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Sample records for extracytoplasmic solute receptor

  1. Crystallization and preliminary X-ray diffraction analysis of two extracytoplasmic solute receptors of the DctP family from Bordetella pertussis

    International Nuclear Information System (INIS)

    Rucktooa, Prakash; Huvent, Isabelle; Antoine, Rudy; Lecher, Sophie; Jacob-Dubuisson, Françoise; Villeret, Vincent; Bompard, Coralie

    2006-01-01

    Sample preparation, crystallization and preliminary X-ray analysis are reported for two B. pertussis extracytoplasmic solute receptors. DctP6 and DctP7 are two Bordetella pertussis proteins which belong to the extracytoplasmic solute receptors (ESR) superfamily. ESRs are involved in the transport of substrates from the periplasm to the cytosol of Gram-negative bacteria. DctP6 and DctP7 have been crystallized and diffraction data were collected using a synchrotron-radiation source. DctP6 crystallized in space group P4 1 2 1 2, with unit-cell parameters a = 108.39, b = 108.39, c = 63.09 Å, while selenomethionyl-derivatized DctP7 crystallized in space group P2 1 2 1 2 1 , with unit-cell parameters a = 64.87, b = 149.83, c = 170.65 Å. The three-dimensional structure of DctP7 will be determined by single-wavelength anomalous diffraction, while the DctP6 structure will be solved by molecular-replacement methods

  2. Crystallization and preliminary X-ray diffraction analysis of two extracytoplasmic solute receptors of the DctP family from Bordetella pertussis

    Energy Technology Data Exchange (ETDEWEB)

    Rucktooa, Prakash; Huvent, Isabelle [UMR8161 CNRS Institut de Biologie de Lille, Laboratoire de Cristallographie Macromoléculaire, 1 Rue du Professeur Calmette, BP 447, 59021 Lille CEDEX (France); IFR 142, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59021 Lille CEDEX (France); Antoine, Rudy; Lecher, Sophie; Jacob-Dubuisson, Françoise, E-mail: francoise.jacob@ibl.fr [IFR 142, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59021 Lille CEDEX (France); INSERM-U629, Lille (France); Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59021 Lille CEDEX (France); Villeret, Vincent, E-mail: francoise.jacob@ibl.fr; Bompard, Coralie [UMR8161 CNRS Institut de Biologie de Lille, Laboratoire de Cristallographie Macromoléculaire, 1 Rue du Professeur Calmette, BP 447, 59021 Lille CEDEX (France); IFR 142, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59021 Lille CEDEX (France)

    2006-10-01

    Sample preparation, crystallization and preliminary X-ray analysis are reported for two B. pertussis extracytoplasmic solute receptors. DctP6 and DctP7 are two Bordetella pertussis proteins which belong to the extracytoplasmic solute receptors (ESR) superfamily. ESRs are involved in the transport of substrates from the periplasm to the cytosol of Gram-negative bacteria. DctP6 and DctP7 have been crystallized and diffraction data were collected using a synchrotron-radiation source. DctP6 crystallized in space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = 108.39, b = 108.39, c = 63.09 Å, while selenomethionyl-derivatized DctP7 crystallized in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 64.87, b = 149.83, c = 170.65 Å. The three-dimensional structure of DctP7 will be determined by single-wavelength anomalous diffraction, while the DctP6 structure will be solved by molecular-replacement methods.

  3. Characterization of the N-Acetyl-5-neuraminic Acid-binding Site of the Extracytoplasmic Solute Receptor (SiaP) of Nontypeable Haemophilus influenzae Strain 2019

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Jason W.; Coussens, Nathan P.; Allen, Simon; Houtman, Jon C.D.; Turner, Keith H.; Zaleski, Anthony; Ramaswamy, S.; Gibson, Bradford W.; Apicella, Michael A. (Iowa); (Buck Inst.)

    2012-11-14

    Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4 {angstrom} resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

  4. Structure-Function Analysis of Cf-9, a Receptor-Like Protein with Extracytoplasmic Leucine-Rich Repeats

    NARCIS (Netherlands)

    Hoorn, van der R.A.L.; Wulff, B.B.H.; Rivas, S.; Durrant, M.C.; Ploeg, van der A.; Wit, de P.J.G.M.; Jones, J.D.G.

    2005-01-01

    The tomato (Lycopersicon pimpinellifolium) resistance protein Cf-9 belongs to a large class of plant proteins with extracytoplasmic Leu-rich repeats (eLRRs). eLRR proteins play key roles in plant defense and development, mainly as receptor-like proteins or receptor-like kinases, conferring

  5. Extracytoplasmic function sigma factors in Pseudomonas syringae

    DEFF Research Database (Denmark)

    Kiil, Kristoffer; Oguiza, J.A.; Ussery, D.W.

    2005-01-01

    Genome analyses of the plant pathogens Pseudomonas syringae pv. tomato DC3000, pv. syringae B728a and pv. phaseolicola 1448A reveal fewer extracytoplasmic function (ECF) sigma factors than in related Pseudomonads with different lifestyles. We highlight the presence of a P. syringae-specific ECF...

  6. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope.

    Science.gov (United States)

    Helmann, John D

    2016-04-01

    Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σ(W) is most closely associated with membrane-active agents, σ(X) with cationic antimicrobial peptide resistance, and σ(V) with resistance to lysozyme. Here, I highlight the role of the σ(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Two-Component Signaling System VgrRS Directly Senses Extracytoplasmic and Intracellular Iron to Control Bacterial Adaptation under Iron Depleted Stress.

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-12-01

    Full Text Available Both iron starvation and excess are detrimental to cellular life, especially for animal and plant pathogens since they always live in iron-limited environments produced by host immune responses. However, how organisms sense and respond to iron is incompletely understood. Herein, we reveal that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, VgrS (also named ColS is a membrane-bound receptor histidine kinase that senses extracytoplasmic iron limitation in the periplasm, while its cognate response regulator, VgrR (ColR, detects intracellular iron excess. Under iron-depleted conditions, dissociation of Fe3+ from the periplasmic sensor region of VgrS activates the VgrS autophosphorylation and subsequent phosphotransfer to VgrR, an OmpR-family transcription factor that regulates bacterial responses to take up iron. VgrR-VgrS regulon and the consensus DNA binding motif of the transcription factor VgrR were dissected by comparative proteomic and ChIP-seq analyses, which revealed that in reacting to iron-depleted environments, VgrR directly or indirectly controls the expressions of hundreds of genes that are involved in various physiological cascades, especially those associated with iron-uptake. Among them, we demonstrated that the phosphorylated VgrR tightly represses the transcription of a special TonB-dependent receptor gene, tdvA. This regulation is a critical prerequisite for efficient iron uptake and bacterial virulence since activation of tdvA transcription is detrimental to these processes. When the intracellular iron accumulates, the VgrR-Fe2+ interaction dissociates not only the binding between VgrR and the tdvA promoter, but also the interaction between VgrR and VgrS. This relieves the repression in tdvA transcription to impede continuous iron uptake and avoids possible toxic effects of excessive iron accumulation. Our results revealed a signaling system that directly senses both extracytoplasmic and intracellular

  8. Solution to the inversely stated transient source-receptor problem

    International Nuclear Information System (INIS)

    Sajo, E.; Sheff, J.R.

    1995-01-01

    Transient source-receptor problems are traditionally handled via the Boltzmann equation or through one of its variants. In the atmospheric transport of pollutants, meteorological uncertainties in the planetary boundary layer render only a few approximations to the Boltzmann equation useful. Often, due to the high number of unknowns, the atmospheric source-receptor problem is ill-posed. Moreover, models to estimate downwind concentration invariably assume that the source term is known. In this paper, an inverse methodology is developed, based on downwind measurement of concentration and that of meterological parameters to estimate the source term

  9. Supramolecular Ferric Porphyrins as Cyanide Receptors in Aqueous Solution

    Science.gov (United States)

    2011-01-01

    All fundamental data about binding of the cyanide to a supramolecular complex composed of a per-O-methylated β-cyclodextrin dimer having an imidazole linker (Im3CD) and an anionic ferric porphyrin (Fe(III)TPPS) indicate that the Fe(III)TPPS/Im3CD complex is much better as an cyanide receptor in vivo than hydroxocobalamin, whose cyanide binding ability is lowered by its strong binding to serum proteins in the blood. PMID:24900285

  10. Effect of extracytoplasmic function sigma factors on autoaggregation, hemagglutination, and cell surface properties of Porphyromonas gingivalis

    Science.gov (United States)

    Kokubu, Eitoyo; Okamoto-Shibayama, Kazuko; Ishihara, Kazuyuki

    2017-01-01

    Porphyromonas gingivalis is a bacterium frequently isolated from chronic periodontal lesions and is involved in the development of chronic periodontitis. To colonize the gingival crevice, P. gingivalis has to adapt to environmental stresses. Microbial gene expression is regulated by transcription factors such as those in two-component systems and extracytoplasmic function (ECF) sigma factors. ECF sigma factors are involved in the regulation of environmental stress response genes; however, the roles of individual ECF sigma factors are largely unknown. The purpose of this study was to investigate the functions, including autoaggregation, hemagglutination, gingipain activity, susceptibility to antimicrobial agents, and surface structure formation, of P. gingivalis ECF sigma factors encoded by SigP (PGN_0274), SigCH (PGN_0319), PGN_0450, PGN_0970, and SigH (PGN_1740). Various physiological aspects of the sigP mutant were affected; autoaggregation was significantly decreased at 60 min (p < 0.001), hemagglutination activity was markedly reduced, and enzymatic activities of Kgp and Rgps were significantly decreased (p < 0.001). The other mutants also showed approximately 50% reduction in Rgps activity. Kgp activity was significantly reduced in the sigH mutant (p < 0.001). No significant differences in susceptibilities to tetracycline and ofloxacin were observed in the mutants compared to those of the wild-type strain. However, the sigP mutant displayed an increased susceptibility to ampicillin, whereas the PGN_0450 and sigH mutants showed reduced susceptibility. Transmission electron microscopy images revealed increased levels of outer membrane vesicles formed at the cell surfaces of the sigP mutant. These results indicate that SigP is important for bacterial surface-associated activities, including gingipain activity, autoaggregation, hemagglutination, vesicle formation, and antimicrobial susceptibility. PMID:28931045

  11. Stability of the neurotensin receptor NTS1 free in detergent solution and immobilized to affinity resin.

    Directory of Open Access Journals (Sweden)

    Jim F White

    2010-09-01

    Full Text Available Purification of recombinant membrane receptors is commonly achieved by use of an affinity tag followed by an additional chromatography step if required. This second step may exploit specific receptor properties such as ligand binding. However, the effects of multiple purification steps on protein yield and integrity are often poorly documented. We have previously reported a robust two-step purification procedure for the recombinant rat neurotensin receptor NTS1 to give milligram quantities of functional receptor protein. First, histidine-tagged receptors are enriched by immobilized metal affinity chromatography using Ni-NTA resin. Second, remaining contaminants in the Ni-NTA column eluate are removed by use of a subsequent neurotensin column yielding pure NTS1. Whilst the neurotensin column eluate contained functional receptor protein, we observed in the neurotensin column flow-through misfolded NTS1.To investigate the origin of the misfolded receptors, we estimated the amount of functional and misfolded NTS1 at each purification step by radio-ligand binding, densitometry of Coomassie stained SDS-gels, and protein content determination. First, we observed that correctly folded NTS1 suffers damage by exposure to detergent and various buffer compositions as seen by the loss of [(3H]neurotensin binding over time. Second, exposure to the neurotensin affinity resin generated additional misfolded receptor protein.Our data point towards two ways by which misfolded NTS1 may be generated: Damage by exposure to buffer components and by close contact of the receptor to the neurotensin affinity resin. Because NTS1 in detergent solution is stabilized by neurotensin, we speculate that the occurrence of aggregated receptor after contact with the neurotensin resin is the consequence of perturbations in the detergent belt surrounding the NTS1 transmembrane core. Both effects reduce the yield of functional receptor protein.

  12. Bacillus subtilis PrsA is required in vivo as an extracytoplasmic chaperone for secretion of active enzymes synthesized either with or without pro-sequences

    DEFF Research Database (Denmark)

    Jabobs, Myra F; Andersen, Jens Bo; Kontinen, Vesa P.

    1993-01-01

    In prsA (protein secretion) mutants of Bacillus subtilis, decreased levels of exoproteins, including alpha-amylase and subtilisins, are found extracellularly. The effect of prsA on subtilisin secretion is elaborated here. Extracytoplasmic folding and secretion of active subtilisin is assisted...

  13. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae [Yonsei University, Seoul (Korea, Republic of)

    2012-02-15

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ{sup PEP}) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ{sup PEP} formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ{sup PEP}. The solution structure of FTZ{sup PEP} in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix.

  14. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    International Nuclear Information System (INIS)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae

    2012-01-01

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ PEP ) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ PEP formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ PEP . The solution structure of FTZ PEP in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix

  15. Field flow fractionation for assessing neonatal Fc receptor and Fcγ receptor binding to monoclonal antibodies in solution.

    Science.gov (United States)

    Pollastrini, Joey; Dillon, Thomas M; Bondarenko, Pavel; Chou, Robert Y-T

    2011-07-01

    Analysis of the strength and stoichiometry of immunoglobulin G (IgG) binding to neonatal Fc receptor (FcRn) and Fcγ receptor (FcγR) is important for evaluating the pharmacokinetics and effector functions of therapeutic monoclonal antibody (mAb) products, respectively. The current standard for assessing FcγR and FcRn binding is composed of cell-based and surface plasmon resonance (SPR) assays. In this work, asymmetrical flow field flow fractionation (AF4) was evaluated to establish the true stoichiometry of IgG binding in solution. AF4 and liquid chromatography-mass spectrometry (LC-MS) were applied to directly observe IgG/FcγR and IgG/FcRn complexes, which were not observed using nonequilibrium size exclusion chromatography (SEC) analysis. Human serum albumin (HSA), an abundant component of human blood and capable of binding FcRn, was studied in combination with FcRn and IgG. AF4 demonstrated that the majority of large complexes of IgG/FcRn/HSA were at an approximate 1:2:1 molar ratio. In addition, affinity measurements of the complex were performed in the sub-micromolar affinity range. A significant decrease in binding was detected for IgG molecules with increased oxidation in the Fc region. AF4 was useful in detecting weak binding between full-length IgG/Fc fragments and Fc receptors and the effect of chemical modifications on binding. AF4 is a useful technique in the assessment of mAb product quality attributes. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. The Extra-Cytoplasmic Function Sigma Factor SigX Modulates Biofilm and Virulence-Related Properties in Pseudomonas aeruginosa

    Science.gov (United States)

    Gicquel, Gwendoline; Bouffartigues, Emeline; Bains, Manjeet; Oxaran, Virginie; Rosay, Thibaut; Lesouhaitier, Olivier; Connil, Nathalie; Bazire, Alexis; Maillot, Olivier; Bénard, Magalie; Cornelis, Pierre; Hancock, Robert E. W.; Dufour, Alain; Feuilloley, Marc G. J.; Orange, Nicole; Déziel, Eric; Chevalier, Sylvie

    2013-01-01

    SigX, one of the 19 extra-cytoplasmic function sigma factors of P. aeruginosa, was only known to be involved in transcription of the gene encoding the major outer membrane protein OprF. We conducted a comparative transcriptomic study between the wildtype H103 strain and its sigX mutant PAOSX, which revealed a total of 307 differentially expressed genes that differed by more than 2 fold. Most dysregulated genes belonged to six functional classes, including the “chaperones and heat shock proteins”, “antibiotic resistance and susceptibility”, “energy metabolism”, “protein secretion/export apparatus”, and “secreted factors”, and “motility and attachment” classes. In this latter class, the large majority of the affected genes were down-regulated in the sigX mutant. In agreement with the array data, the sigX mutant was shown to demonstrate substantially reduced motility, attachment to biotic and abiotic surfaces, and biofilm formation. In addition, virulence towards the nematode Caenorhabditis elegans was reduced in the sigX mutant, suggesting that SigX is involved in virulence-related phenotypes. PMID:24260387

  17. The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization.

    Science.gov (United States)

    Mir, Mushtaq; Asong, Jinkeng; Li, Xiuru; Cardot, Jessica; Boons, Geert-Jan; Husson, Robert N

    2011-07-01

    The Mycobacterium tuberculosis Ser/Thr kinase PknB has been implicated in the regulation of cell growth and morphology in this organism. The extracytoplasmic domain of this membrane protein comprises four penicillin binding protein and Ser/Thr kinase associated (PASTA) domains, which are predicted to bind stem peptides of peptidoglycan. Using a comprehensive library of synthetic muropeptides, we demonstrate that the extracytoplasmic domain of PknB binds muropeptides in a manner dependent on the presence of specific amino acids at the second and third positions of the stem peptide, and on the presence of the sugar moiety N-acetylmuramic acid linked to the peptide. We further show that PknB localizes strongly to the mid-cell and also to the cell poles, and that the extracytoplasmic domain is required for PknB localization. In contrast to strong growth stimulation by conditioned medium, we observe no growth stimulation of M. tuberculosis by a synthetic muropeptide with high affinity for the PknB PASTAs. We do find a moderate effect of a high affinity peptide on resuscitation of dormant cells. While the PASTA domains of PknB may play a role in stimulating growth by binding exogenous peptidoglycan fragments, our data indicate that a major function of these domains is for proper PknB localization, likely through binding of peptidoglycan fragments produced locally at the mid-cell and the cell poles. These data suggest a model in which PknB is targeted to the sites of peptidoglycan turnover to regulate cell growth and cell division.

  18. The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization.

    Directory of Open Access Journals (Sweden)

    Mushtaq Mir

    2011-07-01

    Full Text Available The Mycobacterium tuberculosis Ser/Thr kinase PknB has been implicated in the regulation of cell growth and morphology in this organism. The extracytoplasmic domain of this membrane protein comprises four penicillin binding protein and Ser/Thr kinase associated (PASTA domains, which are predicted to bind stem peptides of peptidoglycan. Using a comprehensive library of synthetic muropeptides, we demonstrate that the extracytoplasmic domain of PknB binds muropeptides in a manner dependent on the presence of specific amino acids at the second and third positions of the stem peptide, and on the presence of the sugar moiety N-acetylmuramic acid linked to the peptide. We further show that PknB localizes strongly to the mid-cell and also to the cell poles, and that the extracytoplasmic domain is required for PknB localization. In contrast to strong growth stimulation by conditioned medium, we observe no growth stimulation of M. tuberculosis by a synthetic muropeptide with high affinity for the PknB PASTAs. We do find a moderate effect of a high affinity peptide on resuscitation of dormant cells. While the PASTA domains of PknB may play a role in stimulating growth by binding exogenous peptidoglycan fragments, our data indicate that a major function of these domains is for proper PknB localization, likely through binding of peptidoglycan fragments produced locally at the mid-cell and the cell poles. These data suggest a model in which PknB is targeted to the sites of peptidoglycan turnover to regulate cell growth and cell division.

  19. Solution Phase Measurement of Both Weak Sigma and C-H---X- Hydrogen Bonding Interactions in Synthetic Anion Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Berryman, Mr. Orion B. [University of Oregon; Sather, Mr. Aaron C [University of Oregon; Hay, Benjamin [ORNL; Meisner, Mr. Jeffrey S. [University of Oregon; Johnson, Prof. Darren W. [University of Oregon

    2008-01-01

    A series of tripodal receptors preorganize electron-deficient aromatic rings to bind halides in organic solvents using weak sigma anion-to-arene interactions or C-H---X- hydrogen bonds. 1H NMR spectroscopy proves to be a powerful technique for quantifying binding in solution, and determining the interaction motifs, even in cases of weak binding.

  20. Sodium Solute Symporter and Cadherin Proteins Act as Bacillus thuringiensis Cry3Ba Toxin Functional Receptors in Tribolium castaneum*

    Science.gov (United States)

    Contreras, Estefanía; Schoppmeier, Michael; Real, M. Dolores; Rausell, Carolina

    2013-01-01

    Understanding how Bacillus thuringiensis (Bt) toxins interact with proteins in the midgut of susceptible coleopteran insects is crucial to fully explain the molecular bases of Bt specificity and insecticidal action. In this work, aminopeptidase N (TcAPN-I), E-cadherin (TcCad1), and sodium solute symporter (TcSSS) have been identified by ligand blot as putative Cry3Ba toxin-binding proteins in Tribolium castaneum (Tc) larvae. RNA interference knockdown of TcCad1 or TcSSS proteins resulted in decreased susceptibility to Cry3Ba toxin, demonstrating the Cry toxin receptor functionality for these proteins. In contrast, TcAPN-I silencing had no effect on Cry3Ba larval toxicity, suggesting that this protein is not relevant in the Cry3Ba toxin mode of action in Tc. Remarkable features of TcSSS protein were the presence of cadherin repeats in its amino acid sequence and that a TcSSS peptide fragment containing a sequence homologous to a binding epitope found in Manduca sexta and Tenebrio molitor Bt cadherin functional receptors enhanced Cry3Ba toxicity. This is the first time that the involvement of a sodium solute symporter protein as a Bt functional receptor has been demonstrated. The role of this novel receptor in Bt toxicity against coleopteran insects together with the lack of receptor functionality of aminopeptidase N proteins might account for some of the differences in toxin specificity between Lepidoptera and Coleoptera insect orders. PMID:23645668

  1. Docking of flexible ligands to flexible receptors in solution by molecular dynamics simulation

    NARCIS (Netherlands)

    Mangoni, R; Roccatano, D; Di Nola, A

    1999-01-01

    In this paper, a method of simulating the docking of small flexible ligands to flexible receptors in water is reported. The method is based on molecular dynamics simulations and is an extension of an algorithm previously reported by Di Nola et al, (Di Nola et al,, Proteins 1994;19:174-182), The

  2. The extracytoplasmic function sigma factor SigY is important for efficient maintenance of the Spβ prophage that encodes sublancin in Bacillus subtilis.

    Science.gov (United States)

    Mendez, Rebecca; Gutierrez, Alba; Reyes, Jasmin; Márquez-Magaña, Leticia

    2012-06-01

    Many strains of the soil bacterium Bacillus subtilis are capable of producing and being resistant to the antibiotic sublancin because they harbor the Spβ prophage. This 135 kb viral genome is integrated into the circular DNA chromosome of B. subtilis, and contains genes for the production of and resistance to sublancin. We investigated the role of SigY in sublancin production and resistance, finding that it is important for efficient maintenance of the Spβ prophage. We were unable to detect the prophage in mutants lacking SigY. Additionally, these mutants were no longer able to produce sublancin, were sensitive to killing by this factor, and displayed a delay in sporulation. Wild-type cells with normal SigY activity were found to partially lose the Spβ prophage during growth and early sporulation, suggesting a mechanism for the bistable outcome of sibling cells capable of killing and of being killed. The appropriate regulation of SigY appears to be essential for growth as evidenced by the inability to disrupt the gene for its putative antisigma. Our results confirm a role for SigY in antibiotic production and resistance, as has been found for other members of the extracytoplasmic function sigma factor family in B. subtilis, and shows that this role is achieved by affecting maintenance of the Spβ prophage.

  3. The extracytoplasmic function sigma factor SigV plays a key role in the original model of lysozyme resistance and virulence of Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    André Le Jeune

    Full Text Available BACKGROUND: Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant. RESULTS: This study revealed that oatA (O-acetyl transferase and dlt (D-Alanylation of lipoteicoic acids genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections. CONCLUSIONS: This work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis.

  4. An extracytoplasmic function sigma factor cotranscribed with its cognate anti-sigma factor confers tolerance to NaCl, ethanol and methylene blue in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Mishra, Mukti Nath; Kumar, Santosh; Gupta, Namrata; Kaur, Simarjot; Gupta, Ankush; Tripathi, Anil K

    2011-04-01

    Azospirillum brasilense, a plant-growth-promoting rhizobacterium, is exposed to changes in its abiotic environment, including fluctuations in temperature, salinity, osmolarity, oxygen concentration and nutrient concentration, in the rhizosphere and in the soil. Since extra-cytoplasmic function (ECF) sigma factors play an important role in stress adaptation, we analysed the role of ECF sigma factor (also known as RpoE or σ(E)) in abiotic stress tolerance in A. brasilense. An in-frame rpoE deletion mutant of A. brasilense Sp7 was carotenoidless and slow-growing, and was sensitive to salt, ethanol and methylene blue stress. Expression of rpoE in the rpoE deletion mutant complemented the defects in growth, carotenoid biosynthesis and sensitivity to different stresses. Based on data from reverse transcriptase-PCR, a two-hybrid assay and a pull-down assay, we present evidence that rpoE is cotranscribed with chrR and the proteins synthesized from these two overlapping genes interact with each other. Identification of the transcription start site by 5' rapid amplification of cDNA ends showed that the rpoE-chrR operon was transcribed by two promoters. The proximal promoter was less active than the distal promoter, whose consensus sequence was characteristic of RpoE-dependent promoters found in alphaproteobacteria. Whereas the proximal promoter was RpoE-independent and constitutively expressed, the distal promoter was RpoE-dependent and strongly induced in response to stationary phase and elevated levels of ethanol, salt, heat and methylene blue. This study shows the involvement of RpoE in controlling carotenoid synthesis as well as in tolerance to some abiotic stresses in A. brasilense, which might be critical in the adaptation, survival and proliferation of this rhizobacterium in the soil and rhizosphere under stressful conditions.

  5. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  6. Solution and gas phase evidence of anion binding through the secondary bonding interactions of a bidentate bis-antimony(iii) anion receptor.

    Science.gov (United States)

    Qiu, J; Song, B; Li, X; Cozzolino, A F

    2017-12-20

    The solution and gas phase halide binding to a bis-antimony(iii) anion receptor was studied. This new class of anion receptors utilizes the strong Sb-centered secondary bonding interactions (SBIs) that are formed opposite to the polar Sb-O primary bond. 1 H NMR titration data were fitted statistically to binding models and solution-phase binding energetics were extracted, while the formation of anion-to-receptor complexes was observed using ESI-MS. Density functional theory calculations suggest that their affinity towards binding halide anions is mitigated by the strong explicit solvation effect in DMSO, which gives insights into future designs that circumvent direct solvent binding and are anticipated to yield tighter and perhaps more selectivity in anion binding.

  7. Solution and solid-state studies on the halide binding affinity of perfluorophenyl-armed uranyl-salophen receptors enhanced by anion-π interactions

    Energy Technology Data Exchange (ETDEWEB)

    Leoni, Luca; Mele, Andrea; Giannicchi, Ilaria; Mihan, Francesco Yafteh; Dalla Cort, Antonella [Dipartimento di Chimica and IMC-CNR, Universita di Roma La Sapienza (Italy); Puttreddy, Rakesh; Jurcek, Ondrej; Rissanen, Kari [University of Jyvaeskylae, Department of Chemistry, Nanoscience Center (Finland)

    2016-12-23

    The enhancement of the binding between halide anions and a Lewis acidic uranyl-salophen receptor has been achieved by the introduction of pendant electron-deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion-π interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding. (copyright 2016 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Analysis by low-angle neutron scattering of the structure of the acetylcholine receptor from Torpedo californica in detergent solution

    International Nuclear Information System (INIS)

    Wise, D.S.; Karlin, A.; Schoenborn, B.P.

    1979-01-01

    The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. In this paper the results of the use of low-angle neutron scattering to investigate the shape of the receptor-detergent complex and separately of its protein and detergent moieties are reported. By adjustment of the neutron-scattering density of the solvent with D 2 O to match that of one or the other of the moieties, its contribution to the scattering can be nearly, if not completely, eliminated. Neutron scattering from Triton X-100 micelles established that this detergent is contrast matched in 18% D 2 O. Scattering measurements on the receptor-detergent complex in this solvent yielded a radius of gyration of the acetylcholine receptor monomer of 46 +- 1 A. The radius of gyration and molecular volume (305,000 A 3 ) of the receptor is inconsistent with a compact spherical shape. These parameters are consistent with, for example, a prolate cylinder of dimensions (length x diameter) 150 x 50 A or an oblate cylinder, 25 x 130 A. More complex shapes are possible and in fact seem to be required to reconcile the present results with previous electron microscopic and x-ray analyses of receptor in membrane and with considerations of the function of the receptor in controlling ion permeability. The neutron-scattering data yield, in addition, an independent determination of the molecular weight of the receptor protein (240,000 +- 40,000), the extent of Triton X-100 binding in the complex (0.4 g/g protein), and from the extended scattering curve, an approximation to the shape of the receptor-Triton X-100 complex, namely an oblate ellipsoid of axial ratio 1:4

  9. Lateral/Basolateral Amygdala Serotonin Type-2 Receptors Modulate Operant Self-administration of a Sweetened Ethanol Solution via Inhibition of Principal Neuron Activity

    Directory of Open Access Journals (Sweden)

    Brian eMccool

    2014-01-01

    Full Text Available The lateral/basolateral amygdala (BLA forms an integral part of the neural circuitry controlling innate anxiety and learned fear. More recently, BLA dependent modulation of self-administration behaviors suggests a much broader role in the regulation of reward evaluation. To test this, we employed a self-administration paradigm that procedurally segregates ‘seeking’ (exemplified as lever-press behaviors from consumption (drinking directed at a sweetened ethanol solution. Microinjection of the nonselective serotonin type-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (-m5HT into the BLA reduced lever pressing behaviors in a dose-dependent fashion. This was associated with a significant reduction in the number of response-bouts expressed during non-reinforced sessions without altering the size of a bout or the rate of responding. Conversely, intra-BLA -m5HT only modestly effected consumption-related behaviors; the highest dose reduced the total time spent consuming a sweetened ethanol solution but did not inhibit the total number of licks, number of lick bouts, or amount of solution consumed during a session. In vitro neurophysiological characterization of BLA synaptic responses showed that -m5HT significantly reduced extracellular field potentials. This was blocked by the 5-HT2A/C antagonist ketanserin suggesting that 5-HT2-like receptors mediate the behavioral effect of -m5HT. During whole-cell patch current-clamp recordings, we subsequently found that -m5HT increased action potential threshold and hyperpolarized the resting membrane potential of BLA pyramidal neurons. Together, our findings show that the activation of BLA 5-HT2A/C receptors inhibits behaviors related to reward-seeking by suppressing BLA principal neuron activity. These data are consistent with the hypothesis that the BLA modulates reward-related behaviors and provides specific insight into BLA contributions during operant self-administration of a

  10. PKC/CREB pathway mediates the expressions of GABAA receptor subunits in cultured hippocampal neurons after low-Mg2+ solution treatment.

    Science.gov (United States)

    Wu, Guofeng; Yu, Jinpeng; Wang, Likun; Ren, Siying; Zhang, Yixia

    2018-02-01

    To investigate the potential effects of the PKC/CREB pathway on the expressions of GABA A receptor subunits α1, γ2, and δ in cultured hippocampal neurons using a model of epilepsy that employed conditions of low magnesium (Mg 2+ ). A total of 108 embryonic rats at the age of 18 embryonic days (E18)prepared from adult female SD rats were used as experimental subjects. Primary rat hippocampal cultures were prepared from the embryonic 18 days rats. The cultured hippocampal neurons were then treated with artificial cerebrospinal fluid containing low Mg 2+ solutions to generate a low Mg 2+ model of epilepsy. The low Mg 2+ stimulation lasted for 3 h and then returned to in maintenance medium for 20 h. The changes of the GABA A receptor subunit α1, γ2, δ were observed by blocking or activating the function of the CREB. The quantification of the GABA A receptor subunit α1, γ2, δ and the CREB were determined by a qRT-PCR and a Western blot method. After the neurons were exposed to a low-Mg 2+ solution for 3 h, GABA A receptor mRNA expression markedly increased compared to the control, and then gradually decreased. In contrast, CREB mRNA levels exhibited a dramatic down-regulation 3 h after terminating low-Mg 2+ treatment, and then peaked at 9 h. Western blot analyses verified that staurosporine suppressed CREB phosphorylation (p-CREB). The mRNA expression of GABA A receptor subunit α1 increased only in the presence of staurosporine, whereas the expressions of subunits γ2 and δ significantly increased in the presence of either KG-501 or staurosporine. Furthermore, phorbol 12-myristate 13-acetate (PMA) decreased the expressions of GABA A subunits α1, γ2, and δ when administered alone. However, the administration of either KG-501 or staurosporine reversed the inhibitory effects of PMA. The PKC/CREB pathway may negatively regulate the expressions of GABA A receptor subunits α1, γ2, and δ in cultured hippocampal neurons in low Mg 2+ model of

  11. The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

    International Nuclear Information System (INIS)

    Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

    1998-01-01

    A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

  12. An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.

    Science.gov (United States)

    Uchiyama, Masaaki; Shimizu, Akira; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

    2013-01-01

    We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.

  13. An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model

    Science.gov (United States)

    Uchiyama, Masaaki; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

    2013-01-01

    Purpose We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. Methods After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. Results After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. Conclusions The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing. PMID:24194635

  14. Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions.

    Science.gov (United States)

    Galistu, Adriana; D'Aquila, Paolo S

    2012-01-18

    The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose, in particular the failure of the former to reduce bout size and the ability of the latter to induce a within-session decrement of bout number resembling either reward devaluation or neuroleptics on instrumental responding, we suggested that activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated on the basis of a dopamine D2-like receptor-mediated reward evaluation. Consistent results were obtained in a study examining the effect of dopamine D2-like receptor antagonism in rats licking for NaCl solutions and water. In this study, we examined the effects of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40 μg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15 M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60 s either after the first lick or after 3 min that the animals were placed in the chambers. Bout size, but not bout number, was decreased at the highest NaCl concentration. SCH 23390 produced a decrease of bout number and of lick number mainly due to the decreased number of subjects engaging in licking behaviour, and failed to reduce bout size for Na Cl and water at a dose which increased the latency to the 1st lick but did not affect the intra-bout lick rate. In agreement with previous observations, these results suggest that dopamine D1-like receptors play an important role in the activation of reward-oriented responses. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Design of a new peptidomimetic agonist for the melanocortin receptors based on the solution structure of the peptide ligand, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2).

    Science.gov (United States)

    Fotsch, Christopher; Smith, Duncan M; Adams, Jeffrey A; Cheetham, Janet; Croghan, Michael; Doherty, Elizabeth M; Hale, Clarence; Jarosinski, Mark A; Kelly, Michael G; Norman, Mark H; Tamayo, Nuria A; Xi, Ning; Baumgartner, James W

    2003-07-21

    The solution structure of a potent melanocortin receptor agonist, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2) (1) was calculated using distance restraints determined from 1H NMR spectroscopy. Eight of the lowest energy conformations from this study were used to identify non-peptide cores that mimic the spatial arrangement of the critical tripeptide region, DPhe-Arg-Trp, found in 1. From these studies, compound 2a, containing the cis-cyclohexyl core, was identified as a functional agonist of the melanocortin-4 receptor (MC4R) with an IC(50) and EC(50) below 10 nM. Compound 2a also showed 36- and 7-fold selectivity over MC3R and MC1R, respectively, in the binding assays. Subtle changes in cyclohexane stereochemistry and removal of functional groups led to analogues with lower affinity for the MC receptors.

  16. The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.

    Science.gov (United States)

    Thom, R E; Elmore, M J; Williams, A; Andrews, S C; Drobniewski, F; Marsh, P D; Tree, J A

    2012-05-02

    Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. The Ca2+ induced two-component system, CvsSR regulates the Type III secretion system and the extracytoplasmic function sigma-factor AlgU in Pseudomonas syringae pv. tomato DC3000.

    Science.gov (United States)

    Fishman, Maxwell R; Zhang, Johnson; Bronstein, Philip A; Stodghill, Paul; Filiatrault, Melanie J

    2017-12-20

    Two-component systems (TCSs) of bacteria regulate many different aspects of the bacterial life cycle including pathogenesis. Most TCSs remain uncharacterized with no information about the signal(s) or regulatory targets and/or role in bacterial pathogenesis. Here, we characterized a TCS in the plant-pathogenic bacterium Pseudomonas syringae pv. tomato DC3000 ( Pto ) composed of the histidine kinase, CvsS, and the response regulator, CvsR. CvsSR is necessary for virulence of Pto , since ΔcvsS and ΔcvsR strains produced fewer symptoms and demonstrated reduced growth on multiple hosts as compared to WT. We discovered that expression of cvsSR is induced by Ca 2+ concentrations found in leaf apoplastic fluid. Thus, Ca 2+ can be added to the list of signals that promote pathogenesis of Pto during host colonization. Through chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and global transcriptome analysis (RNA-seq) we discerned the CvsR regulon. CvsR directly activated expression of the type III secretion system regulators, hrpR and hrpS , that regulates Pto virulence in a type III secretion system dependent manner. CvsR also indirectly repressed transcription of the extracytoplasmic sigma factor algU and production of alginate. Phenotypic analysis determined that CvsSR inversely regulated biofilm formation, swarming motility, and cellulose production in a Ca 2+ -dependent manner. Overall, our results show that CvsSR is a key regulatory hub critical for interaction with host plants. Importance Pathogenic bacteria must be able to react and respond to the surrounding environment, make use of available resources, and avert or counter host immune responses. Often, these abilities rely on two-component systems (TCSs) composed of interacting proteins that modulate gene expression. We identified a TCS in the plant-pathogenic bacterium Pseudomonas syringae that responds to the presence of calcium, which is an important signal during the plant

  18. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  19. Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.

    OpenAIRE

    Smalla, M.; Schmieder, P.; Kelly, M.; Ter Laak, A.; Krause, G.; Ball, L.; Wahl, M.; Bork, P.; Oschkinat, H.

    1999-01-01

    The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize and to mediate specific protein-protein interactions. A highly conserved subclass of SAM domains is present at the intracellular C-terminus of more than 40 Eph receptor tyrosine kinases that are invo...

  20. Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

    Science.gov (United States)

    Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

    2018-03-28

    ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  2. Topological dispositions of lysine α380 and lysine γ486 in the acetylcholine receptor from Torpedo californica

    International Nuclear Information System (INIS)

    Dwyer, B.P.

    1991-01-01

    The locations have been determined, with respect to the plasma membrane, of lysine α380 and lysine γ486 in the α subunit and the γ subunit, respectively, of the nicotinic acetylcholine receptor from Torpedo californica. Immunoadsorbents were constructed that recognize the carboxy terminus of the peptide GVKYIAE released by proteolytic digestion from positions 378-384 in the amino acid sequence of the α subunit of the acetylcholine receptor and the carboxy terminus of the peptide KYVP released by proteolytic digestion from positions 486-489 in the amino acid sequence of the γ subunit. They were used to isolate these peptides from proteolytic digests of polypeptides from the acetylcholine receptor. Sealed vesicles containing the native acetylcholine receptor were labeled with pyridoxal phosphate and sodium [ 3 H]-borohydride. The effect of saponin on the incorporation of pyridoxamine phosphate into lysine α380 and lysine γ486 from the acetylcholine receptor in these vesicles was assessed with the immunoadsorbents. The conclusions that follow from these results are that lysine α380 is on the inside surface of a vesicle and lysine γ486 is on the outside surface. Because a majority (85%) of the total binding sites for α-bungarotoxin bind the toxin in the absence of saponin, the majority of the vesicles are right side out with the inside of the vesicle corresponding to the cytoplasmic surface and the outside of the vesicle corresponding to the extracytoplasmic, synaptic surface. Because lysine α380 and lysine γ486 lie on opposite sides of the membrane, a membrane-spanning segment must be located between the two positions occupied by these two amino acids in the common sequence of a polypeptide of the acetylcholine receptor

  3. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  4. A Bacterial Receptor PcrK Senses the Plant Hormone Cytokinin to Promote Adaptation to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Fang-Fang Wang

    2017-12-01

    Full Text Available Summary: Recognition of the host plant is a prerequisite for infection by pathogenic bacteria. However, how bacterial cells sense plant-derived stimuli, especially chemicals that function in regulating plant development, remains completely unknown. Here, we have identified a membrane-bound histidine kinase of the phytopathogenic bacterium Xanthomonas campestris, PcrK, as a bacterial receptor that specifically detects the plant cytokinin 2-isopentenyladenine (2iP. 2iP binds to the extracytoplasmic region of PcrK to decrease its autokinase activity. Through a four-step phosphorelay, 2iP stimulation decreased the phosphorylation level of PcrR, the cognate response regulator of PcrK, to activate the phosphodiesterase activity of PcrR in degrading the second messenger 3′,5′-cyclic diguanylic acid. 2iP perception by the PcrK-PcrR remarkably improves bacterial tolerance to oxidative stress by regulating the transcription of 56 genes, including the virulence-associated TonB-dependent receptor gene ctrA. Our results reveal an evolutionarily conserved, inter-kingdom signaling by which phytopathogenic bacteria intercept a plant hormone signal to promote adaptation to oxidative stress. : How pathogenic bacteria use receptors to recognize the signals of the host plant is unknown. Wang et al. have identified a bacterial receptor histidine kinase that specifically senses the plant hormone cytokinin. Through a four-step phosphorelay, cytokinin perception triggers degradation of a second messenger, c-di-GMP, to activate the bacterial response to oxidative stress. Keywords: histidine kinase, ligand, cytokinin, autokinase activity, phosphorelay, response regulator, two-component signal transduction system, Xanthomonas campestris pv. campestris, virulence, oxidative stress

  5. Plugging solution

    Energy Technology Data Exchange (ETDEWEB)

    Sharipov, A U; Yangirov, I Z

    1982-01-01

    A clay-powder, cement, and water-base plugging solution is proposed having reduced solution viscosity characteristics while maintaining tensile strength in cement stone. This solution utilizes silver graphite and its ingredients, by mass weight, are as follows: cement 51.2-54.3%; claypowder 6.06-9.1%; silver graphite 0.24-0.33%; with water making up the remainder.

  6. Solution preparation

    International Nuclear Information System (INIS)

    Seitz, M.G.

    1982-01-01

    Reviewed in this statement are methods of preparing solutions to be used in laboratory experiments to examine technical issues related to the safe disposal of nuclear waste from power generation. Each approach currently used to prepare solutions has advantages and any one approach may be preferred over the others in particular situations, depending upon the goals of the experimental program. These advantages are highlighted herein for three approaches to solution preparation that are currently used most in studies of nuclear waste disposal. Discussion of the disadvantages of each approach is presented to help a user select a preparation method for his particular studies. Also presented in this statement are general observations regarding solution preparation. These observations are used as examples of the types of concerns that need to be addressed regarding solution preparation. As shown by these examples, prior to experimentation or chemical analyses, laboratory techniques based on scientific knowledge of solutions can be applied to solutions, often resulting in great improvement in the usefulness of results

  7. Degradation of extracytoplasmic catalysts for protein folding in Bacillus subtilis

    NARCIS (Netherlands)

    Krishnappa, Laxmi; Monteferrante, Carmine G; Neef, Jolanda; Dreisbach, Annette; van Dijl, Jan Maarten

    The general protein secretion pathway of Bacillus subtilis has a high capacity for protein export from the cytoplasm, which is exploited in the biotechnological production of a wide range of enzymes. These exported proteins pass the membrane in an unfolded state, and accordingly, they have to fold

  8. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation

    DEFF Research Database (Denmark)

    Dagil, Robert; Knudsen, Maiken J.; Olsen, Johan Gotthardt

    2012-01-01

    The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane...

  9. Soil Solution

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    The characteristics of the soil solution in the root environment in the greenhouse industry differ much from those for field grown crops. This is caused firstly by the growing conditions in the greenhouse, which strongly differ from those in the field and secondly the function attributed to the soil

  10. Seeding Solutions

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Crucible Group operates on the basis of good faith –– producing best effort non-consensus texts. ..... science and technology-based solutions to agricultural production constraints, it is ...... In 1997 researchers at Case Western Reserve Medical School in Ohio (US) ...... Is there a need to update the system-wide IP audit?

  11. Circular Solutions

    NARCIS (Netherlands)

    Annevelink, E.; Bos, H.L.; Meesters, K.P.H.; Oever, van den M.J.A.; Haas, de W.; Kuikman, P.J.; Rietra, R.P.J.J.; Sikirica, N.

    2016-01-01

    The fifth part of this report on Circular Solutions is about the circular principle From Waste to Resource. The purpose of this study is to select promising options for the implementation of this circular principle and to elaborate these options further.

  12. Podcast solutions

    CERN Document Server

    Geoghegan, Michael W

    2005-01-01

    Podcasting is the art of recording radio show style audio tracks, then distributing them to listeners on the Web via podcasting software such as iPodder. From downloading podcasts to producing a track for fun or profit, ""Podcast Solutions"" covers the entire world of podcasting with insight, humor, and the unmatched wisdom of experience.

  13. Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

    DEFF Research Database (Denmark)

    Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

    2012-01-01

    Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

  14. Solution Prototype

    DEFF Research Database (Denmark)

    Efeoglu, Arkin; Møller, Charles; Serie, Michel

    2013-01-01

    This paper outlines an artifact building and evaluation proposal. Design Science Research (DSR) studies usually consider encapsulated artifact that have relationships with other artifacts. The solution prototype as a composed artifact demands for a more comprehensive consideration in its systematic...... environment. The solution prototype that is composed from blending product and service prototype has particular impacts on the dualism of DSR’s “Build” and “Evaluate”. Since the mix between product and service prototyping can be varied, there is a demand for a more agile and iterative framework. Van de Ven......’s research framework seems to fit this purpose. Van de Ven allows for an iterative research approach to problem solving with flexible starting point. The research activity is the result between the iteration of two dimensions. This framework focuses on the natural evaluation, particularly on ex...

  15. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  16. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  17. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  18. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  19. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

    Science.gov (United States)

    Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

    2009-02-01

    Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

  20. Role of adenosine receptors in caffeine tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, S.G.; Mante, S.; Minneman, K.P. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

  1. Role of adenosine receptors in caffeine tolerance

    International Nuclear Information System (INIS)

    Holtzman, S.G.; Mante, S.; Minneman, K.P.

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity

  2. Phospholipid environment alters hormone-sensitivity of the purified insulin receptor kinase.

    OpenAIRE

    Lewis, R E; Czech, M P

    1987-01-01

    Insulin receptor kinase, affinity-purified by adsorption and elution from immobilized insulin, is stimulated 2-3-fold by insulin in detergent solution. Reconstitution of the receptor kinase into leaky vesicles containing phosphatidylcholine and phosphatidylethanolamine (1:1, w/w) by detergent removal on Sephadex G-50 results in the complete loss of receptor kinase sensitivity to activation by insulin. Insulin receptors in these vesicles also exhibit an increase in their apparent affinity for ...

  3. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  4. A Dual Egalitarian Solution

    NARCIS (Netherlands)

    Klijn, F.; Slikker, M.; Tijs, S.H.

    2000-01-01

    In this note we introduce an egalitarian solution, called the dual egalitarian solution, that is the natural counterpart of the egalitarian solution of Dutta and Ray (1989).We prove, among others, that for a convex game the egalitarian solution coincides with the dual egalitarian solution for its

  5. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  6. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  7. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  9. Solution structure of the parvulin-type PPIase domain of Staphylococcus aureus PrsA – Implications for the catalytic mechanism of parvulins

    Directory of Open Access Journals (Sweden)

    Koskela Harri

    2009-03-01

    Full Text Available Abstract Background Staphylococcus aureus is a Gram-positive pathogenic bacterium causing many kinds of infections from mild respiratory tract infections to life-threatening states as sepsis. Recent emergence of S. aureus strains resistant to numerous antibiotics has created a need for new antimicrobial agents and novel drug targets. S. aureus PrsA is a membrane associated extra-cytoplasmic lipoprotein which contains a parvulin-type peptidyl-prolyl cis-trans isomerase domain. PrsA is known to act as an essential folding factor for secreted proteins in Gram-positive bacteria and thus it is a potential target for antimicrobial drugs against S. aureus. Results We have solved a high-resolution solution structure of the parvulin-type peptidyl-prolyl cis-trans isomerase domain of S. aureus PrsA (PrsA-PPIase. The results of substrate peptide titrations pinpoint the active site and demonstrate the substrate preference of the enzyme. With detailed NMR spectroscopic investigation of the orientation and tautomeric state of the active site histidines we are able to give further insight into the structure of the catalytic site. NMR relaxation analysis gives information on the dynamic behaviour of PrsA-PPIase. Conclusion Detailed structural description of the S. aureus PrsA-PPIase lays the foundation for structure-based design of enzyme inhibitors. The structure resembles hPin1-type parvulins both structurally and regarding substrate preference. Even though a wealth of structural data is available on parvulins, the catalytic mechanism has yet to be resolved. The structure of S. aureus PrsA-PPIase and our findings on the role of the conserved active site histidines help in designing further experiments to solve the detailed catalytic mechanism.

  10. A molecular receptor selective for zwitterionic alanine.

    Science.gov (United States)

    Rubio, Omayra H; Taouil, Rachid; Muñiz, Francisco M; Monleón, Laura M; Simón, Luis; Sanz, Francisca; Morán, Joaquín R

    2017-01-04

    A molecular receptor has been synthesized joining an aza-crown ether with a chiral chromane which mimics the oxyanion hole of the enzymes. With this receptor an apolar host-guest complex with zwitterionic alanine has been achieved through the formation of up to seven H-bonds. This complex allows the extraction of aqueous alanine to a chloroform phase, while other natural amino acids are poorly extracted or are not extracted at all. Due to the chiral nature of the receptor, enantioselective extraction from the aqueous alanine solution to a chloroform phase takes place. X-Ray analysis combined with anisotropic effects, NOE and CD studies revealed the absolute configuration of both strong and weak complexes. Modelling studies also support the proposed structures. The presence of an oxyanion-hole motif in this structure was corroborated by X-ray diffraction studies.

  11. Kerr generalized solution

    International Nuclear Information System (INIS)

    Papoyan, V.V.

    1989-01-01

    A Kerr generalized solution for a stationary axially-symmetric gravitational field of rotating self-gravitational objects is given. For solving the problem Einstein equations and their combinations are used. The particular cases: internal and external Schwarzschild solutions are considered. The external solution of the stationary problem is a Kerr solution generalization. 3 refs

  12. Radiochromic liquid solution

    International Nuclear Information System (INIS)

    Noakes, J.E.; Culp, R.A.

    1983-01-01

    A radiochromic solution which is sensitive to small dosages of ionizing and ultraviolet radiation is described. It consists of a solution of a leucocyanide dye in a clear polar solvent with enough organic acid added to make the solution at least slightly acidic and responds to radiation by permanently changing color. Up to one half of the solution by weight can be replaced by a second solution of an aromatic solvent and an organic fluor. Another modification of the invention is a solution of a leucocyanide dye in a clear polar solvent having an aromatic group, an organic fluor, and enough organic acid to make the solution at least slightly acidic. (author)

  13. Liquid scintillation solutions

    International Nuclear Information System (INIS)

    Long, E.C.

    1976-01-01

    The liquid scintillation solution described includes a mixture of: a liquid scintillation solvent, a primary scintillation solute, a secondary scintillation solute, a variety of appreciably different surfactants, and a dissolving and transparency agent. The dissolving and transparency agent is tetrahydrofuran, a cyclic ether. The scintillation solvent is toluene. The primary scintillation solute is PPO, and the secondary scintillation solute is dimethyl POPOP. The variety of appreciably different surfactants is composed of isooctylphenol-polyethoxyethanol and sodium dihexyl sulphosuccinate [fr

  14. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  15. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  16. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  17. The Anti-sigma Factor RsiV Is a Bacterial Receptor for Lysozyme: Co-crystal Structure Determination and Demonstration That Binding of Lysozyme to RsiV Is Required for σV Activation.

    Directory of Open Access Journals (Sweden)

    Jessica L Hastie

    2016-09-01

    Full Text Available σ factors provide RNA polymerase with promoter specificity in bacteria. Some σ factors require activation in order to interact with RNA polymerase and transcribe target genes. The Extra-Cytoplasmic Function (ECF σ factor, σV, is encoded by several Gram-positive bacteria and is specifically activated by lysozyme. This activation requires the proteolytic destruction of the anti-σ factor RsiV via a process of regulated intramembrane proteolysis (RIP. In many cases proteases that cleave at site-1 are thought to directly sense a signal and initiate the RIP process. We previously suggested binding of lysozyme to RsiV initiated the proteolytic destruction of RsiV and activation of σV. Here we determined the X-ray crystal structure of the RsiV-lysozyme complex at 2.3 Å which revealed that RsiV and lysozyme make extensive contacts. We constructed RsiV mutants with altered abilities to bind lysozyme. We find that mutants that are unable to bind lysozyme block site-1 cleavage of RsiV and σV activation in response to lysozyme. Taken together these data demonstrate that RsiV is a receptor for lysozyme and binding of RsiV to lysozyme is required for σV activation. In addition, the co-structure revealed that RsiV binds to the lysozyme active site pocket. We provide evidence that in addition to acting as a sensor for the presence of lysozyme, RsiV also inhibits lysozyme activity. Thus we have demonstrated that RsiV is a protein with multiple functions. RsiV inhibits σV activity in the absence of lysozyme, RsiV binds lysozyme triggering σV activation and RsiV inhibits the enzymatic activity of lysozyme.

  18. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    Director of ... function of the Lp is to deliver lipids throughout the insect body for metabolism ... Lipid is used as a major energy source for development as well as other metabolic .... LpR4 receptor variant was expressed exclusively in the brain and.

  19. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  20. Colliding black hole solution

    International Nuclear Information System (INIS)

    Ahmed, Mainuddin

    2005-01-01

    A new solution of Einstein equation in general relativity is found. This solution solves an outstanding problem of thermodynamics and black hole physics. Also this work appears to conclude the interpretation of NUT spacetime. (author)

  1. PFP solution stabilization

    International Nuclear Information System (INIS)

    Aftanas, B.L.

    1996-01-01

    This Functional Design Criteria (FDC) addresses remediation of the plutonium-bearing solutions currently in inventory at the Plutonium Finishing Plant (PFP). The recommendation from the Environmental Impact Statement (EIS) is that the solutions be treated thermally and stabilized as a solid for long term storage. For solutions which are not discardable, the baseline plan is to utilize a denitration process to stabilize the solutions prior to packaging for storage

  2. Classical solutions in supergravity

    International Nuclear Information System (INIS)

    Baaklini, N.S.; Ferrara, S.; Nieuwenhuizen Van, P.

    1977-06-01

    Classical solutions of supergravity are obtained by making finite global supersymmetry rotation on known solutions of the field equations of the bosonic sector. The Schwarzschild and the Reissner-Nordstoem solutions of general relativity are extended to various supergravity systems and the modification to the perihelion precession of planets is discussed

  3. Liquid scintillation solution

    International Nuclear Information System (INIS)

    Long, E.C.

    1977-01-01

    A liquid scintillation solution is described which includes (1) a scintillation solvent (toluene and xylene), (2) a primary scintillation solute (PPO and Butyl PBD), (3) a secondary scintillation solute (POPOP and Dimethyl POPOP), (4) a plurality of substantially different surfactants and (5) a filter dissolving and/or transparentizing agent. 8 claims

  4. Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor

    DEFF Research Database (Denmark)

    Svensson, L Anders; Bondensgaard, Kent; Nørskov-Lauritsen, Leif

    2008-01-01

    The crystal structure of the complex between an N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain of the human prolactin receptor (PRLR) was determined at 2.5A resolution by x-ray crystallography. This structure represents the first experimental structure...... studies, the structural data imply that the definition of PRL binding site 1 should be extended to include residues situated in the N-terminal part of loop 1 and in the C terminus. Comparison of the structure of the receptor-bound PRL variant with the structure reported for the unbound form of a similar...... scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. Hydrogen exchange mass spectrometry data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at binding site 1....

  5. Solvent wash solution

    International Nuclear Information System (INIS)

    Neace, J.C.

    1986-01-01

    This patent describes a process for removing diluent degradation products from a solvent extraction solution comprising an admixture of an organic extractant for uranium and plutonium and a non-polar organic liquid diluent, which has been used to recover uranium and plutonium from spent nuclear fuel. Comprising combining a wash solution consisting of: (a) water; and (b) a positive amount up to about, an including, 50 volume percent of at least one highly-polar water-miscible organic solvent, based on the total volume of the water and the highly-polar organic solvent, with the solvent extraction solution after uranium and plutonium values have been stripped from the solvent extraction solution, the diluent degradation products dissolving in the highly-polar organic solvent and the extractant and diluent of the extraction solution not dissolving in the highly-polar organic solvent, and separating the highly-polar organic solvent and the extraction solution to obtain a purified extraction solution

  6. Proteins in solution: Fractal surfaces in solutions

    Directory of Open Access Journals (Sweden)

    R. Tscheliessnig

    2016-02-01

    Full Text Available The concept of the surface of a protein in solution, as well of the interface between protein and 'bulk solution', is introduced. The experimental technique of small angle X-ray and neutron scattering is introduced and described briefly. Molecular dynamics simulation, as an appropriate computational tool for studying the hydration shell of proteins, is also discussed. The concept of protein surfaces with fractal dimensions is elaborated. We finish by exposing an experimental (using small angle X-ray scattering and a computer simulation case study, which are meant as demonstrations of the possibilities we have at hand for investigating the delicate interfaces that connect (and divide protein molecules and the neighboring electrolyte solution.

  7. Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

    NARCIS (Netherlands)

    Rios, Pablo; Carter, Tom S; Mooibroek, Tiddo J; Crump, Matthew P; Lisbjerg, Micke; Pittelkow, Michael; Supekar, Nitin T; Boons, Geert-Jan|info:eu-repo/dai/nl/088245489; Davis, Anthony P

    2016-01-01

    The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside

  8. Solution mining process

    International Nuclear Information System (INIS)

    Showalter, W.E.

    1984-01-01

    A solution mining process which may be used for uranium, thorium, vanadium, copper, nickel, molybdenum, rhenium, and selenium is claimed. During a first injection-and-production phase of between 6 months and 5 years, a leaching solution is injected through at least one well into the formation to solubilize the mineral values and form a pregnant liquor. This liquor is recovered through another well. The leaching solution contains sulfuric acid, nitric acid, hydrochloric acid, carbonic acid, an alkali metal carbonate, an alkali metal bicarbonate, ammonium carbonate or ammonium bicarbonate. Subsequently during a first production-only phase of between about 2 weeks and one year, injection of the leaching solution is suspended but pregnant liquor is still recovered. This stage is followed by a second injection-and-production phase of between 6 months and 5 years and a second production-only phase. The mineral values are separated from the pregnant liquor to form a barren liquor. The leaching agent is introduced into this liquor, and the solution is recycled. In a second claim for the solution mining of uranium, dilute carbonic acid is used as the leaching solution. The solution has a pH less than 7 and a bicarbonate ion concentration between about 380 ppm and 1000 ppm. The injection-and-production phase lasts between one and two years and the production only phase takes between one and four months. Carbon dioxide is introduced into the barren liquor to form a dilute carbonic acid solution and the solution is recycled

  9. GRRR. The EXPECT groundwater model for transport of solutes

    NARCIS (Netherlands)

    Meijers R; Sauter FJ; Veling EJM; van Grinsven JJM; Leijnse A; Uffink GJM; MTV; CWM; LBG

    1994-01-01

    In this report the design and first test results are presented of the EXPECT groundwater module for transport of solutes GRRR (GRoundwater source Receptor Relationships). This model is one of the abiotic compartment modules of the EXPECT model. The EXPECT model is a tool for scenario development

  10. Diquafosol ophthalmic solution for dry eye treatment.

    Science.gov (United States)

    Nakamura, Masatsugu; Imanaka, Takahiro; Sakamoto, Asuka

    2012-07-01

    There has been rapid progress in our understanding of dry eye pathogenesis, as well as the development of improved diagnostic clinical tests. Various types of dry eye treatment drugs have been developed. This review summarizes the basic and clinical research carried out in the development of diquafosol for ophthalmic use. Diquafosol is a dinucleotide, purinoreceptor P2Y(2) receptor agonist. Basic pharmacological studies have shown that it acts on P2Y(2) receptors at the ocular surface, to promote tear and mucin secretion via elevated intracellular Ca(2+) concentrations. Diquafosol also improves tear and mucin secretion in experimental dry eye models. Based on the results of laboratory experiments, the authors conducted a series of clinical studies in patients with dry eye disease. Diquafosol was effective in the treatment of dry eye disease at an optimal dose of 3% six times a day. In comparison to commercially available 0.1% sodium hyaluronate ophthalmic solution, 3% diquafosol ophthalmic solution showed non-inferiority in improving corneal fluorescein staining scores and superiority in improving keratoconjunctival Rose Bengal staining scores. Diquafosol ophthalmic solution has a novel mechanism of action that is characterized by its stimulatory effects on tear and mucin secretion. This drug has the potential to be effective in patients with tear film instability and short break-up time type of dry eye, which are essential factors in dry eye pathogenesis.

  11. Liquid scintillation solution

    International Nuclear Information System (INIS)

    Long, E.C.

    1976-01-01

    The invention deals with a liquid scintillation solution which contains 1) a scintillation solvent (toluol), 2) a primary scintillation solute (PPO), 3) a secondary scintillation solute (dimethyl POPOP), 4) several surfactants (iso-octyl-phenol polyethoxy-ethanol and sodium di-hexyl sulfosuccinate) essentially different from one another and 5) a filter resolution and/or transparent-making agent (cyclic ether, especially tetrahydrofuran). (HP) [de

  12. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  13. PERVASIVE BUSINESS INTELLIGENCE SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Rocsana Tonis (Bucea-Manea

    2011-03-01

    Full Text Available The utility of BI solutions is accepted all over the world in the modern organizations. However, the BI solutions do not offer a constant feedback in line with the organizational activities. In this context, there have been developed pervasive BI solutions which are present at different levels of the organization, so that employees can observe only what is most relevant to their day-to-day tasks. They are organized in vertical silos, with clearly identified performance and expectations. The paper emphasizes the role of pervasive BI solutions in reaching the key performance indicators of the modern organizations, more important in the context of crisis.

  14. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists

    Science.gov (United States)

    2016-08-01

    approximately halfway into the solution. All animals were tested at 60, 15 and 0 min before drug injection. For each animal , the first reading was discarded...approval (December 31, 2015), hiring new personnel, conducting baseline testing for procedures not involving animals , testing equipment, developing...treatment; Analgesia; Nociception; Antinociception; Inflammation; Chemokines; Chemokine receptor antagonists; Opioid analgesics; Animal models of pain

  15. Measurement of anti- acetylcholine receptor auto-antibodies in ...

    African Journals Online (AJOL)

    auto-antibodies in myasthenia gravis. K. J. Steenkamp, W. Duim, M. s. Myer,. S. C. K. Malfeld, R. Anderson. Two different acetylcholine receptor (AChR) preparations derived from ... the detection of AChR auto-antibodies in serum specimens from 20 ... 4°C. Thereafter, 1 ml of washing solution (phosphate- buffered saline ...

  16. Solute-solute interactions in intermetallic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Debashis; Murray, Ryan; Collins, Gary S., E-mail: collins@wsu.edu [Washington State University, Department of Physics and Astronomy (United States); Zacate, Matthew O. [Northern Kentucky University, Department of Physics and Geology (United States)

    2017-11-15

    Experiments were carried out on highly ordered GdAl{sub 2} samples containing extremely dilute mole fractions of{sup 111}In/Cd probe-atom solutes (about 10{sup −11}), intrinsic antisite atoms Al{sub Gd} having mole fractions of order 0-10{sup −2}, and doped with Ag solutes at mole fractions of order 10{sup −2}. Three types of defect interactions were investigated. (1) Quadrupole interactions caused by Ag-solute atoms neighboring{sup 111}In/Cd solute probe atoms were detected using the method of perturbed angular correlation of gamma rays (PAC). Three complexes of pairs of In-probes and Ag-solutes occupying neighboring positions on Gd- and Al-sublattices were identified by comparing site fractions in Gd-poor and Gd-rich GdAl{sub 2}(Ag) samples and from the symmetry of the quadrupole interactions. Interaction enthalpies between solute-atom pairs were determined from temperature dependences of observed site fractions. Repulsive interactions were observed for close-neighbor complexes In{sub Gd}+Ag{sub Gd} and In{sub Gd}+Ag{sub Al} pairs, whereas a slightly attractive interaction was observed for In{sub Al}+Ag{sub Al}. Interaction enthalpies were all small, in the range ±0.15 eV. (2) Quadrupole interactions caused by intrinsic antisite atoms Al{sub Gd} neighboring In{sub Gd} probes were also detected and site fractions measured as a function of temperature, as in previous work on samples not doped with Ag-solutes [Temperature- and composition-driven changes in site occupation of solutes in Gd{sub 1+3x}Al{sub 2−3x}, Zacate and Collins (Phys. Rev. B69, 174202 (1))]. However, the effective binding enthalpy between In{sub Gd} probe and Al{sub Gd} antisite was found to change sign from -0.12 eV (attractive interaction) in undoped samples to + 0.24 eV (repulsive) in Ag-doped samples. This may be attributed to an attractive interaction between Al{sub Gd} antisite atoms and Ag-dopants that competes with the attractive interaction between In{sub Gd} and Al{sub Gd

  17. Assays for calcitonin receptors

    International Nuclear Information System (INIS)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is 125 I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed

  18. Solutions of nuclear pairing

    International Nuclear Information System (INIS)

    Balantekin, A. B.; Pehlivan, Y.

    2007-01-01

    We give the exact solution of orbit dependent nuclear pairing problem between two nondegenerate energy levels using the Bethe ansatz technique. Our solution reduces to previously solved cases in the appropriate limits including Richardson's treatment of reduced pairing in terms of rational Gaudin algebra operators

  19. On Lovelock vacuum solution

    OpenAIRE

    Dadhich, Naresh

    2010-01-01

    We show that the asymptotic large $r$ limit of all Lovelock vacuum and electrovac solutions with $\\Lambda$ is always the Einstein solution in $d \\geq 2n+1$ dimensions. It is completely free of the order $n$ of the Lovelock polynomial indicating universal asymptotic behaviour.

  20. Rational Solutions and Lump Solutions of the Potential YTSF Equation

    Science.gov (United States)

    Sun, Hong-Qian; Chen, Ai-Hua

    2017-07-01

    By using of the bilinear form, rational solutions and lump solutions of the potential Yu-Toda-Sasa-Fukuyama (YTSF) equation are derived. Dynamics of the fundamental lump solution, n1-order lump solutions, and N-lump solutions are studied for some special cases. We also find some interaction behaviours of solitary waves and one lump of rational solutions.

  1. Bolting multicenter solutions

    Energy Technology Data Exchange (ETDEWEB)

    Bena, Iosif [Institut de Physique Théorique, Université Paris Saclay, CEA, CNRS, 91191 Gif-sur-Yvette Cedex (France); Bossard, Guillaume [Centre de Physique Théorique, Ecole Polytechnique, CNRS, Université Paris-Saclay, 91128 Palaiseau Cedex (France); Katmadas, Stefanos; Turton, David [Institut de Physique Théorique, Université Paris Saclay, CEA, CNRS, 91191 Gif-sur-Yvette Cedex (France)

    2017-01-30

    We introduce a solvable system of equations that describes non-extremal multicenter solutions to six-dimensional ungauged supergravity coupled to tensor multiplets. The system involves a set of functions on a three-dimensional base metric. We obtain a family of non-extremal axisymmetric solutions that generalize the known multicenter extremal solutions, using a particular base metric that introduces a bolt. We analyze the conditions for regularity, and in doing so we show that this family does not include solutions that contain an extremal black hole and a smooth bolt. We determine the constraints that are necessary to obtain smooth horizonless solutions involving a bolt and an arbitrary number of Gibbons-Hawking centers.

  2. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  3. TLX: An elusive receptor.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Webb, Paul

    2016-03-01

    TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  5. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  6. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... due to a post- receptor defect (Karadas et al., 2007). Several polymorphisms have ... the detection of the Arg16Gly polymorphism, overnight digestion at. 37°C with 10 U ..... DW, Wood AJ, Stein CM (2004). Beta2-adrenoceptor ...

  7. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  8. Thick brane solutions

    International Nuclear Information System (INIS)

    Dzhunushaliev, Vladimir; Minamitsuji, Masato; Folomeev, Vladimir

    2010-01-01

    This paper gives a comprehensive review on thick brane solutions and related topics. Such models have attracted much attention from many aspects since the birth of the brane world scenario. In many works, it has been usually assumed that a brane is an infinitely thin object; however, in more general situations, one can no longer assume this. It is also widely considered that more fundamental theories such as string theory would have a minimal length scale. Many multidimensional field theories coupled to gravitation have exact solutions of gravitating topological defects, which can represent our brane world. The inclusion of brane thickness can realize a variety of possible brane world models. Given our understanding, the known solutions can be classified into topologically non-trivial solutions and trivial ones. The former class contains solutions of a single scalar (domain walls), multi-scalar, gauge-Higgs (vortices), Weyl gravity and so on. As an example of the latter class, we consider solutions of two interacting scalar fields. Approaches to obtain cosmological equations in the thick brane world are reviewed. Solutions with spatially extended branes (S-branes) and those with an extra time-like direction are also discussed.

  9. Professional Hadoop solutions

    CERN Document Server

    Lublinsky, Boris; Yakubovich, Alexey

    2013-01-01

    The go-to guidebook for deploying Big Data solutions with Hadoop Today's enterprise architects need to understand how the Hadoop frameworks and APIs fit together, and how they can be integrated to deliver real-world solutions. This book is a practical, detailed guide to building and implementing those solutions, with code-level instruction in the popular Wrox tradition. It covers storing data with HDFS and Hbase, processing data with MapReduce, and automating data processing with Oozie. Hadoop security, running Hadoop with Amazon Web Services, best practices, and automating Hadoop processes i

  10. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  11. ERP SOLUTIONS FOR SMEs

    Directory of Open Access Journals (Sweden)

    TUTUNEA MIHAELA FILOFTEIA

    2012-09-01

    Full Text Available The integration of activities, the business processes as well as their optimization, bring the perspective of profitable growth and create significant and competitive advantages in any company. The adoption of some ERP integrated software solutions, from SMEs’ perspective, must be considered as a very important management decision in medium and long term. ERP solutions, along with the transparent and optimized management of all internal processes, also offer an intra and inter companies collaborative platform, which allows a rapid expansion of activities towards e- business and mobile-business environments. This material introduces ERP solutions for SMEs from commercial offer and open source perspective; the results of comparative analysis of the solutions on the specific market, can be an useful aid to the management of the companies, in making the decision to integrate business processes, using ERP as a support.

  12. OIL SOLUTIONS POWDER

    Science.gov (United States)

    Technical product bulletin: aka OIL SOLUTIONS POWDER, SPILL GREEN LS, this miscellaneous oil spill control agent used in cleanups initially behaves like a synthetic sorbent, then as a solidifier as the molecular microencapsulating process occurs.

  13. Conductometry of electrolyte solutions

    Science.gov (United States)

    Safonova, Lyubov P.; Kolker, Arkadii M.

    1992-09-01

    A review is given of the theories of the electrical conductance of electrolyte solutions of different ionic strengths and concentrations, and of the models of ion association. An analysis is made of the methods for mathematical processing of experimental conductometric data. An account is provided of various theories describing the dependence of the limiting value of the ionic electrical conductance on the properties of the solute and solvent. The bibliography includes 115 references.

  14. Solutions to horava gravity.

    Science.gov (United States)

    Lü, H; Mei, Jianwei; Pope, C N

    2009-08-28

    Recently Horava proposed a nonrelativistic renormalizable theory of gravitation, which reduces to Einstein's general relativity at large distances, and that may provide a candidate for a UV completion of Einstein's theory. In this Letter, we derive the full set of equations of motion, and then we obtain spherically symmetric solutions and discuss their properties. We also obtain solutions for the Friedmann-Lemaître-Robertson-Walker cosmological metric.

  15. Piezoelectric Energy Harvesting Solutions

    Science.gov (United States)

    Caliò, Renato; Rongala, Udaya Bhaskar; Camboni, Domenico; Milazzo, Mario; Stefanini, Cesare; de Petris, Gianluca; Oddo, Calogero Maria

    2014-01-01

    This paper reviews the state of the art in piezoelectric energy harvesting. It presents the basics of piezoelectricity and discusses materials choice. The work places emphasis on material operating modes and device configurations, from resonant to non-resonant devices and also to rotational solutions. The reviewed literature is compared based on power density and bandwidth. Lastly, the question of power conversion is addressed by reviewing various circuit solutions. PMID:24618725

  16. Radiolysis of spray solutions

    International Nuclear Information System (INIS)

    Habersbergerova, A.; Janovsky, I.

    1985-01-01

    The factors were studied affecting thiosulfate radiolysis in the so-called spray solution for nuclear power plant containments. The reaction mechanism of primary radiolytic reactions leading to thiosulfate decomposition was studied using pulse radiolysis. Also measured was hydrazine loss in the irradiation of the bubbling solution intended for the capture of volatile chemical forms of radioiodine. Pulse radiolysis was used to study the kinetics of hydrazine reaction with elemental iodine. (author)

  17. Solution Structure of LC4 Transmembrane Segment of CCR5

    OpenAIRE

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 ...

  18. A boring solution

    Energy Technology Data Exchange (ETDEWEB)

    Radiuk, M I; Iushkova, N E; Kozubovskii, A I

    1979-10-25

    A boring solution is being patented for boring for oil and gas, which can be used in wells, where the temperature of the circulating liquid reaches 100/sup 0/. Polyvinyl acetate emulsion (PVE) is added for the purpose of decreasing viscosity of the solution at a temperature of agression into the boring solution containing clay, water, carboxymethylcellulose (CBC), a chloride from the number of sodium, potassium, or magnesium chlorides. The solution has the following composition in %: clay, 10 to 20; CBC, 1.5 to 2.0; chloride, 5 to 20; PVE, 0.5 to 2; water, up to 100. In accordance to GOST 1000-62 for the accepted PVE, the compound has the following composition, in %: monomer, 0.8; dry residue, greater than or equal to 50; plasticizer (tributyl phthalate), 5 to 15. The boring solution is processed according to the following method. The original solution, containing clay, water, salts, receives 1.5 to 2% CBC and afterwards it is processed with 0.5 to 2% PVE.

  19. Nuclear triiodothyronine receptors in rabbit heart

    International Nuclear Information System (INIS)

    Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

    1986-01-01

    Nuclear triiodothyronine receptors from rat liver have been characterized in detail by several investigators. However, little work has been done in this area using heart tissue. In this study they examined and characterized the triiodothyronine binding in rabbit hearts. Nuclei have been prepared from ventricular muscle cells of normal and thyrotoxic rabbits as well as from atrial muscle cells of normal rabbit. Hearts were perfused with a minimum essential medium containing collagenase and bovine serum albumin. Myocardial cells were isolated and then disrupted by sonication and washing with a Triton X-100 buffer solution. A discontinuous sucrose density gradient was then used to isolate the mycoardial nuclei. Radiolabelled triiodothyronine (T 3 ) binding to nuclei was examined using conditions described by established procedures. Scatchard analysis of the binding data yields maximum binding capacity (B/sub max/) of 0.17 +/- 0.2 pmol/mg DNA and apparent dissociation constant (K/sub d/) of 400 +/- 50 pM for normal heart T 3 -receptors. The apparent capacity for T 3 binding is approximately 40% greater in myocardial nuclei prepared from hearts of hyperthyroid rabbits. The binding capacity of atrial muscle nuclei is about fourfold lower than ventricular cell nuclei. The results suggest that binding capacity for T 3 -receptor in the atrium is considerably lower than that found in the ventricle

  20. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  1. Acetylcholine receptors and cholinergic ligands: biochemical and genetic aspects in Torpedo californica and Drosophila melanogaster

    International Nuclear Information System (INIS)

    Rosenthal, L.S.

    1987-01-01

    This study evaluates the biochemical and genetic aspects of the acetylcholine receptor proteins and cholinergic ligands in Drosophila melanogaster and Torpedo californica. Included are (1) a comparative study of nicotinic ligand-induced cation release from acetylcholine receptors isolated from Torpedo californica and from Drosophila melanogaster, (2) solution studies of the cholinergic ligands, nikethamide and ethamivan, aimed at measuring internal molecular rotational barriers in solvents of different polarity; and (3) the isolation and characterization of the gene(s) for the acetylcholine receptor in Drosophila melasogaster. Acetylcholine receptor proteins isolated from Drosphila melanogaster heads were found to behave kinetically similar (with regards to cholinergic ligand-induced 155 Eu: 3+ displacement from prelabeled proteins) to receptor proteins isolated from Torpedo californica electric tissue, providing additional biochemical evidence for the existence of a Drosophila acetylcholine receptor

  2. EphA2 is a functional receptor for the growth factor progranulin.

    Science.gov (United States)

    Neill, Thomas; Buraschi, Simone; Goyal, Atul; Sharpe, Catherine; Natkanski, Elizabeth; Schaefer, Liliana; Morrione, Andrea; Iozzo, Renato V

    2016-12-05

    Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases. © 2016 Neill et al.

  3. Social information solution; Shakai joho solution

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-10

    An information system for government offices is developed, a system that integrally supports operations inside government offices and the staff service operations by combining Intra Net as the basis of an information system with Internet. The objective of the system is as follows: (1) Information sharing in the place of work and utilization of information resources. (2) Improvement in administrative services and vitalization of an interchange of residents through the preparation of Internet environment. (3) Rationalization of staff operations through groupeware. In addition, by building a network system for the entire region, information communication service is to be provided as a solution between the residents and the administration in the occurrence of a disaster as well as for home care, medical and nursing assistance in the health, medical and welfare fields. (translated by NEDO)

  4. Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists.

    Science.gov (United States)

    Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake; Beck, Johannes G; Opperer, Florian; Rechenmacher, Florian; Kessler, Horst; Hruby, Victor J

    2017-08-15

    Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His 6 -d-Nal(2') 7 -NMe-Arg 8 -Trp 9 -Lys]-NH 2 (15) and Ac-Nle-c[Asp-His 6 -d-Nal(2') 7 -NMe-Arg 8 -NMe-Trp 9 -NMe-Lys]-NH 2 (17). It is known that the pharmacophore (His 6 -DNal 7 -Arg 8 -Trp 9 ) of the SHU-9119 peptides occupies a β II-turn-like region with the turn centered about DNal 7 -Arg 8 . The analogues with hMC3R selectivity showed distinct differences in the spatial arrangement of the Trp 9 side chains. In addition to our NMR studies, we also carried out molecular-level interaction studies of these two peptides at the homology model of hMC3R. Earlier chimeric human melanocortin 3 receptor studies revealed insights regarding the binding and functional sites of hMC3R selectivity. Upon docking of peptides 15 and 17 to the binding pocket of hMC3R, it was revealed that Arg 8 and Trp 9 side chains are involved in a majority of the interactions with the receptor. While Arg 8 forms polar contacts with D154 and D158 of hMC3R, Trp 9 utilizes π-π stacking interactions with F295 and F298, located on the transmembrane domain of hMC3R. It is hypothesized that as the frequency of Trp 9 -hMC3R interactions decrease, antagonistic activity increases. The absence of any interactions of the N-methyl groups with hMC3R suggests that their primary function is to modulate backbone conformations of the ligands.

  5. Passive House Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Strom, I.; Joosten, L.; Boonstra, C. [DHV Sustainability Consultants, Eindhoiven (Netherlands)

    2006-05-15

    PEP stands for 'Promotion of European Passive Houses' and is a consortium of European partners, supported by the European Commission, Directorate General for Energy and Transport. In this working paper an overview is given of Passive House solutions. An inventory has been made of Passive House solutions for new build residences applied in each country. Based on this, the most common basic solutions have been identified and described in further detail, including the extent to which solutions are applied in common and best practice and expected barriers for the implementation in each country. An inventory per country is included in the appendix. The analysis of Passive House solutions in partner countries shows high priority with regard to the performance of the thermal envelope, such as high insulation of walls, roofs, floors and windows/ doors, thermal bridge-free construction and air tightness. Due to the required air tightness, special attention must be paid to indoor air quality through proper ventilation. Finally, efficient ((semi-)solar) heating systems for combined space and DHW heating still require a significant amount of attention in most partner countries. Other basic Passive House solutions show a smaller discrepancy with common practice and fewer barriers have been encountered in partner countries. In the next section, the general barriers in partner countries have been inventoried. For each type of barrier a suggested approach has been given. Most frequently encountered barriers in partner countries are: limited know-how; limited contractor skills; and acceptation of Passive Houses in the market. Based on the suggested approaches to overcoming barriers, this means that a great deal of attention must be paid to providing practical information and solutions to building professionals, providing practical training to installers and contractors and communication about the Passive House concept to the market.

  6. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  7. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...... the world covering a wide spectrum from fundamental mechanistic studies to metabolism, clinical studies, and drug development. In this report, we summarize the recent and exciting findings presented by the speakers at the meeting....

  8. Neurotransmitter receptor imaging

    International Nuclear Information System (INIS)

    Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

    1993-01-01

    The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

  9. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  10. Siemens IT solutions for power sector. PROFIT solutions

    International Nuclear Information System (INIS)

    Lunter, P.

    2004-01-01

    The cost reduction, flexibility and revenue increase, potential exploitation, productivity increase, and business opportunities exploitation - that is all what can be required in the races for the promonent positioning on the electricity power market. These requirements can be realized by the sophisticated IT solutions hand-tailored to the special requirements of the electric power producers and tradesmen. This approach makes it possible to achieve greater profit. Our solutions 'PROFIT Solutions', that are symbiosis of the most progressive information technologies and the power plant techniques of the company Siemens, satisfy submitted specifications in substantial measure. The system solutions 'PROFIT Solutions' comprise three solution groups: process, operation a business. The solutions of the group 'IT Process Solutions' increase flexibility and manoeuvrability of equipment, improve the efficiency and contribute to more economical operation of the power generation. Solutions 'IT Process Solutions' simplify and shorten the period of power cycles and conduce to higher labour productivity. Solutions group 'IT Process Solutions' approaches equipment to the market - supports the profit strategies, helps quickly and expertly to determine and predict hazards. The extension PROFIT Cockpit means the nuance to the solutions world 'PROFIT Solutions'. The survey about the whole installation is within reach at the simple touch of a button. It is possible to compile the total system part by part from single solutions 'PROFIT Solutions'. As a matter of fact all single parts can be interconnected with already existing solutions. Routines 'PROFIT Solutions' cooperate with all modern control systems. (author)

  11. Solute segregation during irradiation

    International Nuclear Information System (INIS)

    Wiedersich, H.; Okamoto, P.R.; Lam, N.Q.

    1977-01-01

    Irradiation at elevated temperature induces redistribution of the elements in alloys on a microstructural level. This phenomenon is caused by differences in the coupling of the various alloy constituents to the radiation-induced defect fluxes. A simple model of the segregation process based on coupled reaction-rate and diffusion equations is discussed. The model gives a good description of the experimentally observed consequences of radiation-induced segregation, including enrichment or depletion of solute elements near defect sinks such as surfaces, voids and dislocations; precipitation of second phases in solid solutions; precipitate redistribution in two-phase alloys; and effects of defect-production rates on void-swelling rates in alloys with minor solute additions

  12. Superstrings fermionic solutions

    International Nuclear Information System (INIS)

    Rausch de Traubenberg, M.

    1990-06-01

    The solutions proposed by the superstring theory are classified and compared. In order to obtain some of the equivalences, the demonstration is based on the coincidence of the excitation spectrum and the quantum numbers from different states. The fermionic representation of the heterotical strings is discussed. The conformal invariance and the supersymmetric results extended to two dimensions are investigated. Concerning the fermionic strings, the formalism and a phenomenological solution involving three families of quarks, chiral leptons and leptons from the E 6 gauge group are presented. The equivalence between real and complex fermions is discussed. The similarity between some of the solutions of the Wess-Zumino-Witten model and the orbifolds is considered. The formal calculation program developed for reproducing the theory's low energy spectra, in the fermionic string formalism is given [fr

  13. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  14. Decontamination solution development studies

    International Nuclear Information System (INIS)

    Allen, R.P.; Fetrow, L.K.; Kjarmo, H.E.; Pool, K.H.

    1993-09-01

    This study was conducted for the Westinghouse Hanford Company (WHC) by Pacific Northwest Laboratory (PNL) as part of the Hanford Grout Technology Program (HGTP). The objective of this study was to identify decontamination solutions capable of removing radioactive contaminants and grout from the Grout Treatment Facility (GTF) process equipment and to determine the impact of these solutions on equipment components and disposal options. The reference grout used in this study was prepared with simulated double-shell slurry feed (DSSF) and a dry blend consisting of 40 wt % limestone flour, 28 wt % blast furnace slag, 28 wt % fly ash, and 4 wt % type I/II Portland cement

  15. Calculus problems and solutions

    CERN Document Server

    Ginzburg, Abraham

    2011-01-01

    Ideal for self-instruction as well as for classroom use, this text helps students improve their understanding and problem-solving skills in analysis, analytic geometry, and higher algebra. More than 1,200 problems appear in the text, with concise explanations of the basic notions and theorems to be used in their solution. Many are followed by complete answers; solutions for the others appear at the end of the book. Topics include sequences, functions of a single variable, limit of a function, differential calculus for functions of a single variable, fundamental theorems and applications of dif

  16. In Search of Solutions

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    when pursuing minor performance improvements in existing technologies. However, reliance on internal knowledge sources carries a risk of organizational inertia related to problem understanding and solution development in the shape of path-dependencies and preferences for exploitation and reapplication...... of existing knowledge. Such inertia may imbue innovation processes related to the development of new technologies with reduced novelty and an inability to recognize alternative and potentially more attractive solutions. As a result, over-reliance on internal knowledge sources is likely to inhibit the ability...

  17. Business Intelligence Integrated Solutions

    Directory of Open Access Journals (Sweden)

    Cristescu Marian Pompiliu

    2017-12-01

    Full Text Available A Business Intelligence solution concerns the simple, real-time access to complete information about the business shown in a relevant format of the report, graphic or dashboard type in order help the taking of strategic decisions regarding the direction in which the company goes. Business Intelligence does not produce data, but uses the data produced by the company’s applications. BI solutions extract their data from ERP (Enterprise Resource Planning, CRM (Customer Relationship Management, HCM (Human Capital Management, and Retail, eCommerce or other databases used in the company.

  18. Microsoft big data solutions

    CERN Document Server

    Jorgensen, Adam; Welch, John; Clark, Dan; Price, Christopher; Mitchell, Brian

    2014-01-01

    Tap the power of Big Data with Microsoft technologies Big Data is here, and Microsoft's new Big Data platform is a valuable tool to help your company get the very most out of it. This timely book shows you how to use HDInsight along with HortonWorks Data Platform for Windows to store, manage, analyze, and share Big Data throughout the enterprise. Focusing primarily on Microsoft and HortonWorks technologies but also covering open source tools, Microsoft Big Data Solutions explains best practices, covers on-premises and cloud-based solutions, and features valuable case studies. Best of all,

  19. Identification of Disulphide Stress-responsive Extracytoplasmic Function Sigma Factors in Rothia mucilaginosa

    Science.gov (United States)

    2013-01-01

    Senadheera MD, Lee AWC, Hung DCI, Spatafora GA, Goodman SD, Cvitkovitch DG. The Streptococcus mutans vicX gene product modulates gtfB/C expression, biofilm...Involvement of sensor kinases in the stress tolerance response of Streptococcus mutans . Journal of Bacteriology 2008;190(1):68–77. 18. Meuric V...structures from a persistent apical periodontitis lesion. Sequencing 2010;2010:457236. 15. Wen ZT, Burne RA. LuxS-mediated signaling in Streptococcus

  20. Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma.

    Science.gov (United States)

    Pareja, Fresia; Murray, Melissa P; Jean, Ryan Des; Konno, Fumiko; Friedlander, Maria; Lin, Oscar; Edelweiss, Marcia

    2017-01-01

    Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER.

  1. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  2. Phenomenology of polymer solution dynamics

    National Research Council Canada - National Science Library

    Phillies, George D. J

    2011-01-01

    ... solutions, not dilute solutions or polymer melts. From centrifugation and solvent dynamics to viscosity and diffusion, experimental measurements and their quantitative representations are the core of the discussion...

  3. Aliteracy : causes and solutions

    NARCIS (Netherlands)

    Nielen, Thijs Martinus Johannes

    2016-01-01

    The reading motivation of the majority of students declines in the upper half of primary school, which implies a risk for aliteracy: Students can read but, due to lack of practice, their skills remain underdeveloped (Chapter 2). In this thesis we have explored causes and solutions for this important

  4. Solute transport in soil

    NARCIS (Netherlands)

    Zee, van der S.E.A.T.M.; Leijnse, A.

    2013-01-01

    Solute transport is of importance in view of the movement of nutrient elements, e.g. towards the plant root system, and because of a broad range of pollutants. Pollution is not necessarily man induced, but may be due to geological or geohydrological causes, e.g. in the cases of pollution with

  5. An Inexpensive Solution Calorimeter

    Science.gov (United States)

    Kavanagh, Emma; Mindel, Sam; Robertson, Giles; Hughes, D. E. Peter

    2008-01-01

    We describe the construction of a simple solution calorimeter, using a miniature bead thermistor as a temperature-sensing element. This has a response time of a few seconds and made it possible to carry out a thermometric reaction in under a minute, which led to minimal heat losses. Small temperature changes of 1 K associated with enthalpies of…

  6. Aqueous polyethylene oxide solutions

    International Nuclear Information System (INIS)

    Breen, J.

    1987-01-01

    A number of aspects concerning the reorientation of polymer, water and ion hydration complexes have been studied in aqueous solution of polyethylene oxide (PEO). The polymer dynamics are investigated by 1 H-PEO and 13 C-PEO nuclear relaxation experiments. 162 refs.; 30 figs.; 19 tabs

  7. Solution structure of LC4 transmembrane segment of CCR5.

    Directory of Open Access Journals (Sweden)

    Kazuhide Miyamoto

    Full Text Available CC-chemokine receptor 5 (CCR5 is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1. The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  8. Solution structure of LC4 transmembrane segment of CCR5.

    Science.gov (United States)

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  9. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  10. Adenosine Receptors and Wound Healing

    Directory of Open Access Journals (Sweden)

    Bruce N. Cronstein

    2004-01-01

    Full Text Available Recent studies have demonstrated that application of topical adenosine A2A receptor agonists promotes more rapid wound closure and clinical studies are currently underway to determine the utility of topical A2A adenosine receptor agonists in the therapy of diabetic foot ulcers. The effects of adenosine A2A receptors on the cells and tissues of healing wounds have only recently been explored. We review here the known effects of adenosine A2A receptor occupancy on the cells involved in wound healing.

  11. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.......A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...

  12. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  14. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  15. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  16. Weak solutions of magma equations

    International Nuclear Information System (INIS)

    Krishnan, E.V.

    1999-01-01

    Periodic solutions in terms of Jacobian cosine elliptic functions have been obtained for a set of values of two physical parameters for the magma equation which do not reduce to solitary-wave solutions. It was also obtained solitary-wave solutions for another set of these parameters as an infinite period limit of periodic solutions in terms of Weierstrass and Jacobian elliptic functions

  17. Earnest Rutherford, the solution

    CERN Multimedia

    2003-01-01

    If you did not make it to the Science & Society talk by John Campbell last week and are still wondering about the spelling of "Earnest", here is the solution: Two months after the birth of his fourth child on 30 August 1871 in Spring Grove, New Zealand, James Rutherford registered his son, who was recorded as "Earnest" in the Birth Register. Presumably the Registrar wrote the name down as it sounded and the father failed to notice the mistake when signing the Register.

  18. Molybdenum from uranium solutions

    International Nuclear Information System (INIS)

    Gardner, H.E.

    1981-01-01

    A method of removing molybdenum from a uranium bearing solution is claimed. It comprises adding sufficient reactive lead compound to supply at least 90 percent of the stoichiometric quantity of lead ion required to fully react with the molybdenum present to form insoluble lead molybdate and continuing the reaction with agitation until the desired percentage of the molybdenum present has reacted with the lead ion

  19. Severe service sealing solutions

    International Nuclear Information System (INIS)

    Metcalfe, R.; Wensel, R.

    1994-09-01

    Successful sealing usually requires much more than initial leak-tightness. Friction and wear must also be acceptable, requiring a good understanding of tribology at the sealing interface. This paper describes various sealing solutions for severe service conditions. The CAN2A and CAN8 rotary face seals use tungsten carbide against carbon-graphite to achieve low leakage and long lifetime in nuclear main coolant pumps. The smaller CAN6 seal successfully uses tungsten carbide against silicon carbide in reactor water cleanup pump service. Where friction in CANDU fuelling machine rams must be essentially zero, a hydrostatic seal using two silicon carbide faces is the solution. In the NRU reactor moderator pumps, where pressure is much lower, eccentric seals that prevent boiling at the seal faces are giving excellent service. All these rotary face seals rely on supplementary elastomer seals between their parts. An integrated engineering approach to high performance sealing with O-rings is described. This is epitomized in critical Space Shuttle applications, but is increasingly being applied in CANDU plants. It includes gland design, selection and qualification of material, quality assurance, detection of defects and the effects of lubrication, surface finish, squeeze, stretch and volume constraints. In conclusion, for the severe service applications described, customized solutions have more than paid for themselves by higher reliability, lower maintenance requirements and reduced outage time. (author)

  20. Quantitative analysis of receptor imaging

    International Nuclear Information System (INIS)

    Fu Zhanli; Wang Rongfu

    2004-01-01

    Model-based methods for quantitative analysis of receptor imaging, including kinetic, graphical and equilibrium methods, are introduced in detail. Some technical problem facing quantitative analysis of receptor imaging, such as the correction for in vivo metabolism of the tracer and the radioactivity contribution from blood volume within ROI, and the estimation of the nondisplaceable ligand concentration, is also reviewed briefly

  1. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  2. Identification of an estrogenic hormone receptor in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Mimoto, Ai; Fujii, Madoka; Usami, Makoto; Shimamura, Maki; Hirabayashi, Naoko; Kaneko, Takako; Sasagawa, Noboru; Ishiura, Shoichi

    2007-01-01

    Changes in both behavior and gene expression occur in Caenorhabditis elegans following exposure to sex hormones such as estrogen and progesterone, and to bisphenol A (BPA), an estrogenic endocrine-disrupting compound. However, only one steroid hormone receptor has been identified. Of the 284 known nuclear hormone receptors (NHRs) in C. elegans, we selected nhr-14, nhr-69, and nhr-121 for analysis as potential estrogenic hormone receptors, because they share sequence similarity with the human estrogen receptor. First, the genes were cloned and expressed in Escherichia coli, and then the affinity of each protein for estrogen was determined using a surface plasmon resonance (SPR) biosensor. All three NHRs bound estrogen in a dose-dependent fashion. To evaluate the specificity of the binding, we performed a solution competition assay using an SPR biosensor. According to our results, only NHR-14 was able to interact with estrogen. Therefore, we next examined whether nhr-14 regulates estrogen signaling in vivo. To investigate whether these interactions actually control the response of C. elegans to hormones, we investigated the expression of vitellogenin, an estrogen responsive gene, in an nhr-14 mutant. Semi-quantitative RT-PCR showed that vitellogenin expression was significantly reduced in the mutant. This suggests that NHR-14 is a C. elegans estrogenic hormone receptor and that it controls gene expression in response to estrogen

  3. A versatile optical tool for studying synaptic GABAA receptor trafficking.

    Science.gov (United States)

    Lorenz-Guertin, Joshua M; Wilcox, Madeleine R; Zhang, Ming; Larsen, Mads B; Pilli, Jyotsna; Schmidt, Brigitte F; Bruchez, Marcel P; Johnson, Jon W; Waggoner, Alan S; Watkins, Simon C; Jacob, Tija C

    2017-11-15

    Live-cell imaging methods can provide critical real-time receptor trafficking measurements. Here, we describe an optical tool to study synaptic γ-aminobutyric acid (GABA) type A receptor (GABA A R) dynamics through adaptable fluorescent-tracking capabilities. A fluorogen-activating peptide (FAP) was genetically inserted into a GABA A R γ2 subunit tagged with pH-sensitive green fluorescent protein (γ2 pH FAP). The FAP selectively binds and activates Malachite Green (MG) dyes that are otherwise non-fluorescent in solution. γ2 pH FAP GABA A Rs are expressed at the cell surface in transfected cortical neurons, form synaptic clusters and do not perturb neuronal development. Electrophysiological studies show γ2 pH FAP GABA A Rs respond to GABA and exhibit positive modulation upon stimulation with the benzodiazepine diazepam. Imaging studies using γ2 pH FAP-transfected neurons and MG dyes show time-dependent receptor accumulation into intracellular vesicles, revealing constitutive endosomal and lysosomal trafficking. Simultaneous analysis of synaptic, surface and lysosomal receptors using the γ2 pH FAP-MG dye approach reveals enhanced GABA A R turnover following a bicucculine-induced seizure paradigm, a finding not detected by standard surface receptor measurements. To our knowledge, this is the first application of the FAP-MG dye system in neurons, demonstrating the versatility to study nearly all phases of GABA A R trafficking. © 2017. Published by The Company of Biologists Ltd.

  4. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  5. A Novel Mechanism of Androgen Receptor Action

    National Research Council Canada - National Science Library

    Roberts, Jr, Charles T

    2006-01-01

    .... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

  6. In vitro labeling receptor autoradiography: loss of label during ethanol dehydration and preparative procedures

    International Nuclear Information System (INIS)

    Kuhar, M.J.; Unnerstall, J.R.

    1982-01-01

    Slide-mounted tissue sections of brain were incubated with several reversibly binding [ 3 H]ligands to label receptors. Exposure of these labeled, mounted tissue sections to ethanol solutions for dehydration resulted in a substantial loss of receptor bound ligands in all cases, even when the tissues were fixed with formaldehyde vapors before exposure. Thus, serious problems can be introduced into in vitro labeling autoradiographic procedures by exposure of sections to aqueous or organic media. (Auth.)

  7. Quantitative densitometry of neurotransmitter receptors

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

    1982-01-01

    An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

  8. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  9. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  10. Improved in Vitro Folding of the Y2 G Protein-Coupled Receptor into Bicelles

    Directory of Open Access Journals (Sweden)

    Peter Schmidt

    2018-01-01

    Full Text Available Prerequisite for structural studies on G protein-coupled receptors is the preparation of highly concentrated, stable, and biologically active receptor samples in milligram amounts of protein. Here, we present an improved protocol for Escherichia coli expression, functional refolding, and reconstitution into bicelles of the human neuropeptide Y receptor type 2 (Y2R for solution and solid-state NMR experiments. The isotopically labeled receptor is expressed in inclusion bodies and purified using SDS. We studied the details of an improved preparation protocol including the in vitro folding of the receptor, e.g., the native disulfide bridge formation, the exchange of the denaturating detergent SDS, and the functional reconstitution into bicelle environments of varying size. Full pharmacological functionality of the Y2R preparation was shown by a ligand affinity of 4 nM and G-protein activation. Further, simple NMR experiments are used to test sample quality in high micromolar concentration.

  11. Desensitization of γ-aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane

    International Nuclear Information System (INIS)

    Cash, D.J.; Subbarao, K.

    1987-01-01

    Transmembrane chloride flux mediated by γ-aminobutyric acid (GABA) receptor can be measured with a mammalian brain homogenate preparation containing sealed membrane vesicles. The preparation can be mixed rapidly with solutions of defined composition. Influx of 36 Cl - tracer initiated by mixing with GABA was rapidly terminated by mixing with bicuculline methiodide. The decrease in the isotope influx measurement due to prior incubation of the vesicle preparation with GABA, which increased with preincubation time and GABA concentration, was attributed to desensitization of the GABA receptor. By varying the time of preincubation with GABA between 10 ms and 50 s with quench-flow technique, the desensitization rates could be measured over their whole time course independently of the chloride ion flux rate. Most of the receptor activity decreased in a fast phase of desensitization complete in 200 ms at saturation with GABA. Remaining activity was desensitized in a few seconds. These two phases of desensitization were each kinetically first order and were shown to correspond with two distinguishable GABA receptors on the same membrane. The receptor activities could be estimated, and the faster desensitizing receptor was the predominant one, giving on average ca. 80% of the total activity. The half-response concentrations were similar, 150 and 114 μM for the major and minor receptors, respectively. The dependence on GABA concentration indicated that desensitization is mediated by two GABA binding sites. The fast desensitization rate was approximately 20-fold faster than previously reported rates while the slower desensitization rate was slightly faster than previously reported rates

  12. Acetylcholinesterase and Acetylcholine Receptor.

    Science.gov (United States)

    1986-01-21

    Cl3CCH2OH) binds similarly to its carbon analogue, neopentyl alcohol, and chloral binds better than its carbon analogue, pivalaldehyde. In the latter case...III. Since the 3H-DFP was obtained in propylene glycol , the stability of DFP in the hydroxylic solvent and thus its true concentration was investi...solution of unlabeled DFP in propylene glycol was obtained from NEN for use in model experi- ments and found to have no inhibiting activity. We turned

  13. Solution mining economics

    International Nuclear Information System (INIS)

    Hunkin, G.G.

    1980-01-01

    The field of application of in-situ solution mining of uranium is described and areas of competition with open pit and underground mining identified. The influence of high interest rates and dollar inflation on present values and rate of return is shown to be minimized by low capitalization and short construction lead times typical of in-situ leaching ventures. A scheme of three major project account divisions is presented and basic parameters necessary for mine planning are listed. 1979 cost ranges and useful methods of estimation of capital and operating costs are given for the in-situ uranium mining method

  14. Total Logistic Plant Solutions

    Directory of Open Access Journals (Sweden)

    Dusan Dorcak

    2016-02-01

    Full Text Available The Total Logistics Plant Solutions, plant logistics system - TLPS, based on the philosophy of advanced control processes enables complex coordination of business processes and flows and the management and scheduling of production in the appropriate production plans and planning periods. Main attributes of TLPS is to create a comprehensive, multi-level, enterprise logistics information system, with a certain degree of intelligence, which accepts the latest science and research results in the field of production technology and logistics. Logistic model of company understands as a system of mutually transforming flows of materials, energy, information, finance, which is realized by chain activities and operations

  15. From Goods to Solutions

    DEFF Research Database (Denmark)

    Chakkol, Mehmet; Johnson, Mark; Raja, Jawwad

    2014-01-01

    Purpose – This paper aims to adopt service-dominant logic (SDL) to empirically explore network configurations resulting from the provision of goods, goods and services, and solutions. Design/methodology/approach – This paper uses a single, in-depth, exploratory case study in a truck manufacturer......: dyadic, triadic and tetradic. The extent to which different network actors contribute to value co-creation varies across the offerings. Research limitations/implications – This paper is based on a single, in-depth case study developed in one industrial context. Whilst this represents an appropriate...

  16. A plugging solution

    Energy Technology Data Exchange (ETDEWEB)

    Gen, O P; Azhigaliyev, G K; Dodonova, S Ye; Dyaltlova, N M; Novokhatskaya, I D; Ryabova, L I

    1984-01-01

    The purpose of the invention is to increase the durability of cement stone at 150 to 200C. The patent covers a plugging solution which consists of Portlandcement, sand and water. It additionally contains metal organic complexes of nitrylotrimethylphosphonic acid and organosiliconates of alkali or alkaline earth metals with the following component relationship in percent by mass: Portland cement, 42 to 43; sand, 27 to 28; metal organic complexes of nitrylotrimethylphosphonic acid, 0.01 to 1.5; organosiliconates of alkaline or alkaline earthmetals, 0.0025 to 0.375 and water, the remainder.

  17. Classical solutions and extended supergravity

    International Nuclear Information System (INIS)

    de Alfaro, V.; Fubini, S.; Furlan, G.

    1980-03-01

    The existence and properties of classical solutions for gravity coupled to matter fields have been investigated previously with the limitation to conformally flat solutions. In the search for a guiding criterion to determine the form of the coupling among the fields, one is led to consider supersymmetric theories, and the question arises whether classical solutions persist in these models. It is found that a discrepancy persists between supergravity and standard meron solutions. Owing to the appearance of the scalar field, a new set of meron solutions exists for particular Lagrangian models. In conclusion, the form of solutions in Minkowski space is discussed

  18. Radioactive waste management solutions

    International Nuclear Information System (INIS)

    Siemann, Michael

    2015-01-01

    One of the more frequent questions that arise when discussing nuclear energy's potential contribution to mitigating climate change concerns that of how to manage radioactive waste. Radioactive waste is produced through nuclear power generation, but also - although to a significantly lesser extent - in a variety of other sectors including medicine, agriculture, research, industry and education. The amount, type and physical form of radioactive waste varies considerably. Some forms of radioactive waste, for example, need only be stored for a relatively short period while their radioactivity naturally decays to safe levels. Others remain radioactive for hundreds or even hundreds of thousands of years. Public concerns surrounding radioactive waste are largely related to long-lived high-level radioactive waste. Countries around the world with existing nuclear programmes are developing longer-term plans for final disposal of such waste, with an international consensus developing that the geological disposal of high-level waste (HLW) is the most technically feasible and safe solution. This article provides a brief overview of the different forms of radioactive waste, examines storage and disposal solutions, and briefly explores fuel recycling and stakeholder involvement in radioactive waste management decision making

  19. The Paperless Solution

    Science.gov (United States)

    2001-01-01

    REI Systems, Inc. developed a software solution that uses the Internet to eliminate the paperwork typically required to document and manage complex business processes. The data management solution, called Electronic Handbooks (EHBs), is presently used for the entire SBIR program processes at NASA. The EHB-based system is ideal for programs and projects whose users are geographically distributed and are involved in complex management processes and procedures. EHBs provide flexible access control and increased communications while maintaining security for systems of all sizes. Through Internet Protocol- based access, user authentication and user-based access restrictions, role-based access control, and encryption/decryption, EHBs provide the level of security required for confidential data transfer. EHBs contain electronic forms and menus, which can be used in real time to execute the described processes. EHBs use standard word processors that generate ASCII HTML code to set up electronic forms that are viewed within a web browser. EHBs require no end-user software distribution, significantly reducing operating costs. Each interactive handbook simulates a hard-copy version containing chapters with descriptions of participants' roles in the online process.

  20. Stargazin Modulation of AMPA Receptors

    Directory of Open Access Journals (Sweden)

    Sana A. Shaikh

    2016-10-01

    Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

  1. 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

  2. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  3. XMRV: usage of receptors and potential co-receptors

    Directory of Open Access Journals (Sweden)

    Gaddam Durga

    2011-09-01

    Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

  4. Middle Eastern solutions

    International Nuclear Information System (INIS)

    Boersma, M.

    2001-01-01

    The need to consider the Middle East as a group of distinct countries and not as one single market and to tailor the services offered by companies is stressed. The cultures, political and social conditions, forms of the oil and gas industry in the countries making up the Middle East and their technology requirements are different and vary widely. The approach taken by Shell Global Solutions to these differences is described and illustrated with Shell's experiences in Oman and Saudi Arabia. Shell has found that Omanis are keen to work in their oil and gas industry, and to protect their country's natural environment. Saudi also have intense pride in their oil industry and here Shell supports refinery operators reduce costs while maintaining strict quality control. Shell has been selected to help Saudi Arabia develop its natural gas reserves; as part of the Core Venture 3 project, Shell will build a power desalination plant

  5. Solvent - solute interaction

    International Nuclear Information System (INIS)

    Urbanczyk, A.; Kalinowski, M.K.

    1983-01-01

    The electronic absorption spectrum of vanadyl acetylacetonate has been studied in 15 organic solvents. It has been found that wavenumbers and molar absorptivities of the long-wavelength bands (d-d transitions) can be well described by a complementary Lewis acid-base model including Gutmann's donor number [Gutmann V., Wychera E., Inorg. Nucl. Chem. Letters 2, 257 (1966)] and acceptor number [Mayer U., Gutmann V., Gerger W., Monatsh. Chem. 106, 1235 (1975)] of a solvent. This model describes also the solvent effect of the hyperfine splitting constant, Asub(iso)( 51 V), from e.s.r. spectra of VOacac 2 . These observations are discussed in terms of the donor-acceptor concept for solvent-solute interactions. (Author)

  6. 2010 Water & Aqueous Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Dor Ben-Amotz

    2010-08-13

    Water covers more than two thirds of the surface of the Earth and about the same fraction of water forms the total mass of a human body. Since the early days of our civilization water has also been in the focus of technological developments, starting from converting it to wine to more modern achievements. The meeting will focus on recent advances in experimental, theoretical, and computational understanding of the behavior of the most important and fascinating liquid in a variety of situations and applications. The emphasis will be less on water properties per se than on water as a medium in which fundamental dynamic and reactive processes take place. In the following sessions, speakers will discuss the latest breakthroughs in unraveling these processes at the molecular level: Water in Solutions; Water in Motion I and II; Water in Biology I and II; Water in the Environment I and II; Water in Confined Geometries and Water in Discussion (keynote lecture and poster winners presentations).

  7. Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Fior-Chadi D.R.

    1998-01-01

    Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

  8. Diffusion of aqueous solutions of ionic, zwitterionic, and polar solutes

    Science.gov (United States)

    Teng, Xiaojing; Huang, Qi; Dharmawardhana, Chamila Chathuranga; Ichiye, Toshiko

    2018-06-01

    The properties of aqueous solutions of ionic, zwitterionic, and polar solutes are of interest to many fields. For instance, one of the many anomalous properties of aqueous solutions is the behavior of water diffusion in different monovalent salt solutions. In addition, solutes can affect the stabilities of macromolecules such as proteins in aqueous solution. Here, the diffusivities of aqueous solutions of sodium chloride, potassium chloride, tri-methylamine oxide (TMAO), urea, and TMAO-urea are examined in molecular dynamics simulations. The decrease in the diffusivity of water with the concentration of simple ions and urea can be described by a simple model in which the water molecules hydrogen bonded to the solutes are considered to diffuse at the same rate as the solutes, while the remainder of the water molecules are considered to be bulk and diffuse at almost the same rate as pure water. On the other hand, the decrease in the diffusivity of water with the concentration of TMAO is apparently affected by a decrease in the diffusion rate of the bulk water molecules in addition to the decrease due to the water molecules hydrogen bonded to TMAO. In other words, TMAO enhances the viscosity of water, while urea barely affects it. Overall, this separation of water molecules into those that are hydrogen bonded to solute and those that are bulk can provide a useful means of understanding the short- and long-range effects of solutes on water.

  9. Natural climate solutions

    Science.gov (United States)

    Griscom, Bronson W.; Adams, Justin; Ellis, Peter W.; Houghton, Richard A.; Lomax, Guy; Miteva, Daniela A.; Schlesinger, William H.; Shoch, David; Siikamäki, Juha V.; Smith, Pete; Woodbury, Peter; Zganjar, Chris; Blackman, Allen; Campari, João; Conant, Richard T.; Delgado, Christopher; Elias, Patricia; Gopalakrishna, Trisha; Hamsik, Marisa R.; Herrero, Mario; Kiesecker, Joseph; Landis, Emily; Laestadius, Lars; Leavitt, Sara M.; Minnemeyer, Susan; Polasky, Stephen; Potapov, Peter; Putz, Francis E.; Sanderman, Jonathan; Silvius, Marcel; Wollenberg, Eva; Fargione, Joseph

    2017-10-01

    Better stewardship of land is needed to achieve the Paris Climate Agreement goal of holding warming to below 2 °C; however, confusion persists about the specific set of land stewardship options available and their mitigation potential. To address this, we identify and quantify “natural climate solutions” (NCS): 20 conservation, restoration, and improved land management actions that increase carbon storage and/or avoid greenhouse gas emissions across global forests, wetlands, grasslands, and agricultural lands. We find that the maximum potential of NCS—when constrained by food security, fiber security, and biodiversity conservation—is 23.8 petagrams of CO2 equivalent (PgCO2e) y‑1 (95% CI 20.3–37.4). This is ≥30% higher than prior estimates, which did not include the full range of options and safeguards considered here. About half of this maximum (11.3 PgCO2e y‑1) represents cost-effective climate mitigation, assuming the social cost of CO2 pollution is ≥100 USD MgCO2e‑1 by 2030. Natural climate solutions can provide 37% of cost-effective CO2 mitigation needed through 2030 for a >66% chance of holding warming to below 2 °C. One-third of this cost-effective NCS mitigation can be delivered at or below 10 USD MgCO2‑1. Most NCS actions—if effectively implemented—also offer water filtration, flood buffering, soil health, biodiversity habitat, and enhanced climate resilience. Work remains to better constrain uncertainty of NCS mitigation estimates. Nevertheless, existing knowledge reported here provides a robust basis for immediate global action to improve ecosystem stewardship as a major solution to climate change.

  10. Location Intelligence Solutions

    International Nuclear Information System (INIS)

    Schmidt, D.

    2015-01-01

    Location Intelligence (LI) means using the spatial dimension of information as a key to support business processes. This spatial dimension has to be defined by geographic coordinates. Storing these spatial objects in a database allows for attaching a 'meaning' to them, like 'current position', 'border', 'building' or 'room'. Now the coordinates represent real-world objects, which can be relevant for the measurement, documentation, control or optimization of (parameters of) business processes aiming at different business objectives. But LI can only be applied, if the locations can be determined with an accuracy (in space and time) appropriate for the business process in consideration. Therefore the first step in any development of a LI solution is the analysis of the business process itself regarding its requirements for spatial and time resolution and accuracy. The next step is the detailed analysis of the surrounding conditions of the process: Does the process happen indoor and/or outdoor? Are there moving objects? If yes, how fast are they? How does the relevant environment look like? Is technical infrastructure available? Is the process restricted by regulations? As a result, a proper Location Detection Technology (LDT) has to be chosen in order to get reliable and accurate positions of the relevant objects. At the highly challenging conditions of the business processes IAEA inspectors are working with, the chosen LDTs have to deliver reliable positioning on ''room-level'' accuracy, even if there is no location enabling infrastructure in place, the objects (people) mostly are indoors and have to work under strong regulations. The presentation will give insights into innovative LI solutions based on technologies of different LDT providers. Pros and cons of combinations of different LDT (like multi- GNSS, IMU, camera, and human interaction based positioning) will be discussed from the

  11. Solute diffusivity in undisturbed soil

    DEFF Research Database (Denmark)

    Lægdsmand, Mette; Møldrup, Per; Schjønning, Per

    2012-01-01

    Solute diffusivity in soil plays a major role in many important processes with relation to plant growth and environmental issues. Soil solute diffusivity is affected by the volumetric water content as well as the morphological characteristics of water-filled pores. The solute diffusivity in intact...

  12. Peripheral adrenergic receptors in hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.; Insel, P. A.

    1990-01-01

    Increased sympathoadrenal activity appears to play an important role in the development or maintenance of elevated blood pressure in hypertensive patients and various animal models of hypertension. Alterations of adrenergic receptor number or responsiveness might contribute to this increased

  13. Are olfactory receptors really olfactive?

    DEFF Research Database (Denmark)

    Giorgi, Franco; Maggio, Roberto; Bruni, Luis Emilio

    2011-01-01

    environmental conditions. By adopting this standpoint, the functional attribution as olfactory or chemotactic sensors to these receptors should not be seen neither as a cause conditioning receptor gene expression, nor as a final effect resulting from genetically predetermined programs, but as a direct...... and odor-decoding processes. However, this type of explanation does not entirely justify the role olfactory receptors have played during evolution, since they are also expressed ectopically in different organs and/or tissues. Homologous olfactory genes have in fact been found in such diverse cells and....../or organs as spermatozoa, testis and kidney where they are assumed to act as chemotactic sensors or renin modulators. To justify their functional diversity, homologous olfactory receptors are assumed to share the same basic role: that of conferring a self-identity to cells or tissues under varying...

  14. Nuclear Receptor Signaling Atlas (NURSA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Nuclear Receptor Signaling Atlas (NURSA) is designed to foster the development of a comprehensive understanding of the structure, function, and role in disease...

  15. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  16. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Green, Mark A.

    2000-01-01

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  17. [The receptor theory of atherosclerosis].

    Science.gov (United States)

    Likhoded, V G; Bondarenko, V M; Gintsburg, A L

    2010-01-01

    Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

  18. Xenobiotics and the Glucocorticoid Receptor

    International Nuclear Information System (INIS)

    Gulliver, Linda S M

    2017-01-01

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  19. Xenobiotics and the Glucocorticoid Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Gulliver, Linda S M, E-mail: linda.gulliver@otago.ac.nz

    2017-03-15

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  20. Nuclear Receptors, RXR, and the Big Bang.

    Science.gov (United States)

    Evans, Ronald M; Mangelsdorf, David J

    2014-03-27

    Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Fibroblast growth factor receptors in breast cancer.

    Science.gov (United States)

    Wang, Shuwei; Ding, Zhongyang

    2017-05-01

    Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

  2. Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

    NARCIS (Netherlands)

    Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

    2012-01-01

    BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

  3. Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival

    OpenAIRE

    Zhaochuan Liu; Haotian Lin; Chulong Huang; Wan Chen; Wu Xiang; Yu Geng; Weirong Chen

    2015-01-01

    Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution...

  4. Expression of GABAergic receptors in mouse taste receptor cells.

    Directory of Open Access Journals (Sweden)

    Margaret R Starostik

    Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

  5. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  6. Site-directed cross-linking: establishing the dimeric structure of the aspartate receptor of bacterial chemotaxis

    International Nuclear Information System (INIS)

    Milligan, D.L.; Koshland, D.E. Jr.

    1988-01-01

    Cysteine residues introduced at specific locations in the aspartate receptor of Salmonella typhimurium provide anchor points for cross-linking and serve as chemical markers for structural studies of this oligomeric receptor. These markers have been used to measure the rate of subunit exchange between oligomeric receptors and to show that ligand binding inhibits this exchange. The cysteine-containing receptors can be oxidatively cross-linked to completion within the oligomeric receptor, indicating that the receptor has an even number of subunits. Based on this observation, a technique has been developed that can be used to determine the oligomeric structure of proteins under a variety of experimental conditions. The technique involves the measurement of the effect of dilution by cysteineless receptor subunits on cross-linking and reveals that the aspartate receptor is dimeric in detergent solution, in a mixed-micelle system, and in reconstituted membrane vesicles. Binding of aspartate does not change the oligomeric structure of the receptor, indicating that transmembrane signaling occurs within an oligomeric receptor of constant size

  7. Future climate. Engineering solutions

    Energy Technology Data Exchange (ETDEWEB)

    Ferdinand, J.F.; Hagedorn-Rasmussen, P.; Fonnesbech, B.

    2009-09-15

    Future Climate Engineering Solutions - Joint Report is the common output and a documentation of more than 1 year's effort by 13 engineering associations - in 12 countries - to demonstrate how technologies can combat climate change. The report consists of three parts: Summaries of 10 national climate plans and technology prospects, 5 Key Common Findings, and a Climate Call from Engineers to create a new global climate treaty. The basic assumption of the project is recognition that GHG emissions, and their concentration in the atmosphere, must be reduced to a sustainable level. The project definition of a sustainable level is equivalent to the best-case stabilisation scenario which was presented in the 4th Assessment Report (AR4) by the UN Intergovernmental Panel on Climate Change (IPCC), whereby the global mean temperature is most likely to stabilise at 2.0-2.4 deg. C. The Future Climate website www.futureclimate.info holds more information about the project, including possibility to download project material, including the full national climate plans.

  8. Plutonium solution analyzer

    International Nuclear Information System (INIS)

    Burns, D.A.

    1994-09-01

    A fully automated analyzer has been developed for plutonium solutions. It was assembled from several commercially available modules, is based upon segmented flow analysis, and exhibits precision about an order of magnitude better than commercial units (0.5%-O.05% RSD). The system was designed to accept unmeasured, untreated liquid samples in the concentration range 40-240 g/L and produce a report with sample identification, sample concentrations, and an abundance of statistics. Optional hydraulics can accommodate samples in the concentration range 0.4-4.0 g/L. Operating at a typical rate of 30 to 40 samples per hour, it consumes only 0.074 mL of each sample and standard, and generates waste at the rate of about 1.5 mL per minute. No radioactive material passes through its multichannel peristaltic pump (which remains outside the glovebox, uncontaminated) but rather is handled by a 6-port, 2-position chromatography-type loop valve. An accompanying computer is programmed in QuickBASIC 4.5 to provide both instrument control and data reduction. The program is truly user-friendly and communication between operator and instrument is via computer screen displays and keyboard. Two important issues which have been addressed are waste minimization and operator safety (the analyzer can run in the absence of an operator, once its autosampler has been loaded)

  9. Simple de Sitter solutions

    International Nuclear Information System (INIS)

    Silverstein, Eva

    2008-01-01

    We present a framework for de Sitter model building in type IIA string theory, illustrated with specific examples. We find metastable de Sitter (dS) minima of the potential for moduli obtained from a compactification on a product of two nil three-manifolds (which have negative scalar curvature) combined with orientifolds, branes, fractional Chern-Simons forms, and fluxes. As a discrete quantum number is taken large, the curvature, field strengths, inverse volume, and four-dimensional string coupling become parametrically small, and the de Sitter Hubble scale can be tuned parametrically smaller than the scales of the moduli, Kaluza Klein (KK), and winding mode masses. A subtle point in the construction is that although the curvature remains consistently weak, the circle fibers of the nilmanifolds become very small in this limit (though this is avoided in illustrative solutions at modest values of the parameters). In the simplest version of the construction, the heaviest moduli masses are parametrically of the same order as the lightest KK and winding masses. However, we provide a method for separating these marginally overlapping scales, and more generally the underlying supersymmetry of the model protects against large corrections to the low-energy moduli potential

  10. Plutonium solution analyzer

    Energy Technology Data Exchange (ETDEWEB)

    Burns, D.A.

    1994-09-01

    A fully automated analyzer has been developed for plutonium solutions. It was assembled from several commercially available modules, is based upon segmented flow analysis, and exhibits precision about an order of magnitude better than commercial units (0.5%-O.05% RSD). The system was designed to accept unmeasured, untreated liquid samples in the concentration range 40-240 g/L and produce a report with sample identification, sample concentrations, and an abundance of statistics. Optional hydraulics can accommodate samples in the concentration range 0.4-4.0 g/L. Operating at a typical rate of 30 to 40 samples per hour, it consumes only 0.074 mL of each sample and standard, and generates waste at the rate of about 1.5 mL per minute. No radioactive material passes through its multichannel peristaltic pump (which remains outside the glovebox, uncontaminated) but rather is handled by a 6-port, 2-position chromatography-type loop valve. An accompanying computer is programmed in QuickBASIC 4.5 to provide both instrument control and data reduction. The program is truly user-friendly and communication between operator and instrument is via computer screen displays and keyboard. Two important issues which have been addressed are waste minimization and operator safety (the analyzer can run in the absence of an operator, once its autosampler has been loaded).

  11. Insight solutions are correct more often than analytic solutions

    Science.gov (United States)

    Salvi, Carola; Bricolo, Emanuela; Kounios, John; Bowden, Edward; Beeman, Mark

    2016-01-01

    How accurate are insights compared to analytical solutions? In four experiments, we investigated how participants’ solving strategies influenced their solution accuracies across different types of problems, including one that was linguistic, one that was visual and two that were mixed visual-linguistic. In each experiment, participants’ self-judged insight solutions were, on average, more accurate than their analytic ones. We hypothesised that insight solutions have superior accuracy because they emerge into consciousness in an all-or-nothing fashion when the unconscious solving process is complete, whereas analytic solutions can be guesses based on conscious, prematurely terminated, processing. This hypothesis is supported by the finding that participants’ analytic solutions included relatively more incorrect responses (i.e., errors of commission) than timeouts (i.e., errors of omission) compared to their insight responses. PMID:27667960

  12. Menthol binding and inhibition of α7-nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Abrar Ashoor

    Full Text Available Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+-dependent Cl(- channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+ chelator BAPTA and perfusion with Ca(2+-free bathing solution containing Ba(2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

  13. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    Sakai, Yukio

    1979-01-01

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  14. Properties of scintillator solutes

    International Nuclear Information System (INIS)

    Fluornoy, J.M.

    1998-06-01

    This special report summarizes measurements of the spectroscopic and other properties of the solutes that were used in the preparation of several new liquid scintillators developed at EG and G/Energy Measurements/Santa Barbara Operations (the precursor to Bechtel Nevada/Special Technologies Laboratory) on the radiation-to-light converter program. The data on the individual compounds are presented in a form similar to that used by Prof. Isadore Berlman in his classic handbook of fluorescence spectra. The temporal properties and relative efficiencies of the new scintillators are presented in Table 1, and the efficiencies as a function of wavelength are presented graphically in Figure 1. In addition, there is a descriptive glossary of the abbreviations used herein. Figure 2 illustrates the basic structures of some of the compounds and of the four solvents reported in this summary. The emission spectra generally exhibit more structure than the absorption spectra, with the result that the peak emission wavelength for a given compound may lie several nm away from the wavelength, λ avg , at the geometric center of the emission spectrum. Therefore, the author has chosen to list absorption peaks, λ max , and emission λ avg values in Figures 3--30, as being most illustrative of the differences between the compounds. The compounds, BHTP, BTPB, ADBT, and DPTPB were all developed on this program. P-terphenyl, PBD, and TPB are commercially available blue emitters. C-480 and the other longer-wavelength emitters are laser dyes available commercially from Exciton Corporation. 1 ref., 30 figs

  15. Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Gopez, V.; Delis, F.; Michaelides, M.; Grand, D.K.; Wang, G.-J.; Kunos, G.; Volkow, N.D.

    2011-01-01

    The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

  16. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  17. Scavenger receptors in homeostasis and immunity.

    Science.gov (United States)

    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  18. Photo-antagonism of the GABAA receptor.

    Science.gov (United States)

    Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

    2014-07-29

    Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

  19. CEFR information management system solution

    International Nuclear Information System (INIS)

    Lu Fei; Zhao Jia'ning

    2011-01-01

    Based on finished information resources planning scheme for China sodium cooled experimental fast breeder reactor and the advanced information resources management solution concepts were applied, we got the building solution of CEFR information management systems. At the same time, the technical solutions of systems structures, logic structures, physical structures, development platforms and operation platforms for information resources management system in fast breeder reactors were developed, which provided programmatic introductions for development works in future. (authors)

  20. Indium flotation from hydrometallurgical solutions

    International Nuclear Information System (INIS)

    Sviridov, V.V.; Mal'tsev, G.I.; Petryakova, N.K.; Gomzikov, A.I.

    1980-01-01

    The principal possibility of flotation of indium small quantities (10 -4 gxion/l) is established from sulphuric-acid solutions of leaching converter dusts of the copper melting production in the form of complex compounds with sodium hexametaphosphate and cation-active nitrogen-containing surfactants. It is shown that the flotation process effectiveness is determined by the molar ratio of hexametaphosphate and collector introduced into the solution, solution oxidity and surfactant nature

  1. HGMF of 10-L solutions

    International Nuclear Information System (INIS)

    Larkin, K.A.

    1994-01-01

    This test plan describes the activities associated with the High Gradient Magnetic Filtration (HGMF) of plutonium-bearing solutions (10-L). The 10-L solutions were received from Argonne National Laboratories in 1972, are highly acidic, and are considered unstable. The purpose of the testing is to show that HGMF is an applicable method of removing plutonium precipitates from solution. The plutonium then can be stored safely in a solid form

  2. Structure and dynamics of solutions

    CERN Document Server

    Ohtaki, H

    2013-01-01

    Recent advances in the study of structural and dynamic properties of solutions have provided a molecular picture of solute-solvent interactions. Although the study of thermodynamic as well as electronic properties of solutions have played a role in the development of research on the rate and mechanism of chemical reactions, such macroscopic and microscopic properties are insufficient for a deeper understanding of fast chemical and biological reactions. In order to fill the gap between the two extremes, it is necessary to know how molecules are arranged in solution and how they change their pos

  3. Enhanced safeguards via solution monitoring

    International Nuclear Information System (INIS)

    Burr, T.; Wangen, L.

    1996-09-01

    Solution monitoring is defined as the essentially continuous monitoring of solution level, density, and temperature in all tanks in the process that contain, or could contain, safeguards-significant quantities of nuclear material. This report describes some of the enhancements that solution monitoring could make to international safeguards. The focus is on the quantifiable benefits of solution monitoring, but qualitatively, solution monitoring can be viewed as a form of surveillance. Quantitatively, solution monitoring can in some cases improve diversion detection probability. For example, the authors show that under certain assumptions, solution monitoring can be used to reduce the standard deviation of the annual material balance, σ MB , from approximately 17 kg to approximately 4 kg. Such reduction in σ MB will not always be possible, as they discuss. However, in all cases, solution monitoring would provide assurance that the measurement error models are adequate so that one has confidence in his estimate of σ MB . Some of the results in this report were generated using data that were simulated with prototype solution monitoring software that they are developing. An accompanying document describes that software

  4. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor

    DEFF Research Database (Denmark)

    Rasmussen, Søren Gøgsig Faarup; Choi, Hee-Jung; Rosenbaum, Daniel M

    2007-01-01

    Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was ...

  5. A non-multimacrocyclic heteroditopic receptor that cooperatively binds and effectively extracts KAcO salt.

    Science.gov (United States)

    Zakrzewski, Maciej; Kwietniewska, Natalia; Walczak, Wojciech; Piątek, Piotr

    2018-06-06

    Prepared in only three synthetic steps, a non-multimacrocyclic heteroditopic receptor binds potassium salts of halides and carboxylates with unusually high cooperativity, suggesting salt binding as associated ion-pairs. Unprecedented extraction of highly hydrophilic KAcO salt from water to organic solution is also demonstrated.

  6. A saving solution.

    Science.gov (United States)

    Mckee, N

    1983-10-01

    Dr. Mujibur Rahaman, senior scientist at the International Center for Diarrheal Disease Research in Bangladesh, was interviewed recently in regard to oral rehydration therapy (ORT), a simple and inexpensive way of treating the loss of essential fluids and minerals that accompanies diarrhea. According to Rahaman, ORT, developed quite a while ago, is recently gaining more publicity and wider acceptance as a menas of replacing the water and electrolytes lost during acute diarrhea attack. The standard ingredients of the ORT mixture, as it is used in Bangladesh, are 3.5 gm of sodium chloride, or common salt, 2.5 gm sodium bicarbonate, and 1 gm of potassium chloride. To this one should add either 20 gm of glucose or 40 gm of sugar. This mixture should be dissolved in 1 liter of plain drinking water. Plain sugar is good enough. How much is needed depends on the severity and the duration of diarrhea. Calculations have shown that, as a rule of thumb, a child of 10-12 kg may require little more than a liter in about 24 hours. If the child has diarrhea of sufficient severity, it may require more than a liter. If the diarrhea is prolonged, it may require 2 liters. For children who are in danger of dying from dehydration, parents are warned to be watchful because further treatment and follow-up may be required. In Bangladesh a national program is currently providing the ORT in remote rural areas. At present about 1/3 of Bangladesh is covered. The national health service is distributing the solution free of cost in the villages where they have health volunteers. Although ORT is simple to make and simple to administer, one has to exercise some degree of caution with it in order to prevent infants getting dangerous symptoms like hypernatremia. ORT makes it possible for health educators to enter into the family. It is not totally correct to say water is the main problem or causative factor in producing diarrhea. In infantile diarrhea, the cause is most often a virus. Viral

  7. β2-Adrenergic receptors and G-protein-coupled receptor kinase 2 in rabbit pleural mesothelium.

    Science.gov (United States)

    Sironi, Chiara; Bodega, Francesca; Armilli, Marta; Porta, Cristina; Zocchi, Luciano; Agostoni, Emilio

    2010-09-30

    Former studies on net rate of liquid absorption from small Ringer or 1% albumin-Ringer hydrothoraces in rabbits indicated that Na+ transport and solute-coupled liquid absorption by mesothelium is increased by pleural liquid dilution, and stimulation of β2-adrenoreceptors (β2AR). In this research we tried to provide molecular evidence for β2AR in visceral and parietal mesothelium of rabbit pleura. Moreover, because prolonged stimulation of β2AR may lead to desensitization mediated by G-protein-coupled receptor kinase 2 (GRK2), we also checked whether GRK2 is expressed in pleural mesothelium. To this end we performed immunoblot assays on total protein extracts from scraped visceral and parietal mesothelium, and from cultured pleural mesothelial cells of rabbits. All three samples showed β2AR and GRK2 specific bands. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Upregulation of endothelin ETB receptor-mediated vasoconstriction in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Eskesen, Karen; Edvinsson, Lars

    2006-01-01

    The aim of this study was to examine if endothelin ET(B) receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ET(B) receptors was studied by measuring the change in isometric tension in rings of left anterior......(+)-solution was not modified after 1 day in culture medium. The experiments indicate that organ culture of rat coronary arteries upregulate endothelin ET(B) receptor-mediated contraction by inducing synthesis of new protein....... descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ET(B) receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbecco's Modified Eagle's Medium, Sarafotoxin 6c induced a concentration dependent contraction...

  9. TAM receptor signaling in development.

    Science.gov (United States)

    Burstyn-Cohen, Tal

    2017-01-01

    TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes. Combinatorial ligand-receptor interactions may elicit different molecular and cellular responses. Many of the TAM regulatory functions are essentially developmental, taking place both during embryogenesis and postnatally. This review highlights current knowledge on the role of TAM receptors and their ligands during these developmental processes in the immune, nervous, vascular and reproductive systems.

  10. How calcium makes endocytic receptors attractive

    DEFF Research Database (Denmark)

    Andersen, Christian B F; Moestrup, Søren K

    2014-01-01

    of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

  11. Lessons from crystal structures of kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Frydenvang, Karla Andrea; Pickering, Darryl S

    2017-01-01

    Kainate receptors belong to the family of ionotropic glutamate receptors. These receptors assemble from five subunits (GluK1-5) into tetrameric ion channels. Kainate receptors are located at both pre- and postsynaptic membranes in the central nervous system where they contribute to excitatory...... synaptic transmission and modulate network excitability by regulating neurotransmitter release. Dysfunction of kainate receptors has been implicated in several neurological disorders such as epilepsy, schizophrenia and depression. Here we provide a review on the current understanding of kainate receptor...

  12. Calibration of 232U solution

    International Nuclear Information System (INIS)

    Galan Valera, M. P.; Acena Berrenechea, M. L.

    1988-01-01

    A method for as certain the activity by alpha spectroscopy with semiconductor detectors, of a solution of 232U is presented. It consists of the comparison with a 233U solution activity previously measured in a gridded ionization chamber of 2π geometry. The total measurement uncertainty is about + - 0,02. (Author) 9 refs

  13. Calibration of uranium 232 solution

    International Nuclear Information System (INIS)

    Galan, M.P.; Acena, M.L.

    1988-01-01

    A method for acertainning the activity by alpha spectroscopy with semiconductor detectors, of a solution of Uranium-232 is presented. It consists of the comparison with a Uranium-233 solution activity previously measured in a gridded ionization chamber of 2 π geometry. The total measurement uncertainty is about +- 0,02. (Author)

  14. Requirements Engineering: Solutions and Trends

    NARCIS (Netherlands)

    Ebert, C.; Wieringa, Roelf J.; Aurum, A.; Wohlin, C.

    2005-01-01

    This last chapter of the book describes solutions and trends in the discipline of RE. Starting from a wrap-up of what was presented throughout this book, it suggests a framework of requirements engineering and indicates what current solutions are available in this framework. Beyond providing a short

  15. A Wronskian of Jost solutions

    International Nuclear Information System (INIS)

    Corona-Corona, Gulmaro

    2004-01-01

    Based on the standard fact that any matrix potential u=u(x) determines a family of Jost solutions whose parameter runs analytically (continuously) on the (closed) half planes, respectively, the zeros of a suitable matrix valued Wronskian of a Jost solution pair are explored

  16. Some exact Bradlow vortex solutions

    Energy Technology Data Exchange (ETDEWEB)

    Gudnason, Sven Bjarke [Institute of Modern Physics, Chinese Academy of Sciences,Lanzhou 730000 (China); Nitta, Muneto [Department of Physics, and Research and Education Center for Natural Sciences, Keio University,Hiyoshi 4-1-1, Yokohama, Kanagawa 223-8521 (Japan)

    2017-05-08

    We consider the Bradlow equation for vortices which was recently found by Manton and find a two-parameter class of analytic solutions in closed form on nontrivial geometries with non-constant curvature. The general solution to our class of metrics is given by a hypergeometric function and the area of the vortex domain by the Gaussian hypergeometric function.

  17. Exploring manufacturing solutions for SMEs

    DEFF Research Database (Denmark)

    Radziwon, Agnieszka; Blichfeldt, Henrik; Bilberg, Arne

    This exploratory study provides an overview over current state of manufacturing solutions in small and medium sized enterprises (SMEs) in region of Southern Denmark. Building on manufacturing paradigms, this paper reveals relevant aspects for the development and implementation of improving SMEs...... of manufacturing solutions, which are required to increase their competitiveness and assure sustainable growth....

  18. Thermotransport in interstitial solid solutions

    International Nuclear Information System (INIS)

    Fogel'son, R.L.

    1982-01-01

    On the basis of literature data the problem of thermotransport of impurities (H, N, O, C) in interstitial solid solutions is considered. It is shown that from experimental data on the thermotransport an important parameter of dissolved atoms can be found which characterizes atom state in these solutions-enthalpy of transport

  19. Analytic solutions of hydrodynamics equations

    International Nuclear Information System (INIS)

    Coggeshall, S.V.

    1991-01-01

    Many similarity solutions have been found for the equations of one-dimensional (1-D) hydrodynamics. These special combinations of variables allow the partial differential equations to be reduced to ordinary differential equations, which must then be solved to determine the physical solutions. Usually, these reduced ordinary differential equations are solved numerically. In some cases it is possible to solve these reduced equations analytically to obtain explicit solutions. In this work a collection of analytic solutions of the 1-D hydrodynamics equations is presented. These can be used for a variety of purposes, including (i) numerical benchmark problems, (ii) as a basis for analytic models, and (iii) to provide insight into more complicated solutions

  20. Whole analogy between Daniel Bernoulli solution and direct kinematics solution

    Directory of Open Access Journals (Sweden)

    Filipović Mirjana

    2010-01-01

    Full Text Available In this paper, the relationship between the original Euler-Bernoulli's rod equation and contemporary knowledge is established. The solution which Daniel Bernoulli defined for the simplest conditions is essentially the solution of 'direct kinematics'. For this reason, special attention is devoted to dynamics and kinematics of elastic mechanisms configuration. The Euler-Bernoulli equation and its solution (used in literature for a long time should be expanded according to the requirements of the mechanisms motion complexity. The elastic deformation is a dynamic value that depends on the total mechanism movements dynamics. Mathematical model of the actuators comprises also elasticity forces.

  1. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

  2. Stability of solubilized benzodiazepine receptors

    NARCIS (Netherlands)

    Janssen, M.J; Ensing, K; de Zeeuw, R.A

    1997-01-01

    According to the observations of other researchers, benzodiazepine receptors solubilized with sodium deoxycholate are unstable, but stability can be improved by exchanging deoxycholate for Triton X-100. In our experiments we conclude that the choice of detergent is not the restrictive factor for the

  3. Serum transferrin receptor in polycythemia.

    Science.gov (United States)

    Manteiga, R; Remacha, A F; Sardà, M P; Ubeda, J

    1998-10-01

    We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.

  4. FMRFamide receptors of Helix aspersa

    International Nuclear Information System (INIS)

    Payza, K.

    1988-01-01

    A receptor binding assay and an isolated heart bioassay were used to identify and characterize the FMRFamide receptors in Helix. In the heart bioassay, FMRFamide increased myocardial contraction force. A potent FMRFamide analog, desaminoTyr-Phe-norLeu-arg-Phe-amide (daYFnLRFamide), was used as a radioiodinated receptor ligand. The high affinity binding of 125 I-daYFnLRFamide at 0 degree C to Helix brain membranes was reversible, saturable, pH-dependent and specific, with a K D of 13-14 nM. A lower affinity (245 nM) site was also observed. Radioligand binding sites were also identified in the heart, male reproductive organs and digestive organs. The structure-activity relations (SAR) of cardiostimulation correlated with the specificity of 125 I-daYFnLRFamide binding to brain and heart receptors. The SAR were similar to those of other molluscan FMRFamide bioassays, except that they showed a marked preference for some analogs with blocked amino-terminals

  5. Pharmacological approach of the receptors

    International Nuclear Information System (INIS)

    Puech, A.J.

    1989-01-01

    This paper explains the three main goals for clinical positron emission tomography (PET) studies: detection of receptor abnormalities in groups of patients to propose therapeutic indication of new ligands; validation of current hypothesis of drug effect; rational clinical drug development specially for dose-finding studies. (H.W.)

  6. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik

    2006-01-01

    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...

  7. NMDA receptors and memory encoding.

    Science.gov (United States)

    Morris, Richard G M

    2013-11-01

    It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can

  8. Ror receptor tyrosine kinases: orphans no more

    OpenAIRE

    Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

    2008-01-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

  9. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  10. Synaptic Bistability Due to Nucleation and Evaporation of Receptor Clusters

    KAUST Repository

    Burlakov, V. M.; Emptage, N.; Goriely, A.; Bressloff, P. C.

    2012-01-01

    interacting receptors and is stabilized against clustering by a high nucleation barrier. The other state contains a receptor gas in equilibrium with a large cluster of immobile receptors, which is stabilized by the turnover rate of receptors into and out

  11. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

    1998-01-01

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  12. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  13. Receptores de progesterona en meningioma.

    Directory of Open Access Journals (Sweden)

    Herminio Ojeda Di Ninno

    1995-04-01

    Full Text Available Objetivo: Determinar la presencia de los receptores de progesterona en meningiomas y su frecuencia mediante la inmunohistoquímica. Material y Métodos: Se analizaron 24 muestras provenientes de pacientes intervenidos quirúrgicamente en el Instituto Nacional de Enfermedades Neoplásicas entre los años 1990 y 1992 con diagnóstico anatomopatológico de meningioma. La determinación de los receptores se hizo mediante una técnica de inmunohistoquímica rápida que permite el estudio de tejidos fijados previamente en parafina. Resultados: De los 24 casos estudiados, nueve resultaron ser positivos en la determinación de receptores de progesterona (37%. Se pudo observar un marcado predominio dentro del grupo femenino quienes constituyeron 8/9 casos positivos. Conclusiones: El empleo de esta reciente técnica de inmunohistoquímica aplicada a tejido de fijado en parafina, nos ha permitido confirmar la presencia de receptores de progesterona en meningiomas con una frecuencia elevada que creemos amerita un estudio más amplio de manera sistemática que incluya la intervención terapéutica mediante el uso de antiprogestágenos, como el Mifepristone o RU 486. De este estudio podrían beneficiarse no sólo pacientes operados recientemente sino aquellos que, intervenidos en el pasado sean detectados como portadores de receptores de progesterona mediante la aplicación de esta novedosa técnica (Rev Med Hered 1995; 6: 121-130.

  14. Solutions for the food processing industry; Shokuhin seizogyo solution

    Energy Technology Data Exchange (ETDEWEB)

    Toda, T; Iwami, N [Fuji Electric Co. Ltd., Tokyo (Japan)

    1999-09-10

    To improve quality control and maintain stable operation, the food processing industry requires problem solutions in total, including not only processing and operation control divisions but also quality control, design and production technology, and maintenance divisions. This paper describes solutions for HACCP (hazard analysis critical control point) support, quality control, and maintenance, in order to improve the quality level, ensure traceability and realize stable processing operations. (author)

  15. A new family of insect tyramine receptors

    DEFF Research Database (Denmark)

    Cazzamali, Giuseppe; Klærke, Dan Arne; Grimmelikhuijzen, Cornelis J P

    2005-01-01

    in the genomic databases from the malaria mosquito Anopheles gambiae and the honeybee Apis mellifera. These four tyramine or tyramine-like receptors constitute a new receptor family that is phylogenetically distinct from the previously identified insect octopamine/tyramine receptors. The Drosophila tyramine...

  16. Imaging of receptors in clinical neurosciences

    NARCIS (Netherlands)

    Korf, J

    This article deals with the question why should one determine receptors in the brain with positron and single photon emission tomography (PET and SPECT, respectively). Radiopharmaceuticals for a wide variety of receptors are available now. Receptors studies with PET and SPECT have thus far focused

  17. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, L.D.C.

    2013-01-01

    The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

  18. Molecular pharmacology of human NMDA receptors

    DEFF Research Database (Denmark)

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard

    2012-01-01

    N-methyl-d-aspartate (NMDA) receptors are ionotropic glutamate receptors that mediate excitatory neurotransmission. NMDA receptors are also important drug targets that are implicated in a number of pathophysiological conditions. To facilitate the transition from lead compounds in pre-clinical ani...

  19. Anisotropic solutions by gravitational decoupling

    Science.gov (United States)

    Ovalle, J.; Casadio, R.; da Rocha, R.; Sotomayor, A.

    2018-02-01

    We investigate the extension of isotropic interior solutions for static self-gravitating systems to include the effects of anisotropic spherically symmetric gravitational sources by means of the gravitational decoupling realised via the minimal geometric deformation approach. In particular, the matching conditions at the surface of the star with the outer Schwarzschild space-time are studied in great detail, and we describe how to generate, from a single physically acceptable isotropic solution, new families of anisotropic solutions whose physical acceptability is also inherited from their isotropic parent.

  20. Solution of the Baxter equation

    International Nuclear Information System (INIS)

    Janik, R.A.

    1996-01-01

    We present a method of construction of a family of solutions of the Baxter equation arising in the Generalized Leading Logarithmic Approximation (GLLA) of the QCD pomeron. The details are given for the exchange of N = 2 reggeons but everything can be generalized in a straightforward way to arbitrary N. A specific choice of solutions is shown to reproduce the correct energy levels for half integral conformal weights. It is shown that the Baxter's equation must be supplemented by an additional condition on the solution. (author)

  1. Anisotropic solutions by gravitational decoupling

    Energy Technology Data Exchange (ETDEWEB)

    Ovalle, J. [Silesian University in Opava, Institute of Physics and Research Centre of Theoretical Physics and Astrophysics, Faculty of Philosophy and Science, Opava (Czech Republic); Universidad Simon Bolivar, Departamento de Fisica, Caracas (Venezuela, Bolivarian Republic of); Casadio, R. [Alma Mater Universita di Bologna, Dipartimento di Fisica e Astronomia, Bologna (Italy); Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Rocha, R. da [Universidade Federal do ABC (UFABC), Centro de Matematica, Computacao e Cognicao, Santo Andre, SP (Brazil); Sotomayor, A. [Universidad de Antofagasta, Departamento de Matematicas, Antofagasta (Chile)

    2018-02-15

    We investigate the extension of isotropic interior solutions for static self-gravitating systems to include the effects of anisotropic spherically symmetric gravitational sources by means of the gravitational decoupling realised via the minimal geometric deformation approach. In particular, the matching conditions at the surface of the star with the outer Schwarzschild space-time are studied in great detail, and we describe how to generate, from a single physically acceptable isotropic solution, new families of anisotropic solutions whose physical acceptability is also inherited from their isotropic parent. (orig.)

  2. Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for alpha radionuclide therapy

    International Nuclear Information System (INIS)

    Ogawa, Kazuma; Mizuno, Yoshiaki; Washiyama, Kohshin; Shiba, Kazuhiro; Takahashi, Naruto; Kozaka, Takashi; Watanabe, Shigeki; Shinohara, Atsushi; Odani, Akira

    2015-01-01

    Introduction: Sigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated 131 I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[ 131 I]pIV], which has a high affinity for sigma receptors. Therefore, (+)-[ 131 I]pIV significantly inhibited tumor cell proliferation in tumor-bearing mice. In the present study, we report the synthesis and the in vitro and in vivo characterization of (+)-[ 211 At]pAtV, an 211 At-labeled sigma receptor ligand, that has potential use in alpha-radionuclide receptor therapy. Methods: The radiolabeled sigma receptor ligand (+)-[ 211 At]pAtV was prepared using a standard halogenation reaction generating a 91% radiochemical yield with 98% purity after HPLC purification. The partition coefficient of (+)-[ 211 At]pAtV was measured. Cellular uptake experiments and in vivo biodistribution experiments were performed using a mixed solution of (+)-[ 211 At]pAtV and (+)-[ 125 I]pIV; the human prostate cancer cell line DU-145, which expresses high levels of the sigma receptors, and DU-145 tumor-bearing mice. Results: The lipophilicity of (+)-[ 211 At]pAtV was similar to that of (+)-[ 125 I]pIV. DU-145 cellular uptake and the biodistribution patterns in DU-145 tumor-bearing mice at 1 h post-injection were also similar between (+)-[ 211 At]pAtV and (+)-[ 125 I]pIV. Namely, (+)-[ 211 At]pAtV demonstrated high uptake and retention in tumor via binding to sigma receptors. Conclusion: These results indicate that (+)-[ 211 At]pAtV could function as an new agent for alpha-radionuclide receptor therapy.

  3. Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for alpha radionuclide therapy.

    Science.gov (United States)

    Ogawa, Kazuma; Mizuno, Yoshiaki; Washiyama, Kohshin; Shiba, Kazuhiro; Takahashi, Naruto; Kozaka, Takashi; Watanabe, Shigeki; Shinohara, Atsushi; Odani, Akira

    2015-11-01

    Sigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated (131)I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[(131)I]pIV], which has a high affinity for sigma receptors. Therefore, (+)-[(131)I]pIV significantly inhibited tumor cell proliferation in tumor-bearing mice. In the present study, we report the synthesis and the in vitro and in vivo characterization of (+)-[(211)At]pAtV, an (211)At-labeled sigma receptor ligand, that has potential use in alpha-radionuclide receptor therapy. The radiolabeled sigma receptor ligand (+)-[(211)At]pAtV was prepared using a standard halogenation reaction generating a 91% radiochemical yield with 98% purity after HPLC purification. The partition coefficient of (+)-[(211)At]pAtV was measured. Cellular uptake experiments and in vivo biodistribution experiments were performed using a mixed solution of (+)-[(211)At]pAtV and (+)-[(125)I]pIV; the human prostate cancer cell line DU-145, which expresses high levels of the sigma receptors, and DU-145 tumor-bearing mice. The lipophilicity of (+)-[(211)At]pAtV was similar to that of (+)-[(125)I]pIV. DU-145 cellular uptake and the biodistribution patterns in DU-145 tumor-bearing mice at 1h post-injection were also similar between (+)-[(211)At]pAtV and (+)-[(125)I]pIV. Namely, (+)-[(211)At]pAtV demonstrated high uptake and retention in tumor via binding to sigma receptors. These results indicate that (+)-[(211)At]pAtV could function as an new agent for alpha-radionuclide receptor therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Identifiability and error minimization of receptor model parameters with PET

    International Nuclear Information System (INIS)

    Delforge, J.; Syrota, A.; Mazoyer, B.M.

    1989-01-01

    The identifiability problem and the general framework for experimental design optimization are presented. The methodology is applied to the problem of the receptor-ligand model parameter estimation with dynamic positron emission tomography data. The first attempts to identify the model parameters from data obtained with a single tracer injection led to disappointing numerical results. The possibility of improving parameter estimation using a new experimental design combining an injection of the labelled ligand and an injection of the cold ligand (displacement experiment) has been investigated. However, this second protocol led to two very different numerical solutions and it was necessary to demonstrate which solution was biologically valid. This has been possible by using a third protocol including both a displacement and a co-injection experiment. (authors). 16 refs.; 14 figs

  5. Analytic Solutions and Resonant Solutions of Hyperbolic Partial Differential Equations

    Science.gov (United States)

    Wagenmaker, Timothy Roger

    This dissertation contains two main subject areas. The first deals with solutions to the wave equation Du/Dt + a Du/Dx = 0, where D/Dt and D/Dx represent partial derivatives and a(t,x) is real valued. The question I studied, which arises in control theory, is whether solutions which are real analytic with respect to the time variable are dense in the space of all solutions. If a is real analytic in t and x, the Cauchy-Kovalevsky Theorem implies that the solutions real analytic in t and x are dense, since it suffices to approximate the initial data by polynomials. The same positive result is valid when a is continuously differentiable and independent of t. This is proved by regularization in time. The hypothesis that a is independent of t cannot be replaced by the weaker assumption that a is real analytic in t, even when it is infinitely smooth. I construct a(t,x) for which the solutions which are analytic in time are automatically periodic in time. In particular these solutions are not dense in the space of all solutions. The second area concerns the resonant interaction of oscillatory waves propagating in a compressible inviscid fluid. An asymptotic description given by Andrew Majda, Rodolfo Rosales, and Maria Schonbek (MRS) involves the genuinely nonlinear quasilinear hyperbolic system Du/Dt + D(uu/2)/Dt + v = 0, Dv/Dt - D(vv/2)/Dt - u = 0. They performed many numerical simulations which indicated that small amplitude solutions of this system tend to evade shock formation, and conjectured that "smooth initial data with a sufficiently small amplitude never develop shocks throughout a long time interval of integration.". I proved that for smooth periodic U(x), V(x) and initial data u(0,x) = epsilonU(x), v(0,x) = epsilonV(x), the solution is smooth for time at least constant times | ln epsilon| /epsilon. This is longer than the lifetime order 1/ epsilon of the solution to the decoupled Burgers equations. The decoupled equation describes nonresonant interaction of

  6. Selective solid-liquid extraction of lithium halide salts using a ditopic macrobicyclic receptor.

    Science.gov (United States)

    Mahoney, Joseph M; Beatty, Alicia M; Smith, Bradley D

    2004-11-29

    A ditopic salt receptor that is known to bind and extract solid NaCl, KCl, NaBr, and KBr into organic solution as their contact ion pairs is now shown by NMR and X-ray crystallography to bind and extract solid LiCl and LiBr as water-separated ion pairs. The receptor can transport these salts from an aqueous phase through a liquid organic membrane with a cation selectivity of K+ > Na+ > Li+. However, the selectivity order is strongly reversed when the receptor extracts solid alkali metal chlorides and bromides into organic solution. For a three-component mixture of solid LiCl, NaCl, and KCl, the ratio of salts extracted and complexed to the receptor in CDCl3 was 94:4:2, respectively. The same strong lithium selectivity was also observed in the case of a three-component mixture of solid LiBr, NaBr, and KBr where the ratio of extracted salts was 92:5:3. This observation is attributed to the unusually high solubility of lithium salts in organic solvents. The study suggests that ditopic receptors with an ability to extract solid salts as associated ion pairs may have application in separation processes.

  7. Simple Solutions for Dry Eye

    Science.gov (United States)

    Patient Education Sheet Simple Solutions for Dry Eye The SSF thanks J. Daniel Nelson, MD, Associate Medical Director, Specialty Care HealthPartners Medical Group & Clinics, and Professor of Ophthalmology, University of ...

  8. Soliton solutions for Q3

    International Nuclear Information System (INIS)

    Atkinson, James; Nijhoff, Frank; Hietarinta, Jarmo

    2008-01-01

    We construct N-soliton solutions to the equation called Q3 in the recent Adler-Bobenko-Suris classification. An essential ingredient in the construction is the relationship of (Q3) δ=0 to the equation proposed by Nijhoff, Quispel and Capel in 1983 (the NQC equation). This latter equation has two extra parameters, and depending on their sign choices we get a 4-to-1 relationship from NQC to (Q3) δ=0 . This leads to a four-term background solution, and then to a 1-soliton solution using a Baecklund transformation. Using the 1SS as a guide allows us to get the N-soliton solution in terms of the τ-function of the Hirota-Miwa equation. (fast track communication)

  9. Clean Energy Solutions Center Services

    Energy Technology Data Exchange (ETDEWEB)

    2016-03-01

    The Solutions Center offers no-cost expert policy assistance, webinars and training forums, clean energy policy reports, data, and tools provided in partnership with more than 35 leading international and regional clean energy organizations.

  10. Exact cosmological solutions for MOG

    International Nuclear Information System (INIS)

    Roshan, Mahmood

    2015-01-01

    We find some new exact cosmological solutions for the covariant scalar-tensor-vector gravity theory, the so-called modified gravity (MOG). The exact solution of the vacuum field equations has been derived. Also, for non-vacuum cases we have found some exact solutions with the aid of the Noether symmetry approach. More specifically, the symmetry vector and also the Noether conserved quantity associated to the point-like Lagrangian of the theory have been found. Also we find the exact form of the generic vector field potential of this theory by considering the behavior of the relevant point-like Lagrangian under the infinitesimal generator of the Noether symmetry. Finally, we discuss the cosmological implications of the solutions. (orig.)

  11. Solute carrier transporters: Pharmacogenomics research ...

    African Journals Online (AJOL)

    Aghogho

    2010-12-27

    Dec 27, 2010 ... This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from .... transporters, drug targets, effect or proteins and meta- ... basolateral or apical plasma membrane of polarized cells,.

  12. Transnistria: Prospects for a Solution

    National Research Council Canada - National Science Library

    Urse, Cristian

    2007-01-01

    .... After the conclusion of the agreement that ended the armed conflict, Chisinau and Tiraspol made efforts to find a political solution, under the supervision of a negotiation mechanism that included...

  13. Anthology of dry storage solutions

    Energy Technology Data Exchange (ETDEWEB)

    Allimann, Nathalie; Otton, Camille [AREVA, Paris (France)

    2012-03-15

    Around 35,000 PWR, BWR or Veer used fuel elements with various enrichment value up to 5%, various cooling time down to 2 years and various burn-ups up to 60,000 Mwd/tU are currently stored in AREVA dry storage solutions. These solutions are delivered in the United States, in Japan and in many European countries like Belgium, Switzerland, Italy, Armenia and Germany. With more than 1000 dry storage solutions delivered all over the world AREVA is the leader on this market. Dealing with dry storage is not an easy task. Products have to be flexible, to be adapted to customer needs and to the national regulations which may stipulate very strict tests such as airplane crash or simulation of earthquake. To develop a dry storage solution for a foreign country means to deal with its national competent authorities. All the national competent authorities do not have the same requirements. Storage conditions may also be different.

  14. Anthology of dry storage solutions

    International Nuclear Information System (INIS)

    Allimann, Nathalie; Otton, Camille

    2012-01-01

    Around 35,000 PWR, BWR or Veer used fuel elements with various enrichment value up to 5%, various cooling time down to 2 years and various burn-ups up to 60,000 Mwd/tU are currently stored in AREVA dry storage solutions. These solutions are delivered in the United States, in Japan and in many European countries like Belgium, Switzerland, Italy, Armenia and Germany. With more than 1000 dry storage solutions delivered all over the world AREVA is the leader on this market. Dealing with dry storage is not an easy task. Products have to be flexible, to be adapted to customer needs and to the national regulations which may stipulate very strict tests such as airplane crash or simulation of earthquake. To develop a dry storage solution for a foreign country means to deal with its national competent authorities. All the national competent authorities do not have the same requirements. Storage conditions may also be different

  15. Rapidly Deployable Mobile Security Solution

    Science.gov (United States)

    2016-03-01

    Chapter V, but Android provides default onboard encryption and it is an optional feature for removable media. Wipe the device (to scrub its stored...Mobile Data Solution Since Android has removed the ability to control mobile data, and it is unknown if a creative solution to shut this feature...down exists, then some exploration on this topic is warranted. Android removed the access to this feature under the auspices of preventing

  16. Some theoretical aspects of hormone receptor determination

    International Nuclear Information System (INIS)

    Sluiter, W.J.

    1981-01-01

    Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

  17. PET kinetic analysis --pitfalls and a solution for the Logan plot.

    Science.gov (United States)

    Kimura, Yuichi; Naganawa, Mika; Shidahara, Miho; Ikoma, Yoko; Watabe, Hiroshi

    2007-01-01

    The Logan plot is a widely used algorithm for the quantitative analysis of neuroreceptors using PET because it is easy to use and simple to implement. The Logan plot is also suitable for receptor imaging because its algorithm is fast. However, use of the Logan plot, and interpretation of the formed receptor images should be regarded with caution, because noise in PET data causes bias in the Logan plot estimates. In this paper, we describe the basic concept of the Logan plot in detail and introduce three algorithms for the Logan plot. By comparing these algorithms, we demonstrate the pitfalls of the Logan plot and discuss the solution.

  18. Model for capping of membrane receptors based on boundary surface effects

    Science.gov (United States)

    Gershon, N. D.

    1978-01-01

    Crosslinking of membrane surface receptors may lead to their segregation into patches and then into a single large aggregate at one pole of the cell. This process is called capping. Here, a novel explanation of such a process is presented in which the membrane is viewed as a supersaturated solution of receptors in the lipid bilayer and the adjacent two aqueous layers. Without a crosslinking agent, a patch of receptors that is less than a certain size cannot stay in equilibrium with the solution and thus should dissolve. Patches greater than a certain size are stable and can, in principle, grow by the precipitation of the remaining dissolved receptors from the supersaturated solution. The task of the crosslinking molecules is to form such stable patches. These considerations are based on a qualitative thermodynamic calculation that takes into account the existence of a boundary tension in a patch (in analogy to the surface tension of a droplet). Thermodynamically, these systems should cap spontaneously after the patches have reached a certain size. But, in practice, such a process can be very slow. A suspension of patches may stay practically stable. The ways in which a cell may abolish this metastable equilibrium and thus achieve capping are considered and possible effects of capping inhibitors are discussed. PMID:274724

  19. Reuse of hydroponic waste solution.

    Science.gov (United States)

    Kumar, Ramasamy Rajesh; Cho, Jae Young

    2014-01-01

    Attaining sustainable agriculture is a key goal in many parts of the world. The increased environmental awareness and the ongoing attempts to execute agricultural practices that are economically feasible and environmentally safe promote the use of hydroponic cultivation. Hydroponics is a technology for growing plants in nutrient solutions with or without the use of artificial medium to provide mechanical support. Major problems for hydroponic cultivation are higher operational cost and the causing of pollution due to discharge of waste nutrient solution. The nutrient effluent released into the environment can have negative impacts on the surrounding ecosystems as well as the potential to contaminate the groundwater utilized by humans for drinking purposes. The reuse of non-recycled, nutrient-rich hydroponic waste solution for growing plants in greenhouses is the possible way to control environmental pollution. Many researchers have successfully grown several plant species in hydroponic waste solution with high yield. Hence, this review addresses the problems associated with the release of hydroponic waste solution into the environment and possible reuse of hydroponic waste solution as an alternative resource for agriculture development and to control environmental pollution.

  20. Radiolysis of Aqueous Toluene Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, H C; Gustafson, R

    1971-04-15

    Aqueous toluene solutions have been irradiated with Co gamma-rays. In unbuffered solutions the various cresol isomers are formed in a total yield of 0.45, 0.87 and 0.94 molecules/100 eV absorbed energy in argon-, N{sub 2}O- and air - saturated solutions, respectively. The yields are reduced in acid (pH 3) solutions (G = 0.14, 0.14 and 0.52, respectively) but the reduction is compensated by the formation of 1,2-di-phenylethane in yields of 0.49 and 1.60 in argon- and N{sub 2}O-saturated solutions, respectively. Benzyl radicals are formed through an acid catalysed water elimination reaction from the initially formed hydroxymethylcyclohexadienyl radical. Phenyltolylmethanes, dimethylbiphenyls and partly reduced dimers are also formed during the radiolysis. Hydrogen is formed in the same yield as the molecular yield, g(H{sub 2}). Xylene isomers and benzene are formed in trace quantities. The most remarkable effects of the addition of Fe(III) ions to deaerated acid toluene solutions are the formation of benzyl alcohol and benzaldehyde and an increase in the yield of 1,2-diphenylethane

  1. Radiolysis of Aqueous Toluene Solutions

    International Nuclear Information System (INIS)

    Christensen, H.C.; Gustafson, R.

    1971-04-01

    Aqueous toluene solutions have been irradiated with Co γ-rays. In unbuffered solutions the various cresol isomers are formed in a total yield of 0.45, 0.87 and 0.94 molecules/100 eV absorbed energy in argon-, N 2 O- and air - saturated solutions, respectively. The yields are reduced in acid (pH 3) solutions (G 0.14, 0.14 and 0.52, respectively) but the reduction is compensated by the formation of 1,2-di-phenylethane in yields of 0.49 and 1.60 in argon- and N 2 O-saturated solutions, respectively. Benzyl radicals are formed through an acid catalysed water elimination reaction from the initially formed hydroxymethylcyclohexadienyl radical. Phenyltolylmethanes, dimethylbiphenyls and partly reduced dimers are also formed during the radiolysis. Hydrogen is formed in the same yield as the molecular yield, g(H 2 ). Xylene isomers and benzene are formed in trace quantities. The most remarkable effects of the addition of Fe(III) ions to deaerated acid toluene solutions are the formation of benzyl alcohol and benzaldehyde and an increase in the yield of 1,2-diphenylethane

  2. Transceptors as a functional link of transporters and receptors

    Directory of Open Access Journals (Sweden)

    George Diallinas

    2017-03-01

    Full Text Available Cells need to communicate with their environment in order to obtain nutrients, grow, divide and respond to signals related to adaptation in changing physiological conditions or stress. A very basic question in biology is how cells, especially of those organisms living in rapidly changing habitats, sense their environment. Apparently, this question is of particular importance to all free-living microorganisms. The critical role of receptors, transporters and channels, transmembrane proteins located in the plasma membrane of all types of cells, in signaling environmental changes is well established. A relative newcomer in environment sensing are the so called transceptors, membrane proteins that possess both solute transport and receptor-like signaling activities. Now, the transceptor concept is further enlarged to include micronutrient sensing via the iron and zinc high-affinity transporters of Saccharomyces cerevisiae. Interestingly, what seems to underline the transport and/or sensing function of receptors, transporters and transceptors is ligand-induced conformational alterations recognized by downstream intracellular effectors.

  3. The role of GABAB receptors in morphine self-administration

    Directory of Open Access Journals (Sweden)

    Effat Ramshini

    2013-01-01

    Full Text Available Background: There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration. Methods: This study was performed in four groups of rats: (1 Saline group, which received saline in the self-administration session. (2 Morphine group, which received morphine in saline solution in the self-administration session. (3 Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4 Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded. Results: Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test. Conclusion: Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates.

  4. Technetium recovery from high alkaline solution

    Energy Technology Data Exchange (ETDEWEB)

    Nash, Charles A.

    2016-07-12

    Disclosed are methods for recovering technetium from a highly alkaline solution. The highly alkaline solution can be a liquid waste solution from a nuclear waste processing system. Methods can include combining the solution with a reductant capable of reducing technetium at the high pH of the solution and adding to or forming in the solution an adsorbent capable of adsorbing the precipitated technetium at the high pH of the solution.

  5. [Ceruloplasmin receptor on human erythrocytes].

    Science.gov (United States)

    Saenko, E L; Basevich, V V; Iaropolov, A I

    1988-08-01

    The structural fragments of the human ceruloplasmin (CP) molecule and of erythrocyte receptors which provide for the specific interaction of CP with erythrocytes were identified, and their properties were investigated. The interaction of CP with erythrocytes, both intact and treated with neuroaminidase and proteolytic enzymes (trypsin, chymotrypsin, papaine, pronase E) is described. Experiments with CP reception were performed at 4 degrees C, using [125I]CP and [125I]asialo-CP. The parameters of binding were determined in Scatchard plots. It was demonstrated that the specific binding of CP to erythrocyte receptors is determined by its interaction with two structural sites of the carbohydrate moiety of the CP molecule, i.e., the terminal residues of sialic acids and a site, (formula; see text) located at a large distance from the chain terminus.

  6. Radiolysis of Aqueous Benzene Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, H

    1964-05-15

    Aerated and deaerated aqueous solutions of benzene have been irradiated with {sup 60}Co {gamma}-rays. The products of radiolysis in deaerated, unbuffered or acid, solutions were phenol, biphenyl, hydrogen and in acid solutions also hydrogen peroxide with the following yields: G(phenol) = 0. 37 (0. 37), G(biphenyl) = 1.3 (1.7), G(H{sub 2}) = 0.44 (0. 43) and G(H{sub 2}O{sub 2}) = 0 (0.60), the figures in brackets giving the results for acid solutions. The results are shown to agree with the conclusion that k(e{sup -}{sub aq} + H{sub 2}O{sub 2}) >> k(H + H{sub 2}O{sub 2}). Furthermore, the results indicate that a competition takes place between the reactions: 2 C{sub 6}H{sub 6}OH {center_dot} -> dimer -> biphenyl. C{sub 6}H{sub 7} {center_dot} + C{sub 6}H{sub 6}OH {center_dot} -> dimer -> biphenyl. The yields in aerated, unbuffered or acid, solutions were: G(phenol) = 2.1 (2.3), G(biphenyl) = 0 (0), and G(H{sub 2}O{sub 2}) = 2.2 (3.1), the figures in brackets being valid for acid solutions. The ratio k(H + C{sub 6}H{sub 6})/k(H + O{sub 2}) was 1.4x10{sup -2}. The results indicate that peroxides, or more probably hydroperoxides, take part in the reactions. After the addition of Fe{sup 2+} or Fe{sup 3+} to aerated acid solutions G(phenol) was increased to 6.6 and 3.4 respectively. Oxygen was consumed more rapidly in the presence of Fe. Reaction mechanisms are discussed.

  7. Solute-matrix and Solute-Solute Interactions during Supercritical Fluid Extraction of Sea Buckthorn Leaves

    Czech Academy of Sciences Publication Activity Database

    Sajfrtová, Marie; Sovová, Helena

    2012-01-01

    Roč. 42, SI (2012), s. 1682-1691 E-ISSN 1877-7058. [International Congress of Chemical and Process Engineering CHISA 2012 and 15th Conference PRES 2012 /20./. Prague, 25.08.2012-29.08.2012] R&D Projects: GA TA ČR TA01010578 Institutional support: RVO:67985858 Keywords : supercritical fluid extraction * sea buckthom leaves * solute-solute interaction Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  8. NGA/Insulin receptor scanning

    International Nuclear Information System (INIS)

    Kurtaran, A.; Virgolini, I.

    1994-01-01

    Tc-99m-galactosyl-neoglycoalbumin (NGA) is one of the first receptor-based radiopharmaceuticals which specifically recognizes the hepatic binding protein (HBP) located on the surface of the hepatocytes. The exclusive interactin of NGA with HBP provided the basis for a kinetic model for the evaluation hepatocellular function. During the last years we have used NGA in more than 300 patients with various liver diseases including liver cirrhosis (Stages Child A to Child C), viral hepatitis, and carcinomas. In these studies, the calculated HBP densities, after i.v.-injection of Tc-99m-NGA, significantly correlated with the clinical course of the diseases. Furthermore, similar to conventional Tc-colloid, NGA provided excellent demonstration of 'cold spots' for hepatic masses. In a further approach we used another hepatocyte receptor-seeking radioligand, I-123-Tyr-A14- insulin, and found, that its in vitro-binding to hepatocellular carcinomas is greatly enhanced over normal hepatic tissue. On this basis, we developed a double-tracer method using NGA and insulin in a single study. Thus, areas of 'cold spots' identifying hepatic masses on NGA scans, take up I-123-Tyr-A14-insulin immediately after i.v.-injection. This was true for hepatocellular hepatomas, but not for adenocarcinomas. In conclusion, NGA/insulin receptor scanning could be a novel and save method for the demonstration of hepatocellular hepatomas. (author)

  9. PAF receptor structure: a hypothesis.

    Science.gov (United States)

    Godfroid, J J; Dive, G; Lamotte-Brasseur, J; Batt, J P; Heymans, F

    1991-12-01

    Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong "Cache-orielles" (ear-muff) effect, i.e., two strong electronegative wells (isocontour at -10 Kcal/mole) are located at 180 degrees to each other and at a relatively constant distance. Initial consideration of the "Cache-oreilles" effect implied the structure of a bipolarized cylinder of 10-12 A diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.

  10. NGA/Insulin receptor scanning

    Energy Technology Data Exchange (ETDEWEB)

    Kurtaran, A; Virgolini, I [Vienna Univ. (Austria). Abt. fuer Nuklearmedizin; Angelberger, P [Ludwig Boltzmann-Institut fuer Nuklearmedizin, Vienna (Austria)

    1994-10-01

    Tc-99m-galactosyl-neoglycoalbumin (NGA) is one of the first receptor-based radiopharmaceuticals which specifically recognizes the hepatic binding protein (HBP) located on the surface of the hepatocytes. The exclusive interactin of NGA with HBP provided the basis for a kinetic model for the evaluation hepatocellular function. During the last years we have used NGA in more than 300 patients with various liver diseases including liver cirrhosis (Stages Child A to Child C), viral hepatitis, and carcinomas. In these studies, the calculated HBP densities, after i.v.-injection of Tc-99m-NGA, significantly correlated with the clinical course of the diseases. Furthermore, similar to conventional Tc-colloid, NGA provided excellent demonstration of `cold spots` for hepatic masses. In a further approach we used another hepatocyte receptor-seeking radioligand, I-123-Tyr-A14- insulin, and found, that its in vitro-binding to hepatocellular carcinomas is greatly enhanced over normal hepatic tissue. On this basis, we developed a double-tracer method using NGA and insulin in a single study. Thus, areas of `cold spots` identifying hepatic masses on NGA scans, take up I-123-Tyr-A14-insulin immediately after i.v.-injection. This was true for hepatocellular hepatomas, but not for adenocarcinomas. In conclusion, NGA/insulin receptor scanning could be a novel and save method for the demonstration of hepatocellular hepatomas. (author).

  11. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  12. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  13. Refinement of glucagon-like peptide 1 docking to its intact receptor using mid-region photolabile probes and molecular modeling.

    Science.gov (United States)

    Miller, Laurence J; Chen, Quan; Lam, Polo C-H; Pinon, Delia I; Sexton, Patrick M; Abagyan, Ruben; Dong, Maoqing

    2011-05-06

    The glucagon-like peptide 1 (GLP1) receptor is an important drug target within the B family of G protein-coupled receptors. Its natural agonist ligand, GLP1, has incretin-like actions and the receptor is a recognized target for management of type 2 diabetes mellitus. Despite recent solution of the structure of the amino terminus of the GLP1 receptor and several close family members, the molecular basis for GLP1 binding to and activation of the intact receptor remains unclear. We previously demonstrated molecular approximations between amino- and carboxyl-terminal residues of GLP1 and its receptor. In this work, we study spatial approximations with the mid-region of this peptide to gain insights into the orientation of the intact receptor and the ligand-receptor complex. We have prepared two new photolabile probes incorporating a p-benzoyl-l-phenylalanine into positions 16 and 20 of GLP1(7-36). Both probes bound to the GLP1 receptor specifically and with high affinity. These were each fully efficacious agonists, stimulating cAMP accumulation in receptor-bearing CHO cells in a concentration-dependent manner. Each probe specifically labeled a single receptor site. Protease cleavage and radiochemical sequencing identified receptor residue Leu(141) above transmembrane segment one as its site of labeling for the position 16 probe, whereas the position 20 probe labeled receptor residue Trp(297) within the second extracellular loop. Establishing ligand residue approximation with this loop region is unique among family members and may help to orient the receptor amino-terminal domain relative to its helical bundle region.

  14. Solidification of radioactive aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Aikawa, Hideaki; Kato, Kiyoshi; Wadachi, Yoshiki

    1970-09-07

    A process for solidifying a radioactive waste solution is provided, using as a solidifying agent a mixture of calcined gypsum and burnt vermiculite. The quantity ratio of the mixture is preferred to be 1:1 by volume. The quantity of impregnation is 1/2 of the volume of the total quantity of the solidifying agent. In embodiments, 10 liters of plutonium waste solution was mixed with a mixture of 1:1 calcined gypsum and burnt vermiculite contained in a 20-liter cylindrical steel container lined with asphalt. The plutonium waste solution from the laboratory was neutralized with a caustic soda aqueous solution to prevent explosion due to the nitration of organic compounds. The neutralization is not always necessary. A market available dental gypsum was calcined at 400 to 500/sup 0/C and a vermiculite from Illinois was burnt at 1,100/sup 0/C to prepare the agents. The time required for the impregnation with 10 liters of plutonium solution was four minutes. After impregnation, the temperature rose to 40/sup 0/C within 30 minutes to one hour. Next, it was cooled to room temperature by standing for 3-4 hours. Solidification time was about 1 hour. The Japan Atomic Energy Research Insitute had treated and disposed about 1,000 tons of plutonium waste by this process as of August 19, 1970.

  15. Receptor binding kinetics equations: Derivation using the Laplace transform method.

    Science.gov (United States)

    Hoare, Sam R J

    Measuring unlabeled ligand receptor binding kinetics is valuable in optimizing and understanding drug action. Unfortunately, deriving equations for estimating kinetic parameters is challenging because it involves calculus; integration can be a frustrating barrier to the pharmacologist seeking to measure simple rate parameters. Here, a well-known tool for simplifying the derivation, the Laplace transform, is applied to models of receptor-ligand interaction. The method transforms differential equations to a form in which simple algebra can be applied to solve for the variable of interest, for example the concentration of ligand-bound receptor. The goal is to provide instruction using familiar examples, to enable investigators familiar with handling equilibrium binding equations to derive kinetic equations for receptor-ligand interaction. First, the Laplace transform is used to derive the equations for association and dissociation of labeled ligand binding. Next, its use for unlabeled ligand kinetic equations is exemplified by a full derivation of the kinetics of competitive binding equation. Finally, new unlabeled ligand equations are derived using the Laplace transform. These equations incorporate a pre-incubation step with unlabeled or labeled ligand. Four equations for measuring unlabeled ligand kinetics were compared and the two new equations verified by comparison with numerical solution. Importantly, the equations have not been verified with experimental data because no such experiments are evident in the literature. Equations were formatted for use in the curve-fitting program GraphPad Prism 6.0 and fitted to simulated data. This description of the Laplace transform method will enable pharmacologists to derive kinetic equations for their model or experimental paradigm under study. Application of the transform will expand the set of equations available for the pharmacologist to measure unlabeled ligand binding kinetics, and for other time

  16. Zebrafish GDNF and its co-receptor GFRα1 activate the human RET receptor and promote the survival of dopaminergic neurons in vitro.

    Directory of Open Access Journals (Sweden)

    Tuulia Saarenpää

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1 and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners. We also found that zebrafish GFRα1 and GDNF are comparably active as mammalian cell-produced ones. We also report the first measurements of the affinity of the complex to RET in solution: at least for zebrafish, the Kd for GFRα1-GDNF binding RET is 5.9 μM. Surprisingly, we also found that zebrafish GDNF as well as zebrafish GFRα1 robustly activated human RET signaling and promoted the survival of cultured mouse dopaminergic neurons with comparable efficiency to mammalian GDNF, unlike E. coli-produced human proteins. These results contradict previous studies suggesting that mammalian GFRα1 and GDNF cannot bind and activate non-mammalian RET and vice versa.

  17. Diquafosol ophthalmic solution 3 %: a review of its use in dry eye.

    Science.gov (United States)

    Keating, Gillian M

    2015-05-01

    Diquafosol ophthalmic solution 3 % (Diquas(®)) is a P2Y2 receptor agonist that promotes tear fluid and mucin secretion and is currently approved in Japan and South Korea for the treatment of dry eye. In randomized, double-blind, multicentre trials in patients with dry eye, significantly greater improvements in fluorescein and rose bengal staining scores were seen with diquafosol ophthalmic solution 3 % than with placebo, and diquafosol ophthalmic solution 3 % was noninferior to sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the fluorescein staining score and more effective than sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the rose bengal staining score. The efficacy of diquafosol ophthalmic solution 3 % in the treatment of dry eye was maintained in the longer term, with improvements also seen in subjective dry eye symptoms, and was also shown in a real-world setting. Diquafosol ophthalmic solution 3 % also demonstrated efficacy in various specific dry eye disorders, including aqueous-deficient dry eye, short tear film break-up time dry eye, obstructive meibomian gland dysfunction, dry eye following laser in situ keratomileusis surgery and dry eye following cataract surgery, as well as in contact lens wearers and visual display terminal users. Diquafosol ophthalmic solution 3 % was generally well tolerated in patients with dry eye, with eye irritation the most commonly reported adverse event. In conclusion, diquafosol ophthalmic solution 3 % is a useful option for the treatment of dry eye.

  18. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

    Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

  19. Protein Connectivity in Chemotaxis Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Stephan Eismann

    2015-12-01

    Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

  20. Characterization of astrocytic and neuronal benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bender, A.S.

    1988-01-01

    Primary cultures of astrocytes and neurons express benzodiazepine receptors. Neuronal benzodiazepine receptors were of high-affinity, K{sub D} values were 7.5-43 nM and the densities of receptors (B{sub max}) were 924-4131 fmol/mg protein. Astrocytes posses a high-affinity benzodiazepine receptor, K{sub D} values were 6.6-13 nM. The B{sub max} values were 6,033-12,000 fmol/mg protein. The pharmacological profile of the neuronal benzodiazepine receptor was that of the central-type benzodiazepine receptor, where clonazepam has a high-affinity and Ro 5-4864 (4{prime}-chlorodiazepam) has a low-affinity. Whereas astrocytic benzoidazepine receptor was characteristic of the so called peripheral-type benzodiazepine receptors, which shows a high-affinity towards Ro 5-4863, and a low-affinity towards clonazepam. The astrocytic benzodiazepine receptors was functionally correlated with voltage dependent calcium channels, since dihydropyridines and benzodiazepines interacted with ({sup 3}H) diazepam and ({sup 3}H) nitrendipine receptors with the same rank order of potency, showing a statistically significant correlation. No such correlation was observed in neurons.

  1. Project Management Plan Solution Stabilization

    Energy Technology Data Exchange (ETDEWEB)

    SATO, P.K.

    1999-08-31

    This plan presents the overall objectives, description, justification and planning for the Plutonium Finishing Plant (PFP) Solutions Stabilization subproject. The intent of this plan is to describe how this project will be managed and integrated with other facility stabilization and deactivation activities. This plan supplements the overall integrated plan presented in the Integrated Project Management Plan (IPMP) for the Plutonium Finishing Plant Stabilization and Deactivation Project, HNF-3617. This project plan is the top-level definitive project management document for the PFP Solution Stabilization subproject. It specifies the technical, schedule, requirements and the cost baselines to manage the execution of the Solution Stabilization subproject. Any deviations to the document must be authorized through the appropriate change control process.

  2. Project Management Plan Solution Stabilization

    International Nuclear Information System (INIS)

    SATO, P.K.

    1999-01-01

    This plan presents the overall objectives, description, justification and planning for the Plutonium Finishing Plant (PFP) Solutions Stabilization subproject. The intent of this plan is to describe how this project will be managed and integrated with other facility stabilization and deactivation activities. This plan supplements the overall integrated plan presented in the Integrated Project Management Plan (IPMP) for the Plutonium Finishing Plant Stabilization and Deactivation Project, HNF-3617. This project plan is the top-level definitive project management document for the PFP Solution Stabilization subproject. It specifies the technical, schedule, requirements and the cost baselines to manage the execution of the Solution Stabilization subproject. Any deviations to the document must be authorized through the appropriate change control process

  3. Plagiarism Detection by Online Solutions.

    Science.gov (United States)

    Masic, Izet; Begic, Edin; Dobraca, Amra

    2017-01-01

    The problem of plagiarism represents one of the burning issues of the modern scientific world. Detection of plagiarism is a problem that the Editorial Board encounters in their daily work. Software solutions represent a good solution for the detection of plagiarism. The problem of plagiarism will become most discussed topic of the modern scientific world, especially due to the development of standard measures, which rank the work of one author. Investment in education, education of young research personnel about the importance of scientific research, with paying particular attention on ethical behavior, becomes an imperative of academic staff. Editors have to invest additional effort in the development of the base of reviewers team as well as in their proper guidance, because after all, despite the software solutions, they are the best weapon to fight plagiarism. Peer review process should be a key of successful operation of each journal.

  4. Device for analyzing a solution

    International Nuclear Information System (INIS)

    Marchand, Joseph.

    1978-01-01

    The device enables a solution containing an antigen to be analyzed by the radio-immunology technique without coming up against the problems of antigen-antibody complex and free antigen separation. This device, for analyzing a solution containing a biological compound capable of reacting with an antagonistic compound specific of the biological compound, features a tube closed at its bottom end and a component set and immobilized in the bottom of the tube so as to leave a capacity between the bottom of the tube and its lower end. The component has a large developed surface and is so shaped that it allows the solution to be analyzed to have access to the bottom of the tube; it is made of a material having some elastic deformation and able to take up a given quantity of the biological compound or of the antagonistic compound specific of the biological compound [fr

  5. Analytical Solution of Multicompartment Solute Kinetics for Hemodialysis

    Directory of Open Access Journals (Sweden)

    Przemysław Korohoda

    2013-01-01

    Full Text Available Objective. To provide an exact solution for variable-volume multicompartment kinetic models with linear volume change, and to apply this solution to a 4-compartment diffusion-adjusted regional blood flow model for both urea and creatinine kinetics in hemodialysis. Methods. A matrix-based approach applicable to linear models encompassing any number of compartments is presented. The procedure requires the inversion of a square matrix and the computation of its eigenvalues λ, assuming they are all distinct. This novel approach bypasses the evaluation of the definite integral to solve the inhomogeneous ordinary differential equation. Results. For urea two out of four eigenvalues describing the changes of concentrations in time are about 105 times larger than the other eigenvalues indicating that the 4-compartment model essentially reduces to the 2-compartment regional blood flow model. In case of creatinine, however, the distribution of eigenvalues is more balanced (a factor of 102 between the largest and the smallest eigenvalue indicating that all four compartments contribute to creatinine kinetics in hemodialysis. Interpretation. Apart from providing an exact analytic solution for practical applications such as the identification of relevant model and treatment parameters, the matrix-based approach reveals characteristic details on model symmetry and complexity for different solutes.

  6. Solution chemistry and separation of metal ions in leached solution

    International Nuclear Information System (INIS)

    Shibata, J.

    1991-01-01

    The method to presume a dissolved state of metal ions in an aqueous solution and the technology to separate and concentrate metal ions in a leached solution are described in this paper. It is very important for the separation of metal ions to know the dissolved state of metal ions. If we know the composition of an aqueous solution and the stability constants of metal-ligand complexes, we can calculate and estimate the concentration of each species in the solution. Then, we can decide the policy to separate and concentrate metal ions. There are several methods for separation and purification; hydroxide precipitation method, sulfide precipitation method, solvent extraction method and ion exchange resin method. Solvent extraction has been used in purification processes of copper refinery, uranium refinery, platinum metal refinery and rare earth metal refinery. Fundamental process of solvent extraction, a kind of commercial extractants, a way of determining a suitable extractant and an equipment are discussed. Finally, it will be emphasized how the separation of rare earths is improved in solvent extraction. (author) 21 figs., 8 tabs., 8 refs

  7. Fundamental solutions of singular SPDEs

    International Nuclear Information System (INIS)

    Selesi, Dora

    2011-01-01

    Highlights: → Fundamental solutions of linear SPDEs are constructed. → Wick-convolution product is introduced for the first time. → Fourier transformation maps Wick-convolution into Wick product. → Solutions of linear SPDEs are expressed via Wick-convolution with fundamental solutions. → Stochastic Helmholtz equation is solved. - Abstract: This paper deals with some models of mathematical physics, where random fluctuations are modeled by white noise or other singular Gaussian generalized processes. White noise, as the distributional derivative od Brownian motion, which is the most important case of a Levy process, is defined in the framework of Hida distribution spaces. The Fourier transformation in the framework of singular generalized stochastic processes is introduced and its applications to solving stochastic differential equations involving Wick products and singularities such as the Dirac delta distribution are presented. Explicit solutions are obtained in form of a chaos expansion in the Kondratiev white noise space, while the coefficients of the expansion are tempered distributions. Stochastic differential equations of the form P(ω, D) ◊ u(x, ω) = A(x, ω) are considered, where A is a singular generalized stochastic process and P(ω, D) is a partial differential operator with random coefficients. We introduce the Wick-convolution operator * which enables us to express the solution as u = s*A ◊ I ◊(-1) , where s denotes the fundamental solution and I is the unit random variable. In particular, the stochastic Helmholtz equation is solved, which in physical interpretation describes waves propagating with a random speed from randomly appearing point sources.

  8. Study of liquids and solutions

    International Nuclear Information System (INIS)

    Bellissent-Funel, M.C.

    1994-01-01

    A critical review of what has been achieved on the structure of liquids and solutions and the capabilities and developments of neutron scattering in this domain, are presented. A great variety of simple to complex systems has been investigated with the aim of obtaining a full microscopic description of the structure. Selected examples demonstrate the neutron scattering determination of interaction potentials, intermolecular structures and partial structure factors of complex systems. The isotopic substitution method is illustrated by the application to the study of the solvation of ions in aqueous and non aqueous solutions. (author). 9 figs., 32 refs

  9. Schwarzschild Solution: A Historical Perspective

    Science.gov (United States)

    Bartusiak, Marcia

    2016-03-01

    While eighteenth-century Newtonians had imagined a precursor to the black hole, the modern version has its roots in the first full solution to Einstein's equations of general relativity, derived by the German astronomer Karl Schwarzschild on a World War I battlefront just weeks after Einstein introduced his completed theory in November 1915. This talk will demonstrate how Schwarzschild's solution is linked to the black hole and how it took more than half a century for the physics community to accept that such a bizarre celestial object could exist in the universe.

  10. Electrodialysis operation with buffer solution

    Science.gov (United States)

    Hryn, John N [Naperville, IL; Daniels, Edward J [Orland Park, IL; Krumdick, Greg K [Crete, IL

    2009-12-15

    A new method for improving the efficiency of electrodialysis (ED) cells and stacks, in particular those used in chemical synthesis. The process entails adding a buffer solution to the stack for subsequent depletion in the stack during electrolysis. The buffer solution is regenerated continuously after depletion. This buffer process serves to control the hydrogen ion or hydroxide ion concentration so as to protect the active sites of electrodialysis membranes. The process enables electrodialysis processing options for products that are sensitive to pH changes.

  11. Magnetic Half-Monopole Solutions

    International Nuclear Information System (INIS)

    Teh, Rosy; Lim, Kok-Geng; Koh, Pin-Wai

    2009-01-01

    We present exact SU(2) Yang-Mills-Higgs monopole solutions of one half topological charge. These non-Abelian solutions possess gauge potentials which are singular along either the positive or the negative z-axis and common magnetic fields that are singular only at the origin where the half-monopole is located. These half-monopoles are actually a half Wu-Yang monopole and they can possess a finite point electric charge and become half-dyons. They do not necessarily satisfy the first order Bogomol'nyi equations and they possess infinite energy density at r = 0.

  12. Teaching sustainable solutions in engineering

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Nielsen, Susanne Balslev; Ejlertsen, Marina

    2015-01-01

    's study lines. The objectives of the course 'Sustainability in engineering solutions', is for the participants to understand the basic concept of sustainability and its three dimensions (people, profit, planet), as well as to analyse problems and synthesise solutions that are sustainable throughout...... their life cycle. The course runs over a full time 3-week period and employs project-based learning with several sub-projects/-problems. This paper takes an in-depth discussion of the considerations concerning how to teach such a complicated subject to students of widely differing backgrounds, and reflects...

  13. Fluid mechanics problems and solutions

    CERN Document Server

    Spurk, Joseph H

    1997-01-01

    his collection of over 200 detailed worked exercises adds to and complements the textbook Fluid Mechanics by the same author, and illustrates the teaching material through examples. In the exercises the fundamental concepts of Fluid Mechanics are applied to obtaining the solution of diverse concrete problems, and in doing this the student's skill in the mathematical modeling of practical problems is developed. In addition, 30 challenging questions without detailed solutions have been included, and while lecturers will find these questions suitable for examinations and tests, the student himself can use them to check his understanding of the subject.

  14. Intestinal Farnesoid X Receptor Activation by Pharmacologic Inhibition of the Organic Solute Transporter α-β

    Directory of Open Access Journals (Sweden)

    Sandra M.W. van de Wiel

    2018-01-01

    Conclusions: This study identifies clofazimine as an inhibitor of OSTα-OSTβ in vitro and in vivo, validates OSTα-OSTβ as a drug target to enhance intestinal bile acid signaling, and confirmed the applicability of the Förster Resonance Energy Transfer–bile acid sensor to screen for inhibitors of bile acid efflux pathways.

  15. Crystal Nucleation of Tolbutamide in Solution: Relationship to Solvent, Solute Conformation, and Solution Structure.

    Science.gov (United States)

    Zeglinski, Jacek; Kuhs, Manuel; Khamar, Dikshitkumar; Hegarty, Avril C; Devi, Renuka K; Rasmuson, Åke C

    2018-04-03

    The influence of the solvent in nucleation of tolbutamide, a medium-sized, flexible and polymorphic organic molecule, has been explored by measuring nucleation induction times, estimating solvent-solute interaction enthalpies using molecular modelling and calorimetric data, probing interactions and clustering with spectroscopy, and modelling solvent-dependence of molecular conformation in solution. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: acetonitrilenucleation difficulty is a function of the strength of solvent-solute interaction, with emphasis on the interaction with specific H-bonding polar sites of importance in the crystal structure. A clear exception from this rule is the most difficult nucleation in toluene despite the weakest solvent-solute interactions. However molecular dynamics modelling predicts that tolbutamide assumes an intramolecularly H-bonded conformation in toluene, substantially different from and more stable than the conformation in the crystal structure, and thus presenting an additional barrier to nucleation. This explains why nucleation in toluene is the most difficult and why the relatively higher propensity for aggregation of tolbutamide molecules in toluene solution, as observed with FTIR spectroscopy, does not translate into easier nucleation. Thus, our combined experimental and molecular modelling study suggests that the solvent can influence on the nucleation not only via differences in the desolvation but also through the influence on molecular conformation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Receptor Tyrosine Kinases in Drosophila Development

    Science.gov (United States)

    Sopko, Richelle; Perrimon, Norbert

    2013-01-01

    Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

  17. Receptor binding studies of the living heart

    International Nuclear Information System (INIS)

    Syrota, A.

    1988-01-01

    Receptors form a class of intrinsic membrane proteins (or glycoproteins) defined by the high affinity and specificity with which they bind ligands. Many receptors are associated directly or indirectly with membrane ion channels that open or close after a conformational change of the receptor induced by the binding of the neurotransmitter. Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, and cardiomyopathy as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or postmortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue

  18. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  19. 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.

  20. Acetylcholine receptors in the human retina

    International Nuclear Information System (INIS)

    Hutchins, J.B.; Hollyfield, J.G.

    1985-01-01

    Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

  1. Numerical Asymptotic Solutions Of Differential Equations

    Science.gov (United States)

    Thurston, Gaylen A.

    1992-01-01

    Numerical algorithms derived and compared with classical analytical methods. In method, expansions replaced with integrals evaluated numerically. Resulting numerical solutions retain linear independence, main advantage of asymptotic solutions.

  2. Siemens IT solutions for power sector

    International Nuclear Information System (INIS)

    Lunter, P.

    2004-01-01

    The cost reduction, flexibility and revenue increase, potential exploitation, productivity increase, and business opportunities exploitation - that is all what can be required in the races for the promonent positioning on the electricity power market. These requirements can be realized by the sophisticated IT solutions hand-tailored to the special requirements of the electric power producers and tradesmen. This approach makes it possible to achieve greater profit. Our solutions 'PROFIT Solutions', that are symbiosis of the most progressive information technologies and the power plant techniques of the company Siemens, satisfy submitted specifications in substantial measure. The system solutions 'PROFIT Solutions' comprise three solution groups: process, operation a business. The solutions of the group 'IT Process Solutions' increase flexibility and manoeuvrability of equipment, improve the efficiency and contribute to more economical operation of the power generation. Solutions 'IT Process Solutions' simplify and shorten the period of power cycles and conduce to higher labour productivity. Solutions group 'IT Process Solutions' approaches equipment to the market - supports the profit strategies, helps quickly and expertly to determine and predict hazards. The extension PROFIT Cockpit means the nuance to the solutions world 'PROFIT Solutions'. The survey about the whole installation is within reach at the simple touch of a button. It is possible to compile the total system part by part from single solutions 'PROFIT Solutions'. As a matter of fact all single parts can be interconnected with already existing solutions. Routines 'PROFIT Solutions' cooperate with all modern control systems. (author)

  3. Some new radiating Kerr-Newman solutions

    International Nuclear Information System (INIS)

    Patel, L.K.; Singh, Tajinder; Koppar, S.S.

    1991-01-01

    Three exact non-static solutions of Einstein-Maxwell equations corresponding to a field of flowing null radiation plus an electromagnetic field are presented. These solutions are non-static generalizations of the well known Kerr-Newman solution. The current vector is null in all the three solutions. These solutions are the electromagnetic generalizations of the three generalized radiating Kerr solutions discussed by Vaidya and Patel. The solutions discussed here describe the exterior gravitational fields of rotating radiating charged bodies. Many known solutions are derived as particular cases. (author). 12 refs

  4. Business value of solution architecture

    NARCIS (Netherlands)

    Slot, R.; Dedene, G.; Maes, R.; Proper, E.; Harmsen, F.; Dietz, J.L.G.

    2009-01-01

    The theory and especially the practice of IT architecture have been developed quite vigorously the last years. However, hardly any quantitative data about the value of IT architecture is available. This paper presents the results of a study, which measures the value of IT solution architecture for

  5. COMPOSITE SOLUTIONS IN RAILROAD ENGINEERING

    Directory of Open Access Journals (Sweden)

    Panfilova Marina Ivanovna

    2012-10-01

    Full Text Available Present-day methods of recovery of used wooden railway ties, including burial, chemical neutralization, gasification and subsequent burning, utilization in the capacity of composite materials, are expensive and unsafe for the environment. The authors propose a new method of their utilization. Ash generated in the course of their burning may replace a portion of cement in composite solutions and act as an additive to grouting mortars designated for the filling of the annulus space of manifold tunnels. The chemical composition of the ash was identified by the x-ray method applied to three samples taken during various periods of time from out of a dry-type dust collector. The level of human health/environmental hazard of the ash is based on its chemical composition. Changes in the rheological properties of composite solutions that contained concrete fractions, various ratios of ash, and 5% of liquid glass were studied in the course of the research. The experiments have proven that in the event of replacement of 20% of cement by ash, the strength of the composite solution is approximately the same as the one of the benchmark sample; therefore, this ash content ratio is deemed acceptable. The finding demonstrate that the ash has no toxic effect, and the ecological safety of this solution is thus confirmed. The authors have proven that 20% of cement may be replaced by the ash generated in the course of burning of waste railway ties.

  6. Aqueous Solution Chemistry of Plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Clark, David L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-28

    Things I have learned working with plutonium: Chemistry of plutonium is complex; Redox equilibria make Pu solution chemistry particularly challenging in the absence of complexing ligands; Understanding this behavior is key to successful Pu chemistry experiments; There is no suitable chemical analog for plutonium.

  7. Negative energy solutions and symmetries

    International Nuclear Information System (INIS)

    Sidharth, B.G.

    2011-01-01

    We revisit the negative energy solutions of the Dirac (and Klein–Gordon) equation, which become relevant at very high energies in the context of the Feshbach–Villars formulation, and study several symmetries which follow therefrom. Significant consequences are briefly examined. (author)

  8. Scorpion toxins prefer salt solutions

    Czech Academy of Sciences Publication Activity Database

    Nikouee, A.; Khabiri, Morteza; Cwiklik, Lukasz

    2015-01-01

    Roč. 21, č. 11 (2015), 287/1-287/14 ISSN 1610-2940 R&D Projects: GA ČR GA13-06181S Institutional support: RVO:61388963 ; RVO:61388955 Keywords : ionic solutions * molecular dynamics * nonaqueous media * secondary structure Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.438, year: 2015

  9. In situ solution mining technique

    International Nuclear Information System (INIS)

    Learmont, R.P.

    1978-01-01

    A method of in situ solution mining is disclosed in which a primary leaching process employing an array of 5-spot leaching patterns of production and injection wells is converted to a different pattern by converting to injection wells all the production wells in alternate rows

  10. A pyramid solution at Chernobyl

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    In the Kiev '92 competition to find a solution to the problem of containing the stricken Chernobyl unit 4, the PPROTECTOR proposal, put forward by a British-led international consortium, ranked fifth after the first round of judging. It made extensive use of advanced CAD techniques. (Author)

  11. Solution chemistry of lanthanide complexes

    International Nuclear Information System (INIS)

    Brittain, H.G.

    1979-01-01

    Intermolecular energy transfer from Tb 3+ to Eu 3+ , luminescence intensity measurements, potentiometric titrations, differential absorption spectroscopy, and spectroscopic titrations were all used to study the binding of lanthanide ions by serine and threonine. At low pH (3.0 to 6.0) the complexes are mononuclear and ligand is only weakly bound. In the pH interval of 6.0 to 8.5 stronger interaction takes place between the ligand and the metal (with possible coordination of the undissociated hydroxyl group), and self-association of complexes becomes important. Above pH 8.5, base hydrolysis of the complexes leads to highly associated species in solution and shortly above this pH an insoluble precipitate is formed. It was found that energy could be transferred from Tb 3+ to Eu 3+ more efficiently among complexes prepared from racemic ligands than in complexes made from resolved ligand, but this stereoselectivity was only observed at pH values greater than 6.5 and in solutions having a 1:10 ratio of metal-to-ligand. No stereoselectivity was found in solutions having 1:5 ratios, and this observation was explained by the existence of 1:2 metal-ligand complexes existing in solutions having the higher ratio of metal-to-ligand (only 1:1 complexes are then found at lower ratios of metal-to-ligand). (author)

  12. Hospitality lighting solutions communication framework

    NARCIS (Netherlands)

    Blanch, Anna

    2014-01-01

    Hospitality customers are looking for systems that involve more than just turning the light on and off. They want lighting solutions that are energy-efficient, flexible and that will help enhance the guest experience. Based on on-going research about the impact that light can have in different

  13. Looking to nature for solutions

    Science.gov (United States)

    Turner, Will R.

    2018-01-01

    Completely stopping fossil fuel use may not be enough to avoid dangerous climate change. Recent research on the mitigation potential of conservation, restoration, and improved land management demonstrates that natural solutions can reduce emissions and remove atmospheric CO2 while safeguarding food security and biodiversity.

  14. Decomposition of metal nitrate solutions

    International Nuclear Information System (INIS)

    Haas, P.A.; Stines, W.B.

    1982-01-01

    Oxides in powder form are obtained from aqueous solutions of one or more heavy metal nitrates (e.g. U, Pu, Th, Ce) by thermal decomposition at 300 to 800 deg C in the presence of about 50 to 500% molar concentration of ammonium nitrate to total metal. (author)

  15. Statistical mechanics of protein solutions

    NARCIS (Netherlands)

    Prinsen, P.

    2007-01-01

    We study theoretically thermodynamic properties of spherical globular proteins in aqueous solution with added monovalent salt. We show how one can determine an effective interaction potential between the proteins from experimental data as a function of salt concentration and we apply this to the

  16. CERN single sign on solution

    International Nuclear Information System (INIS)

    Ormancey, E

    2008-01-01

    The need for Single Sign On has always been restricted by the absence of cross platform solutions: a single sign on working only on one platform or technology is nearly useless. The recent improvements in Web Services Federation (WS-Federation) standard enabling federation of identity, attribute, authentication and authorization information can now provide real extended Single Sign On solutions. Various solutions have been investigated at CERN and now, a Web SSO solution using some parts of WS-Federation technology is available. Using the Shibboleth Service Provider module for Apache hosted web sites and Microsoft ADFS as the identity provider linked to Active Directory user, users can now authenticate on any web application using a single authentication platform, providing identity, user information (building, phone...) as well as group membership enabling authorization possibilities. A typical scenario: a CERN user can now authenticate on a Linux/Apache website using Windows Integrated credentials, and his Active Directory group membership can be checked before allowing access to a specific web page

  17. Designing Hyper-V solutions

    CERN Document Server

    Grover, Saurabh

    2015-01-01

    This book is aimed at IT admins, consultants, and architects alike who wish to deploy, manage, and maintain Hyper-V solutions in organizations of various sizes. You are expected to have a working knowledge of managing Windows Server and a fair understanding of networking and storage concepts.

  18. Climate Change. Solutions for Australia

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, T.; Hoegh-Guldberg, O.; Karoly, D.; Lowe, I.; McMichael, T.; Mitchell, C.; Pearman, G.; Scaife, P.; Reynolds, A. (eds.)

    2004-06-01

    The Australian Climate Group was convened in late 2003 by WWF Australia and the Insurance Australia Group (IAG) in response to the increasing need for action on climate change in Australia. This group proposes a set of solutions to lower the risk that climate change will reach a dangerous level.

  19. Archival storage solutions for PACS

    Science.gov (United States)

    Chunn, Timothy

    1997-05-01

    While they are many, one of the inhibitors to the wide spread diffusion of PACS systems has been robust, cost effective digital archive storage solutions. Moreover, an automated Nearline solution is key to a central, sharable data repository, enabling many applications such as PACS, telemedicine and teleradiology, and information warehousing and data mining for research such as patient outcome analysis. Selecting the right solution depends on a number of factors: capacity requirements, write and retrieval performance requirements, scaleability in capacity and performance, configuration architecture and flexibility, subsystem availability and reliability, security requirements, system cost, achievable benefits and cost savings, investment protection, strategic fit and more.This paper addresses many of these issues. It compares and positions optical disk and magnetic tape technologies, which are the predominant archive mediums today. Price and performance comparisons will be made at different archive capacities, plus the effect of file size on storage system throughput will be analyzed. The concept of automated migration of images from high performance, high cost storage devices to high capacity, low cost storage devices will be introduced as a viable way to minimize overall storage costs for an archive. The concept of access density will also be introduced and applied to the selection of the most cost effective archive solution.

  20. Solution properties of hydrophobically modified

    Directory of Open Access Journals (Sweden)

    A.M. Al-Sabagh

    2016-12-01

    Full Text Available We tested nine hydrophobically modified polyacrylamides with molecular weights situated between 1.58 and 0.89 × 106 g/mol for enhanced oil recovery applications. Their solution properties were investigated in the distilled water, brine solution, formation water and sea water. Their critical association concentrations were determined from the relationship between their concentrations and the corresponding apparent viscosities (ηapp at 30 °C at shear rate 6 s−1. They were between 0.4 and 0.5 g/dl. The brine solutions of 0.5 g/dl of HM-PAMs were investigated at different conditions regarding their apparent viscosities. Such conditions were mono and divalent cations, temperature ranging from 30 to 90 °C, the shear rate ranging from 6 to 30 s−1 and the aging time for 45 days. The surface and interfacial tensions for the HM-PAMs were measured for concentration range from 0.01 to 1 g/dl brine solutions at 30 °C and their emulsification efficiencies were investigated for 7 days. The discrepancy in the properties and efficiencies of the tested copolymers was discussed in the light of their chemical structure.

  1. Solutions of Einstein's field equations

    Energy Technology Data Exchange (ETDEWEB)

    Tomonaga, Y [Utsunomiya Univ. (Japan). Faculty of Education

    1978-12-01

    In this paper the author investigates the Einstein's field equations of the non-vacuum case and generalizes the solution of Robertson-Walker by the three dimensional Einstein spaces. In Section 2 the author shortly generalizes the dynamic space-time of G. Lemetre and A. Friedmann by a simple transformation.

  2. Studies on insulin receptor, 1

    International Nuclear Information System (INIS)

    Sakai, Yukio

    1979-01-01

    The present study was designed for the purpose of establishing a method of insulin radioreceptor assay using plasma membranes of guinea pigs as receptor sites. The results obtained are as follows: 1) Insulin receptor in the renal plasma membranes of guinea pigs showed a significantly high affinity to porcine insulin compared with that in the plasma membranes of guinea pig liver or rat kidney and liver. 2) In the insulin radioreceptor assay, an optimum condition was observed by the incubation at 4 0 C for 24 - 48 hours with 100 μg membrane protein of guinea pig kidney and 0.08 ng of 125 I-insulin. This assay method was specific for insulin and showed an accurate biological activity of insulin. 3) The recovery rate of insulin radioreceptor assay was 98.4% and dilution check up to 16 times did not influence on the result. An average of coefficient variation was 3.92% within assay. All of these results indicated the method to be satisfactory. 4) Glucose induced insulin release by perfusion method in isolated Langerhans islets of rats showed an identical pattern of reaction curves between radioreceptor assay and radioimmunoassay, although the values of radioreceptor assay was slightly low. 5) Insulin free serum produced by ultra filtration method was added to the standard assay medium. By this procedure, direct measurement of human serum by radioreceptor assay became possible. 6) The value of human serum insulin receptor binding activity by the radioreceptor assay showed a high correlation with that of insulin radioimmunoassay in sera of normal, borderline or diabetic type defined by glucose tolerance test. (author)

  3. Seventh Symposium on Subtypes of Musccarinic Receptors.

    Science.gov (United States)

    1997-01-01

    nociceptive pain, are less than ideal. For mild to moderate pain, the first line of therapy includes aspirin, acetaminophen/ paracetamol , and nonsteroidal...due to receptor degradation triggered by prolonged carbachol occupancy. This down-regulation was accompanied by uncoupling of the M2-receptors after 24...be under control by the m3 mAChR, suggesting a complex receptor regulation of phosphoinositide metabolism, including degradation and synthesis. Future

  4. Molecular identification of the first SIFamide receptor

    DEFF Research Database (Denmark)

    Jørgensen, Lars M; Hauser, Frank; Cazzamali, Giuseppe

    2006-01-01

    , an impressive sequence conservation (67-77% amino acid sequence identities between the seven-transmembrane areas; 82-87% sequence similarities). The identification of well-conserved SIFamide receptor orthologues in all other insects with a sequenced genome, suggests that the SIFamide/receptor couple must have...... an essential function in arthropods. This paper is the first report on the identification of a SIFamide receptor....

  5. Progesterone receptor modulators in breast cancer

    OpenAIRE

    WIEHLE, Ronald D.

    2015-01-01

    Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptor-depleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in t...

  6. Androgen Receptor Signaling in Bladder Cancer

    OpenAIRE

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in u...

  7. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  8. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

  9. Insights into function of PSI domains from structure of the Met receptor PSI domain

    International Nuclear Information System (INIS)

    Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

    2004-01-01

    PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

  10. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational...

  11. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M.; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric

    2010-01-01

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  12. Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors.

    Science.gov (United States)

    Pediaditakis, Iosif; Iliopoulos, Ioannis; Theologidis, Ioannis; Delivanoglou, Nickoleta; Margioris, Andrew N; Charalampopoulos, Ioannis; Gravanis, Achille

    2015-01-01

    Dehydroepiandosterone (DHEA), the most abundant steroid in humans, affects multiple cellular functions of the endocrine, immune, and nervous systems. However, up to quite recently, no receptor has been described specifically for it, whereas most of its physiological actions have been attributed to its conversion to either androgens or estrogens. DHEA interacts and modulate a variety of membrane and intracellular neurotransmitter and steroid receptors. We have recently reported that DHEA protects neuronal cells against apoptosis, interacting with TrkA, the high-affinity prosurvival receptor of the neurotrophin, nerve growth factor. Intrigued by its pleiotropic effects in the nervous system of a variety of species, we have investigated the ability of DHEA to interact with the other two mammalian neurotrophin receptors, ie, the TrkB and TrkC, as well as their invertebrate counterparts (orthologs) in mollusks Lymnaea and Aplysia and in cephalochordate fish Amphioxus. Amazingly, DHEA binds to all Trk receptors, although with lower affinity by 2 orders of magnitude compared with that of the polypeptidic neurotrophins. DHEA effectively induced the first step of the TrkA and TrkC receptors activation (phosphorylation at tyrosine residues), including the vertebrate neurotrophin nonresponding invertebrate Lymnaea and Aplysia receptors. Based on our data, we hypothesize that early in evolution, DHEA may have acted as a nonspecific neurotrophic factor promoting neuronal survival. The interaction of DHEA with all types of neurotrophin receptors offers new insights into the largely unidentified mechanisms of its actions on multiple tissues and organs known to express neurotrophin receptors.

  13. Characterization of the chicken muscle insulin receptor

    International Nuclear Information System (INIS)

    Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

    1987-01-01

    Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

  14. Human dopamine receptor and its uses

    Energy Technology Data Exchange (ETDEWEB)

    Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

    1999-01-01

    The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

  15. Chapter 8. Activation mechanisms of chemokine receptors

    DEFF Research Database (Denmark)

    Jensen, Pia C; Rosenkilde, Mette M

    2009-01-01

    binding. Attempts to unravel the activation mechanism of 7TM receptors have led to the conclusion that activation involves movements of the transmembrane segments VI and VII in particular, as recently gathered in the Global Toggle Switch Model. However, to understand the activation mechanism completely......, more research has to be done in this field. Chemokine receptors are interesting tools in this matter. First, the chemokine system has a high degree of promiscuity that allows several chemokines to target one receptor in different ways, as well as a single chemokine ligand to target several receptors...

  16. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten

    2010-08-22

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  17. Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

    Science.gov (United States)

    Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

    2015-08-19

    The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

  18. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

    International Nuclear Information System (INIS)

    Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

    2008-01-01

    The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

  19. Fundamental solutions in piezoelectricity. Penny-shaped crack solution

    International Nuclear Information System (INIS)

    Dyka, Ewa; Rogowski, Bogdan

    2006-01-01

    The problem of electroelasticity for piezoelectric materials is considered. For axially symmetric states three potentials are introduced, which determine the displacements, the electric potentials, the stresses, the components of the electric field vector and the electric displacements in a piezoelectric body. These fundamental solutions are utilized to solve the penny-shaped crack problem. Two cases of boundary-value problems are considered, namely the permeable and impermeable crack boundary conditions. Exact solutions are obtained for elastic and electric fields. The main results are the stress intensity factor for singular stress and the electric displacement intensity factor. The numerical results are presented graphically to show the influence of applied mechanical and electrical loading on the analyzed quantities and to clarify the effect of anisotropy of piezoelectric materials. It is show that the influence of anisotropy of the materials on these fields is significant

  20. Purification of rat intestinal receptor for intrinsic factor-vitamin B12 complex

    International Nuclear Information System (INIS)

    Yamada, Shoji; Itaya, Harutaka; Nakazawa, Osamu; Fukuda, Morimichi.

    1977-01-01

    The intrinsic factor (IF) in a rat gastric mucosal extract was bound efficiently to vitamin B 12 -sepharose without significant change in its nature to produce IF-vitamin B 12 -sepharose. The purification of the intestinal receptor for the IF-vitamin B 12 complex was performed by the affinity chromatography using the IF-vitamin B 12 -sepharose as the affinity adsorbent. As a result of admixing the gastric mucosal extract sample with B 12 -sepharose while stirring for 4 hours, the adsorption was performed without any break through. Further, it was recognized that the B 12 -bound protein purified by the affinity chromatography using B 12 -sepharose was not much changed as compared with that before purification. Furthermore, it was recognized that IF-B 12 -sepharose was able to be made by binding IF with B 12 -sepharose which was made by coupling B 12 with the market-available AH-sepharose. The IF-B 12 -sepharose was washed with buffer solution, and then was loaded with the small intestine mucosal extract. Thereafter, the receptor was eluted by making di-valent cation inert with the buffer solution. After the removal of EDTA in the eluted solution by dialysis, the activity of the receptor was measured. 48.5% of the receptor activity loaded was recovered by the elution with EDTA. The specific activity of the receptor represented by the final amount of B 12 (pg)/the amount of protein (mg) in the purified substance was 335 folds of the original activity. (Iwakiri, K.)

  1. Compacton solutions and multiple compacton solutions for a continuum Toda lattice model

    International Nuclear Information System (INIS)

    Fan Xinghua; Tian Lixin

    2006-01-01

    Some special solutions of the Toda lattice model with a transversal degree of freedom are obtained. With the aid of Mathematica and Wu elimination method, more explicit solitary wave solutions, including compacton solutions, multiple compacton solutions, peakon solutions, as well as periodic solutions are found in this paper

  2. G-protein-coupled receptors for free fatty acids

    DEFF Research Database (Denmark)

    Milligan, Graeme; Ulven, Trond; Murdoch, Hannah

    2014-01-01

    of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid...

  3. Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS

    DEFF Research Database (Denmark)

    Leonhardt, Julia; Villela, Daniel C.; Teichmann, Anke

    2017-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may in...

  4. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    NARCIS (Netherlands)

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  5. Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival.

    Science.gov (United States)

    Liu, Zhaochuan; Lin, Haotian; Huang, Chulong; Chen, Wan; Xiang, Wu; Geng, Yu; Chen, Weirong

    2015-11-12

    Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution are also unknown. Thus, we developed 0.1%, 0.2% and 0.5% FTY720 ophthalmic solutions and evaluated their chemical stabilities under various storage conditions with high- performance liquid chromatography. To investigate the ocular irritancy of the FTY720 ophthalmic solution, New Zealand albino rabbits were subjected to the Draize test. Furthermore, classic, well-established rat allogenic penetrating keratoplasty models were used to investigate the anti-rejection efficacy of the tested FTY720 ophthalmic solutions. We found that the non-irritating 0.5% FTY720 ophthalmic solution could prolong corneal allograft survival in rats with significant efficacy for about one month. Furthermore, no significant concentration changes occurred in any of the types of FTY720 ophthalmic solutions within three months. These results revealed crucial profiles of FTY720 ophthalmic solutions and warrant further investigation and optimization of FTY720 in the anti-rejection therapy after keratoplasty.

  6. Receptor saturation in roentgen films

    Energy Technology Data Exchange (ETDEWEB)

    Strid, K G; Reichmann, S [Sahlgrenska Sjukhuset, Goeteborg (Sweden)

    1980-01-01

    Roentgen-film recording of small object details of low attenuation differences (e.g. pulmonary vessels) is regularly seen to be impaired when the film is exposed to yield high values of optical density (D). This high-density failure is due to receptor saturation, which implies that at high exposure values most silver halide grains of the film are made developable, leaving few grains available to receive additional informative photons. The receptor saturation is analysed by means of a mathematical model of a non-screen film yielding Dsub(max) = 2.0. Optimum recording, defined by maximum signal-to-noise ratio in the image, is found at D approximately 0.64, corresponding to, on an average, 1.6 photons absorbed per grain. On the other hand, maximum contrast occurs at D approximately 1.4, where, on the average, 3.6 photons are absorbed per grain. The detective quantum efficiency of the film, i.e. the fraction of the photons actually contributing to the information content of the image, drops from 41 per cent at maximum signal-to-noise ratio to a mere 10 per cent at maximum contrast.

  7. Androgen receptor drives cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yelena Mirochnik

    Full Text Available The accepted androgen receptor (AR role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

  8. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  9. Posttransplant chimeric antigen receptor therapy.

    Science.gov (United States)

    Smith, Melody; Zakrzewski, Johannes; James, Scott; Sadelain, Michel

    2018-03-08

    Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.

  10. Extracytoplasmic proteases determining the cleavage and release of secreted proteins, lipoproteins, and membrane proteins in Bacillus subtilis

    NARCIS (Netherlands)

    Krishnappa, Laxmi; Dreisbach, Annette; Otto, Andreas; Goosens, Vivianne J; Cranenburgh, Rocky M; Harwood, Colin R; Becher, Dörte; van Dijl, Jan Maarten

    2013-01-01

    Gram-positive bacteria are known to export many proteins to the cell wall and growth medium, and accordingly, many studies have addressed the respective protein export mechanisms. In contrast, very little is known about the subsequent fate of these proteins. The present studies were therefore aimed

  11. Major Tom to Ground Control: How Lipoproteins Communicate Extracytoplasmic Stress to the Decision Center of the Cell.

    Science.gov (United States)

    Laloux, Géraldine; Collet, Jean-François

    2017-11-01

    The envelope of bacteria is a complex multilayered shield that ensures multiple essential functions, including protecting the cell from external assaults. Hence, bacterial cells have evolved intricate mechanisms called envelope stress response systems (ESRS) to monitor all kinds of perturbations affecting the integrity of their envelope and to mount an appropriate response to contain or repair the damage. In the model bacterium Escherichia coli , several ESRS are built around a two-component system, in which envelope stress triggers a phosphotransfer between a sensor protein in the inner membrane of the envelope and a response regulator in the cytoplasm. In this review, we focus on two major ESRS in E. coli , the Rcs and Cpx pathways, in which additional proteins not directly involved in the phosphotransfer modulate signal transduction. Both the Rcs and Cpx systems can be turned on by a lipoprotein anchored in the outer membrane, RcsF and NlpE, respectively, providing a molecular connection between the most exterior layer of the envelope and the ground control center in the cytoplasm. Here, we review how these two lipoproteins, which share a striking set of features while being distinct in several aspects, act as sentinels at the front line of the bacterium by sensing and transducing stress to the downstream components of the Rcs and Cpx systems. Copyright © 2017 American Society for Microbiology.

  12. Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

    NARCIS (Netherlands)

    Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

    2009-01-01

    Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

  13. Fissile solution dynamics: Student research

    Energy Technology Data Exchange (ETDEWEB)

    Hetrick, D.L.

    1994-09-01

    There are two research projects in criticality safety at the University of Arizona: one in dynamic simulation of hypothetical criticality accidents in fissile solutions, and one in criticality benchmarks using transport theory. We have used the data from nuclear excursions in KEWB, CRAC, and SILENE to help in building models for solution excursions. An equation of state for liquids containing gas bubbles has been developed and coupled to point-reactor dynamics in an attempt to predict fission rate, yield, pressure, and kinetic energy. It appears that radiolytic gas is unimportant until after the first peak, but that it does strongly affect the shape of the subsequent power decrease and also the dynamic pressure.

  14. Automatic validation of numerical solutions

    DEFF Research Database (Denmark)

    Stauning, Ole

    1997-01-01

    This thesis is concerned with ``Automatic Validation of Numerical Solutions''. The basic theory of interval analysis and self-validating methods is introduced. The mean value enclosure is applied to discrete mappings for obtaining narrow enclosures of the iterates when applying these mappings...... differential equations, but in this thesis, we describe how to use the methods for enclosing iterates of discrete mappings, and then later use them for discretizing solutions of ordinary differential equations. The theory of automatic differentiation is introduced, and three methods for obtaining derivatives...... are described: The forward, the backward, and the Taylor expansion methods. The three methods have been implemented in the C++ program packages FADBAD/TADIFF. Some examples showing how to use the three metho ds are presented. A feature of FADBAD/TADIFF not present in other automatic differentiation packages...

  15. Dynamic viscosity of polymer solutions

    Energy Technology Data Exchange (ETDEWEB)

    Peterlin, A

    1982-03-01

    The dynamic viscosity investigation of solutions of long chain polymers in very viscous solvents has definitely shown the existence of the low and high frequency plateau with the gradual transition between them. In both extreme cases the extrapolation of the measured Newtonian viscosities of the plateaus to the infinite dilution yields the limiting intrinsic viscosities. Such a behavior is expected from the dynamic intrinsic viscosity of the necklace model of the linear polymer with finite internal viscosity. The plateau at low frequency shows up in any model of polymer solution. This work shows the constant dynamic intrinsic viscosity in both extreme cases is well reproducible by the necklace model with the internal viscosity acting only between the beads on the same link. 20 references.

  16. Solution assay instrument operations manual

    International Nuclear Information System (INIS)

    Li, T.K.; Marks, T.; Parker, J.L.

    1983-09-01

    An at-line solution assay instrument (SAI) has been developed and installed in a plutonium purification and americium recovery process area in the Los Alamos Plutonium Processing Facility. The instrument was designed for accurate, timely, and simultaneous nondestructive analysis of plutonium and americium in process solutions that have a wide range of concentrations and americium/plutonium ratios and for routine operation by process technicians who lack instrumentation background. The SAI, based on transmission-corrected, high-resolution gamma-ray spectroscopy, has two measurement stations attached to a single multichannel analyzer/computer system. To ensure the quality of assay results, the SAI has an internal measurement control program, which requires daily and weekly check runs and monitors key aspects of all assay runs. For a 25-ml sample, the assay precision is 5 g/l within a 2000-s count time

  17. Restoration of uranium solution mining deposits

    International Nuclear Information System (INIS)

    Devries, F.W.; Lawes, B.C.

    1982-01-01

    A process is provided for restoring an ore deposit after uranium solution mining using ammonium carbonate leaching solutions has ceased. The process involves flushing the deposit with an aqueous solution of a potassium salt during which potassium ions exchange with ammonium ions remaining in the deposit. The ammonium containing flushing solution is withdrawn from the deposit for disposal

  18. Gold and Silver Extraction from Leach Solutions

    OpenAIRE

    Bagdaulet K. Kenzhaliyev; Renata R. Iskhakova; Zamzagul D. Dosymbaeva; Esen N. Sulejmenov

    2014-01-01

    There has been carried out an investigation on the extraction of gold and silver from thiosulfate solutions: standard test and technological solutions of chemical and electrochemical leaching. The influence of related metals on the process of extracting gold from solution was studied. There has been conducted a comparative study of the IR spectra of solutions after the sorption of gold, silver and related metals.

  19. Restoration of uranium solution mining deposits

    Energy Technology Data Exchange (ETDEWEB)

    Devries, F.W.; Lawes, B.C.

    1982-01-19

    A process is provided for restoring an ore deposit after uranium solution mining using ammonium carbonate leaching solutions has ceased. The process involves flushing the deposit with an aqueous solution of a potassium salt during which potassium ions exchange with ammonium ions remaining in the deposit. The ammonium containing flushing solution is withdrawn from the deposit for disposal.

  20. Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

    Science.gov (United States)

    Khodadadi, M; Zendehdel, M; Baghbanzadeh, A; Babapour, V

    2017-10-01

    1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB 1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg). Experiments 2-4 were similar to Experiment 1 except birds were injected with either 6-OHDA (6-hydroxydopamine as dopamine synthesis inhibitor; 150 nmol), SCH23390 (D1 receptor antagonist; 5 nmol) and AMI-193 (D2 receptor antagonist; 5 nmol) instead of l-DOPA, respectively. Additionally, Experiments 5-8 followed the previous ones using the same dose of l-DOPA, 6-OHDA and dopamine antagonists except that birds were injected with CB65 (CB2 receptor agonist; 5 µg) instead of 2-AG. Coadministrations were at the same dose for each experiment. Cumulative feed intakes were measured until 120 min after each injection. 3. ICV administration of 6-OHDA and AMI-193 significantly attenuated 2-AG-induced hyperphagia. Interestingly, the hyperphagic effect of CB65 was significantly attenuated by administration of l-DOPA, whereas the administration of 6-OHDA and AMI-193 together amplified the hyperphagic effect of CB65. 4. It was concluded that cannabinoid-induced feeding behaviour is probably modulated by dopamine receptors in neonatal layer-type chickens. It seems that their interaction may be mediated by the D2-dopamine receptor.

  1. Exact solutions to quadratic gravity

    Czech Academy of Sciences Publication Activity Database

    Pravda, Vojtěch; Pravdová, Alena; Podolský, J.; Švarc, J.

    2017-01-01

    Roč. 95, č. 8 (2017), č. článku 084025. ISSN 2470-0010 R&D Projects: GA ČR GB14-37086G Institutional support: RVO:67985840 Keywords : quadratic gravity * exact solutions * Kundt spacetimes Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals.aps.org/prd/abstract/10.1103/PhysRevD.95.084025

  2. Providing solutions to engineering problems

    International Nuclear Information System (INIS)

    Connop, R.P.P.

    1991-01-01

    BNFL has acquired unique experience over a period of 40 years in specifying, designing and constructing spent fuel reprocessing and associated waste management plant. This experience is currently used to support a pound 5.5 billion capital investment programme. This paper reviews a number of engineering problems and their solutions to highlight BNFL experience in providing comprehensive specification, design and engineering and project management services. (author)

  3. New regular black hole solutions

    International Nuclear Information System (INIS)

    Lemos, Jose P. S.; Zanchin, Vilson T.

    2011-01-01

    In the present work we consider general relativity coupled to Maxwell's electromagnetism and charged matter. Under the assumption of spherical symmetry, there is a particular class of solutions that correspond to regular charged black holes whose interior region is de Sitter, the exterior region is Reissner-Nordstroem and there is a charged thin-layer in-between the two. The main physical and geometrical properties of such charged regular black holes are analyzed.

  4. ATM security via "Stargate" solution

    OpenAIRE

    Hensley, Katrina; Ludden, Fredrick

    1999-01-01

    Approved for public release, distribution unlimited. In today's world of integrating voice, video and data into a single network, Asynchronous Transfer Mode (ATM) networks have become prevalent in the Department of Defense. The Department of Defense's critical data will have to pass through public networks, which causes concern for security. This study presents an efficient solution aimed at authenticating communications over public ATM networks. The authenticating device, Stargate, utiliz...

  5. Clean Energy Solutions Center (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Reategui, S.

    2012-07-01

    The Clean Energy Ministerial launched the Clean Energy Solutions Center in April, 2011 for major economy countries, led by Australia and U.S. with other CEM partners. Partnership with UN-Energy is extending scope to support all developing countries: 1. Enhance resources on policies relating to energy access, small to medium enterprises (SMEs), and financing programs; 2. Offer expert policy assistance to all countries; 3. Expand peer to peer learning, training, and deployment and policy data for developing countries.

  6. Combinatorial solutions to integrable hierarchies

    Science.gov (United States)

    Kazarian, M. E.; Lando, S. K.

    2015-06-01

    This paper reviews modern approaches to the construction of formal solutions to integrable hierarchies of mathematical physics whose coefficients are answers to various enumerative problems. The relationship between these approaches and the combinatorics of symmetric groups and their representations is explained. Applications of the results to the construction of efficient computations in problems related to models of quantum field theories are described. Bibliography: 34 titles.

  7. Exact solutions to quadratic gravity

    Czech Academy of Sciences Publication Activity Database

    Pravda, Vojtěch; Pravdová, Alena; Podolský, J.; Švarc, J.

    2017-01-01

    Roč. 95, č. 8 (2017), č. článku 084025. ISSN 2470-0010 R&D Projects: GA ČR GB14-37086G Institutional support: RVO:67985840 Keywords : quadratic gravity * exact solutions * Kundt spacetimes Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals. aps .org/prd/abstract/10.1103/PhysRevD.95.084025

  8. Solution Prototyping with Design Thinking

    DEFF Research Database (Denmark)

    Efeoglu, Arkin; Møller, Charles; Serie, Michel

    2014-01-01

    are tried to be broken and Design Thinking advantages are increasingly preferred by man- agement. This case study based paper provides key insights into how DT phases and behavior can be changed for creating synergy across employees, manage- ment and products from which the end-consumer benefits. The Social...... Media for SAP store case study combines a conceptual and product oriented solution deri- vation with Design Thinking....

  9. Solution Prototyping with Design Thinking

    DEFF Research Database (Denmark)

    Efeoglu, Arkin; Møller, Charles; Serie, Michel

    are tried to be broken and Design Thinking advantages are increasingly preferred by man- agement. This case study based paper provides key insights into how DT phases and behavior can be changed for creating synergy across employees, manage- ment and products from which the end-consumer benefits. The Social...... Media for SAP store case study combines a conceptual and product oriented solution deri- vation with Design Thinking....

  10. Renormgroup symmetry for solution functionals

    International Nuclear Information System (INIS)

    Shirkov, D.V.; Kovalev, V.F.

    2004-01-01

    The paper contains generalization of the renormgroup algorithm for boundary value problems of mathematical physics and related concept of the renormgroup symmetry, formulated earlier by the authors with reference to models based on differential equations. These algorithm and symmetry are formulated now for models with nonlocal (integral) equations. We discuss in detail and illustrate by examples the applications of the generalized algorithm to models with nonlocal terms which appear as linear functionals of the solution. (author)

  11. Experimental Designs Exercises and Solutions

    CERN Document Server

    Kabe, DG

    2007-01-01

    This volume provides a collection of exercises together with their solutions in design and analysis of experiments. The theoretical results, essential for understanding, are given first. These exercises have been collected during the authors teaching courses over a long period of time. These are particularly helpful to the students studying the design of experiments and instructors and researchers engaged in the teaching and research of design by experiment.

  12. One Monopole-Antimonopole Pair Solutions

    International Nuclear Information System (INIS)

    Teh, Rosy; Wong, K.-M.

    2009-01-01

    We present new classical generalized one monopole-antimonopole pair solutions of the SU(2) Yang-Mills-Higgs theory with the Higgs field in the adjoint representation. We show that in general the one monopole-antimonopole solution need not be solved by imposing mθ-winding number to be integer greater than one. We also show that this solution can be solved when m = 1 by transforming the large distance asymptotic solutions to general solutions that depend on a parameter p. Secondly we show that these large distance asymptotic solutions can be further generalized to the Jacobi elliptic functions. We focus our numerical calculation on the Jacobi elliptic functions solution when the nφ-winding number is one and show that this generalized Jacobi elliptic 1-MAP solution possesses lower energy. All these solutions are numerical finite energy non-BPS solutions of the Yang-Mills-Higgs field theory.

  13. Linear superposition solutions to nonlinear wave equations

    International Nuclear Information System (INIS)

    Liu Yu

    2012-01-01

    The solutions to a linear wave equation can satisfy the principle of superposition, i.e., the linear superposition of two or more known solutions is still a solution of the linear wave equation. We show in this article that many nonlinear wave equations possess exact traveling wave solutions involving hyperbolic, triangle, and exponential functions, and the suitable linear combinations of these known solutions can also constitute linear superposition solutions to some nonlinear wave equations with special structural characteristics. The linear superposition solutions to the generalized KdV equation K(2,2,1), the Oliver water wave equation, and the k(n, n) equation are given. The structure characteristic of the nonlinear wave equations having linear superposition solutions is analyzed, and the reason why the solutions with the forms of hyperbolic, triangle, and exponential functions can form the linear superposition solutions is also discussed

  14. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  15. Excitatory amino acid receptors and disease.

    Science.gov (United States)

    Meldrum, B S

    1992-08-01

    Recent advances in the molecular biology of excitatory amino acid receptors are reviewed. Evidence that drugs blocking the excitatory action of glutamate at the N-methyl-D-aspartate (NMDA) and non-NMDA receptors may be of clinical use in epilepsy, Parkinson's disease, cerebral ischaemia and trauma, acquired immune deficiency syndrome (AIDS) encephalopathy and neuropathic pain is summarized.

  16. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Sander, Tommy; Bruun, Anne T; Balle, Thomas

    2010-01-01

    Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural...

  17. Structural Studies of Nicotinic Acetylcholine Receptors

    DEFF Research Database (Denmark)

    Shahsavar, Azadeh; Gajhede, Michael; Kastrup, Jette

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) are members of the pentameric ligand-gated ion channel superfamily that play important roles in control of neurotransmitter release in the central and peripheral nervous system. These receptors are important therapeutic targets for development of drugs...

  18. In vivo studies of opiate receptors

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

  19. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  20. Receptor study of psychiatric disorders using PET

    International Nuclear Information System (INIS)

    Suhara, Tetsuya

    1992-01-01

    Recent receptor studies of psychiatric disorders using PET have been focused on the change in the number of D 2 dopamine receptors in the striatum of drug-naive schizophrenic patients. One study confirmed an increase in D 2 receptors, while another study denied it. Although there were some differences in the approaches of the two groups, the reason for the discrepancy is not clear yet. Looking to psychiatric disorders other than schizophrenia, our recent study revealed a possible role of dopamine D 1 receptors in bipolar mood disorders. However, some problems must be resolved for further receptor studies with PET. For example, our recent study shows that desipamine decreases the in vivo binding of dopramine D 1 and D 2 receptors whereas these is no effect on dopamine D 1 and D 2 receptors in vitro. Additionally significant methodological problems lie in the method of evaluation of the non-specific binding and the effect of endogenous neurotransmitters. Moreover, difficulties in the diagnosis of psychiatric disorders and ethical problems in psychiatric research are critical factors in receptor studies with PET in psychiatric disorders. (author)

  1. P2X receptors in epithelia

    DEFF Research Database (Denmark)

    Leipziger, Jens Georg

    2015-01-01

    P2X receptors are ubiquitously expressed in all epithelial tissues but their functional roles are less well studied. Here we review the current state of knowledge by focusing on functional effects of P2X receptor in secretory and in absorptive tissues. In glandular tissue like the parotid gland...

  2. Structural Mapping of Adenosine Receptor Mutations

    DEFF Research Database (Denmark)

    Jespers, Willem; Schiedel, Anke C; Heitman, Laura H

    2018-01-01

    The four adenosine receptors (ARs), A1, A2A, A2B, and A3, constitute a subfamily of G protein-coupled receptors (GPCRs) with exceptional foundations for structure-based ligand design. The vast amount of mutagenesis data, accumulated in the literature since the 1990s, has been recently supplemente...

  3. Emerging functions for neuropeptide Y5 receptors

    NARCIS (Netherlands)

    Bischoff, A.; Michel, M. C.

    1999-01-01

    The Y5 subtype of neuropeptide Y (NPY) receptors has raised considerable interest as a mediator of NPY-stimulated food intake, but with the advent of recent data, this hypothesis has come into question. Moreover, Y5 receptor-selective drugs might not be specific for food intake because additional

  4. Immunohistochemical assessment of oestrogen and progesterone receptors

    DEFF Research Database (Denmark)

    Grabau, D A; Thorpe, S M; Knoop, A

    2000-01-01

    Two different methods to determine steroid receptors were analysed with respect to their ability to estimate prognosis in primary breast cancer patients. The immunohistochemical assay (IHA) was compared with the dextran-coated charcoal (DCC) method of receptor determination. A random sample of 28...... distinction between benign and malignant tissue is possible using the IHAmethod. Thus, IHAresults appear to be more clinically relevant....

  5. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

    In this study, receptors that may be involved in the uptake of low density lipoproteins (LDL) and low density lipoproteins which have been modified by acetylation (AcLDL), were characterized. Aortic epithelial cells were used and a cell culture system which closely resembled the in vivo monolayer was established. Endothelial cell and lipoprotein interactions were examined by incubating the cells with 125 l-labelled lipoproteins under various conditions. The receptor affinity of bovine aortic endothelial cells was higher for AcLDL than that for LDL. Competition studies demonstrated that there were two distinct receptors for LDL and AcLDL on the endothelial cells. AcLDL did not compete with LDL for the LDL receptor, and conversely LDL did not compete with AcLDL for the AcLDL receptor. The receptor activities for LDL and AcLDL were examined as a function of culture age. Whereas the LDL receptor could be regulated, the AcLDL receptor was not as susceptible to regulation. Upon exposing endothelial cells for 72 h to either LDL or AcLDL, it was found that the total amount of cellular cholesterol increased by about 50%. However, the increase of total cholesterol was largely in the form of free cholesterol. This is in contrast to macrophages, where the increase in total cholesterol upon exposure to AcLDL is largely in the form cholesteryl esters

  6. Thermogenic characterization of ghrelin receptor null mice

    Science.gov (United States)

    Ghrelin is the only known circulating orexigenic hormone that increases food intake and promotes adiposity, and these physiological functions of ghrelin are mediated through its receptor growth hormone secretagogue receptor (GHS-R). Ghrelin/GHS-R signaling plays a crucial role in energy homeostasis....

  7. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond

    2017-01-01

    pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...

  8. Neutral anion receptors: design and application

    NARCIS (Netherlands)

    Antonisse, M.M.G.; Reinhoudt, David

    1998-01-01

    After the development of synthetic cation receptors in the late 1960s, only in the past decade has work started on the development of synthetic neutral anion receptors. Combination and preorganization of different anion binding groups, like amides, urea moieties, or Lewis acidic metal centers lead

  9. NRSAS: Nuclear Receptor Structure Analysis Servers.

    NARCIS (Netherlands)

    Bettler, E.J.M.; Krause, R.; Horn, F.; Vriend, G.

    2003-01-01

    We present a coherent series of servers that can perform a large number of structure analyses on nuclear hormone receptors. These servers are part of the NucleaRDB project, which provides a powerful information system for nuclear hormone receptors. The computations performed by the servers include

  10. Transient receptor potential channels in essential hypertension

    DEFF Research Database (Denmark)

    Liu, Daoyan; Scholze, Alexandra; Zhu, Zhiming

    2006-01-01

    The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated.......The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated....

  11. Receptor tyrosine kinase signaling: a view from quantitative proteomics

    DEFF Research Database (Denmark)

    Dengjel, Joern; Kratchmarova, Irina; Blagoev, Blagoy

    2009-01-01

    Growth factor receptor signaling via receptor tyrosine kinases (RTKs) is one of the basic cellular communication principals found in all metazoans. Extracellular signals are transferred via membrane spanning receptors into the cytoplasm, reversible tyrosine phosphorylation being the hallmark of all...

  12. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    Directory of Open Access Journals (Sweden)

    Hiroki Ide

    2015-01-01

    Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

  13. Exact Solutions for Two Equation Hierarchies

    International Nuclear Information System (INIS)

    Song-Lin, Zhao; Da-Jun, Zhang; Jie, Ji

    2010-01-01

    Bilinear forms and double-Wronskian solutions are given for two hierarchies, the (2+1)-dimensional breaking Ablowitz–Kaup–Newell–Segur (AKNS) hierarchy and the negative order AKNS hierarchy. According to some choices of the coefficient matrix in the Wronskian condition equation set, we obtain some kinds of solutions for these two hierarchies, such as solitons, Jordan block solutions, rational solutions, complexitons and mixed solutions. (general)

  14. Stabilization of functional recombinant cannabinoid receptor CB(2 in detergent micelles and lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Krishna Vukoti

    Full Text Available Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB(2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB(2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB(2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of (2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB(2 in dodecyl maltoside (DDM/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB(2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at

  15. Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

    Directory of Open Access Journals (Sweden)

    María S. Aymerich

    2011-01-01

    Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

  16. β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

    International Nuclear Information System (INIS)

    Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

    1987-01-01

    Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

  17. Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

    Science.gov (United States)

    Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

    2016-04-12

    Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. Copyright © 2016, American Association for the Advancement of Science.

  18. The ABA receptors -- we report you decide.

    Science.gov (United States)

    McCourt, Peter; Creelman, Robert

    2008-10-01

    The plant hormone abscisic acid (ABA) has been implicated in a variety of physiological responses ranging from seed dormancy to stomatal conductance. Recently, three groups have reported the molecular identification of three disparate ABA receptors. Unlike the identification of other hormone receptors, in these three cases high affinity binding to ABA rather than the isolation of ABA insensitive mutants led to these receptor genes. Interestingly, two of the receptors encode genes involved in floral timing and chlorophyll biosynthesis, which are not considered traditional ABA responses. And the third receptor has been clouded in issues of its molecular identity. To clearly determine the roles of these genes in ABA perception it will require placing of these ABA-binding proteins into the rich ABA physiological context that has built up over the years.

  19. Sigma-2 receptor ligands QSAR model dataset

    Directory of Open Access Journals (Sweden)

    Antonio Rescifina

    2017-08-01

    Full Text Available The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2 receptor ligands selective over Sigma-1 (σ1 receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together. Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included.

  20. Computer modeling of Cannabinoid receptor type 1

    Directory of Open Access Journals (Sweden)

    Sapundzhi Fatima

    2018-01-01

    Full Text Available Cannabinoid receptors are important class of receptors as they are involved in various physiological processes such as appetite, pain-sensation, mood, and memory. It is important to design receptor-selective ligands in order to treat a particular disorder. The aim of the present study is to model the structure of cannabinoid receptor CB1 and to perform docking between obtained models and known ligands. Two models of CBR1 were prepared with two different methods (Modeller of Chimera and MOE. They were used for docking with GOLD 5.2. It was established a high correlation between inhibitory constant Ki of CB1 cannabinoid ligands and the ChemScore scoring function of GOLD, which concerns both models. This suggests that the models of the CB1 receptors obtained could be used for docking studies and in further investigation and design of new potential, selective and active cannabinoids with the desired effects.

  1. The AT2 Receptor and Inflammation

    DEFF Research Database (Denmark)

    Esquitino, Veronica Valero; Danyel, Leon Alexander; Steckelings, Ulrike M.

    2015-01-01

    This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed...... by a review of the existing literature addressing the role of the AT2 receptor in a wide range of disorders, in which acute or chronic inflammation is an essential contributor to the pathology. These disorders comprise cardiovascular, cerebrovascular, renal, and autoimmune diseases.Taken as a whole......, the vast majority of data support an anti-inflammatory and immunomodulatory role of the AT2 receptor. In light of the current development of AT2 receptor agonists as future drugs for clinical use, diseases with a marked inflammatory component may become a major area of therapeutic use...

  2. Ror receptor tyrosine kinases: orphans no more.

    Science.gov (United States)

    Green, Jennifer L; Kuntz, Steven G; Sternberg, Paul W

    2008-11-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these mysterious proteins and, in particular, we focus on their function as Wnt receptors.

  3. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  4. Androgen insensitivity syndrome: gonadal androgen receptor activity

    International Nuclear Information System (INIS)

    Coulam, C.B.; Graham, M.L.; Spelsberg, T.C.

    1984-01-01

    To determine whether abnormalities of the androgen receptor previously observed in skin fibroblasts from patients with androgen insensitivity syndrome also occur in the gonads of affected individuals, androgen receptor activity in the gonads of a patient with testicular feminization syndrome was investigated. Using conditions for optimal recovery of androgen receptor from human testes established by previous studies, we detected the presence of a high-affinity (dissociation constant . 3.2 X 10(-10) mol/L), low-capacity (4.2 X 10(-12) mol/mg DNA), androgen-binding protein when tritium-labeled R1881 was incubated at 4 degrees C with nuclear extracts from the gonads of control patients or from a patient with testicular feminization syndrome but not when incubated at 37 degrees C. Thus this patient has an androgen receptor with a temperature lability similar to that of receptors from normal persons

  5. Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors.

    Science.gov (United States)

    Kwon, S G; Roh, D H; Yoon, S Y; Choi, S R; Choi, H S; Moon, J Y; Kang, S Y; Kim, H W; Han, H J; Beitz, A J; Oh, S B; Lee, J H

    2016-04-01

    The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats. Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αβmeATP. Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain. © 2015 European Pain Federation - EFIC®

  6. Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

    DEFF Research Database (Denmark)

    Sivertsen, B; Holliday, N; Madsen, A N

    2013-01-01

    UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

  7. Activation of glucocorticoid receptors increases 5-HT2A receptor levels

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

    2009-01-01

    an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

  8. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  9. New compacton solutions and solitary wave solutions of fully nonlinear generalized Camassa-Holm equations

    International Nuclear Information System (INIS)

    Tian Lixin; Yin Jiuli

    2004-01-01

    In this paper, we introduce the fully nonlinear generalized Camassa-Holm equation C(m,n,p) and by using four direct ansatzs, we obtain abundant solutions: compactons (solutions with the absence of infinite wings), solitary patterns solutions having infinite slopes or cups, solitary waves and singular periodic wave solutions and obtain kink compacton solutions and nonsymmetry compacton solutions. We also study other forms of fully nonlinear generalized Camassa-Holm equation, and their compacton solutions are governed by linear equations

  10. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    Science.gov (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  11. Commercial Lighting Solutions Webtool Peer Review Report, Office Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Beeson, Tracy A.; Jones, Carol C.

    2010-02-01

    The Commercial Lighting Solutions (CLS) project directly supports the U.S. Department of Energy’s Commercial Building Energy Alliance efforts to design high performance buildings. CLS creates energy efficient best practice lighting designs for widespread use, and they are made available to users via an interactive webtool that both educates and guides the end user through the application of the Lighting Solutions. This report summarizes the peer review of the CLS webtool for offices. The methodology for the peer review process included data collection (stakeholder input), analysis of the comments, and organization of the input into categories for prioritization of the comments against a set of criteria. Based on this process, recommendations were developed for the release of version 2.0 of the webtool at the Lightfair conference in Las Vegas in May 2010. The report provides a list of the top ten most significant and relevant improvements that will be made within the webtool for version 2.0 as well as appendices containing the comments and short-term priorities in additional detail. Peer review comments that are considered high priority by the reviewers and the CLS team but cannot be completed for Version 2.0 are listed as long-term recommendations.

  12. The repertoire of trace amine G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Gloriam, David E.; Bjarnadóttir, Thóra K; Yan, Yi-Lin

    2005-01-01

    eukaryotic species for receptors similar to the mammalian trace amine (TA) receptor subfamily. We identified 18 new receptors in rodents that are orthologous to the previously known TA-receptors. Remarkably, we found 57 receptors (and 40 pseudogenes) of this type in the zebrafish (Danio rerio), while fugu...... (Takifugu rubripes) had only eight receptors (and seven pseudogenes). We mapped 47 of the zebrafish TA-receptors on chromosomes using radiation hybrid panels and meiotic mapping. The results, together with the degree of conservation and phylogenetic relationships displayed among the zebrafish receptors...

  13. Exclusive nuclear location of estrogen receptors in Squalus testis.

    Science.gov (United States)

    Callard, G V; Mak, P

    1985-01-01

    An estrogen (E)-binding molecule having both occupied and unoccupied sites is restricted to nuclear subfractions in the testis of the spiny dogfish (Squalus acanthias). We investigated the hypothesis that a species characterized by high body-fluid osmolarity (1010 mosM) has an estrogen receptor (ER) that binds to chromatin with high affinity and consequently resists redistribution during tissue processing. Although the steroid binding and sedimentation properties of the Squalus nuclear ER conformed to those of classical ER, its elution maximum from DNA-cellulose was unusually high (0.55 M NaCl). A tendency to adhere tightly to cell nuclei was reflected in the high salt concentration (0.43 M KCl) required to extract 50% of the receptors from the nuclear compartment during homogenization and in the stability of the nuclear ER population in the presence of high concentrations of a nonionic solute (urea) or increased buffer volume. Mixing and redistribution experiments showed that nuclear ER could be quantitatively and qualitatively measured in cytosolic extracts, ruling out the possibility that soluble receptors were being masked. Although Squalus oviduct ER was similar to that of testis, ER in the testis and liver of a related elasmobranch (Potamotrygon) that maintains osmotic equilibrium at 300 mosM more closely resembled mammalian ER in its elution maximum from DNA-cellulose (0.22 M NaCl) and cytosolic/nuclear ratios in low-salt buffers. We conclude that Squalus testis has a single ER pool located exclusively in the nuclear compartment. These observations support a revised concept of steroid action and further indicate that the chromatin affinity of the hormone-ER complex is an important factor in determining subfractional distribution during tissue processing. PMID:3856265

  14. Alkylating derivative of oxotremorine interacts irreversibly with the muscarinic receptor

    International Nuclear Information System (INIS)

    Ehlert, F.J.; Jenden, D.J.; Ringdahl, B.

    1984-01-01

    A 2-chloroethylamine derivative of oxotremorine was studied in pharmacological experiments and muscarinic receptor binding assays. The compound, N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone (BM 123), forms an aziridinium ion in aqueous solution at neutral pH that stimulates contractions of guinea pig ileum with a potency similar to that of oxotremorine. Following the initial stimulation, there is a long lasting period of lack of sensitivity of the guinea pig ileum to muscarinic agonists. BM 123 also produces muscarinic effects in vivo. When homogenates of the rat cerebral cortex were incubated with BM 123 and assayed subsequently in muscarinic receptor binding assays, a loss of binding capacity for the muscarinic antagonist, [ 3 H]N-methylscopolamine ([ 3 H]NMS), was noted without a change in affinity. Similar observations were made in [ 3 H]1-3-quinuclidinyl benzilate ([ 3 H]-QNB) binding assays on the forebrains of mice that had been injected with BM 123 24 hr earlier. The loss in receptor capacity for both [ 3 H]NMS and [ 3 H]-QNB was prevented by atropine treatment. Kinetic studies of the interaction of BM 123 with homogenates of the rat cerebral cortex in vitro showed that the half-time for the loss of [ 3 H]-QNB binding sites increased from 10 to 45 min as the concentration of BM 123 decreased from 10 to 1 μM. In contrast to the aziridinium ion, the parent 2-chloroethylamine compound and the alcoholic hydrolysis product were largely devoid of pharmacological and binding activity

  15. Approximate solutions to Mathieu's equation

    Science.gov (United States)

    Wilkinson, Samuel A.; Vogt, Nicolas; Golubev, Dmitry S.; Cole, Jared H.

    2018-06-01

    Mathieu's equation has many applications throughout theoretical physics. It is especially important to the theory of Josephson junctions, where it is equivalent to Schrödinger's equation. Mathieu's equation can be easily solved numerically, however there exists no closed-form analytic solution. Here we collect various approximations which appear throughout the physics and mathematics literature and examine their accuracy and regimes of applicability. Particular attention is paid to quantities relevant to the physics of Josephson junctions, but the arguments and notation are kept general so as to be of use to the broader physics community.

  16. Fuel cell vehicles: technological solution

    International Nuclear Information System (INIS)

    Lopez Martinez, J. M.

    2004-01-01

    Recently it takes a serious look at fuel cell vehicles, a leading candidate for next-generation vehicle propulsion systems. The green house effect and air quality are pressing to the designers of internal combustion engine vehicles, owing to the manufacturers to find out technological solutions in order to increase the efficiency and reduce emissions from the vehicles. On the other hand, energy source used by currently propulsion systems is not renewable, the well are limited and produce CO 2 as a product from the combustion process. In that situation, why fuel cell is an alternative of internal combustion engine?

  17. Greenhouse effect: there are solutions

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    A review of solutions that may be undertaken in order to reduce the greenhouse effect gas emissions is presented: clean energy generation through municipal, agricultural and industrial waste processing, reducing energy consumption through public transportation promotion, clean fuel buses and vehicles, or using energy efficient boilers, reduction of carbon dioxide emission from industry through process optimization, waste recycling, energy substitution and conservation, diminution of CO 2 emissions in commercial and residential sectors through space heating and air conditioning retrofitting, lighting substitution. Pollution abatement potentials are evaluated in each case, notably in France

  18. Integrated solution for field operations

    Energy Technology Data Exchange (ETDEWEB)

    Aubin, Renaud; Dionis, Francois [EDF, Chatou (France)

    2014-08-15

    This document presents our approach to design and to implement mobile applications for field operations. Internal on-field studies yield to the fact that the value added by mobile solutions is correlated with the easiness of their integration with each other and with the underlying information systems. Moreover, the fast-growing mobile market brings new concepts to the mass and industrial applications design can benefit from these. As a consequence, a simple components-based approach has been applied to design and develop mobile applications for field operations and on-site experiments of the resulting applications have been conducted.

  19. Integrated solution for field operations

    International Nuclear Information System (INIS)

    Aubin, Renaud; Dionis, Francois

    2014-01-01

    This document presents our approach to design and to implement mobile applications for field operations. Internal on-field studies yield to the fact that the value added by mobile solutions is correlated with the easiness of their integration with each other and with the underlying information systems. Moreover, the fast-growing mobile market brings new concepts to the mass and industrial applications design can benefit from these. As a consequence, a simple components-based approach has been applied to design and develop mobile applications for field operations and on-site experiments of the resulting applications have been conducted

  20. Silverlight 4 Problem - Design - Solution

    CERN Document Server

    Lecrenski, Nick

    2010-01-01

    A hands-on guide to Microsoft's latest rich application development technology: Silverlight 4. Silverlight 4 is the newest version of the rich Internet application toolkit that provides support for .NET capabilities over the Internet. With this latest release of Silverlight, Microsoft has revolutionized the way that Web applications can be created. This book uses the popular Problem – Design – Solution strategy to demonstrate how to harness the power and abilities of Silverlight 4 to add value to the overall user experience of a Web site. Using a Web site created by the author as a reference p

  1. Symmetries and Dirac equation solutions

    International Nuclear Information System (INIS)

    Souza, Marcio Lima de.

    1991-06-01

    The purpose of this thesis is the extension to be relativistic case of a method that has proved useful for the solution of various potential problems in non relativistic situation. This method, the method of dynamical symmetries, is based on the Baker-Campbell-Hausdorf formulae and developed first for the particular example of the relativistic Coulomb problem. Here we generalize the method for a Hamiltonian that can be written as a linear combination of generators of the SO(2,1) group. As illustrative examples, we solve the problem of a charged particle in a constant magnetic field and the exponential magnetic field. (author). 21 refs

  2. Integrated solution for field operations

    International Nuclear Information System (INIS)

    Aubin, Renaud; Dionis, Francois

    2014-01-01

    This paper presents the authors' approach to design and to implement mobile applications for field operations. Internal on-field studies can yield the fact that the value-added by mobile solutions is correlated with the easiness of their integration with each other and with the underlying information systems. Moreover, the fast-growing mobile market brings new concepts to the mass and industrial applications design can benefit from these. As a consequence, a simple components-based approach has been applied to design and develop mobile applications for field operations and on-site experiments of the resulting applications have been conducted. (author)

  3. MIGRATION – EFFECTS AND SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Raluca Cruceru

    2012-12-01

    Full Text Available There are three main flows that influence workforce performance—worker migration, the dissemination of knowledge, and overseas development assistance. For the present paper we decided to deal with the analyses of these three, yet mainly migration. We considered it to be one of the most important phenomenon existent on the market at this hour and with the highest negative impact on the economic and social situation. We presented a case study regarding the situation of migration in Romania and the main candidates to Romanian intelligence imports, the main issues and possible solutions to the problems encountered.

  4. Transition state structures in solution

    International Nuclear Information System (INIS)

    Bertran, J.; Lluch, J. M.; Gonzalez-Lafont, A.; Dillet, V.; Perez, V.

    1995-01-01

    In the present paper the location of transition state structures for reactions in solution has been studied. Continuum model calculations have been carried out on the Friedel-Crafts alkylation reaction and a proton transfer through a water molecule between two oxygen atoms in formic acid. In this model the separation between the chemical system and the solvent has been introduced. On the other hand, the discrete Monte Carlo methodology has also been used to simulate the solvent effect on dissociative electron transfer processes. In this model, the hypothesis of separability is not assumed. Finally, the validity of both approaches is discussed

  5. Lanthanide complexation in aqueous solutions

    International Nuclear Information System (INIS)

    Choppin, G.R.

    1984-01-01

    The lanthanide elements form an extended series of cations with the same charge, slightly varying radii and useful magnetic and spectroscopic properties. Their use in technology is growing rapidly as their properties are more fully explored. The lanthanides also offer scientists valuable and often unique probes for investigating a variety of chemical and physical phenomena. This review has attempted to call attention to these latter uses without trying to provide a thorough discussion of all the relevant literature. Hopefully, awareness of the more interesting facets of present studies of lanthanide complexes in aqueous solution will spur even more advances in the use of these elements. (Auth.)

  6. Renaturation of the androgen receptor after denaturation in SDS

    International Nuclear Information System (INIS)

    Johnson, M.P.; Young, C.Y.F.; Rowley, D.R.; Tindall, D.J.

    1986-01-01

    Renaturation of the steroid binding activity of receptor proteins is a potentially useful tool for their purification and analysis. Cytosol was prepared from rat Dunning prostate tumor in buffer containing molybdate and then denatured by addition of SDS buffer and heating. Aliquots were precipitated in cold acetone and the resulting pellets were washed and solubilized with a small volume of solution containing a chaotropic agent such as 6M guanidine, 8M urea, or 5M sodium iodide. After a 20-minute incubation, samples were diluted 20-fold with buffer containing 4nM [ 3 H]dihydrotestosterone with or without excess unlabeled dihydrotestosterone. Diluted samples were incubated at 0 0 C for varying periods of time prior to assay of bound radioactivity using hydroxylapatite. A time-course of renaturation after exposure to guanidine showed a steady increase of specific binding activity during the first 7 hrs post-dilution that remained stable up to 22 hrs. Experiments with guanidine consistently demonstrated that 25-50% of binding activity was recoverable. Preliminary results using urea or sodium iodide were similar. Efforts to optimize recovery and to characterize the renatured androgen receptor are in progress

  7. Metazoan-like signaling in a unicellular receptor tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Schultheiss Kira P

    2013-02-01

    Full Text Available Abstract Background Receptor tyrosine kinases (RTKs are crucial components of signal transduction systems in multicellular animals. Surprisingly, numerous RTKs have been identified in the genomes of unicellular choanoflagellates and other protists. Here, we report the first biochemical study of a unicellular RTK, namely RTKB2 from Monosiga brevicollis. Results We cloned, expressed, and purified the RTKB2 kinase, and showed that it is enzymatically active. The activity of RTKB2 is controlled by autophosphorylation, as in metazoan RTKs. RTKB2 possesses six copies of a unique domain (designated RM2 in its C-terminal tail. An isolated RM2 domain (or a synthetic peptide derived from the RM2 sequence served as a substrate for RTKB2 kinase. When phosphorylated, the RM2 domain bound to the Src homology 2 domain of MbSrc1 from M. brevicollis. NMR structural studies of the RM2 domain indicated that it is disordered in solution. Conclusions Our results are consistent with a model in which RTKB2 activation stimulates receptor autophosphorylation within the RM2 domains. This leads to recruitment of Src-like kinases (and potentially other M. brevicollis proteins and further phosphorylation, which may serve to increase or dampen downstream signals. Thus, crucial features of signal transduction circuitry were established prior to the evolution of metazoans from their unicellular ancestors.

  8. Radiosynthesis of [11C]SB-705498, a selective transient receptor potential Vanilloid 1 (TRPV1) receptor antagonist

    International Nuclear Information System (INIS)

    Dolle, F.; Bramoulle, Y.; Deverre, J.R.; Bottlaender, M.; Passchier, J.

    2011-01-01

    column (eluent: H 2 O / CH 3 CN / TFA: 72 / 28 / 0.1 (v/v/v) - flowrate: 8 mL/min), and finally (D) removal of the HPLC solvents using a SepPak R Plus C18 device (recovery of [ 11 C]SB-705498 ([ 11 C]-1) as ethanol solution), sterile-filtration (Millex FG 0.22 μm filter, Millipore) and final formulation as an i.v. injectable solution. Results: [ 11 C]SB-705498 ([ 11 C]-1) was obtained in 8.9-13.6% non-decay-corrected yields, based on starting [ 11 C]methane. Starting from a 26 GBq cyclotron-produced [ 11 C]methane batch, 2.3 to 3.5 GBq of [ 11 C]SB-705498 ([ 11 C]-1), ≥ 99% radiochemically pure and ready-to-inject, were obtained in a one-pot two-step process within 30 minutes (including HPLC-purification, Rt: 9-10 min, and formulation). Specific radioactivities ranged from 75 to 150 GBq/μmol. Conclusions: SB-705498 (1) was isotopically labelled with carbon-11 at its urea function using [ 11 C]phosgene. The non-decay-corrected overall yields for the preparation of [ 11 C]SB-705498 were 8.9%-13.6%. Dynamic PET studies in baboons are currently underway to evaluate the potential of [ 11 C]SB-705498 to image central transient receptor potential Vanilloid 1 (TRPV1) receptor in vivo

  9. Action mechanisms of Liver X Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Gabbi, Chiara; Warner, Margaret [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Gustafsson, Jan-Åke, E-mail: jgustafs@central.uh.edu [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Department of Biosciences and Nutrition, Karolinska Institutet, Novum S-141 86 (Sweden)

    2014-04-11

    Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors.

  10. Action mechanisms of Liver X Receptors

    International Nuclear Information System (INIS)

    Gabbi, Chiara; Warner, Margaret; Gustafsson, Jan-Åke

    2014-01-01

    Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors

  11. The cellular receptors of exogenous RNA

    Directory of Open Access Journals (Sweden)

    Patryk Reniewicz

    2016-04-01

    Full Text Available One of the key determinants of survival for organisms is proper recognition of exogenous and endogenous nucleic acids. Therefore, high eukaryotes developed a number of receptors that allow for discrimination between friend or foe DNA and RNA. Appearance of exogenous RNA in cytoplasm provides a signal of danger and triggers cellular responses that facilitate eradication of a pathogen. Recognition of exogenous RNA is additionally complicated by fact that large amount of endogenous RNA is present in cytoplasm Thus, number of different receptors, found in eukaryotic cells, is able to recognize that nucleic acid. First group of those receptors consist endosomal Toll like receptors, namely TLR3, TLR7, TLR8 and TLR13. Those receptors recognize RNA released from pathogens that enter the cell by endocytosis. The second group includes cytoplasmic sensors like PKR and the family of RLRs comprised of RIG-I, MDA5 and LGP2. Cytoplasmic receptors recognize RNA from pathogens invading the cell by non-endocytic pathway. In both cases binding of RNA by its receptors results in activation of the signalling cascades that lead to the production of interferon and other cytokines.

  12. Receptor mapping in psychiatric patients with SPECT

    International Nuclear Information System (INIS)

    Schlegel, S.

    1997-01-01

    This paper summarizes some data of our studies with the single-photon-emission-computerized tomography (SPECT), focussing on the dopamine-D2- and the benzodiazepine receptor mapping. Benzodiazepine receptors: Central benzodiazepine receptors (BZr) can be visualized with iomazenil which is an analogue of the benzodiazepine antagonist flumazenil, labeled with 123-iodine. Since the involvement of the BZr system is discussed in the pathogenesis of anxiety and depression, patients with these disorders were investigated. A third study investigated the BZr-occupancy during benzodiazepine treatment (lorazepam). Results: (a) Patients with panic disorders had lower iomazenil uptake values compared to epileptic patients. (b) Depressed patients showed a positive correlation between severity of illness and frontal uptake. (c) BZr occupancy during lorazepam treatment was measurable, but not associated with lorazepam plasma levels. Dopamine-D2-receptors: With 123-I-iodobenzamide (IBZM), and iodine-labeled dopamine receptor ligand, the D2 receptor density can be measured by a semiquantitative approach (striatum/frontal cortex=ST/FC). Therefore, we investigated the D2-receptor occupancy during treatment with typical and atypical neuroleptics in relationship to dosages (normalized with different formulas of chlorpromazine equivalents), side effects, and prolactin plasma levels. Results: Dependent on the selected formula for chlorpromazine equivalents, the ST/FC ratio was correlated with dosages. Side effects and prolactin plasma levels showed a negative association with lower ST/FC ratios. (orig.) [de

  13. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  14. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    Rosenvinge, Erik C. von; Raufman, Jean-Pierre

    2011-01-01

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

  15. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  16. Psychopharmacology of 5-HT1A receptors

    International Nuclear Information System (INIS)

    Cowen, Philip J.

    2000-01-01

    Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

  17. Tachykinin receptors in the equine pelvic flexure

    International Nuclear Information System (INIS)

    Sonea, I.M.; Wilson, D.V.; Bowker, R.M.; Robinson, N.E.

    1997-01-01

    Tachykinins, of which substance P (SP) is the prototype, are neuropeptides which are widely distributed in the nervous systems. In the equine gut, SP is present in enteric nerves and is a powerful constrictor of enteric muscle; in other species, SP is also known to have potent vasodilatory and pro-inflammatory effects. The specific effects of SP are determined by the subtype of receptor present in the target tissue. There are 3 known subtypes of tachykinin receptors, distinguished by their relative affinities for SP and other tachykinins. The distribution of SP binding sites in the equine pelvic flexure was determined using 125I-Bolton Hunter SP (I-BHSP) autoradiography. Most I-BHSP binding sites were determined to be saturable and specific, therefore presumably representing tachykinin receptors. The greatest degree of I-BHSP binding occurred over very small vessels, and over the muscularis mucosae; I-BHSP binding was also intense over the circular muscle of the muscularis externa and mucosa, and present, although less intense, over the longitudinal muscle of the muscularis externa. Competition of I-BHSP with specific receptor agonists for binding sites in the equine pelvic flexure were used to determine the subtypes of tachykinin receptors present. The neurokinin-1 receptor subtype predominated in the equine pelvic flexure, followed by the neurokinin-3 receptor subtype

  18. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  19. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  20. Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

    Science.gov (United States)

    Peñas-Cazorla, Raúl; Vilaró, M Teresa

    2015-11-01

    Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

  1. Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

    Science.gov (United States)

    Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

    2012-05-01

    The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  2. N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

    Science.gov (United States)

    Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

    2017-07-01

    N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

  3. Research on cloud computing solutions

    Directory of Open Access Journals (Sweden)

    Liudvikas Kaklauskas

    2015-07-01

    Full Text Available Cloud computing can be defined as a new style of computing in which dynamically scala-ble and often virtualized resources are provided as a services over the Internet. Advantages of the cloud computing technology include cost savings, high availability, and easy scalability. Voas and Zhang adapted six phases of computing paradigms, from dummy termi-nals/mainframes, to PCs, networking computing, to grid and cloud computing. There are four types of cloud computing: public cloud, private cloud, hybrid cloud and community. The most common and well-known deployment model is Public Cloud. A Private Cloud is suited for sensitive data, where the customer is dependent on a certain degree of security.According to the different types of services offered, cloud computing can be considered to consist of three layers (services models: IaaS (infrastructure as a service, PaaS (platform as a service, SaaS (software as a service. Main cloud computing solutions: web applications, data hosting, virtualization, database clusters and terminal services. The advantage of cloud com-puting is the ability to virtualize and share resources among different applications with the objective for better server utilization and without a clustering solution, a service may fail at the moment the server crashes.DOI: 10.15181/csat.v2i2.914

  4. Peritoneal solute transport and inflammation.

    Science.gov (United States)

    Davies, Simon J

    2014-12-01

    The speed with which small solutes cross the peritoneal membrane, termed peritoneal solute transport rate (PSTR), is a key measure of individual membrane performance. PSTR can be quantified easily by using the 4-hour dialysate to plasma creatinine ratio, which, although only an approximation to the diffusive characteristics of the membrane, has been well validated clinically in terms of its relationship to patient survival and changes in longitudinal membrane function. This has led to changes in peritoneal dialysis modality use and dialysis prescription. An important determinant of PSTR is intraperitoneal inflammation, as exemplified by local interleukin 6 production, which is largely independent of systemic inflammation and its relationship to comorbid conditions and increased mortality. There is no strong evidence to support the contention that the peritoneal membrane in some individuals with high PSTR is qualitatively different at the start of treatment; rather, it represents a spectrum that is determined in part by genetic factors. Both clinical and experimental evidence support the view that persistent intraperitoneal inflammation, detected as a continuously high or increasing PSTR, may predispose the membrane to progressive fibrosis. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  5. INTERCULTURAL MISUNDERSTANDINGS: CAUSES AND SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Майкл Б Хиннер

    2017-12-01

    Full Text Available Intercultural misunderstandings involve a number of complex causes which can easily escalate into conflicts. Since conflicts are also complex, it is not easy to find solutions because there is no one solution for all problems. Systems Theory, transdisciplinarity, and the social ecological model take a holistic approach in investigating complex phenomena. They permit the creation of a theoretical framework based on previous empirical research and theories across scientific disciplines to identify the relevant elements of complex phenomena and to understand the interrelationship of these elements. Intercultural misunderstandings and conflicts are very complex phenomena because they include culture, perception, identity, ethnocentrism, relationships, trust building and conflict management as well as intercultural commu-nication competence which entails cognition, metacognition, and social metacognition. Since most em-pirical studies focus on isolated, individual elements in specific contexts, this article describes the theoretical framework of how the various findings and theories developed in different scientific disciplines can be used to form a cohesive framework to help circumvent intercultural misunderstandings and conflicts. In so doing, it follows the general principles of Systems Theory, transdisciplinarity, and the social ecological model.

  6. Evolution of endothelin receptors in vertebrates.

    Science.gov (United States)

    Braasch, Ingo; Schartl, Manfred

    2014-12-01

    Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

  7. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Wolverton, C.

    2007-01-01

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  8. Lactate Transport and Receptor Actions in Retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken

    2016-01-01

    known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions......In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also...

  9. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    Science.gov (United States)

    Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

  10. A competitive solution for cooperative truckload delivery

    NARCIS (Netherlands)

    Hezarkhani, B.; Slikker, M.; Woensel, van T.

    2016-01-01

    This paper introduces a solution for gain sharing in consortia of logistic providers where joint planning of truckload deliveries enables the reduction of empty kilometers. The highly competitive nature of freight transport markets necessitates solutions that distinguish among the logistics

  11. Mean-field learning for satisfactory solutions

    KAUST Repository

    Tembine, Hamidou; Tempone, Raul; Vilanova, Pedro

    2013-01-01

    One of the fundamental challenges in distributed interactive systems is to design efficient, accurate, and fair solutions. In such systems, a satisfactory solution is an innovative approach that aims to provide all players with a satisfactory payoff

  12. Perturbation of an exact strong gravity solution

    International Nuclear Information System (INIS)

    Baran, S.A.

    1982-10-01

    Perturbations of an exact strong gravity solution are investigated. It is shown, by using the new multipole expansions previously presented, that this exact and static spherically symmetric solution is stable under odd parity perturbations. (author)

  13. 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.

  14. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

    Science.gov (United States)

    Mattila, Pieta K.; Batista, Facundo D.

    2016-01-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

  15. Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]angiotensin II

    International Nuclear Information System (INIS)

    Gibson, R.E.; Beauchamp, H.T.; Fioravanti, C.; Brenner, N.; Burns, H.D.

    1994-01-01

    The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [ 125 I][Sar 1 , Ile 8 ]angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [ 123 I][Sar 1 , Ile 8 ]angiotensin II were obtained in the rat kidney and Rhesus monkey liver. (author)

  16. Gold and Silver Extraction from Leach Solutions

    Directory of Open Access Journals (Sweden)

    Bagdaulet K. Kenzhaliyev

    2014-03-01

    Full Text Available There has been carried out an investigation on the extraction of gold and silver from thiosulfate solutions: standard test and technological solutions of chemical and electrochemical leaching. The influence of related metals on the process of extracting gold from solution was studied. There has been conducted a comparative study of the IR spectra of solutions after the sorption of gold, silver and related metals.

  17. Engineering report (conceptual design) PFP solution stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Witt, J.B.

    1997-07-17

    This Engineering Report (Conceptual Design) addresses remediation of the plutonium-bearing solutions currently in inventory at the Plutonium Finishing Plant (PFP). The recommendation from the Environmental Impact Statement (EIS) is that the solutions be treated thermally and stabilized as a solid for long term storage. For solutions which are not discardable, the baseline plan is to utilize a denitration process to stabilize the solutions prior to packaging for storage.

  18. Engineering report (conceptual design) PFP solution stabilization

    International Nuclear Information System (INIS)

    Witt, J.B.

    1997-01-01

    This Engineering Report (Conceptual Design) addresses remediation of the plutonium-bearing solutions currently in inventory at the Plutonium Finishing Plant (PFP). The recommendation from the Environmental Impact Statement (EIS) is that the solutions be treated thermally and stabilized as a solid for long term storage. For solutions which are not discardable, the baseline plan is to utilize a denitration process to stabilize the solutions prior to packaging for storage

  19. Exact solutions and singularities in string theory

    International Nuclear Information System (INIS)

    Horowitz, G.T.; Tseytlin, A.A.

    1994-01-01

    We construct two new classes of exact solutions to string theory which are not of the standard plane wave of gauged WZW type. Many of these solutions have curvature singularities. The first class includes the fundamental string solution, for which the string coupling vanishes near the singularity. This suggests that the singularity may not be removed by quantum corrections. The second class consists of hybrids of plane wave and gauged WZW solutions. We discuss a four-dimensional example in detail

  20. On polynomial solutions of the Heun equation

    International Nuclear Information System (INIS)

    Gurappa, N; Panigrahi, Prasanta K

    2004-01-01

    By making use of a recently developed method to solve linear differential equations of arbitrary order, we find a wide class of polynomial solutions to the Heun equation. We construct the series solution to the Heun equation before identifying the polynomial solutions. The Heun equation extended by the addition of a term, -σ/x, is also amenable for polynomial solutions. (letter to the editor)

  1. Mobility needs and wireless solutions

    DEFF Research Database (Denmark)

    Saugstrup, Dan; Henten, Anders

    The main purpose of this report is to spell out a methodological approach to the analysis of user needs with respect to mobility. Furthermore, this methodological approach is used in an exemplary analysis of the relationship between user needs and technology solutions offered by different wireless...... technologies. The report is based on a research approach, emphasizing important aspects in relation to developing more user oriented mobile services and applications in a heterogeneous network environment. As a staring point, Scandinavian research within the field of social science concerning mobility...... is described and discussed. Furthermore different wireless technologies are briefly described and discussed in relation to possible transmission capacities and coverage areas. In addition to this, a preliminary framework regarding the implications of mobility on the use and development of mobile services...

  2. Multivariate statistics exercises and solutions

    CERN Document Server

    Härdle, Wolfgang Karl

    2015-01-01

    The authors present tools and concepts of multivariate data analysis by means of exercises and their solutions. The first part is devoted to graphical techniques. The second part deals with multivariate random variables and presents the derivation of estimators and tests for various practical situations. The last part introduces a wide variety of exercises in applied multivariate data analysis. The book demonstrates the application of simple calculus and basic multivariate methods in real life situations. It contains altogether more than 250 solved exercises which can assist a university teacher in setting up a modern multivariate analysis course. All computer-based exercises are available in the R language. All R codes and data sets may be downloaded via the quantlet download center  www.quantlet.org or via the Springer webpage. For interactive display of low-dimensional projections of a multivariate data set, we recommend GGobi.

  3. Solution synthesis of germanium nanocrystals

    Science.gov (United States)

    Gerung, Henry [Albuquerque, NM; Boyle, Timothy J [Kensington, MD; Bunge, Scott D [Cuyahoga Falls, OH

    2009-09-22

    A method for providing a route for the synthesis of a Ge(0) nanometer-sized material from. A Ge(II) precursor is dissolved in a ligand heated to a temperature, generally between approximately 100.degree. C. and 400.degree. C., sufficient to thermally reduce the Ge(II) to Ge(0), where the ligand is a compound that can bond to the surface of the germanium nanomaterials to subsequently prevent agglomeration of the nanomaterials. The ligand encapsulates the surface of the Ge(0) material to prevent agglomeration. The resulting solution is cooled for handling, with the cooling characteristics useful in controlling the size and size distribution of the Ge(0) materials. The characteristics of the Ge(II) precursor determine whether the Ge(0) materials that result will be nanocrystals or nanowires.

  4. A solution to nonlinearity problems

    International Nuclear Information System (INIS)

    Neuffer, D.V.

    1989-01-01

    New methods of correcting dynamic nonlinearities resulting from the multipole content of a synchrotron or transport line are presented. In a simplest form, correction elements are places at the center (C) of the accelerator half-cells as well as near the focusing (F) and defocusing (D) quadrupoles. In a first approximation, the corrector strengths follow Simpson's Rule, forming an accurate quasi-local canceling approximation to the nonlinearity. The F, C, and D correctors may also be used to obtain precise control of the horizontal, coupled, and vertical motion. Correction by three or more orders of magnitude can be obtained, and simple solutions to a fundamental problem in beam transport have been obtained. 13 refs., 1 fig., 1 tab

  5. Pure energy solutions - pure tomorrows

    International Nuclear Information System (INIS)

    Allison, J.

    2006-01-01

    HTC is an energy technology company whose mandate is to deliver 'Carbon Clear Solutions' to address the pending challenges the energy sector is facing in meeting the environmental impact of Greenhouse Gas emissions, and energy security. HTC will speak on its comprehensive suite of technologies including hydrogen production, CO 2 capture and CO 2 sequestration. HTC has patented technologies that produce H 2 from a broad variety of feedstocks such as Natural gas, Diesel, Gasoline, Bio-fuels i.e. ethanol, methanol and Coal Gasification. HTC Hydrogen reformation systems are unique in their method of delivering pure Hydrogen. Dry Reformation Reactor - New catalyst system designed to eliminate contamination problems (i.e. coking) while at the same time operate at a low temperature. Water Gas Shift Reactor - Plus - improved and redesigned catalyst that improves operating temperature and hydrogen production efficiency. Two stage catalyst reactor that provides near balance of the endothermic and exothermic reaction temperatures for efficient energy balance

  6. Selective thyroid hormone receptor modulators

    Directory of Open Access Journals (Sweden)

    Girish Raparti

    2013-01-01

    Full Text Available Thyroid hormone (TH is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various thyroid hormone receptors (TR isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in therapeutics. These findings were followed by search of compounds with isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1 isoform of TR. More recently, eprotirome was developed and has been studied in humans. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity. Another compound, 3,5-diiodothyropropionic acid (DITPA, binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in heart failure (HF. In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in thyrotoxicosis and cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.

  7. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  8. Teleost Chemokines and Their Receptors

    Directory of Open Access Journals (Sweden)

    Steve Bird

    2015-11-01

    Full Text Available Chemokines are a superfamily of cytokines that appeared about 650 million years ago, at the emergence of vertebrates, and are responsible for regulating cell migration under both inflammatory and physiological conditions. The first teleost chemokine gene was reported in rainbow trout in 1998. Since then, numerous chemokine genes have been identified in diverse fish species evidencing the great differences that exist among fish and mammalian chemokines, and within the different fish species, as a consequence of extensive intrachromosomal gene duplications and different infectious experiences. Subsequently, it has only been possible to establish clear homologies with mammalian chemokines in the case of some chemokines with well-conserved homeostatic roles, whereas the functionality of other chemokine genes will have to be independently addressed in each species. Despite this, functional studies have only been undertaken for a few of these chemokine genes. In this review, we describe the current state of knowledge of chemokine biology in teleost fish. We have mainly focused on those species for which more research efforts have been made in this subject, specially zebrafish (Danio rerio, rainbow trout (Oncorhynchus mykiss and catfish (Ictalurus punctatus, outlining which genes have been identified thus far, highlighting the most important aspects of their expression regulation and addressing any known aspects of their biological role in immunity. Finally, we summarise what is known about the chemokine receptors in teleosts and provide some analysis using recently available data to help characterise them more clearly.

  9. Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

    OpenAIRE

    Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

    2009-01-01

    High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

  10. Regional Transmission Projects: Finding Solutions

    Energy Technology Data Exchange (ETDEWEB)

    The Keystone Center

    2005-06-15

    The Keystone Center convened and facilitated a year-long Dialogue on "Regional Transmission Projects: Finding Solutions" to develop recommendations that will help address the difficult and contentious issues related to expansions of regional electric transmission systems that are needed for reliable and economic transmission of power within and across regions. This effort brought together a cross-section of affected stakeholders and thought leaders to address the problem with the collective wisdom of their experience and interests. Transmission owners sat at the table with consumer advocates and environmental organizations. Representatives from regional transmission organizations exchanged ideas with state and federal regulators. Generation developers explored common interests with public power suppliers. Together, the Dialogue participants developed consensus solutions about how to begin unraveling some of the more intractable issues surrounding identification of need, allocation of costs, and reaching consensus on siting issues that can frustrate the development of regional transmission infrastructure. The recommendations fall into three broad categories: 1. Recommendations on appropriate institutional arrangements and processes for achieving regional consensus on the need for new or expanded transmission infrastructure 2. Recommendations on the process for siting of transmission lines 3. Recommendations on the tools needed to support regional planning, cost allocation, and siting efforts. List of Dialogue participants: List of Dialogue Participants: American Electric Power American Transmission Company American Wind Energy Association California ISO Calpine Corporation Cinergy Edison Electric Institute Environmental Defense Federal Energy Regulatory Commission Great River Energy International Transmission Company ISO-New England Iowa Public Utility Board Kanner & Associates Midwest ISO National Association of Regulatory Utility Commissioners National Association

  11. New interior solution describing relativistic fluid sphere

    Indian Academy of Sciences (India)

    Anewexact solution of embedding class I is presented for a relativistic anisotropicmassive fluid sphere. The new exact solution satisfies Karmarkar condition, is well-behaved in all respects, and therefore is suitable for the modelling of superdense stars. Consequently, using this solution, we have studied in detail two ...

  12. Extremal black holes as exact string solutions

    International Nuclear Information System (INIS)

    Horowitz, G.T.; Tseytlin, A.A.

    1994-01-01

    We show that the leading order solution describing an extremal electrically charged black hole in string theory is, in fact, an exact solution to all orders in α' when interpreted in a Kaluza-Klein fashion. This follows from the observation that it can be obtained via dimensional reduction from a five-dimensional background which is proved to be an exact string solution

  13. Homoclinic solutions for Davey-Stewartson equation

    International Nuclear Information System (INIS)

    Huang Jian; Dai Zhengde

    2008-01-01

    In this paper, we firstly prove the existence of homoclinic solutions for Davey-Stewartson I equation (DSI) with the periodic boundary condition. Then we obtain a set of exact homoclinic solutions by the novel method-Hirota's method. Moreover, the structure of homoclinic solutions has been investigated. At the same time, we give some numerical simulations which validate these theoretical results

  14. Special solutions of neutral functional differential equations

    Directory of Open Access Journals (Sweden)

    Győri István

    2001-01-01

    Full Text Available For a system of nonlinear neutral functional differential equations we prove the existence of an -parameter family of "special solutions" which characterize the asymptotic behavior of all solutions at infinity. For retarded functional differential equations the special solutions used in this paper were introduced by Ryabov.

  15. Requirements elicitation for geo-information solutions

    NARCIS (Netherlands)

    Robbi Sluter, Claudia; van Elzakker, Corné P.J.M.; Ivanova, Ivana

    2017-01-01

    Geo-information solutions can achieve a higher level of quality if they are developed in accordance with a user-centred design that requires definition of the user requirements in the first step of solution construction. We treat a geo-information solution as a system designed to support human-based

  16. Exact solution of super Liouville model

    International Nuclear Information System (INIS)

    Yang Zhanying; Zhao Liu; Zhen Yi

    2000-01-01

    Using Leznov-Saveliev algebraic analysis and Drinfeld-Sokolov construction, the authors obtained the explicit solutions to the super Liouville system in super covariant form and component form. The explicit solution in component form reduces naturally into the Egnchi-Hanson instanton solution of the usual Liouville equation if all the Grassmann odd components are set equal to zero

  17. The stability of the strong gravity solution

    International Nuclear Information System (INIS)

    Baran, S.A.

    1978-01-01

    The perturbation of the classical solution to a strong gravity model given by Salam and Strathdee is investigated. Using the Hamiltonian formalism it is shown that this static and spherically symmetric solution is stable under the odd parity perturbations provided some parameters in the solution are suitably restricted

  18. 21 CFR 522.900 - Euthanasia solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Euthanasia solution. 522.900 Section 522.900 Food... Euthanasia solution. (a) Specifications. Each milliliter (mL) of solution contains: (1) 390 milligrams (mg.... For humane, painless, and rapid euthanasia. (2) Amount. One mL per 10 pounds of body weight. (3...

  19. Unique specification of Yang-Mills solutions

    International Nuclear Information System (INIS)

    Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

    1980-01-01

    Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

  20. Electrochemical regeneration of chrome etching solution

    NARCIS (Netherlands)

    Andel, van Y.; Janssen, L.J.J.

    2002-01-01

    A metal surface is chromatized with a chromic acid solution to obtain a good adherence of polymer coatings. In this process Cr(VI) is reduced to Cr(III). The oxidation strength of the solution decreases during use. The chrome solution needs to be regenerated and purified. A new anode material,