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Sample records for sedlin forms homodimers

  1. Nicotinamidase/pyrazinamidase of Mycobacterium tuberculosis forms homo-dimers stabilized by disulfide bonds.

    Science.gov (United States)

    Rueda, Daniel; Sheen, Patricia; Gilman, Robert H; Bueno, Carlos; Santos, Marco; Pando-Robles, Victoria; Batista, Cesar V; Zimic, Mirko

    2014-12-01

    Recombinant wild-pyrazinamidase from H37Rv Mycobacterium tuberculosis was analyzed by gel electrophoresis under differential reducing conditions to evaluate its quaternary structure. PZAse was fractionated by size exclusion chromatography under non-reducing conditions. PZAse activity was measured and mass spectrometry analysis was performed to determine the identity of proteins by de novo sequencing and to determine the presence of disulfide bonds. This study confirmed that M. tuberculosis wild type PZAse was able to form homo-dimers in vitro. Homo-dimers showed a slightly lower specific PZAse activity compared to monomeric PZAse. PZAse dimers were dissociated into monomers in response to reducing conditions. Mass spectrometry analysis confirmed the existence of disulfide bonds (C72-C138 and C138-C138) stabilizing the quaternary structure of the PZAse homo-dimer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. ThWRKY4 from Tamarix hispida Can Form Homodimers and Heterodimers and Is Involved in Abiotic Stress Responses

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    Liuqiang Wang

    2015-11-01

    Full Text Available WRKY proteins are a large family of transcription factors that are involved in diverse developmental processes and abiotic stress responses in plants. However, our knowledge of the regulatory mechanisms of WRKYs participation in protein–protein interactions is still fragmentary, and such protein–protein interactions are fundamental in understanding biological networks and the functions of proteins. In this study, we report that a WRKY protein from Tamarix hispida, ThWRKY4, can form both homodimers and heterodimers with ThWRKY2 and ThWRKY3. In addition, ThWRKY2 and ThWRKY3 can both bind to W-box motif with binding affinities similar to that of ThWRKY4. Further, the expression patterns of ThWRKY2 and ThWRKY3 are similar to that of ThWRKY4 when plants are exposed to abscisic acid (ABA. Subcellular localization shows that these three ThWRKY proteins are nuclear proteins. Taken together, these results demonstrate that ThWRKY4 is a dimeric protein that can form functional homodimers or heterodimers that are involved in abiotic stress responses.

  3. ThWRKY4 from Tamarix hispida Can Form Homodimers and Heterodimers and Is Involved in Abiotic Stress Responses.

    Science.gov (United States)

    Wang, Liuqiang; Zheng, Lei; Zhang, Chunrui; Wang, Yucheng; Lu, Mengzhu; Gao, Caiqiu

    2015-11-13

    WRKY proteins are a large family of transcription factors that are involved in diverse developmental processes and abiotic stress responses in plants. However, our knowledge of the regulatory mechanisms of WRKYs participation in protein-protein interactions is still fragmentary, and such protein-protein interactions are fundamental in understanding biological networks and the functions of proteins. In this study, we report that a WRKY protein from Tamarix hispida, ThWRKY4, can form both homodimers and heterodimers with ThWRKY2 and ThWRKY3. In addition, ThWRKY2 and ThWRKY3 can both bind to W-box motif with binding affinities similar to that of ThWRKY4. Further, the expression patterns of ThWRKY2 and ThWRKY3 are similar to that of ThWRKY4 when plants are exposed to abscisic acid (ABA). Subcellular localization shows that these three ThWRKY proteins are nuclear proteins. Taken together, these results demonstrate that ThWRKY4 is a dimeric protein that can form functional homodimers or heterodimers that are involved in abiotic stress responses.

  4. Comparison of MukB homodimer versus MukBEF complex molecular architectures by electron microscopy reveals a higher-order multimerization

    International Nuclear Information System (INIS)

    Matoba, Kyoko; Yamazoe, Mitsuyoshi; Mayanagi, Kouta; Morikawa, Kosuke; Hiraga, Sota

    2005-01-01

    The complex of MukF, MukE, and MukB proteins participates in organization of sister chromosomes and partitioning into both daughter cells in Escherichia coli. We purified the MukB homodimer and the MukBEF complex and analyzed them by electron microscopy to compare both structures. A MukB homodimer shows a long rod-hinge-rod v-shape with small globular domains at both ends. The MukBEF complex shows a similar structure having larger globular domains than those of the MukB homodimer. These results suggest that MukF and MukE bind to the globular domains of a MukB homodimer. The globular domains of the MukBEF complex frequently associate with each other in an intramolecular fashion, forming a ring. In addition, MukBEF complex molecules tend to form multimers by the end-to-end joining with other MukBEF molecules in an intermolecular fashion, resulting in fibers and rosette-form structures in the absence of ATP and DNA in vitro

  5. Observation of an E2 (Ubc9-homodimer by crystallography

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    Aileen Y. Alontaga

    2016-06-01

    Full Text Available Post-translational modifications by the small ubiquitin-like modifiers (SUMO, in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009 [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2 for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A. This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1, SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015 [2–10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999 [10,11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C. The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The data presented here are related

  6. Relish2 mediates bursicon homodimer-induced prophylactic immunity in the mosquito Aedes aegypti

    Science.gov (United States)

    Bursicon is a neuropeptide hormone consisting of two cystine-knot proteins (burs a and burs ß), responsible for cuticle tanning and other developmental processes in insects. Recent studies show that each bursicon subunit forms homodimers that induce prophylactic immunity in Drosophila melanogaster. ...

  7. Insect neuropeptide bursicon homodimers induce innate immune and stress genes during molting by activating the NF-κB transcription factor Relish.

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    Shiheng An

    Full Text Available BACKGROUND: Bursicon is a heterodimer neuropeptide composed of two cystine knot proteins, bursicon α (burs α and bursicon β (burs β, that elicits cuticle tanning (melanization and sclerotization through the Drosophila leucine-rich repeats-containing G protein-coupled receptor 2 (DLGR2. Recent studies show that both bursicon subunits also form homodimers. However, biological functions of the homodimers have remained unknown until now. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show in Drosophila melanogaster that both bursicon homodimers induced expression of genes encoding antimicrobial peptides (AMPs in neck-ligated adults following recombinant homodimer injection and in larvae fat body after incubation with recombinant homodimers. These AMP genes were also up-regulated in 24 h old unligated flies (when the endogenous bursicon level is low after injection of recombinant homodimers. Up-regulation of AMP genes by the homodimers was accompanied by reduced bacterial populations in fly assay preparations. The induction of AMP expression is via activation of the NF-κB transcription factor Relish in the immune deficiency (Imd pathway. The influence of bursicon homodimers on immune function does not appear to act through the heterodimer receptor DLGR2, i.e. novel receptors exist for the homodimers. CONCLUSIONS/SIGNIFICANCE: Our results reveal a mechanism of CNS-regulated prophylactic innate immunity during molting via induced expression of genes encoding AMPs and genes of the Turandot family. Turandot genes are also up-regulated by a broader range of extreme insults. From these data we infer that CNS-generated bursicon homodimers mediate innate prophylactic immunity to both stress and infection during the vulnerable molting cycle.

  8. NMR Study of Solvation Effect on Geometry of Proton-Bound Homodimers of Increasing Size

    KAUST Repository

    Gurinov, Andrei A.

    2017-10-24

    Hydrogen bond geometries in the proton-bound homodimers of quinoline and acridine derivatives in an aprotic polar solution have been experimentally studied using 1H NMR at 120 K. The reported results show that increase of the dielec-tric permittivity of the medium results in contraction of the N…N distance. The degree of contraction depends on the homodimer\\'s size and its substituent-specific solvation features. Neither of these effects can be reproduced using conven-tional implicit solvent models employed in computational studies. In general, the N…N distance in the homodimers of pyridine, quinoline, and acridine derivatives decreases in the sequence gas phase > solid state > polar solvent.

  9. Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers

    Science.gov (United States)

    Ghosh, Ritwik; Narasanna, Archana; Wang, Shizhen Emily; Liu, Shuying; Chakrabarty, Anindita; Balko, Justin M.; González-Angulo, Ana María; Mills, Gordon B.; Penuel, Elicia; Winslow, John; Sperinde, Jeff; Dua, Rajiv; Pidaparthi, Sailaja; Mukherjee, Ali; Leitzel, Kim; Kostler, Wolfgang J.; Lipton, Allan; Bates, Michael; Arteaga, Carlos L.

    2011-01-01

    In breast cancer cells with HER2 gene amplification, HER2 receptors exist on the cell surface as monomers, homodimers and heterodimers with EGFR/HER3. The therapeutic antibody trastuzumab, an approved therapy for HER2+ breast cancer, cannot block ligand-induced HER2 heterodimers, suggesting it cannot effectively inhibit HER2 signaling. Hence, HER2 oligomeric states may predict the odds of a clinical response to trastuzumab in HER2-driven tumors. To test this hypothesis, we generated non-transformed human MCF10A mammary epithelial cells stably expressing a chimeric HER2-FKBP molecule that could be conditionally induced to homodimerize by adding the FKBP ligand AP1510, or instead induced to heterodimerize with EGFR or HER3 by adding the heterodimer ligands EGF/TGFα or heregulin. AP1510, EGF, and heregulin each induced growth of MCF10A cells expressing HER2-FKBP. As expected, trastuzumab inhibited homodimer-mediated but not heterodimer-mediated cell growth. In contrast, the HER2 antibody pertuzumab, which blocks HER2 heterodimerization, inhibited growth induced by heregulin but not AP1510. Lastly, HER2/EGFR tyrosine kinase inhibitor lapatinib blocked both homodimer- and heterodimer-induced growth. AP1510 triggered phosphorylation of Erk1/2 but not AKT, whereas trastuzumab inhibited AP1510-induced Erk1/2 phosphorylation and Shc-HER2 homodimer binding, but not TGFα-induced AKT phosphorylation. Consistent with these observations, high levels of HER2 homodimers correlated with longer time to progression following trastuzumab therapy in a cohort of HER2-overexpressing patients. Together, our findings corroborate the hypothesis that HER2 oligomeric states regulate HER2 signaling, also arguing that trastuzumab sensitivity of homodimers reflects an inability to activate the PI3K/AKT pathway. One of the most important clinical implications of our results is that high levels of HER2 homodimers may predict a positive response to trastuzumab. PMID:21324925

  10. NMR Study of Solvation Effect on Geometry of Proton-Bound Homodimers of Increasing Size

    KAUST Repository

    Gurinov, Andrei A.; Denisov, Gleb S.; Borissova, Alexandra O.; Goloveshkin, Alexander S.; Greindl, Julian; Limbach, Hans-Heinrich; Shenderovich, Ilya G.

    2017-01-01

    Hydrogen bond geometries in the proton-bound homodimers of quinoline and acridine derivatives in an aprotic polar solution have been experimentally studied using 1H NMR at 120 K. The reported results show that increase of the dielec-tric permittivity of the medium results in contraction of the N…N distance. The degree of contraction depends on the homodimer's size and its substituent-specific solvation features. Neither of these effects can be reproduced using conven-tional implicit solvent models employed in computational studies. In general, the N…N distance in the homodimers of pyridine, quinoline, and acridine derivatives decreases in the sequence gas phase > solid state > polar solvent.

  11. Beta2-adrenergic receptor homodimers: Role of transmembrane domain 1 and helix 8 in dimerization and cell surface expression.

    Science.gov (United States)

    Parmar, Vikas K; Grinde, Ellinor; Mazurkiewicz, Joseph E; Herrick-Davis, Katharine

    2017-09-01

    Even though there are hundreds of reports in the published literature supporting the hypothesis that G protein-coupled receptors (GPCR) form and function as dimers this remains a highly controversial area of research and mechanisms governing homodimer formation are poorly understood. Crystal structures revealing homodimers have been reported for many different GPCR. For adrenergic receptors, a potential dimer interface involving transmembrane domain 1 (TMD1) and helix 8 (H8) was identified in crystal structures of the beta 1 -adrenergic (β 1 -AR) and β 2 -AR. The purpose of this study was to investigate a potential role for TMD1 and H8 in dimerization and plasma membrane expression of functional β 2 -AR. Charged residues at the base of TMD1 and in the distal portion of H8 were replaced, singly and in combination, with non-polar residues or residues of opposite charge. Wild type and mutant β 2 -AR, tagged with YFP and expressed in HEK293 cells, were evaluated for plasma membrane expression and function. Homodimer formation was evaluated using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and fluorescence correlation spectroscopy. Amino acid substitutions at the base of TMD1 and in the distal portion of H8 disrupted homodimer formation and caused receptors to be retained in the endoplasmic reticulum. Mutations in the proximal region of H8 did not disrupt dimerization but did interfere with plasma membrane expression. This study provides biophysical evidence linking a potential TMD1/H8 interface with ER export and the expression of functional β 2 -AR on the plasma membrane. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant

    Energy Technology Data Exchange (ETDEWEB)

    Atwell, Shane; Brouillette, Christie G.; Conners, Kris; Emtage, Spencer; Gheyi, Tarun; Guggino, William B.; Hendle, Jorg; Hunt, John F.; Lewis, Hal A.; Lu, Frances; Protasevich, Irina I.; Rodgers, Logan A.; Romero, Rich; Wasserman, Stephen R.; Weber, Patricia C.; Wetmore, Diana; Zhang, Feiyu F.; Zhao, Xun (Cystic); (UAB); (JHU); (Columbia); (Lilly)

    2010-04-26

    Upon removal of the regulatory insert (RI), the first nucleotide binding domain (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be heterologously expressed and purified in a form that remains stable without solubilizing mutations, stabilizing agents or the regulatory extension (RE). This protein, NBD1 387-646({Delta}405-436), crystallizes as a homodimer with a head-to-tail association equivalent to the active conformation observed for NBDs from symmetric ATP transporters. The 1.7-{angstrom} resolution X-ray structure shows how ATP occupies the signature LSGGQ half-site in CFTR NBD1. The {Delta}F508 version of this protein also crystallizes as a homodimer and differs from the wild-type structure only in the vicinity of the disease-causing F508 deletion. A slightly longer construct crystallizes as a monomer. Comparisons of the homodimer structure with this and previously published monomeric structures show that the main effect of ATP binding at the signature site is to order the residues immediately preceding the signature sequence, residues 542-547, in a conformation compatible with nucleotide binding. These residues likely interact with a transmembrane domain intracellular loop in the full-length CFTR channel. The experiments described here show that removing the RI from NBD1 converts it into a well-behaved protein amenable to biophysical studies yielding deeper insights into CFTR function.

  13. Comparative analysis of three-dimensional structures of homodimers of uridine phosphorylase from Salmonella typhimurium in the unligated state and in a complex with potassium ion

    International Nuclear Information System (INIS)

    Lashkov, A. A.; Zhukhlistova, N. E.; Gabdulkhakov, A. G.; Mikhailov, A. M.

    2009-01-01

    The spatial organization of the homodimer of unligated uridine phosphorylase from Salmonella typhimurium (St UPh) was determined with high accuracy. The structure was refined at 1.80 A resolution to R work = 16.1% and R free = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 A, 1.042 o , and 0.071 o , respectively. The coordinate error estimated by the Luzzati plot is 0.166 A. The coordinate error based on the maximum likelihood is 0.199 A. A comparative analysis of the spatial organization of the homodimer in two independently refined structures and the structure of the homodimer St UPh in the complex with a K + ion was performed. The substrate-binding sites in the homodimers StUPhs in the unligated state were found to act asynchronously. In the presence of a potassium ion, the three-dimensional structures of the subunits in the homodimer are virtually identical, which is apparently of importance for the synchronous action of both substrate-binding sites. The atomic coordinates of the refined structure of the homodimer and structure factors have been deposited in the Protein Data Bank (PDB ID code 3DPS).

  14. Comparative analysis of three-dimensional structures of homodimers of uridine phosphorylase from Salmonella typhimurium in the unligated state and in a complex with potassium ion

    Energy Technology Data Exchange (ETDEWEB)

    Lashkov, A. A.; Zhukhlistova, N. E.; Gabdulkhakov, A. G.; Mikhailov, A. M., E-mail: amm@ns.crys.ras.ru [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2009-03-15

    The spatial organization of the homodimer of unligated uridine phosphorylase from Salmonella typhimurium (St UPh) was determined with high accuracy. The structure was refined at 1.80 A resolution to R{sub work} = 16.1% and R{sub free} = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 A, 1.042{sup o}, and 0.071{sup o}, respectively. The coordinate error estimated by the Luzzati plot is 0.166 A. The coordinate error based on the maximum likelihood is 0.199 A. A comparative analysis of the spatial organization of the homodimer in two independently refined structures and the structure of the homodimer St UPh in the complex with a K{sup +} ion was performed. The substrate-binding sites in the homodimers StUPhs in the unligated state were found to act asynchronously. In the presence of a potassium ion, the three-dimensional structures of the subunits in the homodimer are virtually identical, which is apparently of importance for the synchronous action of both substrate-binding sites. The atomic coordinates of the refined structure of the homodimer and structure factors have been deposited in the Protein Data Bank (PDB ID code 3DPS).

  15. APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

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    Hilla Fogel

    2014-06-01

    Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

  16. Origin of Asymmetric Charge Partitioning in the Dissociation of Gas-Phase Protein Homodimers

    OpenAIRE

    Jurchen, John C.; Williams, Evan R.

    2003-01-01

    The origin of asymmetric charge and mass partitioning observed for gas-phase dissociation of multiply charged macromolecular complexes has been hotly debated. These experiments hold the potential to provide detailed information about the interactions between the macromolecules within the complex. Here, this unusual phenomenon of asymmetric charge partitioning is investigated for several protein homodimers. Asymmetric charge partitioning in these ions depends on a number of factors, including ...

  17. Chemical shift imprint of intersubunit communication in a symmetric homodimer

    Science.gov (United States)

    Falk, Bradley T.; Sapienza, Paul J.; Lee, Andrew L.

    2016-01-01

    Allosteric communication is critical for protein function and cellular homeostasis, and it can be exploited as a strategy for drug design. However, unlike many protein–ligand interactions, the structural basis for the long-range communication that underlies allostery is not well understood. This lack of understanding is most evident in the case of classical allostery, in which a binding event in one protomer is sensed by a second symmetric protomer. A primary reason why study of interdomain signaling is challenging in oligomeric proteins is the difficulty in characterizing intermediate, singly bound species. Here, we use an NMR approach to isolate and characterize a singly ligated state (“lig1”) of a homodimeric enzyme that is otherwise obscured by rapid exchange with apo and saturated forms. Mixed labeled dimers were prepared that simultaneously permit full population of the lig1 state and isotopic labeling of either protomer. Direct visualization of peaks from lig1 yielded site-specific ligand-state multiplets that provide a convenient format for assessing mechanisms of intersubunit communication from a variety of NMR measurements. We demonstrate this approach on thymidylate synthase from Escherichia coli, a homodimeric enzyme known to be half-the-sites reactive. Resolving the dUMP1 state shows that active site communication occurs not upon the first dUMP binding, but upon the second. Surprisingly, for many sites, dUMP1 peaks are found beyond the limits set by apo and dUMP2 peaks, indicating that binding the first dUMP pushes the enzyme ensemble to further conformational extremes than the apo or saturated forms. The approach used here should be generally applicable to homodimers. PMID:27466406

  18. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

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    Michael B Tropak

    2016-01-01

    Full Text Available Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA. Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP, and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM, CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.

  19. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

    Science.gov (United States)

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

  20. Probing intermolecular protein-protein interactions in the calcium-sensing receptor homodimer using bioluminescence resonance energy transfer (BRET)

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Hansen, Jakob L; Sheikh, Søren P

    2002-01-01

    -induced intermolecular movements in the CaR homodimer using the new bioluminescence resonance energy transfer technique, BRET2, which is based on the transference of energy from Renilla luciferase (Rluc) to the green fluorescent protein mutant GFP2. We tagged CaR with Rluc and GFP2 at different intracellular locations...

  1. Secreted Progranulin Is a Homodimer and Is Not a Component of High Density Lipoproteins (HDL)*

    Science.gov (United States)

    Nguyen, Andrew D.; Nguyen, Thi A.; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C.; Davidson, W. Sean; Farese, Robert V.

    2013-01-01

    Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170–180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180–190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL. PMID:23364791

  2. Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL).

    Science.gov (United States)

    Nguyen, Andrew D; Nguyen, Thi A; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C; Davidson, W Sean; Farese, Robert V

    2013-03-22

    Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170-180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180-190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL.

  3. PDB-NMA of a protein homodimer reproduces distinct experimental motility asymmetry

    Science.gov (United States)

    Tirion, Monique M.; ben-Avraham, Daniel

    2018-03-01

    We have extended our analytically derived PDB-NMA formulation, Atomic Torsional Modal Analysis or ATMAN (Tirion and ben-Avraham 2015 Phys. Rev. E 91 032712), to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3 {\\mathringA} resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50 {\\mathringA} sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.

  4. Plasmon-mediated binding forces on gold or silver homodimer and heterodimer

    International Nuclear Information System (INIS)

    Liaw, Jiunn-Woei; Kuo, Ting-Yu; Kuo, Mao-Kuen

    2016-01-01

    This study theoretically investigates plasmon-mediated optical binding forces, which are exerted on metal homo or heterodimers, induced by the normal illumination of a linearly polarized plane wave or Gaussian beam. Using the multiple multipole method, we analyzed the optical force in terms of Maxwell's stress tensor for various interparticle distance at some specific wavelengths. Numerical results show that for a given wavelength there are several stable equilibrium distances between two nanoparticles (NPs) of a homodimer, which are slightly shorter than some integer multiples of the wavelength in medium, such that metal dimer acts as bonded together. At these specific interparticle distances, the optical force between dimer is null and serves a restoring force, which is repulsive and attractive, respectively, as the two NPs are moving closer to and away from each other. The spring constant of the restoring force at the first stable equilibrium is always the largest, indicating that the first stable equilibrium distance is the most stable one. Moreover, the central line (orientation) of a dimer tends to be perpendicular to the polarization of light. For the cases of heterodimers, the phenomenon of stable equilibrium interparticle distance still exists, except there is an extra net photophoretic force drifting the heterodimer as one. Moreover, gradient force provided by a Gaussian beam may reduce the stability of these equilibriums, so larger NPs are preferred to stabilize a dimer under illumination of Gaussian beam. The finding may pave the way for using optical manipulation on the gold or silver colloidal self-assembly. - Highlights: • Optical binding force on Au/Ag dimer by linearly polarized light is studied. • For a wavelength several stable equilibriums for homodimer bound together exist. • The central line of a dimer tends to be perpendicular to the polarization of light. • For a heterodimer, stable equilibriums still exist with a net photophoretic

  5. The asymmetric binding of PGC-1α to the ERRα and ERRγ nuclear receptor homodimers involves a similar recognition mechanism.

    Directory of Open Access Journals (Sweden)

    Maria Takacs

    Full Text Available PGC-1α is a crucial regulator of cellular metabolism and energy homeostasis that functionally acts together with the estrogen-related receptors (ERRα and ERRγ in the regulation of mitochondrial and metabolic gene networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC-1α and other coactivators, eventually leading to transactivation. It was suggested recently (Devarakonda et al that PGC-1α binds in a strikingly different manner to ERRγ ligand-binding domains (LBDs compared to its mode of binding to ERRα and other nuclear receptors (NRs, where it interacts directly with the two ERRγ homodimer subunits.Here, we show that PGC-1α receptor interacting domain (RID binds in an almost identical manner to ERRα and ERRγ homodimers. Microscale thermophoresis demonstrated that the interactions between PGC-1α RID and ERR LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and low-affinity L2 interactions. NMR studies further defined the limits of PGC-1α RID that interacts with ERRs. Consistent with these findings, the solution structures of PGC-1α/ERRα LBDs and PGC-1α/ERRγ LBDs complexes share an identical architecture with an asymmetric binding of PGC-1α to homodimeric ERR.These studies provide the molecular determinants for the specificity of interactions between PGC-1α and the ERRs, whereby negative cooperativity prevails in the binding of the coactivators to these receptors. Our work indicates that allosteric regulation may be a general mechanism controlling the binding of the coactivators to homodimers.

  6. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  7. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats

    Science.gov (United States)

    Marroquin Belaunzaran, Osiris; Kleber, Sascha; Schauer, Stefan; Hausmann, Martin; Nicholls, Flora; Van den Broek, Maries; Payeli, Sravan; Ciurea, Adrian; Milling, Simon; Stenner, Frank; Shaw, Jackie; Kollnberger, Simon; Bowness, Paul; Petrausch, Ulf; Renner, Christoph

    2015-01-01

    Objectives HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM). HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules. Conclusion HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders. PMID:26125554

  8. Optical determination of the electronic coupling and intercalation geometry of thiazole orange homodimer in DNA

    Science.gov (United States)

    Cunningham, Paul D.; Bricker, William P.; Díaz, Sebastián A.; Medintz, Igor L.; Bathe, Mark; Melinger, Joseph S.

    2017-08-01

    Sequence-selective bis-intercalating dyes exhibit large increases in fluorescence in the presence of specific DNA sequences. This property makes this class of fluorophore of particular importance to biosensing and super-resolution imaging. Here we report ultrafast transient anisotropy measurements of resonance energy transfer (RET) between thiazole orange (TO) molecules in a complex formed between the homodimer TOTO and double-stranded (ds) DNA. Biexponential homo-RET dynamics suggest two subpopulations within the ensemble: 80% intercalated and 20% non-intercalated. Based on the application of the transition density cube method to describe the electronic coupling and Monte Carlo simulations of the TOTO/dsDNA geometry, the dihedral angle between intercalated TO molecules is estimated to be 81° ± 5°, corresponding to a coupling strength of 45 ± 22 cm-1. Dye intercalation with this geometry is found to occur independently of the underlying DNA sequence, despite the known preference of TOTO for the nucleobase sequence CTAG. The non-intercalated subpopulation is inferred to have a mean inter-dye separation distance of 19 Å, corresponding to coupling strengths between 0 and 25 cm-1. This information is important to enable the rational design of energy transfer systems that utilize TOTO as a relay dye. The approach used here is generally applicable to determining the electronic coupling strength and intercalation configuration of other dimeric bis-intercalators.

  9. Use of the α-mannosidase I inhibitor kifunensine allows the crystallization of apo CTLA-4 homodimer produced in long-term cultures of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Yu, Chao; Crispin, Max; Sonnen, Andreas F.-P.; Harvey, David J.; Chang, Veronica T.; Evans, Edward J.; Scanlan, Christopher N.; Stuart, David I.; Gilbert, Robert J. C.; Davis, Simon J.

    2011-01-01

    The α-mannosidase I inhibitor kifunensine inhibited N-glycan processing in long-term cultures of Chinese hamster ovary cells, allowing deglycosylation and crystallization of the homodimeric extracellular region of the inhibitory glycoprotein receptor CTLA-4 (CD152). Glycoproteins present problems for structural analysis since they often have to be glycosylated in order to fold correctly and because their chemical and conformational heterogeneity generally inhibits crystallization. It is shown that the α-mannosidase I inhibitor kifunensine, which has previously been used for the purpose of glycoprotein crystallization in short-term (3–5 d) cultures, is apparently stable enough to be used to produce highly endoglycosidase H-sensitive glycoprotein in long-term (3–4 week) cultures of stably transfected Chinese hamster ovary (CHO) cells. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based analysis of the extracellular region of the cytotoxic T-lymphocyte antigen 4 (CTLA-4; CD152) homodimer expressed in long-term CHO cell cultures in the presence of kifunensine revealed that the inhibitor restricted CTLA-4 glycan processing to Man 9 GlcNAc 2 and Man 5 GlcNAc 2 structures. Complex-type glycans were undetectable, suggesting that the inhibitor was active for the entire duration of the cultures. Endoglycosidase treatment of the homodimer yielded protein that readily formed orthorhombic crystals with unit-cell parameters a = 43.9, b = 51.5, c = 102.9 Å and space group P2 1 2 1 2 1 that diffracted to Bragg spacings of 1.8 Å. The results indicate that kifunensine will be effective in most, if not all, transient and long-term mammalian cell-based expression systems

  10. Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway.

    Science.gov (United States)

    Jantaree, Phatcharida; Lirdprapamongkol, Kriengsak; Kaewsri, Wilailak; Thongsornkleeb, Charnsak; Choowongkomon, Kiattawee; Atjanasuppat, Korakot; Ruchirawat, Somsak; Svasti, Jisnuson

    2017-03-22

    The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model. Here, we evaluated the antimetastatic potential of the food additive divanillin, the homodimer of vanillin, and their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells. The Transwell invasion assay showed that the dimeric forms exhibited a potency higher than those of vanillin and apocynin in inhibiting invasion, with IC 50 values of 23.3 ± 7.4 to 41.3 ± 4.2 μM for the dimers, which are 26-34-fold lower than IC 50 values of vanillin and apocynin (p vanillin and apocynin to the Y397 pocket of the FAK FERM domain. Thus, the food additive divanillin has antimetastatic potential greater than that of the flavoring agent vanillin.

  11. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity.

    Science.gov (United States)

    Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

    2015-01-01

    The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates.

  12. Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock.

    Directory of Open Access Journals (Sweden)

    Gila Arad

    2011-09-01

    Full Text Available Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.

  13. Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

    KAUST Repository

    Cheung, Lydia W T; Walkiewicz, Katarzyna Wiktoria; Besong, Tabot M.D.; Guo, Huifang; Hawke, David H.; Arold, Stefan T.; Mills, Gordon B.

    2015-01-01

    The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomerdimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development. © Cheung et al.

  14. Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

    KAUST Repository

    Cheung, Lydia W T

    2015-07-29

    The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomerdimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development. © Cheung et al.

  15. Self-homodimerization of an actinoporin by disulfide bridging reveals implications for their structure and pore formation.

    Science.gov (United States)

    Valle, Aisel; Pérez-Socas, Luis Benito; Canet, Liem; Hervis, Yadira de la Patria; de Armas-Guitart, German; Martins-de-Sa, Diogo; Lima, Jônatas Cunha Barbosa; Souza, Adolfo Carlos Barros; Barbosa, João Alexandre Ribeiro Gonçalves; de Freitas, Sonia Maria; Pazos, Isabel Fabiola

    2018-04-26

    The Trp111 to Cys mutant of sticholysin I, an actinoporin from Stichodactyla helianthus sea anemone, forms a homodimer via a disulfide bridge. The purified dimer is 193 times less hemolytic than the monomer. Ultracentrifugation, dynamic light scattering and size-exclusion chromatography demonstrate that monomers and dimers are the only independent oligomeric states encountered. Indeed, circular dichroism and fluorescence spectroscopies showed that Trp/Tyr residues participate in homodimerization and that the dimer is less thermostable than the monomer. A homodimer three-dimensional model was constructed and indicates that Trp147/Tyr137 are at the homodimer interface. Spectroscopy results validated the 3D-model and assigned 85° to the disulfide bridge dihedral angle responsible for dimerization. The homodimer model suggests that alterations in the membrane/carbohydrate-binding sites in one of the monomers, as result of dimerization, could explain the decrease in the homodimer ability to form pores.

  16. Role of α-Helical Structure in Organic Solvent-Activated Homodimer of Elastase Strain K

    Directory of Open Access Journals (Sweden)

    Chee Fah Wong

    2011-09-01

    Full Text Available Recombinant elastase strain K overexpressed from E. coli KRX/pCon2(3 was purified to homogeneity by a combination of hydrophobic interaction chromatography and ion exchange chromatography, with a final yield of 48% and a 25-fold increase in specific activity. The purified protein had exhibited a first ever reported homodimer size of 65 kDa by SDS-PAGE and MALDI-TOF, a size which is totally distinct from that of typically reported 33 kDa monomer from P. aeruginosa. The organic solvent stability experiment had demonstrated a stability pattern which completely opposed the rules laid out in previous reports in which activity stability and enhancement were observed in hydrophilic organic solvents such as DMSO, methanol, ethanol and 1-propanol. The high stability and enhancement of the enzyme in hydrophilic solvents were explained from the view of alteration in secondary structures. Elastinolytic activation and stability were observed in 25 and 50% of methanol, respectively, despite slight reduction in α-helical structure caused upon the addition of the solvent. Further characterization experiments had postulated great stability and enhancement of elastase strain K in broad range of temperatures, pHs, metal ions, surfactants, denaturing agents and substrate specificity, indicating its potential application in detergent formulation.

  17. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

    International Nuclear Information System (INIS)

    Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

    2014-01-01

    Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

  18. BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy: BECN2 CCD Structure and Interaction with ATG14

    Energy Technology Data Exchange (ETDEWEB)

    Su, Minfei; Li, Yue; Wyborny, Shane; Neau, David; Chakravarthy, Srinivas; Levine, Beth; Colbert, Christopher L.; Sinha, Sangita C. (NDSU); (IIT); (Cornell); (UTSMC)

    2017-03-12

    ATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here, we show that the α-helical, coiled-coil domain (CCD) of BECN2, a recently identified mammalian BECN1 paralog, forms an antiparallel, curved homodimer with seven pairs of nonideal packing interactions, while the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer stabilized by multiple, conserved polar interactions. Compared to BECN1, the BECN2 CCD forms a weaker homodimer, but binds more tightly to the ATG14 CCD. Mutation of nonideal BECN2 interface residues to more ideal pairs improves homodimer self-association and thermal stability. Unlike BECN1, all BECN2 CCD mutants bind ATG14, although more weakly than wild type. Thus, polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. These structure-based mechanistic differences in BECN1 and BECN2 homodimerization and heterodimerization likely dictate competitive ATG14 recruitment.

  19. The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription

    International Nuclear Information System (INIS)

    Simon, Priscilla S.; Sharman, Sarah K.; Lu, Chunwan; Yang, Dafeng; Paschall, Amy V.; Tulachan, Sidhartha S.; Liu, Kebin

    2015-01-01

    observed that the p65/p65 and p50/p50 homodimers, not the canonical p65/p50 heterodimer, directly binds to the nos2 promoter to regulate iNOS expression in myeloid cells. IFNγ-induced IRF8 acts in concert with NF-κB to regulate iNOS expression in both colon carcinoma and myeloid cells. In myeloid cells, the NF-κB complexes that bind to the nos2 promoter are p65/p65 and p50/p50 homodimers

  20. Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

    International Nuclear Information System (INIS)

    Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

    2010-01-01

    CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

  1. Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer.

    Science.gov (United States)

    LoPiccolo, Jaclyn; Kim, Seung Joong; Shi, Yi; Wu, Bin; Wu, Haiyan; Chait, Brian T; Singer, Robert H; Sali, Andrej; Brenowitz, Michael; Bresnick, Anne R; Backer, Jonathan M

    2015-12-18

    Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that are activated by growth factor and G-protein-coupled receptors and propagate intracellular signals for growth, survival, proliferation, and metabolism. p85α, a modular protein consisting of five domains, binds and inhibits the enzymatic activity of class IA PI3K catalytic subunits. Here, we describe the structural states of the p85α dimer, based on data from in vivo and in vitro solution characterization. Our in vitro assembly and structural analyses have been enabled by the creation of cysteine-free p85α that is functionally equivalent to native p85α. Analytical ultracentrifugation studies showed that p85α undergoes rapidly reversible monomer-dimer assembly that is highly exothermic in nature. In addition to the documented SH3-PR1 dimerization interaction, we identified a second intermolecular interaction mediated by cSH2 domains at the C-terminal end of the polypeptide. We have demonstrated in vivo concentration-dependent dimerization of p85α using fluorescence fluctuation spectroscopy. Finally, we have defined solution conditions under which the protein is predominantly monomeric or dimeric, providing the basis for small angle x-ray scattering and chemical cross-linking structural analysis of the discrete dimer. These experimental data have been used for the integrative structure determination of the p85α dimer. Our study provides new insight into the structure and assembly of the p85α homodimer and suggests that this protein is a highly dynamic molecule whose conformational flexibility allows it to transiently associate with multiple binding proteins. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Structure of the Unbound Form of HIV-1 Subtype A Protease: Comparison with Unbound Forms of Proteases from other HIV Subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, Arthur H.; Coman, Roxana M.; Bracho-Sanchez, Edith; Fernandez, Marty A.; Gilliland, C.Taylor; Li, Mi; Agbandje-McKenna, Mavis; Wlodawer, Alexander; Dunn, Ben M.; McKenna, Robert (NCI); (Florida)

    2010-03-12

    The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 {angstrom} resolution and refined as a homodimer in the hexagonal space group P6{sub 1} to an R{sub cryst} of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.

  3. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

    2014-03-07

    Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

  4. In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

    Energy Technology Data Exchange (ETDEWEB)

    Lashkov, A. A., E-mail: alashkov83@gmail.com; Sotnichenko, S. E.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2013-03-15

    Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

  5. Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer.

    Science.gov (United States)

    Blackwell, Daniel J; Zak, Taylor J; Robia, Seth L

    2016-09-20

    The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. The Escherichia coli BolA Protein IbaG Forms a Histidine-Ligated [2Fe-2S]-Bridged Complex with Grx4.

    Science.gov (United States)

    Dlouhy, Adrienne C; Li, Haoran; Albetel, Angela-Nadia; Zhang, Bo; Mapolelo, Daphne T; Randeniya, Sajini; Holland, Ashley A; Johnson, Michael K; Outten, Caryn E

    2016-12-13

    Two ubiquitous protein families have emerged as key players in iron metabolism, the CGFS-type monothiol glutaredoxins (Grxs) and the BolA proteins. Monothiol Grxs and BolA proteins form heterocomplexes that have been implicated in Fe-S cluster assembly and trafficking. The Escherichia coli genome encodes members of both of these proteins families, namely, the monothiol glutaredoxin Grx4 and two BolA family proteins, BolA and IbaG. Previous work has demonstrated that E. coli Grx4 and BolA interact as both apo and [2Fe-2S]-bridged heterodimers that are spectroscopically distinct from [2Fe-2S]-bridged Grx4 homodimers. However, the physical and functional interactions between Grx4 and IbaG are uncharacterized. Here we show that co-expression of Grx4 with IbaG yields a [2Fe-2S]-bridged Grx4-IbaG heterodimer. In vitro interaction studies indicate that IbaG binds the [2Fe-2S] Grx4 homodimer to form apo Grx4-IbaG heterodimer as well as the [2Fe-2S] Grx4-IbaG heterodimer, altering the cluster stability and coordination environment. Additionally, spectroscopic and mutagenesis studies provide evidence that IbaG ligates the Fe-S cluster via the conserved histidine that is present in all BolA proteins and by a second conserved histidine that is present in the H/C loop of two of the four classes of BolA proteins. These results suggest that IbaG may function in Fe-S cluster assembly and trafficking in E. coli as demonstrated for other BolA homologues that interact with monothiol Grxs.

  7. Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.

    Science.gov (United States)

    Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

    2016-10-26

    Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.

  8. Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.

    Science.gov (United States)

    Huang, Weidong; Reinholz, Monica; Weidler, Jodi; Yolanda, Lie; Paquet, Agnes; Whitcomb, Jeannette; Lingle, Wilma; Jenkins, Robert B; Chen, Beiyun; Larson, Jeffrey S; Tan, Yuping; Sherwood, Thomas; Bates, Michael; Perez, Edith A

    2010-08-01

    The accuracy and reliability of immunohistochemical analysis and in situ hybridization for the assessment of HER2 status remains a subject of debate. We developed a novel assay (HERmark Breast Cancer Assay, Monogram Biosciences, South San Francisco, CA) that provides precise quantification of total HER2 protein expression (H2T) and HER2 homodimers (H2D) in formalin-fixed, paraffin-embedded tissue specimens. H2T and H2D results of 237 breast cancers were compared with those of immunohistochemical studies and fluorescence in situ hybridization (FISH) centrally performed at the Mayo Clinic, Rochester, MN. H2T described a continuum across a wide dynamic range ( approximately 2.5 log). Excluding the equivocal cases, HERmark showed 98% concordance with immunohistochemical studies for positive and negative assay values. For the 94 immunohistochemically equivocal cases, 67% and 39% concordance values were observed between HERmark and FISH for positive and negative assay values, respectively. Polysomy 17 in the absence of HER2 gene amplification did not result in HER2 overexpression as evaluated quantitatively using the HERmark assay.

  9. Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation.

    Science.gov (United States)

    Shizu, Ryota; Min, Jungki; Sobhany, Mack; Pedersen, Lars C; Mutoh, Shingo; Negishi, Masahiko

    2018-01-05

    The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor α (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CAR's DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion. Phosphomimetic substitution of Thr-38 with Asp increased co-immunoprecipitation of the CAR DBD with CAR LBD in Huh-7 cells. Isothermal titration calorimetry assays also revealed that recombinant CAR DBD-T38D, but not nonphosphorylated CAR DBD, bound the CAR LBD peptide. This DBD-LBD interaction masked CAR's dimer interface, preventing CAR homodimer formation. Of note, EGF signaling weakened the interaction of CAR DBD T38D with CAR LBD, converting CAR to the homodimer form. The DBD-T38D-LBD interaction also prevented CAR from forming a heterodimer with RXRα. However, this interaction opened up a CAR surface, allowing interaction with protein phosphatase 2A. Thr-38 dephosphorylation then dissociated the DBD-LBD interaction, allowing CAR heterodimer formation with RXRα. We conclude that the intramolecular interaction of phosphorylated DBD with the LBD enables CAR to adapt a transient monomer configuration that can be converted to either the inactive homodimer or the active heterodimer.

  10. Elucidation of the Specific Formation of Homo- and Heterodimeric Forms of ThbZIP1 and Its Role in Stress

    Directory of Open Access Journals (Sweden)

    Xianguang Nie

    2014-06-01

    Full Text Available Protein–protein interactions are important for the molecular understanding of the biological processes of proteins. The dimerization of bZIPs (basic leucine zipper proteins is involved in modifying binding site specificities, altering dimer stability, and permitting a new set of specific protein-to-protein interactions to occur at the promoter. In the present study, we studied the whether ThbZIP1 form homo- and heterodimers using the yeast two-hybrid method. Five bZIP genes were cloned from Tamarix hispida to investigate their interaction with ThbZIP1. Our results showed that ThbZIP1 can form homodimers with itself, and three out of five bZIPs could interact with the ThbZIP1 protein to form heterodimers. Real-time RT-PCR results suggested that these ThbZIPs can all respond to abiotic stresses and abscisic acid (ABA, and shared very similar expression patterns in response to NaCl, ABA or PEG6000. Subcellular localization studies showed that all ThbZIPs are targeted to the nucleus. Our results showed that ThbZIP1 are dimeric proteins, which can form homo- or heterodimers.

  11. A theoretical and spectroscopic study of co-amorphous naproxen and indomethacin

    DEFF Research Database (Denmark)

    Löbmann, Korbinian; Laitinen, Riikka; Grohganz, Holger

    2013-01-01

    . In this study, the co-amorphous drug mixture containing naproxen (NAP) and indomethacin (IND) was investigated using infrared spectroscopy (IR) and quantum mechanical calculations. The structures of both drugs were optimized as monomer, homodimer and heterodimer using density functional theory and used...... for the calculation of IR spectra. Conformational analysis confirmed that the optimized structures were suitable for the theoretical prediction of the spectra. Vibrational modes from the calculation could be matched with experimentally observed spectra for crystalline and amorphous NAP and IND, and it could be shown...... that both drugs exist as homodimers in their respective individual amorphous form. With the results from the experimental single amorphous drugs and theoretical homodimers, a detailed analysis of the experimental co-amorphous and theoretical heterodimer spectra was performed and evaluated. It is suggested...

  12. Dimerization of nitrophorin 4 at low pH and comparison to the K1A mutant of nitrophorin 1.

    Science.gov (United States)

    Berry, Robert E; Yang, Fei; Shokhireva, Tatiana K; Amoia, Angela M; Garrett, Sarah A; Goren, Allena M; Korte, Stephanie R; Zhang, Hongjun; Weichsel, Andrzej; Montfort, William R; Walker, F Ann

    2015-01-20

    Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer-dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and (1)H{(15)N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The "closed loop" form of the A-B and G-H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.

  13. Identification of the Dimer Exchange Interface of the Bacterial DNA Damage Response Protein UmuD.

    Science.gov (United States)

    Murison, David A; Timson, Rebecca C; Koleva, Bilyana N; Ordazzo, Michael; Beuning, Penny J

    2017-09-12

    The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both nonmutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product UmuD' and UmuC form the Y-family polymerase DNA Pol V (UmuD' 2 C) capable of performing TLS. UmuD and UmuD' exist as homodimers, but their subunits can readily exchange to form UmuDD' heterodimers preferentially. Heterodimer formation is an essential step in the degradation pathway of UmuD'. The recognition sequence for ClpXP protease is located within the first 24 amino acids of full-length UmuD, and the partner of full-length UmuD, whether UmuD or UmuD', is degraded by ClpXP. To better understand the mechanism by which UmuD subunits exchange, we measured the kinetics of exchange of a number of fluorescently labeled single-cysteine UmuD variants as detected by Förster resonance energy transfer. Labeling sites near the dimer interface correlate with increased rates of exchange, indicating that weakening the dimer interface facilitates exchange, whereas labeling sites on the exterior decrease the rate of exchange. In most but not all cases, homodimer and heterodimer exchange exhibit similar rates, indicating that somewhat different molecular surfaces mediate homodimer exchange and heterodimer formation.

  14. The human dopamine transporter forms a tetramer in the plasma membrane: cross-linking of a cysteine in the fourth transmembrane segment is sensitive to cocaine analogs.

    Science.gov (United States)

    Hastrup, Hanne; Sen, Namita; Javitch, Jonathan A

    2003-11-14

    Using cysteine cross-linking, we demonstrated previously that the dopamine transporter (DAT) is at least a homodimer, with the extracellular end of transmembrane segment (TM) 6 at a symmetrical dimer interface. We have now explored the possibility that DAT exists as a higher order oligomer in the plasma membrane. Cysteine cross-linking of wild type DAT resulted in bands on SDS-PAGE consistent with dimer, trimer, and tetramer, suggesting that DAT forms a tetramer in the plasma membrane. A cysteine-depleted DAT (CD-DAT) into which only Cys243 or Cys306 was reintroduced was cross-linked to dimer, suggesting that these endogenous cysteines in TM4 and TM6, respectively, were cross-linked at a symmetrical dimer interface. Reintroduction of both Cys243 and Cys306 into CD-DAT led to a pattern of cross-linking indistinguishable from that of wild type, with dimer, trimer, and tetramer bands. This indicated that the TM4 interface and the TM6 interface are distinct and further suggested that DAT may exist in the plasma membrane as a dimer of dimers, with two symmetrical homodimer interfaces. The cocaine analog MFZ 2-12 and other DAT inhibitors, including benztropine and mazindol, protected Cys243 against cross-linking. In contrast, two substrates of DAT, dopamine and tyramine, did not significantly impact cross-linking. We propose that the impairment of cross-linking produced by the inhibitors results from a conformational change at the TM4 interface, further demonstrating that these compounds are not neutral blockers but by themselves have effects on the structure of the transporter.

  15. Nodeless vibrational amplitudes and quantum nonadiabatic dynamics in the nested funnel for a pseudo Jahn-Teller molecule or homodimer

    Science.gov (United States)

    Peters, William K.; Tiwari, Vivek; Jonas, David M.

    2017-11-01

    The nonadiabatic states and dynamics are investigated for a linear vibronic coupling Hamiltonian with a static electronic splitting and weak off-diagonal Jahn-Teller coupling through a single vibration with a vibrational-electronic resonance. With a transformation of the electronic basis, this Hamiltonian is also applicable to the anti-correlated vibration in a symmetric homodimer with marginally strong constant off-diagonal coupling, where the non-adiabatic states and dynamics model electronic excitation energy transfer or self-exchange electron transfer. For parameters modeling a free-base naphthalocyanine, the nonadiabatic couplings are deeply quantum mechanical and depend on wavepacket width; scalar couplings are as important as the derivative couplings that are usually interpreted to depend on vibrational velocity in semiclassical curve crossing or surface hopping theories. A colored visualization scheme that fully characterizes the non-adiabatic states using the exact factorization is developed. The nonadiabatic states in this nested funnel have nodeless vibrational factors with strongly avoided zeroes in their vibrational probability densities. Vibronic dynamics are visualized through the vibrational coordinate dependent density of the time-dependent dipole moment in free induction decay. Vibrational motion is amplified by the nonadiabatic couplings, with asymmetric and anisotropic motions that depend upon the excitation polarization in the molecular frame and can be reversed by a change in polarization. This generates a vibrational quantum beat anisotropy in excess of 2/5. The amplitude of vibrational motion can be larger than that on the uncoupled potentials, and the electronic population transfer is maximized within one vibrational period. Most of these dynamics are missed by the adiabatic approximation, and some electronic and vibrational motions are completely suppressed by the Condon approximation of a coordinate-independent transition dipole between

  16. Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization.

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Kangawa, Kenji; Minamino, Naoto

    2017-07-01

    Atrial natriuretic peptide (ANP) is primarily produced in the heart tissue and plays a pivotal role in maintaining cardiovascular homeostasis in endocrine and autocrine/paracrine systems and has clinical applications as a biomarker and a therapeutic agent for cardiac diseases. ANP is synthesized by atrial cardiomyocytes as a preprohormone that is processed by a signal peptidase and stored in secretory granules as a prohormone. Subsequent proteolytic processing of ANP by corin during the secretion process results in a bioactive form consisting of 28 amino acid residues. Mechanical stretch of the atrial wall and multiple humoral factors directly stimulates the transcription and secretion of ANP. Secreted ANP elicits natriuretic and diuretic effects via cyclic guanosine monophosphate produced through binding to the guanylyl cyclase-A/natriuretic peptide receptor-A. Circulating ANP is subjected to rapid clearance by a natriuretic peptide receptor-C-mediated mechanism and proteolytic degradation by neutral endopeptidase. In humans, ANP is present as three endogenous molecular forms: bioactive α-ANP, a homodimer of α-ANP designated as β-ANP, and an ANP precursor designated as proANP (also referred to as γ-ANP). The proANP and especially β-ANP, as minor forms in circulation, are notably increased in patients with cardiac diseases, suggesting the utility of monitoring the pathophysiological conditions that result in abnormal proANP processing that cannot be monitored by inactive N-terminal proANP-related fragments. Emerging plate-based sandwich immunoassays for individual quantitation of the three ANP forms enables evaluation of diagnostic implications and net ANP bioactivity. This new tool may provide further understanding in the pathophysiology of cardiac diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  17. New insights into the molecular mechanism of E-cadherin-mediated cell adhesion by free energy calculations

    DEFF Research Database (Denmark)

    Doro, Fabio; Saladino, Giorgio; Belvisi, Laura

    2015-01-01

    Three-dimensional domain swapping is an important mode of protein association leading to the formation of stable dimers. Monomers associating via this mechanism mutually exchange a domain to form a homodimer. Classical cadherins, an increasingly important target for anticancer therapy, use domain...... swapping to mediate cell adhesion. However, despite its importance, the molecular mechanism of domain swapping is still debated. Here, we study the conformational changes that lead to activation and dimerization via domain swapping of E-cadherin. Using state-of-the-art enhanced sampling atomistic......" mechanism in which monomers in an active conformational state bind to form a homodimer, analogous to the conformational selection mechanism often observed in ligand-target binding. Moreover, we find that the open state population is increased in the presence of calcium ions at the extracellular boundary...

  18. Analytical Validation of a Highly Quantitative, Sensitive, Accurate, and Reproducible Assay (HERmark® for the Measurement of HER2 Total Protein and HER2 Homodimers in FFPE Breast Cancer Tumor Specimens

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Larson

    2010-01-01

    Full Text Available We report here the results of the analytical validation of assays that measure HER2 total protein (H2T and HER2 homodimer (H2D expression in Formalin Fixed Paraffin Embedded (FFPE breast cancer tumors as well as cell line controls. The assays are based on the VeraTag technology platform and are commercially available through a central CAP-accredited clinical reference laboratory. The accuracy of H2T measurements spans a broad dynamic range (2-3 logs as evaluated by comparison with cross-validating technologies. The measurement of H2T expression demonstrates a sensitivity that is approximately 7–10 times greater than conventional immunohistochemistry (IHC (HercepTest. The HERmark assay is a quantitative assay that sensitively and reproducibly measures continuous H2T and H2D protein expression levels and therefore may have the potential to stratify patients more accurately with respect to response to HER2-targeted therapies than current methods which rely on semiquantitative protein measurements (IHC or on indirect assessments of gene amplification (FISH.

  19. A STUDY OF INTERMEDIATES INVOLVED IN THE FOLDING PATHWAY FOR RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR (M-CSF) - EVIDENCE FOR 2 DISTINCT FOLDING PATHWAYS

    NARCIS (Netherlands)

    WILKINS, JA; CONE, J; RANDHAWA, ZI; WOOD, D; WARREN, MK; WITKOWSKA, HE

    The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding

  20. DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor.

    Science.gov (United States)

    Vonderach, Matthias; Byrne, Dominic P; Barran, Perdita E; Eyers, Patrick A; Eyers, Claire E

    2018-06-05

    The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKA c ) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKA c - and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKA c -regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA. Graphical Abstract ᅟ.

  1. Dissection of structural and functional requirements that underlie the interaction of ERdj3 protein with substrates in the endoplasmic reticulum.

    Science.gov (United States)

    Otero, Joel H; Lizák, Beata; Feige, Matthias J; Hendershot, Linda M

    2014-10-03

    ERdj3, a mammalian endoplasmic reticulum (ER) Hsp40/DnaJ family member, binds unfolded proteins, transfers them to BiP, and concomitantly stimulates BiP ATPase activity. However, the requirements for ERdj3 binding to and release from substrates in cells are not well understood. We found that ERdj3 homodimers that cannot stimulate the ATPase activity of BiP (QPD mutants) bound to unfolded ER proteins under steady state conditions in much greater amounts than wild-type ERdj3. This was due to reduced release from these substrates as opposed to enhanced binding, although in both cases dimerization was strictly required for substrate binding. Conversely, heterodimers consisting of one wild-type and one mutant ERdj3 subunit bound substrates at levels comparable with wild-type ERdj3 homodimers, demonstrating that release requires only one protomer to be functional in stimulating BiP ATPase activity. Co-expressing wild-type ERdj3 and a QPD mutant, which each exclusively formed homodimers, revealed that the release rate of wild-type ERdj3 varied according to the relative half-lives of substrates, suggesting that ERdj3 release is an important step in degradation of unfolded client proteins in the ER. Furthermore, pulse-chase experiments revealed that the binding of QPD mutant homodimers remained constant as opposed to increasing, suggesting that ERdj3 does not normally undergo reiterative binding cycles with substrates. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli.

    Science.gov (United States)

    Grönlund, Hans; Bergman, Tomas; Sandström, Kristofer; Alvelius, Gunvor; Reininger, Renate; Verdino, Petra; Hauswirth, Alexander; Liderot, Karin; Valent, Peter; Spitzauer, Susanne; Keller, Walter; Valenta, Rudolf; van Hage-Hamsten, Marianne

    2003-10-10

    Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE-mediated allergy. Attempts to produce tetrameric folded major allergen Fel d 1 by recombinant methods with structural features similar to the natural allergen have been only partially successful. In this study, a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart was produced. A synthetic gene coding for direct fusion of the Fel d 1 chain 2 N-terminally to chain 1 was constructed by overlapping oligonucleotides in PCR. Escherichia coli expression resulted in a non-covalently associated homodimer with an apparent molecular mass of 30 kDa defined by size exclusion chromatography. Furthermore, each 19,177-Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, i.e. Cys3(1) Cys73(2), Cys44(1)-Cys48(2), Cys70(1)-Cys7(2), as determined by electrospray mass spectrometry after tryptic digestion. Circular dichroism analysis showed identical folds of natural and recombinant Fel d 1. Furthermore, recombinant Fel d l reacted specifically with serum IgE, inducing expression of CD203c on basophils and lymphoproliferative responses in cat-allergic patients. The results show that the overall fold and immunological properties of the recombinant Fel d 1 are very similar to those of natural Fel d 1. Moreover, the recombinant Fel d 1 construct provides a tool for defining the three-dimensional structure of Fel d 1 and represents a reagent for diagnosis and allergen-specific immunotherapy of cat allergy.

  3. Structural basis of the 9-fold symmetry of centrioles.

    Science.gov (United States)

    Kitagawa, Daiju; Vakonakis, Ioannis; Olieric, Natacha; Hilbert, Manuel; Keller, Debora; Olieric, Vincent; Bortfeld, Miriam; Erat, Michèle C; Flückiger, Isabelle; Gönczy, Pierre; Steinmetz, Michel O

    2011-02-04

    The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus.

    Science.gov (United States)

    Tucakov, Anna Katharina; Yavuz, Sabine; Schürmann, Eva-Maria; Mischler, Manjula; Klingebeil, Anne; Meyers, Gregor

    2018-01-01

    The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein E rns is an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked E rns homodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G. J Virol 2009;83:4823-4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked E rns homodimers. In transient expression studies E rns mutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt E rns . Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and E rns dimerization.

  5. Diverse oligomeric states of CEACAM IgV domains.

    Science.gov (United States)

    Bonsor, Daniel A; Günther, Sebastian; Beadenkopf, Robert; Beckett, Dorothy; Sundberg, Eric J

    2015-11-03

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6-CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6-CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.

  6. A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  7. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  8. Spectroscopic and functional characterization of iron-bound forms of Azotobacter vinelandii (Nif)IscA.

    Science.gov (United States)

    Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

    2012-10-16

    The ability of Azotobacter vinelandii(Nif)IscA to bind Fe has been investigated to assess the role of Fe-bound forms in NIF-specific Fe-S cluster biogenesis. (Nif)IscA is shown to bind one Fe(III) or one Fe(II) per homodimer and the spectroscopic and redox properties of both the Fe(III)- and Fe(II)-bound forms have been characterized using the UV-visible absorption, circular dichroism, and variable-temperature magnetic circular dichroism, electron paramagnetic resonance, Mössbauer and resonance Raman spectroscopies. The results reveal a rhombic intermediate-spin (S = 3/2) Fe(III) center (E/D = 0.33, D = 3.5 ± 1.5 cm(-1)) that is most likely 5-coordinate with two or three cysteinate ligands and a rhombic high spin (S = 2) Fe(II) center (E/D = 0.28, D = 7.6 cm(-1)) with properties similar to reduced rubredoxins or rubredoxin variants with three cysteinate and one or two oxygenic ligands. Iron-bound (Nif)IscA undergoes reversible redox cycling between the Fe(III)/Fe(II) forms with a midpoint potential of +36 ± 15 mV at pH 7.8 (versus NHE). l-Cysteine is effective in mediating release of free Fe(II) from both the Fe(II)- and Fe(III)-bound forms of (Nif)IscA. Fe(III)-bound (Nif)IscA was also shown to be a competent iron source for in vitro NifS-mediated [2Fe-2S] cluster assembly on the N-terminal domain of NifU, but the reaction occurs via cysteine-mediated release of free Fe(II) rather than direct iron transfer. The proposed roles of A-type proteins in storing Fe under aerobic growth conditions and serving as iron donors for cluster assembly on U-type scaffold proteins or maturation of biological [4Fe-4S] centers are discussed in light of these results.

  9. Cold denaturation of the HIV-1 protease monomer

    DEFF Research Database (Denmark)

    Rösner, Heike Ilona; Caldarini, Martina; Prestel, Andreas

    2017-01-01

    The HIV-1-protease is a complex protein which in its active form adopts a homodimer dominated by -sheet structures. We have discovered a cold-denatured state of the monomeric subunit of HIV-1-protease which is populated above 0ºC and therefore directly accessible to various spectroscopic approac...

  10. Malachite green mediates homodimerization of antibody VL domains to form a fluorescent ternary complex with singular symmetric interfaces

    Science.gov (United States)

    Szent-Gyorgyi, Chris; Stanfield, Robyn L.; Andreko, Susan; Dempsey, Alison; Ahmed, Mushtaq; Capek, Sara; Waggoner, Alan; Wilson, Ian A.; Bruchez, Marcel P.

    2013-01-01

    We report that a symmetric small molecule ligand mediates the assembly of antibody light chain variable domains (VLs) into a correspondent symmetric ternary complex with novel interfaces. The L5* Fluorogen Activating Protein (FAP) is a VL domain that binds malachite green dye (MG) to activate intense fluorescence. Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with inclusive C2 symmetry, where MG is almost entirely encapsulated between an antiparallel arrangement of the two VL domains. Unliganded L5* VL domains crystallize as a similar antiparallel VL/VL homodimer. The complementarity determining regions (CDRs) are spatially oriented to form novel VL/VL and VL/ligand interfaces that tightly constrain a propeller conformer of MG. Binding equilibrium analysis suggests highly cooperative assembly to form a very stable VL/MG/VL complex, such that MG behaves as a strong chemical inducer of dimerization. Fusion of two VL domains into a single protein tightens MG binding over 1,000-fold to low picomolar affinity without altering the large binding enthalpy, suggesting that bonding interactions with ligand and restriction of domain movements make independent contributions to binding. Fluorescence activation of a symmetrical fluorogen provides a selection mechanism for the isolation and directed evolution of ternary complexes where unnatural symmetric binding interfaces are favored over canonical antibody interfaces. As exemplified by L5*, these self-reporting complexes may be useful as modulators of protein association or as high affinity protein tags and capture reagents. PMID:23978698

  11. Properties and crystal structure of methylenetetrahydrofolate reductase from Thermus thermophilus HB8.

    Directory of Open Access Journals (Sweden)

    Sayaka Igari

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is one of the enzymes involved in homocysteine metabolism. Despite considerable genetic and clinical attention, the reaction mechanism and regulation of this enzyme are not fully understood because of difficult production and poor stability. While recombinant enzymes from thermophilic organisms are often stable and easy to prepare, properties of thermostable MTHFRs have not yet been reported.MTHFR from Thermus thermophilus HB8, a homologue of Escherichia coli MetF, has been expressed in E. coli and purified. The purified MTHFR was chiefly obtained as a heterodimer of apo- and holo-subunits, that is, one flavin adenine dinucleotide (FAD prosthetic group bound per dimer. The crystal structure of the holo-subunit was quite similar to the β(8α(8 barrel of E. coli MTHFR, while that of the apo-subunit was a previously unobserved closed form. In addition, the intersubunit interface of the dimer in the crystals was different from any of the subunit interfaces of the tetramer of E. coli MTHFR. Free FAD could be incorporated into the apo-subunit of the purified Thermus enzyme after purification, forming a homodimer of holo-subunits. Comparison of the crystal structures of the heterodimer and the homodimer revealed different intersubunit interfaces, indicating a large conformational change upon FAD binding. Most of the biochemical properties of the heterodimer and the homodimer were the same, except that the homodimer showed ≈50% activity per FAD-bound subunit in folate-dependent reactions.The different intersubunit interfaces and rearrangement of subunits of Thermus MTHFR may be related to human enzyme properties, such as the allosteric regulation by S-adenosylmethionine and the enhanced instability of the Ala222Val mutant upon loss of FAD. Whereas E. coli MTHFR was the only structural model for human MTHFR to date, our findings suggest that Thermus MTHFR will be another useful model for this important enzyme.

  12. The roles of the RIIβ linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of the type IIβ protein kinase A: a small angle x-ray and neutron scattering study.

    Science.gov (United States)

    Blumenthal, Donald K; Copps, Jeffrey; Smith-Nguyen, Eric V; Zhang, Ping; Heller, William T; Taylor, Susan S

    2014-10-10

    Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RIIβ is structurally unique in that the type IIβ holoenzyme is much more compact than the free RIIβ homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RIIβ C-terminal deletion mutant (RIIβ(1-280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type IIβ holoenzyme and the RIIβ domains that contribute to stabilizing the holoenzyme conformation. Our results demonstrate that compaction of the type IIβ holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RIIβ homodimer. The structural rearrangements are significantly greater than seen previously with RIIα and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type IIβ isoform of PKA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

    DEFF Research Database (Denmark)

    Vognsen, Tina Reinholdt; Kristensen, Ole

    2012-01-01

    The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a ß-sheet and three a-helices forming...

  14. 16 kDa heat shock protein from heat-inactivated Mycobacterium tuberculosis is a homodimer - suitability for diagnostic applications with specific llama VHH monoclonals.

    Directory of Open Access Journals (Sweden)

    Saurabh K Srivastava

    Full Text Available BACKGROUND: The 16 kDa heat shock protein (HSP is an immuno-dominant antigen, used in diagnosis of infectious Mycobacterium tuberculosis (M.tb. causing tuberculosis (TB. Its use in serum-based diagnostics is limited, but for the direct identification of M.tb. bacteria in sputum or cultures it may represent a useful tool. Recently, a broad set of twelve 16 kDa specific heavy chain llama antibodies (VHH has been isolated, and their utility for diagnostic applications was explored. METHODOLOGY/PRINCIPAL FINDINGS: To identify the epitopes recognized by the nine (randomly selected from a set of twelve 16 kDa specific VHH antibodies distinct VHH antibodies, 14 overlapping linear epitopes (each 20 amino acid long were characterized using direct and sandwich ELISA techniques. Seven out of 14 epitopes were recognized by 8 out of 9 VHH antibodies. The two highest affinity binders B-F10 and A-23 were found to bind distinct epitopes. Sandwich ELISA and SPR experiments showed that only B-F10 was suitable as secondary antibody with both B-F10 and A-23 as anchoring antibodies. To explain this behavior, the epitopes were matched to the putative 3D structure model. Electrospray ionization time-of-flight mass spectrometry and size exclusion chromatography were used to determine the higher order conformation. A homodimer model best explained the differential immunological reactivity of A-23 and B-F10 against heat-treated M.tb. lysates. CONCLUSIONS/SIGNIFICANCE: The concentrations of secreted antigens of M.tb. in sputum are too low for immunological detection and existing kits are only used for identifying M.tb. in cultures. Here we describe how specific combinations of VHH domains could be used to detect the intracellular HSP antigen. Linked to methods of pre-concentrating M.tb. cells prior to lysis, HSP detection may enable the development of protein-based diagnostics of sputum samples and earlier diagnosis of diseases.

  15. New insights into the organization of plasma membrane and its role in signal transduction.

    Science.gov (United States)

    Suzuki, Kenichi G N

    2015-01-01

    Plasma membranes have heterogeneous structures for efficient signal transduction, required to perform cell functions. Recent evidence indicates that the heterogeneous structures are produced by (1) compartmentalization by actin-based membrane skeleton, (2) raft domains, (3) receptor-receptor interactions, and (4) the binding of receptors to cytoskeletal proteins. This chapter provides an overview of recent studies on diffusion, clustering, raft association, actin binding, and signal transduction of membrane receptors, especially glycosylphosphatidylinositol (GPI)-anchored receptors. Studies on diffusion of GPI-anchored receptors suggest that rafts may be small and/or short-lived in plasma membranes. In steady state conditions, GPI-anchored receptors form transient homodimers, which may represent the "standby state" for the stable homodimers and oligomers upon ligation. Furthermore, It is proposed that upon ligation, the binding of GPI-anchored receptor clusters to cytoskeletal actin filaments produces a platform for downstream signaling, and that the pulse-like signaling easily maintains the stability of the overall signaling activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Usher protein functions in hair cells and photoreceptors

    OpenAIRE

    Cosgrove, Dominic; Zallocchi, Marisa

    2013-01-01

    The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber,...

  17. Structure of the Reston ebolavirus VP30 C-terminal domain.

    Science.gov (United States)

    Clifton, Matthew C; Kirchdoerfer, Robert N; Atkins, Kateri; Abendroth, Jan; Raymond, Amy; Grice, Rena; Barnes, Steve; Moen, Spencer; Lorimer, Don; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

    2014-04-01

    The ebolaviruses can cause severe hemorrhagic fever. Essential to the ebolavirus life cycle is the protein VP30, which serves as a transcriptional cofactor. Here, the crystal structure of the C-terminal, NP-binding domain of VP30 from Reston ebolavirus is presented. Reston VP30 and Ebola VP30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface.

  18. Spectroscopic and functional characterization of iron-sulfur cluster-bound forms of Azotobacter vinelandii (Nif)IscA.

    Science.gov (United States)

    Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

    2012-10-16

    The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly proteins, in general, and the specific role of (Nif)IscA in the maturation of nitrogen fixation proteins are currently unknown. To address these questions, in vitro spectroscopic studies (UV-visible absorption/CD, resonance Raman and Mössbauer) have been used to investigate the mechanism of [4Fe-4S] cluster assembly on Azotobacter vinelandii(Nif)IscA, and the ability of (Nif)IscA to accept clusters from NifU and to donate clusters to the apo form of the nitrogenase Fe-protein. The results show that (Nif)IscA can rapidly and reversibly cycle between forms containing one [2Fe-2S](2+) and one [4Fe-4S](2+) cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe-2S](2+) clusters and O(2)-induced [4Fe-4S](2+) oxidative cleavage. This unique type of cluster interconversion in response to cellular redox status and oxygen levels is likely to be important for the specific role of A-type proteins in the maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or oxidative stress conditions. Only the [4Fe-4S](2+)-(Nif)IscA was competent for rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo-(Nif)IscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid intact cluster transfer, indicating a potential role as a cluster carrier for delivery of clusters assembled on NifU. Overall the results support the proposal that A-type proteins can function as carrier proteins for clusters assembled on U-type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under aerobic or oxidative stress growth conditions.

  19. N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization

    DEFF Research Database (Denmark)

    Nørskov-Lauritsen, Lenea; Jørgensen, Stine; Bräuner-Osborne, Hans

    2015-01-01

    Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expr...... covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed....

  20. Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

    Directory of Open Access Journals (Sweden)

    Maia Amanda M

    2012-07-01

    Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

  1. UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage–specific manner

    Science.gov (United States)

    Toyama, Takuya; Nakamura, Yuki; Tamada, Kentaro; Shimizu, Hitomi; Ninagawa, Satoshi; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Aoyama, Eriko; Takigawa, Masaharu

    2017-01-01

    The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen. In this study, we show that this vacuolization step requires both ATF6 and BBF2H7 as UPR transducers and that BBF2H7 regulates a complete set of genes (Sec23/24/13/31, Tango1, Sedlin, and KLHL12) essential for the enlargement of COPII vesicles to accommodate long-chain collagen for export, leading to the formation of the perinotochordal basement membrane. Thus, the most appropriate UPR transducer is activated to cope with the differing physiological ER stresses of different content types depending on developmental stage. PMID:28500182

  2. Role of α and β Transmembrane Domains in Integrin Clustering

    Directory of Open Access Journals (Sweden)

    Amir Shamloo

    2015-11-01

    Full Text Available Integrins are transmembrane proteins playing a crucial role in the mechanical signal transduction from the outside to the inside of a cell, and vice versa. Nevertheless, this signal transduction could not be implemented by a single protein. Rather, in order for integrins to be able to participate in signal transduction, they need to be activated and produce clusters first. As integrins consist of α- and β-subunits that are separate in the active state, studying both subunits separately is of a great importance, for, in the active state, the distance between α- and β-subunits is long enough that they do not influence one another significantly. Thus, this study aims to investigate the tendency of transmembrane domains of integrins to form homodimers. We used both Steered and MARTINI Coarse-grained molecular dynamics method to perform our simulations, mainly because of a better resolution and computational feasibility that each of these methods could provide to us. Using the Steered molecular dynamics method for α- and β-subunits, we found that the localized lipid packing prevented them from clustering. Nonetheless, the lipid packing phenomenon was found to be an artifact after investigating this process using a coarse grained (CG model. Exploiting the coarse-grained molecular dynamics simulations, we found that α- and β-subunits tend to form a stable homo-dimer.

  3. The Specificity of Innate Immune Responses Is Enforced by Repression of Interferon Response Elements by NF-κB p50

    Science.gov (United States)

    Cheng, Christine S.; Feldman, Kristyn E.; Lee, James; Verma, Shilpi; Huang, De-Bin; Huynh, Kim; Chang, Mikyoung; Ponomarenko, Julia V.; Sun, Shao-Cong; Benedict, Chris A.; Ghosh, Gourisankar; Hoffmann, Alexander

    2011-01-01

    The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. Members of the nuclear factor κB (NF-κB) and interferon (IFN) regulatory factor (IRF) transcription factor families bind to the κB site and the IFN response element (IRE), respectively, of target genes, and they are activated in macrophages after exposure to pathogens. However, how these factors produce pathogen-specific inflammatory and immune responses remains poorly understood. Combining top-down and bottom-up systems biology approaches, we have identified the NF-κB p50 homodimer as a regulator of IRF responses. Unbiased genome-wide expression and biochemical and structural analyses revealed that the p50 homodimer repressed a subset of IFN-inducible genes through a previously uncharacterized subclass of guanine-rich IRE (G-IRE) sequences. Mathematical modeling predicted that the p50 homodimer might enforce the stimulus specificity of composite promoters. Indeed, the production of the antiviral regulator IFN-β was rendered stimulus-specific by the binding of the p50 homodimer to the G-IRE–containing IFNβ enhancer to suppress cytotoxic IFN signaling. Specifically, a deficiency in p50 resulted in the inappropriate production of IFN-β in response to bacterial DNA sensed by Toll-like receptor 9. This role for the NF-κB p50 homodimer in enforcing the specificity of the cellular response to pathogens by binding to a subset of IRE sequences alters our understanding of how the NF-κB and IRF signaling systems cooperate to regulate antimicrobial immunity. PMID:21343618

  4. Crystal structure of a human single domain antibody dimer formed through V(H-V(H non-covalent interactions.

    Directory of Open Access Journals (Sweden)

    Toya Nath Baral

    Full Text Available Single-domain antibodies (sdAbs derived from human V(H are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2 sdAbs, Gr3 and Gr6, from a synthetic human V(H phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 Å resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the V(H-V(L heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions.

  5. Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex.

    Science.gov (United States)

    Su'etsugu, Masayuki; Shimuta, Toh-Ru; Ishida, Takuma; Kawakami, Hironori; Katayama, Tsutomu

    2005-02-25

    In Escherichia coli, the activity of ATP-bound DnaA protein in initiating chromosomal replication is negatively controlled in a replication-coordinated manner. The RIDA (regulatory inactivation of DnaA) system promotes DnaA-ATP hydrolysis to produce the inactivated form DnaA-ADP in a manner depending on the Hda protein and the DNA-loaded form of the beta-sliding clamp, a subunit of the replicase holoenzyme. A highly functional form of Hda was purified and shown to form a homodimer in solution, and two Hda dimers were found to associate with a single clamp molecule. Purified mutant Hda proteins were used in a staged in vitro RIDA system followed by a pull-down assay to show that Hda-clamp binding is a prerequisite for DnaA-ATP hydrolysis and that binding is mediated by an Hda N-terminal motif. Arg(168) in the AAA(+) Box VII motif of Hda plays a role in stable homodimer formation and in DnaA-ATP hydrolysis, but not in clamp binding. Furthermore, the DnaA N-terminal domain is required for the functional interaction of DnaA with the Hda-clamp complex. Single cells contain approximately 50 Hda dimers, consistent with the results of in vitro experiments. These findings and the features of AAA(+) proteins, including DnaA, suggest the following model. DnaA-ATP is hydrolyzed at a binding interface between the AAA(+) domains of DnaA and Hda; the DnaA N-terminal domain supports this interaction; and the interaction of DnaA-ATP with the Hda-clamp complex occurs in a catalytic mode.

  6. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...

  7. The step-wise pathway of septin hetero-octamer assembly in budding yeast.

    Science.gov (United States)

    Weems, Andrew; McMurray, Michael

    2017-05-25

    Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.

  8. Crystal structures of Hsp104 N-terminal domains from Saccharomyces cerevisiae and Candida albicans suggest the mechanism for the function of Hsp104 in dissolving prions

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Peng; Li, Jingzhi; Weaver, Clarissa; Lucius, Aaron; Sha, Bingdong

    2017-03-31

    Hsp104 is a yeast member of the Hsp100 family which functions as a molecular chaperone to disaggregate misfolded polypeptides. To understand the mechanism by which the Hsp104 N-terminal domain (NTD) interacts with its peptide substrates, crystal structures of the Hsp104 NTDs fromSaccharomyces cerevisiae(ScHsp104NTD) andCandida albicans(CaHsp104NTD) have been determined at high resolution. The structures of ScHsp104NTD and CaHsp104NTD reveal that the yeast Hsp104 NTD may utilize a conserved putative peptide-binding groove to interact with misfolded polypeptides. In the crystal structures ScHsp104NTD forms a homodimer, while CaHsp104NTD exists as a monomer. The consecutive residues Gln105, Gln106 and Lys107, and Lys141 around the putative peptide-binding groove mediate the monomer–monomer interactions within the ScHsp104NTD homodimer. Dimer formation by ScHsp104NTD suggests that the Hsp104 NTD may specifically interact with polyQ regions of prion-prone proteins. The data may reveal the mechanism by which Hsp104 NTD functions to suppress and/or dissolve prions.

  9. Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

    Directory of Open Access Journals (Sweden)

    Makenzie Saoura

    Full Text Available The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether and functions as a monomer. The amino domain retains the flexible arm responsible for substrate recognition and binding while the carboxy domain retains the active site. The linker region was explored by Ala-scanning through two conserved regions of D. melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain proximal to the linker, and Tflex, a flexible site in the linker. Periodic substitutions in a hydrophobic patch (F329 and L332 at the carboxy end of NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively, accompanied by reduced linker flexibility at N-T inside the Ndom- linker boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher catalytic efficiency than wild type and locally decreased flexibility, while the Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in pre-tRNA processing kinetics and protein flexibility are interpreted in light of a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of local changes in hydrophobicity into the skeleton of the amino domain.

  10. The E. coli monothiol glutaredoxin GrxD forms homodimeric and heterodimeric FeS cluster containing complexes.

    Science.gov (United States)

    Yeung, N; Gold, B; Liu, N L; Prathapam, R; Sterling, H J; Willams, E R; Butland, G

    2011-10-18

    Monothiol glutaredoxins (mono-Grx) represent a highly evolutionarily conserved class of proteins present in organisms ranging from prokaryotes to humans. Mono-Grxs have been implicated in iron sulfur (FeS) cluster biosynthesis as potential scaffold proteins and in iron homeostasis via an FeS-containing complex with Fra2p (homologue of E. coli BolA) in yeast and are linked to signal transduction in mammalian systems. However, the function of the mono-Grx in prokaryotes and the nature of an interaction with BolA-like proteins have not been established. Recent genome-wide screens for E. coli genetic interactions reported the synthetic lethality (combination of mutations leading to cell death; mutation of only one of these genes does not) of a grxD mutation when combined with strains defective in FeS cluster biosynthesis (isc operon) functions [Butland, G., et al. (2008) Nature Methods 5, 789-795]. These data connected the only E. coli mono-Grx, GrxD to a potential role in FeS cluster biosynthesis. We investigated GrxD to uncover the molecular basis of this synthetic lethality and observed that GrxD can form FeS-bound homodimeric and BolA containing heterodimeric complexes. These complexes display substantially different spectroscopic and functional properties, including the ability to act as scaffold proteins for intact FeS cluster transfer to the model [2Fe-2S] acceptor protein E. coli apo-ferredoxin (Fdx), with the homodimer being significantly more efficient. In this work, we functionally dissect the potential cellular roles of GrxD as a component of both homodimeric and heterodimeric complexes to ultimately uncover if either of these complexes performs functions linked to FeS cluster biosynthesis. © 2011 American Chemical Society

  11. Structural and dynamic studies of the dimerization and DNA-binding domains of the transcription factors v-Myc and Max

    International Nuclear Information System (INIS)

    Fieber, W.

    2001-05-01

    In the present work, solution structural and dynamic properties of the dimerization and DNA binding domains of the transcription factors v-Myc and Max were characterized by NMR and CD spectroscopy. It could be demonstrated that v-Myc in the absence of its authentic binding partner Max does not homodimerize, but exists in a monomeric and prestructured form. Two separated α-helical regions in the leucine zipper region and in the basic-H1 region, respectively, could be identified, while the latter appeared to be less stable. Both helices lack stabilizing tertiary side chain interactions and represent exceptional examples for loosely coupled, structured segments in a native protein. The structure of v-Myc is dynamic and can be described as a distribution of conformational substates. Motion within the substates comprise fast (picosecond to nanosecond) local backbone fluctuations like helical fraying, whereas motion between the substates comprise the relative orientation of the two helices and occur at larger time scales (microsecond to millisecond). The preformation of the specific protein and DNA binding sites, leucine zipper and the basic region, presumably allows rapid and accurate recognition of the respective binding partners. v-Myc-Max and Max-Max protein preparations were shown to form stable dimers. Thermodynamic analysis of the dissociation reactions of v-Myc-Max revealed a significant higher stability of the heterodimer than of the Max-Max homodimer over the whole temperature range. It could be demonstrated that the restricted conformational space of the v-Myc bHLHZip domain reduces the entropy penalty associated with dimerization and contributes to the preference of Max to form heterodimers with v-Myc rather than homodimers. (author)

  12. Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

    Science.gov (United States)

    Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

    2017-03-01

    A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Densified waste form and method for forming

    Science.gov (United States)

    Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

    2015-08-25

    Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

  14. A comparative study of three cytotoxicity test methods for nanomaterials using sodium lauryl sulfate.

    Science.gov (United States)

    Kwon, Jae-Sung; Kim, Kwang-Mahn; Kim, Kyoung-Nam

    2014-10-01

    The biocompatibility evaluation of nanomaterials is essential for their medical diagnostic and therapeutic usage, where a cytotoxicity test is the simplest form of biocompatibility evaluation. Three methods have been commonly used in previous studies for the cytotoxicity testing of nanomaterials: trypan blue exclusion, colorimetric assay using water soluble tetrazolium (WST), and imaging under a microscope following calcein AM/ethidium homodimer-1 staining. However, there has yet to be a study to compare each method. Therefore, in this study three methods were compared using the standard reference material of sodium lauryl sulfate (SLS). Each method of the cytotoxicity test was carried out using mouse fibroblasts of L-929 exposed to different concentrations of SLS. Compared to the gold standard trypan blue exclusion test, both colorimetric assay using water soluble tetrazolium (WST) and imaging under microscope with calcein AM/ethidium homodimer-1 staining showed results that were not statistically different. Also, each method exhibited various advantages and disadvantages, which included the need of equipment, time taken for the experiment, and provision of additional information such as cell morphology. Therefore, this study concludes that all three methods of cytotoxicity testing may be valid, though careful consideration will be needed when selecting tests with regard to time, finances, and the amount of information required by the researcher(s).

  15. Structural features of the KPI domain control APP dimerization, trafficking, and processing.

    Science.gov (United States)

    Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2012-02-01

    The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

  16. GPCR Interaction: 157 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000907.2 ...

  17. GPCR Interaction: 156 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000697.1 ...

  18. GPCR Interaction: 154 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR a...eceptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000045.1 ... ...using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

  19. GPCR Interaction: 155 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available n of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR ...receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000907.2 ... ... using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

  20. In situ detection of estrogen receptor dimers in breast carcinoma cells in archival materials using proximity ligation assay (PLA).

    Science.gov (United States)

    Iwabuchi, Erina; Miki, Yasuhiro; Ono, Katsuhiko; Onodera, Yoshiaki; Suzuki, Takashi; Hirakawa, Hisashi; Ishida, Takanori; Ohuchi, Noriaki; Sasano, Hironobu

    2017-01-01

    Estrogen receptor (ER) is required for carcinoma cell proliferation in the great majority of breast cancer and also functions as a dimer. ER dimeric proteins have been largely identified by BRET/FRET analyses but their in situ visualization have not yet been reported. Recently, in situ Proximity Ligation Assay (PLA) has been developed as the methods detecting protein interactions in situ. Therefore, in this study we firstly demonstrated the dimerization of ERα in breast carcinoma cell lines and tissues using PLA. The human breast carcinoma cell lines MCF-7, T-47D and MDA-MB-231 were used in this study. Cells were treated with ER agonist or antagonist and fixed in 4% PFA, and ER dimers were subsequently detected using PLA. The evaluation of ER dimers in breast carcinoma cell lines were quantified by measuring the area of dots localized in the nuclei using image analysis. We also firstly demonstrated the visualization of ER dimer patterns in 10% formalin-fixed paraffin-embedded tissues of breast cancer using PLA technique. Estradiol (E2) administration induced ERα homodimers in the nuclei of MCF-7 and T-47D but not in ER-negative MDA-MB-231. 4-OH tamoxifen also induced ERα homodimers but the subcellular localization of these ERα homodimers was predominant in cytoplasm instead of the nuclei induced by E2 treatment. ICI182,780 treatment did decrease the number of formation of ERα homodimers in MCF-7. In breast cancer patients, ERα PLA score was significantly correlated positively with ERα- or PgR (progesterone receptor) immunohistochemical scores and inversely with Ki-67-labeling index, respectively. We also demonstrated the ERα/β heterodimer as well as ERα homodimers in both breast carcinoma cell lines and surgical pathology specimens. In summary, we did firstly succeed in the visualization of ER dimeric proteins using PLA method. The evaluation of ER dimer patterns could provide pivotal information as to the prediction of response to endocrine therapy of

  1. Dimerization and DNA-binding of ASR1, a small hydrophilic protein abundant in plant tissues suffering from water loss

    International Nuclear Information System (INIS)

    Maskin, Laura; Frankel, Nicolas; Gudesblat, Gustavo; Demergasso, Maria J.; Pietrasanta, Lia I.; Iusem, Norberto D.

    2007-01-01

    The Asr gene family is present in Spermatophyta. Its members are generally activated under water stress. We present evidence that tomato ASR1, one of the proteins of the family, accumulates in seed during late stages of embryogenesis, a physiological process characterized by water loss. In vitro, electrophoretic assays show a homo-dimeric structure for ASR1 and highlight strong non-covalent interactions between monomers prone to self-assemble. Direct visualization of single molecules by atomic force microscopy (AFM) confirms that ASR1 forms homodimers and that uncovers both monomers and dimers bind double stranded DNA

  2. Biochemical characterization of the small hydrophobic protein of avian metapneumovirus.

    Science.gov (United States)

    Deng, Qiji; Song, Minxun; Demers, Andrew; Weng, Yuejin; Lu, Wuxun; Wang, Dan; Kaushik, Radhey S; Yu, Qingzhong; Li, Feng

    2012-08-01

    Avian metapneumovirus (AMPV) is a paramyxovirus that has three membrane proteins (G, F, and SH). Among them, the SH protein is a small type II integral membrane protein that is incorporated into virions and is only present in certain paramyxoviruses. In the present study, we show that the AMPV SH protein is modified by N-linked glycans and can be released into the extracellular environment. Furthermore, we demonstrate that glycosylated AMPV SH proteins form homodimers through cysteine-mediated disulfide bonds, which has not been reported previously for SH proteins of paramyxoviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Crystal structure of enolase from Drosophila melanogaster.

    Science.gov (United States)

    Sun, Congcong; Xu, Baokui; Liu, Xueyan; Zhang, Zhen; Su, Zhongliang

    2017-04-01

    Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase from Drosophila melanogaster (DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space group R32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

  4. Harmonic Maass forms and mock modular forms

    CERN Document Server

    Bringmann, Kathrin; Ono, Ken

    2017-01-01

    Modular forms and Jacobi forms play a central role in many areas of mathematics. Over the last 10-15 years, this theory has been extended to certain non-holomorphic functions, the so-called "harmonic Maass forms". The first glimpses of this theory appeared in Ramanujan's enigmatic last letter to G. H. Hardy written from his deathbed. Ramanujan discovered functions he called "mock theta functions" which over eighty years later were recognized as pieces of harmonic Maass forms. This book contains the essential features of the theory of harmonic Maass forms and mock modular forms, together with a wide variety of applications to algebraic number theory, combinatorics, elliptic curves, mathematical physics, quantum modular forms, and representation theory.

  5. Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering.

    Science.gov (United States)

    Der, Bryan S; Edwards, David R; Kuhlman, Brian

    2012-05-08

    Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient for formation of a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate with a rate acceleration of 10(5) and a k(cat)/K(M) of 630 M(-1) s(-1) and 4-nitrophenyl phosphate with a rate acceleration of 10(4) and a k(cat)/K(M) of 14 M(-1) s(-1). These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggest that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, three-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.

  6. Binding Affects the Tertiary and Quaternary Structures of the Shigella Translocator Protein IpaB and its Chaperone IpgC†

    Science.gov (United States)

    Adam, Philip R.; Patil, Mrinalini K.; Dickenson, Nicholas E.; Choudhari, Shyamal; Barta, Michael; Geisbrecht, Brian V.; Picking, Wendy L.; Picking, William D.

    2012-01-01

    Shigella flexneri uses its type III secretion system (T3SS) to promote invasion of human intestinal epithelial cells as the first step in causing shigellosis, a life threatening form of dysentery. The Shigella type III secretion apparatus (T3SA) consists of a basal body that spans the bacterial envelope and an exposed needle that injects effector proteins into target cells. The nascent Shigella T3SA needle is topped with a pentamer of the needle tip protein invasion plasmid antigen D (IpaD). Bile salts trigger recruitment of the first hydrophobic translocator protein, IpaB, to the tip complex where it senses contact with a host membrane. In the bacterial cytoplasm, IpaB exists in a complex with its chaperone IpgC. Several structures of IpgC have been solved and we recently reported the 2.1-Å crystal structure of the N-terminal domain (IpaB74.224) of IpaB. Like IpgC, the IpaB N-terminal domain exists as a homodimer in solution. We now report that when the two are mixed, these homodimers dissociate and form heterodimers having a nanomolar dissociation constant. This is consistent with the equivalent complexes co-purified after being co-expressed in E. coli. Fluorescence data presented here also indicate that the N-terminal domain of IpaB possesses two regions that appear to contribute additively to chaperone binding. It is also likely that the IpaB N terminus adopts an alternative conformation as a result of chaperone binding. The importance of these findings within the functional context of these proteins is discussed. PMID:22497344

  7. Crystal Structure and Functional Characterization of the Complement Regulator Mannose-binding Lectin (MBL)/Ficolin-associated Protein-1 (MAP-1)

    DEFF Research Database (Denmark)

    Skjoedt, M.-o.; Roversi, P.; Hummelshoj, T.

    2012-01-01

    .5 nM, respectively. We studied structural aspects of MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a calcium-dependent homo-dimer in solution. We were able to determine the crystal structure of MAP-1, which also contains a head-to-tail dimer approximately 146 Angstrom...... long. This structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety. Finally we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong dose dependent inhibitory effect on the lectin pathway activation, as measured by levels...

  8. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster.

    Science.gov (United States)

    Vognsen, Tina; Kristensen, Ole

    2012-03-30

    The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Improving the forming capability of laser dynamic forming by using rubber as a forming medium

    Science.gov (United States)

    Shen, Zongbao; Liu, Huixia; Wang, Xiao; Wang, Cuntang

    2016-04-01

    Laser dynamic forming (LDF) is a novel high velocity forming technique, which employs laser-generated shock wave to load the sample. The forming velocity induced by the high energy laser pulse may exceed the critical forming velocity, resulting in the occurrence of premature fracture. To avoid the above premature fracture, rubber is introduced in LDF as a forming medium to prolong the loading duration in this paper. Laser induced shock wave energy is transferred to the sample in different forming stages, so the forming velocity can be kept below the critical forming velocity when the initial laser energy is high for fracture. Bulge forming experiments with and without rubber were performed to study the effect of rubber on loading duration. The experimental results show that, the shock wave energy attenuates during the propagation through the rubber layer, the rubber can avoid the premature fracture. So the plastic deformation can continue, the forming capability of LDF is improved. Due to the severe plastic deformation under rubber compression, adiabatic shear bands (ASB) occur in LDF with rubber. The material softening in ASB leads to the irregular fracture, which is different from the premature fracture pattern (regular fracture) in LDF without rubber. To better understand this deformation behavior, Johnson-Cook model is used to simulate the dynamic response and the evolution of ASB of copper sample. The simulation results also indicate the rubber can prolong the loading duration.

  10. The guanylyl cyclase family at Y2K.

    Science.gov (United States)

    Wedel, B; Garbers, D

    2001-01-01

    During the 1980s the purification, cloning, and expression of various forms of guanylyl cyclase (GC) revealed that they served as receptors for extracellular signals. Seven membrane forms, which presumably exist as homodimers, and four subunits of apparent heterodimers (commonly referred to as the soluble forms) are known, but in animals such as nematodes, much larger numbers of GCs are expressed. The number of transmembrane segments (none, one, or multiple) divide the GC family into three groups. Those with no or one transmembrane segment bind nitric oxide/carbon monoxide (NO/CO) or peptides. There are no known ligands for the multiple transmembrane segment class of GCs. Mutational and structural analyses support a model where catalysis requires a shared substrate binding site between the subunits, whether homomeric or heteromeric in nature. Because some cyclases or cyclase ligand genes lack specific GC inhibitors, disruption of either has been used to define the functions of individual cyclases, as well as to define human genetic disease counterparts.

  11. Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

    Science.gov (United States)

    Guo, Peng-Chao; Bao, Zhang-Zhi; Ma, Xiao-Xiao; Xia, Qingyou; Li, Wei-Fang

    2014-09-01

    Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 75 FR 51093 - Agency Information Collection Activities: Form I-864, Form I-864A, Form I-864EZ, and Form I-864W...

    Science.gov (United States)

    2010-08-18

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services Agency Information... of Homeland Security, U.S. Citizenship and Immigration Services (USCIS) will be submitting the...: Form I-864, Form I-864A, Form I-864EZ, and Form I-864W; U.S. Citizenship and Immigration Services...

  13. Towards an exact theory of linear absorbance and circular dichroism of pigment-protein complexes: Importance of non-secular contributions

    International Nuclear Information System (INIS)

    Dinh, Thanh-Chung; Renger, Thomas

    2015-01-01

    A challenge for the theory of optical spectra of pigment-protein complexes is the equal strength of the pigment-pigment and the pigment-protein couplings. Treating both on an equal footing so far can only be managed by numerically costly approaches. Here, we exploit recent results on a normal mode analysis derived spectral density that revealed the dominance of the diagonal matrix elements of the exciton-vibrational coupling in the exciton state representation. We use a cumulant expansion technique that treats the diagonal parts exactly, includes an infinite summation of the off-diagonal parts in secular and Markov approximations, and provides a systematic perturbative way to include non-secular and non-Markov corrections. The theory is applied to a model dimer and to chlorophyll (Chl) a and Chl b homodimers of the reconstituted water-soluble chlorophyll-binding protein (WSCP) from cauliflower. The model calculations reveal that the non-secular/non-Markov effects redistribute oscillator strength from the strong to the weak exciton transition in absorbance and they diminish the rotational strength of the exciton transitions in circular dichroism. The magnitude of these corrections is in a few percent range of the overall signal, providing a quantitative explanation of the success of time-local convolution-less density matrix theory applied earlier. A close examination of the optical spectra of Chl a and Chl b homodimers in WSCP suggests that the opening angle between Q y transition dipole moments in Chl b homodimers is larger by about 9 ∘ than for Chl a homodimers for which a crystal structure of a related WSCP complex exists. It remains to be investigated whether this change is due to a different mutual geometry of the pigments or due to the different electronic structures of Chl a and Chl b

  14. Towards an exact theory of linear absorbance and circular dichroism of pigment-protein complexes: Importance of non-secular contributions

    Energy Technology Data Exchange (ETDEWEB)

    Dinh, Thanh-Chung; Renger, Thomas, E-mail: thomas.renger@jku.at [Institut für Theoretische Physik, Johannes Kepler University Linz, Altenberger Str. 69, 4040 Linz (Austria)

    2015-01-21

    A challenge for the theory of optical spectra of pigment-protein complexes is the equal strength of the pigment-pigment and the pigment-protein couplings. Treating both on an equal footing so far can only be managed by numerically costly approaches. Here, we exploit recent results on a normal mode analysis derived spectral density that revealed the dominance of the diagonal matrix elements of the exciton-vibrational coupling in the exciton state representation. We use a cumulant expansion technique that treats the diagonal parts exactly, includes an infinite summation of the off-diagonal parts in secular and Markov approximations, and provides a systematic perturbative way to include non-secular and non-Markov corrections. The theory is applied to a model dimer and to chlorophyll (Chl) a and Chl b homodimers of the reconstituted water-soluble chlorophyll-binding protein (WSCP) from cauliflower. The model calculations reveal that the non-secular/non-Markov effects redistribute oscillator strength from the strong to the weak exciton transition in absorbance and they diminish the rotational strength of the exciton transitions in circular dichroism. The magnitude of these corrections is in a few percent range of the overall signal, providing a quantitative explanation of the success of time-local convolution-less density matrix theory applied earlier. A close examination of the optical spectra of Chl a and Chl b homodimers in WSCP suggests that the opening angle between Q{sub y} transition dipole moments in Chl b homodimers is larger by about 9{sup ∘} than for Chl a homodimers for which a crystal structure of a related WSCP complex exists. It remains to be investigated whether this change is due to a different mutual geometry of the pigments or due to the different electronic structures of Chl a and Chl b.

  15. Advances in metal forming expert system for metal forming

    CERN Document Server

    Hingole, Rahulkumar Shivajirao

    2015-01-01

    This comprehensive book offers a clear account of the theory and applications of advanced metal forming. It provides a detailed discussion of specific forming processes, such as deep drawing, rolling, bending extrusion and stamping. The author highlights recent developments of metal forming technologies and explains sound, new and powerful expert system techniques for solving advanced engineering problems in metal forming. In addition, the basics of expert systems, their importance and applications to metal forming processes, computer-aided analysis of metalworking processes, formability analysis, mathematical modeling and case studies of individual processes are presented.

  16. The molecular mechanism underlying anthocyanin metabolism in apple using the MdMYB16 and MdbHLH33 genes.

    Science.gov (United States)

    Xu, Haifeng; Wang, Nan; Liu, Jingxuan; Qu, Changzhi; Wang, Yicheng; Jiang, Shenghui; Lu, Ninglin; Wang, Deyun; Zhang, Zongying; Chen, Xuesen

    2017-05-01

    MdMYB16 forms homodimers and directly inhibits anthocyanin synthesis via its C-terminal EAR repressor. It weakened the inhibitory effect of MdMYB16 on anthocyanin synthesis when overexpressing MdbHLH33 in callus overexpressing MdMYB16. MdMYB16 could interact with MdbHLH33. Anthocyanins are strong antioxidants that play a key role in the prevention of cardiovascular disease, cancer, and diabetes. The germplasm of Malus sieversii f. neidzwetzkyana is important for the study of anthocyanin metabolism. To date, only limited studies have examined the negative regulatory mechanisms underlying anthocyanin synthesis in apple. Here, we analyzed the relationship between anthocyanin levels and MdMYB16 expression in mature Red Crisp 1-5 apple (M. domestica) fruit, generated an evolutionary tree, and identified an EAR suppression sequence and a bHLH binding motif of the MdMYB16 protein using protein sequence analyses. Overexpression of MdMYB16 or MdMYB16 without bHLH binding sequence (LBSMdMYB16) in red-fleshed callus inhibited MdUFGT and MdANS expression and anthocyanin synthesis. However, overexpression of MdMYB16 without the EAR sequence (LESMdMYB16) in red-fleshed callus had no inhibitory effect on anthocyanin. The yeast one-hybrid assay showed that MdMYB16 and LESMdMYB16 interacted the promoters of MdANS and MdUFGT, respectively. Yeast two-hybrid, pull-down, and bimolecular fluorescence complementation assays showed that MdMYB16 formed homodimers and interacted with MdbHLH33, however, the LBSMdMYB16 could not interact with MdbHLH33. We overexpressed MdbHLH33 in callus overexpressing MdMYB16 and found that it weakened the inhibitory effect of MdMYB16 on anthocyanin synthesis. Together, these results suggested that MdMYB16 and MdbHLH33 may be important part of the regulatory network controlling the anthocyanin biosynthetic pathway.

  17. Influence of styryl dyes on blood erythrocytes

    Science.gov (United States)

    Nizomov, Negmat; Barakaeva, Mubaro; Kurtaliev, Eldar N.; Rahimov, Sherzod I.; Khakimova, Dilorom P.; Khodjayev, Gayrat; Yashchuk, Valeriy N.

    2008-08-01

    It was studied the influence of F, Sbt, Sil, Sbo monomer and homodimer Dst-5, Dst-10, Dbt-5, Dbt-10, Dil-10, Dbo-10 styryl dyes on blood erythrocytes of white rats. It was shown that the homodimer styryl dyes Dst-5, Dbt-5 and Dbo-10 decrease the erythrocytes quantity by 1.5-2 times more as compared with monomer dyes Sbt and Sbo. The main cause of dyes different action is the different oxidation degree of intracellular hemoglobin evoked by these dyes. It was established that the observed effects was connected with different penetration of these dyes through membrane of erythrocytes and with interaction of these dyes with albumin localized in membranes of cells.

  18. (EOI) Form

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

    Dorine Odongo

    COLLABORATING TECHNICAL AGENCIES: EXPRESSION OF INTEREST FORM. • Please read the information provided about the initiative and the eligibility requirements in the Prospectus before completing this application form. • Ensure all the sections of the form are accurately completed and saved in PDF format.

  19. Post-translational regulation of Oct4 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  20. Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2

    DEFF Research Database (Denmark)

    Henriksen, Ulla Birk; Fog, Jacob U; Litman, Thomas

    2005-01-01

    cysteines predicted to be on the extracellular face of ABCG2. Upon mutation of Cys-592 or Cys-608 to alanine (C592A and C608A), ABCG2 migrated as a dimer in SDS-PAGE under non-reducing conditions; however, mutation of Cys-603 to Ala (C603A) caused the transporter to migrate as a single monomeric band....... Despite this change, C603A displayed efficient membrane targeting and preserved transport function. Because the transporter migrated as a dimer in SDS-PAGE, when only Cys-603 was present (C592A-C608A), the data suggest that Cys-603 forms a symmetrical intermolecular disulfide bridge in the ABCG2 homodimer...

  1. Modular forms

    NARCIS (Netherlands)

    Edixhoven, B.; van der Geer, G.; Moonen, B.; Edixhoven, B.; van der Geer, G.; Moonen, B.

    2008-01-01

    Modular forms are functions with an enormous amount of symmetry that play a central role in number theory, connecting it with analysis and geometry. They have played a prominent role in mathematics since the 19th century and their study continues to flourish today. Modular forms formed the

  2. Functional NifD-K fusion protein in Azotobacter vinelandii is a homodimeric complex equivalent to the native heterotetrameric MoFe protein

    International Nuclear Information System (INIS)

    Lahiri, Surobhi; Pulakat, Lakshmi; Gavini, Nara

    2005-01-01

    The MoFe protein of the complex metalloenzyme nitrogenase folds as a heterotetramer containing two copies each of the homologous α and β subunits, encoded by the nifD and the nifK genes respectively. Recently, the functional expression of a fusion NifD-K protein of nitrogenase was demonstrated in Azotobacter vinelandii, strongly implying that the MoFe protein is flexible as it could accommodate major structural changes, yet remain functional [M.H. Suh, L. Pulakat, N. Gavini, J. Biol. Chem. 278 (2003) 5353-5360]. This finding led us to further explore the type of interaction between the fused MoFe protein units. We aimed to determine whether an interaction exists between the two fusion MoFe proteins to form a homodimer that is equivalent to native heterotetrameric MoFe protein. Using the Bacteriomatch Two-Hybrid System, translationally fused constructs of NifD-K (fusion) with the full-length λCI of the pBT bait vector and also NifD-K (fusion) with the N-terminal α-RNAP of the pTRG target vector were made. To compare the extent of interaction between the fused NifD-K proteins to that of the β-β interactions in the native MoFe protein, we proceeded to generate translationally fused constructs of NifK with the α-RNAP of the pTRG vector and λCI protein of the pBT vector. The strength of the interaction between the proteins in study was determined by measuring the β-galactosidase activity and extent of ampicillin resistance of the colonies expressing these proteins. This analysis demonstrated that direct protein-protein interaction exists between NifD-K fusion proteins, suggesting that they exist as homodimers. As the interaction takes place at the β-interfaces of the NifD-K fusion proteins, we propose that these homodimers of NifD-K fusion protein may function in a similar manner as that of the heterotetrameric native MoFe protein. The observation that the extent of protein-protein interaction between the β-subunits of the native MoFe protein in Bacterio

  3. Novel structural features in two ZHX homeodomains derived from a systematic study of single and multiple domains

    Directory of Open Access Journals (Sweden)

    Owens Raymond J

    2010-05-01

    Full Text Available Abstract Background Zhx1 to 3 (zinc-fingers and homeoboxes form a set of paralogous genes encoding multi-domain proteins. ZHX proteins consist of two zinc fingers followed by five homeodomains. ZHXs have biological roles in cell cycle control by acting as co-repressors of the transcriptional regulator Nuclear Factor Y. As part of a structural genomics project we have expressed single and multi-domain fragments of the different human ZHX genes for use in structure determination. Results A total of 30 single and multiple domain ZHX1-3 constructs selected from bioinformatics protocols were screened for soluble expression in E. coli using high throughput methodologies. Two homeodomains were crystallized leading to structures for ZHX1 HD4 and ZHX2 HD2. ZHX1 HD4, although closest matched to homeodomains from 'homez' and 'engrailed', showed structural differences, notably an additional C-terminal helix (helix V which wrapped over helix I thereby making extensive contacts. Although ZHX2 HD2-3 was successfully expressed and purified, proteolysis occurred during crystallization yielding crystals of just HD2. The structure of ZHX2 HD2 showed an unusual open conformation with helix I undergoing 'domain-swapping' to form a homodimer. Conclusions Although multiple-domain constructs of ZHX1 selected by bioinformatics studies could be expressed solubly, only single homeodomains yielded crystals. The crystal structure of ZHX1 HD4 showed additional hydrophobic interactions relative to many known homeodomains via extensive contacts formed by the novel C-terminal helix V with, in particular, helix I. Additionally, the replacement of some charged covariant residues (which are commonly observed to form salt bridges in non-homeotherms such as the Drosophila 'engrailed' homeodomain, by apolar residues further increases hydrophobic contacts within ZHX1 HD4, and potentially stability, relative to engrailed homeodomain. ZHX1 HD4 helix V points away from the normally

  4. Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

    DEFF Research Database (Denmark)

    Danielsen, E M

    1990-01-01

    of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic......The pig intestinal brush border enzymes aminopeptidase N (EC 3.4.11.2) and lactase-phlorizin hydrolase (EC 3.2.1.23-62) are present in the microvillar membrane as homodimers. Dimethyl adipimidate was used to cross-link the two [35S]methionine-labeled brush border enzymes from cultured mucosal...... explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation...

  5. Against Logical Form

    Directory of Open Access Journals (Sweden)

    P N Johnson-Laird

    2010-10-01

    Full Text Available An old view in logic going back to Aristotle is that an inference is valid in virtue of its logical form. Many psychologists have adopted the same point of view about human reasoning: the first step is to recover the logical form of an inference, and the second step is to apply rules of inference that match these forms in order to prove that the conclusion follows from the premises. The present paper argues against this idea. The logical form of an inference transcends the grammatical forms of the sentences used to express it, because logical form also depends on context. Context is not readily expressed in additional premises. And the recovery of logical form leads ineluctably to the need for infinitely many axioms to capture the logical properties of relations. An alternative theory is that reasoning depends on mental models, and this theory obviates the need to recover logical form.

  6. Forming processes and mechanics of sheet metal forming

    NARCIS (Netherlands)

    Burchitz, I.A.

    2004-01-01

    The report is dealing with the numerical analysis of forming processes. Forming processes is the large group of manufacturing processes used to obtain various product shapes by means of plastic deformations. The report is organized as follows. An overview of the deformation processes and the

  7. Pre-form ceramic matrix composite cavity and method of forming and method of forming a ceramic matrix composite component

    Science.gov (United States)

    Monaghan, Philip Harold; Delvaux, John McConnell; Taxacher, Glenn Curtis

    2015-06-09

    A pre-form CMC cavity and method of forming pre-form CMC cavity for a ceramic matrix component includes providing a mandrel, applying a base ply to the mandrel, laying-up at least one CMC ply on the base ply, removing the mandrel, and densifying the base ply and the at least one CMC ply. The remaining densified base ply and at least one CMC ply form a ceramic matrix component having a desired geometry and a cavity formed therein. Also provided is a method of forming a CMC component.

  8. On good ETOL forms

    DEFF Research Database (Denmark)

    Skyum, Sven

    1978-01-01

    This paper continues the study of ETOL forms and good EOL forms done by Maurer, Salomaa and Wood. It is proven that binary very complete ETOL forms exist, good synchronized ETOL forms exist and that no propagating or synchronized ETOL form can be very complete.......This paper continues the study of ETOL forms and good EOL forms done by Maurer, Salomaa and Wood. It is proven that binary very complete ETOL forms exist, good synchronized ETOL forms exist and that no propagating or synchronized ETOL form can be very complete....

  9. Designing usable web forms- Empirical evaluation of web form improvement guidelines

    DEFF Research Database (Denmark)

    Seckler, Mirjam; Heinz, Silvia; Bargas-Avila, Javier A.

    2014-01-01

    This study reports a controlled eye tracking experiment (N = 65) that shows the combined effectiveness of 20 guidelines to improve interactive online forms when applied to forms found on real company websites. Results indicate that improved web forms lead to faster completion times, fewer form...... submission trials, and fewer eye movements. Data from subjective questionnaires and interviews further show increased user satisfaction. Overall, our findings highlight the importance for web designers to improve their web forms using UX guidelines....

  10. Methods of forming semiconductor devices and devices formed using such methods

    Science.gov (United States)

    Fox, Robert V; Rodriguez, Rene G; Pak, Joshua

    2013-05-21

    Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

  11. Electroweak form factors

    International Nuclear Information System (INIS)

    Singh, S.K.

    2002-01-01

    The present status of electroweak nucleon form factors and the N - Δ transition form factors is reviewed. Particularly the determination of dipole mass M A in the axial vector form factor is discussed

  12. Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, A.; Wong, S; Yuan, Y

    2009-01-01

    Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.

  13. PowerForms

    DEFF Research Database (Denmark)

    Brabrand, Claus; Møller, Anders; Ricky, Mikkel

    2000-01-01

    All uses of HTML forms may benefit from validation of the specified input field values. Simple validation matches individual values against specified formats, while more advanced validation may involve interdependencies of form fields. There is currently no standard for specifying or implementing...

  14. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Philip D Townsend

    Full Text Available The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  15. Characterization and Functional Analysis of Five MADS-Box B Class Genes Related to Floral Organ Identification in Tagetes erecta.

    Directory of Open Access Journals (Sweden)

    Ye Ai

    Full Text Available According to the floral organ development ABC model, B class genes specify petal and stamen identification. In order to study the function of B class genes in flower development of Tagetes erecta, five MADS-box B class genes were identified and their expression and putative functions were studied. Sequence comparisons and phylogenetic analyses indicated that there were one PI-like gene-TePI, two euAP3-like genes-TeAP3-1 and TeAP3-2, and two TM6-like genes-TeTM6-1 and TeTM6-2 in T. erecta. Strong expression levels of these genes were detected in stamens of the disk florets, but little or no expression was detected in bracts, receptacles or vegetative organs. Yeast hybrid experiments of the B class proteins showed that TePI protein could form a homodimer and heterodimers with all the other four B class proteins TeAP3-1, TeAP3-2, TeTM6-1 and TeTM6-2. No homodimer or interaction was observed between the euAP3 and TM6 clade members. Over-expression of five B class genes of T. erecta in Nicotiana rotundifolia showed that only the transgenic plants of 35S::TePI showed altered floral morphology compared with the non-transgenic line. This study could contribute to the understanding of the function of B class genes in flower development of T. erecta, and provide a theoretical basis for further research to change floral organ structures and create new materials for plant breeding.

  16. Activities and specificities of homodimeric TALENs in Saccharomyces cerevisiae

    KAUST Repository

    Aouida, Mustapha; Piatek, Marek J.; Bangarusamy, Dhinoth Kumar; Mahfouz, Magdy M.

    2013-01-01

    The development of highly efficient genome engineering reagents is of paramount importance to launch the next wave of biotechnology. TAL effectors have been developed as an adaptable DNA binding scaffold that can be engineered to bind to any user-defined sequence. Thus, TAL-based DNA binding modules have been used to generate chimeric proteins for a variety of targeted genome modifications across eukaryotic species. For example, TAL effectors fused to the catalytic domain of FokI endonuclease (TALENs) were used to generate site-specific double strand breaks (DSBs), the repair of which can be harnessed to dictate user-desired, genome-editing outcomes. To cleave DNA, FokI endonuclease must dimerize which can be achieved using a pair of TALENs that bind to the DNA targeted in a tail-to-tail orientation with proper spacing allowing the dimer formation. Because TALENs binding to DNA are dependent on their repeat sequences and nucleotides binding specificities, homodimers and heterodimers binding can be formed. In the present study, we used several TALEN monomers with increased repeats binding degeneracy to allow homodimer formation at increased number of genomic loci. We assessed their binding specificities and genome modification activities. Our results indicate that homodimeric TALENs could be used to modify the yeast genome in a site-specific manner and their binding to the promoter regions might modulate the expression of target genes. Taken together, our data indicate that homodimeric TALENs could be used to achieve different engineering possibilities of biotechnological applications and that their transcriptional modulations need to be considered when analyzing their phenotypic effects. © 2013 Springer-Verlag.

  17. Activities and specificities of homodimeric TALENs in Saccharomyces cerevisiae

    KAUST Repository

    Aouida, Mustapha

    2013-10-01

    The development of highly efficient genome engineering reagents is of paramount importance to launch the next wave of biotechnology. TAL effectors have been developed as an adaptable DNA binding scaffold that can be engineered to bind to any user-defined sequence. Thus, TAL-based DNA binding modules have been used to generate chimeric proteins for a variety of targeted genome modifications across eukaryotic species. For example, TAL effectors fused to the catalytic domain of FokI endonuclease (TALENs) were used to generate site-specific double strand breaks (DSBs), the repair of which can be harnessed to dictate user-desired, genome-editing outcomes. To cleave DNA, FokI endonuclease must dimerize which can be achieved using a pair of TALENs that bind to the DNA targeted in a tail-to-tail orientation with proper spacing allowing the dimer formation. Because TALENs binding to DNA are dependent on their repeat sequences and nucleotides binding specificities, homodimers and heterodimers binding can be formed. In the present study, we used several TALEN monomers with increased repeats binding degeneracy to allow homodimer formation at increased number of genomic loci. We assessed their binding specificities and genome modification activities. Our results indicate that homodimeric TALENs could be used to modify the yeast genome in a site-specific manner and their binding to the promoter regions might modulate the expression of target genes. Taken together, our data indicate that homodimeric TALENs could be used to achieve different engineering possibilities of biotechnological applications and that their transcriptional modulations need to be considered when analyzing their phenotypic effects. © 2013 Springer-Verlag.

  18. Basic Concepts in G-Protein-Coupled Receptor Homo- and Heterodimerization

    Directory of Open Access Journals (Sweden)

    Rafael Franco

    2007-01-01

    Full Text Available Until recently, heptahelical G-protein-coupled receptors (GPCRs were considered to be expressed as monomers on the cell surface of neuronal and non-neuronal cells. It is now becoming evident that this view must be overtly changed since these receptors can form homodimers, heterodimers, and higher-order oligomers on the plasma membrane. Here we discuss some of the basics and some new concepts of receptor homo- and heteromerization. Dimers-oligomers modify pharmacology, trafficking, and signaling of receptors. First of all, GPCR dimers must be considered as the main molecules that are targeted by neurotransmitters or by drugs. Thus, binding data must be fitted to dimer-based models. In these models, it is considered that the conformational changes transmitted within the dimer molecule lead to cooperativity. Cooperativity must be taken into account in the binding of agonists-antagonists-drugs and also in the binding of the so-called allosteric modulators. Cooperativity results from the intramolecular cross-talk in the homodimer. As an intramolecular cross-talk in the heterodimer, the binding of one neurotransmitter to one receptor often affects the binding of the second neurotransmitter to the partner receptor. Coactivation of the two receptors in a heterodimer can change completely the signaling pathway triggered by the neurotransmitter as well as the trafficking of the receptors. Heterodimer-specific drugs or dual drugs able to activate the two receptors in the heterodimer simultaneously emerge as novel and promising drugs for a variety of central nervous system (CNS therapeutic applications.

  19. Voice as Form of Life and Life Form

    Directory of Open Access Journals (Sweden)

    Sandra Laugier

    2015-10-01

    Full Text Available This paper studies the concept of form of life as central to ordinary language philosophy (as understood in Wittgenstein’s, Austin’s and Stanley Cavell’s work: philosophy of our language as spoken; pronounced by a human voice within a form of life. Such an approach to Wittgenstein’s later philosophy shifts the question of the common use of language – central to Wittgenstein’s Investigations – to the definition of the subject as voice, and to the reinvention of subjectivity in language. The voice is both a subjective and common expression: it is what makes it possible for my individual voice, or claim, to become shared and for our forms of life to be intertwined with a lifeform.

  20. 76 FR 21946 - Proposed Collection; Comment Request for Form 990-BL; Schedule A (Form 990-BL), Form 6069

    Science.gov (United States)

    2011-04-19

    ... Initial Excise Tax Return for Black Lung Benefit Trusts and Certain Related Persons, and Form 6069, Return of Excise Tax on Excess Contributions to Black Lung Benefit Trust Under Section 4953 and Computation...: Form 990-BL, Schedule A (Form 990-BL), Information and Initial Excise Tax Return for Black Lung Benefit...

  1. Dominant negative umuD mutations decreasing RecA-mediated cleavage suggest roles for intact UmuD in modulation of SOS mutagenesis

    International Nuclear Information System (INIS)

    Battista, J.R.; Ohta, Toshihiro; Nohmi, Takehiko; Sun, W.; Walker, G.C.

    1990-01-01

    The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli. The UmuD protein shares homology with a family of proteins that includes LexA and several bacteriophage repressors. UmuD is posttranslationally activated for its role n mutagenesis by a RecA-mediated proteolytic cleavage that yields UmuD'. A set of missense mutants of umuD was isolated and shown to encode mutant UmuD proteins that are deficient in RecA-mediated cleavage in vivo. Most of these mutations are dominant to umuD + with respect to UV mutagenesis yet do not interfere with SOS induction. Although both UmuD and UmuD' form homodimers, the authors provide evidence that they preferentially form heterodimers. The relationship of UmuD to LexA, λ repressor, and other members of the family of proteins is discussed and possible roles intact UmuD in modulating SOS mutagenesis are discussed

  2. (β-dicarbonyl) arylmethanes and dihydropyridine from dimedone in

    African Journals Online (AJOL)

    N. Bayou-Khier, M. Amari, M. Fodili, S.G.Grau, P. Hoffmann

    2016-09-01

    Sep 1, 2016 ... http://www.jfas.info ... arylmethane derivatives have attracted considerable attention ... In this work, we have obtained selectively, the homodimer 3 of dimedone .... impact ionization mass spectra were recorded on a Nermag ...

  3. Micro metal forming

    CERN Document Server

    2013-01-01

    Micro Metal Forming, i. e. forming of parts and features with dimensions below 1 mm, is a young area of research in the wide field of metal forming technologies, expanding the limits for applying metal forming towards micro technology. The essential challenges arise from the reduced geometrical size and the increased lot size. In order to enable potential users to apply micro metal forming in production, information about the following topics are given: tribological behavior: friction between tool and work piece as well as tool wear mechanical behavior: strength and formability of the work piece material, durability of the work pieces size effects: basic description of effects occurring due to the fact, that the quantitative relation between different features changes with decreasing size process windows and limits for forming processes tool making methods numerical modeling of processes and process chains quality assurance and metrology All topics are discussed with respect to the questions relevant to micro...

  4. Phase transitions of antibiotic clarithromycin forms I, IV and new form VII crystals.

    Science.gov (United States)

    Ito, Masataka; Shiba, Rika; Watanabe, Miteki; Iwao, Yasunori; Itai, Shigeru; Noguchi, Shuji

    2018-06-01

    Metastable crystal form I of the antibiotic clarithromycin has a pharmaceutically valuable characteristic that its crystalline phase transition can be applied for its sustained release from tablets. The phase transition of form I was investigated in detail by single crystal and powder X-ray analyses, dynamic vapor sorption analysis and thermal analysis. The single crystal structure of form I revealed that form I was not an anhydrate crystal but contained a partially occupied water molecule in the channel-like void space. Dynamic vapor sorption (DVS) analysis demonstrated that form I crystals reversibly sorbed water molecules in two steps when the relative humidity (RH) increased and finally transited to hydrate form IV at 95% RH. DVS analysis also showed that when the RH decreased form IV crystals lost water molecules at 40% RH and transited to the newly identified anhydrate crystal form VII. Form VII reversibly transited to form IV at lower RH than form I, suggesting that form I is more suitable for manufacturing a sustained-release tablet of CAM utilizing the crystalline phase transition. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Conjoint Forming - Technologies for Simultaneous Forming and Joining

    International Nuclear Information System (INIS)

    Groche, P; Wohletz, S; Mann, A; Krech, M; Monnerjahn, V

    2016-01-01

    The market demand for new products optimized for e. g. lightweight applications or smart components leads to new challenges in production engineering. Hybrid structures represent one promising approach. They aim at higher product performance by using a suitable combination of different materials. The developments of hybrid structures stimulate the research on joining of dissimilar materials. Since they allow for joining dissimilar materials without external heating technologies based on joining by plastic deformation seem to be of special attractiveness. The paper at hand discusses the conjoint forming approach. This approach combines forming and joining in one process. Two or more workpieces are joined while at least one workpiece is plastically deformed. After presenting the fundamental joining mechanisms, the conjoint forming approach is discussed comprehensively. Examples of conjoint processes demonstrate the effectiveness and reveal the underlying phenomena. (paper)

  6. Differential forms orthogonal to holomorphic functions or forms, and their properties

    CERN Document Server

    Aizenberg, L A

    1983-01-01

    The authors consider the problem of characterizing the exterior differential forms which are orthogonal to holomorphic functions (or forms) in a domain D\\subset {\\mathbf C}^n with respect to integration over the boundary, and some related questions. They give a detailed account of the derivation of the Bochner-Martinelli-Koppelman integral representation of exterior differential forms, which was obtained in 1967 and has already found many important applications. They study the properties of \\overline \\partial-closed forms of type (p, n - 1), 0\\leq p\\leq n - 1, which turn out to be the duals (with respect to the orthogonality mentioned above) to holomorphic functions (or forms) in several complex variables, and resemble holomorphic functions of one complex variable in their properties.

  7. Unified form language

    DEFF Research Database (Denmark)

    Alnæs, Martin S.; Logg, Anders; Ølgaard, Kristian Breum

    2014-01-01

    We present the Unied Form Language (UFL), which is a domain-specic language for representing weak formulations of partial dierential equations with a view to numerical approximation. Features of UFL include support for variational forms and functionals, automatic dierentiation of forms and expres...... libraries to generate concrete low-level implementations. Some application examples are presented and libraries that support UFL are highlighted....

  8. Mesonic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  9. Biomimicry of Palm Tree Leaves Form and Pattern on Building Form

    Directory of Open Access Journals (Sweden)

    Agus Salim N.A.

    2014-01-01

    Full Text Available This article is a study on biomimicry of palm tree towards a building form. It is to find a suitable form and pattern that can be applied to building shell to ease building maintenance operation beside to enhance the aesthetic value of a building architecture. The research has been carried out by observation and modeling on some various species of palm tree’s patterns and forms. The result expectation can be found at the end of this research by producing the best pattern of palm tree that can be adapted to building envelop as the whole form of a building.

  10. Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains.

    Science.gov (United States)

    Zhao, Huaying; Lomash, Suvendu; Chittori, Sagar; Glasser, Carla; Mayer, Mark L; Schuck, Peter

    2017-10-23

    Ion conductivity and the gating characteristics of tetrameric glutamate receptor ion channels are determined by their subunit composition. Competitive homo- and hetero-dimerization of their amino-terminal domains (ATDs) is a key step controlling assembly. Here we measured systematically the thermodynamic stabilities of homodimers and heterodimers of kainate and AMPA receptors using fluorescence-detected sedimentation velocity analytical ultracentrifugation. Measured affinities span many orders of magnitude, and complexes show large differences in kinetic stabilities. The association of kainate receptor ATD dimers is generally weaker than the association of AMPA receptor ATD dimers, but both show a general pattern of increased heterodimer stability as compared to the homodimers of their constituents, matching well physiologically observed receptor combinations. The free energy maps of AMPA and kainate receptor ATD dimers provide a framework for the interpretation of observed receptor subtype combinations and possible assembly pathways.

  11. In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

    Directory of Open Access Journals (Sweden)

    Incilay Sinici

    Full Text Available The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively, and the GM2-activator protein (GM2AP, encoded by the GM2A gene. Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750. Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1 and a new more extensive hybrid (H2, with our documented in cellulo (live cell- based assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

  12. Method of forming aluminum oxynitride material and bodies formed by such methods

    Science.gov (United States)

    Bakas, Michael P [Ammon, ID; Lillo, Thomas M [Idaho Falls, ID; Chu, Henry S [Idaho Falls, ID

    2010-11-16

    Methods of forming aluminum oxynitride (AlON) materials include sintering green bodies comprising aluminum orthophosphate or another sacrificial material therein. Such green bodies may comprise aluminum, oxygen, and nitrogen in addition to the aluminum orthophosphate. For example, the green bodies may include a mixture of aluminum oxide, aluminum nitride, and aluminum orthophosphate or another sacrificial material. Additional methods of forming aluminum oxynitride (AlON) materials include sintering a green body including a sacrificial material therein, using the sacrificial material to form pores in the green body during sintering, and infiltrating the pores formed in the green body with a liquid infiltrant during sintering. Bodies are formed using such methods.

  13. Adaptive municipal electronic forms

    NARCIS (Netherlands)

    Kuiper, Pieternel; van Dijk, Elisabeth M.A.G.; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

    Adaptation of electronic forms (e-forms) seems to be a step forward to reduce the burden for people who fill in forms. Municipalities more and more offer e-forms online that can be used by citizens to request a municipal product or service or by municipal employees to place a request on behalf of a

  14. Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition.

    Science.gov (United States)

    Hu, Xiao-Qian; Guo, Peng-Chao; Ma, Jin-Di; Li, Wei-Fang

    2013-11-01

    The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopts an (α/β)8-barrel structure and has a highly conserved cofactor-binding pocket. Structural comparison revealed that induced fit upon NADPH binding yielded an intact active-site pocket that recognizes the substrate. Moreover, the crystal structures combined with computational simulation defined an open substrate-binding site to accommodate various substrates that possess a dicarbonyl group.

  15. GPCR Interaction: 82 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available agonists increase BRET values for MT1BR but not for MT1AR homodimers in living cells and isolated plasma membranes. 11940583 Immunoprecipitation, BRET ... NP_005949.1 ... ... upon agonist and antagonist binding. Agonists, neutral antagonists, and inverse

  16. GPCR Interaction: 83 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available agonists increase BRET values for MT1BR but not for MT1AR homodimers in living cells and isolated plasma membranes. 11940583 Immunoprecipitation, BRET ... NP_005950.1 ... ... upon agonist and antagonist binding. Agonists, neutral antagonists, and inverse

  17. Protonated form: the potent form of potassium-competitive acid blockers.

    Directory of Open Access Journals (Sweden)

    Hua-Jun Luo

    Full Text Available Potassium-competitive acid blockers (P-CABs are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

  18. Protonated form: the potent form of potassium-competitive acid blockers.

    Science.gov (United States)

    Luo, Hua-Jun; Deng, Wei-Qiao; Zou, Kun

    2014-01-01

    Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

  19. Forms Management Policy

    Science.gov (United States)

    To establish EPA’s Forms Management Program; to describe the requisite roles, responsibilities, and procedures necessary for the successful management of EPA forms; and to more clearly fulfill EPA’s obligations in this regard.

  20. Science on form

    International Nuclear Information System (INIS)

    Ishizaka, Shozo; Kato, Yoshihiro; Takaki, Ryuji; Toriwaki, Jun-ichiro

    1987-01-01

    The purpose of the Symposium was to discuss interdisciplinal science aspects of form. 'Form' depends on the material and the changes. But, it is the form that appears evident at once and endures. Form is absorbed from every field as media of information. One part of the work covers the description of non-periodic phenomena, morphogenesis or evolution. Irreducible stubborn facts as diseases or social problems, or whatever else that could not be analyzed are integrally challenged to be systematized by computer simulation. The other part covers the finding of laws for determining how systems behave. Attention should be paid to pattern recognition, image processing and pattern formation. The Symposium proceeded with no parallel sessions, and participants from various fields made exciting discussions in an interdisciplinal atmosphere. (Auth.)

  1. Automorphic Forms and Mock Modular Forms in String Theory

    Science.gov (United States)

    Nazaroglu, Caner

    We study a variety of modular invariant objects in relation to string theory. First, we focus on Jacobi forms over generic rank lattices and Siegel forms that appear in N = 2, D = 4 compactifications of heterotic string with Wilson lines. Constraints from low energy spectrum and modularity are employed to deduce the relevant supersymmetric partition functions entirely. This procedure is applied on models that lead to Jacobi forms of index 3, 4, 5 as well as Jacobi forms over root lattices A2 and A3. These computations are then checked against an explicit orbifold model which can be Higgsed to the models under question. Models with a single Wilson line are then studied in detail with their relation to paramodular group Gammam as T-duality group made explicit. These results on the heterotic string side are then turned into predictions for geometric invariants using TypeII - Heterotic duality. Secondly, we study theta functions for indenite signature lattices of generic signature. Building on results in literature for signature (n-1,1) and (n-2,2) lattices, we work out the properties of generalized error functions which we call r-tuple error functions. We then use these functions to build such indenite theta functions and describe their modular completions.

  2. Forms of Arthritis

    Science.gov (United States)

    ... this page please turn Javascript on. Forms of Arthritis Past Issues / Fall 2006 Table of Contents Today, ... of Linda Saisselin Osteoarthritis (OA) — the form of arthritis typically occurring during middle or old age, this ...

  3. Directory of energy data collection forms. Forms in use as of October 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-01

    This is an authoritative listing of selected public use forms currently used as basic energy information gathering tools by the Department of Energy (DOE). This directory provides an overview of DOE`s energy information collection programs for decisionmakers in Government and industry. Forms designed to collect energy information and used by the Energy Information Administration (EIA) as of October 1995 are included in this directory. For each form listed in this directory, an abstract is included that describes the form`s uses, its respondents, and the data collected. For the reader`s convenience in finding specific types of collections, several indices have been provided in this directory. A listing of the forms grouped by energy source and function begins on page 26. Beginning on page 38 are the publications derived from the collections, and on page 50, are the forms linked to general respondent categories.

  4. Radial-rotation profile forming: A new processing technology of incremental sheet metal forming

    Science.gov (United States)

    Laue, Robert; Härtel, Sebastian; Awiszus, Birgit

    2018-05-01

    Incremental forming processes (i.e., spinning) of sheet metal blanks into cylindrical cups are suitable for lower lot sizes. The produced cups were frequently used as preforms to produce workpieces in further forming steps with additional functions like profiled hollow parts [1]. The incremental forming process radial-rotation profile forming has been developed to enable the production of profiled hollow parts with low sheet thinning and good geometrical accuracy. The two principal forming steps are the production of the preform by rotational swing-folding [2] and the subsequent radial profiling of the hollow part in one clamping position. The rotational swing-folding process is based on a combination of conventional spinning and swing-folding. Therefore, a round blank rotates on a profiled mandrel and due to the swinging of a cylindrical forming tool, the blank is formed to a cup with low sheet thinning. In addition, thickening results at the edge of the blank and wrinkling occurs. However, the wrinkles are formed into the indentation of the profiled mandrel and can be reshaped as an advantage in the second process step, the radial profiling. Due to the rotation and continuous radial feed of a profiled forming tool to the profiled mandrel, the axial profile is formed in the second process step. Because of the minor relative movement in axial direction between tool and blank, low sheet thinning occurs. This is an advantage of the principle of the process.

  5. In silico insights into protein-protein interactions and folding dynamics of the saposin-like domain of Solanum tuberosum aspartic protease.

    Directory of Open Access Journals (Sweden)

    Dref C De Moura

    Full Text Available The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L. plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family.

  6. A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins.

    Directory of Open Access Journals (Sweden)

    Ricardo Núñez Miguel

    2007-08-01

    Full Text Available The Toll-like receptor 4 (TLR4 is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3 and nuclear factor kappaB (NFkappaB respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu.

  7. Getting in-formed

    DEFF Research Database (Denmark)

    Hansbøl, Mikala

    det vi undersøger på form gennem vores beskrivelser. Paperet tager afsæt i empiriske eksempler fra et postdoc projekt om et såkaldt 'serious game' - Mingoville. Projektet følger circuleringer og etableringer af Mingoville 'på en global markedsplads'. I paperet diskuteres hvordan vi som forskere samler....../performer de fænomener vi forsker i. Aktør-Netværks-Teoretiker Bruno Latour (2005) pointerer at enhver beskrivelse også er en form for forklaring. En form for forklaring, der putter ting ind i et skript og dermed også putter ting på form. Paperet diskuterer to tilgange til at gøre serious games og derved skabe viden om...... engagementer med disse fænomener i serious games forskning: experimentel og etnografisk....

  8. Pre-exposure to moving form enhances static form sensitivity.

    Directory of Open Access Journals (Sweden)

    Thomas S A Wallis

    Full Text Available BACKGROUND: Motion-defined form can seem to persist briefly after motion ceases, before seeming to gradually disappear into the background. Here we investigate if this subjective persistence reflects a signal capable of improving objective measures of sensitivity to static form. METHODOLOGY/PRINCIPAL FINDINGS: We presented a sinusoidal modulation of luminance, masked by a background noise pattern. The sinusoidal luminance modulation was usually subjectively invisible when static, but visible when moving. We found that drifting then stopping the waveform resulted in a transient subjective persistence of the waveform in the static display. Observers' objective sensitivity to the position of the static waveform was also improved after viewing moving waveforms, compared to viewing static waveforms for a matched duration. This facilitation did not occur simply because movement provided more perspectives of the waveform, since performance following pre-exposure to scrambled animations did not match that following pre-exposure to smooth motion. Observers did not simply remember waveform positions at motion offset, since removing the waveform before testing reduced performance. CONCLUSIONS/SIGNIFICANCE: Motion processing therefore interacts with subsequent static visual inputs in a way that can improve performance in objective sensitivity measures. We suggest that the brief subjective persistence of motion-defined forms that can occur after motion offsets is a consequence of the decay of a static form signal that has been transiently enhanced by motion processing.

  9. FORMS OF YOUTH TRAVEL

    OpenAIRE

    Moisã Claudia Olimpia; Moisã Claudia Olimpia

    2011-01-01

    Taking into account the suite of motivation that youth has when practicing tourism, it can be said that the youth travel takes highly diverse forms. These forms are educational tourism, volunteer programs and “work and travel”, cultural exchanges or sports tourism and adventure travel. In this article, we identified and analyzed in detail the main forms of youth travel both internationally and in Romania. We also illustrated for each form of tourism the specific tourism products targeting you...

  10. Giro form reading machine

    Science.gov (United States)

    Minh Ha, Thien; Niggeler, Dieter; Bunke, Horst; Clarinval, Jose

    1995-08-01

    Although giro forms are used by many people in daily life for money remittance in Switzerland, the processing of these forms at banks and post offices is only partly automated. We describe an ongoing project for building an automatic system that is able to recognize various items printed or written on a giro form. The system comprises three main components, namely, an automatic form feeder, a camera system, and a computer. These components are connected in such a way that the system is able to process a bunch of forms without any human interactions. We present two real applications of our system in the field of payment services, which require the reading of both machine printed and handwritten information that may appear on a giro form. One particular feature of giro forms is their flexible layout, i.e., information items are located differently from one form to another, thus requiring an additional analysis step to localize them before recognition. A commercial optical character recognition software package is used for recognition of machine-printed information, whereas handwritten information is read by our own algorithms, the details of which are presented. The system is implemented by using a client/server architecture providing a high degree of flexibility to change. Preliminary results are reported supporting our claim that the system is usable in practice.

  11. Structures of a putative ζ-class glutathione S-transferase from the pathogenic fungus Coccidioides immitis

    International Nuclear Information System (INIS)

    Edwards, Thomas E.; Bryan, Cassie M.; Leibly, David J.; Dieterich, Shellie H.; Abendroth, Jan; Sankaran, Banumathi; Sivam, Dhileep; Staker, Bart L.; Van Voorhis, Wesley C.; Myler, Peter J.; Stewart, Lance J.

    2011-01-01

    The pathogenic fungus C. immitis causes coccidioidomycosis, a potentially fatal disease. Here, apo and glutathione-bound crystal structures of a previously uncharacterized protein from C. immitis that appears to be a ζ-class glutathione S-transferase are presented. Coccidioides immitis is a pathogenic fungus populating the southwestern United States and is a causative agent of coccidioidomycosis, sometimes referred to as Valley Fever. Although the genome of this fungus has been sequenced, many operons are not properly annotated. Crystal structures are presented for a putative uncharacterized protein that shares sequence similarity with ζ-class glutathione S-transferases (GSTs) in both apo and glutathione-bound forms. The apo structure reveals a nonsymmetric homodimer with each protomer comprising two subdomains: a C-terminal helical domain and an N-terminal thioredoxin-like domain that is common to all GSTs. Half-site binding is observed in the glutathione-bound form. Considerable movement of some components of the active site relative to the glutathione-free form was observed, indicating an induced-fit mechanism for cofactor binding. The sequence homology, structure and half-site occupancy imply that the protein is a ζ-class glutathione S-transferase, a maleylacetoacetate isomerase (MAAI)

  12. Quantifying the topography of the intrinsic energy landscape of flexible biomolecular recognition

    Science.gov (United States)

    Chu, Xiakun; Gan, Linfeng; Wang, Erkang; Wang, Jin

    2013-01-01

    Biomolecular functions are determined by their interactions with other molecules. Biomolecular recognition is often flexible and associated with large conformational changes involving both binding and folding. However, the global and physical understanding for the process is still challenging. Here, we quantified the intrinsic energy landscapes of flexible biomolecular recognition in terms of binding–folding dynamics for 15 homodimers by exploring the underlying density of states, using a structure-based model both with and without considering energetic roughness. By quantifying three individual effective intrinsic energy landscapes (one for interfacial binding, two for monomeric folding), the association mechanisms for flexible recognition of 15 homodimers can be classified into two-state cooperative “coupled binding–folding” and three-state noncooperative “folding prior to binding” scenarios. We found that the association mechanism of flexible biomolecular recognition relies on the interplay between the underlying effective intrinsic binding and folding energy landscapes. By quantifying the whole global intrinsic binding–folding energy landscapes, we found strong correlations between the landscape topography measure Λ (dimensionless ratio of energy gap versus roughness modulated by the configurational entropy) and the ratio of the thermodynamic stable temperature versus trapping temperature, as well as between Λ and binding kinetics. Therefore, the global energy landscape topography determines the binding–folding thermodynamics and kinetics, crucial for the feasibility and efficiency of realizing biomolecular function. We also found “U-shape” temperature-dependent kinetic behavior and a dynamical cross-over temperature for dividing exponential and nonexponential kinetics for two-state homodimers. Our study provides a unique way to bridge the gap between theory and experiments. PMID:23754431

  13. Method for forming materials

    Science.gov (United States)

    Tolle, Charles R [Idaho Falls, ID; Clark, Denis E [Idaho Falls, ID; Smartt, Herschel B [Idaho Falls, ID; Miller, Karen S [Idaho Falls, ID

    2009-10-06

    A material-forming tool and a method for forming a material are described including a shank portion; a shoulder portion that releasably engages the shank portion; a pin that releasably engages the shoulder portion, wherein the pin defines a passageway; and a source of a material coupled in material flowing relation relative to the pin and wherein the material-forming tool is utilized in methodology that includes providing a first material; providing a second material, and placing the second material into contact with the first material; and locally plastically deforming the first material with the material-forming tool so as mix the first material and second material together to form a resulting material having characteristics different from the respective first and second materials.

  14. A numerical analysis on forming limits during spiral and concentric single point incremental forming

    Science.gov (United States)

    Gipiela, M. L.; Amauri, V.; Nikhare, C.; Marcondes, P. V. P.

    2017-01-01

    Sheet metal forming is one of the major manufacturing industries, which are building numerous parts for aerospace, automotive and medical industry. Due to the high demand in vehicle industry and environmental regulations on less fuel consumption on other hand, researchers are innovating new methods to build these parts with energy efficient sheet metal forming process instead of conventionally used punch and die to form the parts to achieve the lightweight parts. One of the most recognized manufacturing process in this category is Single Point Incremental Forming (SPIF). SPIF is the die-less sheet metal forming process in which the single point tool incrementally forces any single point of sheet metal at any process time to plastic deformation zone. In the present work, finite element method (FEM) is applied to analyze the forming limits of high strength low alloy steel formed by single point incremental forming (SPIF) by spiral and concentric tool path. SPIF numerical simulations were model with 24 and 29 mm cup depth, and the results were compare with Nakajima results obtained by experiments and FEM. It was found that the cup formed with Nakajima tool failed at 24 mm while cups formed by SPIF surpassed the limit for both depths with both profiles. It was also notice that the strain achieved in concentric profile are lower than that in spiral profile.

  15. Adaptive Municipal e-forms

    NARCIS (Netherlands)

    Kuiper, P.M.; van Dijk, Elisabeth M.A.G.; Boerma, A.K.; Weibelzahl, S.; Cristea, A.

    2006-01-01

    Adaptation of electronic forms seems to be a step forward to reduce the burden for people who fill in forms. Municipalities more and more offer eforms online that can be used to request a municipal product or service. To create adaptive e-forms that satisfy the need of end-users, involvement of

  16. Biological Sensors Using DNA Functionalized Multiwalled Carbon Nanotubes

    Science.gov (United States)

    2009-10-01

    hydrodynamic voltammetry and the results have been discussed. 5 2. Experimental Methods Reagents GOD (EC 1.1.3.4, Aspergillus niger , >100 U...is of practical use, stable and inexpensive. GOD from Aspergillus , is a homodimer containing two tightly bound flavine adenine dinucleotide (FAD

  17. Electron transfer reactivity of the Arabidopsis thaliana sulfhydryl oxidase AtErv1

    DEFF Research Database (Denmark)

    Farver, Ole; Vitu, Elvira; Wherland, Scot

    2009-01-01

    The redox reactivity of the three disulfide bridges and the flavin present in each protomer of the wild-type Arabidopsis thaliana mitochondrial sulfhydryl oxidase (AtErv1) homodimer has been investigated. Pulse radiolytically produced CO2- radical ions were found to reduce the disulfide bridges...

  18. Hydrogen bonding of formamide, urea, urea monoxide and their thio

    Indian Academy of Sciences (India)

    Ab initio and DFT methods have been employed to study the hydrogen bonding ability of formamide, urea, urea monoxide, thioformamide, thiourea and thiourea monoxide with one water molecule and the homodimers of the selected molecules. The stabilization energies associated with themonohydrated adducts and ...

  19. SuperFormLab: showing SuperFormLab

    DEFF Research Database (Denmark)

    2013-01-01

    bachelor program, followed by two years of master studies. The courses are offered equally to students from other design disciplines, e.g. industrial design. Teaching is mainly in English as the program is attended by a relatively large group of non-Danish students, who seek exactly this combination......3D-printing in clay and ceramic objects shaped by your own sounds and movements! Digital form transferred via CNC-milling to ornamental ceramic wall-cladding. Brave New World… Students and their teacher at SuperFormLab, the new ceramic workshop of the School of Design at the Royal Danish Academy...... of Fine Arts in Copenhagen, will be showing results of their investigations into the potential of combining digital technologies with ceramic materials. It is now possible to shape the most complex mathematical, virtual 3D objects through the use of advanced software-programs. And more than that – you can...

  20. Method for forming ammonia

    Science.gov (United States)

    Kong, Peter C.; Pink, Robert J.; Zuck, Larry D.

    2008-08-19

    A method for forming ammonia is disclosed and which includes the steps of forming a plasma; providing a source of metal particles, and supplying the metal particles to the plasma to form metal nitride particles; and providing a substance, and reacting the metal nitride particles with the substance to produce ammonia, and an oxide byproduct.

  1. Forms of global governence

    Directory of Open Access Journals (Sweden)

    Maxim V. Kharkevich

    2014-01-01

    Full Text Available Global governance as a concept defines the meaning of contemporary world politics both as a discipline and as reality. Interdependent and globalized world requires governance, and a global government has not been formed yet. The theoretical possibility of global governance without global government is proved and justified. The purpose of this article is to analytically identify possible forms of global governance. Three such forms of global governance are identified: hierarchical, market and network. In a hierarchy the governance is due to the asymmetry of power between the parties. Market control happens via anonymous pricing mechanism. Network, in contrast to the market is characterized by a closer value link between the actors, but unlike the hierarchical relationship actors are free to leave the network. Global governance takes three forms and is being implemented by different actors. To determine the most efficient form of global governance is impossible. Efficiency depends on the match between a form and an object of government. It should be noted that meta governance is likely to remain a monopoly of institutionally strong states in global governance.

  2. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors formed by such methods

    Science.gov (United States)

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2014-09-09

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  3. U-Form vs. M-Form: How to Understand Decision Autonomy Under Healthcare Decentralization?

    Science.gov (United States)

    Bustamante, Arturo Vargas

    2016-01-01

    For more than three decades healthcare decentralization has been promoted in developing countries as a way of improving the financing and delivery of public healthcare. Decision autonomy under healthcare decentralization would determine the role and scope of responsibility of local authorities. Jalal Mohammed, Nicola North, and Toni Ashton analyze decision autonomy within decentralized services in Fiji. They conclude that the narrow decision space allowed to local entities might have limited the benefits of decentralization on users and providers. To discuss the costs and benefits of healthcare decentralization this paper uses the U-form and M-form typology to further illustrate the role of decision autonomy under healthcare decentralization. This paper argues that when evaluating healthcare decentralization, it is important to determine whether the benefits from decentralization are greater than its costs. The U-form and M-form framework is proposed as a useful typology to evaluate different types of institutional arrangements under healthcare decentralization. Under this model, the more decentralized organizational form (M-form) is superior if the benefits from flexibility exceed the costs of duplication and the more centralized organizational form (U-form) is superior if the savings from economies of scale outweigh the costly decision-making process from the center to the regions. Budgetary and financial autonomy and effective mechanisms to maintain local governments accountable for their spending behavior are key decision autonomy variables that could sway the cost-benefit analysis of healthcare decentralization. PMID:27694684

  4. Forming of superplastic ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Lesuer, D.R.; Wadsworth, J.; Nieh, T.G.

    1994-05-01

    Superplasticity in ceramics has now advanced to the stage that technologically viable superplastic deformation processing can be performed. In this paper, examples of superplastic forming and diffusion bonding of ceramic components are given. Recent work in biaxial gas-pressure forming of several ceramics is provided. These include yttria-stabilized, tetragonal zirconia (YTZP), a 20% alumina/YTZP composite, and silicon. In addition, the concurrent superplastic forming and diffusion bonding of a hybrid ceramic-metal structure are presented. These forming processes offer technological advantages of greater dimensional control and increased variety and complexity of shapes than is possible with conventional ceramic shaping technology.

  5. Measuring the Thermophysical and Structural Properties of Glass-Forming and Quasicrystal-Forming Liquids

    Science.gov (United States)

    Hyers, Robert W.; Bradshaw, Richard C.; Rogers, Jan R.; Gangopadhyay, Anup K.; Kelton, Ken F.

    2006-01-01

    The thermophysical properties of glass-forming and quasicrystal-forming alloys show many interesting features in the undercooled liquid range. Some of the features in the thermophysical property curves are expected to reflect changes in the structure and coordination of the liquid. These measurements require containerless processing such as electrostatic levitation to access the undercooled liquid regime. An overview of the state of the art in measuring the thermophysical properties and structure of undercooled liquid glass-forming and quasicrystal-forming alloys will be presented, along with the status of current measurements.

  6. Effect of multiple forming tools on geometrical and mechanical properties in incremental sheet forming

    Science.gov (United States)

    Wernicke, S.; Dang, T.; Gies, S.; Tekkaya, A. E.

    2018-05-01

    The tendency to a higher variety of products requires economical manufacturing processes suitable for the production of prototypes and small batches. In the case of complex hollow-shaped parts, single point incremental forming (SPIF) represents a highly flexible process. The flexibility of this process comes along with a very long process time. To decrease the process time, a new incremental forming approach with multiple forming tools is investigated. The influence of two incremental forming tools on the resulting mechanical and geometrical component properties compared to SPIF is presented. Sheets made of EN AW-1050A were formed to frustums of a pyramid using different tool-path strategies. Furthermore, several variations of the tool-path strategy are analyzed. A time saving between 40% and 60% was observed depending on the tool-path and the radii of the forming tools while the mechanical properties remained unchanged. This knowledge can increase the cost efficiency of incremental forming processes.

  7. Crystallization and preliminary X-ray crystallographic analysis of two vascular apoptosis-inducing proteins (VAPs) from Crotalus atrox venom

    International Nuclear Information System (INIS)

    Igarashi, Tomoko; Oishi, Yuko; Araki, Satohiko; Mori, Hidezo; Takeda, Soichi

    2006-01-01

    Vascular apoptosis-inducing protein 1 (VAP1) and VAP2 from C. atrox venom were crystallized in variety of different crystal forms. Diffraction data sets were obtained to 2.5 and 2.15 Å resolution for VAP1 and VAP2, respectively. VAPs are haemorrhagic snake-venom toxins belonging to the reprolysin family of zinc metalloproteinases. In vitro, VAPs induce apoptosis specifically in cultured vascular endothelial cells. VAPs have a modular structure that bears structural homology to mammalian ADAMs (a disintegrin and metalloproteinases). VAP1 is a homodimer with a MW of 110 kDa in which the monomers are connected by a single disulfide bridge. VAP2 is homologous to VAP1 and exists as a monomer with a MW of 55 kDa. In the current study, several crystal forms of VAP1 and VAP2 were obtained using the vapour-diffusion method and diffraction data sets were collected using SPring-8 beamlines. The best crystals of VAP1 and VAP2 generated data sets to 2.5 and 2.15 Å resolution, respectively

  8. Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode

    International Nuclear Information System (INIS)

    Ye, Q.; Li, X.; Wong, A.; Wei, Q.; Jia, Z.

    2006-01-01

    Calcineurin is a calmodulin-binding protein in brain and the only serine/threonine protein phosphatase under the control of Ca 2+ /calmodulin (CaM), which plays a critical role in coupling Ca 2+ signals to cellular responses. CaM up-regulates the phosphatase activity of calcineurin by binding to the CaM-binding domain (CBD) of calcineurin subunit A. Here, we report crystal structural studies of CaM bound to a CBD peptide. The chimeric protein containing CaM and the CBD peptide forms an intimate homodimer, in which CaM displays a native-like extended conformation and the CBD peptide shows -helical structure. Unexpectedly, the N-terminal lobe from one CaM and the C-terminal lobe from the second molecule form a combined binding site to trap the peptide. Thus, the dimer provides two binding sites, each of which is reminiscent of the fully collapsed conformation of CaM commonly observed in complex with, for example, the myosin light chain kinase (MLCK) peptide. The interaction between the peptide and CaM is highly specific and similar to MLCK

  9. Structure and assembly mechanism for heteromeric kainate receptors.

    Science.gov (United States)

    Kumar, Janesh; Schuck, Peter; Mayer, Mark L

    2011-07-28

    Native glutamate receptor ion channels are tetrameric assemblies containing two or more different subunits. NMDA receptors are obligate heteromers formed by coassembly of two or three divergent gene families. While some AMPA and kainate receptors can form functional homomeric ion channels, the KA1 and KA2 subunits are obligate heteromers which function only in combination with GluR5-7. The mechanisms controlling glutamate receptor assembly involve an initial step in which the amino terminal domains (ATD) assemble as dimers. Here, we establish by sedimentation velocity that the ATDs of GluR6 and KA2 coassemble as a heterodimer of K(d) 11 nM, 32,000-fold lower than the K(d) for homodimer formation by KA2; we solve crystal structures for the GluR6/KA2 ATD heterodimer and heterotetramer assemblies. Using these structures as a guide, we perform a mutant cycle analysis to probe the energetics of assembly and show that high-affinity ATD interactions are required for biosynthesis of functional heteromeric receptors. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. 17 CFR 270.30a-2 - Certification of Form N-CSR and Form N-Q.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certification of Form N-CSR... Form N-CSR and Form N-Q. (a) Each report filed on Form N-CSR (§§ 249.331 and 274.128 of this chapter) or Form N-Q (§§ 249.332 and 274.130 of this chapter) by a registered management investment company...

  11. Soil Forming Factors

    Science.gov (United States)

    It! What is Soil? Chip Off the Old Block Soil Forming Factors Matters of Life and Death Underneath It All Wise Choices A World of Soils Soil Forming Factors 2 A Top to Bottom Guide 3 Making a Soil Monolith 4 Soil Orders 5 State Soil Monoliths 6 Where in the Soil World Are You? >> A Top to

  12. Sheet-bulk metal formingforming of functional components from sheet metals

    Directory of Open Access Journals (Sweden)

    Merklein Marion

    2015-01-01

    Full Text Available The paper gives an overview on the application of sheet-bulk metal forming operations in both scientific and industrial environment. Beginning with the need for an innovative forming technology, the definition of this new process class is introduced. The rising challenges of the application of bulk metal forming operations on sheet metals are presented and the demand on a holistic investigation of this topic is motivated. With the help of examples from established production processes, the latest state of technology and the lack on fundamental knowledge is shown. Furthermore, perspectives regarding new research topics within sheet-bulk metal forming are presented. These focus on processing strategies to improve the quality of functional components by the application of process-adapted semi-finished products as well as the local adaption of the tribological system.

  13. Confectionery-based dose forms.

    Science.gov (United States)

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

  14. A splice variant of RILP induces lysosomal clustering independent of dynein recruitment

    International Nuclear Information System (INIS)

    Marsman, Marije; Jordens, Ingrid; Rocha, Nuno; Kuijl, Coenraad; Janssen, Lennert; Neefjes, Jacques

    2006-01-01

    The small GTPase Rab7 controls fusion and transport of late endocytic compartments. A critical mediator is the Rab7 effector RILP that recruits the minus-end dynein-dynactin motor complex to these compartments. We identified a natural occurring splice variant of RILP (RILPsv) lacking only 27 amino acids encoded by exon VII. Both variants bind Rab7, prolong its GTP-bound state, and induce clustering of late endocytic compartments. However, RILPsv does not recruit the dynein-dynactin complex, implicating exon VII in motor recruitment. Clustering might still occur via dimerization, since both RILP and RILPsv are able to form hetero- and homo-dimers. Moreover, both effectors compete for Rab7 binding but with different outcome for dynein-dynactin recruitment and transport. Hence, RILPsv provides an extra dimension to the control of vesicle fusion and transport by the small GTPase Rab7

  15. Yeast Mitochondrial ADP/ATP Carriers Are Monomeric in Detergents as Demonstrated by Differential Affinity Purification

    NARCIS (Netherlands)

    Bamber, Lisa; Slotboom, Dirk-Jan; Kunji, Edmund R.S.; Barber, L

    2007-01-01

    Most mitochondrial carriers carry out equimolar exchange of substrates and they are believed widely to exist as homo-dimers. Here we show by differential tagging that the yeast mitochondrial ADP/ATP carrier AAC2 is a monomer in mild detergents. Carriers with and without six-histidine or

  16. INFORMATIONAL EFFECT OF A FORM

    Directory of Open Access Journals (Sweden)

    Kovalenko V.F.

    2016-02-01

    Full Text Available The study was conducted by method of light scattering of laser emission. The influence of the form field, mutual influence of mental informational and form torsional fields as well as the following exposure of water samples in the form field after the cease of informational influence on water structure were examined. Paper forms of a pyramid, a cylinder, and a prism were used. The experimental findings show that mechanism of mutual influence on water structure of the form and informational torsional fields depended on the initial conditions of spin restructuring process – the configuration of a form, the type of the form field (internal and external ones, and the initial water structure. The influence of the form field on informational aftereffect was determined, the character of which was defined by ratio of intensities of torsional form field and an informational soliton. The phenomenon of the abnormally large amplification of the informational aftereffect in the internal field of a pyramid demonstrating the attributes of positive reverse connection between the informational soliton and torsional field of water structure and selection of generated cluster sizes were discovered.

  17. Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

    Science.gov (United States)

    Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

    2017-08-04

    Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

  18. Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase.

    Science.gov (United States)

    Navarro, Gemma; Cordomí, Arnau; Casadó-Anguera, Verónica; Moreno, Estefanía; Cai, Ning-Sheng; Cortés, Antoni; Canela, Enric I; Dessauer, Carmen W; Casadó, Vicent; Pardo, Leonardo; Lluís, Carme; Ferré, Sergi

    2018-03-28

    G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A 2A receptor and dopamine D 2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.

  19. Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Miyatake

    Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

  20. Gravitation and quadratic forms

    International Nuclear Information System (INIS)

    Ananth, Sudarshan; Brink, Lars; Majumdar, Sucheta; Mali, Mahendra; Shah, Nabha

    2017-01-01

    The light-cone Hamiltonians describing both pure (N=0) Yang-Mills and N=4 super Yang-Mills may be expressed as quadratic forms. Here, we show that this feature extends to theories of gravity. We demonstrate how the Hamiltonians of both pure gravity and N=8 supergravity, in four dimensions, may be written as quadratic forms. We examine the effect of residual reparametrizations on the Hamiltonian and the resulting quadratic form.

  1. Three forms of relativity

    International Nuclear Information System (INIS)

    Strel'tsov, V.N.

    1992-01-01

    The physical sense of three forms of the relativity is discussed. The first - instant from - respects in fact the traditional approach based on the concept of instant distance. The normal form corresponds the radar formulation which is based on the light or retarded distances. The front form in the special case is characterized by 'observable' variables, and the known method of k-coefficient is its obvious expression. 16 refs

  2. Gravitation and quadratic forms

    Energy Technology Data Exchange (ETDEWEB)

    Ananth, Sudarshan [Indian Institute of Science Education and Research,Pune 411008 (India); Brink, Lars [Department of Physics, Chalmers University of Technology,S-41296 Göteborg (Sweden); Institute of Advanced Studies and Department of Physics & Applied Physics,Nanyang Technological University,Singapore 637371 (Singapore); Majumdar, Sucheta [Indian Institute of Science Education and Research,Pune 411008 (India); Mali, Mahendra [School of Physics, Indian Institute of Science Education and Research,Thiruvananthapuram, Trivandrum 695016 (India); Shah, Nabha [Indian Institute of Science Education and Research,Pune 411008 (India)

    2017-03-31

    The light-cone Hamiltonians describing both pure (N=0) Yang-Mills and N=4 super Yang-Mills may be expressed as quadratic forms. Here, we show that this feature extends to theories of gravity. We demonstrate how the Hamiltonians of both pure gravity and N=8 supergravity, in four dimensions, may be written as quadratic forms. We examine the effect of residual reparametrizations on the Hamiltonian and the resulting quadratic form.

  3. Visual search for motion-form conjunctions: is form discriminated within the motion system?

    Science.gov (United States)

    von Mühlenen, A; Müller, H J

    2001-06-01

    Motion-form conjunction search can be more efficient when the target is moving (a moving 45 degrees tilted line among moving vertical and stationary 45 degrees tilted lines) rather than stationary. This asymmetry may be due to aspects of form being discriminated within a motion system representing only moving items, whereas discrimination of stationary items relies on a static form system (J. Driver & P. McLeod, 1992). Alternatively, it may be due to search exploiting differential motion velocity and direction signals generated by the moving-target and distractor lines. To decide between these alternatives, 4 experiments systematically varied the motion-signal information conveyed by the moving target and distractors while keeping their form difference salient. Moving-target search was found to be facilitated only when differential motion-signal information was available. Thus, there is no need to assume that form is discriminated within the motion system.

  4. Polyphony and verb forms

    Directory of Open Access Journals (Sweden)

    Jelena Rajić

    2012-12-01

    Full Text Available This paper examines some special uses of indicative and subjunctive verb forms in Spanish, which contemporary linguistics explains using the notions of polyphony, evidentials, echoic representation, quotatives, etc. These terms, even though they refer to different characteristics and belong to different theoretical frameworks, share one common feature: they all refer to diverse linguistic forms (discourse markers, linguistic negation, quotatives, echoic utterances, etc. characterized by the presence and interaction of different voices or points of view in one discourse sequence. In this study we are interested in a description of quotative or polyphonic meanings expressed by specific verb forms and tenses, the imperfect and the conditional, and also by indicative forms in subordinate substantive clauses with a negative main verb and by subjunctive forms in subordinate concessive clauses. Our research focuses on the analysis of the linguistic conditions that make possible the evidential use of the conditional, the imperfect and the echoic (metarepresentative interpretation of indicative and subjunctive forms in the above-mentioned contexts. The examples we discuss show that evidential and echoic interpretations are inferential meanings derived from the extralinguistic situation and the knowledge that speakers have of the world.

  5. The C-terminal helix of ribosomal P stalk recognizes a hydrophobic groove of elongation factor 2 in a novel fashion.

    Science.gov (United States)

    Tanzawa, Takehito; Kato, Koji; Girodat, Dylan; Ose, Toyoyuki; Kumakura, Yuki; Wieden, Hans-Joachim; Uchiumi, Toshio; Tanaka, Isao; Yao, Min

    2018-04-06

    Archaea and eukaryotes have ribosomal P stalks composed of anchor protein P0 and aP1 homodimers (archaea) or P1•P2 heterodimers (eukaryotes). These P stalks recruit translational GTPases to the GTPase-associated center in ribosomes to provide energy during translation. The C-terminus of the P stalk is known to selectively recognize GTPases. Here we investigated the interaction between the P stalk and elongation factor 2 by determining the structures of Pyrococcus horikoshii EF-2 (PhoEF-2) in the Apo-form, GDP-form, GMPPCP-form (GTP-form), and GMPPCP-form bound with 11 C-terminal residues of P1 (P1C11). Helical structured P1C11 binds to a hydrophobic groove between domain G and subdomain G' of PhoEF-2, where is completely different from that of aEF-1α in terms of both position and sequence, implying that such interaction characteristic may be requested by how GTPases perform their functions on the ribosome. Combining PhoEF-2 P1-binding assays with a structural comparison of current PhoEF-2 structures and molecular dynamics model of a P1C11-bound GDP form, the conformational changes of the P1C11-binding groove in each form suggest that in response to the translation process, the groove has three states: closed, open, and release for recruiting and releasing GTPases.

  6. Neutron electromagnetic form factors

    International Nuclear Information System (INIS)

    Finn, J.M.; Madey, R.; Eden, T.; Markowitz, P.; Rutt, P.M.; Beard, K.; Anderson, B.D.; Baldwin, A.R.; Keane, D.; Manley, D.M.; Watson, J.W.; Zhang, W.M.; Kowalski, S.; Bertozzi, W.; Dodson, G.; Farkhondeh, M.; Dow, K.; Korsch, W.; Tieger, D.; Turchinetz, W.; Weinstein, L.; Gross, F.; Mougey, J.; Ulmer, P.; Whitney, R.; Reichelt, T.; Chang, C.C.; Kelly, J.J.; Payerle, T.; Cameron, J.; Ni, B.; Spraker, M.; Barkhuff, D.; Lourie, R.; Verst, S.V.; Hyde-Wright, C.; Jiang, W.-D.; Flanders, B.; Pella, P.; Arenhoevel, H.

    1992-01-01

    Nucleon form factors provide fundamental input for nuclear structure and quark models. Current knowledge of neutron form factors, particularly the electric form factor of the neutron, is insufficient to meet these needs. Developments of high-duty-factor accelerators and polarization-transfer techniques permit new experiments that promise results with small sensitivities to nuclear models. We review the current status of the field, our own work at the MIT/Bates linear accelerator, and future experimental efforts

  7. Forms of address in Isizulu

    OpenAIRE

    2014-01-01

    M.A. (African Studies) The study deals with forms of address in isiZulu. Therefore, the various aspects of speech that play roles when addressing a person, the factors affecting forms of address in isiZulu and the effect of languages such as English, Afrikaans and other African languages on the forms of address in isiZulu are of interest. Research was conducted on forms of address in isiZulu in parts of Soweto and it was discovered that form of address are determined by different factors i...

  8. 33 CFR 138.40 - Forms.

    Science.gov (United States)

    2010-07-01

    ...) § 138.40 Forms. All forms referred to in this subpart may be obtained from NPFC by requesting them in writing at the address given in § 138.45(a) or by clicking on the Forms link at the NPFC E-COFR Web site... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Forms. 138.40 Section 138.40...

  9. MAPS Appraisal Report Form

    CERN Multimedia

    HR Department

    2005-01-01

    As announced in Weekly Bulletin 48/2004, from now onwards, the paper MAPS appraisal report form has been replaced by an electronic form, which is available via EDH (on the EDH desktop under Other Tasks / HR & Training) No changes have been made to the contents of the form. Practical information will be available on the web page http://cern.ch/ais/projs/forms/maps/info.htm, and information meetings will be held on the following dates: 18 January 2005: MAIN AUDITORIUM (500-1-001) from 14:00 to 15:30. 20 January 2005: AB AUDITORIUM II (864-1-D02) from14:00 to 15:30. 24 January 2005: AT AUDITORIUM (30-7-018) from 10:00 to 11:30. Human Resources Department Tel. 73566

  10. Access Customized Forms

    OpenAIRE

    Cosma Emil; Jeflea Victor

    2010-01-01

    By using Word, Excel or PowerPoint one can automate routine operations using the VBA language (Visual Basic for Applications). This language is also used in Access, allowing access to data stored in tables or queries. Thus, Access and VBA resources can be used together. Access is designed for programming forms and reports (among other things), so there won’t be found any of the VBA editor’s specific forms.

  11. Forming Limits in Sheet Metal Forming for Non-Proportional Loading Conditions - Experimental and Theoretical Approach

    International Nuclear Information System (INIS)

    Ofenheimer, Aldo; Buchmayr, Bruno; Kolleck, Ralf; Merklein, Marion

    2005-01-01

    The influence of strain paths (loading history) on material formability is well known in sheet forming processes. Sophisticated experimental methods are used to determine the entire shape of strain paths of forming limits for aluminum AA6016-T4 alloy. Forming limits for sheet metal in as-received condition as well as for different pre-deformation are presented. A theoretical approach based on Arrieux's intrinsic Forming Limit Stress Curve (FLSC) concept is employed to numerically predict the influence of loading history on forming severity. The detailed experimental strain paths are used in the theoretical study instead of any linear or bilinear simplified loading histories to demonstrate the predictive quality of forming limits in the state of stress

  12. ATP forms a stable complex with the essential histidine kinase WalK (YycG) domain

    Energy Technology Data Exchange (ETDEWEB)

    Celikel, Reha; Veldore, Vidya Harini [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Mathews, Irimpan [Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Devine, Kevin M., E-mail: kdevine@tcd.ie [Trinity College Dublin, Dublin 2 (Ireland); Varughese, Kottayil I., E-mail: kdevine@tcd.ie [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2012-07-01

    The histidine WalK (YycG) plays a crucial role in coordinating murein synthesis with cell division and the crystal structure of its ATP binding domain has been determined. Interestingly the bound ATP was not hydrolyzed during crystallization and remains intact in the crystal lattice. In Bacillus subtilis, the WalRK (YycFG) two-component system coordinates murein synthesis with cell division. It regulates the expression of autolysins that function in cell-wall remodeling and of proteins that modulate autolysin activity. The transcription factor WalR is activated upon phosphorylation by the histidine kinase WalK, a multi-domain homodimer. It autophosphorylates one of its histidine residues by transferring the γ-phosphate from ATP bound to its ATP-binding domain. Here, the high-resolution crystal structure of the ATP-binding domain of WalK in complex with ATP is presented at 1.61 Å resolution. The bound ATP remains intact in the crystal lattice. It appears that the strong binding interactions and the nature of the binding pocket contribute to its stability. The triphosphate moiety of ATP wraps around an Mg{sup 2+} ion, providing three O atoms for coordination in a near-ideal octahedral geometry. The ATP molecule also makes strong interactions with the protein. In addition, there is a short contact between the exocyclic O3′ of the sugar ring and O2B of the β-phosphate, implying an internal hydrogen bond. The stability of the WalK–ATP complex in the crystal lattice suggests that such a complex may exist in vivo poised for initiation of signal transmission. This feature may therefore be part of the sensing mechanism by which the WalRK two-component system is so rapidly activated when cells encounter conditions conducive for growth.

  13. Application of a widely-used tropical anti-worm agent, mebendazole ...

    African Journals Online (AJOL)

    well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical .... Bcl-2 and related proteins, encoded by the Bcl-2 oncogene ... homodimer that acts as an apoptosis inducer, while the ... Figure 1: Schematic presentation of proposed mebendazole anticancer mechanisms of action in.

  14. 48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

    Science.gov (United States)

    2010-10-01

    ... information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following... specified in subpart 4.4 and the clause at 52.204-2: (a) DD Form 254 (Department of Defense (DOD)), Contract...

  15. Star-forming Filament Models

    International Nuclear Information System (INIS)

    Myers, Philip C.

    2017-01-01

    New models of star-forming filamentary clouds are presented in order to quantify their properties and to predict their evolution. These 2D axisymmetric models describe filaments that have no core, one low-mass core, and one cluster-forming core. They are based on Plummer-like cylinders and spheroids that are bounded by a constant-density surface of finite extent. In contrast to 1D Plummer-like models, they have specific values of length and mass, they approximate observed column density maps, and their distributions of column density ( N -pdfs) are pole-free. Each model can estimate the star-forming potential of a core-filament system by identifying the zone of gas dense enough to form low-mass stars and by counting the number of enclosed thermal Jeans masses. This analysis suggests that the Musca central filament may be near the start of its star-forming life, with enough dense gas to make its first ∼3 protostars, while the Coronet filament is near the midpoint of its star formation, with enough dense gas to add ∼8 protostars to its ∼20 known stars. In contrast, L43 appears to be near the end of its star-forming life, since it lacks enough dense gas to add any new protostars to the two young stellar objectsalready known.

  16. Star-forming Filament Models

    Energy Technology Data Exchange (ETDEWEB)

    Myers, Philip C., E-mail: pmyers@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2017-03-20

    New models of star-forming filamentary clouds are presented in order to quantify their properties and to predict their evolution. These 2D axisymmetric models describe filaments that have no core, one low-mass core, and one cluster-forming core. They are based on Plummer-like cylinders and spheroids that are bounded by a constant-density surface of finite extent. In contrast to 1D Plummer-like models, they have specific values of length and mass, they approximate observed column density maps, and their distributions of column density ( N -pdfs) are pole-free. Each model can estimate the star-forming potential of a core-filament system by identifying the zone of gas dense enough to form low-mass stars and by counting the number of enclosed thermal Jeans masses. This analysis suggests that the Musca central filament may be near the start of its star-forming life, with enough dense gas to make its first ∼3 protostars, while the Coronet filament is near the midpoint of its star formation, with enough dense gas to add ∼8 protostars to its ∼20 known stars. In contrast, L43 appears to be near the end of its star-forming life, since it lacks enough dense gas to add any new protostars to the two young stellar objectsalready known.

  17. Comparative waste forms study

    International Nuclear Information System (INIS)

    Wald, J.W.; Lokken, R.O.; Shade, J.W.; Rusin, J.M.

    1980-12-01

    A number of alternative process and waste form options exist for the immobilization of nuclear wastes. Although data exists on the characterization of these alternative waste forms, a straightforward comparison of product properties is difficult, due to the lack of standardized testing procedures. The characterization study described in this report involved the application of the same volatility, mechanical strength and leach tests to ten alternative waste forms, to assess product durability. Bulk property, phase analysis and microstructural examination of the simulated products, whose waste loading varied from 5% to 100% was also conducted. The specific waste forms investigated were as follows: Cold Pressed and Sintered PW-9 Calcine; Hot Pressed PW-9 Calcine; Hot Isostatic Pressed PW-9 Calcine; Cold Pressed and Sintered SPC-5B Supercalcine; Hot Isostatic pressed SPC-5B Supercalcine; Sintered PW-9 and 50% Glass Frit; Glass 76-68; Celsian Glass Ceramic; Type II Portland Cement and 10% PW-9 Calcine; and Type II Portland Cement and 10% SPC-5B Supercalcine. Bulk property data were used to calculate and compare the relative quantities of waste form volume produced at a spent fuel processing rate of 5 metric ton uranium/day. This quantity ranged from 3173 L/day (5280 Kg/day) for 10% SPC-5B supercalcine in cement to 83 L/day (294 Kg/day) for 100% calcine. Mechanical strength, volatility, and leach resistance tests provide data related to waste form durability. Glass, glass-ceramic and supercalcine ranked high in waste form durability where as the 100% PW-9 calcine ranked low. All other materials ranked between these two groupings

  18. Overexpression of chloroplast NADPH-dependent thioredoxin reductase in Arabidopsis enhances leaf growth and elucidates in-vivo function of reductase and thioredoxin domains

    Directory of Open Access Journals (Sweden)

    Jouni eToivola

    2013-10-01

    Full Text Available Plant chloroplasts have versatile thioredoxin systems including two thioredoxin reductases and multiple types of thioredoxins. Plastid-localized NADPH-dependent thioredoxin reductase (NTRC contains both reductase (NTRd and thioredoxin (TRXd domains in a single polypeptide and forms homodimers. To study the action of NTRC and NTRC domains in vivo, we have complemented the ntrc knockout line of Arabidopsis with the wild type and full-length NTRC genes, in which 2-Cys motifs either in NTRd, or in TRXd were inactivated. The ntrc line was also transformed either with the truncated NTRd or TRXd alone. Overexpression of wild-type NTRC promoted plant growth by increasing leaf size and biomass yield of the rosettes. Complementation of the ntrc line with the full-length NTRC gene containing an active reductase but an inactive thioredoxin domain, or vice versa, recovered wild-type chloroplast phenotype and, partly, rosette biomass production, indicating that the NTRC domains are capable of interacting with other chloroplast thioredoxin systems. Overexpression of truncated NTRd or TRXd in ntrc background did not restore wild-type phenotype. Modelling of the 3-dimensional structure of the NTRC dimer indicates extensive interactions between the NTR domains and the TRX domains further stabilize the dimeric structure. The long linker region between the NTRd and TRXd, however, allows flexibility for the position of the TRXd in the dimer. Supplementation of the TRXd in the NTRC homodimer model by free chloroplast thioredoxins indicated that TRXf is the most likely partner to interact with NTRC. We propose that overexpression of NTRC promotes plant biomass yield both directly by stimulation of chloroplast biosynthetic and protected pathways controlled by NTRC and indirectly via free chloroplast thioredoxins. Our data indicate that overexpression of chloroplast thiol redox-regulator has a potential to increase biofuel yield in plant and algal species suitable for

  19. FORM version 4.0

    Science.gov (United States)

    Kuipers, J.; Ueda, T.; Vermaseren, J. A. M.; Vollinga, J.

    2013-05-01

    We present version 4.0 of the symbolic manipulation system FORM. The most important new features are manipulation of rational polynomials and the factorization of expressions. Many other new functions and commands are also added; some of them are very general, while others are designed for building specific high level packages, such as one for Gröbner bases. New is also the checkpoint facility, that allows for periodic backups during long calculations. Finally, FORM 4.0 has become available as open source under the GNU General Public License version 3. Program summaryProgram title: FORM. Catalogue identifier: AEOT_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOT_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 151599 No. of bytes in distributed program, including test data, etc.: 1 078 748 Distribution format: tar.gz Programming language: The FORM language. FORM itself is programmed in a mixture of C and C++. Computer: All. Operating system: UNIX, LINUX, Mac OS, Windows. Classification: 5. Nature of problem: FORM defines a symbolic manipulation language in which the emphasis lies on fast processing of very large formulas. It has been used successfully for many calculations in Quantum Field Theory and mathematics. In speed and size of formulas that can be handled it outperforms other systems typically by an order of magnitude. Special in this version: The version 4.0 contains many new features. Most important are factorization and rational arithmetic. The program has also become open source under the GPL. The code in CPC is for reference. You are encouraged to upload the most recent sources from www.nikhef.nl/form/formcvs.php because of frequent bug fixes. Solution method: See "Nature of Problem", above. Additional comments: NOTE: The code in CPC is for reference. You are encouraged

  20. Soaking suggests "alternative facts": Only co-crystallization discloses major ligand-induced interface rearrangements of a homodimeric tRNA-binding protein indicating a novel mode-of-inhibition.

    Directory of Open Access Journals (Sweden)

    Frederik Rainer Ehrmann

    Full Text Available For the efficient pathogenesis of Shigella, the causative agent of bacillary dysentery, full functionality of tRNA-guanine transglycosylase (TGT is mandatory. TGT performs post-transcriptional modifications of tRNAs in the anticodon loop taking impact on virulence development. This suggests TGT as a putative target for selective anti-shigellosis drug therapy. Since bacterial TGT is only functional as homodimer, its activity can be inhibited either by blocking its active site or by preventing dimerization. Recently, we discovered that in some crystal structures obtained by soaking the full conformational adaptation most likely induced in solution upon ligand binding is not displayed. Thus, soaked structures may be misleading and suggest irrelevant binding modes. Accordingly, we re-investigated these complexes by co-crystallization. The obtained structures revealed large conformational rearrangements not visible in the soaked complexes. They result from spatial perturbations in the ribose-34/phosphate-35 recognition pocket and, consequently, an extended loop-helix motif required to prevent access of water molecules into the dimer interface loses its geometric integrity. Thermodynamic profiles of ligand binding in solution indicate favorable entropic contributions to complex formation when large conformational adaptations in the dimer interface are involved. Native MS titration experiments reveal the extent to which the homodimer is destabilized in the presence of each inhibitor. Unexpectedly, one ligand causes a complete rearrangement of subunit packing within the homodimer, never observed in any other TGT crystal structure before. Likely, this novel twisted dimer is catalytically inactive and, therefore, suggests that stabilizing this non-productive subunit arrangement may be used as a further strategy for TGT inhibition.

  1. Electromagnetic form factors of hadrons

    International Nuclear Information System (INIS)

    Zidell, V.S.

    1976-01-01

    A vector meson dominance model of the electromagnetic form factors of hadrons is developed which is based on the use of unstable particle propagators. Least-square fits are made to the proton, neutron, pion and kaon form factor data in both the space and time-like regions. A good fit to the low-energy nucleon form factor data is obtained using only rho, ω, and phi dominance, and leads to a determination of the vector meson resonance parameters in good agreement with experiment. The nucleon-vector meson coupling constants obey simple sum rules indicating that there exists no hard core contribution to the form factors within theoretical uncertainties. The prediction for the electromagnetic radii of the proton is in reasonable agreement with recent experiments. The pion and kaon charge form factors as deduced from the nucleon form factors assuming vector meson universality are compared to the data. The pion form factor agrees with the data in both the space and time-like regions. The pion charge radius is in agreement with the recent Dubna result, but the isovector P-wave pion-pion phase shift calculated from the theory disagrees with experiment. A possible contribution to the form factors from a heavy rho meson is also evaluated

  2. Electromagnetic Hadronic Form-Factors

    International Nuclear Information System (INIS)

    Edwards, Robert G.

    2005-01-01

    We present a calculation of the nucleon electromagnetic form-factors as well as the pion and rho to pion transition form-factors in a hybrid calculation with domain wall valence quarks and improved staggered (Asqtad) sea quarks

  3. Directory of Energy Data Collection Forms: Forms in use as of October 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    This is the twentieth edition of the Directory of Energy Collection Data Forms, an authoritative listing of selected public use forms currently used as basic energy information gathering tools by the Department of Energy.

  4. A compiler for variational forms

    OpenAIRE

    Kirby, Robert C.; Logg, Anders

    2011-01-01

    As a key step towards a complete automation of the finite element method, we present a new algorithm for automatic and efficient evaluation of multilinear variational forms. The algorithm has been implemented in the form of a compiler, the FEniCS Form Compiler FFC. We present benchmark results for a series of standard variational forms, including the incompressible Navier-Stokes equations and linear elasticity. The speedup compared to the standard quadrature-based approach is impressive; in s...

  5. Crystallization behavior of nuclear waste forms

    International Nuclear Information System (INIS)

    Rusin, J.M.; Lokken, R.O.; May, R.P.; Wald, J.W.

    1981-09-01

    Several waste form options have been or are being developed for the immobilization of high-level wastes. The final selection of a waste form must take into consideration both waste form product as well as process factors. Crystallization behavior has an important role in nuclear waste form technology. For glass or vitreous waste forms, crystallization is generally controlled to a minimum by appropriate glass formulation and heat treatment schedules. With glass ceramic waste forms, crystallization is essential to convert glass products to highly crystalline waste forms with a minimum residual glass content. In the case of ceramic waste forms, additives and controlled sintering schedules are used to contain the radionuclides in specific tailored crystalline phases

  6. Disjoint forms in graphical user interfaces

    NARCIS (Netherlands)

    Evers, S.; Achten, P.M.; Plasmeijer, M.J.; Loidl, H.W.

    Forms are parts of a graphical user interface (GUI) that show a set of values and allow the user to update them. The declarative form construction library FunctionalForms is extended with disjoint form combinators to capture some common patterns in which the form structure expresses a choice. We

  7. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation

    NARCIS (Netherlands)

    Wang, J.; Zheng, Y.; Zhao, J.; Liu, T.; Gao, L.; Gu, Z.; Wu, G.

    2012-01-01

    Objectives To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Material and Methods Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created

  8. Form Filling with SCC in a Vertical Form

    DEFF Research Database (Denmark)

    Thrane, Lars Nyholm

    2004-01-01

    This paper presents the results obtained from two different vertical form filling experiments with SCC that have been completed as part of the experimental work in an ongoing Ph.D project. The project is carried out at the Danish Technological Institute in collaboration with the Technical...

  9. Anticipation of visual form independent of knowing where the form will occur/

    DEFF Research Database (Denmark)

    Bruhn, Pernille; Bundesen, Claus

    2012-01-01

    We investigated how selective preparation for specific forms is affected by concurrent preknowledge of location when upcoming visual stimuli are anticipated. In three experiments, participants performed a two-choice response time (RT) task in which they discriminated between standard upright...... of our effects suggested that preknowledge of form and location, respectively, affected two functionally independent, serial stages of processing. We suggest that the two stages were, first, direction of attention to the stimulus location and, subsequently, discrimination between upright and rotated...... stimuli. Presumably, preknowledge of location advanced the point in time at which attention was directed at the stimulus location, whereas preknowledge of form reduced the time subsequently taken for stimulus discrimination....

  10. Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments.

    Science.gov (United States)

    Belenguer, Ana M; Lampronti, Giulio I; Sanders, Jeremy K M

    2018-01-23

    The equilibrium outcomes of ball mill grinding can dramatically change as a function of even tiny variations in the experimental conditions such as the presence of very small amounts of added solvent. To reproducibly and accurately capture this sensitivity, the experimentalist needs to carefully consider every single factor that can affect the ball mill grinding reaction under investigation, from ensuring the grinding jars are clean and dry before use, to accurately adding the stoichiometry of the starting materials, to validating that the delivery of solvent volume is accurate, to ensuring that the interaction between the solvent and the powder is well understood and, if necessary, a specific soaking time is added to the procedure. Preliminary kinetic studies are essential to determine the necessary milling time to achieve equilibrium. Only then can exquisite phase composition curves be obtained as a function of the solvent concentration under ball mill liquid assisted grinding (LAG). By using strict and careful procedures analogous to the ones here presented, such milling equilibrium curves can be obtained for virtually all milling systems. The system we use to demonstrate these procedures is a disulfide exchange reaction starting from the equimolar mixture of two homodimers to obtain at equilibrium quantitative heterodimer. The latter is formed by ball mill grinding as two different polymorphs, Form A and Form B. The ratio R = [Form B] / ([Form A] + [Form B]) at milling equilibrium depends on the nature and concentration of the solvent in the milling jar.

  11. 46 CFR 308.409 - Standard form of War Risk Builder's Risk Insurance Policy, Form MA-283.

    Science.gov (United States)

    2010-10-01

    ... Policy, Form MA-283. 308.409 Section 308.409 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF... of War Risk Builder's Risk Insurance Policy, Form MA-283. The standard form of War Risk Builder's Risk Insurance Policy, Form MA-283 may be obtained from the American War Risk Agency or MARAD. ...

  12. Undercuts by Laser Shock Forming

    International Nuclear Information System (INIS)

    Wielage, Hanna; Vollertsen, Frank

    2011-01-01

    In laser shock forming TEA-CO 2 -laser induced shock waves are used to form metal foils, such as aluminum or copper. The process utilizes an initiated plasma shock wave on the target surface, which leads to a forming of the foil. A challenge in forming technologies is the manufacturing of undercuts. By conventional forming methods these special forms are not feasible. In this article, it is presented that undercuts in the micro range can be produced by laser shock deep drawing. Different drawing die diameters, drawing die depths and the material aluminum in the thicknesses 20 and 50 μm were investigated. It will be presented that smaller die diameters facilitate undercuts compared to bigger die diameters. The phenomena can be explained by Barlow's formula. Furthermore, it is shown which maximum undercut depth at different die diameters can be reached. To this end, cross-sections of the different parameter combinations are displayed.

  13. Package materials, waste form

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The schedules for waste package development for the various host rocks were presented. The waste form subtask activities were reviewed, with the papers focusing on high-level waste, transuranic waste, and spent fuel. The following ten papers were presented: (1) Waste Package Development Approach; (2) Borosilicate Glass as a Matrix for Savannah River Plant Waste; (3) Development of Alternative High-Level Waste Forms; (4) Overview of the Transuranic Waste Management Program; (5) Assessment of the Impacts of Spent Fuel Disassembly - Alternatives on the Nuclear Waste Isolation System; (6) Reactions of Spent Fuel and Reprocessing Waste Forms with Water in the Presence of Basalt; (7) Spent Fuel Stabilizer Screening Studies; (8) Chemical Interactions of Shale Rock, Prototype Waste Forms, and Prototype Canister Metals in a Simulated Wet Repository Environment; (9) Impact of Fission Gas and Volatiles on Spent Fuel During Geologic Disposal; and (10) Spent Fuel Assembly Decay Heat Measurement and Analysis

  14. STUDI KOMPARASI KINERJA HULL FORM METODE SCHELTEMA DENGAN HULL FORM KAPAL IKAN TRADISIONAL TIPE DAERAH BATANG

    OpenAIRE

    A.F. Zakki; Parlindungan Manik

    2012-01-01

    This study comparation of hull form performance was analysed becaused there was suggestion that a ship was built by hull form scheming this time (Scheltema, Formdata, NPL Series) is better than a ship that was built traditionally because there is no basic erudite calculation in hull form design. So hull form design was result of natural adaptation. Such performance are ship’s resistance, stability, and ship’s navigation.This research about hull form performance is expected can giv...

  15. Molecular mechanisms in the activation of abscisic acid receptor PYR1.

    Directory of Open Access Journals (Sweden)

    Lyudmyla Dorosh

    Full Text Available The pyrabactin resistance 1 (PYR1/PYR1-like (PYL/regulatory component of abscisic acid (ABA response (RCAR proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodimers (PYR1 and PYLs 1-3 or mediate basal inhibition of downstream target type 2C protein phosphatases (PP2Cs; PYLs 4-10 respectively in vitro. Addition of ABA has been shown to release the apo-homodimers yielding ABA-bound monomeric holo-receptors that can interact with PP2Cs; highlighting a competitive-interaction process. Interaction selectivity has been shown to be mediated by subtle structural variations of primary sequence and ligand binding effects. Now, the dynamical contributions of ligand binding on interaction selectivity are investigated through extensive molecular dynamics (MD simulations of apo and holo-PYR1 in monomeric and dimeric form as well as in complex with a PP2C, homology to ABA insensitive 1 (HAB1. Robust comparative interpretations were enabled by a novel essential collective dynamics approach. In agreement with recent experimental findings, our analysis indicates that ABA-bound PYR1 should efficiently bind to HAB1. However, both ABA-bound and ABA-extracted PYR1-HAB1 constructs have demonstrated notable similarities in their dynamics, suggesting that apo-PYR1 should also be able to make a substantial interaction with PP2Cs, albeit likely with slower complex formation kinetics. Further analysis indicates that both ABA-bound and ABA-free PYR1 in complex with HAB1 exhibit a higher intra-molecular structural stability and stronger inter-molecular dynamic correlations, in comparison with either holo- or apo-PYR1 dimers, supporting a model that includes apo-PYR1 in complex with HAB1. This possibility of a conditional functional apo-PYR1-PP2C complex was validated in vitro. These findings are generally consistent with the competitive

  16. Cold-formed steel design

    CERN Document Server

    Yu, Wei-Wen

    2010-01-01

    The definitive text in the field, thoroughly updated and expanded Hailed by professionals around the world as the definitive text on the subject, Cold-Formed Steel Design is an indispensable resource for all who design for and work with cold-formed steel. No other book provides such exhaustive coverage of both the theory and practice of cold-formed steel construction. Updated and expanded to reflect all the important developments that have occurred in the field over the past decade, this Fourth Edition of the classic text provides you with more of the detailed, up-to-the-minute techni

  17. Tectonics: The meaning of form

    DEFF Research Database (Denmark)

    Christiansen, Karl; Brandt, Per Aage

    Tectonics – The meaning of form deals with one of the core topics of architecture: the relationship between form and content. In the world of architecture, form is not only made from brick, glass and wood. Form means something. When a material is processed with sufficient technical skill and insi...... perspectives. You can read the chapters in any order you like – from the beginning, end or the middle. There is no correct order. The project is methodologically inductive: the more essays you read, the broader your knowledge of tectonics get....

  18. 8 CFR 265.1 - Forms.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Forms. 265.1 Section 265.1 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS NOTICES OF ADDRESS § 265.1 Forms. Except... under section 262 of the Act shall report each change of address and new address within 10 days on Form...

  19. 29 CFR 1904.29 - Forms.

    Science.gov (United States)

    2010-07-01

    ... OSHA 300 Log. Instead, enter “privacy case” in the space normally used for the employee's name. This...) Basic requirement. You must use OSHA 300, 300-A, and 301 forms, or equivalent forms, for recordable injuries and illnesses. The OSHA 300 form is called the Log of Work-Related Injuries and Illnesses, the 300...

  20. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors and intermediate products formed by such methods

    Science.gov (United States)

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2012-12-04

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  1. A structural model of pestivirus E(rns) based on disulfide bond connectivity and homology modeling reveals an extremely rare vicinal disulfide

    NARCIS (Netherlands)

    Langedijk, J.P.M.; Veelen, van P.A.; Schaaper, W.M.M.; Ru, de A.H.; Meloen, R.H.; Hulst, M.M.

    2002-01-01

    Erns is a pestivirus envelope glycoprotein and is the only known viral surface protein with RNase activity. Erns is a disulfide-linked homodimer of 100 kDa; it is found on the surface of pestivirus-infected cells and is secreted into the medium. In this study, the disulfide arrangement of the nine

  2. Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane.

    Science.gov (United States)

    Elazar, Assaf; Weinstein, Jonathan; Biran, Ido; Fridman, Yearit; Bibi, Eitan; Fleishman, Sarel Jacob

    2016-01-29

    Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self-association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers.

  3. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

    International Nuclear Information System (INIS)

    Vognsen, Tina; Kristensen, Ole

    2012-01-01

    Highlights: ► The crystal structure of the NTF2-like domain of Rasputin protein is presented. ► Differences to known ligand binding sites of nuclear transport factor 2 are discussed. ► A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

  4. Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression*

    Science.gov (United States)

    Coke, Christopher J.; Scarlett, Kisha A.; Chetram, Mahandranauth A.; Jones, Kia J.; Sandifer, Brittney J.; Davis, Ahriea S.; Marcus, Adam I.

    2016-01-01

    The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. PMID:26841863

  5. Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs.

    Science.gov (United States)

    Navarro, Gemma; Cordomí, Arnau; Zelman-Femiak, Monika; Brugarolas, Marc; Moreno, Estefania; Aguinaga, David; Perez-Benito, Laura; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Pardo, Leonardo; García-Sáez, Ana J; McCormick, Peter J; Franco, Rafael

    2016-04-05

    G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function.

  6. A regression-based Kansei engineering system based on form feature lines for product form design

    Directory of Open Access Journals (Sweden)

    Yan Xiong

    2016-06-01

    Full Text Available When developing new products, it is important for a designer to understand users’ perceptions and develop product form with the corresponding perceptions. In order to establish the mapping between users’ perceptions and product design features effectively, in this study, we presented a regression-based Kansei engineering system based on form feature lines for product form design. First according to the characteristics of design concept representation, product form features–product form feature lines were defined. Second, Kansei words were chosen to describe image perceptions toward product samples. Then, multiple linear regression and support vector regression were used to construct the models, respectively, that predicted users’ image perceptions. Using mobile phones as experimental samples, Kansei prediction models were established based on the front view form feature lines of the samples. From the experimental results, these two predict models were of good adaptability. But in contrast to multiple linear regression, the predict performance of support vector regression model was better, and support vector regression is more suitable for form regression prediction. The results of the case showed that the proposed method provided an effective means for designers to manipulate product features as a whole, and it can optimize Kansei model and improve practical values.

  7. Chemical forms of radioiodine

    International Nuclear Information System (INIS)

    Tachikawa, Enzo

    1979-01-01

    Release of radioiodine built-up during reactor operations presents a potential problem from the standpoint of environmental safety. Among the chemical forms of radioiodine, depending upon the circumstances, organic iodides cast a most serious problem because of its difficulties in the trapping and because of its stability compared to other chemical forms. Furthermore, pellet-cladding interaction (PCl) fuel failures in LWR fuel rods are believed to be stress corrosion cracks caused by embrittling fission product species, radioiodine. To deal with these problems, knowledge is required on the chemical behaviors of radioiodine in and out of fuels, as well as the release behaviors from fuels. Here a brief review is given of these respects, in aiming at clearing-up the questions still remaining unknown. The data seem to indicate that radioiodine exists as a combined form in fuels. upon heating slightly irradiated fuels, the iodine atoms are released in a chemical form associated with uranium atoms. Experiments, however, as needed with specimen of higher burnup, where the interactions of radioiodine with metallic fission products could be favored. The dominant release mechanism of radioiodine under normal operating temperatures will be diffusion to grain boundaries leading to open surfaces. Radiation-induced internal traps, however, after the rate of diffusion significantly. The carbon sources of organic iodides formed under various conditions and its formation mechanisms have also been considered. (author)

  8. Forms of Life

    Directory of Open Access Journals (Sweden)

    Peter Hacker

    2015-10-01

    Full Text Available The phrase ‘Lebensform’ (form of life had a long and varied history prior to Wittgenstein’s use of it on a mere three occasions in the Philosophical Investigations. It is not a pivotal concept in Wittgenstein’s philosophy. But it is a minor signpost of a major reorientation of philosophy, philosophy of language and logic, and philosophy of mathematics that Wittgenstein instigated. For Wittgenstein sought to replace the conception of a language as a meaning calculus (Frege, Russell, the Tractatus by an anthropological or ethnological conception. A language is not a class of sentences that can be formed from a set of axioms (definitions, formation and transformation rules and the meanings of which is given by their truth-conditions, but an open-ended series of interlocking language-games constituting a form of life or way of living (a culture. Wittgenstein’s uses of ‘Lebensform’ and its cognates, both in the Investigations and in his Nachlass are severally analysed, and various exegetical misinterpretations are clarified.

  9. Variational principles for locally variational forms

    International Nuclear Information System (INIS)

    Brajercik, J.; Krupka, D.

    2005-01-01

    We present the theory of higher order local variational principles in fibered manifolds, in which the fundamental global concept is a locally variational dynamical form. Any two Lepage forms, defining a local variational principle for this form, differ on intersection of their domains, by a variationally trivial form. In this sense, but in a different geometric setting, the local variational principles satisfy analogous properties as the variational functionals of the Chern-Simons type. The resulting theory of extremals and symmetries extends the first order theories of the Lagrange-Souriau form, presented by Grigore and Popp, and closed equivalents of the first order Euler-Lagrange forms of Hakova and Krupkova. Conceptually, our approach differs from Prieto, who uses the Poincare-Cartan forms, which do not have higher order global analogues

  10. Electroweak form factors of the Skyrmion

    International Nuclear Information System (INIS)

    Braaten, E.; Sze-Man Tse; Willcox, C.

    1986-01-01

    The electroweak form factors of baryons are studied in the semiclassical approximation to the Skyrme model. General expressions for the form factors are given for arbitrary choices of the Skyrme-model Lagrangian. They are applied to the original two-parameter Skyrme model to compute the electric, magnetic, and axial-vector form factors of the nucleon and the electromagnetic nucleon-Δ transition form factors. The dependence of the form factors on the momentum transfer is compared with phenomenological dipole parametrizations

  11. Forms of Life, Forms of Reality

    Directory of Open Access Journals (Sweden)

    Piergiorgio Donatelli

    2015-10-01

    Full Text Available The article explores aspects of the notion of forms of life in the Wittgensteinian tradition especially following Iris Murdoch’s lead. On the one hand, the notion signals the hardness and inexhaustible character of reality, as the background needed in order to make sense of our lives in various ways. On the other, the hardness of reality is the object of a moral work of apprehension and deepening to the point at which its distinctive character dissolves into the family of connections we have gained for ourselves. The two movements of thought are connected and necessary.

  12. Form 6 - gas balancing agreement

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    In 1988, a special Committee of the Rocky Mountain Mineral Law Foundation undertook a project to draft a model from gas balancing agreement. This project was initiated at the request of a number of Foundation members who felt that a model form gas balancing agreement would facilitate the negotiation of operating agreement, since gas balancing issues had become sticking points in the process. The Committee was composed of attorneys representing a wide cross-section of the oil and gas industry including both major and independent oil companies, production companies with interstate pipeline affiliates, and private practitioners. The Committee attempted to address the more controversial issues in gas balancing with optional provisions in the Form. To facilitate the negotiation process, the number of optional provisions was minimized. This form may be used as an Appendix to the new A.A.P.L. Form 610-1989 Model Form Operating Agreement. This book includes provision of this Form which are: Ownership of gas production; Balancing of production accounts; Cash balancing upon depletion; Deliverability tests; Nominations; Statements; Payment of taxes; Operating expenses; Overproducing allowable; Payment of leasehold burdens; Operator's liability; Successors and assigns; Audits; Arbitration; and Operator's fees

  13. 76 FR 82003 - Submission for Review: DD 1918 Establishment Information Form, DD 1919 Wage Data Collection Form...

    Science.gov (United States)

    2011-12-29

    ... OFFICE OF PERSONNEL MANAGEMENT Submission for Review: DD 1918 Establishment Information Form, DD 1919 Wage Data Collection Form, DD 1919C Wage Data Collection Continuation Form AGENCY: U.S. Office of... existing information collection request (ICR) 3206-0036, Establishment Information Form (DD 1918), Wage...

  14. 76 FR 50771 - Submission for Review: DD 1918 Establishment Information Form, DD 1919 Wage Data Collection Form...

    Science.gov (United States)

    2011-08-16

    ... OFFICE OF PERSONNEL MANAGEMENT Submission for Review: DD 1918 Establishment Information Form, DD 1919 Wage Data Collection Form, DD 1919C Wage Data Collection Continuation Form AGENCY: U.S. Office of... existing information collection request (ICR) 3206-0036, Establishment Information Form (DD 1918), Wage...

  15. Amorphous drugs and dosage forms

    DEFF Research Database (Denmark)

    Grohganz, Holger; Löbmann, K.; Priemel, P.

    2013-01-01

    The transformation to an amorphous form is one of the most promising approaches to address the low solubility of drug compounds, the latter being an increasing challenge in the development of new drug candidates. However, amorphous forms are high energy solids and tend to recry stallize. New...... formulation principles are needed to ensure the stability of amorphous drug forms. The formation of solid dispersions is still the most investigated approach, but additional approaches are desirable to overcome the shortcomings of solid dispersions. Spatial separation by either coating or the use of micro-containers...... before single molecules are available for the formation of crystal nuclei, thus stabilizing the amorphous form....

  16. Automated Test-Form Generation

    Science.gov (United States)

    van der Linden, Wim J.; Diao, Qi

    2011-01-01

    In automated test assembly (ATA), the methodology of mixed-integer programming is used to select test items from an item bank to meet the specifications for a desired test form and optimize its measurement accuracy. The same methodology can be used to automate the formatting of the set of selected items into the actual test form. Three different…

  17. Mastering HTML5 forms

    CERN Document Server

    Gupta, Gaurav

    2013-01-01

    This tutorial will show you how to create stylish forms, not only visually appealing, but interactive and customized, in order to gather valuable user inputs and information.Enhance your skills in building responsive and dynamic web forms using HTML5, CSS3, and related technologies. All you need is a basic understanding of HTML and PHP.

  18. 49 CFR 191.19 - Report forms.

    Science.gov (United States)

    2010-10-01

    ... forms. Copies of the prescribed report forms are available without charge upon request from the address... 49 Transportation 3 2010-10-01 2010-10-01 false Report forms. 191.19 Section 191.19 Transportation... size and kind of paper. In addition, the information required by these forms may be submitted by any...

  19. Ceramic and glass radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Readey, D.W.; Cooley, C.R. (comps.)

    1977-01-01

    This report contains 14 individual presentations and 6 group reports on the subject of glass and polycrystalline ceramic radioactive waste forms. It was the general consensus that the information available on glass as a waste form provided a good basis for planning on the use of glass as an initial waste form, that crystalline ceramic forms could also be good waste forms if much more development work were completed, and that prediction of the chemical and physical stability of the waste form far into the future would be much improved if the basic synergistic effects of low temperature, radiation and long times were better understood. Continuing development of the polycrystalline ceramic forms was recommended. It was concluded that the leach rate of radioactive species from the waste form is an important criterion for evaluating its suitability, particularly for the time period before solidified waste is permanently placed in the geologic isolation of a Federal repository. Separate abstracts were prepared for 12 of the individual papers; the remaining two were previously abstracted.

  20. N-terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

    Science.gov (United States)

    Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

    2016-01-01

    Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

  1. Secondary Waste Form Down-Selection Data Package—Fluidized Bed Steam Reforming Waste Form

    Energy Technology Data Exchange (ETDEWEB)

    Qafoku, Nikolla; Westsik, Joseph H.; Strachan, Denis M.; Valenta, Michelle M.; Pires, Richard P.

    2011-09-12

    The Hanford Site in southeast Washington State has 56 million gallons of radioactive and chemically hazardous wastes stored in 177 underground tanks (ORP 2010). The U.S. Department of Energy (DOE), Office of River Protection (ORP), through its contractors, is constructing the Hanford Tank Waste Treatment and Immobilization Plant (WTP) to convert the radioactive and hazardous wastes into stable glass waste forms for disposal. Within the WTP, the pretreatment facility will receive the retrieved waste from the tank farms and separate it into two treated process streams. These waste streams will be vitrified, and the resulting waste canisters will be sent to offsite (high-level waste [HLW]) and onsite (immobilized low-activity waste [ILAW]) repositories. As part of the pretreatment and ILAW processing, liquid secondary wastes will be generated that will be transferred to the Effluent Treatment Facility (ETF) on the Hanford Site for further treatment. These liquid secondary wastes will be converted to stable solid waste forms that will be disposed of in the Integrated Disposal Facility (IDF). To support the selection of a waste form for the liquid secondary wastes from WTP, Washington River Protection Solutions (WRPS) has initiated secondary waste form testing work at Pacific Northwest National Laboratory (PNNL). In anticipation of a down-selection process for a waste form for the Solidification Treatment Unit to be added to the ETF, PNNL is developing data packages to support that down-selection. The objective of the data packages is to identify, evaluate, and summarize the existing information on the four waste forms being considered for stabilizing and solidifying the liquid secondary wastes. At the Hanford Site, the FBSR process is being evaluated as a supplemental technology for treating and immobilizing Hanford LAW radioactive tank waste and for treating secondary wastes from the WTP pretreatment and LAW vitrification processes.

  2. An unusual dimeric structure and assembly for TLR4 regulator RP105-MD-1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Hong, Minsun; Wilson, Ian A [Scripps

    2011-11-16

    RP105-MD-1 modulates the TLR4-MD-2-mediated, innate immune response against bacterial lipopolysaccharide (LPS). The crystal structure of the bovine 1:1 RP105-MD-1 complex bound to a putative endogenous lipid at 2.9 Å resolution shares a similar overall architecture to its homolog TLR4-MD-2 but assembles into an unusual 2:2 homodimer that differs from any other known TLR-ligand assembly. The homodimer is assembled in a head-to-head orientation that juxtaposes the N-terminal leucine-rich repeats (LRRs) of the two RP105 chains, rather than the usual tail-to-tail configuration of C-terminal LRRs in ligand-activated TLR dimers, such as TLR1-TRL2, TLR2-TLR6, TLR3-TLR3 and TLR4-TLR4. Another unusual interaction is mediated by an RP105-specific asparagine-linked glycan, which wedges MD-1 into the co-receptor binding concavity on RP105. This unique mode of assembly represents a new paradigm for TLR complexes and suggests a molecular mechanism for regulating LPS responses.

  3. Thermoelectric generator and method of forming same

    International Nuclear Information System (INIS)

    Wilson, K.T.

    1981-01-01

    A thermoelectric device is disclosed which comprises the formation of a multiplicity of thermocouples on a substrate in a narrow strip form, the thermocouples being formed by printing with first and second inks formed of suitable different powdered metals with a proper binder or flux. The thermocouples are formed in series and the opposed coupled areas are melted to form an intermingling of the two metals and the strips may be formed in substantial lengths and rolled onto a reel, or in relatively short strip form and disposed in a side-by-side abutting relationship in substantial numbers to define a generally rectangular panel form with opposed ends in electrical connection. The method of forming the panels includes the steps of feeding a suitable substrate, either in a continuous roll or sheet form, through first and second printers to form the series connected multiplicity of thermocouples thereon. From the printers the sheet or strip passes through a melter such as an induction furnace and from the furnace it passes through a sheeter, if the strip is in roll form. The sheets are then slit into narrow strips relative to the thermocouples, printed thereon and the strips are then formed into a bundle. A predetermined number of bundles are assembled into a panel form

  4. Waste-form development

    International Nuclear Information System (INIS)

    Neilson, R.M. Jr.; Colombo, P.

    1982-01-01

    Contemporary solidification agents are being investigated relative to their applications to major fuel cycle and non-fuel cycle low-level waste (LLW) streams. Work is being conducted to determine the range of conditions under which these solidification agents can be applied to specific LLW streams. These studies are directed primarily towards defining operating parameters for both improved solidification of problem wastes and solidification of new LLW streams generated from advanced volume reduction technologies. Work is being conducted to measure relevant waste form properties. These data will be compiled and evaluated to demonstrate compliance with waste form performance and shallow land burial acceptance criteria and transportation requirements

  5. Comparative analysis of JKR Sarawak form of contract and Malaysia Standard form of building contract (PWD203A)

    Science.gov (United States)

    Yunus, A. I. A.; Muhammad, W. M. N. W.; Saaid, M. N. F.

    2018-04-01

    Standard form of contract is normally being used in Malaysia construction industry in establishing legal relation between contracting parties. Generally, most of Malaysia federal government construction project used PWD203A which is a standard form of contract to be used where Bills of Quantities Form Part of the Contract and it is issued by Public Works Department (PWD/JKR). On the other hand in Sarawak, the largest state in Malaysia, the state government has issued their own standard form of contract namely JKR Sarawak Form of Contract 2006. Even both forms have been used widely in construction industry; there is still lack of understanding on both forms. The aim of this paper is to identify significant provision on both forms of contract. Document analysis has been adopted in conducting an in-depth review on both forms. It is found that, both forms of contracts have differences and similarities on several provisions specifically matters to definitions and general; execution of the works; payments, completion and final account; and delay, dispute resolution and determination.

  6. Physical forms of MIPs.

    Science.gov (United States)

    Biffis, Andrea; Dvorakova, Gita; Falcimaigne-Cordin, Aude

    2012-01-01

    The current state of the art in the development of methodologies for the preparation of MIPs in predetermined physical forms is critically reviewed, with particular attention being paid to the forms most widely employed in practical applications, such as spherical beads in the micro- to nanometer range, microgels, monoliths, membranes. Although applications of the various MIP physical forms are mentioned, the focus of the paper is mainly on the description of the various preparative methods. The aim is to provide the reader with an overview of the latest achievements in the field, as well as with a mean for critically evaluating the various proposed methodologies towards an envisaged application. The review covers the literature up to early 2010, with special emphasis on the developments of the last 10 years.

  7. Two novel antimicrobial defensins from rice identified by gene coexpression network analyses.

    Science.gov (United States)

    Tantong, Supaluk; Pringsulaka, Onanong; Weerawanich, Kamonwan; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Sarnthima, Rakrudee; Roytrakul, Sittiruk; Sirikantaramas, Supaart

    2016-10-01

    Defensins form an antimicrobial peptides (AMP) family, and have been widely studied in various plants because of their considerable inhibitory functions. However, their roles in rice (Oryza sativa L.) have not been characterized, even though rice is one of the most important staple crops that is susceptible to damaging infections. Additionally, a previous study identified 598 rice genes encoding cysteine-rich peptides, suggesting there are several uncharacterized AMPs in rice. We performed in silico gene expression and coexpression network analyses of all genes encoding defensin and defensin-like peptides, and determined that OsDEF7 and OsDEF8 are coexpressed with pathogen-responsive genes. Recombinant OsDEF7 and OsDEF8 could form homodimers. They inhibited the growth of the bacteria Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, and Erwinia carotovora subsp. atroseptica with minimum inhibitory concentration (MIC) ranging from 0.6 to 63μg/mL. However, these OsDEFs are weakly active against the phytopathogenic fungi Helminthosporium oryzae and Fusarium oxysporum f.sp. cubense. This study describes a useful method for identifying potential plant AMPs with biological activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The yeast cell fusion protein Prm1p requires covalent dimerization to promote membrane fusion.

    Directory of Open Access Journals (Sweden)

    Alex Engel

    2010-05-01

    Full Text Available Prm1p is a multipass membrane protein that promotes plasma membrane fusion during yeast mating. The mechanism by which Prm1p and other putative regulators of developmentally controlled cell-cell fusion events facilitate membrane fusion has remained largely elusive. Here, we report that Prm1p forms covalently linked homodimers. Covalent Prm1p dimer formation occurs via intermolecular disulfide bonds of two cysteines, Cys-120 and Cys-545. PRM1 mutants in which these cysteines have been substituted are fusion defective. These PRM1 mutants are normally expressed, retain homotypic interaction and can traffic to the fusion zone. Because prm1-C120S and prm1-C545S mutants can form covalent dimers when coexpressed with wild-type PRM1, an intermolecular C120-C545 disulfide linkage is inferred. Cys-120 is adjacent to a highly conserved hydrophobic domain. Mutation of a charged residue within this hydrophobic domain abrogates formation of covalent dimers, trafficking to the fusion zone, and fusion-promoting activity. The importance of intermolecular disulfide bonding informs models regarding the mechanism of Prm1-mediated cell-cell fusion.

  9. Structure of N-acetyl-[beta]-D-glucosaminidase (GcnA) from the Endocarditis Pathogen Streptococcus gordonii and its Complex with the Mechanism-based Inhibitor NAG-thiazoline

    Energy Technology Data Exchange (ETDEWEB)

    Langley, David B.; Harty, Derek W.S.; Jacques, Nicholas A.; Hunter, Neil; Guss, J. Mitchell; Collyer, Charles A. (Sydney); (Westmead)

    2008-09-17

    The crystal structure of GcnA, an N-acetyl-{beta}-D-glucosaminidase from Streptococcus gordonii, was solved by multiple wavelength anomalous dispersion phasing using crystals of selenomethionine-substituted protein. GcnA is a homodimer with subunits each comprised of three domains. The structure of the C-terminal {alpha}-helical domain has not been observed previously and forms a large dimerization interface. The fold of the N-terminal domain is observed in all structurally related glycosidases although its function is unknown. The central domain has a canonical ({beta}/{alpha}){sub 8} TIM-barrel fold which harbours the active site. The primary sequence and structure of this central domain identifies the enzyme as a family 20 glycosidase. Key residues implicated in catalysis have different conformations in two different crystal forms, which probably represent active and inactive conformations of the enzyme. The catalytic mechanism for this class of glycoside hydrolase, where the substrate rather than the enzyme provides the cleavage-inducing nucleophile, has been confirmed by the structure of GcnA complexed with a putative reaction intermediate analogue, N-acetyl-{beta}-D-glucosamine-thiazoline. The catalytic mechanism is discussed in light of these and other family 20 structures.

  10. Topography and stoichiometry of acidic proteins in large ribosomal subunits from Artemia salina as determined by crosslinking

    International Nuclear Information System (INIS)

    Uchiumi, T.; Wahba, A.J.; Traut, R.R.

    1987-01-01

    The 60S subunits isolated from Artemia salina ribosomes were treated with the crosslinking reagent 2-iminothiolane under mild conditions. Proteins were extracted and fractions containing crosslinked acidic proteins were obtained by stepwise elution from CM-cellulose. Each fraction was analyzed by diagonal (two-dimensional nonreducing-reducing) NaDodSO 4 /polyacrylamide gel electrophoresis. Crosslinked proteins below the diagonal were radioiodinated and identified by two-dimensional acidic urea-NaDodSO 4 gel electrophoresis. Each of the acidic proteins P1 and P2 was crosslinked individually to the same third protein, PO. The fractions containing acidic proteins were also analyzed by two-dimensional nonequilibrium isoelectric focusing-NaDodSO 4 /polyacrylamide gel electrophoresis. Two crosslinked complexes were observed that coincide in isoelectric positions with monomeric P1 and P2, respectively. Both P1 and P2 appear to form crosslinked homodimers. These results suggest the presence in the 60S subunit of (P1) 2 and (P2) 2 dimers, each of which is anchored to PO. Protein PO appears to play the same role as L10 in Escherichia coli ribosomes and may form a pentameric complex with the two dimers in the 60S subunits

  11. TRASYS form factor matrix normalization

    Science.gov (United States)

    Tsuyuki, Glenn T.

    1992-01-01

    A method has been developed for adjusting a TRASYS enclosure form factor matrix to unity. This approach is not limited to closed geometries, and in fact, it is primarily intended for use with open geometries. The purpose of this approach is to prevent optimistic form factors to space. In this method, nodal form factor sums are calculated within 0.05 of unity using TRASYS, although deviations as large as 0.10 may be acceptable, and then, a process is employed to distribute the difference amongst the nodes. A specific example has been analyzed with this method, and a comparison was performed with a standard approach for calculating radiation conductors. In this comparison, hot and cold case temperatures were determined. Exterior nodes exhibited temperature differences as large as 7 C and 3 C for the hot and cold cases, respectively when compared with the standard approach, while interior nodes demonstrated temperature differences from 0 C to 5 C. These results indicate that temperature predictions can be artificially biased if the form factor computation error is lumped into the individual form factors to space.

  12. Effect of food service form on eating rate: meal served in a separated form might lower eating rate.

    Science.gov (United States)

    Suh, Hyung Joo; Jung, Eun Young

    2016-01-01

    In this study, we investigated the association between food form (mixed vs separated) and eating rate. The experiment used a within-subjects design (n=29, young healthy women with normal weight). Test meals (white rice and side dishes) with the same content and volume were served at lunch in a mixed or separated form. The form in which the food was served had significant effects on consumption volume and eating rate; subjects ate significantly more (p<0.05) when a test meal was served as a mixed form (285 g, 575 kcal) compared to a separated form (244 g, 492 kcal). Moreover, subjects also ate significantly faster (p<0.05) when the test meal was served as a mixed form (22.4 g/min) as compared to a separated form (16.2 g/min). Despite consuming more when the test meal was served as a mixed form than when served as a separated form, the subjects did not feel significantly fuller. In conclusion, we confirmed that meals served in a separated form might lower the eating rate and, moreover, slower eating might be associated with less energy intake, without compromising satiety.

  13. Relationship Domain of Form Six Teachers Thinking in Teaching with External Factors of Form Six Teachers

    Science.gov (United States)

    bin Pet, Mokhtar; Sihes, Ahmad Johari Hj

    2015-01-01

    This study aims to examine the external factors of form six teachers who can influence thinking domain form six teachers in their teaching. This study was conducted using a quantitative approach using questionnaires. A total of 300 form six teacher schools in Johor were chosen as respondents. The findings were obtained as student background…

  14. Spin-forming Project Report

    Energy Technology Data Exchange (ETDEWEB)

    Switzner, Nathan; Henry, Dick

    2009-03-20

    In a second development order, spin-forming equipment was again evaluated using the test shape, a hemispherical shell. In this second development order, pure vanadium and alloy titanium (Ti-6Al-4V) were spin-formed, as well as additional copper and 21-6-9 stainless. In the first development order the following materials had been spin-formed: copper (alloy C11000 ETP), 6061 aluminum, 304L stainless steel, 21-6-9 stainless steel, and tantalum-2.5% tungsten. Significant challenges included properly adjusting the rotations-per-minute (RPM), cracking at un-beveled edges and laser marks, redressing of notches, surface cracking, non-uniform temperature evolution in the titanium, and cracking of the tailstock. Lessons learned were that 300 RPM worked better than 600 RPM for most materials (at the feed rate of 800 mm/min); beveling the edges to lower the stress reduces edge cracking; notches, laser marks, or edge defects in the preform doom the process to cracking and failure; coolant is required for vanadium spin-forming; increasing the number of passes to nine or more eliminates surface cracking for vanadium; titanium develops a hot zone in front of the rollers; and the tailstock should be redesigned to eliminate the cylindrical stress concentrator in the center.

  15. Methods for forming particles

    Science.gov (United States)

    Fox, Robert V.; Zhang, Fengyan; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin

    2016-06-21

    Single source precursors or pre-copolymers of single source precursors are subjected to microwave radiation to form particles of a I-III-VI.sub.2 material. Such particles may be formed in a wurtzite phase and may be converted to a chalcopyrite phase by, for example, exposure to heat. The particles in the wurtzite phase may have a substantially hexagonal shape that enables stacking into ordered layers. The particles in the wurtzite phase may be mixed with particles in the chalcopyrite phase (i.e., chalcopyrite nanoparticles) that may fill voids within the ordered layers of the particles in the wurtzite phase thus produce films with good coverage. In some embodiments, the methods are used to form layers of semiconductor materials comprising a I-III-VI.sub.2 material. Devices such as, for example, thin-film solar cells may be fabricated using such methods.

  16. Differential forms theory and practice

    CERN Document Server

    Weintraub, Steven H

    2014-01-01

    Differential forms are utilized as a mathematical technique to help students, researchers, and engineers analyze and interpret problems where abstract spaces and structures are concerned, and when questions of shape, size, and relative positions are involved. Differential Forms has gained high recognition in the mathematical and scientific community as a powerful computational tool in solving research problems and simplifying very abstract problems through mathematical analysis on a computer. Differential Forms, 2nd Edition, is a solid resource for students and professionals needing a solid g

  17. Forming Refractory Insulation On Copper Wire

    Science.gov (United States)

    Setlock, J.; Roberts, G.

    1995-01-01

    Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

  18. FormCalc 9 and extensions

    International Nuclear Information System (INIS)

    Hahn, T.; Passehr, S.; Schappacher, C.

    2016-04-01

    We present Version 9 of the Feynman-diagram calculator FormCalc and a flexible new suite of shell scripts and Mathematica packages based on FormCalc, which can be adapted and used as a template for calculations.

  19. Ore-forming environment and ore-forming system of carbonaceous-siliceous-pelitic rock type uranium deposit in China

    International Nuclear Information System (INIS)

    Qi Fucheng; Zhang Zilong; Li Zhixing; He Zhongbo; Wang Wenquan

    2012-01-01

    It is proposed that there are four types of ore-forming systems about carbonaceous-siliceous-pelitic rock type uranium deposit in China based on systematic study on structural environment and distribution regularity of uraniferous construction of marine carbonaceous-siliceous-pelitic rock in China: continental margin rift valley ore-forming systems, continental margin rifting deep fracture zone ore-forming systems, landmass boundary borderland basin ore-forming systems and epicontinental mobile belt downfaulted aulacogen ore-forming systems. It is propounded definitely that it is controlled by margin rift valley ore-forming systems and continental margin rifting deep fracture zone ore-forming systems for large-scale uranium mineralization of carbonaceous-siliceous-pelitic rock type uranium deposit in China, which is also controlled by uraniferous marine carbonaceous-siliceous-pelitic rock construction made up of silicalite, siliceous phosphorite and carbonaceous-siliceous-pelitic rock, which settled down accompany with submarine backwash and sub marine volcanic eruption in margin rift valley and continental margin rifting mineralizing environment. Continental mar gin rift valley and continental margin rifting thermal sedimentation or exhalation sedimentation is the mechanism of forming large-scale uraniferous marine carbonaceous-siliceous-pelitic rock construction Early Palaeozoic Era in China or large-scale uranium-polymetallic mineralization. (authors)

  20. Article and method of forming an article

    Science.gov (United States)

    Lacy, Benjamin Paul; Kottilingam, Srikanth Chandrudu; Dutta, Sandip; Schick, David Edward

    2017-12-26

    Provided are an article and a method of forming an article. The method includes providing a metallic powder, heating the metallic powder to a temperature sufficient to joint at least a portion of the metallic powder to form an initial layer, sequentially forming additional layers in a build direction by providing a distributed layer of the metallic powder over the initial layer and heating the distributed layer of the metallic powder, repeating the steps of sequentially forming the additional layers in the build direction to form a portion of the article having a hollow space formed in the build direction, and forming an overhang feature extending into the hollow space. The article includes an article formed by the method described herein.

  1. Form factors in (HI,HI') direct reactions

    International Nuclear Information System (INIS)

    Chu, Y.H.

    1981-01-01

    Using the semiclassical theory, the inelastic transition form factors are analyzed. For the first order form factors, we find that: (i) In the strong absorption limit, the Austern-Blair theory is a good approximation to the inelastic form factor--even in highly mismatched reactions. (ii) In weak to moderate absorption, the amplitude of the inelastic form factor oscillates due to overlapping potential resonances. The internal part of the form factor can be expressed in a simple form, which may easily be used to analyze heavy-ion inelastic scattering. (iii) In the presence of an isolated resonance, the inelastic form factor is enhanced greatly at the resonance due to multiple reflections inside the potential well. The second order form factors contain two terms, i.e. the one-step direct process (OSD) term and the two-step process (TS) term. It is found that: (i) In the strong absorption limit, OSD and TS form factors are equally important and interfere destructively near the grazing angular momentum. The Austern-Blair theory gives satisfactory results for well-matched reactions. The angular distributions of the mutual and double excitations are out of phase compared with that of the single excitation. (ii) For the weak absorption case, the internal part of the TS form factor is so enhanced that the OSD form factor can simply be neglected. The internal TS form factor can be parameterized in a form proportional to the internal-wave elastic Smatrix, where the angular distribution shows characteristically refractive phenomenon

  2. Standardized waste form test methods

    International Nuclear Information System (INIS)

    Slate, S.C.

    1984-01-01

    The Materials Characterization Center (MCC) is developing standard tests to characterize nuclear waste forms. Development of the first thirteen tests was originally initiated to provide data to compare different high-level waste (HLW) forms and to characterize their basic performance. The current status of the first thirteen MCC tests and some sample test results are presented: the radiation stability tests (MCC-6 and 12) and the tensile-strength test (MCC-11) are approved; the static leach tests (MCC-1, 2, and 3) are being reviewed for full approval; the thermal stability (MCC-7) and microstructure evaluation (MCC-13) methods are being considered for the first time; and the flowing leach test methods (MCC-4 and 5), the gas generation methods (MCC-8 and 9), and the brittle fracture method (MCC-10) are indefinitely delayed. Sample static leach test data on the ARM-1 approved reference material are presented. Established tests and proposed new tests will be used to meet new testing needs. For waste form production, tests on stability and composition measurement are needed to provide data to ensure waste form quality. In transporation, data are needed to evaluate the effects of accidents on canisterized waste forms. The new MCC-15 accident test method and some data are presented. Compliance testing needs required by the recent draft repository waste acceptance specifications are described. These specifications will control waste form contents, processing, and performance

  3. Standardized waste form test methods

    International Nuclear Information System (INIS)

    Slate, S.C.

    1984-11-01

    The Materials Characterization Center (MCC) is developing standard tests to characterize nuclear waste forms. Development of the first thirteen tests was originally initiated to provide data to compare different high-level waste (HLW) forms and to characterize their basic performance. The current status of the first thirteen MCC tests and some sample test results is presented: The radiation stability tests (MCC-6 and 12) and the tensile-strength test (MCC-11) are approved; the static leach tests (MCC-1, 2, and 3) are being reviewed for full approval; the thermal stability (MCC-7) and microstructure evaluation (MCC-13) methods are being considered for the first time; and the flowing leach tests methods (MCC-4 and 5), the gas generation methods (MCC-8 and 9), and the brittle fracture method (MCC-10) are indefinitely delayed. Sample static leach test data on the ARM-1 approved reference material are presented. Established tests and proposed new tests will be used to meet new testing needs. For waste form production, tests on stability and composition measurement are needed to provide data to ensure waste form quality. In transportation, data are needed to evaluate the effects of accidents on canisterized waste forms. The new MCC-15 accident test method and some data are presented. Compliance testing needs required by the recent draft repository waste acceptance specifications are described. These specifications will control waste form contents, processing, and performance. 2 references, 2 figures

  4. New CERN Health Insurance Scheme (CHIS) forms

    CERN Multimedia

    HR Department

    2015-01-01

    New versions of the following forms for claims and requests to the CERN Health Insurance Scheme (CHIS) have been released:   form for claiming reimbursement of medical expenses,   form for requesting advance reimbursement, and   dental estimate form (for treatments foreseen to exceed 800 CHF).   The new forms are available in French and English. They can either be completed electronically before being printed and signed, or completed in paper form. New detailed instructions can be found at the back of the claim form; CHIS members are invited to read them carefully. The electronic versions (PDF) of all the forms are available on the CHIS website and on the UNIQA Member Portal. CHIS Members are requested to use these new forms forthwith and to discard any previous version. Questions regarding the above should be addressed directly to UNIQA (72730 or 022.718 63 00 or uniqa.assurances@cern.ch).

  5. Cubical version of combinatorial differential forms

    DEFF Research Database (Denmark)

    Kock, Anders

    2010-01-01

    The theory of combinatorial differential forms is usually presented in simplicial terms. We present here a cubical version; it depends on the possibility of forming affine combinations of mutual neighbour points in a manifold, in the context of synthetic differential geometry.......The theory of combinatorial differential forms is usually presented in simplicial terms. We present here a cubical version; it depends on the possibility of forming affine combinations of mutual neighbour points in a manifold, in the context of synthetic differential geometry....

  6. 48 CFR 53.301-1427 - Standard Form 1427, Inventory Schedule A-Construction Sheet (Metals in Mill Product Form).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Standard Form 1427, Inventory Schedule A-Construction Sheet (Metals in Mill Product Form). 53.301-1427 Section 53.301-1427... Illustrations of Forms 53.301-1427 Standard Form 1427, Inventory Schedule A—Construction Sheet (Metals in Mill...

  7. 49 CFR 387.413 - Forms and procedure.

    Science.gov (United States)

    2010-10-01

    ... Forms and procedures. (f) Termination of Forms BMC-32 and BMC-34 for freight forwarders of property other than household goods. Form BMC-32 endorsements and Form BMC-34 certificates of insurance issued to...

  8. Waste form development

    International Nuclear Information System (INIS)

    Neilson, R.M. Jr.; Colombo, P.

    1982-01-01

    In this program, contemporary solidification agents are being investigated relative to their applications to major fuel cycle and non-fuel cycle low-level waste (LLW) streams. Work is being conducted to determine the range of conditions under which these solidification agents can be applied to specific LLW streams. These studies are directed primarily towards defining operating parameters for both improved solidification of problem wastes and solidification of new LLW streams generated from advanced volume reduction technologies. Work is being conducted to measure relevant waste form properties. These data will be compiled and evaluated to demonstrate compliance with waste form performance and shallow land burial acceptance criteria and transportation requirements (both as they exist and as they are modified with time). 6 tables

  9. Electromagnetic form factors

    International Nuclear Information System (INIS)

    Desplanques, B.

    1987-01-01

    Electromagnetic form factors, in first approximation, are sensitive to spatial distribution of nucleons and to their current. In second approximation, more precise effects are concerned, whose role is increasing with momentum transfer and participating essentially of short range nuclei description. They concern of course the nucleon-nucleon interaction while approaching each other and keeping their free-state identity, but also mutually polarizing one the other. In this last effect, radial and orbital excitations of nucleon, the nucleon mesonic cloud modification and the nucleon antinucleon pair excitation are included. In this paper, these contributions are discussed while trying to find the important elements for a good description of form factors. Current questions are also discussed. Light nuclei are essentially concerned [fr

  10. Review of high-level waste form properties

    International Nuclear Information System (INIS)

    Rusin, J.M.

    1980-12-01

    This report is a review of waste form options for the immobilization of high-level-liquid wastes from the nuclear fuel cycle. This review covers the status of international research and development on waste forms as of May 1979. Although the emphasis in this report is on waste form properties, process parameters are discussed where they may affect final waste form properties. A summary table is provided listing properties of various nuclear waste form options. It is concluded that proposed waste forms have properties falling within a relatively narrow range. In regard to crystalline versus glass waste forms, the conclusion is that either glass of crystalline materials can be shown to have some advantage when a single property is considered; however, at this date no single waste form offers optimum properties over the entire range of characteristics investigated. A long-term effort has been applied to the development of glass and calcine waste forms. Several additional waste forms have enough promise to warrant continued research and development to bring their state of development up to that of glass and calcine. Synthetic minerals, the multibarrier approach with coated particles in a metal matrix, and high pressure-high temperature ceramics offer potential advantages and need further study. Although this report discusses waste form properties, the total waste management system should be considered in the final selection of a waste form option. Canister design, canister materials, overpacks, engineered barriers, and repository characteristics, as well as the waste form, affect the overall performance of a waste management system. These parameters were not considered in this comparison

  11. High-level waste-form-product performance evaluation

    International Nuclear Information System (INIS)

    Bernadzikowski, T.A.; Allender, J.S.; Stone, J.A.; Gordon, D.E.; Gould, T.H. Jr.; Westberry, C.F. III.

    1982-01-01

    Seven candidate waste forms were evaluated for immobilization and geologic disposal of high-level radioactive wastes. The waste forms were compared on the basis of leach resistance, mechanical stability, and waste loading. All forms performed well at leaching temperatures of 40, 90, and 150 0 C. Ceramic forms ranked highest, followed by glasses, a metal matrix form, and concrete. 11 tables

  12. Current assisted superplastic forming of titanium alloy

    Directory of Open Access Journals (Sweden)

    Wang Guofeng

    2015-01-01

    Full Text Available Current assisted superplastic forming combines electric heating technology and superplastic forming technology, and can overcome some shortcomings of traditional superplastic forming effectively, such as slow heating rate, large energy loss, low production efficiency, etc. Since formability of titanium alloy at room temperature is poor, current assisted superplastic forming is suitable for titanium alloy. This paper mainly introduces the application of current assisted superplastic forming in the field of titanium alloy, including forming technology of double-hemisphere structure and bellows.

  13. Developing the Scale for Quality of Life in Pediatric Oncology Patients Aged 13-18: Adolescent Form and Parent Form.

    Science.gov (United States)

    Bektas, Murat; Akdeniz Kudubes, Aslı; Ugur, Ozlem; Vergin, Canan; Demirag, Bengü

    2016-06-01

    This study aimed to develop the Scale for Quality of Life in Pediatric Oncology Patients Aged 13-18: Adolescent Form and Parent Form. We used the child and parent information form, Visual Quality of Life Scale, and our own scale, the Scale for Quality of Life in Pediatric Oncology Patients Aged 13-18: Adolescent Form and Parent Form. We finalized the 35-item scale to determine the items, received opinions from 14 specialists on the scale, and pilot-tested the scale in 25 children and their parents. We used Pearson correlation analysis, Cronbach α coefficient, factor analysis and receiver operating characteristics analysis to analyze the data. The total Cronbach α of the parent form was .97, the total factor load was .60-.97 and the total variance was 80.4%. The cutoff point of the parent form was 85.50. The total Cronbach α of the adolescent form was .98, the total factor load was .62-.96, and the total variance explained was 83.4%. The cutoff point of the adolescent form was 75.50. As a result of the parent form factor analysis, we determined the Kaiser-Meyer-Olkin coefficient as .83, the Barlett test χ(2) as 12,615.92; the factor coefficients of all items of the parent form ranged from .63 to .98. The factor coefficients of all items of the adolescent form ranged from .34 to .99. As a result of the adolescent form factor analysis, we determined the KMO as .79, and the Barlett test χ(2) as 13,970.62. Conclusively, we found that the adolescent form and the parent form were valid and reliable in assessing the children's quality of life. Copyright © 2016. Published by Elsevier B.V.

  14. Comparative assessment of TRU waste forms and processes. Volume I. Waste form and process evaluations

    International Nuclear Information System (INIS)

    Ross, W.A.; Lokken, R.O.; May, R.P.; Roberts, F.P.; Timmerman, C.L.; Treat, R.L.; Westsik, J.H. Jr.

    1982-09-01

    This study provides an assesses seven waste forms and eight processes for immobilizing transuranic (TRU) wastes. The waste forms considered are cast cement, cold-pressed cement, FUETAP (formed under elevated temperature and pressure) cement, borosilicate glass, aluminosilicate glass, basalt glass-ceramic, and cold-pressed and sintered silicate ceramic. The waste-immobilization processes considered are in-can glass melting, joule-heated glass melting, glass marble forming, cement casting, cement cold-pressing, FUETAP cement processing, ceramic cold-pressing and sintering, basalt glass-ceramic processing. Properties considered included gas generation, chemical durability, mechanical strength, thermal stability, and radiation stability. The ceramic products demonstrated the best properties, except for plutonium release during leaching. The glass and ceramic products had similar properties. The cement products generally had poorer properties than the other forms, except for plutonium release during leaching. Calculations of the Pu release indicated that the waste forms met the proposed NRC release rate limit of 1 part in 10 5 per year in most test conditions. The cast-cement process had the lowest processing cost, followed closely by the cold-pressed and FUETAP cement processes. Joule-heated glass melting had the lower cost of the glass processes. In-can melting in a high-quality canister had the highest cost, and cold-pressed and sintered ceramic the second highest. Labor and canister costs for in-can melting were identified. The major contributor to costs of disposing of TRU wastes in a defense waste repository is waste processing costs. Repository costs could become the dominant cost for disposing of TRU wastes in a commercial repository. It is recommended that cast and FUETAP cement and borosilicate glass waste-form systems be considered. 13 figures, 16 tables

  15. Regulation of CCR7-dependent cell migration through?CCR7 homodimer formation

    OpenAIRE

    Kobayashi, Daichi; Endo, Masataka; Ochi, Hirotaka; Hojo, Hironobu; Miyasaka, Masayuki; Hayasaka, Haruko

    2017-01-01

    The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers,...

  16. Microdomain forming proteins in oncogenesis

    Directory of Open Access Journals (Sweden)

    I. B. Zborovskaya

    2016-01-01

    Full Text Available Lipid rafts are lateral assembles of cholesterol, sphingomyelin, glicosphingolipids and specific proteins within cell plasma membrane. These microdomains are involved into a number of important cellular processes including membrane rearrangement, protein internalization, signal transduction, entry of viruses into the cell. Some of lipid rafts are stabilized by special microdomain-forming proteins such as caveolins, SPFH domain containing superfamily, tetraspanins, galectins, which maintain integrity of rafts and regulate signal transduction via forming of “signalosomes”. Involvement of the different lipid rafts is necessary in many situations such as binding of growth factors with their receptors, integrin regulation, cytoskeleton and extracellular matrix rearrangements, vesicular transport, etc. However, such classes of microdomain-forming proteins are still considered separately from each other. In this review we tried to perform complex analysis of microdomain-forming proteins in regulation of cancer assotiated processes.

  17. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Vognsen, Tina, E-mail: tv@farma.ku.dk [Biostructural Research, Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Kristensen, Ole, E-mail: ok@farma.ku.dk [Biostructural Research, Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer The crystal structure of the NTF2-like domain of Rasputin protein is presented. Black-Right-Pointing-Pointer Differences to known ligand binding sites of nuclear transport factor 2 are discussed. Black-Right-Pointing-Pointer A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 A resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a {beta}-sheet and three {alpha}-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

  18. Iodine bonding stabilizes iodomethane in MIDAS pesticide. Theoretical study of intermolecular interactions between iodomethane and chloropicrin.

    Science.gov (United States)

    Glaser, Rainer; Prugger, Kaitlan

    2012-02-22

    The results are reported of a theoretical study of iodomethane (H(3)C-I, 1) and chloropicrin (Cl(3)C-NO(2), 2), of the heterodimers 3-6 formed by aggregation of 1 and 2, and of their addition products 7 and 8 and their possible fragmentation reactions to 9-18. Mixtures of iodomethane and chloropicrin are not expected to show chemistry resulting from their reactions with each other. The structures and stabilities are discussed of the iodine-bonded molecular aggregates (IBMA) 3 and 4 and of the hydrogen- and iodine-bonded molecular aggregates (IHBMA) 5 and 6. The mixed aggregates 3-5 are bound on the free enthalpy surface relative to the homodimers of 1 and 2, and the IBMA structures 3 and 4 are most stable. This result suggests that the mixture of chloropicrin and iodomethane in the pesticide Midas is a good choice to reduce the volatility of iodomethane because of thermodynamically stabilizing iodine bonding.

  19. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

    Science.gov (United States)

    Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

    2015-01-01

    Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

  20. Structure of the intact ATM/Tel1 kinase

    Science.gov (United States)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-01

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  1. 25 CFR 67.6 - Application forms.

    Science.gov (United States)

    2010-04-01

    ... application form is filed by a sponsor, the name and address of the sponsor and the sponsor's relationship to... the applicant's mailing address on the application form. Thereafter, the applicant or sponsor shall... applicant. Otherwise, the mailing address as stated on the application form shall be accepted as the address...

  2. 25 CFR 61.6 - Application forms.

    Science.gov (United States)

    2010-04-01

    ... is claimed. (2) If the application form is filed by a sponsor, the name and address of sponsor and... furnish the applicant's mailing address on the application form. Thereafter, the applicant or sponsor... identification of the application, otherwise the mailing address as stated on the form shall be acceptable as the...

  3. 19 CFR 143.24 - Preparation of Customs Form 7501 and Customs Form 368 or 368A (serially numbered).

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Preparation of Customs Form 7501 and Customs Form 368 or 368A (serially numbered). 143.24 Section 143.24 Customs Duties U.S. CUSTOMS AND BORDER... Informal Entry § 143.24 Preparation of Customs Form 7501 and Customs Form 368 or 368A (serially numbered...

  4. Method of forming composite fiber blends

    Science.gov (United States)

    McMahon, Paul E. (Inventor); Chung, Tai-Shung (Inventor); Ying, Lincoln (Inventor)

    1989-01-01

    The instant invention involves a process used in preparing fibrous tows which may be formed into polymeric plastic composites. The process involves the steps of (a) forming a tow of strong filamentary materials; (b) forming a thermoplastic polymeric fiber; (c) intermixing the two tows; and (d) withdrawing the intermixed tow for further use.

  5. Theory of Single Point Incremental Forming

    DEFF Research Database (Denmark)

    Martins, P.A.F.; Bay, Niels; Skjødt, Martin

    2008-01-01

    This paper presents a closed-form theoretical analysis modelling the fundamentals of single point incremental forming and explaining the experimental and numerical results available in the literature for the past couple of years. The model is based on membrane analysis with bi-directional in-plan......-plane contact friction and is focused on the extreme modes of deformation that are likely to be found in single point incremental forming processes. The overall investigation is supported by experimental work performed by the authors and data retrieved from the literature.......This paper presents a closed-form theoretical analysis modelling the fundamentals of single point incremental forming and explaining the experimental and numerical results available in the literature for the past couple of years. The model is based on membrane analysis with bi-directional in...

  6. Usability of Public Administration Electronic Forms

    Directory of Open Access Journals (Sweden)

    Miloslav Hub

    2015-06-01

    Full Text Available This paper is focused on the testing and evaluating of public administration electronic forms from the usability point of view. Its objective is to design a suitable methodology for usability testing of electronic forms and their description and distribution to public administration information systems professionals. Firstly, methods of usability engineering are summarized and a suitable method for usability testing and evaluation of electronic forms is selected. Farther, the methodology of electronic forms usability testing that uses the selected method is suggested. In the last part of the paper the case study that uses the proposed methodology is suggested and performed. The main benefit of the work is the design of testing methodology and proposition of the set of recommendations for new public administration electronic forms design.

  7. Radionuclide Retention in Concrete Waste Forms

    Energy Technology Data Exchange (ETDEWEB)

    Mattigod, Shas V.; Bovaird, Chase C.; Wellman, Dawn M.; Wood, Marcus I.

    2010-09-30

    Assessing long-term performance of Category 3 waste cement grouts for radionuclide encasement requires knowledge of the radionuclide-cement interactions and mechanisms of retention (i.e., sorption or precipitation); the mechanism of contaminant release; the significance of contaminant release pathways; how waste form performance is affected by the full range of environmental conditions within the disposal facility; the process of waste form aging under conditions that are representative of processes occurring in response to changing environmental conditions within the disposal facility; the effect of waste form aging on chemical, physical, and radiological properties; and the associated impact on contaminant release. This knowledge will enable accurate prediction of radionuclide fate when the waste forms come in contact with groundwater. The information presented in the report provides data that 1) quantify radionuclide retention within concrete waste form materials similar to those used to encapsulate waste in the Low-Level Waste Burial Grounds (LLBG); 2) measure the effect of concrete waste form properties likely to influence radionuclide migration; and 3) quantify the stability of uranium-bearing solid phases of limited solubility in concrete.

  8. A Framework for Interactively Helpful Web Forms

    DEFF Research Database (Denmark)

    Bohøj, Morten; Bouvin, Niels Olof; Gammelmark, Henrik

    2012-01-01

    AdapForms is a framework for adaptive forms, consisting of a form definition language designating structure and constraints upon acceptable input, and a software architecture that continuously validates and adapts the form presented to the user. The validation is performed server-side, which enab...

  9. Education fees – New forms

    CERN Multimedia

    2015-01-01

    The application forms for the payment of education fees have been updated and are now available in the Admin e-guide (under the “Useful Documents” heading):   Payment of education fees (including language course fees) – AC12A (form to be used by staff members recruited before 1 January 2007, with the exception of former “local staff”).   Payment of education fees – AC12B (form to be used by staff members recruited on or after 1 January 2007, by fellows, scientific associates and guest professors and by former “local staff” whose contracts started before 1 January 2007). The Education Fees service will continue to accept the old forms until the end of the current academic year, i.e. until 31 August 2015. Members of the personnel are reminded that any false declaration or failure to declare information with a view to deceiving others or achieving a gain that would result in a financial loss for CERN or...

  10. Das Zeichen als Form und die Form des Rechtszeichens / The Sign as Form and the Form of the Law Sign

    Directory of Open Access Journals (Sweden)

    Thomas-M. Seibert

    2014-03-01

    Full Text Available Diskutiert wird Luhmanns Konzept vom „Zeichen als Form“ vor dem Hintergrund der Formgebungen bei Peirce und Serres mit einem Erbschaftsfall im Vordergrund. Die These lautet: Zweiteilung als Ergebnis amputiert die grundlegende Operation der Formbildung, indem der Operator ausgesperrt wird. Operator ist der Interpretant, den Luhmann als Beobachter (unterschiedlicher Stufe anschließend wieder einführt. Aber er lässt sich nicht aussperren, er ist fortwährend anwesend – als Parasit (Serres. An einem praktischen Fall wird das demonstriert: Eine Frau in einem Heim verfasst ein Testament und setzt den Heimleiter und seine Frau als Erben ein. Man benutzt die Rechtsform formularmäßig und meint, mit diesem Formular das Testament fachgerecht zu verfassen und die Interpretation auszusperren. Das spätere Rechtsverfahren der Verwandten gegen den Heimleiter kehrt die Verhältnisse um. Die Operation, sich auf Recht als ein Objekt so zu beziehen, dass die Operation sich wie dieses Objekt auf Recht bezieht und damit selbst zu einem Rechtszeichen wird (Peirce, ist parasitär. Sie plant ungeplante, überraschende Störungen ein. Luhmann’s concept of the „sign as form“ is discussed in the broader context of Peirce and Serres’ concepts of formation, with an inheritance in the foreground. The assertion is: bifurcation as a result amputates the fundamental operation of form-building by excluding the operator. The operator is the interpretant, who Luhmann subsequently re-introduces as an observer (at a different level. But the interpretant does not permit itself to be excluded; it is always present – as a parasite (Serres. This is demonstrated using a practical case: A woman living in a home writes her will, in which she instates the home warden and his wife as her heirs. One uses a standardized form in the assumption that one is adhering to the prescribed legal form and thereby eliminating any need for further interpretation. The legal proceedings

  11. 48 CFR 49.602-2 - Inventory forms.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Inventory forms. 49.602-2... TERMINATION OF CONTRACTS Contract Termination Forms and Formats 49.602-2 Inventory forms. Standard Form (SF) 1428, Inventory Disposal Schedule, and SF 1429, Inventory Disposal Schedule—Continuation Sheet, shall...

  12. Review on Cold-Formed Steel Connections

    Science.gov (United States)

    Tan, Cher Siang; Mohammad, Shahrin; Md Tahir, Mahmood; Shek, Poi Ngian

    2014-01-01

    The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed. PMID:24688448

  13. Composite materials formed with anchored nanostructures

    Science.gov (United States)

    Seals, Roland D; Menchhofer, Paul A; Howe, Jane Y; Wang, Wei

    2015-03-10

    A method of forming nano-structure composite materials that have a binder material and a nanostructure fiber material is described. A precursor material may be formed using a mixture of at least one metal powder and anchored nanostructure materials. The metal powder mixture may be (a) Ni powder and (b) NiAl powder. The anchored nanostructure materials may comprise (i) NiAl powder as a support material and (ii) carbon nanotubes attached to nanoparticles adjacent to a surface of the support material. The process of forming nano-structure composite materials typically involves sintering the mixture under vacuum in a die. When Ni and NiAl are used in the metal powder mixture Ni.sub.3Al may form as the binder material after sintering. The mixture is sintered until it consolidates to form the nano-structure composite material.

  14. Disability and Bureaucratic Forms of Life

    Directory of Open Access Journals (Sweden)

    Thomas Abrams

    2015-06-01

    Full Text Available This paper employs a hybrid actor-network theory/phenomenological approach to a frequent bother in the lives of disabled persons: bureaucratic forms. I argue that these forms are key sites where disabled personhood emerges, something I examine through the lens of what philosopher Annemarie Mol calls ‘ontological politics’. To be disabled is to be entered into the bureaucratic form of life. These forms translate human existence into a categorize-able, transportable and combinable object, to be administered through ‘centers of calculation’. Combining Heidegger’s fundamental ontology with Latour’s theory of paperwork, I suggest that these forms represent disability in terms of ‘objective presence’, as a mere pre-existing thing, rather than a human way of being. I conclude with suggestions for further phenomenological research that takes embodied difference as its point of departure.

  15. Research needs in cement-based waste forms

    International Nuclear Information System (INIS)

    McDaniel, E.W.; Spence, R.D.; Tallent, O.K.

    1990-01-01

    Cement-based waste forms are one of the most widely used waste disposal options, yet definitive knowledge of the fate of the waste species inside the waste form is lacking. A fundamental understanding of the chemistry and microstructure of the waste forms would lead to a better understanding of the mass transfer of the waste species, more confidence in predicting and extrapolating waste form performance, and design of better waste forms. Better and cheaper leach tests would lead to quicker and more cost effective screening of waste form alternatives. In addition, assessment of durability may be important to predicting waste form performance in the field. It should be noted that the research needs discussed in this report are from the perspective of investigators working in applied waste management areas, while the proposed investigations are fundamental or basic. Details as to experimental methods and tools to be used in achieving the objectives of the proposed are research beyond the scope of this paper and are better filled in by others. In broad terms, the research topics discussed are correlation of cement-based waste form physical properties to performance, waste-form fundamental chemistry and microstructure, and product performance testing

  16. Waste forms for plutonium disposition

    International Nuclear Information System (INIS)

    Johnson, S.G.; O'Holleran, T.P.; Frank, S.M.; Meyer, M.K.; Hanson, M.; Staples, B.A.; Knecht, D.A.; Kong, P.C.

    1997-01-01

    The field of plutonium disposition is varied and of much importance, since the Department of Energy has decided on the hybrid option for disposing of the weapons materials. This consists of either placing the Pu into mixed oxide fuel for reactors or placing the material into a stable waste form such as glass. The waste form used for Pu disposition should exhibit certain qualities: (1) provide for a suitable deterrent to guard against proliferation; (2) be of minimal volume, i.e., maximize the loading; and (3) be reasonably durable under repository-like conditions. This paper will discuss several Pu waste forms that display promising characteristics

  17. Lie algebra of conformal Killing–Yano forms

    International Nuclear Information System (INIS)

    Ertem, Ümit

    2016-01-01

    We provide a generalization of the Lie algebra of conformal Killing vector fields to conformal Killing–Yano forms. A new Lie bracket for conformal Killing–Yano forms that corresponds to slightly modified Schouten–Nijenhuis bracket of differential forms is proposed. We show that conformal Killing–Yano forms satisfy a graded Lie algebra in constant curvature manifolds. It is also proven that normal conformal Killing–Yano forms in Einstein manifolds also satisfy a graded Lie algebra. The constructed graded Lie algebras reduce to the graded Lie algebra of Killing–Yano forms and the Lie algebras of conformal Killing and Killing vector fields in special cases. (paper)

  18. 48 CFR 13.307 - Forms.

    Science.gov (United States)

    2010-10-01

    ...) Other than commercial items. (1) Except when quotations are solicited electronically or orally, the SF 1449; SF 18, Request for Quotations; or an agency form/automated format may be used. Each agency request for quotations form/automated format should conform with the SF 18 or SF 1449 to the maximum...

  19. Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Melisa Gualdron-López

    Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

  20. Electrically assisted forming modeling and control

    CERN Document Server

    Salandro, Wesley A; Bunget, Cristina; Mears, Laine; Roth, John T

    2015-01-01

    Maximizing reader insights into the latest research findings and applications of Electrically-Assisted Forming (EAF) – whereby metals are formed under an electric current field – this book explains how such a process produces immediate improved formability of metals beyond the extent of thermal softening, and allows metals to be formed to greater elongation with lower mechanical energy as well as allowing for lightweight brittle metals such as magnesium and titanium to be formed without external heating or annealing, enabling the more effective use of these lightweight metals in design. Including case studies that illustrate and support the theoretical content and real-world applications of the techniques discussed, this book also serves to enrich readers understanding of the underlying theories that influence electro-plastic behaviour. The authors have extensive experience in studying Electrically-Assisted Forming and have written extensively on the topic with publications including experimental works, t...

  1. Normal form theory and spectral sequences

    OpenAIRE

    Sanders, Jan A.

    2003-01-01

    The concept of unique normal form is formulated in terms of a spectral sequence. As an illustration of this technique some results of Baider and Churchill concerning the normal form of the anharmonic oscillator are reproduced. The aim of this paper is to show that spectral sequences give us a natural framework in which to formulate normal form theory. © 2003 Elsevier Science (USA). All rights reserved.

  2. Chou-Yang model and PHI form factor

    Energy Technology Data Exchange (ETDEWEB)

    Fazal-e-Aleem; Saleem, M.; Rafique, M.

    1988-03-01

    By using the deduced differential cross-section data for PHIp elastic scattering at 175 GeV/c in the Chou-Yang model, the PHI form factor has been computed and parametrized. Then in conjunction with the proton form factor this form factor is used in the pristine Chou-Yang model to obtain differential cross-section data at Fermilab energies. The theoretical results agree with the experimental measurements, endorsing the conjecture that the hadronic form factor of neutral particle is proportional to its magnetic form factor.

  3. 17 CFR 239.14 - Form N-2 for closed end management investment companies registered on Form N-8A.

    Science.gov (United States)

    2010-04-01

    ... management investment companies registered on Form N-8A. 239.14 Section 239.14 Commodity and Securities... Registration Statements § 239.14 Form N-2 for closed end management investment companies registered on Form N... closed end management investment companies registered under the Investment Company Act of 1940 on form N...

  4. The effect of the model posture on the forming quality in the CNC incremental forming

    International Nuclear Information System (INIS)

    Zhu, H; Zhang, W; Bai, J L; Yu, C; Xing, Y F

    2015-01-01

    Sheet rupture caused by a sheet metal thickness non-uniformity persists in CNC (Computer Numerical Control) incremental forming. Because the forming half cone angle is determined by the orientation of the model to be formed, so is the sheet metal's uniformity. The finite element analysis models for the two kinds of the postures of the model were established, and the digital simulation was conducted by using the ANSYS/LA-DYNA software. The effect of the model's posture on the sheet thickness distribution and the sheet thickness thinning rate were studied by comparing the simulation results of two kinds of the finite elements analyzes. (paper)

  5. NETWORK CODING BY BEAM FORMING

    DEFF Research Database (Denmark)

    2013-01-01

    Network coding by beam forming in networks, for example, in single frequency networks, can provide aid in increasing spectral efficiency. When network coding by beam forming and user cooperation are combined, spectral efficiency gains may be achieved. According to certain embodiments, a method...... cooperating with the plurality of user equipment to decode the received data....

  6. 13 CFR 120.194 - Use of computer forms.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  7. Substrate system for spray forming

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Men G. (Export, PA); Chernicoff, William P. (Harrisburg, PA)

    2002-01-01

    A substrate system for receiving a deposit of sprayed metal droplets including a movable outer substrate on which the sprayed metal droplets are deposited. The substrate system also includes an inner substrate disposed adjacent the outer substrate where the sprayed metal droplets are deposited on the outer substrate. The inner substrate includes zones of differing thermal conductivity to resist substrate layer porosity and to resist formation of large grains and coarse constituent particles in a bulk layer of the metal droplets which have accumulated on the outer substrate. A spray forming apparatus and associated method of spray forming a molten metal to form a metal product using the substrate system of the invention is also provided.

  8. Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression.

    Science.gov (United States)

    Coke, Christopher J; Scarlett, Kisha A; Chetram, Mahandranauth A; Jones, Kia J; Sandifer, Brittney J; Davis, Ahriea S; Marcus, Adam I; Hinton, Cimona V

    2016-05-06

    The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Size-dependent variation in plant form.

    Science.gov (United States)

    Niklas, Karl J; Cobb, Edward D

    2017-09-11

    The study of organic form has a long and distinguished history going at least as far back as Aristotle's Historia Anima¯lium, wherein he identified five basic biological processes that define the forms of animals (metabolism, temperature regulation, information processing, embryo development, and inheritance). Unfortunately, all of Aristotle's writings about plant forms are lost. We know of them only indirectly from his student Theophrastus's companion books, collectively called Historia Plantarum, wherein plant forms are categorized into annual herbs, herbaceous perennials, shrubs, and trees. The study of plant forms did not truly begin until the romantic poet and naturalist Goethe proposed the concept of a hypothetical 'Plant Archetype', declared "Alles ist Blatt", and first coined the word morphologie, which inspired the French anatomist Cuvier (who established the field of comparative morphology), the English naturalist Darwin (who saw his theory of evolution reinforced by it), and the Scottish mathematician D'Arcy Thompson (who attempted to quantify it). Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 32 CFR 516.25 - DA Form 4.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense... LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2... properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b) Preparation at...

  11. Heavy meson form factors from QCD

    International Nuclear Information System (INIS)

    Falk, A.F.; Georgi, H.; Grinstein, B.

    1990-01-01

    We calculate the leading QCD radiative corrections to the relations which follow from the decoupling of the heavy quark spin as the quark mass goes infinity and from the symmetry between systems with different heavy quarks. One of the effects we calculate gives the leading q 2 -dependence of the form factor of a heavy quark, which in turn dominates the q 2 -dependence of the form factors of bound states of the heavy quark with light quarks. This, combined with the normalization of the form factor provided by symmetry, gives us a first principles calculation of the heavy meson (or baryon) form factors in the limit of very large heavy quark mass. (orig.)

  12. Make Projects Small Form Factor PCs

    CERN Document Server

    Wessels, Duane

    2006-01-01

    Shoebox sized and smaller, small-form-factor PCs can pack as much computing muscle as a full-sized desktop computer. They consumer less power, have few or no moving parts, and are very quiet. Whether you plan to use one as a standalone PC or want to embed it in your next hacking project, a small-form-factor PC can be a lot of fun to build. Make Projects: Small Form Factor PCs is the only book available that shows you how to build small-form-factor PCs -- from kits and from scratch -- that are more interesting and more personalized than what a full-sized PC can give you. Included in the book

  13. Special waste-form lysimeters: Arid

    International Nuclear Information System (INIS)

    Jones, T.L.; Serne, R.J.

    1987-08-01

    The release of contaminant from solidified low-level waste forms is being studied in a field lysimeter facility at the Hanford Site in southeastern Washington State. Duplicate samples of five different waste forms have been buried in 10 lysimeters since March 1984. Waste-form samples represent three different waste streams and four solidification agents (masonry cement, Portland III cement, Dow polymer /sup (a)/, and bitumen). Most precipitation at the Hanford Site arrives as winter snow; this contributes to a strong seasonal pattern in water storage and drainage observed in the lysimeters. The result is an annual range in the volumetric soil water content from 11% in late winter to 7% in the late summer and early fall, as well as annual changes in pore water velocities from approximately 1 cm/wk in early spring to less than 0.05 cm/wk in early fall. Measurable quantities of tritium and cobalt-60 are being collected in lysimeter drainage water. Approximately 30% of the original tritium inventory has been leached from two lysimeters originally containing tritium. Cobalt-60 is present in all waste forms; it is being collected in the leachate from five lysimeters. The total amount released varies, but in each case it is less than 0.1% of the original cobalt inventory of the waste sample. Nonradioactive constituents contained in the waste form, such as sodium, boron, and sulfate, are also being leached

  14. In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic Transformation of Rifampicin: From Form II to Form I.

    Science.gov (United States)

    Guo, Nannan; Hou, Baohong; Wang, Na; Xiao, Yan; Huang, Jingjing; Guo, Yanmei; Zong, Shuyi; Hao, Hongxun

    2018-01-01

    In this article, the solution-mediated polymorphic transformation of rifampicin was investigated and simulated in 3 solvents at 30°C. The solid-state form I and form II of rifampicin was characterized by powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). To explore the relative stability, solubility data of form I and form II of rifampicin in butan-1-ol were determined using a dynamical method. In addition, Raman spectroscopy and focused beam reflectance measurement were used to in situ monitor the transformation of rifampicin from form II to form I. The liquid state concentration of rifampicin was measured by UV spectroscopic method. To investigate the effect of solvent on transformation, the transformation experiments were carried out in 3 solvents. Furthermore, a mathematical model was built to describe the kinetics of dissolution, nucleation, and growth processes during transformation by using experimental data. By combination of experimental and simulation results, it was found that the transformation process of rifampicin is controlled by dissolution of form II in heptane, whereas the transformation in hexane and octane was firstly controlled by dissolution of solid-state form and then controlled by growth of form I. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Sixth form pure mathematics

    CERN Document Server

    Plumpton, C

    1968-01-01

    Sixth Form Pure Mathematics, Volume 1, Second Edition, is the first of a series of volumes on Pure Mathematics and Theoretical Mechanics for Sixth Form students whose aim is entrance into British and Commonwealth Universities or Technical Colleges. A knowledge of Pure Mathematics up to G.C.E. O-level is assumed and the subject is developed by a concentric treatment in which each new topic is used to illustrate ideas already treated. The major topics of Algebra, Calculus, Coordinate Geometry, and Trigonometry are developed together. This volume covers most of the Pure Mathematics required for t

  16. Stainless steel-zirconium alloy waste forms

    International Nuclear Information System (INIS)

    McDeavitt, S.M.; Abraham, D.P.; Keiser, D.D. Jr.; Park, J.Y.

    1996-01-01

    An electrometallurgical treatment process has been developed by Argonne National Laboratory to convert various types of spent nuclear fuels into stable storage forms and waste forms for repository disposal. The first application of this process will be to treat spent fuel alloys from the Experimental Breeder Reactor-II. Three distinct product streams emanate from the electrorefining process: (1) refined uranium; (2) fission products and actinides extracted from the electrolyte salt that are processed into a mineral waste form; and (3) metallic wastes left behind at the completion of the electrorefining step. The third product stream (i.e., the metal waste stream) is the subject of this paper. The metal waste stream contains components of the chopped spent fuel that are unaffected by the electrorefining process because of their electrochemically ''noble'' nature; this includes the cladding hulls, noble metal fission products (NMFP), and, in specific cases, zirconium from metal fuel alloys. The selected method for the consolidation and stabilization of the metal waste stream is melting and casting into a uniform, corrosion-resistant alloy. The waste form casting process will be carried out in a controlled-atmosphere furnace at high temperatures with a molten salt flux. Spent fuels with both stainless steel and Zircaloy cladding are being evaluated for treatment; thus, stainless steel-rich and Zircaloy-rich waste forms are being developed. Although the primary disposition option for the actinides is the mineral waste form, the concept of incorporating the TRU-bearing product into the metal waste form has enough potential to warrant investigation

  17. A generalized definition for waste form durability

    International Nuclear Information System (INIS)

    Fanning, T. H.; Bauer, T. H.; Morris, E. E.; Wigeland, R. A.

    2002-01-01

    When evaluating waste form performance, the term ''durability'' often appears in casual discourse, but in the technical literature, the focus is often on waste form ''degradation'' in terms of mass lost per unit area per unit time. Waste form degradation plays a key role in developing models of the long-term performance in a repository environment, but other factors also influence waste form performance. These include waste form geometry; density, porosity, and cracking; the presence of cladding; in-package chemistry feedback; etc. The paper proposes a formal definition of waste form ''durability'' which accounts for these effects. Examples from simple systems as well as from complex models used in the Total System Performance Assessment of Yucca Mountain are provided. The application of ''durability'' in the selection of bounding models is also discussed

  18. [Galenic forms for oral medication].

    Science.gov (United States)

    El Semman, Ousseid; Certain, Agnès; Bouziane, Faouzia; Arnaud, Philippe

    2012-10-01

    Galenic science is interested in the art and the way of formulating an active principle with an excipient in order for it to be administered to the patient. The pharmaceutical forms envisage different administration routes, including by mouth. Nurses need to handle and sometimes modify the pharmaceutical form of a drug to make it easier for the patient to take. This requires vigilance.

  19. Creep age forming of Al-Cu-Li alloy: Application to thick sheet forming of double curvature aircraft panel

    Directory of Open Access Journals (Sweden)

    Younes Wael

    2016-01-01

    Full Text Available Creep-age-forming of a thick Al-Cu-Li sheet is studied. An industrial stamping press is used to form a double curvature panel at a reduced scale. This forming, which includes several relaxation steps, is modelled using ABAQUS. A material model describing an elasto-viscoplastic behaviour with anisotropy effect has been identified and implemented in ABAQUS using Fortran subroutine. The numerical model is validated by comparing experiments and numerical results in terms of deformed shapes and an improved forming cycle is suggested.

  20. Circle of Form

    DEFF Research Database (Denmark)

    Jaeger, Thomas Arvid

    2012-01-01

    a common professional language like in mathematics, colour and music. The result is a weaker professionalism in the aesthetic competences compared to the professionalism and competences in other areas. A research project [1] on contrasts or opposites in form investigated the phenomenon in the fields...

  1. Mathematics and Forms of Life

    Directory of Open Access Journals (Sweden)

    Severin Schroeder

    2015-10-01

    Full Text Available According to Wittgenstein, mathematics is embedded in, and partly constituting, a form of life. Hence, to imagine different, alternative forms of elementary mathematics, we should have to imagine different practices, different forms of life in which they could play a role. If we tried to imagine a radically different arithmetic we should think either of a strange world (in which objects unaccountably vanish or appear or of people acting and responding in very peculiar ways. If such was their practice, a calculus expressing the norms of representation they applied could not be called false. Rather, our criticism could only be to dismiss such a practice as foolish and to dismiss their norms as too different from ours to be called ‘mathematics’.

  2. Color-kinematic duality for form factors

    International Nuclear Information System (INIS)

    Boels, Rutger H.; Kniehl, Bernd A.; Tarasov, Oleg V.; Yang, Gang

    2012-12-01

    Recently a powerful duality between color and kinematics has been proposed for integrands of scattering amplitudes in quite general gauge theories. In this paper the duality proposal is extended to the more general class of gauge theory observables formed by form factors. After a discussion of the general setup the existence of the duality is verified in two and three loop examples in four dimensional maximally supersymmetric Yang-Mills theory which involve the stress energy tensor multiplet. In these cases the duality reproduces known results in a particularly transparent and uniform way. As a non-trivial application we obtain a very simple form of the integrand of the four-loop two-point (Sudakov) form factor which passes a large set of unitarity cut checks.

  3. Color-kinematic duality for form factors

    Energy Technology Data Exchange (ETDEWEB)

    Boels, Rutger H.; Kniehl, Bernd A.; Tarasov, Oleg V.; Yang, Gang [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2012-12-15

    Recently a powerful duality between color and kinematics has been proposed for integrands of scattering amplitudes in quite general gauge theories. In this paper the duality proposal is extended to the more general class of gauge theory observables formed by form factors. After a discussion of the general setup the existence of the duality is verified in two and three loop examples in four dimensional maximally supersymmetric Yang-Mills theory which involve the stress energy tensor multiplet. In these cases the duality reproduces known results in a particularly transparent and uniform way. As a non-trivial application we obtain a very simple form of the integrand of the four-loop two-point (Sudakov) form factor which passes a large set of unitarity cut checks.

  4. Subclinical form of the American visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Mônica Elinor Alves Gama

    2004-12-01

    Full Text Available The subclinical form of visceral leishmaniasis (VL shows nonspecific clinical manifestations, with difficulties being frequently met in its clinical characterization and diagnostic confirmation. Thus, the objective of the present study was to define the clinical-laboratory profile of this clinical form. A cohort study was conducted in the state of Maranhão, Brazil, from January/1998 to December/2000, with monthly follow-up of 784 children aged 0-5 years. Based on the clinical-laboratory parameters reported in the literature, four categories were established, with the children being classified (according to their clinical-evolutive behavior as asymptomatic (N = 144, as having the subclinical form (N = 33 or the acute form (N = 12 or as subjects "without VL" (N = 595. Multiple discriminant analysis demonstrated that the combination of fever, hepatomegaly, hyperglobulinemia, and increased blood sedimentation rate (BSR can predict the subclinical form of VL as long as it is not associated with splenomegaly or leukopenia. Subjects with the subclinical form did not show prolonged or intermittent evolution or progression to the acute form of VL. Subclinical cases have a profile differing from the remaining clinical forms of VL, being best characterized by the combination of fever, hepatomegaly, hyperglobulinemia, and increased BSR.

  5. New Visions on Form and Growth

    International Nuclear Information System (INIS)

    Howard, M

    2005-01-01

    It is now nearly 90 years since the publication of D'Arcy Thompson's book On Growth and Form, a classic work that attempted a unification of pattern-forming phenomena in systems ranging from inanimate to living matter. Thompson's book came early in the development of mathematical techniques in biology. His work has had enormous influence in succeeding decades and has helped inspire the rapid growth in the application of theoretical techniques to biological phenomena. Pelce's book New Visions on Form and Growth takes its inspiration and title directly from D'Arcy Thompson. Furthermore, Pelce attempts what could not be achieved in D'Arcy Thompson's time, namely the presentation of a quantitative analysis of pattern forming phenomena. However, it should be emphasised that the vast majority of this book is concerned with inanimate matter, with rather little discussion of biology. The book begins with a presentation of the basic physics, including surface tension, first-order phase transition kinetics and a brief outline of chemical kinetics. With the essential physics established, Pelce then investigates simple growth forms, before showing how these regular geometries are destabilized into more complex forms by instabilities. The problem of velocity selection of growing patterns is then extensively discussed, before the question of (secondary) instabilities of the more complex growth forms is analysed. A chapter on stochastic patterns is also included. For the most part, the book concentrates on a few intensively studied pattern forming systems in physics, particularly viscous fingering in Hele-Shaw cells, the growth of dendrites, electrodeposition, flames, and, in the chapter on stochastic patterns, diffusion-limited aggregation. Only in a rather brief final chapter is a more speculative link made with biological pattern formation and morphogenesis. In general, I found the book to be a useful reference work on the theory of pattern forming systems. However, the

  6. Slab edge insulating form system and methods

    Science.gov (United States)

    Lee, Brain E [Corral de Tierra, CA; Barsun, Stephan K [Davis, CA; Bourne, Richard C [Davis, CA; Hoeschele, Marc A [Davis, CA; Springer, David A [Winters, CA

    2009-10-06

    A method of forming an insulated concrete foundation is provided comprising constructing a foundation frame, the frame comprising an insulating form having an opening, inserting a pocket former into the opening; placing concrete inside the foundation frame; and removing the pocket former after the placed concrete has set, wherein the concrete forms a pocket in the placed concrete that is accessible through the opening. The method may further comprise sealing the opening by placing a sealing plug or sealing material in the opening. A system for forming an insulated concrete foundation is provided comprising a plurality of interconnected insulating forms, the insulating forms having a rigid outer member protecting and encasing an insulating material, and at least one gripping lip extending outwardly from the outer member to provide a pest barrier. At least one insulating form has an opening into which a removable pocket former is inserted. The system may also provide a tension anchor positioned in the pocket former and a tendon connected to the tension anchor.

  7. Asymptotics of Heavy-Meson Form Factors

    CERN Document Server

    Grozin, A.G.; Grozin, Andrey G.; Neubert, Matthias

    1997-01-01

    Using methods developed for hard exclusive QCD processes, we calculate the asymptotic behaviour of heavy-meson form factors at large recoil. It is determined by the leading- and subleading-twist meson wave functions. For $1\\ll |v\\cdot v'|\\ll m_Q/\\Lambda$, the form factors are dominated by the Isgur--Wise function, which is determined by the interference between the wave functions of leading and subleading twist. At $|v\\cdot v'|\\gg m_Q/\\Lambda$, they are dominated by two functions arising at order $1/m_Q$ in the heavy-quark expansion, which are determined by the leading-twist wave function alone. The sum of these contributions describes the form factors in the whole region $|v\\cdot v'|\\gg 1$. As a consequence, there is an exact zero in the form factor for the scattering of longitudinally polarized $B^*$ mesons at some value $v\\cdot v'\\sim m_b/\\Lambda$, and an approximate zero in the form factor of $B$ mesons in the timelike region ($v\\cdot v'\\sim -m_b/\\Lambda$). We obtain the evolution equations and sum rules ...

  8. Disjoint sum forms in reliability theory

    Directory of Open Access Journals (Sweden)

    B. Anrig

    2014-01-01

    Full Text Available The structure function f of a binary monotone system is assumed to be known and given in a disjunctive normal form, i.e. as the logical union of products of the indicator variables of the states of its subsystems. Based on this representation of f, an improved Abraham algorithm is proposed for generating the disjoint sum form of f. This form is the base for subsequent numerical reliability calculations. The approach is generalized to multivalued systems. Examples are discussed.

  9. Forming Behaviour in Laser Shock Drawing

    OpenAIRE

    Schulze Niehoff, H.; Vollertsen, F.; Wielage, H.

    2008-01-01

    Through the continuing trend of miniaturization new cost efficient and fast methods for processing small parts are required. In this paper a new non-mechanical process for the forming process of micro deep drawing is presented. This new deep drawing process utilizes a laser initiated plasma shock wave at the target, which forms the sheet. Several pulses can be applied at one point and therefore high forming degrees can be reached without increasing the energy density. In this paper the pressu...

  10. Toroidal helical quartz forming machine

    International Nuclear Information System (INIS)

    Hanks, K.W.; Cole, T.R.

    1977-01-01

    The Scyllac fusion experimental machine used 10 cm diameter smooth bore discharge tubes formed into a simple toroidal shape prior to 1974. At about that time, it was discovered that a discharge tube was required to follow the convoluted shape of the load coil. A machine was designed and built to form a fused quartz tube with a toroidal shape. The machine will accommodate quartz tubes from 5 cm to 20 cm diameter forming it into a 4 m toroidal radius with a 1 to 5 cm helical displacement. The machine will also generate a helical shape on a linear tube. Two sets of tubes with different helical radii and wavelengths have been successfully fabricated. The problems encountered with the design and fabrication of this machine are discussed

  11. Hereditary forms of breast cancer

    International Nuclear Information System (INIS)

    Bella, V.

    2009-01-01

    Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)

  12. In Vitro Study of Taenia solium Postoncospheral Form.

    Directory of Open Access Journals (Sweden)

    Nancy Chile

    2016-02-01

    Full Text Available The transitional period between the oncosphere and the cysticercus of Taenia solium is the postoncospheral (PO form, which has not yet been completely characterized. The aim of this work was to standardize a method to obtain T. solium PO forms by in vitro cultivation. We studied the morphology of the PO form and compared the expression of antigenic proteins among the PO form, oncosphere, and cysticerci stages.T. solium activated oncospheres were co-cultured with ten cell lines to obtain PO forms, which we studied at three stages of development--days 15, 30, and 60. A high percentage (32% of PO forms was obtained using HCT-8 cells in comparison to the other cell lines. The morphology was observed by bright field, scanning, and transmission electron microscopy. Morphology of the PO form changed over time, with the six hooks commonly seen in the oncosphere stage disappearing in the PO forms, and vesicles and microtriches observed in the tegument. The PO forms grew as they aged, reaching a diameter of 2.5 mm at 60 days of culture. 15-30 day PO forms developed into mature cysticerci when inoculated into rats. Antigenic proteins expressed in the PO forms are also expressed by the oncosphere and cysticerci stages, with more cysticerci antigenic proteins expressed as the PO forms ages.This is the first report of an in vitro production method of T. solium PO forms. The changes observed in protein expression may be useful in identifying new targets for vaccine development. In vitro culture of PO form will aid in understanding the host-parasite relationship, since the structural changes of the developing PO forms may reflect the parasite's immunoprotective mechanisms. A wider application of this method could significantly reduce the use of animals, and thus the costs and time required for further experimental investigations.

  13. In Vitro Study of Taenia solium Postoncospheral Form.

    Science.gov (United States)

    Chile, Nancy; Clark, Taryn; Arana, Yanina; Ortega, Ynes R; Palma, Sandra; Mejia, Alan; Angulo, Noelia; Kosek, Jon C; Kosek, Margaret; Gomez-Puerta, Luis A; Garcia, Hector H; Gavidia, Cesar M; Gilman, Robert H; Verastegui, Manuela

    2016-02-01

    The transitional period between the oncosphere and the cysticercus of Taenia solium is the postoncospheral (PO) form, which has not yet been completely characterized. The aim of this work was to standardize a method to obtain T. solium PO forms by in vitro cultivation. We studied the morphology of the PO form and compared the expression of antigenic proteins among the PO form, oncosphere, and cysticerci stages. T. solium activated oncospheres were co-cultured with ten cell lines to obtain PO forms, which we studied at three stages of development--days 15, 30, and 60. A high percentage (32%) of PO forms was obtained using HCT-8 cells in comparison to the other cell lines. The morphology was observed by bright field, scanning, and transmission electron microscopy. Morphology of the PO form changed over time, with the six hooks commonly seen in the oncosphere stage disappearing in the PO forms, and vesicles and microtriches observed in the tegument. The PO forms grew as they aged, reaching a diameter of 2.5 mm at 60 days of culture. 15-30 day PO forms developed into mature cysticerci when inoculated into rats. Antigenic proteins expressed in the PO forms are also expressed by the oncosphere and cysticerci stages, with more cysticerci antigenic proteins expressed as the PO forms ages. This is the first report of an in vitro production method of T. solium PO forms. The changes observed in protein expression may be useful in identifying new targets for vaccine development. In vitro culture of PO form will aid in understanding the host-parasite relationship, since the structural changes of the developing PO forms may reflect the parasite's immunoprotective mechanisms. A wider application of this method could significantly reduce the use of animals, and thus the costs and time required for further experimental investigations.

  14. Wars of Forms

    DEFF Research Database (Denmark)

    Clausen, Lars

    2013-01-01

    , both political and military, war between the two forms, the post-napoleonic, Fichtean notion of nationality (1807-8) and the historical notion of imperium. “Nationality” entered the political semantics witch such a force and shook the existing political order of empires to the ground because of its...

  15. Forms of Inattentiveness

    DEFF Research Database (Denmark)

    Knudsen, Morten

    2011-01-01

    and kept out of sight in the decision processes by looking at a specific case study involving the construction of a model intended to control, and render transparent, the quality of health services in Denmark. This paper outlines the forms of inattentiveness which make communication blind to information...

  16. Innovative forming and fabrication technologies : new opportunities.

    Energy Technology Data Exchange (ETDEWEB)

    Davis, B.; Hryn, J.; Energy Systems; Kingston Process Metallurgy, Inc.

    2008-01-31

    The advent of light metal alloys and advanced materials (polymer, composites, etc.) have brought the possibility of achieving important energy reductions into the full life cycle of these materials, especially in transportation applications. 1 These materials have gained acceptance in the aerospace industry but use of light metal alloys needs to gain wider acceptance in other commercial transportation areas. Among the main reasons for the relatively low use of these materials are the lack of manufacturability, insufficient mechanical properties, and increased material costs due to processing inefficiencies. Considering the enormous potential energy savings associated with the use of light metal alloys and advanced materials in transportation, there is a need to identify R&D opportunities in the fields of materials fabrication and forming aimed at developing materials with high specific mechanical properties combined with energy efficient processes and good manufacturability. This report presents a literature review of the most recent developments in the areas of fabrication and metal forming focusing principally on aluminum alloys. In the first section of the document, the different sheet manufacturing technologies including direct chill (DC) casting and rolling, spray forming, spray rolling, thin slab, and strip casting are reviewed. The second section of the document presents recent research on advanced forming processes. The various forming processes reviewed are: superplastic forming, electromagnetic forming, age forming, warm forming, hydroforming, and incremental forming. Optimization of conventional forming processes is also discussed. Potentially interesting light metal alloys for high structural efficiency including aluminum-scandium, aluminum-lithium, magnesium, titanium, and amorphous metal alloys are also reviewed. This section concludes with a discussion on alloy development for manufacturability. The third section of the document reviews the latest

  17. Synroc tailored waste forms for actinide immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Gregg, Daniel J.; Vance, Eric R. [Australian Nuclear Science and Technology Organisation, Kirrawee (Australia). ANSTOsynroc, Inst. of Materials Engineering

    2017-07-01

    Since the end of the 1970s, Synroc at the Australian Nuclear Science and Technology Organisation (ANSTO) has evolved from a focus on titanate ceramics directed at PUREX waste to a platform waste treatment technology to fabricate tailored glass-ceramic and ceramic waste forms for different types of actinide, high- and intermediate level wastes. The particular emphasis for Synroc is on wastes which are problematic for glass matrices or existing vitrification process technologies. In particular, nuclear wastes containing actinides, notably plutonium, pose a unique set of requirements for a waste form, which Synroc ceramic and glass-ceramic waste forms can be tailored to meet. Key aspects to waste form design include maximising the waste loading, producing a chemically durable product, maintaining flexibility to accommodate waste variations, a proliferation resistance to prevent theft and diversion, and appropriate process technology to produce waste forms that meet requirements for actinide waste streams. Synroc waste forms incorporate the actinides within mineral phases, producing products which are much more durable in water than baseline borosilicate glasses. Further, Synroc waste forms can incorporate neutron absorbers and {sup 238}U which provide criticality control both during processing and whilst within the repository. Synroc waste forms offer proliferation resistance advantages over baseline borosilicate glasses as it is much more difficult to retrieve the actinide and they can reduce the radiation dose to workers compared to borosilicate glasses. Major research and development into Synroc at ANSTO over the past 40 years has included the development of waste forms for excess weapons plutonium immobilization in collaboration with the US and for impure plutonium residues in collaboration with the UK, as examples. With a waste loading of 40-50 wt.%, Synroc would also be considered a strong candidate as an engineered waste form for used nuclear fuel and highly

  18. Effects of Processing Parameters on the Forming Quality of C-Shaped Thermosetting Composite Laminates in Hot Diaphragm Forming Process

    Science.gov (United States)

    Bian, X. X.; Gu, Y. Z.; Sun, J.; Li, M.; Liu, W. P.; Zhang, Z. G.

    2013-10-01

    In this study, the effects of processing temperature and vacuum applying rate on the forming quality of C-shaped carbon fiber reinforced epoxy resin matrix composite laminates during hot diaphragm forming process were investigated. C-shaped prepreg preforms were produced using a home-made hot diaphragm forming equipment. The thickness variations of the preforms and the manufacturing defects after diaphragm forming process, including fiber wrinkling and voids, were evaluated to understand the forming mechanism. Furthermore, both interlaminar slipping friction and compaction behavior of the prepreg stacks were experimentally analyzed for showing the importance of the processing parameters. In addition, autoclave processing was used to cure the C-shaped preforms to investigate the changes of the defects before and after cure process. The results show that the C-shaped prepreg preforms with good forming quality can be achieved through increasing processing temperature and reducing vacuum applying rate, which obviously promote prepreg interlaminar slipping process. The process temperature and forming rate in hot diaphragm forming process strongly influence prepreg interply frictional force, and the maximum interlaminar frictional force can be taken as a key parameter for processing parameter optimization. Autoclave process is effective in eliminating voids in the preforms and can alleviate fiber wrinkles to a certain extent.

  19. 12 CFR 335.221 - Forms for registration of securities; optional forms for small business issuers; and...

    Science.gov (United States)

    2010-01-01

    ... forms for small business issuers; and incorporation of Regulation FD (Fair Disclosure). 335.221 Section... forms for small business issuers; and incorporation of Regulation FD (Fair Disclosure). (a) The.... Industry Guide 3, Statistical Disclosure by Bank Holding Companies, is codified at 17 CFR 229.802. (c) A...

  20. Inflation and dark energy from three-forms

    International Nuclear Information System (INIS)

    Koivisto, Tomi S.; Nunes, Nelson J.

    2009-01-01

    Three-forms can give rise to viable cosmological scenarios of inflation and dark energy with potentially observable signatures distinct from standard single scalar field models. In this study, the background dynamics and linear perturbations of self-interacting three-form cosmology are investigated. The phase space of cosmological solutions possesses (super)-inflating attractors and saddle points, which can describe three-form driven inflation or dark energy. The quantum generation and the classical evolution of perturbations is considered. The scalar and tensor spectra from a three-form inflation and the impact from the presence of a three-form on matter perturbations are computed. Stability properties and equivalence of the model with alternative formulations are discussed.

  1. Towards the first generation micro bulk forming system

    DEFF Research Database (Denmark)

    Arentoft, Mogens; Eriksen, Rasmus Solmer; Hansen, Hans Nørgaard

    2011-01-01

    . This work describes a number of prototype system units, which collectively form a desktop sized micro forming production system. The system includes a billet preparation module, an integrated transfer system, a temperature controlled forming tool, including process simulation, and a dedicated micro forming......The industrial demand for micro mechanical components has surged in the later years with the constant introduction of more integrated products. The micro bulk forming process holds a promising pledge of delivering high quality micro mechanical components at low cost and high production rates...... press. The system is demonstrated on an advanced micro forming case where a dental component is formed in medical grade Titanium....

  2. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    Science.gov (United States)

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. A clinical study to evaluate the correlation between maxillary central incisor tooth form and face form in an Indian population.

    Science.gov (United States)

    Koralakunte, Pavankumar R; Budihal, Dhanyakumar H

    2012-09-01

    A study was performed to examine the correlation between maxillary central incisor tooth form and face form in males and females in an Indian population. The selection of prosthetic teeth for edentulous patients is a primary issue in denture esthetics, especially in the case of maxillary central incisors, which are the most prominent teeth in the arch. Two hundred dental students of Indian origin comprising 79 males and 121 females aged 18-28 years studying at Bapuji Dental College and Hospital were randomly selected as the study subjects. A standardized photographic procedure was used to obtain images of the face and the maxillary central incisors. The outline forms of the face and the maxillary right central incisor tooth were determined using a standardized method. The outline forms obtained were used to classify both face form and tooth form on the basis of visual and William's methods. The means were considered after evaluation by five prosthodontists, and the results were tabulated. Statistical analysis was performed using the chi-squared test for association and Z-test for equality of proportions. A correlation greater than 50% was observed between tooth form and face form by the visual method, compared with one of 31.5% by William's method. There was no highly defined correlation between maxillary central incisor tooth form and face form among the male and female Indian subjects studied.

  4. On local invariants of singular symplectic forms

    Science.gov (United States)

    Domitrz, Wojciech

    2017-04-01

    We find a complete set of local invariants of singular symplectic forms with the structurally stable Martinet hypersurface on a 2 n-dimensional manifold. In the C-analytic category this set consists of the Martinet hypersurface Σ2, the restriction of the singular symplectic form ω to TΣ2 and the kernel of ω n - 1 at the point p ∈Σ2. In the R-analytic and smooth categories this set contains one more invariant: the canonical orientation of Σ2. We find the conditions to determine the kernel of ω n - 1 at p by the other invariants. In dimension 4 we find sufficient conditions to determine the equivalence class of a singular symplectic form-germ with the structurally smooth Martinet hypersurface by the Martinet hypersurface and the restriction of the singular symplectic form to it. We also study the singular symplectic forms with singular Martinet hypersurfaces. We prove that the equivalence class of such singular symplectic form-germ is determined by the Martinet hypersurface, the canonical orientation of its regular part and the restriction of the singular symplectic form to its regular part if the Martinet hypersurface is a quasi-homogeneous hypersurface with an isolated singularity.

  5. Analysis of forming limit in tube hydroforming

    International Nuclear Information System (INIS)

    Kim, Chan Il; Yang, Seung Hang; Kim, Young Suk

    2013-01-01

    The automotive industry has shown increasing interest in tube hydroforming. Despite many automobile structural parts being produced from cylindrical tubes, failures frequently occur during tube hydroforming under improper forming conditions. These problems include wrinkling, buckling, folding back, and bursting. We perform analytical studies to determine forming limits in tube hydroforming and demonstrate how these forming limits are influenced by the loading path. Theoretical results for the forming limits of wrinkling and bursting are compared with experimental results for an aluminum tube.

  6. Numerical Simulation of Explosive Forming Using Detonating Fuse

    OpenAIRE

    H Iyama; Y Higa; M Nishi; S Itoh

    2017-01-01

    The explosive forming is a characteristic method. An underwater shock wave is generated by underwater explosion of an explosive. A metal plate is affected high strain rate by the shock loading and is formed along a metal die. Although this method has the advantage of mirroring the shape of the die, a free forming was used in this paper. An expensive metal die is not necessary for this free forming. It is possible that a metal plate is formed with simple supporting parts. However, the forming ...

  7. Cooperative Station History Forms

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Various forms, photographs and correspondence documenting the history of Cooperative station instrumentation, location changes, inspections, and...

  8. Electronic Capitalization Asset Form -

    Data.gov (United States)

    Department of Transportation — National Automated Capitalization Authorization Form used by ATO Engineering Services, Logistics, Accounting for the purpose of identifying and capturing FAA project...

  9. A retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensitivity in transcriptional activation of the lactoferrin gene.

    Science.gov (United States)

    Lee, M O; Liu, Y; Zhang, X K

    1995-08-01

    The lactoferrin gene is highly expressed in many different tissues, and its expression is controlled by different regulators. In this report, we have defined a retinoic acid response element (RARE) in the 5'-flanking region of the lactoferrin gene promoter. The lactoferrin-RARE is composed of two AGGTCA-like motifs arranged as a direct repeat with 1-bp spacing (DR-1). A gel retardation assay demonstrated that it bound strongly with retinoid X receptor (RXR) homodimers and RXR-retinoic acid receptor (RAR) heterodimers as well as chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan receptor. In CV-1 cells, the lactoferrin-RARE linked with a heterologous thymidine kinase promoter was strongly activated by RXR homodimers in response to 9-cis-retinoic acid (9-cis-RA) but not to all-trans-RA. When the COUP-TF orphan receptor was cotransfected, the 9-cis-RA-induced RXR homodimer activity was strongly repressed. A unique feature of the lactoferrin-RARE is that it has an AGGTCA-like motif in common with an estrogen-responsive element (ERE). The composite RARE/ERE contributes to the functional interaction between retinoid receptors and the estrogen receptor (ER) and their ligands. In CV-1 cells, cotransfection of the retinoid and estrogen receptors led to mutual inhibition of the other's activity, while an RA-dependent inhibition of ER activity was observed in breast cancer cells. Furthermore, the lactoferrin-RARE/ERE showed differential transactivation activity in different cell types. RAs could activate the lactoferrin-RARE/ERE in human leukemia HL-60 cells and U937 cells but not in human breast cancer cells. By gel retardation analyses, we demonstrated that strong binding of the endogenous COUP-TF in breast cancer cells to the composite element contributed to diminished RA response in these cells. Thus, the lactoferrin-RARE/ERE functions as a signaling switch module that mediates multihormonal responsiveness in the regulation of lactoferrin gene

  10. Iodine waste form summary report (FY 2007)

    International Nuclear Information System (INIS)

    Krumhansl, James Lee; Nenoff, Tina Maria; McMahon, Kevin A.; Gao, Huizhen; Rajan, Ashwath Natech

    2007-01-01

    This new program at Sandia is focused on Iodine waste form development for GNEP cycle needs. Our research has a general theme of 'Waste Forms by Design' in which we are focused on silver loaded zeolite waste forms and related metal loaded zeolites that can be validated for chosen GNEP cycle designs. With that theme, we are interested in materials flexibility for iodine feed stream and sequestration material (in a sense, the ability to develop a universal material independent on the waste stream composition). We also are designing the flexibility to work in a variety of repository or storage scenarios. This is possible by studying the structure/property relationship of existing waste forms and optimizing them to our current needs. Furthermore, by understanding the properties of the waste and the storage forms we may be able to predict their long-term behavior and stability. Finally, we are working collaboratively with the Waste Form Development Campaign to ensure materials durability and stability testing

  11. Magnetic form factors of the trinucleons

    Energy Technology Data Exchange (ETDEWEB)

    Schiavilla, R; Pandharipande, V R; Riska, Dan-Olof

    1989-11-01

    The magnetic form factors of 3H and 3He are calculated with the Monte Carlo method from variational ground-state wave functions obtained for the Argonne and Urbana two- and three-nucleon interactions. The electromagnetic current operator contains one- and two-body terms that are constructed so as to satisfy the continuity equation with the two-nucleon potential in the Hamiltonian. The results obtained with the Argonne two-nucleon interaction are in overall agreement with the empirical values. It appears that the remaining theoretical uncertainty, in the calculation of these form factors from a given interaction model, is dominated by that in the electromagnetic form factors of the nucleon. It is found that the isovector magnetic form factors are rather sensitive to the details of the isospin-dependent tensor force, and they are much better reproduced with the Argonne than the Urbana potential. The isoscalar magnetic form factors appear to be sensitive to the spin-orbit interactions, and are better reproduced with the Urbana potential. The Argonne potential has a stronger τ1∙τ2 tensor force, while the Urbana one has a shorter-range spin-orbit interaction.

  12. Technetium Immobilization Forms Literature Survey

    Energy Technology Data Exchange (ETDEWEB)

    Westsik, Joseph H.; Cantrell, Kirk J.; Serne, R. Jeffrey; Qafoku, Nikolla

    2014-05-01

    Of the many radionuclides and contaminants in the tank wastes stored at the Hanford site, technetium-99 (99Tc) is one of the most challenging to effectively immobilize in a waste form for ultimate disposal. Within the Hanford Tank Waste Treatment and Immobilization Plant (WTP), the Tc will partition between both the high-level waste (HLW) and low-activity waste (LAW) fractions of the tank waste. The HLW fraction will be converted to a glass waste form in the HLW vitrification facility and the LAW fraction will be converted to another glass waste form in the LAW vitrification facility. In both vitrification facilities, the Tc is incorporated into the glass waste form but a significant fraction of the Tc volatilizes at the high glass-melting temperatures and is captured in the off-gas treatment systems at both facilities. The aqueous off-gas condensate solution containing the volatilized Tc is recycled and is added to the LAW glass melter feed. This recycle process is effective in increasing the loading of Tc in the LAW glass but it also disproportionally increases the sulfur and halides in the LAW melter feed which increases both the amount of LAW glass and either the duration of the LAW vitrification mission or the required supplemental LAW treatment capacity.

  13. [Oral films as perspective dosage form].

    Science.gov (United States)

    Walicová, Veronika; Gajdziok, Jan

    Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

  14. Noncommutative differential forms on the kappa-deformed space

    International Nuclear Information System (INIS)

    Meljanac, Stjepan; Kresic-Juric, Sasa

    2009-01-01

    We construct a differential algebra of forms on the kappa-deformed space. For a given realization of noncommutative coordinates as formal power series in the Weyl algebra we find an infinite family of one-forms and nilpotent exterior derivatives. We derive explicit expressions for the exterior derivative and one-forms in covariant and noncovariant realizations. We also introduce higher order forms and show that the exterior derivative satisfies the graded Leibniz rule. The differential forms are generally not graded commutative, but they satisfy the graded Jacobi identity. We also consider the star-product of classical differential forms. The star-product is well defined if the commutator between the noncommutative coordinates and one-forms is closed in the space of one-forms alone. In addition, we show that in certain realizations the exterior derivative acting on the star-product satisfies the undeformed Leibniz rule.

  15. New directions in Dirichlet forms

    CERN Document Server

    Jost, Jürgen; Mosco, Umberto; Rockner, Michael; Sturm, Karl-Theodor

    1998-01-01

    The theory of Dirichlet forms brings together methods and insights from the calculus of variations, stochastic analysis, partial differential and difference equations, potential theory, Riemannian geometry and more. This book features contributions by leading experts and provides up-to-date, authoritative accounts on exciting developments in the field and on new research perspectives. Topics covered include the following: stochastic analysis on configuration spaces, specifically a mathematically rigorous approach to the stochastic dynamics of Gibbs measures and infinite interacting particle systems; subelliptic PDE, homogenization, and fractals; geometric aspects of Dirichlet forms on metric spaces and function theory on such spaces; generalized harmonic maps as nonlinear analogues of Dirichlet forms, with an emphasis on non-locally compact situations; and a stochastic approach based on Brownian motion to harmonic maps and their regularity. Various new connections between the topics are featured, and it is de...

  16. Measurement of the pion form factor

    International Nuclear Information System (INIS)

    Dally, E.; Hauptman, J.; May, C.

    1977-01-01

    The pion form factor has been measured in the momentum transfer range of 0.03( 2 by scattering pions from atomic electrons in a liquid hydrogen target. The pion form factor is defined to be the elastic scattering cross section divided by that predicted for a point pion. The experiment has been performed in a 100 GeV/c negative pion beam incident on a 50 cm liquid hydrogen target at Fermi laboratory. The corrected form factor equals 0.33+-0.06 f 2 . Vector dominance predicts 0.40 f 2

  17. Forming Tests for Laser Welded Blanks

    DEFF Research Database (Denmark)

    Bagger, Claus; Olsen, Flemming Ove; Rasmussen, Mads

    1998-01-01

    Ratio test (LDR)Tensile testBulge testMarziniak testPractical examples obtained for laser welded blanks are shown. In combination, tensile tests and the Bulge test can form the so-called Forming Limiting Curves and examples of curves obtained from laser welded blanks are shown.......In this paper different means for testing the formability of new material combinations used as tailored blanks in the automotive industry are presented. The following forming techniques will be described and their benefits and drawbacks presented :Limiting Dome Height test (LDH)Limiting Drawing...

  18. Nonlinear dynamics exploration through normal forms

    CERN Document Server

    Kahn, Peter B

    2014-01-01

    Geared toward advanced undergraduates and graduate students, this exposition covers the method of normal forms and its application to ordinary differential equations through perturbation analysis. In addition to its emphasis on the freedom inherent in the normal form expansion, the text features numerous examples of equations, the kind of which are encountered in many areas of science and engineering. The treatment begins with an introduction to the basic concepts underlying the normal forms. Coverage then shifts to an investigation of systems with one degree of freedom that model oscillations

  19. IMO Fireball report form: results and prospects

    Science.gov (United States)

    Hankey, M.; Perlerin, V.

    2015-01-01

    At the 2014 IMC, we presented the new IMO (International Meteor Organization) online, Fireball report (available at fireballs.imo.net). This fireball report form was specifically designed for use by people with no astronomy experience who witnessed a fireball, a bolide or a suspected similar phenomenon. The IMO version of the form has been officially launched in February 2015. Since then, the form has been translated in different languages and customized for organizations around the world. In this paper, we will present preliminary results of the form and provide tips to improve the online presence of local organizations, in order to promote usage. We will also highlight procedures to be followed by local organizations to get a custom version of the form.

  20. Formulation of Forming Load in V-Bending

    Directory of Open Access Journals (Sweden)

    Koumura Yuki

    2016-01-01

    Full Text Available A novel method is described to calculate the forming load in V-bending by a press brake. The data of forming load are collected by FEM analysis. With an increase of the punch stroke in V-bending, the forming load increases gradually after the elastic limit, and then decreases after showing the maximum value. The proposal formulation to trace the variations in the forming load curve includes the calculating method of the load of the elastic limit, the maximum load in air bending and the variations of the forming load before/after the bending stroke of the maximum load. The calculated precision is confirmed by comparing with the measured load-stroke curves in V-bending with a press brake.

  1. Forms of Approximate Radiation Transport

    CERN Document Server

    Brunner, G

    2002-01-01

    Photon radiation transport is described by the Boltzmann equation. Because this equation is difficult to solve, many different approximate forms have been implemented in computer codes. Several of the most common approximations are reviewed, and test problems illustrate the characteristics of each of the approximations. This document is designed as a tutorial so that code users can make an educated choice about which form of approximate radiation transport to use for their particular simulation.

  2. 26 CFR 31.6051-2 - Information returns on Form W-3 and Internal Revenue Service copies of Forms W-2.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Information returns on Form W-3 and Internal Revenue Service copies of Forms W-2. 31.6051-2 Section 31.6051-2 Internal Revenue INTERNAL REVENUE SERVICE... returns on Form W-3 and Internal Revenue Service copies of Forms W-2. (a) In general. Every employer who...

  3. Strategy for Qualification of the Plutonium Immobilized Form

    International Nuclear Information System (INIS)

    Marra, J.C.; Marra, S.L.; Bibler, N.E.; Strachan, D.M.; Shaw, H.F.

    1998-01-01

    In order to dispose of a radioactive waste form in a federal high- level waste repository, a waste form qualification strategy and program must be developed. The waste form qualification program must include the acceptance specifications for the product, show how compliance with these specifications will be met, and then demonstrate compliance. An important element of this program is developing a measure to demonstrate product consistency. For the can- in-canister option, waste form qualification is needed not only for the Pu immobilized form but also for the high-level waste glass canister containing the Pu waste form. The latter will require close interaction and coordination with the U.S. Department of Energy - Office of Environmental Management (DOE-EM) who, through their contractor at the Savannah River Site (SRS), is the producer of the high-level waste form at the Defense Waste Processing Facility (DWPF). In this paper a waste form qualification strategy for the plutonium ceramic form is described that utilizes, as much as possible, the qualification strategy successfully used for vitrified high-level waste

  4. Summary: special waste form lysimeters - arid program

    International Nuclear Information System (INIS)

    Skaggs, R.L.; Walter, M.B.

    1987-01-01

    The purpose of the Special Waste Form Lysimeters - Arid Program is to determine the performance of solidified commercial low-level waste forms using a field-scale lysimeter facility constructed for measuring the release and migration of radionuclides from the waste forms. The performance of these waste forms, as measured by radionuclide concentrations in lysimeter effluent, will be compared to that predicted by laboratory characterization of the waste forms. Waste forms being tested include nuclear power reactor waste streams that have been solidified in cement, Dow polymer, and bitumen. To conduct the field leaching experiments a lysimeter facility was built to measure leachate under actual environmental conditions. Field-scale samples of waste were buried in lysimeters equipped to measure water balance components, effluent radionuclide concentrations, and to a limited extent, radionuclide concentrations in lysimeter soil samples. The waste forms are being characterized by standard laboratory leach tests to obtain estimates of radionuclide release. These estimates will be compared to leach rates observed in the field. Adsorption studies are being conducted to determine the amount of contaminant available for transport after the release. Theoretical solubility calculations will also be performed to investigate whether common solid phases could be controlling radionuclide release. 4 references, 8 figures, 1 table

  5. 1 CFR 5.8 - Form of citation.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Form of citation. 5.8 Section 5.8 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.8 Form of citation. Without prejudice to any other form of citation, Federal Register material may be cited by volume...

  6. 19 CFR 24.14 - Salable Customs forms.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Salable Customs forms. 24.14 Section 24.14 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS FINANCIAL AND ACCOUNTING PROCEDURE § 24.14 Salable Customs forms. (a) Customs forms for sale to...

  7. Form Filling with Self-Compacting Concrete

    DEFF Research Database (Denmark)

    Thrane, Lars Nyholm

    2002-01-01

    This paper describes a newly started Ph.D. project with the aim of simulating the form filling ability of Self-Compacting Concrete (SCC) taking into account the form geometry, reinforcement configuration, casting technique, and the rheological properties of the concrete. Comparative studies...

  8. Charge-symmetry-breaking nucleon form factors

    International Nuclear Information System (INIS)

    Kubis, Bastian

    2011-01-01

    A quantitative understanding of charge-symmetry breaking is an increasingly important ingredient for the extraction of the nucleon’s strange vector form factors. We review the theoretical understanding of the charge-symmetry-breaking form factors, both for single nucleons and for 4 He.

  9. Comparative assessment of TRU waste forms and processes. Volume II. Waste form data, process descriptions, and costs

    International Nuclear Information System (INIS)

    Ross, W.A.; Lokken, R.O.; May, R.P.; Roberts, F.P.; Thornhill, R.E.; Timmerman, C.L.; Treat, R.L.; Westsik, J.H. Jr.

    1982-09-01

    This volume contains supporting information for the comparative assessment of the transuranic waste forms and processes summarized in Volume I. Detailed data on the characterization of the waste forms selected for the assessment, process descriptions, and cost information are provided. The purpose of this volume is to provide additional information that may be useful when using the data in Volume I and to provide greater detail on particular waste forms and processes. Volume II is divided into two sections and two appendixes. The first section provides information on the preparation of the waste form specimens used in this study and additional characterization data in support of that in Volume I. The second section includes detailed process descriptions for the eight processes evaluated. Appendix A lists the results of MCC-1 leach test and Appendix B lists additional cost data. 56 figures, 12 tables

  10. Chern-Simons forms in gravitation theories

    International Nuclear Information System (INIS)

    Zanelli, Jorge

    2012-01-01

    The Chern-Simons (CS) form evolved from an obstruction in mathematics into an important object in theoretical physics. In fact, the presence of CS terms in physics is more common than one may think: they seem to play an important role in high Tc superconductivity and in recently discovered topological insulators. In classical physics, the minimal coupling in electromagnetism and to the action for a mechanical system in Hamiltonian form are examples of CS functionals. CS forms are also the natural generalization of the minimal coupling between the electromagnetic field and a point charge when the source is not point like but an extended fundamental object, a membrane. They are found in relation with anomalies in quantum field theories, and as Lagrangians for gauge fields, including gravity and supergravity. A cursory review of the role of CS forms in gravitation theories is presented at an introductory level. (topical review)

  11. Chern-Simons forms in gravitation theories

    Science.gov (United States)

    Zanelli, Jorge

    2012-07-01

    The Chern-Simons (CS) form evolved from an obstruction in mathematics into an important object in theoretical physics. In fact, the presence of CS terms in physics is more common than one may think: they seem to play an important role in high Tc superconductivity and in recently discovered topological insulators. In classical physics, the minimal coupling in electromagnetism and to the action for a mechanical system in Hamiltonian form are examples of CS functionals. CS forms are also the natural generalization of the minimal coupling between the electromagnetic field and a point charge when the source is not point like but an extended fundamental object, a membrane. They are found in relation with anomalies in quantum field theories, and as Lagrangians for gauge fields, including gravity and supergravity. A cursory review of the role of CS forms in gravitation theories is presented at an introductory level.

  12. Laser based micro forming and assembly.

    Energy Technology Data Exchange (ETDEWEB)

    MacCallum, Danny O' Neill; Wong, Chung-Nin Channy; Knorovsky, Gerald Albert; Steyskal, Michele D.; Lehecka, Tom (Pennsylvania State University, Freeport, PA); Scherzinger, William Mark; Palmer, Jeremy Andrew

    2006-11-01

    It has been shown that thermal energy imparted to a metallic substrate by laser heating induces a transient temperature gradient through the thickness of the sample. In favorable conditions of laser fluence and absorptivity, the resulting inhomogeneous thermal strain leads to a measurable permanent deflection. This project established parameters for laser micro forming of thin materials that are relevant to MESA generation weapon system components and confirmed methods for producing micrometer displacements with repeatable bend direction and magnitude. Precise micro forming vectors were realized through computational finite element analysis (FEA) of laser-induced transient heating that indicated the optimal combination of laser heat input relative to the material being heated and its thermal mass. Precise laser micro forming was demonstrated in two practical manufacturing operations of importance to the DOE complex: micrometer gap adjustments of precious metal alloy contacts and forming of meso scale cones.

  13. Increasing the Robustness of the Sheet Metal Forming Simulation by the Prediction of the Forming Limit Band

    Science.gov (United States)

    Banabic, D.; Vos, M.; Paraianu, L.; Jurco, P.

    2007-05-01

    The experimental research on the formability of metal sheets has shown that there is a significant dispersion of the limit strains in an area delimited by two curves: a lower curve (LFLC) and an upper one (UFLC). The region between the two curves defines the so-called Forming Limit Band (FLB). So far, this forming band has only been determined experimentally. In this paper the authors suggested a method to predict the Forming Limit Band. The proposed method is illustrated on the AA6111-T43 aluminium alloy.

  14. Increasing the Robustness of the Sheet Metal Forming Simulation by the Prediction of the Forming Limit Band

    International Nuclear Information System (INIS)

    Banabic, D.; Paraianu, L.; Vos, M.; Jurco, P.

    2007-01-01

    The experimental research on the formability of metal sheets has shown that there is a significant dispersion of the limit strains in an area delimited by two curves: a lower curve (LFLC) and an upper one (UFLC). The region between the two curves defines the so-called Forming Limit Band (FLB). So far, this forming band has only been determined experimentally. In this paper the authors suggested a method to predict the Forming Limit Band. The proposed method is illustrated on the AA6111-T43 aluminium alloy

  15. BEL β-trefoil: a novel lectin with antineoplastic properties in king bolete (Boletus edulis) mushrooms.

    Science.gov (United States)

    Bovi, Michele; Cenci, Lucia; Perduca, Massimiliano; Capaldi, Stefano; Carrizo, Maria E; Civiero, Laura; Chiarelli, Laurent R; Galliano, Monica; Monaco, Hugo L

    2013-05-01

    A novel lectin was purified from the fruiting bodies of king bolete mushrooms (Boletus edulis, also called porcino, cep or penny bun). The lectin was structurally characterized i.e its amino acid sequence and three-dimensional structure were determined. The new protein is a homodimer and each protomer folds as β-trefoil domain and therefore we propose the name Boletus edulis lectin (BEL) β-trefoil to distinguish it from the other lectin that has been described in these mushrooms. The lectin has potent anti-proliferative effects on human cancer cells, which confers to it an interesting therapeutic potential as an antineoplastic agent. Several crystal forms of the apoprotein and of complexes with different carbohydrates were studied by X-ray diffraction. The structure of the apoprotein was solved at 1.12 Å resolution. The interaction of the lectin with lactose, galactose, N-acetylgalactosamine and T-antigen disaccharide, Galβ1-3GalNAc, was examined in detail. All the three potential binding sites present in the β-trefoil fold are occupied in at least one crystal form and are described in detail in this paper. No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein.

  16. Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

    Science.gov (United States)

    Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

    2017-01-01

    Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

  17. 17 CFR 239.15 - Form N-1 for open-end management investment companies registered on Form N-8A.

    Science.gov (United States)

    2010-04-01

    ... management investment companies registered on Form N-8A. 239.15 Section 239.15 Commodity and Securities... Registration Statements § 239.15 Form N-1 for open-end management investment companies registered on Form N-8A...-end management investment companies that are separate accounts of insurance companies as defined by...

  18. Charge-symmetry-breaking nucleon form factors

    Energy Technology Data Exchange (ETDEWEB)

    Kubis, Bastian, E-mail: kubis@hiskp.uni-bonn.de [Universitaet Bonn, Helmholtz-Institut fuer Strahlen- und Kernphysik (Theorie) and Bethe Center for Theoretical Physics (Germany)

    2011-11-15

    A quantitative understanding of charge-symmetry breaking is an increasingly important ingredient for the extraction of the nucleon's strange vector form factors. We review the theoretical understanding of the charge-symmetry-breaking form factors, both for single nucleons and for {sup 4}He.

  19. New organizational forms, controls, and institutions

    NARCIS (Netherlands)

    Annosi, Maria Carmela; Brunetta, Federica

    2017-01-01

    This book highlights the growing number of 'post-bureaucratic' firms that are abandoning hierarchical organizational forms in favor of self-managing teams. Addressing the need to outperform, these new organization types foresee the benefits of an organic structure with new and more indirect forms of

  20. Cubic metaplectic forms and theta functions

    CERN Document Server

    Proskurin, Nikolai

    1998-01-01

    The book is an introduction to the theory of cubic metaplectic forms on the 3-dimensional hyperbolic space and the author's research on cubic metaplectic forms on special linear and symplectic groups of rank 2. The topics include: Kubota and Bass-Milnor-Serre homomorphisms, cubic metaplectic Eisenstein series, cubic theta functions, Whittaker functions. A special method is developed and applied to find Fourier coefficients of the Eisenstein series and cubic theta functions. The book is intended for readers, with beginning graduate-level background, interested in further research in the theory of metaplectic forms and in possible applications.

  1. Conference L-Functions and Automorphic Forms

    CERN Document Server

    Kohnen, Winfried; LAF

    2017-01-01

    This book presents a collection of carefully refereed research articles and lecture notes stemming from the Conference "Automorphic Forms and L-Functions", held at the University of Heidelberg in 2016.  The theory of automorphic forms and their associated L-functions is one of the central research areas in modern number theory, linking number theory, arithmetic geometry, representation theory, and complex analysis in many profound ways.  The 19 papers cover a wide range of topics within the scope of the conference, including automorphic L-functions and their special values, p-adic modular forms, Eisenstein series, Borcherds products, automorphic periods, and many more.

  2. 8 CFR 1299.1 - Use of immigration forms.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Use of immigration forms. 1299.1 Section 1299.1 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS IMMIGRATION REVIEW FORMS § 1299.1 Use of immigration forms. In addition to forms...

  3. Forming of AHSS using Servo-Presses

    Science.gov (United States)

    Groseclose, Adam Richard

    Stamping of Advanced High Strength Steel (AHSS) alloys poses several challenges due to the material's higher strength and low formability compared to conventional steels and other problems such as (a) inconsistency of incoming material properties, (b) ductile fracture during forming, (c) higher contact pressure and temperature rise during forming, (d) higher die wear leading to reduced tool life, (e) higher forming load/press capacity, and (f) large springback leading to dimensional inaccuracy in the formed part. [Palaniswamy et. al., 2007]. The use of AHSS has been increasing steadily in automotive stamping. New AHSS alloys (TRIP, TWIP) may replace some of the Hot Stamping applications. Stamping of AHSS alloys, especially higher strength materials, 780 MPa and higher, present new challenges in obtaining good part definition (corner and fillet radii), formability (fracture and resulting scrap) and in reducing springback. Servo-drive presses, having the capability to have infinitely variable and adjustable ram speed and dwell at BDC, offer a potential improvement in quality, part definition, and springback reduction especially when the infinitely adjustable slide motion is used in combination with a CNC hydraulic cushion. Thus, it is desirable to establish a scientific/engineering basis for improving the stamping conditions in forming AHSS using a servo-drive press.

  4. 12 CFR 569.2 - Form of proxies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Form of proxies. 569.2 Section 569.2 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PROXIES § 569.2 Form of proxies. Every form of proxy shall conform to the following requirements: (a) The proxy shall be revocable at will by...

  5. Two Forms of Philosophical Argument or Critique

    Science.gov (United States)

    Marshall, James D.

    2004-01-01

    In this paper the author looks at two forms of philosophical argument or critique. These are derived by himself from the work of the late Kantian scholar, Stephan Korner who, in his book "What is Philosophy?" (1969), draws a number of distinctions between different forms of "philosophical" argument or critique. The two forms of derived argument,…

  6. Methods for forming particles from single source precursors

    Science.gov (United States)

    Fox, Robert V [Idaho Falls, ID; Rodriguez, Rene G [Pocatello, ID; Pak, Joshua [Pocatello, ID

    2011-08-23

    Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

  7. Opening science: New publication forms in science

    Directory of Open Access Journals (Sweden)

    Scheliga, Kaja

    2014-12-01

    Full Text Available [english] Digital technologies change how scientists access and process information and consequently impact publication forms in science. Even though the core of scientific publications has remained the same, established publication formats, such as the scientific paper or book, are succumbing to the transitions caused by digital technologies. At the same time, new online tools enable new publication forms, such as blogs, microblogs or wikis, to emerge. This article explores the changing and emerging publications forms in science and also reflects upon the changing role of libraries. The transformations of publishing forms are discussed in the context of open science.

  8. Closed forms and multi-moment maps

    DEFF Research Database (Denmark)

    Madsen, Thomas Bruun; Swann, Andrew Francis

    2013-01-01

    We extend the notion of multi-moment map to geometries defined by closed forms of arbitrary degree. We give fundamental existence and uniqueness results and discuss a number of essential examples, including geometries related to special holonomy. For forms of degree four, multi-moment maps are gu...

  9. 5 CFR 847.303 - Election forms.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Election forms. 847.303 Section 847.303...) ELECTIONS OF RETIREMENT COVERAGE BY CURRENT AND FORMER EMPLOYEES OF NONAPPROPRIATED FUND INSTRUMENTALITIES Procedures for Elections Under the Retroactive Provisions § 847.303 Election forms. (a) Eligible employees...

  10. Advanced waste forms from spent nuclear fuel

    International Nuclear Information System (INIS)

    Ackerman, J.P.; McPheeters, C.C.

    1995-01-01

    More than one hundred spent nuclear fuel types, having an aggregate mass of more than 5000 metric tons (2700 metric tons of heavy metal), are stored by the United States Department of Energy. This paper proposes a method for converting this wide variety of fuel types into two waste forms for geologic disposal. The method is based on a molten salt electrorefining technique that was developed for conditioning the sodium-bonded, metallic fuel from the Experimental Breeder Reactor-II (EBR-II) for geologic disposal. The electrorefining method produces two stable, optionally actinide-free, high-level waste forms: an alloy formed from stainless steel, zirconium, and noble metal fission products, and a ceramic waste form containing the reactive metal fission products. Electrorefining and its accompanying head-end process are briefly described, and methods for isolating fission products and fabricating waste forms are discussed

  11. Differential forms on electromagnetic networks

    CERN Document Server

    Balasubramanian, N V; Sen Gupta, D P

    2013-01-01

    Differential Forms on Electromagnetic Networks deals with the use of combinatorial techniques in electrical circuit, machine analysis, and the relationship between circuit quantities and electromagnetic fields. The monograph is also an introduction to the organization of field equations by the methods of differential forms. The book covers topics such as algebraic structural relations in an electric circuit; mesh and node-pair analysis; exterior differential structures; generalized Stoke's theorem and tensor analysis; and Maxwell's electromagnetic equation. Also covered in the book are the app

  12. Flexible forms of working hours

    OpenAIRE

    Knapp, Viktor

    2017-01-01

    66 Abstract - Flexible forms of working hours This diploma thesis deals with the flexible forms of working hours and its goal is to describe this issue in intelligible and comprehensive way. It is being very interesting and current theme which is to a great extent not subject to direct legal regulations and provides its contracting parties with a big amount of freedom of contract. This fact assists in bigger flexibilization of labour market and represents a significant instrument in the fight...

  13. Stability of the spherical form of nuclei

    International Nuclear Information System (INIS)

    Sabry, A.A.

    1976-08-01

    An extension of the mass formula for a spherical nucleus in the drop model to include a largely deformed nucleus of different forms is investigated. It is found that although the spherical form is stable under small deformations from equilibrium, there exists for heavier nuclei another more favourable stable form, which can be approximated by two, or three touching prolate ellipsoids of revolution

  14. Forms of Address in Chilean Spanish

    Science.gov (United States)

    Bishop, Kelley; Michnowicz, Jim

    2010-01-01

    The present investigation examines possible social and linguistic factors that influence forms of address used in Chilean Spanish with various interlocutors. A characteristic of the Spanish of Chile is the use of a variety of forms of address for the second person singular, "tu", "vos", and "usted", with corresponding…

  15. Calculation of nucleon electromagnetic form factors

    International Nuclear Information System (INIS)

    Renner, D.B.; Brower, R.; Dolgov, D.; Eicker, N.; Lippert, Th.; Negele, J.W.; Pochinsky, A.; Schilling, K.

    2003-01-01

    The formalism is developed to express nucleon matrix elements of the electromagnetic current in terms of form factors consistent with the translational, rotational, and parity symmetries of a cubic lattice. We calculate the number of these form factors and show how appropriate linear combinations approach the continuum limit

  16. Timeability in Extensive-Form Games

    DEFF Research Database (Denmark)

    Jakobsen, Sune K.; Sørensen, Troels Bjerre; Conitzer, Vincent

    2016-01-01

    Extensive-form games constitute the standard representation scheme for games with a temporal component. But do all extensive-form games correspond to protocols that we can implement in the real world? We often rule out games with imperfect recall, which prescribe that an agent forget something...... that she knew before. In this paper, we show that even some games with perfect recall can be problematic to implement. Specifically, we show that if the agents have a sense of time passing (say, access to a clock), then some extensive-form games can no longer be implemented; no matter how we attempt...... to time the game, some information will leak to the agents that they are not supposed to have. We say such a game is not exactly timeable. We provide easy-to-check necessary and sufficient conditions for a game to be exactly timeable. Most of the technical depth of the paper concerns how to approximately...

  17. Induction interview form in EDH

    CERN Multimedia

    Information technology Department, AIS (Administrative Information Services) Group,

    2007-01-01

    As part of the efforts to rationalise administrative procedures, the IT and HR Departments have developed a new EDH form for induction interviews, which can be accessed using the link below. In accordance with Administrative Circular No. 2 ('Recruitment, Appointment and possible developments regarding the contractual position of Staff Members', Rev. 3), the work and training objectives to be achieved during the probation period shall be specified in writing to all new staff members during an induction interview. The interview shall take place between the new staff member and his supervisor within six weeks of him taking up his duties at the latest. https://edh.cern.ch/Document/MAPS/Induction (or from the EDH desktop, by clicking on 'Other Tasks' and going to the 'HR & Training' heading) Please note that this form is to be used exclusively for new staff members. A separate EDH form will be developed for fellows. Information technology Department, AIS (Administrative Information Services) Group Human...

  18. Induction interview form in EDH

    CERN Document Server

    Information technology Department, AIS (Administrative Information Services) Group

    2007-01-01

    As part of the efforts to rationalise administrative procedures, the IT and HR Departments have developed a new EDH form for induction interviews, which can be accessed using the link below. In accordance with Administrative Circular No. 2 ('Recruitment, Appointment and possible developments regarding the contractual position of Staff Members', Rev. 3), the work and training objectives to be achieved during the probation period shall be specified in writing to all new staff members during an induction interview. The interview shall take place between the new staff member and his supervisor within six weeks of his taking up his duties at the latest. https://edh.cern.ch/Document/MAPS/Induction1) (or from the EDH desktop, by clicking on 'Other Tasks' and going to the 'HR & Training' heading) Please note that this form is to be used exclusively for new staff members. A separate EDH form will be developed for fellows.Information technology Department, AIS (Administrative Information Services) Group Human Re...

  19. Diffusion from cylindrical waste forms

    International Nuclear Information System (INIS)

    Thomas, G.F.

    1985-05-01

    The diffusion of a single component material from a finite cylindrical waste form, initially containing a uniform concentration of the material, is investigated. Under the condition that the cylinder is maintained in a well-stirred bath, expressions for the fractional inventory leached and the leach rate are derived with allowance for the possible permanent immobilization of the diffusant through its decay to a stable product and/or its irreversible reaction with the waste form matrix. The usefulness of the reported results in nuclear waste disposal applications is emphasized. The results reported herein are related to those previously derived at Oak Ridge National Laboratory by Bell and Nestor. A numerical scheme involving the partial decoupling of nested infinite summations and the use of rapidly converging rational approximants is recommended for the efficient implementation of the expressions derived to obtain reliable estimates of the bulk diffusion constant and the rate constant describing the diffusant-waste form interaction from laboratory data

  20. Modular forms a classical approach

    CERN Document Server

    Cohen, Henri

    2017-01-01

    The theory of modular forms is a fundamental tool used in many areas of mathematics and physics. It is also a very concrete and "fun" subject in itself and abounds with an amazing number of surprising identities. This comprehensive textbook, which includes numerous exercises, aims to give a complete picture of the classical aspects of the subject, with an emphasis on explicit formulas. After a number of motivating examples such as elliptic functions and theta functions, the modular group, its subgroups, and general aspects of holomorphic and nonholomorphic modular forms are explained, with an emphasis on explicit examples. The heart of the book is the classical theory developed by Hecke and continued up to the Atkin-Lehner-Li theory of newforms and including the theory of Eisenstein series, Rankin-Selberg theory, and a more general theory of theta series including the Weil representation. The final chapter explores in some detail more general types of modular forms such as half-integral weight, Hilbert, Jacob...

  1. Methods of forming aluminum oxynitride-comprising bodies, including methods of forming a sheet of transparent armor

    Science.gov (United States)

    Chu, Henry Shiu-Hung [Idaho Falls, ID; Lillo, Thomas Martin [Idaho Falls, ID

    2008-12-02

    The invention includes methods of forming an aluminum oxynitride-comprising body. For example, a mixture is formed which comprises A:B:C in a respective molar ratio in the range of 9:3.6-6.2:0.1-1.1, where "A" is Al.sub.2O.sub.3, "B" is AlN, and "C" is a total of one or more of B.sub.2O.sub.3, SiO.sub.2, Si--Al--O--N, and TiO.sub.2. The mixture is sintered at a temperature of at least 1,600.degree. C. at a pressure of no greater than 500 psia effective to form an aluminum oxynitride-comprising body which is at least internally transparent and has at least 99% maximum theoretical density.

  2. Canonical forms for single-qutrit Clifford+T operators

    OpenAIRE

    Glaudell, Andrew N.; Ross, Neil J.; Taylor, Jacob M.

    2018-01-01

    We introduce canonical forms for single qutrit Clifford+T circuits and prove that every single-qutrit Clifford+T operator admits a unique such canonical form. We show that our canonical forms are T-optimal in the sense that among all the single-qutrit Clifford+T circuits implementing a given operator our canonical form uses the least number of T gates. Finally, we provide an algorithm which inputs the description of an operator (as a matrix or a circuit) and constructs the canonical form for ...

  3. ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

    Directory of Open Access Journals (Sweden)

    Derkach SA

    2015-04-01

    Full Text Available Nowadays the vital problem of modern medicine is a tendency to emerging of both nosocomial and community-acquired strains before antibiotic resistance forming. The complexity of antibiotic therapy of diseases caused by methicillin resistant staphylococci having high poly resistance almost to every classes of antibacterial agents is of prime importance. One of the ways to improve antibacterial preparations still remains the development of their liposomal forms. This work studies antistaphylococcal activity (according to MIC of the liposomal form of lincomycin developed in the Institute of Dermatology and Venereology of Ukraine by Ivanova N. N., the Candidate of Сhemical Sciences.The purpose of this research work was to study liposomal inhibiting concentration of the liposomalny form of lincomycin and a commercial preparation lincomycin (produced by CJSC “Pharmaceutical firm "Darnitsa". Determination of the minimum inhibiting concentration was carried out by a tablet micromethod by consecutive cultivations of the samples under study.It is shown that MIC of liposomal lincomycin is eight times as low as usual lincomycin (0,23mkg/ml to 1,87 mkg/ml. Antibacterial activity of the liposomal form of lincomycin is studied concerning the patients selected from the different biotopes with pyo inflammatory diseases of staphylococcus strains (15 strains – methicillin sensitive, 12 strains - methicillin resistant.It is shown authentically the higher sensitivity of S. aureus strains to the liposomal form of lincomycin in comparison with usual lincomycin . Also 50.0% of MRSA strains were sensitive to the liposomalny form of lincomycin that shows the perspective for the development of the liposomal forms of antibiotics to cure staphylococcal infections.

  4. Method of forming an HTS article

    Science.gov (United States)

    Bhattacharya, Raghu N.; Zhang, Xun; Selvamanickam, Venkat

    2014-08-19

    A method of forming a superconducting article includes providing a substrate tape, forming a superconducting layer overlying the substrate tape, and depositing a capping layer overlying the superconducting layer. The capping layer includes a noble metal and has a thickness not greater than about 1.0 micron. The method further includes electrodepositing a stabilizer layer overlying the capping layer using a solution that is non-reactive to the superconducting layer. The superconducting layer has an as-formed critical current I.sub.C(AF) and a post-stabilized critical current I.sub.C(PS). The I.sub.C(PS) is at least about 95% of the I.sub.C(AF).

  5. Algebra and Arithmetic of Modular Forms

    DEFF Research Database (Denmark)

    Rustom, Nadim

    In [Rus14b] and [Rus14a], we study graded rings of modular forms over congruence subgroups, with coefficients in subrings A of C, and determine bounds of the weights of modular forms constituting a minimal set of generators, as well as on the degree of the generators of the ideal of relations...... between them. We give an algorithm that computes the structures of these rings, and formulate conjectures on the minimal generating weight for modular forms with coefficients in Z. We discuss questions of finiteness of systems of Hecke eigenvalues modulo pm, for a prime p and an integer m ≥ 2, in analogy...

  6. ANSTO's waste forms for the 31. century

    International Nuclear Information System (INIS)

    Vance, E.R.; Begg, B. D.; Day, R. A.; Moricca, S.; Perera, D. S.; Stewart, M. W. A.; Carter, M. L.; McGlinn, P. J.; Smith, K. L.; Walls, P. A.; Robina, M. La

    2004-01-01

    ANSTO waste form development for high-level radioactive waste is directed towards practical applications, particularly problematic niche wastes that do not readily lend themselves to direct vitrification. Integration of waste form chemistry and processing method is emphasised. Some longstanding misconceptions about titanate ceramics are dealt with. We have a range of titanate-bearing waste form products aimed at immobilisation of tank wastes and sludges, actinide-rich wastes, INEEL calcines and Na-bearing liquid wastes, Al-rich wastes arising from reprocessing of Al-clad fuels, Mo-rich wastes arising from reprocessing of U-Mo fuels, partitioned Cs-rich wastes, and 99 Tc. Waste form production techniques cover hot isostatic and uniaxial pressing, sintering, and cold-crucible melting, and these are strongly integrated into waste form design. Speciation and leach resistance of Cs and alkalis in cementitious products and geo-polymers are being studied. Recently we have embarked on studies of candidate inert matrix fuels for Pu burning. We also have a considerable program directed at basic understanding of the waste forms in regard to crystal chemistry, dissolution behaviour in aqueous media, radiation damage effects and optimum processing techniques. (authors)

  7. ANSTO's waste forms for the 31. century

    Energy Technology Data Exchange (ETDEWEB)

    Vance, E R; Begg, B D; Day, R A; Moricca, S; Perera, D S; Stewart, M W. A.; Carter, M L; McGlinn, P J; Smith, K L; Walls, P A; Robina, M La

    2004-07-01

    ANSTO waste form development for high-level radioactive waste is directed towards practical applications, particularly problematic niche wastes that do not readily lend themselves to direct vitrification. Integration of waste form chemistry and processing method is emphasised. Some longstanding misconceptions about titanate ceramics are dealt with. We have a range of titanate-bearing waste form products aimed at immobilisation of tank wastes and sludges, actinide-rich wastes, INEEL calcines and Na-bearing liquid wastes, Al-rich wastes arising from reprocessing of Al-clad fuels, Mo-rich wastes arising from reprocessing of U-Mo fuels, partitioned Cs-rich wastes, and {sup 99}Tc. Waste form production techniques cover hot isostatic and uniaxial pressing, sintering, and cold-crucible melting, and these are strongly integrated into waste form design. Speciation and leach resistance of Cs and alkalis in cementitious products and geo-polymers are being studied. Recently we have embarked on studies of candidate inert matrix fuels for Pu burning. We also have a considerable program directed at basic understanding of the waste forms in regard to crystal chemistry, dissolution behaviour in aqueous media, radiation damage effects and optimum processing techniques. (authors)

  8. Electromagnetic form factors of a massive neutrino

    International Nuclear Information System (INIS)

    Dvornikov, M.S.; Studenikin, A.I.

    2004-01-01

    Electromagnetic form factors of a massive neutrino are studied in a minimally extended standard model in an arbitrary R ξ gauge and taking into account the dependence on the masses of all interacting particles. The contribution from all Feynman diagrams to the electric, magnetic, and anapole form factors, in which the dependence of the masses of all particles as well as on gauge parameters is accounted for exactly, are obtained for the first time in explicit form. The asymptotic behavior of the magnetic form factor for large negative squares of the momentum of an external photon is analyzed and the expression for the anapole moment of a massive neutrino is derived. The results are generalized to the case of mixing between various flavors of the neutrino. Explicit expressions are obtained for the electric, magnetic, and electric dipole and anapole transitional form factors as well as for the transitional electric dipole moment

  9. 13 CFR 108.100 - Business form.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Business form. 108.100 Section 108.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Organizing A Nmvc Company § 108.100 Business form. A NMVC...

  10. Correlation energy functional within the GW -RPA: Exact forms, approximate forms, and challenges

    Science.gov (United States)

    Ismail-Beigi, Sohrab

    2010-05-01

    In principle, the Luttinger-Ward Green’s-function formalism allows one to compute simultaneously the total energy and the quasiparticle band structure of a many-body electronic system from first principles. We present approximate and exact expressions for the correlation energy within the GW -random-phase approximation that are more amenable to computation and allow for developing efficient approximations to the self-energy operator and correlation energy. The exact form is a sum over differences between plasmon and interband energies. The approximate forms are based on summing over screened interband transitions. We also demonstrate that blind extremization of such functionals leads to unphysical results: imposing physical constraints on the allowed solutions (Green’s functions) is necessary. Finally, we present some relevant numerical results for atomic systems.

  11. Processes for production of alternative waste forms

    International Nuclear Information System (INIS)

    Ross, W.A.; Rusin, J.M.; McElroy, J.L.

    1979-01-01

    During the past 20 years, numerous waste forms and processes have been proposed for solidification of high-level radioactive wastes (HLW). The number has increased significantly during the past 3 to 4 years. At least five factors must be considered in selecting the waste form and process method: 1) processing flexibility, 2) waste loading, 3) canister size and stability, 4) waste form inertness and stability, and 5) processing complexity. This paper describes various waste form processes and operations, and a simple system is proposed for making comparisons. This system suggests that one goal for processes would be to reduce the number of process steps, thereby providing less complex processing systems

  12. Terra firma-forme dermatosis

    Directory of Open Access Journals (Sweden)

    Emel Erkek

    2012-01-01

    Full Text Available Terra firma-forme dermatosis is characterized by ′dirty′ brown-grey cutaneous patches and plaques that can simply be eradicated by forceful swabbing with alcohol pads. The pathogenesis has been attributed to abnormal and delayed keratinization. Although affected patients present with typical lesions, the disorder is not well-known by dermatologists. In this report, we describe two patients with terra firma-forme dermatosis in the setting of xerosis cutis and atopic dermatitis. From a clinical point of view, we lay emphasis on its unique expression and diagnosis/treatment. From a histological perspective, we highlight its resemblance to dermatosis neglecta and speculate on the role of ′neglect′ in a patient with seemingly adequate hygiene. The role of urea containing emollients in the development of this disorder remains to be determined.

  13. 7 CFR 58.729 - Forming containers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Forming containers. 58.729 Section 58.729 Agriculture... Procedures § 58.729 Forming containers. Containers either lined or unlined shall be assembled and stored in a sanitary manner to prevent contamination. The handling of containers by filler crews should be done with...

  14. Microstructure evolution of 7050 Al alloy during age-forming

    International Nuclear Information System (INIS)

    Chen, Junfeng; Zou, Linchi; Li, Qiang; Chen, Yulong

    2015-01-01

    The microstructure evolution of the 7050 Al alloy treated by age-forming was studied using a designed device which can simulate the age-forming process. The grain shape, grain boundary misorientation and grain orientation evolution of 7050 Al alloy during age-forming have been quantitatively characterized by electron backscattering diffraction technique. The results show that age-forming produced abundant low-angle boundaries and elongated grains, which attributed to stress induced dislocation movement and grain boundary migration during the age-forming process. On the other side, the stress along rolling direction caused some unstable orientation grains to rotate towards the Brass and S orientations during the age-forming process. Hence, the intensity of the rolling texture orientation in age-formed samples is enhanced. But this effect decays gradually with increasing aging time, since stress decreases and precipitation hardening occurs during the age-forming process. - Highlights: • Quantitative analysis of grain evolution of 7050 Al alloys during age-forming • Stress induces some grain rotation of 7050 Al alloys during age-forming. • Creep leads to elongate grain of 7050 Al alloys during age-forming. • Obtains a trend on texture evolution during age-forming applied stress

  15. Re-discovering an Organizational Form

    DEFF Research Database (Denmark)

    Leixnering, Stephan; Meyer, Renate

    The corporation is the iconic emblem of modern capitalism. While the corporate form is today widely perceived as an instrument to maximize shareholder value, its institutionalization as an organizational form heavily built on the orientation towards public interests as a constitutive element....... In this paper, we trace public interest-orientation in the history of the Austrian corporation, where it has continuously been present for about 200 years. In 1937, public interest-orientation became a codified obligation that, slightly reworded in 1965, has remained an integral part of corporate law until...

  16. Codimension two Kaehler submanifolds of space forms

    International Nuclear Information System (INIS)

    Ferreira, M.J.; Tribuzy, R.

    2001-03-01

    In this article we study isometric immersions from Kaehler manifolds whose (1,1) part of the second fundamental form is parallel, the ppmc isometric immersions. When the domain is a Riemann surface these immersions are precisely those with parallel mean curvature. P. J. Ryan has classified the Kaehler manifolds that admit isometric immersions, as real hypersurfaces, in space forms. We classify the codimension two ppmc isometric immersions into space forms. (author)

  17. Developing a simplified consent form for biobanking.

    Science.gov (United States)

    Beskow, Laura M; Friedman, Joëlle Y; Hardy, N Chantelle; Lin, Li; Weinfurt, Kevin P

    2010-10-08

    Consent forms have lengthened over time and become harder for participants to understand. We sought to demonstrate the feasibility of creating a simplified consent form for biobanking that comprises the minimum information necessary to meet ethical and regulatory requirements. We then gathered preliminary data concerning its content from hypothetical biobank participants. We followed basic principles of plain-language writing and incorporated into a 2-page form (not including the signature page) those elements of information required by federal regulations and recommended by best practice guidelines for biobanking. We then recruited diabetes patients from community-based practices and randomized half (n = 56) to read the 2-page form, first on paper and then a second time on a tablet computer. Participants were encouraged to use "More information" buttons on the electronic version whenever they had questions or desired further information. These buttons led to a series of "Frequently Asked Questions" (FAQs) that contained additional detailed information. Participants were asked to identify specific sentences in the FAQs they thought would be important if they were considering taking part in a biorepository. On average, participants identified 7 FAQ sentences as important (mean 6.6, SD 14.7, range: 0-71). No one sentence was highlighted by a majority of participants; further, 34 (60.7%) participants did not highlight any FAQ sentences. Our preliminary findings suggest that our 2-page form contains the information that most prospective participants identify as important. Combining simplified forms with supplemental material for those participants who desire more information could help minimize consent form length and complexity, allowing the most substantively material information to be better highlighted and enabling potential participants to read the form and ask questions more effectively.

  18. NOAA Form 370 Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data set contains information from submitted NOAA Form 370s, also known as the Fisheries Certificate of Origin, for imported shipments of frozen and/or processed...

  19. 77 FR 74010 - Proposed Changes to FCC Form 499-A, FCC Form 499-Q, and Accompanying Instructions

    Science.gov (United States)

    2012-12-12

    ... changed to ``2012.'' 4. Web Pages. Hyperlinks were revised as appropriate throughout the Form 499-A... identification number (EIN) for the filer's holding company. 10. Definition of Affiliate. The definition of the... Instructions. This definition is the same as the definition contained in Appendix A of the Form 499-A...

  20. P-nflation: generating cosmic Inflation with p-forms

    Energy Technology Data Exchange (ETDEWEB)

    Germani, Cristiano [LUTH, Observatoire de Paris, CNRS UMR 8102, Universite Paris Diderot, 5 Place Jules Janssen, 92195 Meudon Cedex (France); Kehagias, Alex, E-mail: cristiano.germani@obspm.fr, E-mail: kehagias@central.ntua.gr [Department of Physics, National Technical University of Athens, GR-15773, Zografou, Athens (Greece)

    2009-03-15

    We show that an inflationary background might be realized by using any p-form non-minimally coupled to gravity. Standard scalar field inflation corresponds to the 0-form case and vector inflation to the 1-form. Moreover, we show that the 2- and 3-form fields are dual to a new vector and scalar inflationary theories where the kinetic terms are non-minimally coupled to gravity.

  1. Normal forms of Hopf-zero singularity

    International Nuclear Information System (INIS)

    Gazor, Majid; Mokhtari, Fahimeh

    2015-01-01

    The Lie algebra generated by Hopf-zero classical normal forms is decomposed into two versal Lie subalgebras. Some dynamical properties for each subalgebra are described; one is the set of all volume-preserving conservative systems while the other is the maximal Lie algebra of nonconservative systems. This introduces a unique conservative–nonconservative decomposition for the normal form systems. There exists a Lie-subalgebra that is Lie-isomorphic to a large family of vector fields with Bogdanov–Takens singularity. This gives rise to a conclusion that the local dynamics of formal Hopf-zero singularities is well-understood by the study of Bogdanov–Takens singularities. Despite this, the normal form computations of Bogdanov–Takens and Hopf-zero singularities are independent. Thus, by assuming a quadratic nonzero condition, complete results on the simplest Hopf-zero normal forms are obtained in terms of the conservative–nonconservative decomposition. Some practical formulas are derived and the results implemented using Maple. The method has been applied on the Rössler and Kuramoto–Sivashinsky equations to demonstrate the applicability of our results. (paper)

  2. Normal forms of Hopf-zero singularity

    Science.gov (United States)

    Gazor, Majid; Mokhtari, Fahimeh

    2015-01-01

    The Lie algebra generated by Hopf-zero classical normal forms is decomposed into two versal Lie subalgebras. Some dynamical properties for each subalgebra are described; one is the set of all volume-preserving conservative systems while the other is the maximal Lie algebra of nonconservative systems. This introduces a unique conservative-nonconservative decomposition for the normal form systems. There exists a Lie-subalgebra that is Lie-isomorphic to a large family of vector fields with Bogdanov-Takens singularity. This gives rise to a conclusion that the local dynamics of formal Hopf-zero singularities is well-understood by the study of Bogdanov-Takens singularities. Despite this, the normal form computations of Bogdanov-Takens and Hopf-zero singularities are independent. Thus, by assuming a quadratic nonzero condition, complete results on the simplest Hopf-zero normal forms are obtained in terms of the conservative-nonconservative decomposition. Some practical formulas are derived and the results implemented using Maple. The method has been applied on the Rössler and Kuramoto-Sivashinsky equations to demonstrate the applicability of our results.

  3. Electromagnetic form factors in the light-front dynamics

    International Nuclear Information System (INIS)

    Karmanov, V.A.; Smirnov, A.V.

    1992-01-01

    It is shown that the electromagnetic vertex of a nucleus (and of any bound system), expressed through the wave function in the light-front dynamics at relativistic values of momentum transfer, contains a contribution of nonphysical form factors which increases the total number of invariant form factors (for the deuteron from 3 up to 11). This fact explains an ambiguity in the form factors calculated previously. The physical and nonphysical form factors are covariantly separated. Explicit expressions for physical form factors of systems with spin 0, 1/2 and 1 through the vertex functions are obtained. (orig.)

  4. Corrosion studies on PREPP waste form

    International Nuclear Information System (INIS)

    Welch, J.M.; Neilson, R.M. Jr.

    1984-05-01

    Deformation or Failure Test and Accelerated Corrosion Test procedures were conducted to investigate the effect of formulation variables on the corrosion of oversize waste in Process Experimental Pilot Plant (PREPP) concrete waste forms. The Deformation or Failure Test did not indicate substantial waste form swelling from corrosion. The presence or absence of corrosion inhibitor was the most significant factor relative to measured half-cell potentials identified in the Accelerated Corrosion Test. However, corrosion inhibitor was determined to be only marginally beneficial. While this study produced no evidence that corrosion is of sufficient magnitude to produce serious degradation of PREPP waste forms, the need for corrosion rate testing is suggested. 11 references, 4 figures, 8 tables

  5. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

    OpenAIRE

    Baranowski, Przemysław; Karolewicz, Bożena; Gajda, Maciej; Pluta, Janusz

    2014-01-01

    This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to...

  6. VMS forms Output Tables

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These output tables contain parsed and format validated data from the various VMS forms that are sent from any given vessel, while at sea, from the VMS devices on...

  7. Readability of Invasive Procedure Consent Forms.

    Science.gov (United States)

    Eltorai, Adam E M; Naqvi, Syed S; Ghanian, Soha; Eberson, Craig P; Weiss, Arnold-Peter C; Born, Christopher T; Daniels, Alan H

    2015-12-01

    Informed consent is a pillar of ethical medicine which requires patients to fully comprehend relevant issues including the risks, benefits, and alternatives of an intervention. Given the average reading skill of US adults is at the 8th grade level, the American Medical Association (AMA) and the National Institutes of Health (NIH) recommend patient information materials should not exceed a 6th grade reading level. We hypothesized that text provided in invasive procedure consent forms would exceed recommended readability guidelines for medical information. To test this hypothesis, we gathered procedure consent forms from all surgical inpatient hospitals in the state of Rhode Island. For each consent form, readability analysis was measured with the following measures: Flesch Reading Ease Formula, Flesch-Kincaid Grade Level, Fog Scale, SMOG Index, Coleman-Liau Index, Automated Readability Index, and Linsear Write Formula. These readability scores were used to calculate a composite Text Readability Consensus Grade Level. Invasive procedure consent forms were found to be written at an average of 15th grade level (i.e., third year of college), which is significantly higher than the average US adult reading level of 8th grade (p readability guidelines for patient materials of 6th grade (p readability levels which makes comprehension difficult or impossible for many patients. Efforts to improve the readability of procedural consent forms should improve patient understanding regarding their healthcare decisions. © 2015 Wiley Periodicals, Inc.

  8. Baryon electromagnetic form factors at BESIII

    Directory of Open Access Journals (Sweden)

    Dbeyssi Alaa

    2017-01-01

    Full Text Available Electromagnetic form factors are fundamental quantities which parameterize the electric and magnetic structure of hadrons. This contribution reports on the measurements of baryon electromagnetic form factors at the BESIII experiment in Beijing. The Beijing e+e− collider BEPCII is a double-ring symmetric collider running at √s between 2.0 and 4.6 GeV. Baryon electromagnetic form factors can be measured at BESIII in direct e+e−-annihilation and in initial state radiation processes. Based on the data collected by the BESIII detector at 12 center of mass energies between 2.23 and 3.67 GeV, the e+e− → p̄p cross section and the time-like proton form factor is measured. Preliminary results from the analysis of the initial state radiation process e+e− → p̄pγ using a data set of 7.408 fb−1 collected at center-of-mass energies between 3.773 and 4.6 GeV, are also presented. The cross section for e+e−→Λ¯Λ${e^ + }{e^ - } \\to \\bar \\Lambda \\Lambda $ is measured based on 40.5 pb−1 data collected at 4 energy points from the threshold up to 3.08 GeV. Preliminary results on the total cross section and the Λ effective form factor are shown. Ongoing analysis based on the high luminosity energy scan from 2015 and from radiative return at different √s are also described.

  9. Observed characteristics of auroral forms

    International Nuclear Information System (INIS)

    Davis, T.N.

    1978-01-01

    Observations indicate that the extended auroral arc is the basic form of the discrete aurora, the brightest and most obvious kind of aurora. Both motions of auroral arcs and their distortions into convoluted forms indicate the presence of shear processes involving substantial charge excesses and magnetic field-aligned currents. Consequently, strong electric fields, both horizontal and vertical, characterize the discrete aurora. The observations of auroral arcs and observations of associated charged-particle fluxes, electric fields and currents fit together into a relatively cohesive description of the auroral arc which is compatible with at least one proposed model of the causative processes. On the other hand, an equally important type of aurora - pulsating aurora - exhibits quite different characteristics which distinguish it from the discrete aurora and which are difficult to interpret satisfactorily in terms of existing proposed models of particle precipitation and excitation of auroral emission. The lack of shearing behavior in the pulsating aurora indicates that substantial electric fields are not associated with it. Transitional forms of auroras exhibit an intermediate degree of shear motion. (Auth.)

  10. CLASSIFICATION OF VARIOUS FORMS OF TOURISM

    Directory of Open Access Journals (Sweden)

    Ana-Maria Ghete

    2016-12-01

    Full Text Available In this article I have tried to highlight the many criteria according to which tourism is classified and what are its main forms. Tourism is considered to be the most developed industry at the European level with a strong economic impact and the highest annual growth rate. Because of its scale and its various elements , but also because of the value and originality of these elements, tourism is the main motivation of all that is tourist traffic . A particular area or landmark is an interest to travel as far as that can provide tourist activity. The tourism potential of an area can be defined as all the elements that make up the sights with facilities to receive tourists representative. The main types of tourism that will be detailed in this article are: tourism, recreation and leisure, healthcare tourism, tourism or curative spa, cultural tourism, educational, social, or complex-type shopping tourism. The criteria according to which can be classified tourism are: distance, length of stay, geographic origin of tourists, type of transport used, how to organize your stay, the conduct of the stay, peculiarities destination, interaction travelers with the destination, the price paid, tourist`s age, the number of tourists. Depending on the area of origin, tourism and domestic tourism are classified in international tourism. Such, international tourism is classified in inbound tourism and outbound tourism. Any travel between these two forms is particular between which there is no definite boundary but some interdependence that helps promote tourism activities. Depending on the degree of mobility of tourists, tourism classified in tourism accommodation and tourism traffic. Tourism residence has three forms, namely long-stay tourism, tourism stay average stay lasting tourism and stay for a brief stay. Seasonality is another factor that affects tourist flows. This tourism classified into 3 types: winter tourism, summer and circumstance. Depending on the

  11. Nucleon Form Factors Using Spin Degrees of Freedom

    International Nuclear Information System (INIS)

    Jones, Mark

    2002-01-01

    An overview of recent measurements of the neutron and proton electromagnetic form factors from double polarization experiments. Spin observables are sensitive to the product of nucleon form factor which allows access to the small nucleon electric form factors

  12. A new form of the rotating C-metric

    International Nuclear Information System (INIS)

    Hong, Kenneth; Teo, Edward

    2005-01-01

    In a previous paper, we showed that the traditional form of the charged C-metric can be transformed, by a change of coordinates, into one with an explicitly factorizable structure function. This new form of the C-metric has the advantage that its properties become much simpler to analyse. In this paper, we propose an analogous new form for the rotating charged C-metric, with structure function G(ξ) = (1 - ξ 2 )(1 + r + Aξ)(1 + r - Aξ), where r ± are the usual locations of the horizons in the Kerr-Newman black hole. Unlike the non-rotating case, this new form is not related to the traditional one by a coordinate transformation. We show that the physical distinction between these two forms of the rotating C-metric lies in the nature of the conical singularities causing the black holes to accelerate apart: the new form is free of torsion singularities and therefore does not contain any closed timelike curves. We claim that this new form should be considered the natural generalization of the C-metric with rotation

  13. Forming lead-based anodes

    Energy Technology Data Exchange (ETDEWEB)

    Ogorodnichuk, V I; Voitsekhovich, R I

    1972-01-01

    Lead-based anodes can be produced by forming a layer of lead dioxide by chemical treatment in a solution of sulfuric acid in potassium permanganate at 80 to 100/sup 0/. The solution is mixed by compressed air. (RWR)

  14. Spring-back of flexible roll forming bending process

    International Nuclear Information System (INIS)

    Zhang, Y; Kim, D H; Jung, D W

    2015-01-01

    Simulations are now widely used in the field of roll forming because of their convenience. Simulations provide a low cost, secure and fast analysis tool. Flexible roll forming provides the desired shapes with a one time forming process. For roll forming, the velocity of the sheet and friction are important factors to attain an ideal shape. Because it is a complicated process, simulations provide a better understanding of the roll forming process. Simulations were peformed using ABAQUS software linked to elastic-plastic modules which we developed taking into account of interactions between these fields [1]. The application of this method makes it possible to highlight the strain-stress and mechanical behaviour laws and the spring-back. Thus, the flexible roll forming and bending process can be well described by the simulation software and guide the actual machine. (paper)

  15. Siegel modular forms and black hole entropy

    Energy Technology Data Exchange (ETDEWEB)

    Belin, Alexandre; Castro, Alejandra [Institute for Theoretical Physics, University of Amsterdam,Science Park 904, Postbus 94485, 1090 GL Amsterdam (Netherlands); Gomes, João [Institute for Theoretical Physics, University of Amsterdam,Science Park 904, Postbus 94485, 1090 GL Amsterdam (Netherlands); Institute for Theoretical Physics, University of Utrecht,Leuvenlaan 3584 CE Utrecht (Netherlands); Keller, Christoph A. [Department of Mathematics, ETH Zurich,CH-8092 Zurich (Switzerland)

    2017-04-11

    We discuss the application of Siegel Modular Forms to Black Hole entropy counting. The role of the Igusa cusp form χ{sub 10} in the D1D5P system is well-known, and its transformation properties are what allows precision microstate counting in this case. We apply a similar method to extract the Fourier coefficients of other Siegel modular and paramodular forms, and we show that they could serve as candidates for other types of black holes. We investigate the growth of their coefficients, identifying the dominant contributions and the leading logarithmic corrections in various regimes. We also discuss similarities and differences to the behavior of χ{sub 10}, and possible physical interpretations of such forms both from a microscopic and gravitational point of view.

  16. Over-Expression, Purification and Crystallization of Human Dihydrolipoamide Dehydrogenase

    Science.gov (United States)

    Hong, Y. S.; Ciszak, Ewa; Patel, Mulchand

    2000-01-01

    Dehydrolipoamide dehydrogenase (E3; dihydrolipoan-tide:NAD+ oxidoreductase, EC 1.8.1.4) is a common catalytic component found in pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, and branched-chain cc-keto acid dehydrogenase complex. E3 is also a component (referred to as L protein) of the glycine cleavage system in bacterial metabolism (2). Active E3 forms a homodimer with four distinctive subdomain structures (FAD binding, NAD+ binding, central and interface domains) with non-covalently but tightly bound FAD in the holoenzyme. Deduced amino acids from cloned full-length human E3 gene showed a total of 509 amino acids with a leader sequence (N-terminal 35 amino acids) that is excised (mature form) during transportation of expressed E3 into mitochondria membrane. So far, three-dimensional structure of human E3 has not been reported. Our effort to achieve the elucidation of the X-ray crystal structure of human E3 will be presented. Recombinant pPROEX-1 expression vector (from GIBCO BRL Life Technologies) having the human E3 gene without leader sequence was constructed by Polymerase Chain Reaction (PCR) and subsequent ligation, and cloned in E.coli XL1-Blue by transformation. Since pPROEX-1 vector has an internal His-tag (six histidine peptide) located at the upstream region of a multicloning site, one-step affinity purification of E3 using nickelnitriloacetic acid (Ni-NTA) agarose resin, which has a strong affinity to His-tag, was feasible. Also a seven-amino-acid spacer peptide and a recombinant tobacco etch virus protease recognition site (seven amino acids peptide) found between His-tag and first amino acid of expressed E3 facilitated the cleavage of His-tag from E3 after the affinity purification. By IPTG induction, ca. 15 mg of human E3 (mature form) was obtained from 1L LB culture with overnight incubation at 25C. Over 98% of purity of E3 from one-step Ni-NTA agarose affinity purification was confirmed by SDS-PAGE analysis. For

  17. GRACE with FORM

    International Nuclear Information System (INIS)

    Fujimoto, J.; Ishikawa, T.; Kato, K.; Kaneko, T.; Nakazawa, N..; Shimizu, Y.; Vermaseren, J.; Yasui, Y.

    2006-01-01

    A new version of GRACE/1-loop, a system for the automatic calculation of 1-loop Feynman diagrams, has been developed after the replacement of its symbolic manipulation engine from REDUCE to FORM. This enables us the efficient memory management that is essential for the handling of a tremendous number of Feynman diagrams, so that the performance of GRACE/1-loop is significantly improved as demonstrated in the text

  18. On form factors of boundary changing operators

    Energy Technology Data Exchange (ETDEWEB)

    Bajnok, Z., E-mail: bajnok.zoltan@wigner.mta.hu [MTA Lendület Holographic QFT Group, Wigner Research Centre for Physics, P.O.B. 49, H-1525 Budapest 114 (Hungary); Hollo, L., E-mail: hollo.laszlo@wigner.mta.hu [MTA Lendület Holographic QFT Group, Wigner Research Centre for Physics, P.O.B. 49, H-1525 Budapest 114 (Hungary); Laboratoire de Physique Théorique, École Normale Supérieure, 24, rue Lhomond, 75005 Paris (France)

    2016-04-15

    We develop a form factor bootstrap program to determine the matrix elements of local, boundary condition changing operators. We propose axioms for these form factors and determine their solutions in the free boson and Lee–Yang models. The sudden change in the boundary condition, caused by an operator insertion, can be interpreted as a local quench and the form factors provide the overlap of any state before the quench with any outgoing state after the quench.

  19. Alternative High-Performance Ceramic Waste Forms

    Energy Technology Data Exchange (ETDEWEB)

    Sundaram, S. K. [Alfred Univ., NY (United States)

    2017-02-01

    This final report (M5NU-12-NY-AU # 0202-0410) summarizes the results of the project titled “Alternative High-Performance Ceramic Waste Forms,” funded in FY12 by the Nuclear Energy University Program (NEUP Project # 12-3809) being led by Alfred University in collaboration with Savannah River National Laboratory (SRNL). The overall focus of the project is to advance fundamental understanding of crystalline ceramic waste forms and to demonstrate their viability as alternative waste forms to borosilicate glasses. We processed single- and multiphase hollandite waste forms based on simulated waste streams compositions provided by SRNL based on the advanced fuel cycle initiative (AFCI) aqueous separation process developed in the Fuel Cycle Research and Development (FCR&D). For multiphase simulated waste forms, oxide and carbonate precursors were mixed together via ball milling with deionized water using zirconia media in a polyethylene jar for 2 h. The slurry was dried overnight and then separated from the media. The blended powders were then subjected to melting or spark plasma sintering (SPS) processes. Microstructural evolution and phase assemblages of these samples were studied using x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersion analysis of x-rays (EDAX), wavelength dispersive spectrometry (WDS), transmission electron spectroscopy (TEM), selective area x-ray diffraction (SAXD), and electron backscatter diffraction (EBSD). These results showed that the processing methods have significant effect on the microstructure and thus the performance of these waste forms. The Ce substitution into zirconolite and pyrochlore materials was investigated using a combination of experimental (in situ XRD and x-ray absorption near edge structure (XANES)) and modeling techniques to study these single phases independently. In zirconolite materials, a transition from the 2M to the 4M polymorph was observed with increasing Ce content. The resulting

  20. Fabrication Aware Form-finding

    DEFF Research Database (Denmark)

    Egholm Pedersen, Ole; Larsen, Niels Martin; Pigram, Dave

    2014-01-01

    This paper describes a design and construction method that combines two distinct material systems with fabrication aware form-finding and file-to-factory workflows. The method enables the fluent creation of complex materially efficient structures comprising high populations of geometrically uniqu...

  1. Form coefficient of helical toroidal solenoids

    International Nuclear Information System (INIS)

    Amelin, V.Z.; Kunchenko, V.B.

    1982-01-01

    For toroidal solenoids with continuous spiral coil, winded according to the laws of equiinclined and simple cylindrical spirals with homogeneous, linearly increasing to the coil periphery and ''Bitter'' distribution of current density, the analytical expressions for the dependence between capacity consumed and generated magnetic field, expressions for coefficients of form similar to Fabry coefficient for cylindrical solenoids are obtained and dependence of the form coefficient and relative volume of solenoid conductor on the number of revolutions of screw line per one circumvention over the large torus radius is also investigated. Analytical expressions of form coefficients and graphical material permit to select the optimum geometry as to capacity consumed both for spiral (including ''force-free'') and conventional toroidal solenoids of magnetic systems in thermonulear installations

  2. Mixed low-level waste form evaluation

    International Nuclear Information System (INIS)

    Pohl, P.I.; Cheng, Wu-Ching; Wheeler, T.; Waters, R.D.

    1997-01-01

    A scoping level evaluation of polyethylene encapsulation and vitreous waste forms for safe storage of mixed low-level waste was performed. Maximum permissible radionuclide concentrations were estimated for 15 indicator radionuclides disposed of at the Hanford and Savannah River sites with respect to protection of the groundwater and inadvertent intruder pathways. Nominal performance improvements of polyethylene and glass waste forms relative to grout are reported. These improvements in maximum permissible radionuclide concentrations depend strongly on the radionuclide of concern and pathway. Recommendations for future research include improving the current understanding of the performance of polymer waste forms, particularly macroencapsulation. To provide context to these estimates, the concentrations of radionuclides in treated DOE waste should be compared with the results of this study to determine required performance

  3. Hadronic form factors in kaon photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Syukurilla, L., E-mail: tmart@fisika.ui.ac.id; Mart, T., E-mail: tmart@fisika.ui.ac.id [Department Fisika, FMIPA, Universitas Indonesia, Depok, 164242 (Indonesia)

    2014-09-25

    We have revisited the effect of hadronic form factors in kaon photoproduction process by utilizing an isobaric model developed for kaon photoproduction off the proton. The model is able to reproduce the available experimental data nicely as well as to reveal the origin of the second peak in the total cross section, which was the main source of confusion for decades. Different from our previous study, in the present work we explore the possibility of using different hadronic form factors in each of the KΛN vertices. The use of different hadronic form factors, e.g. dipole, Gaussian, and generalized dipole, has been found to produce a more flexible isobar model, which can provide a significant improvement in the model.

  4. 21 CFR 1305.17 - Preservation of DEA Forms 222.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Preservation of DEA Forms 222. 1305.17 Section... II CONTROLLED SUBSTANCES DEA Form 222 § 1305.17 Preservation of DEA Forms 222. (a) The purchaser must retain Copy 3 of each executed DEA Form 222 and all copies of unaccepted or defective forms with each...

  5. The Textile Form of Sound

    DEFF Research Database (Denmark)

    Bendixen, Cecilie

    Sound is a part of architecture, and sound is complex. Upon this, sound is invisible. How is it then possible to design visual objects that interact with the sound? This paper addresses the problem of how to get access to the complexity of sound and how to make textile material revealing the form...... goemetry by analysing the sound pattern at a specific spot. This analysis is done theoretically with algorithmic systems and practical with waves in water. The paper describes the experiments and the findings, and explains how an analysis of sound can be catched in a textile form....

  6. Reducing Approximation Error in the Fourier Flexible Functional Form

    Directory of Open Access Journals (Sweden)

    Tristan D. Skolrud

    2017-12-01

    Full Text Available The Fourier Flexible form provides a global approximation to an unknown data generating process. In terms of limiting function specification error, this form is preferable to functional forms based on second-order Taylor series expansions. The Fourier Flexible form is a truncated Fourier series expansion appended to a second-order expansion in logarithms. By replacing the logarithmic expansion with a Box-Cox transformation, we show that the Fourier Flexible form can reduce approximation error by 25% on average in the tails of the data distribution. The new functional form allows for nested testing of a larger set of commonly implemented functional forms.

  7. Cocrystals of 5-fluorocytosine. I. Coformers with fixed hydrogen-bonding sites.

    Science.gov (United States)

    Tutughamiarso, Maya; Wagner, Guido; Egert, Ernst

    2012-08-01

    The antifungal drug 5-fluorocytosine (4-amino-5-fluoro-1,2-dihydropyrimidin-2-one) was cocrystallized with five complementary compounds in order to better understand its drug-receptor interaction. The first two compounds, 2-aminopyrimidine (2-amino-1,3-diazine) and N-acetylcreatinine (N-acetyl-2-amino-1-methyl-5H-imidazol-4-one), exhibit donor-acceptor sites for R(2)(2)(8) heterodimer formation with 5-fluorocytosine. Such a heterodimer is observed in the cocrystal with 2-aminopyrimidine (I); in contrast, 5-fluorocytosine and N-acetylcreatinine [which forms homodimers in its crystal structure (II)] are connected only by a single hydrogen bond in (III). The other three compounds 6-aminouracil (6-amino-2,4-pyrimidinediol), 6-aminoisocytosine (2,6-diamino-3H-pyrimidin-4-one) and acyclovir [acycloguanosine or 2-amino-9-[(2-hydroxyethoxy)methyl]-1,9-dihydro-6H-purin-6-one] possess donor-donor-acceptor sites; therefore, they can interact with 5-fluorocytosine to form a heterodimer linked by three hydrogen bonds. In the cocrystals with 6-aminoisocytosine (Va)-(Vd), as well as in the cocrystal with the antiviral drug acyclovir (VII), the desired heterodimers are observed. However, they are not formed in the cocrystal with 6-aminouracil (IV), where the components are connected by two hydrogen bonds. In addition, a solvent-free structure of acyclovir (VI) was obtained. A comparison of the calculated energies released during dimer formation helped to rationalize the preference for hydrogen-bonding interactions in the various cocrystal structures.

  8. Development of solid radionuclide waste forms in the United States

    International Nuclear Information System (INIS)

    Crandall, J.L.

    1979-01-01

    New ways of reworking the wastes require a new classification in terms of the final waste forms. This paper surveys the candidate forms: encapsulation binders, in-place solidification waste forms, glass and ceramic waste forms, mineral waste forms, matrix waste forms, gaseous waste forms (fixation), and canisters and engineered barriers. Participants in the US-high-level waste form development program are listed. Requirements and selection of waste forms are also discussed. 26 references

  9. Integrated Manufacturing of Aerospace Components by Superplastic Forming Technology

    Directory of Open Access Journals (Sweden)

    Ju Min Kyung

    2015-01-01

    Full Text Available Aerospace vehicle requires lightweight structures to obtain weight saving and fuel efficiency. It is known that superplastic characteristics of some materials provide significant opportunity for forming complicated, lightweight components of aerospace structure. One of the most important advantages of using superplastic forming process is its simplicity to form integral parts and economy in tooling[1]. For instance, it can be applied to blow-forming, in which a metal sheet is deformed due to the pressure difference of hydrostatic gas on both sides of the sheet. Since the loading medium is gas pressure difference, this forming is different from conventional sheet metal forming technique in that this is stress-controlled rather than strain and strain rate controlled. This method is especially advantageous when several sheet metals are formed into complex shapes. In this study, it is demonstrated that superplastic forming process with titanium and steel alloy can be applied to manufacturing lightweight integral structures of aerospace structural parts and rocket propulsion components. The result shows that the technology to design and develop the forming process of superplastic forming can be applied for near net shape forming of a complex contour of a thrust chamber and a toroidal fuel tank.

  10. Summer School and Conference : Computations with Modular Forms

    CERN Document Server

    Wiese, Gabor

    2014-01-01

    This volume contains original research articles, survey articles and lecture notes related to the Computations with Modular Forms 2011 Summer School and Conference, held at the University of Heidelberg. A key theme of the Conference and Summer School was the interplay between theory, algorithms and experiment. The 14 papers offer readers both, instructional courses on the latest algorithms for computing modular and automorphic forms, as well as original research articles reporting on the latest developments in the field. The three Summer School lectures provide an introduction to modern algorithms together with some theoretical background for computations of and with modular forms, including computing cohomology of arithmetic groups, algebraic automorphic forms, and overconvergent modular symbols. The 11 Conference papers cover a wide range of themes related to computations with modular forms, including lattice methods for algebraic modular forms on classical groups, a generalization of the Maeda conjecture, ...

  11. Decoupled Simulation Method For Incremental Sheet Metal Forming

    International Nuclear Information System (INIS)

    Sebastiani, G.; Brosius, A.; Tekkaya, A. E.; Homberg, W.; Kleiner, M.

    2007-01-01

    Within the scope of this article a decoupling algorithm to reduce computing time in Finite Element Analyses of incremental forming processes will be investigated. Based on the given position of the small forming zone, the presented algorithm aims at separating a Finite Element Model in an elastic and an elasto-plastic deformation zone. Including the elastic response of the structure by means of model simplifications, the costly iteration in the elasto-plastic zone can be restricted to the small forming zone and to few supporting elements in order to reduce computation time. Since the forming zone moves along the specimen, an update of both, forming zone with elastic boundary and supporting structure, is needed after several increments.The presented paper discusses the algorithmic implementation of the approach and introduces several strategies to implement the denoted elastic boundary condition at the boundary of the plastic forming zone

  12. Molecular mechanisms in the selective basal activation of pyrabactin receptor 1: Comparative analysis of mutants.

    Science.gov (United States)

    Dorosh, Lyudmyla; Rajagopalan, Nandhakishore; Loewen, Michele C; Stepanova, Maria

    2014-01-01

    Pyrabactin receptors (PYR) play a central role in abscisic acid (ABA) signal transduction; they are ABA receptors that inhibit type 2C protein phosphatases (PP2C). Molecular aspects contributing to increased basal activity of PYR against PP2C are studied by molecular dynamics (MD) simulations. An extensive series of MD simulations of the apo-form of mutagenized PYR1 as a homodimer and in complex with homology to ABA-insensitive 1 (HAB1) phosphatase are reported. In order to investigate the detailed molecular mechanisms mediating PYR1 activity, the MD data was analyzed by essential collective dynamics (ECD), a novel approach that allows the identification, with atomic resolution, of persistent dynamic correlations based on relatively short MD trajectories. Employing the ECD method, the effects of select mutations on the structure and dynamics of the PYR1 complexes were investigated and considered in the context of experimentally determined constitutive activities against HAB1. Approaches to rationally design constitutively active PYR1 constructs to increase PP2C inhibition are discussed.

  13. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    2014-03-01

    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  14. Characterization of a unique class C acid phosphatase from Clostridium perfringens.

    Science.gov (United States)

    Reilly, Thomas J; Chance, Deborah L; Calcutt, Michael J; Tanner, John J; Felts, Richard L; Waller, Stephen C; Henzl, Michael T; Mawhinney, Thomas P; Ganjam, Irene K; Fales, William H

    2009-06-01

    Clostridium perfringens is a gram-positive anaerobe and a pathogen of medical importance. The detection of acid phosphatase activity is a powerful diagnostic indicator of the presence of C. perfringens among anaerobic isolates; however, characterization of the enzyme has not previously been reported. Provided here are details of the characterization of a soluble recombinant form of this cell-associated enzyme. The denatured enzyme was approximately 31 kDa and a homodimer in solution. It catalyzed the hydrolysis of several substrates, including para-nitrophenyl phosphate, 4-methylumbelliferyl phosphate, and 3' and 5' nucleoside monophosphates at pH 6. Calculated K(m)s ranged from 0.2 to 0.6 mM with maximum velocity ranging from 0.8 to 1.6 micromol of P(i)/s/mg. Activity was enhanced in the presence of some divalent cations but diminished in the presence of others. Wild-type enzyme was detected in all clinical C. perfringens isolates tested and found to be cell associated. The described enzyme belongs to nonspecific acid phosphatase class C but is devoid of lipid modification commonly attributed to this class.

  15. Structure of a CRISPR-associated protein Cas2 from Desulfovibrio vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Samai, Poulami; Smith, Paul; Shuman, Stewart [Molecular Biology Program, Sloan-Kettering Institute for Cancer Research (United States)

    2010-12-01

    A 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. CRISPRs (clustered regularly interspaced short palindromic repeats) provide bacteria and archaea with RNA-guided acquired immunity to invasive DNAs. CRISPR-associated (Cas) proteins carry out the immune effector functions. Cas2 is a universal component of the CRISPR system. Here, a 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. DvuCas2 is a homodimer, with each protomer consisting of an N-terminal βαββαβ ferredoxin fold (amino acids 1–78) to which is appended a C-terminal segment (amino acids 79–102) that includes a short 3{sub 10}-helix and a fifth β-strand. The β5 strands align with the β4 strands of the opposite protomers, resulting in two five-stranded antiparallel β-sheets that form a sandwich at the dimer interface. The DvuCas2 dimer is stabilized by a distinctive network of hydrophilic cross-protomer side-chain interactions.

  16. Structure of a CRISPR-associated protein Cas2 from Desulfovibrio vulgaris

    International Nuclear Information System (INIS)

    Samai, Poulami; Smith, Paul; Shuman, Stewart

    2010-01-01

    A 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. CRISPRs (clustered regularly interspaced short palindromic repeats) provide bacteria and archaea with RNA-guided acquired immunity to invasive DNAs. CRISPR-associated (Cas) proteins carry out the immune effector functions. Cas2 is a universal component of the CRISPR system. Here, a 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. DvuCas2 is a homodimer, with each protomer consisting of an N-terminal βαββαβ ferredoxin fold (amino acids 1–78) to which is appended a C-terminal segment (amino acids 79–102) that includes a short 3 10 -helix and a fifth β-strand. The β5 strands align with the β4 strands of the opposite protomers, resulting in two five-stranded antiparallel β-sheets that form a sandwich at the dimer interface. The DvuCas2 dimer is stabilized by a distinctive network of hydrophilic cross-protomer side-chain interactions

  17. A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

    International Nuclear Information System (INIS)

    Grum, Daniel; Boom, Johannes van den; Neumann, Daniel; Matena, Anja; Link, Nina M.; Mueller, Jonathan W.

    2010-01-01

    3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Foerster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that - in spite of its low quantum yield - is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.

  18. Review of high-level waste form properties. [146 bibliographies

    Energy Technology Data Exchange (ETDEWEB)

    Rusin, J.M.

    1980-12-01

    This report is a review of waste form options for the immobilization of high-level-liquid wastes from the nuclear fuel cycle. This review covers the status of international research and development on waste forms as of May 1979. Although the emphasis in this report is on waste form properties, process parameters are discussed where they may affect final waste form properties. A summary table is provided listing properties of various nuclear waste form options. It is concluded that proposed waste forms have properties falling within a relatively narrow range. In regard to crystalline versus glass waste forms, the conclusion is that either glass of crystalline materials can be shown to have some advantage when a single property is considered; however, at this date no single waste form offers optimum properties over the entire range of characteristics investigated. A long-term effort has been applied to the development of glass and calcine waste forms. Several additional waste forms have enough promise to warrant continued research and development to bring their state of development up to that of glass and calcine. Synthetic minerals, the multibarrier approach with coated particles in a metal matrix, and high pressure-high temperature ceramics offer potential advantages and need further study. Although this report discusses waste form properties, the total waste management system should be considered in the final selection of a waste form option. Canister design, canister materials, overpacks, engineered barriers, and repository characteristics, as well as the waste form, affect the overall performance of a waste management system. These parameters were not considered in this comparison.

  19. 45 CFR 30.6 - Form of payment.

    Science.gov (United States)

    2010-10-01

    ... Form of payment. Claims may be paid in the form of money or, when a contractual basis exists, the Department may demand the return of specific property or the performance of specific services. ...

  20. Roll forming of eco-friendly stud

    Science.gov (United States)

    Keum, Y. T.; Lee, S. Y.; Lee, T. H.; Sim, J. K.

    2013-12-01

    In order to manufacture an eco-friendly stud, the sheared pattern is designed by the Taguchi method and expanded by the side rolls. The seven geometrical shape of sheared pattern are considered in the structural and thermal analyses to select the best functional one in terms of the durability and fire resistance of dry wall. For optimizing the size of the sheared pattern chosen, the L9 orthogonal array and smaller-the-better characteristics of the Taguchi method are used. As the roll gap causes forming defects when the upper-and-lower roll type is adopted for expanding the sheared pattern, the side roll type is introduced. The stress and strain distributions obtained by the FEM simulation of roll-forming processes are utilized for the design of expanding process. The expanding process by side rolls shortens the length of expanding process and minimizes the cost of dies. Furthermore, the stud manufactured by expanding the sheared pattern of the web is an eco-friend because of the scrapless roll-forming process. In addition, compared to the conventionally roll-formed stud, the material cost is lessened about 13.6% and the weight is lightened about 15.5%.

  1. FILAMENTARY STRUCTURE OF STAR-FORMING COMPLEXES

    International Nuclear Information System (INIS)

    Myers, Philip C.

    2009-01-01

    The nearest young stellar groups are associated with 'hubs' of column density exceeding 10 22 cm -2 , according to recent observations. These hubs radiate multiple 'filaments' of parsec length, having lower column density and fewer stars. Systems with many filaments tend to have parallel filaments with similar spacing. Such 'hub-filament structure' is associated with all of the nine young stellar groups within 300 pc, forming low-mass stars. Similar properties are seen in infrared dark clouds forming more massive stars. In a new model, an initial clump in a uniform medium is compressed into a self-gravitating, modulated layer. The outer layer resembles the modulated equilibrium of Schmid-Burgk with nearly parallel filaments. The filaments converge onto the compressed clump, which collapses to form stars with high efficiency. The initial medium and condensations have densities similar to those in nearby star-forming clouds and clumps. The predicted structures resemble observed hub-filament systems in their size, shape, and column density, and in the appearance of their filaments. These results suggest that HFS associated with young stellar groups may arise from compression of clumpy gas in molecular clouds.

  2. The pion form factor from first principles

    International Nuclear Information System (INIS)

    Heide, J. van der

    2004-01-01

    We calculate the electromagnetic form factor of the pion in quenched lattice QCD. The non-perturbatively improved Sheikoleslami-Wohlert lattice action is used together with the O(a) improved current. We calculate form factor for pion masses down to mπ = 380 MeV. We compare the mean square radius for the pion extracted from our form factors to the value obtained from the 'Bethe Salpeter amplitude'. Using (quenched) chiral perturbation theory, we extrapolate our results towards the physical pion mass

  3. Method of forming buried oxide layers in silicon

    Science.gov (United States)

    Sadana, Devendra Kumar; Holland, Orin Wayne

    2000-01-01

    A process for forming Silicon-On-Insulator is described incorporating the steps of ion implantation of oxygen into a silicon substrate at elevated temperature, ion implanting oxygen at a temperature below 200.degree. C. at a lower dose to form an amorphous silicon layer, and annealing steps to form a mixture of defective single crystal silicon and polycrystalline silicon or polycrystalline silicon alone and then silicon oxide from the amorphous silicon layer to form a continuous silicon oxide layer below the surface of the silicon substrate to provide an isolated superficial layer of silicon. The invention overcomes the problem of buried isolated islands of silicon oxide forming a discontinuous buried oxide layer.

  4. Glass Forming Ability in Systems with Competing Orderings

    Science.gov (United States)

    Russo, John; Romano, Flavio; Tanaka, Hajime

    2018-04-01

    Some liquids, if cooled rapidly enough to avoid crystallization, can be frozen into a nonergodic glassy state. The tendency for a material to form a glass when quenched is called "glass-forming ability," and it is of key significance both fundamentally and for materials science applications. Here, we consider liquids with competing orderings, where an increase in the glass-forming ability is signaled by a depression of the melting temperature towards its minimum at triple or eutectic points. With simulations of two model systems where glass-forming ability can be tuned by an external parameter, we are able to interpolate between crystal-forming and glass-forming behavior. We find that the enhancement of the glass-forming ability is caused by an increase in the structural difference between liquid and crystal: stronger competition in orderings towards the melting point minimum makes a liquid structure more disordered (more complex). This increase in the liquid-crystal structure difference can be described by a single adimensional parameter, i.e., the interface energy cost scaled by the thermal energy, which we call the "thermodynamic interface penalty." Our finding may provide a general physical principle for not only controlling the glass-forming ability but also the emergence of glassy behavior of various systems with competing orderings, including orderings of structural, magnetic, electronic, charge, and dipolar origin.

  5. Emotional Effects of Positive Forms of Communication

    Directory of Open Access Journals (Sweden)

    Светлана Валентиновна Ионова

    2015-12-01

    Full Text Available The article discusses the problem of emotional significance of a positive form of speech. Based on the methodology of emotions linguistics, linguoecology, communicative linguistics and the methods of description, comparison and discourse analysis, the author distinguishes some types of speech situations that demonstrate visible differences between positive expression of emotions and their content and the pragmatic effect. The difference between the notions of “positive communication” and “positive form of communication” is demonstrated. Special attention is given to the following types of positive emotional communication: tolerant emotional communication, emotional emphasis, emotional neglect, and emotional tabooing. The utterances in situations of real and textual communication demonstrate negative effects of statements expressed in a positive form and identify the specifics of positive forms of emotional communication in comparison with rational communication.

  6. Lubricant Test Methods for Sheet Metal Forming

    DEFF Research Database (Denmark)

    Bay, Niels; Olsson, David Dam; Andreasen, Jan Lasson

    2008-01-01

    appearing in different sheet forming operations such as stretch forming, deep drawing, ironing and punching. The laboratory tests have been especially designed to model the conditions in industrial production. Application of the tests for evaluating new lubricants before introducing them in production has......Sheet metal forming of tribologically difficult materials such as stainless steel, Al-alloys and Ti-alloys or forming in tribologically difficult operations like ironing, punching or deep drawing of thick plate requires often use of environmentally hazardous lubricants such as chlorinated paraffin...... oils in order to avoid galling. The present paper describes a systematic research in the development of new, environmentally harmless lubricants focusing on the lubricant testing aspects. A system of laboratory tests has been developed to study the lubricant performance under the very varied conditions...

  7. a Recursive Approach to Compute Normal Forms

    Science.gov (United States)

    HSU, L.; MIN, L. J.; FAVRETTO, L.

    2001-06-01

    Normal forms are instrumental in the analysis of dynamical systems described by ordinary differential equations, particularly when singularities close to a bifurcation are to be characterized. However, the computation of a normal form up to an arbitrary order is numerically hard. This paper focuses on the computer programming of some recursive formulas developed earlier to compute higher order normal forms. A computer program to reduce the system to its normal form on a center manifold is developed using the Maple symbolic language. However, it should be stressed that the program relies essentially on recursive numerical computations, while symbolic calculations are used only for minor tasks. Some strategies are proposed to save computation time. Examples are presented to illustrate the application of the program to obtain high order normalization or to handle systems with large dimension.

  8. Study on Explosive Forming of Aluminum Alloy

    Directory of Open Access Journals (Sweden)

    H Iyama

    2016-09-01

    Full Text Available Now, the aluminum alloy is often used as auto parts, for example, body, engine. For example, there are the body, a cylinder block, a piston, a connecting rod, interior, exterior parts, etc. These are practical used the characteristic of a light and strong aluminum alloy efficiently. However, although an aluminum alloy is lighter than steel, the elongation is smaller than that. Therefore, in press forming, some problems often occur. We have proposed use of explosive forming, in order to solve this problem. In the explosive forming, since a blank is formed at high speed, a strain rate effect becomes large and it can be made the elongation is larger. Then, in order to clarify this feature, we carried out experimental research and numerical analysis. In this paper, these contents will be discussed.

  9. Silicon nitride-fabrication, forming and properties

    International Nuclear Information System (INIS)

    Yehezkel, O.

    1983-01-01

    This article, which is a literature survey of the recent years, includes description of several methods for the formation of silicone nitride, and five methods of forming: Reaction-bonded silicon nitride, sintering, hot pressing, hot isostatic pressing and chemical vapour deposition. Herein are also included data about mechanical and physical properties of silicon nitride and the relationship between the forming method and the properties. (author)

  10. A Historical Review of High Speed Metal Forming

    OpenAIRE

    Zittel, G.

    2010-01-01

    This paper will present a Historical Review of High Speed Metal Forming beginning with the first thought of forming metal by using an electromagnetic impulse to today, whereby High Speed Metal Forming is an accepted production process. Although this paper will briefly cover the basic physics of the process, it will not dwell on it. It will rather show how the industrial acceptance of High Speed Metal Forming is tightly connected to the knowledge acquired from many applications studies. These ...

  11. Ink-Jet Printer Forms Solar-Cell Contacts

    Science.gov (United States)

    Alexander, Paul, Jr.; Vest, R. W.; Binford, Don A.; Tweedell, Eric P.

    1988-01-01

    Contacts formed in controllable patterns with metal-based inks. System forms upper metal contact patterns on silicon photovoltaic cells. Uses metallo-organic ink, decomposes when heated, leaving behind metallic, electrically conductive residue in printed area.

  12. 8 CFR 1299.2 - Specific immigration review forms.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Specific immigration review forms. 1299.2 Section 1299.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS IMMIGRATION REVIEW FORMS § 1299.2 Specific immigration review forms. The Director of...

  13. Zeros in the electromagnetic and hadronic form factors

    International Nuclear Information System (INIS)

    Martini, A.F.; Menon, M.J.; Montanha, J.

    2004-01-01

    We discuss the evidences for the existence of zeros in the electric and in the hadronic form factors of the proton. We show that the shape of both form factors are similar, but there is indication that the hadronic form factors can depend on the energy. (author)

  14. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

    Directory of Open Access Journals (Sweden)

    Przemysław Baranowski

    2014-01-01

    Full Text Available This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient’s compliance.

  15. West Coast Canopy-Forming Kelp, 1989-2014

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data include the general extents of canopy-forming kelp surveys from 1989 to 2014 and a compilation of existing data sets delineating canopy-forming kelp beds...

  16. Documentary form no. 1

    International Nuclear Information System (INIS)

    2002-12-01

    This first documentary form, edited by the national association of local commissions of information about nuclear activities (ANCLI), briefly presents the radioactivity phenomenon, the ionising radiations, the characteristics of radiation sources (activity, half life, energy), and the dosimetry (absorbed, equivalent, efficient doses). (J.S.)

  17. Inequalities for Differential Forms

    CERN Document Server

    Agarwal, Ravi P

    2009-01-01

    Presents a series of local and global estimates and inequalities for differential forms, in particular the ones that satisfy the A-harmonic equations. This work focuses on the Hardy-Littlewood, Poincare, Cacciooli, imbedded and reverse Holder inequalities. It is for researchers, instructors and graduate students

  18. New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium

    Directory of Open Access Journals (Sweden)

    Olga Michalak

    2015-07-01

    Full Text Available The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2 of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.

  19. Alternate Forms of the State-Trait Anxiety Inventory.

    Science.gov (United States)

    Devito, Anthony J.; Kubis, Joseph F.

    1983-01-01

    Alternate forms of the state anxiety (A-State) and trait anxiety (A-Trait) scales of the State-Trait Anxiety Inventory (STAI) were constructed by dividing the 20 items of each scale into two briefer forms having 10 items each. The alternate forms and item statistics are presented. (Author/BW)

  20. 17 CFR 259.0-1 - Availability of forms.

    Science.gov (United States)

    2010-04-01

    ... may inspect the forms at this address and at the Commission's regional and district offices. (See... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Availability of forms. 259.0-1 Section 259.0-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) FORMS...