Unit, 2Institute of Radiology, Department and Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil; 3Experimental Therapeutics and Pathophysiology Branch (ETPB, National Institute of Mental Health, NIMH NIH, Bethesda, MD, USAIntroduction: Impairments in facial emotion recognition (FER have been reported in bipolar disorder (BD subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls.Material and methods: Thirty-nine euthymic BD I (type I subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus.Results: The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness.Conclusion: Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning.Keywords: bipolar disorder, social cognition, facial emotion recognition

Enhancement of GABAergic transmission by zolpidem, an imidazopyridine with preferential affinity for type I benzodiazepine receptors.

Science.gov (United States)

Biggio, G; Concas, A; Corda, M G; Serra, M

1989-02-28

The effect of zolpidem, an imidazopyridine derivative with high affinity at the type I benzodiazepine recognition site, on the function of the GABAA/ionophore receptor complex was studied in vitro. Zolpidem, mimicking the action of diazepam, increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced [35S]TBPS binding in rat cortical membrane preparations. Zolpidem was less effective than diazepam on the above parameters. Zolpidem induced a lower increase of [3H]GABA binding (23 vs. 35%) and muscimol-stimulated 36Cl- uptake (22 vs. 40%) and a smaller decrease of [35S]TBPS binding (47 vs. 77%) than diazepam. The finding that zolpidem enhanced the function of GABAergic synapses with an efficacy qualitatively and quantitatively different from that of diazepam suggests that this compound is a partial agonist at the benzodiazepine recognition site. Thus, our results are consistent with the view that the biochemical and pharmacological profile of a benzodiazepine recognition site ligand reflects its efficacy to enhance GABAergic transmission. Whether the preferential affinity of zolpidem at the type I site is involved in its atypical biochemical and pharmacological profile remains to be clarified.

New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

Energy Technology Data Exchange (ETDEWEB)

Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko [Takasago International Corp., Kanagawa (Japan)] [and others

1995-12-31

Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

Evaluation of several novel diamide based ligands for selective extraction of tetravalent plutonium

Energy Technology Data Exchange (ETDEWEB)

Sivaramakrishna, Mallampalli; Nayak, Shashikant K. [Heavy Water Board, V.S. Bhavan, Mumbai (India); Raut, Dhaval R.; Mohapatra, Prasanta K. [Bhabha Atomic Research Center, Mumbai (India). Radiochemistry Division; Nayak, Sandip K. [Bhabha Atomic Research Center, Mumbai (India). Bioorganic Division

2017-06-01

The present paper describes the selective extraction of tetravalent plutonium employing several diamide ligands containing aromatic spacer groups. The ligands containing two amide functional groups attached to a 2,4,6-tri-phenyl pyridine moiety with different substituents viz.; L{sub I} (iso-butyl), L{sub II}(n-butyl), L{sub III}(n-octyl), L{sub IV} (2-ethylhexyl) at the amidic nitrogen atom were evaluated for the extraction of Pu(IV) using their nitrobenzene solutions. The distribution ratio values of Pu(IV) with the diamide ligands followed the order: L{sub II}>L{sub I}>L{sub III}>L{sub IV} and were significantly higher than those of metal ions such as Cs(I), Sr(II), Am(III) and Eu(III). The distribution ratio values of U(VI) were about 2-3 orders magnitude lower than those of Pu(IV). The extraction and stripping kinetics were found to be moderately fast and it took less than 30 min (less than 5 min for L{sub I} and L{sub IV}) to obtain equilibrium D values. The extraction was found to be increasing with the aqueous phase nitric acid concentration conforming to a solvation mechanism of extraction. The extracted species contained two ligand molecules for L{sub I} and L{sub II} while monosolvates were observed for the other two extractants. The ligands showed good radiation stability up to an absorbed dose of 630 kGy.

Functions of galectins as 'self/non-self'-recognition and effector factors.

Science.gov (United States)

Vasta, Gerardo R; Feng, Chiguang; González-Montalbán, Nuria; Mancini, Justin; Yang, Lishi; Abernathy, Kelsey; Frost, Graeme; Palm, Cheyenne

2017-07-31

Carbohydrate structures on the cell surface encode complex information that through specific recognition by carbohydrate-binding proteins (lectins) modulates interactions between cells, cells and the extracellular matrix, or mediates recognition of potential microbial pathogens. Galectins are a family of ß-galactoside-binding lectins, which are evolutionary conserved and have been identified in most organisms, from fungi to invertebrates and vertebrates, including mammals. Since their discovery in the 1970s, their biological roles, initially understood as limited to recognition of endogenous carbohydrate ligands in embryogenesis and development, have expanded in recent years by the discovery of their roles in tissue repair and regulation of immune homeostasis. More recently, evidence has accumulated to support the notion that galectins can also bind glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity, thus establishing a new paradigm. Furthermore, some parasites 'subvert' the recognition roles of the vector/host galectins for successful attachment or invasion. These recent findings have revealed a striking functional diversification in this structurally conserved lectin family. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Self-recognition of avatar motion: how do I know it's me?

Science.gov (United States)

Cook, Richard; Johnston, Alan; Heyes, Cecilia

2012-02-22

When motion is isolated from form cues and viewed from third-person perspectives, individuals are able to recognize their own whole body movements better than those of friends. Because we rarely see our own bodies in motion from third-person viewpoints, this self-recognition advantage may indicate a contribution to perception from the motor system. Our first experiment provides evidence that recognition of self-produced and friends' motion dissociate, with only the latter showing sensitivity to orientation. Through the use of selectively disrupted avatar motion, our second experiment shows that self-recognition of facial motion is mediated by knowledge of the local temporal characteristics of one's own actions. Specifically, inverted self-recognition was unaffected by disruption of feature configurations and trajectories, but eliminated by temporal distortion. While actors lack third-person visual experience of their actions, they have a lifetime of proprioceptive, somatosensory, vestibular and first-person-visual experience. These sources of contingent feedback may provide actors with knowledge about the temporal properties of their actions, potentially supporting recognition of characteristic rhythmic variation when viewing self-produced motion. In contrast, the ability to recognize the motion signatures of familiar others may be dependent on configural topographic cues.

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

Science.gov (United States)

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-06-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (psocial interaction deficits in the poly I:C model (p0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.

Scavenger receptor-mediated recognition of maleyl bovine plasma albumin and the demaleylated protein in human monocyte macrophages

International Nuclear Information System (INIS)

Haberland, M.E.; Fogelman, A.M.

1985-01-01

Maleyl bovine plasma albumin competed on an equimolar basis with malondialdehyde low density lipoprotein (LDL) in suppressing the lysosomal hydrolysis of 125 I-labeled malondialdehyde LDL mediated by the scavenger receptor of human monocyte macrophages. Maleyl bovine plasma albumin, in which 94% of the amino groups were modified, exhibited an anodic mobility in agarose electrophoresis 1.7 times that of the native protein. Incubation of maleyl bovine plasma albumin at pH 3.5 regenerated the free amino groups and restored the protein to the same electrophoretic mobility as native albumin. Although ligands recognized by the scavenger receptor typically are anionic, the authors propose that addition of new negative charge achieved by maleylation, rather than directly forming the receptor binding site(s), induces conformational changes in albumin as a prerequisite to expression of the recognition domain(s). They conclude that the primary sequence of albumin, rather than addition of new negative charge, provides the recognition determinant(s) essential for interaction of maleyl bovine plasma albumin with the scavenger receptor

Stein and Honneth on Empathy and Emotional Recognition

DEFF Research Database (Denmark)

Jardine, James Alexander

2015-01-01

My aim in this paper is to make use of Edith Stein’s phenomenological analyses of empathy, emotion, and personhood to clarify and critically assess the recent suggestion by Axel Honneth that a basic form of recognition is affective in nature. I will begin by considering Honneth’s own presentation...... of this claim in his discussion of the role of affect in recognitive gestures, as well as in his notion of ‘elementary recognition,’ arguing that while his account contains much of value it also generates problems. On the basis of this analysis, I will try to show that Stein’s account of empathy demarcates...... an elementary form of recognition in a less problematic fashion than does Honneth’s own treatment of this issue. I will then spell out the consequences of this move for the emotional recognition thesis, arguing that Stein’s treatment lends it further credence, before ending with some remarks on the connection...

Ruthenium(II) carbonyl compounds with the 4'-chloro-2,2':6',2''-terpyridine ligand.

Science.gov (United States)

Tatikonda, Rajendhraprasad; Haukka, Matti

2017-04-01

Two ruthenium carbonyl complexes with the 4'-chloro-2,2':6',2''-terpyridine ligand (tpy-Cl, C 15 H 10 ClN 3 ), i.e. [RuCl(tpy-Cl)(CO) 2 ][RuCl 3 (CO) 3 ] (I) [systematic name: cis -di-carbonyl-chlorido(4'-chloro-2,2':6',2''-terpyridine-κ 3 N )ruthenium(II) fac -tricarbonyltri-chlorido-ruthenate(II)], and [RuCl 2 (tpy-Cl)(CO) 2 ] (II) [ cis -dicarbonyl- trans -di-chlorido(4'-chloro-2,2':6',2''-terpyridine-κ 2 N 1 , N 1' )ruthenium(II)], were synthesized and characterized by single-crystal X-ray diffraction. The Ru II atoms in both centrosymmetric structures (I) and (II) display similar, slightly distorted octa-hedral coordination spheres. The coordination sphere in the complex cation in compound (I) is defined by three N atoms of the tridentate tpy-Cl ligand, two carbonyl carbon atoms and one chlorido ligand; the charge is balanced by an octa-hedral [Ru(CO) 3 Cl 3 ] - counter-anion. In the neutral compound (II), the tpy-Cl ligand coordinates to the metal only through two of its N atoms. The coordination sphere of the Ru II atom is completed by two carbonyl and two chlorido ligands. In the crystal structures of both (I) and (II), weak C-H⋯Cl inter-actions are observed.

Effects of electrostatic interactions on ligand dissociation kinetics

Science.gov (United States)

Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

2018-02-01

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

A Thrust Allocation Method for Efficient Dynamic Positioning of a Semisubmersible Drilling Rig Based on the Hybrid Optimization Algorithm

Directory of Open Access Journals (Sweden)

Luman Zhao

2015-01-01

Full Text Available A thrust allocation method was proposed based on a hybrid optimization algorithm to efficiently and dynamically position a semisubmersible drilling rig. That is, the thrust allocation was optimized to produce the generalized forces and moment required while at the same time minimizing the total power consumption under the premise that forbidden zones should be taken into account. An optimization problem was mathematically formulated to provide the optimal thrust allocation by introducing the corresponding design variables, objective function, and constraints. A hybrid optimization algorithm consisting of a genetic algorithm and a sequential quadratic programming (SQP algorithm was selected and used to solve this problem. The proposed method was evaluated by applying it to a thrust allocation problem for a semisubmersible drilling rig. The results indicate that the proposed method can be used as part of a cost-effective strategy for thrust allocation of the rig.

Ligand Access Channels in Cytochrome P450 Enzymes: A Review

Directory of Open Access Journals (Sweden)

Philippe Urban

2018-05-01

Full Text Available Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role.

Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites

Science.gov (United States)

Vukovic, Sinisa; Brennan, Paul E.; Huggins, David J.

2016-09-01

The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites.

Science.gov (United States)

Vukovic, Sinisa; Brennan, Paul E; Huggins, David J

2016-09-01

The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

Advisory expert system for test rig operator

International Nuclear Information System (INIS)

Zielczynski, P.

1994-01-01

The advisory expert system MAESTRO (Modular Advisory Expert System for Test Rig Operator) has been designed to guide the operator of large experimental installation during start-up, steady state and shut down. The installation is located in the research reactor MARIA in the Institute of Atomic Energy in Swierk, Poland. The system acquires and analyses on line signals from installation and performs two tasks in real time: leading the operator and monitoring of the installation (including signal validation). Systems tasks, architecture and knowledge representation concepts are described. The system is based on expert systems techniques what makes in phases of continuous change of process parameters and it has been achieved by special knowledge representation allowing its dynamical modification. (author). 147 refs, 42 figs, 5 tab

Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation.

Science.gov (United States)

Peeters, M C; van Westen, G J P; Li, Q; IJzerman, A P

2011-01-01

G protein-coupled receptors (GPCRs) are the major drug target of medicines on the market today. Therefore, much research is and has been devoted to the elucidation of the function and three-dimensional structure of this large family of membrane proteins, which includes multiple conserved transmembrane domains connected by intra- and extracellular loops. In the last few years, the less conserved extracellular loops have garnered increasing interest, particularly after the publication of several GPCR crystal structures that clearly show the extracellular loops to be involved in ligand binding. This review will summarize the recent progress made in the clarification of the ligand binding and activation mechanism of class-A GPCRs and the role of extracellular loops in this process. Copyright © 2010 Elsevier Ltd. All rights reserved.

Descriptor Data Bank (DDB): A Cloud Platform for Multiperspective Modeling of Protein-Ligand Interactions.

Science.gov (United States)

Ashtawy, Hossam M; Mahapatra, Nihar R

2018-01-22

Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Currently, a large number of hypotheses and perspectives to model these interaction forces are scattered throughout the literature and largely forgotten. Instead, had they been assembled and utilized collectively, they would have substantially improved the accuracy of predicting binding affinity of protein-ligand complexes. In this work, we present Descriptor Data Bank (DDB), a data-driven platform on the cloud for facilitating multiperspective modeling of PL interactions. DDB is an open-access hub for depositing, hosting, executing, and sharing descriptor extraction tools and data for a large number of interaction modeling hypotheses. The platform also implements a machine-learning (ML) toolbox for automatic descriptor filtering and analysis and scoring function (SF) fitting and prediction. The descriptor filtering module is used to filter out irrelevant and/or noisy descriptors and to produce a compact subset from all available features. We seed DDB with 16 diverse descriptor extraction tools developed in-house and collected from the literature. The tools altogether generate over 2700 descriptors that characterize (i) proteins, (ii) ligands, and (iii) protein-ligand complexes. The in-house descriptors we extract are protein-specific which are based on pairwise primary and tertiary alignment of protein structures followed by clustering and trilateration. We built and used DDB's ML library to fit SFs to the in-house descriptors and those collected from the literature. We then evaluated them on several data sets that were constructed to reflect real-world drug screening scenarios. We found that multiperspective SFs that were constructed using a large number

Bidentate Ligand-passivated CsPbI3 Perovskite Nanocrystals for Stable Near-unity Photoluminescence Quantum Yield and Efficient Red Light-emitting Diodes

KAUST Repository

Pan, Jun

2017-12-17

Although halide perovskite nanocrystals (NCs) are promising materials for optoelectronic devices, they suffer severely from chemical and phase instabilities. Moreover, the common capping ligands like oleic acid and oleylamine that encapsulate the NCs will form an insulating layer, precluding their utility in optoelectronic devices. To overcome these limitations, we develop a post-synthesis passivation process for CsPbI3 NCs by using a bidentate ligand, namely 2,2’-Iminodibenzoic acid. Our passivated NCs exhibit narrow red photoluminescence with exceptional quantum yield (close to unity) and substantially improved stability. The passivated NCs enabled us to realize red light-emitting diodes (LEDs) with 5.02% external quantum efficiency and 748 cd/m2 luminance, surpassing by far LEDs made from the non-passivated NCs.

Bidentate Ligand-passivated CsPbI3 Perovskite Nanocrystals for Stable Near-unity Photoluminescence Quantum Yield and Efficient Red Light-emitting Diodes

KAUST Repository

Pan, Jun; Shang, Yuequn; Yin, Jun; de Bastiani, Michele; Peng, Wei; Dursun, Ibrahim; Sinatra, Lutfan; El-Zohry, Ahmed M.; Hedhili, Mohamed N.; Emwas, Abdul-Hamid M.; Mohammed, Omar F.; Ning, Zhijun; Bakr, Osman

2017-01-01

Although halide perovskite nanocrystals (NCs) are promising materials for optoelectronic devices, they suffer severely from chemical and phase instabilities. Moreover, the common capping ligands like oleic acid and oleylamine that encapsulate the NCs will form an insulating layer, precluding their utility in optoelectronic devices. To overcome these limitations, we develop a post-synthesis passivation process for CsPbI3 NCs by using a bidentate ligand, namely 2,2’-Iminodibenzoic acid. Our passivated NCs exhibit narrow red photoluminescence with exceptional quantum yield (close to unity) and substantially improved stability. The passivated NCs enabled us to realize red light-emitting diodes (LEDs) with 5.02% external quantum efficiency and 748 cd/m2 luminance, surpassing by far LEDs made from the non-passivated NCs.

Mechanical Design of a Performance Test Rig for the Turbine Air-Flow Task (TAFT)

Science.gov (United States)

Forbes, John C.; Xenofos, George D.; Farrow, John L.; Tyler, Tom; Williams, Robert; Sargent, Scott; Moharos, Jozsef

2004-01-01

To support development of the Boeing-Rocketdyne RS84 rocket engine, a full-flow, reaction turbine geometry was integrated into the NASA-MSFC turbine air-flow test facility. A mechanical design was generated which minimized the amount of new hardware while incorporating all test and instrumentation requirements. This paper provides details of the mechanical design for this Turbine Air-Flow Task (TAFT) test rig. The mechanical design process utilized for this task included the following basic stages: Conceptual Design. Preliminary Design. Detailed Design. Baseline of Design (including Configuration Control and Drawing Revision). Fabrication. Assembly. During the design process, many lessons were learned that should benefit future test rig design projects. Of primary importance are well-defined requirements early in the design process, a thorough detailed design package, and effective communication with both the customer and the fabrication contractors.

Slant rigs offer big payoffs in shallow drilling

International Nuclear Information System (INIS)

Smith, J.; Edwards, B.

1992-01-01

Slant hole drilling technology can result in considerable savings over conventionally drilled deviated holes because mud motors and deviation control with measurement while drilling tools are usually unnecessary. The benefits of using slant hole rigs for development drilling improve after the bit walk tendencies and the correct bottom hole assemblies have been determined for a particular area. This article discusses three recent drilling operations that successfully used slant drilling technology on land-based projects: drilling for heavy oil in Alberta, drilling for gas in Alberta, and drilling a river crossing for a gas pipeline in British Columbia. These examples demonstrate the flexibility of slant drilling technology

Practical calibration of design data to technical capabilities of horizontal directional drilling rig

Science.gov (United States)

Toropov, S. Yu; Toropov, V. S.

2018-05-01

In order to design more accurately trenchless pipeline passages, a technique has been developed for calculating the passage profile, based on specific parameters of the horizontal directional drilling rig, including the range of possible drilling angles and a list of compatible drill pipe sets. The algorithm for calculating the parameters of the trenchless passage profile is shown in the paper. This algorithm is based on taking into account the features of HDD technology, namely, three different stages of production. The authors take into account that the passage profile is formed at the first stage of passage construction, that is, when drilling a pilot well. The algorithm involves calculating the profile by taking into account parameters of the drill pipes used and angles of their deviation relative to each other during the pilot drilling. This approach allows us to unambiguously calibrate the designed profile for the HDD rig capabilities and the auxiliary and navigation equipment used in the construction process.

Small-Scale Testing Rig for Long-Term Cyclically Loaded Monopiles in Cohesionless Soil

DEFF Research Database (Denmark)

Roesen, Hanne Ravn; Ibsen, Lars Bo; Andersen, Lars Vabbersgaard

2012-01-01

, and the period of the cyclic loading. However, the design guidance on these issues is limited. Thus, in order to investigate the pile behaviour for cyclically long-term loaded monopiles, a test setup for small-scale tests in saturated dense cohesionless soil is constructed and presented in here. The cyclic...... loading is applied mechanically by means of a testing rig, where the important input parameters: mean level, amplitude, number of cycles, and period of the loading can be varied. The results from a monotonic and a cyclic loading test on an open-ended aluminium pile with diameter = 100 mm and embedded...... length = 600 mm proves that the test setup is capable of applying the cyclic long-term loading. The plastic deformations during loading depend not only on the loading applied but also of the relative density of the soil and, thus, the tests are carried out with relative densities of 77-88%, i.e. similar...

Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

Science.gov (United States)

El-Boraey, Hanaa A.

2012-11-01

Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.

Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy.

Science.gov (United States)

Duan, Lili; Liu, Xiao; Zhang, John Z H

2016-05-04

Efficient and reliable calculation of protein-ligand binding free energy is a grand challenge in computational biology and is of critical importance in drug design and many other molecular recognition problems. The main challenge lies in the calculation of entropic contribution to protein-ligand binding or interaction systems. In this report, we present a new interaction entropy method which is theoretically rigorous, computationally efficient, and numerically reliable for calculating entropic contribution to free energy in protein-ligand binding and other interaction processes. Drastically different from the widely employed but extremely expensive normal mode method for calculating entropy change in protein-ligand binding, the new method calculates the entropic component (interaction entropy or -TΔS) of the binding free energy directly from molecular dynamics simulation without any extra computational cost. Extensive study of over a dozen randomly selected protein-ligand binding systems demonstrated that this interaction entropy method is both computationally efficient and numerically reliable and is vastly superior to the standard normal mode approach. This interaction entropy paradigm introduces a novel and intuitive conceptual understanding of the entropic effect in protein-ligand binding and other general interaction systems as well as a practical method for highly efficient calculation of this effect.

Phosphorescent emissions of phosphine copper(I) complexes bearing 8-hydroxyquinoline carboxylic acid analogue ligands

Energy Technology Data Exchange (ETDEWEB)

Małecki, Jan G., E-mail: gmalecki@us.edu.pl [Department of Crystallography, Institute of Chemistry, University of Silesia, Szkolna 9 street, 40-006 Katowice (Poland); Łakomska, Iwona, E-mail: iwolak@chem.umk.pl [Department of Chemistry, Nicolaus Copernicus University, Toruń (Poland); Maroń, Anna [Department of Crystallography, Institute of Chemistry, University of Silesia, Szkolna 9 street, 40-006 Katowice (Poland); Szala, Marcin [Institute of Chemistry, University of Silesia, ul. Szkolna 9, 40-006 Katowice (Poland); Fandzloch, Marzena [Department of Chemistry, Nicolaus Copernicus University, Toruń (Poland); Nycz, Jacek E., E-mail: jacek.nycz@us.edu.pl [Institute of Chemistry, University of Silesia, ul. Szkolna 9, 40-006 Katowice (Poland)

2015-05-15

The pseudotetrahedral complexes of [Cu(PPh{sub 3}){sub 2}(L)], where L=8-hydroxy-2-methylquinoline-7-carboxylic acid (1), 8-hydroxy-2,5-dimethylquinoline-7-carboxylic acid (2) or 5-chloro-8-hydroxy-2-methylquinoline-7-carboxylic acid (3) have been synthesized and structurally characterized by X-ray crystallography. Their properties have been examined through combinations of IR, NMR, electronic absorption spectroscopy and cyclic voltammetry. The complexes exhibit extraordinary photophysical properties. Complex (1) in solid state exhibits an emission quantum yield of 4.67% and an excited life time of 1.88 ms (frozen DCM solution up to 6.7 ms). When dissolved in a coordinating solvent (acetonitrile) the charge transfer emission was quenched on a microsecond scale. - Highlights: • Synthesis of copper(I) complexes with 8-hydroxyquinoline carboxylic acid ligands. • Very long lived phosphorescent copper(I) complexes. • [Cu(PPh{sub 3}){sub 2}(L)] where L=8-hydroxy-2-methylquinoline-7-carboxylic acid luminesce in the solid state exhibits extremely long lifetime on millisecond scale (1.9 ms). • In frozen MeOH:EtOH solution lifetime increases to 7 ms. • Quantum efficiency equal to 4.7%.

Design of Seismic Test Rig for Control Rod Drive Mechanism of Jordan Research and Training Reactor

International Nuclear Information System (INIS)

Sun, Jongoh; Kim, Gyeongho; Yoo, Yeonsik; Cho, Yeonggarp; Kim, Jong In

2014-01-01

The reactor assembly is submerged in a reactor pool filled with water and its reactivity is controlled by locations of four control absorber rods(CARs) inside the reactor assembly. Each CAR is driven by a stepping motor installed at the top of the reactor pool and they are connected to each other by a tie rod and an electromagnet. The CARs scram the reactor by de-energizing the electromagnet in the event of a safe shutdown earthquake(SSE). Therefore, the safety function of the control rod drive mechanism(CRDM) which consists of a drive assembly, tie rod and CARs is to drop the CAR into the core within an appropriate time in case of the SSE. As well known, the operability for complex equipment such as the CRDM during an earthquake is very hard to be demonstrated by analysis and should be verified through tests. One of them simulates the reactor assembly and the guide tube of the CAR, and the other one does the pool wall where the drive assembly is installed. In this paper, design of the latter test rig and how the test is performed are presented. Initial design of the seismic test rig and excitation table had its first natural frequency at 16.3Hz and could not represent the environment where the CRDM was installed. Therefore, experimental modal analyses were performed and an FE model for the test rig and table was obtained and tuned based on the experimental results. Using the FE model, the design of the test rig and table was modified in order to have higher natural frequency than the cutoff frequency. The goal was achieved by changing its center of gravity and the stiffness of its sliding bearings

Design of Seismic Test Rig for Control Rod Drive Mechanism of Jordan Research and Training Reactor

Energy Technology Data Exchange (ETDEWEB)

Sun, Jongoh; Kim, Gyeongho; Yoo, Yeonsik; Cho, Yeonggarp; Kim, Jong In [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

The reactor assembly is submerged in a reactor pool filled with water and its reactivity is controlled by locations of four control absorber rods(CARs) inside the reactor assembly. Each CAR is driven by a stepping motor installed at the top of the reactor pool and they are connected to each other by a tie rod and an electromagnet. The CARs scram the reactor by de-energizing the electromagnet in the event of a safe shutdown earthquake(SSE). Therefore, the safety function of the control rod drive mechanism(CRDM) which consists of a drive assembly, tie rod and CARs is to drop the CAR into the core within an appropriate time in case of the SSE. As well known, the operability for complex equipment such as the CRDM during an earthquake is very hard to be demonstrated by analysis and should be verified through tests. One of them simulates the reactor assembly and the guide tube of the CAR, and the other one does the pool wall where the drive assembly is installed. In this paper, design of the latter test rig and how the test is performed are presented. Initial design of the seismic test rig and excitation table had its first natural frequency at 16.3Hz and could not represent the environment where the CRDM was installed. Therefore, experimental modal analyses were performed and an FE model for the test rig and table was obtained and tuned based on the experimental results. Using the FE model, the design of the test rig and table was modified in order to have higher natural frequency than the cutoff frequency. The goal was achieved by changing its center of gravity and the stiffness of its sliding bearings.

Scavenger receptor AI/II truncation, lung function and COPD

DEFF Research Database (Denmark)

Thomsen, M; Nordestgaard, B G; Tybjaerg-Hansen, A

2011-01-01

The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...

Ligand and Metal Based Multielectron Redox Chemistry of Cobalt Supported by Tetradentate Schiff Bases.

Science.gov (United States)

Andrez, Julie; Guidal, Valentin; Scopelliti, Rosario; Pécaut, Jacques; Gambarelli, Serge; Mazzanti, Marinella

2017-06-28

We have investigated the influence of bound cations on the reduction of cobalt complexes of redox active ligands and explored the reactivity of reduced species with CO 2 . The one electron reduction of [Co II ( R salophen)] with alkali metals (M = Li, Na, K) leads to either ligand-centered or metal-centered reduction depending on the alkali ion. It affords either the [Co I ( R salophen)K] complexes or the [Co II 2 (bis-salophen)M 2 ] (M = Li, Na) dimers that are present in solution in equilibrium with the respective [Co I (salophen)M] complexes. The two electron reduction of [Co II ( OMe salophen)] results in both ligand centered and metal centered reduction affording the Co(I)-Co(II)-Co(I) [Co 3 (tris- OMe salophen)Na 6 (THF) 6 ], 6 complex supported by a bridging deca-anionic tris- OMe salophen 10- ligand where three OMe salophen units are connected by two C-C bonds. Removal of the Na ion from 6 leads to a redistribution of the electrons affording the complex [(Co( OMe salophen)) 2 Na][Na(cryptand)] 3 , 7. The EPR spectrum of 7 suggests the presence of a Co(I) bound to a radical anionic ligand. Dissolution of 7 in pyridine leads to the isolation of [Co I 2 (bis- OMe salophen)Na 2 Py 4 ][Na(cryptand)] 2 , 8. Complex 6 reacts with ambient CO 2 leading to multiple CO 2 reduction products. The product of CO 2 addition to the OMe salophen ligand, [Co( OMe salophen-CO 2 )Na] 2 [Na(cryptand)] 2 , 9, was isolated but CO 3 2- formation in 53% yield was also detected. Thus, the electrons stored in the reversible C-C bonds may be used for the transformation of carbon dioxide.

A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

Science.gov (United States)

Poznański, Jarosław; Poznańska, Anna; Shugar, David

2014-01-01

Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

Analysis and modification of a single-mesh gear fatigue rig for use in diagnostic studies

Science.gov (United States)

Zakrajsek, James J.; Townsend, Dennis P.; Oswald, Fred B.; Decker, Harry J.

1992-01-01

A single-mesh gear fatigue rig was analyzed and modified for use in gear mesh diagnostic research. The fatigue rig allowed unwanted vibration to mask the test-gear vibration signal, making it difficult to perform diagnostic studies. Several possible sources and factors contributing to the unwanted components of the vibration signal were investigated. Sensor mounting location was found to have a major effect on the content of the vibration signal. In the presence of unwanted vibration sources, modal amplification made unwanted components strong. A sensor location was found that provided a flatter frequency response. This resulted in a more useful vibration signal. A major network was performed on the fatigue rig to reduce the influence of the most probable sources of the noise in the vibration signal. The slave gears were machined to reduce weight and increase tooth loading. The housing and the shafts were modified to reduce imbalance, looseness, and misalignment in the rotating components. These changes resulted in an improved vibration signal, with the test-gear mesh frequency now the dominant component in the signal. Also, with the unwanted sources eliminated, the sensor mounting location giving the most robust representation of the test-gear meshing energy was found to be at a point close to the test gears in the load zone of the bearings.

Looking for myself: current multisensory input alters self-face recognition.

Science.gov (United States)

Tsakiris, Manos

2008-01-01

How do I know the person I see in the mirror is really me? Is it because I know the person simply looks like me, or is it because the mirror reflection moves when I move, and I see it being touched when I feel touch myself? Studies of face-recognition suggest that visual recognition of stored visual features inform self-face recognition. In contrast, body-recognition studies conclude that multisensory integration is the main cue to selfhood. The present study investigates for the first time the specific contribution of current multisensory input for self-face recognition. Participants were stroked on their face while they were looking at a morphed face being touched in synchrony or asynchrony. Before and after the visuo-tactile stimulation participants performed a self-recognition task. The results show that multisensory signals have a significant effect on self-face recognition. Synchronous tactile stimulation while watching another person's face being similarly touched produced a bias in recognizing one's own face, in the direction of the other person included in the representation of one's own face. Multisensory integration can update cognitive representations of one's body, such as the sense of ownership. The present study extends this converging evidence by showing that the correlation of synchronous multisensory signals also updates the representation of one's face. The face is a key feature of our identity, but at the same time is a source of rich multisensory experiences used to maintain or update self-representations.

Computational Analysis of a South African Mobile Trailer-Type Medium Sized Tyre Test Rig

CSIR Research Space (South Africa)

Sharma, Shikar

2015-04-01

Full Text Available To support the South African National Defence Force with their vehicle mobility needs, the CSIR has begun characterising tyres by using a medium, trailer-type, tyre test rig. Two different Pacejka tyre models were generated using two independent...

77 FR 23117 - Rigging Equipment for Material Handling Construction Standard; Correction and Technical Amendment

Science.gov (United States)

2012-04-18

... Equipment for Material Handling Construction Standard; Correction and Technical Amendment AGENCY... AND HEALTH REGULATIONS FOR CONSTRUCTION Subpart H--Materials Handling, Storage, Use, and Disposal 0 1... amendment. SUMMARY: OSHA is correcting its sling standard for construction titled ``Rigging Equipment for...

Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

Science.gov (United States)

Sankararamakrishnan, Ramasubbu

2006-04-01

One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

Trappin-2/elafin modulate innate immune responses of human endometrial epithelial cells to PolyI:C.

Directory of Open Access Journals (Sweden)

Anna G Drannik

Full Text Available BACKGROUND: Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs. Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr and its cleaved form, elafin (E, are alarm antimicrobials secreted by multiple cells, including genital epithelia. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated whether and how each Tr and E (Tr/E contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways. CONCLUSIONS AND SIGNIFICANCE: This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract.

Monoclonal antibody-assisted structure-function analysis of the carbohydrate recognition domain of surfactant protein D

DEFF Research Database (Denmark)

Hartshorn, Kevan L; White, Mitchell R; Rynkiewicz, Michael

2010-01-01

Surfactant protein D (SP-D) plays important roles in host defense against a variety of pathogens including influenza A virus (IAV). Ligand binding by SP-D is mediated by the trimeric neck and carbohydrate recognition domain (NCRD). We used monoclonal antibodies (mAbs) against human SP-D and a panel...

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

Science.gov (United States)

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

Deviation from the <i>trans> -Effect in Ligand-Exchange Reactions of Zeise’s Ions PtCl₃(C₂H₄)^- with Heavier Halides (Br^–, I^- )

Energy Technology Data Exchange (ETDEWEB)

Hou, Gao-Lei [Physical; Govind, Niranjan [Environmental; Xantheas, Sotiris S. [Advanced; Department; Wang, Xue-Bin [Physical

2018-01-16

Four new Zeise’s family ions with mixed-halide ligands, i.e., PtCl_nX_3-n(C₂H₄)^- (X = Br, I; n = 1, 2), were synthesized via ligand-exchange reactions of KX salts with KPtCl₃(C₂H₄) in aqueous solutions, and were detected in vacuum via electrospray ionization mass spectrometry. Their photoelectron spectra reveal a series of well-resolved spectral peaks with their electron binding energies (EBEs) decreasing with increasing halide size, with I having a much stronger effect than Br, i.e., 4.57 (–Cl₃) > 4.56 (–Cl₂Br) > 4.53 (–ClBr₂) > 4.34 (–Cl₂I) > 4.30 eV (–ClI₂). Ab initio electronic structure calculations including spin-orbit coupling (SOC) predict that the cis- and trans-isomers are nearly isoenergetic with the cis-isomer for –Cl₂X, and the trans-isomer for –ClX₂ slightly favored, respectively. Excited-state spectra calculated with time-dependent density functional theory (TDDFT), and their comparison with the observed ones, suggest that for each species, both the cis- and trans-configurations coexist in the experiments and contribute to the observed spectra, a fact that clearly violates the prediction of the widely accepted trans-effect, which suggests that only one isomer would have formed.

Phenanthroline-2,9-bistriazoles as selective G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, Mads Corvinius; Larsen, Anders Foller; Abdikadir, Faisal Hussein

2014-01-01

G-quadruplex (G4) ligands are currently receiving considerable attention as potential anticancer therapeutics. A series of phenanthroline-2,9-bistriazoles carrying tethered positive end groups has been synthesized and evaluated as G4 stabilizers. The compounds were efficiently assembled by copper......(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in CH2Cl2 and water in the presence of a complexing agent. Characterization of the target compounds on telomeric and c-KIT G4 sequences led to the identification of guanidinium-substituted compounds as potent G4 DNA ligands with high selectivity over duplex DNA....... The diisopropylguanidium ligands exhibited high selectivity for the proto-oncogenic sequence c-KIT over the human telomeric sequence in the surface plasmon resonance (SPR) assay, whereas the compounds appeared potent on both G4 structures in the FRET melting temperature assay. The phenanthroline-2,9-bistriazole ligands...