National Library of Energy BETA

Sample records for bind deleted domain

  1. Cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  2. Cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

    1998-11-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  3. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  4. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  5. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1996-03-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 15 figs.

  6. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1996-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  7. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1997-09-23

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  8. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1997-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  9. Methods of detection using a cellulose binding domain fusion product

    DOE Patents [OSTI]

    Shoseyov, Oded (Shimshon, IL); Shpiegl, Itai (North Gallilea, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1999-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  10. Methods of detection using a cellulose binding domain fusion product

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1999-01-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 34 figs.

  11. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    SciTech Connect (OSTI)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  12. Kits and methods of detection using cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.

    1998-04-14

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  13. Kits and methods of detection using cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  14. Structural and Energetic Analysis of Activiation by a Cyclic Nucleotide Binding Domain

    SciTech Connect (OSTI)

    Altieri,S.; Clayton, G.; Silverman, W.; Olivares, A.; De La Cruz, E.; Thomas, L.; Morais-Cabral, J.

    2008-01-01

    MlotiK1 is a prokaryotic homolog of cyclic-nucleotide-dependent ion channels that contains an intracellular C-terminal cyclic nucleotide binding (CNB) domain. X-ray structures of the CNB domain have been solved in the absence of ligand and bound to cAMP. Both the full-length channel and CNB domain fragment are easily expressed and purified, making MlotiK1 a useful model system for dissecting activation by ligand binding. We have used X-ray crystallography to determine three new MlotiK1 CNB domain structures: a second apo configuration, a cGMP-bound structure, and a second cAMP-bound structure. In combination, the five MlotiK1 CNB domain structures provide a unique opportunity for analyzing, within a single protein, the structural differences between the apo state and the bound state, and the structural variability within each state. With this analysis as a guide, we have probed the nucleotide selectivity and importance of specific residue side chains in ligand binding and channel activation. These data help to identify ligand-protein interactions that are important for ligand dependence in MlotiK1 and, more globally, in the class of nucleotide-dependent proteins.

  15. LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins

    SciTech Connect (OSTI)

    Sosa, Brian A.; Rothballer, Andrea; Kutay, Ulrike; Schwartz, Thomas U.

    2012-08-31

    Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear envelope and are composed of KASH and SUN proteins residing in the outer and inner nuclear membrane, respectively. LINC formation relies on direct binding of KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that can transmit forces for chromosome movements, nuclear migration, and anchorage. We present crystal structures of the human SUN2-KASH1/2 complex, the core of the LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. The peptides bind in three deep and expansive grooves formed between adjacent SUN domains, effectively acting as molecular glue. In addition, a disulfide between conserved cysteines on SUN and KASH covalently links both proteins. The structure provides the basis of LINC complex formation and suggests a model for how LINC complexes might arrange into higher-order clusters to enhance force-coupling.

  16. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Qiu, Wei; Lam, Robert; Voytyuk, Oleksandr; Romanov, Vladimir; Gordon, Roni; Gebremeskel, Simon; Vodsedalek, Jakub; Thompson, Christine; Beletskaya, Irina; Battaile, Kevin P.; et al

    2014-07-31

    The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated β-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, themore » high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors.« less

  17. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2

    SciTech Connect (OSTI)

    Qiu, Wei; Lam, Robert; Voytyuk, Oleksandr; Romanov, Vladimir; Gordon, Roni; Gebremeskel, Simon; Vodsedalek, Jakub; Thompson, Christine; Beletskaya, Irina; Battaile, Kevin P.; Pai, Emil F.; Rottapel, Robert; Chirgadze, Nickolay Y.

    2014-07-31

    The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated ?-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, the high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors.

  18. BuD, a helixloophelix DNA-binding domain for genome modification

    SciTech Connect (OSTI)

    Stella, Stefano; Molina, Rafael; Lpez-Mndez, Blanca; Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza; Campos-Olivas, Ramon; Duchateau, Phillippe; Montoya, Guillermo

    2014-07-01

    Crystal structures of BurrH and the BurrHDNA complex are reported. DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific proteinDNA interactions in protein scaffolds is key to providing toolkits for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19 bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helixloophelix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin ? (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing.

  19. The roles of RIIbeta linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of Type IIbeta Protein Kinase A. A small angle X-ray and neutron scattering study

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

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

    2014-08-11

    Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. Moreover, 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 ismore » 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. These 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.« less

  20. Membrane binding mode of intrinsically disordered cytoplasmic domains of T cell receptor signaling subunits depends on lipid composition

    SciTech Connect (OSTI)

    Sigalov, Alexander B., E-mail: Alexander.sigalov@umassmed.edu [University of Massachusetts Medical School, Worcester, MA 01655 (United States); Hendricks, Gregory M. [University of Massachusetts Medical School, Worcester, MA 01655 (United States)] [University of Massachusetts Medical School, Worcester, MA 01655 (United States)

    2009-11-13

    Intrinsically disordered cytoplasmic domains of T cell receptor (TCR) signaling subunits including {zeta}{sub cyt} and CD3{epsilon}{sub cyt} all contain one or more copies of an immunoreceptor tyrosine-based activation motif (ITAM), tyrosine residues of which are phosphorylated upon receptor triggering. Membrane binding-induced helical folding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} ITAMs is thought to control TCR activation. However, the question whether or not lipid binding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} is necessarily accompanied by a folding transition of ITAMs remains open. In this study, we investigate whether the membrane binding mechanisms of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} depend on the membrane model used. Circular dichroic and fluorescence data indicate that binding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} to detergent micelles and unstable vesicles is accompanied by a disorder-to-order transition, whereas upon binding to stable vesicles these proteins remain unfolded. Using electron microscopy and dynamic light scattering, we show that upon protein binding, unstable vesicles fuse and rupture. In contrast, stable vesicles remain intact under these conditions. This suggests different membrane binding modes for {zeta}{sub cyt} and CD3{epsilon}{sub cyt} depending on the bilayer stability: (1) coupled binding and folding, and (2) binding without folding. These findings explain the long-standing puzzle in the literature and highlight the importance of the choice of an appropriate membrane model for protein-lipid interactions studies.

  1. Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

    SciTech Connect (OSTI)

    Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.

    2010-09-21

    LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

  2. Binding of flexible and constrained ligands to the Grb2 SH2 domain: structural effects of ligand preorganization

    SciTech Connect (OSTI)

    Clements, John H.; DeLorbe, John E.; Benfield, Aaron P.; Martin, Stephen F.

    2010-10-01

    Structures of the Grb2 SH2 domain complexed with a series of flexible and constrained replacements of the phosphotyrosine residue in tripeptides derived from Ac-pYXN (where X = V, I, E and Q) were compared to determine what, if any, structural differences arise as a result of ligand preorganization. Structures of the Grb2 SH2 domain complexed with a series of pseudopeptides containing flexible (benzyl succinate) and constrained (aryl cyclopropanedicarboxylate) replacements of the phosphotyrosine (pY) residue in tripeptides derived from Ac-pYXN-NH{sub 2} (where X = V, I, E and Q) were elucidated by X-ray crystallography. Complexes of flexible/constrained pairs having the same pY + 1 amino acid were analyzed in order to ascertain what structural differences might be attributed to constraining the phosphotyrosine replacement. In this context, a given structural dissimilarity between complexes was considered to be significant if it was greater than the corresponding difference in complexes coexisting within the same asymmetric unit. The backbone atoms of the domain generally adopt a similar conformation and orientation relative to the ligands in the complexes of each flexible/constrained pair, although there are some significant differences in the relative orientations of several loop regions, most notably in the BC loop that forms part of the binding pocket for the phosphate group in the tyrosine replacements. These variations are greater in the set of complexes of constrained ligands than in the set of complexes of flexible ligands. The constrained ligands make more direct polar contacts to the domain than their flexible counterparts, whereas the more flexible ligand of each pair makes more single-water-mediated contacts to the domain; there was no correlation between the total number of proteinligand contacts and whether the phosphotyrosine replacement of the ligand was preorganized. The observed differences in hydrophobic interactions between the complexes of each flexible/constrained ligand pair were generally similar to those observed upon comparing such contacts in coexisting complexes. The average adjusted B factors of the backbone atoms of the domain and loop regions are significantly greater in the complexes of constrained ligands than in the complexes of the corresponding flexible ligands, suggesting greater thermal motion in the crystalline state in the former complexes. There was no apparent correlation between variations in crystal packing and observed structural differences or similarities in the complexes of flexible and constrained ligands, but the possibility that crystal packing might result in structural variations cannot be rigorously excluded. Overall, it appears that there are more variations in the three-dimensional structure of the protein and the ligand in complexes of the constrained ligands than in those of their more flexible counterparts.

  3. Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action

    SciTech Connect (OSTI)

    Baram, David; Pyetan, Erez; Sittner, Assa; Auerbach-Nevo, Tamar; Bashan, Anat; Yonath, Ada (WIS-I)

    2010-07-13

    Trigger factor (TF), the first chaperone in eubacteria to encounter the emerging nascent chain, binds to the large ribosomal subunit in the vicinity of the protein exit tunnel opening and forms a sheltered folding space. Here, we present the 3.5-{angstrom} crystal structure of the physiological complex of the large ribosomal subunit from the eubacterium Deinococcus radiodurans with the N-terminal domain of TF (TFa) from the same organism. For anchoring, TFa exploits a small ribosomal surface area in the vicinity of proteins L23 and L29, by using its 'signature motif' as well as additional structural elements. The molecular details of TFa interactions reveal that L23 is essential for the association of TF with the ribosome and may serve as a channel of communication with the nascent chain progressing in the tunnel. L29 appears to induce a conformational change in TFa, which results in the exposure of TFa hydrophobic patches to the opening of the ribosomal exit tunnel, thus increasing its affinity for hydrophobic segments of the emerging nascent polypeptide. This observation implies that, in addition to creating a protected folding space for the emerging nascent chain, TF association with the ribosome prevents aggregation by providing a competing hydrophobic environment and may be critical for attaining the functional conformation necessary for chaperone activity.

  4. The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

    SciTech Connect (OSTI)

    Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

    2010-11-10

    We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7{sub 39-98} localized mostly to the nucleus. The GST-11E7 and GST-11cE7{sub 39-98} were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

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  6. Structural dynamics and ssDNA binding activity of the three N-terminal domains of the large subunit of Replication Protein A from small angle X-ray scattering

    SciTech Connect (OSTI)

    Pretto, Dalyir I.; Tsutakawa, Susan; Brosey, Chris A.; Castillo, Amalchi; Chagot, Marie-Eve; Smith, Jarrod A.; Tainer, John A.; Chazin, Walter J.

    2010-03-11

    Replication Protein A (RPA) is the primary eukaryotic ssDNA binding protein utilized in diverse DNA transactions in the cell. RPA is a heterotrimeric protein with seven globular domains connected by flexible linkers, which enable substantial inter-domain motion that is essential to its function. Small angle X-ray scattering (SAXS) experiments on two multi-domain constructs from the N-terminus of the large subunit (RPA70) were used to examine the structural dynamics of these domains and their response to the binding of ssDNA. The SAXS data combined with molecular dynamics simulations reveal substantial interdomain flexibility for both RPA70AB (the tandem high affinity ssDNA binding domains A and B connected by a 10-residue linker) and RPA70NAB (RPA70AB extended by a 70-residue linker to the RPA70N protein interaction domain). Binding of ssDNA to RPA70NAB reduces the interdomain flexibility between the A and B domains, but has no effect on RPA70N. These studies provide the first direct measurements of changes in orientation of these three RPA domains upon binding ssDNA. The results support a model in which RPA70N remains structurally independent of RPA70AB in the DNA bound state and therefore freely available to serve as a protein recruitment module.

  7. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors

    SciTech Connect (OSTI)

    Lin, David Yin-wei; Tanaka, Yoshimasa; Iwasaki, Masashi; Gittis, Apostolos G.; Su, Hua-Poo; Mikami, Bunzo; Okazaki, Taku; Honjo, Tasuku; Minato, Nagahiro; Garboczi, David N. (NIH); (Kyoto)

    2008-07-29

    Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the maintenance of peripheral immune tolerance. Release from PD-1 inhibitory signaling revives 'exhausted' virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with human PD-L1. PD-1 and PD-L1 interact through the conserved front and side of their Ig variable (IgV) domains, as do the IgV domains of antibodies and T cell receptors. This places the loops at the ends of the IgV domains on the same side of the PD-1/PD-L1 complex, forming a surface that is similar to the antigen-binding surface of antibodies and T cell receptors. Mapping conserved residues allowed the identification of residues that are important in forming the PD-1/PD-L1 interface. Based on the structure, we show that some reported loss-of-binding mutations involve the PD-1/PD-L1 interaction but that others compromise protein folding. The PD-1/PD-L1 interaction described here may be blocked by antibodies or by designed small-molecule drugs to lower inhibitory signaling that results in a stronger immune response. The immune receptor-like loops offer a new surface for further study and potentially the design of molecules that would affect PD-1/PD-L1 complex formation and thereby modulate the immune response.

  8. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P

    SciTech Connect (OSTI)

    Green, Todd J.; Luo, Ming

    2009-10-05

    The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.

  9. Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved ?-helix for Act1 binding and IL-17 signaling

    SciTech Connect (OSTI)

    Zhang, Bing [Oklahoma State University, Stillwater, OK 74078 (United States); Liu, Caini; Qian, Wen [Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Han, Yue [Oklahoma State University, Stillwater, OK 74078 (United States); Li, Xiaoxia, E-mail: lix@ccf.org [Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Deng, Junpeng, E-mail: lix@ccf.org [Oklahoma State University, Stillwater, OK 74078 (United States)

    2014-05-01

    Crystal structure of the SEFIR domain from human IL-17 receptor A provides new insights into IL-17 signaling. Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated proteinprotein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional ?-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand ?C and helix ?C in IL-17RA SEFIR is mostly well ordered, displaying a helix (?CC?{sub ins}) and a flexible loop (CC?). The DD? loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90 with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 to accommodate the ?CC?{sub ins} helix without forming any knots. Helix ?C was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIRSEFIR association via helix ?C is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix ?C could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.

  10. Activated RhoA Binds to the Pleckstrin Homology (PH) Domain of PDZ-RhoGEF, a Potential Site for Autoregulation

    SciTech Connect (OSTI)

    Chen, Zhe; Medina, Frank; Liu, Mu-ya; Thomas, Celestine; Sprang, Stephen R.; Sternweis, Paul C.

    2010-07-19

    Guanine nucleotide exchange factors (GEFs) catalyze exchange of GDP for GTP by stabilizing the nucleotide-free state of the small GTPases through their Dbl homology/pleckstrin homology (DH {center_dot} PH) domains. Unconventionally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly to both nucleotide-free and activated RhoA (RhoA {center_dot} GTP). We have characterized the interaction between PRG and activated RhoA and determined the structure of the PRG-DH {center_dot} PH-RhoA {center_dot} GTP{gamma}S (guanosine 5{prime}-O-[{gamma}-thio]triphosphate) complex. The interface bears striking similarity to a GTPase-effector interface and involves the switch regions in RhoA and a hydrophobic patch in PRG-PH that is conserved among all Lbc RhoGEFs. The two surfaces that bind activated and nucleotide-free RhoA on PRG-DH {center_dot} PH do not overlap, and a ternary complex of PRG-DH {center_dot} PH bound to both forms of RhoA can be isolated by size-exclusion chromatography. This novel interaction between activated RhoA and PH could play a key role in regulation of RhoGEF activity in vivo.

  11. delete me | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    delete me delete me More Documents & Publications EIS-0423: Notice of Intent to Prepare an Environmental Impact Statement EIS-0424: Notice of Intent to Prepare an Environmental Impact Statement Paducah Community Relations Plan

  12. Help:Deleting pages | Open Energy Information

    Open Energy Info (EERE)

    a candidate for uncontroversial deletion. If nobody objects, the article is deleted after seven days. There are three steps to the proposed deletion process An article or other...

  13. Category:Proposed deletion | Open Energy Information

    Open Energy Info (EERE)

    History Category:Proposed deletion Jump to: navigation, search This category contains articles which have been proposed for deletion. To tag an article for proposed deletion use...

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    Open Energy Info (EERE)

    search This is the PleaseDelete template. Its primary intent is to propose specific pages for deletion. This template will add a page to the Category:Proposed deletion....

  15. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

    SciTech Connect (OSTI)

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

  16. Synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  17. Structure and Ca[superscript 2+]-Binding Properties of the Tandem...

    Office of Scientific and Technical Information (OSTI)

    and Casuperscript 2+-Binding Properties of the Tandem Csubscript 2 Domains of E-Syt2 Citation Details In-Document Search Title: Structure and Casuperscript 2+-Binding ...

  18. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J. (Bellport, NY); Quesada, Mark A. (Horseheads, NY); Randesi, Matthew (New York, NY)

    2001-01-01

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment in the context of a cloning vector which contains an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment. Also disclosed is a method for producing single-stranded DNA probes utilizing the same cloning vector. An optimal vector, PZIP is described. Methods for introducing unidirectional deletions into a terminal location of a cloned DNA sequence which is inserted into the vector of the present invention are also disclosed. These methods are useful for introducing deletions into either or both ends of a cloned DNA insert, for high throughput sequencing of any DNA of interest.

  19. Deletion of Caldicellulosiruptor bescii CelA reveals its crucial role in the deconstruction of lignocellulosic biomass

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Young, Jenna; Chung, Daehwan; Bomble, Yannick J.; Himmel, Michael E.; Westpheling, Janet

    2014-10-09

    Background: Members of the bacterial genus Caldicellulosiruptor are the most thermophilic cellulolytic organisms described to date, and have the ability to grow on lignocellulosic biomass without conventional pretreatment. Different species vary in their abilities to degrade cellulose, and the presence of CelA, a bifunctional glycoside hydrolase that contains a Family 48 and a Family 9 catalytic domain, correlates well with cellulolytic ability in members of this genus. For example, C. hydrothermalis, which does not contain a CelA homolog, or a GH48 Family or GH9 Family glycoside hydrolase, is the least cellulolytic of the Caldicellulosiruptor species so far described. C. bescii,more » which contains CelA and expresses it constitutively, is among the most cellulolytic. In fact, CelA is the most abundant extracellular protein produced in C. bescii. The enzyme contains two catalytic units, a Family 9A-CBM3c processive endoglucanase and a Family 48 exoglucanase, joined by two Family 3b carbohydrate-binding domains. Although there are two non-reducing end-specific Family 9 and three reducing end-specific Family 48 glycoside hydrolases (producing primarily glucose and cellobiose; and cellobiose and cellotriose, respectively) in C. bescii, CelA is the only protein that combines both enzymatic activities. Results: A deletion of the celA gene resulted in a dramatic reduction in the microorganism’s ability to grow on crystalline cellulose (Avicel) and diminished growth on lignocellulosic biomass. A comparison of the overall endoglucanase and exoglucanase activities of the mutant compared with the wild-type suggests that the loss of the endoglucanase activity provided by the GH9 family domain is perhaps compensated for by other enzymes produced by the cell. In contrast, it appears that no other enzymes in the C. bescii secretome can compensate for the loss of exoglucanase activity. The change in enzymatic activity in the celA mutant resulted in a 15-fold decrease in sugar release on Avicel compared with the parent and wild-type strains. In conclusion: The exoglucanase activity of the GH48 domain of CelA plays a major role in biomass degradation within the suite of C. bescii biomass-degrading enzymes.« less

  20. Synthetic heparin-binding factor analogs

    DOE Patents [OSTI]

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  1. PartialDeletion for web.cdr

    Office of Legacy Management (LM)

    States Department of Energy Grand Junction Office F A C T S H E E T Partial Deletion of Monticello Mill Tailings Site From the National Priorities List July 2003 The U.S. Department of Energy has completed the cleanup of the Non-Surface and Ground-Water Impacted Peripheral Properties that are part of Operable Unit II of the Monticello (Utah) Mill Tailings Site. These properties can now be removed from the U.S. Environmental Protection Agency's National Priorities List. This fact sheet provides a

  2. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, J.J.; Quesada, M.A.; Randesi, M.

    1999-07-27

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector. The cloning vector has an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe. 1 fig.

  3. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J. (Bellport, NY); Quesada, Mark A. (Middle Island, NY); Randesi, Matthew (Upton, NY)

    1999-07-27

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector, the cloning vector having an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe.

  4. Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

    SciTech Connect (OSTI)

    Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.; Briant, Douglas J.; Zarrine-Afsar, Arash; Sicheri, Frank; Kay, Lewis E.; Pawson, Tony (Mount Sinai Hospital); (Toronto)

    2012-10-23

    The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.

  5. Help:Sysop deleting and undeleting | Open Energy Information

    Open Energy Info (EERE)

    the page is still linked to prominently from many places. All incoming links will become red links if you proceed with the delete. Ideally all incoming links should be changed...

  6. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  7. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  8. Haem Recognition By a Staphylococcus Aureus NEAT Domain

    SciTech Connect (OSTI)

    Grigg, J.C.; Vermeiren, C.; Heinrichs, D.E.; Murphy, M.E.P.

    2009-06-01

    Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.

  9. A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type

    Office of Scientific and Technical Information (OSTI)

    Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 (Journal Article) | SciTech Connect A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 Citation Details In-Document Search Title: A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 Authors: Jégouzo, Sabine A.F. ; Feinberg, Hadar ; Dungarwalla,

  10. Edison scratch files will be deleted on 11/30/2015 when Edison...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    scratch files will be deleted on 11302015 when Edison moves Edison scratch files will be deleted on 11302015 when Edison moves November 15, 2015 by Zhengji Zhao Edison is...

  11. A 1.3-Å Structure of Zinc-bound N-terminal Domain of Calmodulin...

    Office of Scientific and Technical Information (OSTI)

    of Zinc-bound N-terminal Domain of Calmodulin Elucidates Potential Early Ion-binding Step Citation Details In-Document Search Title: A 1.3- Structure of Zinc-bound ...

  12. Axion domain wall baryogenesis

    SciTech Connect (OSTI)

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  13. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    DOE Patents [OSTI]

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  14. Discovery and Characterization of a Cell-Permeable, Small-Molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site

    SciTech Connect (OSTI)

    Yang, Jingsong; Campobasso, Nino; Biju, Mangatt P.; Fisher, Kelly; Pan, Xiao-Qing; Cottom, Josh; Galbraith, Sarah; Ho, Thau; Zhang, Hong; Hong, Xuan; Ward, Paris; Hofmann, Glenn; Siegfried, Brett; Zappacosta, Francesca; Washio, Yoshiaki; Cao, Ping; Qu, Junya; Bertrand, Sophie; Wang, Da-Yuan; Head, Martha S.; Li, Hu; Moores, Sheri; Lai, Zhihong; Johanson, Kyung; Burton, George; Erickson-Miller, Connie; Simpson, Graham; Tummino, Peter; Copeland, Robert A.; Oliff, Allen

    2014-10-02

    c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the {alpha}I helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the {alpha}I helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. DPH represents the first cell-permeable, small-molecule tool compound for c-Abl activation.

  15. Structure of Human Toll-like Receptor 3 (TLR3) Ligand-binding...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Human Toll-like Receptor 3 (TLR3) Ligand-binding Domain Jungwoo Choe1, Matthew S. Kelker1, and Ian A. Wilson1 1Department of Molecular Biology and The Skaggs Institute for Chemical...

  16. MCM ring hexamerization is a prerequisite for DNA-binding

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Froelich, Clifford A.; Nourse, Amanda; Enemark, Eric J.

    2015-09-13

    The hexameric Minichromosome Maintenance (MCM) protein complex forms a ring that unwinds DNA at the replication fork in eukaryotes and archaea. Our recent crystal structure of an archaeal MCM N-terminal domain bound to single-stranded DNA (ssDNA) revealed ssDNA associating across tight subunit interfaces but not at the loose interfaces, indicating that DNA-binding is governed not only by the DNA-binding residues of the subunits (MCM ssDNA-binding motif, MSSB) but also by the relative orientation of the subunits. We now extend these findings to show that DNA-binding by the MCM N-terminal domain of the archaeal organism Pyrococcus furiosus occurs specifically in themore » hexameric oligomeric form. We show that mutants defective for hexamerization are defective in binding ssDNA despite retaining all the residues observed to interact with ssDNA in the crystal structure. One mutation that exhibits severely defective hexamerization and ssDNA-binding is at a conserved phenylalanine that aligns with the mouse Mcm4(Chaos3) mutation associated with chromosomal instability, cancer, and decreased intersubunit association.« less

  17. Structure and Ca[superscript 2+]-Binding Properties of the Tandem

    Office of Scientific and Technical Information (OSTI)

    C[subscript 2] Domains of E-Syt2 (Journal Article) | SciTech Connect and Ca[superscript 2+]-Binding Properties of the Tandem C[subscript 2] Domains of E-Syt2 Citation Details In-Document Search Title: Structure and Ca[superscript 2+]-Binding Properties of the Tandem C[subscript 2] Domains of E-Syt2 Authors: Xu, Junjie ; Bacaj, Taulant ; Zhou, Amy ; Tomchick, Diana R. ; Südhof, Thomas C. ; Rizo, Josep [1] ; UTSMC) [2] + Show Author Affiliations (Stanford-MED) ( Publication Date: 2014-12-23

  18. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante; Juhasz, Szilvia; Morocz, Monika; Gali, Himabindu; Dhe-Paganon, Sirano; Venclovas, Česlovas; Haracska, Lajos

    2015-09-08

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteinsmore » retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. We suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal.« less

  19. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    2001-10-09

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  20. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Carolyn (Albany, CA)

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  1. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    1999-01-01

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  2. Fractional diffusion on bounded domains

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  3. Pinkbar is an epithelial-specific BAR domain protein that generates planar membrane structures

    SciTech Connect (OSTI)

    Pyklinen, Anette; Boczkowska, Malgorzata; Zhao, Hongxia; Saarikangas, Juha; Rebowski, Grzegorz; Jansen, Maurice; Hakanen, Janne; Koskela, Essi V.; Pernen, Johan; Vihinen, Helena; Jokitalo, Eija; Salminen, Marjo; Ikonen, Elina; Dominguez, Roberto; Lappalainen, Pekka

    2013-05-29

    Bin/amphipysin/Rvs (BAR)-domain proteins sculpt cellular membranes and have key roles in processes such as endocytosis, cell motility and morphogenesis. BAR domains are divided into three subfamilies: BAR- and F-BAR-domain proteins generate positive membrane curvature and stabilize cellular invaginations, whereas I-BAR-domain proteins induce negative curvature and stabilize protrusions. We show that a previously uncharacterized member of the I-BAR subfamily, Pinkbar, is specifically expressed in intestinal epithelial cells, where it localizes to Rab13-positive vesicles and to the plasma membrane at intercellular junctions. Notably, the BAR domain of Pinkbar does not induce membrane tubulation but promotes the formation of planar membrane sheets. Structural and mutagenesis analyses reveal that the BAR domain of Pinkbar has a relatively flat lipid-binding interface and that it assembles into sheet-like oligomers in crystals and in solution, which may explain its unique membrane-deforming activity.

  4. Deletion of the Cel48S cellulase from Clostridium thermocellum

    SciTech Connect (OSTI)

    Olson, Daniel G; Tripathi, Shital A.; Giannone, Richard J; Lo, Jonathan; Caiazza, Nicky; Hogsett, David A; Hettich, Robert {Bob} L; Guss, Adam M; Dubrovsky, Genia; Lynd, Lee R

    2010-01-01

    Clostridium thermocellum is a thermophilic anaerobic bacterium that rapidly solubilizes cellulose with the aid of a multienzyme cellulosome complex. Creation of knockout mutants for Cel48S (also known as CelS, SS, and S8), the most abundant cellulosome subunit, was undertaken to gain insight into its role in enzymatic and microbial cellulose solubilization. Cultures of the Cel48S deletion mutant (S mutant) were able to completely solubilize 10 g/L crystalline cellulose. The cellulose hydrolysis rate of the S mutant strain was 60% lower than the parent strain, with the S mutant strain also exhibiting a 40% reduction in cell yield. The cellulosome produced by the S mutant strain was purified by affinity digestion, characterized enzymatically, and found to have a 35% lower specific activity on Avicel. The composition of the purified cellulosome was analyzed by tandem mass spectrometry with APEX quantification and no significant changes in abundance were observed in any of the major (>1% of cellulosomal protein) enzymatic subunits. Although most cellulolytic bacteria have one family 48 cellulase, C. thermocellum has two, Cel48S and Cel48Y. Cellulose solubilization by a Cel48S and Cel48Y double knockout was essentially the same as that of the Cel48S single knockout. Our results indicate that solubilization of crystalline cellulose by C. thermocellum can proceed to completion without expression of a family 48 cellulase.

  5. A 1.3-Å Structure of Zinc-bound N-terminal Domain of Calmodulin Elucidates

    Office of Scientific and Technical Information (OSTI)

    Potential Early Ion-binding Step (Journal Article) | SciTech Connect A 1.3-Å Structure of Zinc-bound N-terminal Domain of Calmodulin Elucidates Potential Early Ion-binding Step Citation Details In-Document Search Title: A 1.3-Å Structure of Zinc-bound N-terminal Domain of Calmodulin Elucidates Potential Early Ion-binding Step Authors: Warren, Julia T. ; Guo, Qing ; Tang, Wei-Jen [1] + Show Author Affiliations (UC) Publication Date: 2015-11-02 OSTI Identifier: 1222846 Resource Type: Journal

  6. New perspective on glycoside hydrolase binding to lignin from pretreated corn stover

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yarbrough, John M.; Mittal, Ashutosh; Mansfield, Elisabeth; Taylor, II, Larry E.; Hobdey, Sarah E.; Sammond, Deanne W.; Bomble, Yannick J.; Crowley, Michael F.; Decker, Stephen R.; Himmel, Michael E.; et al

    2015-12-18

    In this study, non-specific binding of cellulases to lignin has been implicated as a major factor in the loss of cellulase activity during biomass conversion to sugars. It is believed that this binding may strongly impact process economics through loss of enzyme activities during hydrolysis and enzyme recycling scenarios. The current model suggests glycoside hydrolase activities are lost though non-specific/non-productive binding of carbohydrate-binding domains to lignin, limiting catalytic site access to the carbohydrate components of the cell wall.

  7. Why did someone delete the Utility Rate Database Page? | OpenEI...

    Open Energy Info (EERE)

    Why did someone delete the Utility Rate Database Page? Home > Groups > Utility Rate Can someone fix this? I can't access the Utility Rate Database Page It looks like someone...

  8. How to recreate a table after deletion | OpenEI Community

    Open Energy Info (EERE)

    recreate a table after deletion Home > Groups > Databus Hello, First things first. I'm new to this group and to Databus usage, this will be a "hello" as much as a question post ;)...

  9. The structure of the catalytic domain of a plant cellulose synthase and its assembly into dimers

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Olek, Anna T.; Rayon, Catherine; Makowski, Lee; Kim, Hyung Rae; Ciesielski, Peter; Badger, John; Paul, Lake N.; Ghosh, Subhangi; Kihara, Daisuke; Crowley, Michael; et al

    2014-07-10

    Cellulose microfibrils are para-crystalline arrays of several dozen linear (1→4)-β-d-glucan chains synthesized at the surface of the cell membrane by large, multimeric complexes of synthase proteins. Recombinant catalytic domains of rice (Oryza sativa) CesA8 cellulose synthase form dimers reversibly as the fundamental scaffold units of architecture in the synthase complex. Specificity of binding to UDP and UDP-Glc indicates a properly folded protein, and binding kinetics indicate that each monomer independently synthesizes single glucan chains of cellulose, i.e., two chains per dimer pair. In contrast to structure modeling predictions, solution x-ray scattering studies demonstrate that the monomer is a two-domain, elongatedmore » structure, with the smaller domain coupling two monomers into a dimer. The catalytic core of the monomer is accommodated only near its center, with the plant-specific sequences occupying the small domain and an extension distal to the catalytic domain. This configuration is in stark contrast to the domain organization obtained in predicted structures of plant CesA. As a result, the arrangement of the catalytic domain within the CesA monomer and dimer provides a foundation for constructing structural models of the synthase complex and defining the relationship between the rosette structure and the cellulose microfibrils they synthesize.« less

  10. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    SciTech Connect (OSTI)

    Knott, Michael [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom)] [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Best, Robert B., E-mail: robertbe@helix.nih.gov [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 (United States)

    2014-05-07

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an induced fit or conformational selection mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD.

  11. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conservedmore » when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.« less

  12. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    SciTech Connect (OSTI)

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into classical and non-classical inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.

  13. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein

    SciTech Connect (OSTI)

    Arpino, James A. J. [Cardiff University, Park Place, Cardiff CF10 3AT Wales (United Kingdom); Rizkallah, Pierre J., E-mail: rizkallahp@cardiff.ac.uk [Cardiff University, Heath Park, Cardiff CF14 4XN Wales (United Kingdom); Jones, D. Dafydd, E-mail: rizkallahp@cardiff.ac.uk [Cardiff University, Park Place, Cardiff CF10 3AT Wales (United Kingdom)

    2014-08-01

    The beneficial engineered single-amino-acid deletion variants EGFP{sup D190?} and EGFP{sup A227?} have been studied. Single-amino-acid deletions are a common part of the natural evolutionary landscape but are rarely sampled during protein engineering owing to limited and prejudiced molecular understanding of mutations that shorten the protein backbone. Single-amino-acid deletion variants of enhanced green fluorescent protein (EGFP) have been identified by directed evolution with the beneficial effect of imparting increased cellular fluorescence. Biophysical characterization revealed that increased functional protein production and not changes to the fluorescence parameters was the mechanism that was likely to be responsible. The structure EGFP{sup D190?} containing a deletion within a loop revealed propagated changes only after the deleted residue. The structure of EGFP{sup A227?} revealed that a flipping mechanism was used to adjust for residue deletion at the end of a ?-strand, with amino acids C-terminal to the deletion site repositioning to take the place of the deleted amino acid. In both variants new networks of short-range and long-range interactions are generated while maintaining the integrity of the hydrophobic core. Both deletion variants also displayed significant local and long-range changes in dynamics, as evident by changes in B factors compared with EGFP. Rather than being detrimental, deletion mutations can introduce beneficial structural effects through altering core protein properties, folding and dynamics, as well as function.

  14. The C-Terminal RpoN Domain of sigma54 Forms an unpredictedHelix-Turn-Helix Motif Similar to domains of sigma70

    SciTech Connect (OSTI)

    Doucleff, Michaeleen; Malak, Lawrence T.; Pelton, Jeffrey G.; Wemmer, David E.

    2005-11-01

    The ''{delta}'' subunit of prokaryotic RNA-polymerase allows gene-specific transcription initiation. Two {sigma} families have been identified, {sigma}{sup 70} and {sigma}{sup 54}, which use distinct mechanisms to initiate transcription and share no detectable sequence homology. Although the {sigma}{sup 70}-type factors have been well characterized structurally by x-ray crystallography, no high-resolution structural information is available for the {sigma}{sup 54}-type factors. Here we present the NMR derived structure of the C-terminal domain of {sigma}{sup 54} from Aquifex aeolicus. This domain (Thr323 to Gly389), which contains the highly conserved RpoN box sequence, consists of a poorly structured N-terminal tail followed by a three-helix bundle, which is surprisingly similar to domains of the {sigma}{sup 70}-type proteins. Residues of the RpoN box, which have previously been shown to be critical for DNA binding, form the second helix of an unpredicted helix-turn-helix motif. This structure's homology with other DNA binding proteins, combined with previous biochemical data, suggest how the C-terminal domain of {sigma}{sup 54} binds to DNA.

  15. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Slow Dynamics of Orbital Domains in Manganite Print Wednesday, 25 June 2008 00:00 At the ALS, an international team of researchers has...

  16. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    SciTech Connect (OSTI)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun Nishina, Hiroshi

    2014-01-17

    Highlights: Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAPs functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAPs co-activation of TEAD-mediated CTGF transcription.

  17. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Hidden Rotational Symmetries in Magnetic Domain Patterns Print Wednesday, 27 June 2012 00:00 Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and

  18. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    how it binds to microtubules and gives some hints into the fascinating question of how communication passes along the stalk from the MTBD to the rest of the motor. Lucky Break...

  19. Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh

    SciTech Connect (OSTI)

    Ramirez, Ursula D.; Focia, Pamela J.; Freymann, Douglas M.

    2008-10-01

    Crystal structures of the Ffh NG GTPase domain at < 1.24 resolution reveal multiple overlapping nucleotide binding modes. Two structures of the nucleotide-bound NG domain of Ffh, the GTPase subunit of the bacterial signal recognition particle (SRP), have been determined at ultrahigh resolution in similar crystal forms. One is GDP-bound and one is GMPPCP-bound. The asymmetric unit of each structure contains two protein monomers, each of which exhibits differences in nucleotide-binding conformation and occupancy. The GDP-bound Ffh NG exhibits two binding conformations in one monomer but not the other and the GMPPCP-bound protein exhibits full occupancy of the nucleotide in one monomer but only partial occupancy in the other. Thus, under the same solution conditions, each crystal reveals multiple binding states that suggest that even when nucleotide is bound its position in the Ffh NG active site is dynamic. Some differences in the positioning of the bound nucleotide may arise from differences in the crystal-packing environment and specific factors that have been identified include the relative positions of the N and G domains, small conformational changes in the P-loop, the positions of waters buried within the active site and shifts in the closing loop that packs against the guanine base. However, loose binding may have biological significance in promoting facile nucleotide exchange and providing a mechanism for priming the SRP GTPase prior to its activation in its complex with the SRP receptor.

  20. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules How Dynein Binds to Microtubules Print Wednesday, 29 April 2009 00:00 Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses,

  1. Crystal Structure of the HP1-EMSY Complex Reveals an Unusual Mode of HP1 Binding

    SciTech Connect (OSTI)

    Huang,Y.; Myers, M.; Xu, R.

    2006-01-01

    Heterochromatin protein-1 (HP1) plays an essential role in both the assembly of higher-order chromatin structure and epigenetic inheritance. The C-terminal chromo shadow domain (CSD) of HP1 is responsible for homodimerization and interaction with a number of chromatin-associated nonhistone proteins, including EMSY, which is a BRCA2-interacting protein that has been implicated in the development of breast and ovarian cancer. We have determined the crystal structure of the HP1{beta} CSD in complex with the N-terminal domain of EMSY at 1.8 Angstroms resolution. Surprisingly, the structure reveals that EMSY is bound by two HP1 CSD homodimers, and the binding sequences differ from the consensus HP1 binding motif PXVXL. This structural information expands our understanding of HP1 binding specificity and provides insights into interactions between HP1 homodimers that are likely to be important for heterochromatin formation.

  2. Secondary PDZ domain-binding site on class B plexins enhances...

    Office of Scientific and Technical Information (OSTI)

    Argonne, IL (US) Sponsoring Org: NIHOTHER Country of Publication: United States Language: ENGLISH Word Cloud More Like This Full Text Journal Articles DOI: 10.1073pnas.150893111

  3. Domain wall conduction in multiaxial ferroelectrics

    SciTech Connect (OSTI)

    Eliseev, E. A.; Morozovska, A. N.; Svechnikov, S. V.; Maksymovych, Petro; Kalinin, Sergei V

    2012-01-01

    The conductance of domain wall structures consisting of either stripes or cylindrical domains in multiaxial ferroelectric-semiconductors is analyzed. The effects of the flexoelectric coupling, domain size, wall tilt, and curvature on charge accumulation are analyzed using the Landau-Ginsburg Devonshire theory for polarization vector combined with the Poisson equation for charge distributions. The proximity and size effect of the electron and donor accumulation/depletion by thin stripe domains and cylindrical nanodomains are revealed. In contrast to thick domain stripes and wider cylindrical domains, in which the carrier accumulation (and so the static conductivity) sharply increases at the domain walls only, small nanodomains of radii less than 5-10 correlation lengths appeared conducting across the entire cross-section. Implications of such conductive nanosized channels may be promising for nanoelectronics.

  4. Allostery Is an Intrinsic Property of the Protease Domain of DegS Implications for Enzyme Function and Evolution

    SciTech Connect (OSTI)

    Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T. (MIT)

    2010-12-02

    DegS is a periplasmic Escherichia coli protease, which functions as a trimer to catalyze the initial rate-limiting step in a proteolytic cascade that ultimately activates transcription of stress response genes in the cytoplasm. Each DegS subunit consists of a protease domain and a PDZ domain. During protein folding stress, DegS is allosterically activated by peptides exposed in misfolded outer membrane porins, which bind to the PDZ domain and stabilize the active protease. It is not known whether allostery is conferred by the PDZ domains or is an intrinsic feature of the trimeric protease domain. Here, we demonstrate that free DegS{sup {Delta}PDZ} equilibrates between active and inactive trimers with the latter species predominating. Substrate binding stabilizes active DegS{sup {Delta}PDZ} in a positively cooperative fashion. Mutations can also stabilize active DegS{sup {Delta}PDZ} and produce an enzyme that displays hyperbolic kinetics and degrades substrate with a maximal velocity within error of that for fully activated, intact DegS. Crystal structures of multiple DegS{sup {Delta}PDZ} variants, in functional and non-functional conformations, support a two-state model in which allosteric switching is mediated by changes in specific elements of tertiary structure in the context of an invariant trimeric base. Overall, our results indicate that protein substrates must bind sufficiently tightly and specifically to the functional conformation of DegS{sup {Delta}PDZ} to assist their own degradation. Thus, substrate binding alone may have regulated the activities of ancestral DegS trimers with subsequent fusion of the protease domain to a PDZ domain, resulting in ligand-mediated regulation.

  5. Time domain electromagnetic metal detectors

    SciTech Connect (OSTI)

    Hoekstra, P.

    1996-04-01

    This presentation focuses on illustrating by case histories the range of applications and limitations of time domain electromagnetic (TDEM) systems for buried metal detection. Advantages claimed for TDEM metal detectors are: independent of instrument response (Geonics EM61) to surrounding soil and rock type; simple anomaly shape; mitigation of interference by ambient electromagnetic noise; and responsive to both ferrous and non-ferrous metallic targets. The data in all case histories to be presented were acquired with the Geonics EM61 TDEM system. Case histories are a test bed site on Molokai, Hawaii; Fort Monroe, Virginia; and USDOE, Rocky Flats Plant. The present limitations of this technology are: discrimination capabilities in terms of type of ordnance, and depth of burial is limited, and ability of resolving targets with small metallic ambient needs to be improved.

  6. Molecular dynamics investigation of the substrate binding mechanism in carboxylesterase

    SciTech Connect (OSTI)

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; Xu, Jian-he

    2015-01-01

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of the substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, we further predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase rPPEs, which will help guide future development of more efficient rPPE variants.

  7. Analysis of human HPRT deletion mutations with X-linked probes and pulsed field gel electrophoresis

    SciTech Connect (OSTI)

    Nicklas, J.A.; Lippert, M.J.; Hunter, T.C.; O'Neil, J.P.; Albertini, R.J. )

    1991-01-01

    Because the human hprt gene is used in numerous mutation studies, it is important to fully characterize this gene. Therefore, the authors laboratory has undertaken to map the region around the hprt gene at band q26 of the human X chromosome. Utilizing hprt mutant T-cell clones isolated using the hprt clonal assay, which have deletions of all of part of the hprt gene, the authors have ordered 5 anonymous probes previously known to map in Xq26. Results suggest that this region include between 460 kb and 18 Mb of DNA, which is at least 10 times the size of the hprt gene itself (43 kb). Pulsed field gel analysis of the region is underway to determine the exact distances between each of the anonymous probes and hprt and to determine deletion sizes in the mutant T-cell clones.

  8. EIA - 2008 New Electric Power EIA-923 Form Summary of New and Deleted

    U.S. Energy Information Administration (EIA) Indexed Site

    Elements 923 Summary of New and Deleted Data Elements for New Form EIA-923, "Power Plant Operations Report" NEW Data Elements On Schedule 2, required information from plants 50 MW and above that consume fossil fuels: Commodity Cost in cents per MMBtu - for coal and natural gas fuels. These data will be kept confidential. Mercury Content in coal, parts per million (ppm) Fuel Transportation Modes - reported by code. For natural gas, either Firm or Interruptible transportation

  9. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  10. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  11. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  12. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  13. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  14. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  15. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  16. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hidden Rotational Symmetries in Magnetic Domain Patterns Print Magnetic thin films have complicated domain patterns that may or may not repeat with each cycle through a hysteresis loop. A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are disordered over a macroscopic length scale, and intuitively we do not expect to observe any symmetry in such systems. Scientists at the

  17. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A magnetic thin film with perpendicular anisotropy, such as that used in computer hard drives, for example, commonly exhibits labyrinthine domain patterns. These patterns are...

  18. Hidden Rotational Symmetries in Magnetic Domain Patterns

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    California, San Diego, have recently used coherent soft x-ray scattering with angular Fourier analysis to discover that the disordered domain patterns do, in fact, exhibit...

  19. Using Non-Government Domain Names

    Broader source: Energy.gov [DOE]

    There may be occasion where it is necessary to utilize a non-government domain. The OMB Policies for Federal Agency Public Websites  states:

  20. A Geometric Rendezvous-Based Domain Model

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    University of Wisconsin - Madison 1500 Engineering Dr. Madison, WI 53716 sslattery@wisc.edu March 20, 2013 1 A Geometric Rendezvous-Based Domain Model for Data Transfer...

  1. Amplifications and deletions in clinical ovarian cancer detected by Comparative Genomic Hybridization (CGH)

    SciTech Connect (OSTI)

    Sakunaga, H.; Sakamoto, M.; Kallioniemi, A.; Kallioniemi, O.; Sudar, D.; Pinkel, D.; Gray, I.W. ); Yang-Feng, T. )

    1993-01-01

    CGH is a new powerful method for surveying the whole genome for DNA sequence copy number changes in a single hybridization. The method is based on the competition between biotinylated total tumor DNA and a digoxigenin-labeled normal genomic reference DNA during hybridization to normal metaphase chromosomes. After immunofluorescent staining with avidin-FITC and antidigoxigenin Rhodamine, variation of DNA sequence copy numbers in the tumor are detected as variations in the ratios of green and red fluorescence along each chromosome. The authors applied CGH analysis to DNA extracted from surgically removed ovarian cancer specimens (27 cases). Seven amplified regions were identified by CGH analysis. Three loci, 1p32-p34 (most likely, MYCL), 8q23-q24 (MYC), 12q12 (KRAS2), were known to be amplified in solid tumors and four other loci (3q26, 6p22, 9q31-q33, 17q22) were previously unknown to be amplified. Many regions indicating physical deletions were also identified by the analysis. Chromosomal regions showing frequent deletion were 1p, 3p, 17p, 17q, 19p, 19q and Xp. There were also significant similarities of the regions with amplifications and deletions between bilateral ovarian tumors or among several different tumors form the same ovarian cancer cases, suggesting that the genetic changes observed might be relatively early events during the progression of ovarian cancer.

  2. Optical coherence domain reflectometry guidewire

    DOE Patents [OSTI]

    Colston, Billy W. (Livermore, CA); Everett, Matthew (Pleasanton, CA); Da Silva, Luiz B. (Danville, CA); Matthews, Dennis (Moss Beach, CA)

    2001-01-01

    A guidewire with optical sensing capabilities is based on a multiplexed optical coherence domain reflectometer (OCDR), which allows it to sense location, thickness, and structure of the arterial walls or other intra-cavity regions as it travels through the body during minimally invasive medical procedures. This information will be used both to direct the guidewire through the body by detecting vascular junctions and to evaluate the nearby tissue. The guidewire contains multiple optical fibers which couple light from the proximal to distal end. Light from the fibers at the distal end of the guidewire is directed onto interior cavity walls via small diameter optics such as gradient index lenses and mirrored corner cubes. Both forward viewing and side viewing fibers can be included. The light reflected or scattered from the cavity walls is then collected by the fibers, which are multiplexed at the proximal end to the sample arm of an optical low coherence reflectometer. The guidewire can also be used in nonmedical applications.

  3. Candidate Cell and Matrix Interaction Domains on the Collagen Fibril, the Predominant Protein of Vertebrates

    SciTech Connect (OSTI)

    Sweeney, Shawn M.; Orgel, Joseph P.; Fertala, Andrzej; McAuliffe, Jon D.; Turner, Kevin R.; Di Lullo, Gloria A.; Chen, Steven; Antipova, Olga; Perumal, Shiamalee; Ala-Kokko, Leena; Forlinoi, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.; San Antonio, James D.

    2008-07-18

    Type I collagen, the predominant protein of vertebrates, polymerizes with type III and V collagens and non-collagenous molecules into large cable-like fibrils, yet how the fibril interacts with cells and other binding partners remains poorly understood. To help reveal insights into the collagen structure-function relationship, a data base was assembled including hundreds of type I collagen ligand binding sites and mutations on a two-dimensional model of the fibril. Visual examination of the distribution of functional sites, and statistical analysis of mutation distributions on the fibril suggest it is organized into two domains. The 'cell interaction domain' is proposed to regulate dynamic aspects of collagen biology, including integrin-mediated cell interactions and fibril remodeling. The 'matrix interaction domain' may assume a structural role, mediating collagen cross-linking, proteoglycan interactions, and tissue mineralization. Molecular modeling was used to superimpose the positions of functional sites and mutations from the two-dimensional fibril map onto a three-dimensional x-ray diffraction structure of the collagen microfibril in situ, indicating the existence of domains in the native fibril. Sequence searches revealed that major fibril domain elements are conserved in type I collagens through evolution and in the type II/XI collagen fibril predominant in cartilage. Moreover, the fibril domain model provides potential insights into the genotype-phenotype relationship for several classes of human connective tissue diseases, mechanisms of integrin clustering by fibrils, the polarity of fibril assembly, heterotypic fibril function, and connective tissue pathology in diabetes and aging.

  4. The structure of the cyanobactin domain of unknown function from PatG in the patellamide gene cluster

    SciTech Connect (OSTI)

    Mann, Greg; Koehnke, Jesko; Bent, Andrew F.; Graham, Rachael; Houssen, Wael; Jaspars, Marcel; Schwarz-Linek, Uli; Naismith, James H.

    2014-11-14

    The highly conserved domain of unknown function in the cyanobactin superfamily has a novel fold. The protein does not appear to bind the most plausible substrates, leaving questions as to its role. Patellamides are members of the cyanobactin family of ribosomally synthesized and post-translationally modified cyclic peptide natural products, many of which, including some patellamides, are biologically active. A detailed mechanistic understanding of the biosynthetic pathway would enable the construction of a biotechnological toolkit to make novel analogues of patellamides that are not found in nature. All but two of the protein domains involved in patellamide biosynthesis have been characterized. The two domains of unknown function (DUFs) are homologous to each other and are found at the C-termini of the multi-domain proteins PatA and PatG. The domain sequence is found in all cyanobactin-biosynthetic pathways characterized to date, implying a functional role in cyanobactin biosynthesis. Here, the crystal structure of the PatG DUF domain is reported and its binding interactions with plausible substrates are investigated.

  5. Automotion of domain walls for spintronic interconnects

    SciTech Connect (OSTI)

    Nikonov, Dmitri E.; Manipatruni, Sasikanth; Young, Ian A.

    2014-06-07

    We simulate “automotion,” the transport of a magnetic domain wall under the influence of demagnetization and magnetic anisotropy, in nanoscale spintronic interconnects. In contrast to spin transfer driven magnetic domain wall motion, the proposed interconnects operate without longitudinal charge current transfer, with only a transient current pulse at domain wall creation and have favorable scaling down to the 20 nm dimension. Cases of both in-plane and out-of-plane magnetization are considered. Analytical dependence of the velocity of domain walls on the angle of magnetization are compared with full micromagnetic simulations. Deceleration, attenuation and disappearance, and reflection of domain walls are demonstrated through simulation. Dependences of the magnetization angle on the current pulse parameters are studied. The energy and delay analysis suggests that automotion is an attractive option for spintronic logic interconnects.

  6. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  7. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  8. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  9. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, Gisela K.

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  10. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  11. EIA - 2008 New Electric Power EIA-860 Form Summary of New and Deleted

    U.S. Energy Information Administration (EIA) Indexed Site

    Elements 860 Summary of New and Deleted Data Elements for New Form EIA-860, "Annual Electric Generator Report" NEW Data Elements On Schedule 1 "Identification" - whether the reporting entity is an electric utility On Schedule 2 "Power Plant Data": Steam Plant status (line 10) Steam Plant type plant type (line 11) Name of the owner of the transmission or distribution system to which the power plant is interconnected and the grid voltage at the point of

  12. Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain

    SciTech Connect (OSTI)

    Xu, Xueqing; Francischetti, Ivo M.B.; Lai, Ren; Ribeiro, Jos M.C.; Andersen, John F.

    2012-08-10

    The antihemostatic/antiangiogenic protein tablysin-15 is a member of the CAP (cysteine-rich secretory, antigen 5, and pathogenesis-related 1 protein) superfamily and has been shown to bind the integrins {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub V}{beta}{sub 3} by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the x-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II {beta}-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin {alpha}V{beta}3. The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E{sub 4}-tablysin-15 complex shows that the ligand binds with the nonfunctionalized end of the fatty acid chain buried in the hydrophobic pocket, whereas the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.

  13. Model for Eukaryotic Tail-anchored Protein Binding Based on the Structure

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of Get3 Model for Eukaryotic Tail-anchored Protein Binding Based on the Structure of Get3 Targeting of newly synthesized membrane proteins to the endoplasmic reticulum (ER) is an important cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle (SRP). A number of membrane proteins (eg. SNAREs, apoptosis factors, and protein translocation components) are 'tail-anchored' by a single carboxy-terminal transmembrane domain. Due to

  14. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the...

  15. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    we can understand the movement of the electronic domain structure. A typical image from a digital camera for x rays (CCD) showing a soft x-ray speckle pattern. The close-up...

  16. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    technique with photons of light that have wavelengths a billion times smaller than radio waves in order to study their domain motion. By using these soft x rays generated at...

  17. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Slow Dynamics of Orbital Domains in Manganite Print Wednesday, 25 June 2008 00:00 At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of

  18. An Insertion Mutation That Distorts Antibody Binding Site Architecture Enhances Function of a Human Antibody

    SciTech Connect (OSTI)

    Krause, Jens C.; Ekiert, Damian C.; Tumpey, Terrence M.; Smith, Patricia B.; Wilson, Ian A.; Crowe, Jr., James E.

    2011-09-02

    The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen.

  19. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    SciTech Connect (OSTI)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  20. Human-computer interface incorporating personal and application domains

    DOE Patents [OSTI]

    Anderson, Thomas G.

    2004-04-20

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  1. Human-computer interface incorporating personal and application domains

    DOE Patents [OSTI]

    Anderson, Thomas G. (Albuquerque, NM)

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  2. Structures of Adnectin/Protein Complexes Reveal an Expanded Binding Footprint

    SciTech Connect (OSTI)

    Ramamurthy, Vidhyashankar; Krystek, Jr., Stanley R.; Bush, Alexander; Wei, Anzhi; Emanuel, Stuart L.; Gupta, Ruchira Das; Janjua, Ahsen; Cheng, Lin; Murdock, Melissa; Abramczyk, Bozena; Cohen, Daniel; Lin, Zheng; Morin, Paul; Davis, Jonathan H.; Dabritz, Michael; McLaughlin, Douglas C.; Russo, Katie A.; Chao, Ginger; Wright, Martin C.; Jenny, Victoria A.; Engle, Linda J.; Furfine, Eric; Sheriff, Steven

    2014-10-02

    Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin ({sup 10}Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three {sup 10}Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the {beta} strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these {beta} strand interactions, indicating that these nonloop residues can expand the available binding footprint.

  3. Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh

    SciTech Connect (OSTI)

    Ramirez, U.D.; Focia, P.J.; Freymann, D.M.

    2008-10-24

    Two structures of the nucleotide-bound NG domain of Ffh, the GTPase subunit of the bacterial signal recognition particle (SRP), have been determined at ultrahigh resolution in similar crystal forms. One is GDP-bound and one is GMPPCP-bound. The asymmetric unit of each structure contains two protein monomers, each of which exhibits differences in nucleotide-binding conformation and occupancy. The GDP-bound Ffh NG exhibits two binding conformations in one monomer but not the other and the GMPPCP-bound protein exhibits full occupancy of the nucleotide in one monomer but only partial occupancy in the other. Thus, under the same solution conditions, each crystal reveals multiple binding states that suggest that even when nucleotide is bound its position in the Ffh NG active site is dynamic. Some differences in the positioning of the bound nucleotide may arise from differences in the crystal-packing environment and specific factors that have been identified include the relative positions of the N and G domains, small conformational changes in the P-loop, the positions of waters buried within the active site and shifts in the closing loop that packs against the guanine base. However, 'loose' binding may have biological significance in promoting facile nucleotide exchange and providing a mechanism for priming the SRP GTPase prior to its activation in its complex with the SRP receptor.

  4. Dual-domain point diffraction interferometer

    DOE Patents [OSTI]

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2000-01-01

    A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.

  5. Jamming Behavior of Domains in a Spiral Antiferromagnetic System

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Jamming Behavior of Domains in a Spiral Antiferromagnetic System Jamming Behavior of Domains in a Spiral Antiferromagnetic System Print Tuesday, 04 June 2013 13:34 This schematic...

  6. Time-Domain Electromagnetics At Soda Lake Area (Combs 2006) ...

    Open Energy Info (EERE)

    Time-Domain Electromagnetics At Soda Lake Area (Combs 2006) Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Soda...

  7. Category:Time-Domain Electromagnetics | Open Energy Information

    Open Energy Info (EERE)

    Time-Domain Electromagnetics Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Geothermalpower.jpg Looking for the Time-Domain Electromagnetics page? For detailed...

  8. Statistical and Domain Analytics Applied to PV Module Lifetime...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Statistical and Domain Analytics Applied to PV Module Lifetime and Degradation Science Statistical and Domain Analytics Applied to PV Module Lifetime and Degradation Science...

  9. Category:Controlled Source Frequency-Domain Magnetics | Open...

    Open Energy Info (EERE)

    Controlled Source Frequency-Domain Magnetics Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Geothermalpower.jpg Looking for the Controlled Source Frequency-Domain...

  10. Insights into substrate specificity of NlpC/P60 cell wall hydrolases containing bacterial SH3 domains

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.; Patin, Delphine; Farr, Carol L.; Grant, Joanna C.; Chiu, Hsiu -Ju; Jaroszewski, Lukasz; Knuth, Mark W.; Godzik, Adam; et al

    2015-09-15

    Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. In addition, these enzymes all have γ-d-Glu-A2pm (A2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structure consisting ofmore » two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes, show that they may have evolved from a common molecular architecture, where the substrate preference is modulated by local changes. These results also suggest that new pathways for recycling PG turnover products, such as tracheal cytotoxin, may have evolved in bacteria in the human gut microbiome that involve NlpC/P60 cell wall hydrolases.« less

  11. Binding Organic Liquids - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    More Like This Return to Search Binding Organic Liquids Pacific Northwest National Laboratory Contact PNNL About This Technology Technology Marketing Summary Researchers at...

  12. Standing gravitational waves from domain walls

    SciTech Connect (OSTI)

    Gogberashvili, Merab; Myrzakul, Shynaray; Singleton, Douglas

    2009-07-15

    We construct a plane symmetric, standing gravitational wave for a domain wall plus a massless scalar field. The scalar field can be associated with a fluid which has the properties of 'stiff' matter, i.e., matter in which the speed of sound equals the speed of light. Although domain walls are observationally ruled out in the present era, the solution has interesting features which might shed light on the character of exact nonlinear wave solutions to Einstein's equations. Additionally this solution may act as a template for higher dimensional 'brane-world' model standing waves.

  13. The pilus usher controls protein interactions via domain masking and is functional as an oligomer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Werneburg, Glenn T.; Li, Huilin; Henderson, Nadine S.; Portnoy, Erica B.; Sarowar, Samema; Hultgren, Scott J.; Thanassi, David G.

    2015-06-08

    The chaperone/usher (CU) pathway is responsible for biogenesis of organelles termed pili or fimbriae in Gram-negative bacteria. Type 1 pili expressed by uropathogenic Escherichia coli are prototypical structures assembled by the CU pathway. Assembly and secretion of pili by the CU pathway requires a dedicated periplasmic chaperone and a multidomain outer membrane protein termed the usher (FimD). We show that the FimD C-terminal domains provide the high-affinity substrate binding site, but that these domains are masked in the resting usher. Domain masking requires the FimD plug domain, which served as a central switch controlling usher activation. In addition, we demonstratemore » that usher molecules can act in trans for pilus biogenesis, providing conclusive evidence for a functional usher oligomer. These results reveal mechanisms by which molecular machines such as the usher regulate and harness protein-protein interactions, and suggest that ushers may interact in a cooperative manner during pilus assembly in bacteria.« less

  14. Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface

    SciTech Connect (OSTI)

    Zhang, Rong; Li, Xiaofeng; Boggon, Titus J.

    2015-10-14

    Cerebral cavernous malformations (CCM) are vascular dysplasias that usually occur in the brain and are associated with mutations in the KRIT1/CCM1, CCM2/MGC4607/OSM/Malcavernin, and PDCD10/CCM3/ TFAR15 genes. Here we report the 2.9 Å crystal structure of the ankyrin repeat domain (ARD) and FERM domain of the protein product of KRIT1 (KRIT1; Krev interaction trapped 1). The crystal structure reveals that the KRIT1 ARD contains 4 ankyrin repeats. There is also an unusual conformation in the ANK4 repeat that is stabilized by Trp-404, and the structure reveals a solvent exposed ankyrin groove. Domain orientations of the three copies within the asymmetric unit suggest a stable interaction between KRIT1 ARD and FERM domains, indicating a globular ARD–FERM module. It resembles the additional F0 domain found N-terminal to the FERM domain of talin. Structural analysis of KRIT1 ARD–FERM highlights surface regions of high evolutionary conservation, and suggests potential sites that could mediate interaction with binding partners. The structure therefore provides a better understanding of KRIT1 at the molecular level.

  15. Characterization of a large deletion in the {beta}-globin gene cluster in a newborn with hemoglobin FE

    SciTech Connect (OSTI)

    Louie, E.; Dietz, L.; Shafer, F.

    1994-09-01

    A sample on a newborn with hemoglobin FE screen results was obtained to investigate whether E/E or B/{beta}{degrees} thalassemia was present using polymerase chain reaction (PCR) methodology. The newborn appeared homozygous for the hemoglobin E mutation in our initial study, but the parents` genotypes did not support this diagnosis. The father is homozygous for the absence of the hemoglobin E mutation (non E/non E) and the mother is heterozygous (E/non E) for this mutation. The limitation of PCR analysis is an assumption that the amplification of the two {beta}-globin alleles is equivalent. A large deletion on one {beta}-globin gene, which would produce E/{beta}{degrees} thalassemia, would be missed if it included part or the entire region subjected to amplification. The family results were consistent with either non-paternity, sample mix-up or such a deletion of the {beta}-globin gene in the father and child. To rule out the possibility of non-paternity, two polymorphic loci (HLA on chromosome 6 and a VNTR system of chromosome 17) that are outside of the {beta}-globin gene were analyzed and show that inheritance is consistent and the likelihood of a sample mix-up is then reduced. We therefore believe there is a gene deletion in this family. At the present time, analyses of the RFLPs that are 5{prime} of the {beta}-globin gene cluster show that the polymorphisms most distal from the 5{prime} {beta}-globin gene are not being inherited as expected. These results support our interpretation that a deletion exists in the father and was inherited by the child. The father`s clinical picture of possible HPFH (the father has 12% hemoglobin F) also supports the interpretation of a deletion in this family. Deletions of the {beta}-globin gene within this ethnic group are rare. Currently, Southern blots on the family are being probed to determine the extent of the putative deletion.

  16. Nicotinamide mononucleotide adenylyltransferase displays alternate binding

    Office of Scientific and Technical Information (OSTI)

    modes for nicotinamide nucleotides (Journal Article) | SciTech Connect Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides Citation Details In-Document Search Title: Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides Authors: Pfoh, Roland ; Pai, Emil F. ; Saridakis, Vivian [1] ; Toronto) [2] + Show Author Affiliations (York) ( Publication Date: 2015-11-23 OSTI Identifier:

  17. Improved flow cytometer measurement of binding assays

    DOE Patents [OSTI]

    Saunders, G.C.

    1984-05-30

    The invention relates to a method of measuring binding assays carried out with different size particles wherein the binding assay sample is run through a flow cytometer without separating the sample from the marking agent. The amount of a binding reactant present in a sample is determined by providing particles with a coating of binder and also a known quantity of smaller particles with a coating of binder reactant. The binding reactant is the same as the binding reactant present in the sample. The smaller particles also contain a fluorescent chemical. The particles are combined with the sample and the binding reaction is allowed to occur for a set length of time followed by combining the smaller particles with the mixture of the particles and the sample produced and allowing the binding reactions to proceed to equilibrium. The fluorescence and light scatter of the combined mixture is then measured as the combined mixture passes through a flow cytometer equipped with a laser to bring about fluorescence, and the number and strength of fluorescent events are compared. A similar method is also provided for determining the amount of antigen present in the sample by providing spheres with an antibody coating and some smaller spheres with an antigen coating. (LEW)

  18. LHC RF System Time-Domain Simulation

    SciTech Connect (OSTI)

    Mastorides, T.; Rivetta, C.

    2010-09-14

    Non-linear time-domain simulations have been developed for the Positron-Electron Project (PEP-II) and the Large Hadron Collider (LHC). These simulations capture the dynamic behavior of the RF station-beam interaction and are structured to reproduce the technical characteristics of the system (noise contributions, non-linear elements, and more). As such, they provide useful results and insight for the development and design of future LLRF feedback systems. They are also a valuable tool for the study of diverse longitudinal beam dynamics effects such as coupled-bunch impedance driven instabilities and single bunch longitudinal emittance growth. Results from these studies and related measurements from PEP-II and LHC have been presented in multiple places. This report presents an example of the time-domain simulation implementation for the LHC.

  19. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  20. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  1. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  2. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  3. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  4. Slow Dynamics of Orbital Domains in Manganite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Slow Dynamics of Orbital Domains in Manganite Print At the ALS, an international team of researchers has used low-energy coherent x rays to extract new knowledge about the correlated motion of groups of self-assembled, outer-lying electrons in the extremely complex electronic system found in manganites. The manganite family of materials has puzzled physicists for years by defying standard models for the motion of electrons in crystals. By controlling the properties of the incident x rays, the

  5. The structure of the SBP-Tagstreptavidin complex reveals a novel helical scaffold bridging binding pockets on separate subunits

    SciTech Connect (OSTI)

    Barrette-Ng, Isabelle H.; Wu, Sau-Ching; Tjia, Wai-Mui; Wong, Sui-Lam; Ng, Kenneth K. S.

    2013-05-01

    The structure of the SBP-Tagstreptavidin complex reveals a novel mode of peptide recognition in which a single peptide binds simultaneously to biotin-binding pockets from adjacent subunits of streptavidin. The molecular details of peptide recognition suggest how the SBP-Tag can be further modified to become an even more useful tag for a wider range of biotechnological applications. The 38-residue SBP-Tag binds to streptavidin more tightly (K{sub d} ? 2.54.9 nM) than most if not all other known peptide sequences. Crystallographic analysis at 1.75 resolution shows that the SBP-Tag binds to streptavidin in an unprecedented manner by simultaneously interacting with biotin-binding pockets from two separate subunits. An N-terminal HVV peptide sequence (residues 1214) and a C-terminal HPQ sequence (residues 3133) form the bulk of the direct interactions between the SBP-Tag and the two biotin-binding pockets. Surprisingly, most of the peptide spanning these two sites (residues 1728) adopts a regular ?-helical structure that projects three leucine side chains into a groove formed at the interface between two streptavidin protomers. The crystal structure shows that residues 110 and 3538 of the original SBP-Tag identified through in vitro selection and deletion analysis do not appear to contact streptavidin and thus may not be important for binding. A 25-residue peptide comprising residues 1134 (SBP-Tag2) was synthesized and shown using surface plasmon resonance to bind streptavidin with very similar affinity and kinetics when compared with the SBP-Tag. The SBP-Tag2 was also added to the C-terminus of ?-lactamase and was shown to be just as effective as the full-length SBP-Tag in affinity purification. These results validate the molecular structure of the SBP-Tagstreptavidin complex and establish a minimal bivalent streptavidin-binding tag from which further rational design and optimization can proceed.

  6. Hardware device binding and mutual authentication

    DOE Patents [OSTI]

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04

    Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

  7. DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1

    SciTech Connect (OSTI)

    Lerner, Mikael; Harada, Masako; Loven, Jakob; Castro, Juan; Davis, Zadie; Oscier, David; Henriksson, Marie; Sangfelt, Olle; Grander, Dan; Corcoran, Martin M.

    2009-10-15

    The microRNAs miR-15a and miR-16-1 are downregulated in multiple tumor types and are frequently deleted in chronic lymphocytic leukemia (CLL), myeloma and mantle cell lymphoma. Despite their abundance in most cells the transcriptional regulation of miR-15a/16-1 remains unclear. Here we demonstrate that the putative tumor suppressor DLEU2 acts as a host gene of these microRNAs. Mature miR-15a/miR-16-1 are produced in a Drosha-dependent process from DLEU2 and binding of the Myc oncoprotein to two alterative DLEU2 promoters represses both the host gene transcript and levels of mature miR-15a/miR-16-1. In line with a functional role for DLEU2 in the expression of the microRNAs, the miR-15a/miR-16-1 locus is retained in four CLL cases that delete both promoters of this gene and expression analysis indicates that this leads to functional loss of mature miR-15a/16-1. We additionally show that DLEU2 negatively regulates the G1 Cyclins E1 and D1 through miR-15a/miR-16-1 and provide evidence that these oncoproteins are subject to miR-15a/miR-16-1-mediated repression under normal conditions. We also demonstrate that DLEU2 overexpression blocks cellular proliferation and inhibits the colony-forming ability of tumor cell lines in a miR-15a/miR-16-1-dependent way. Together the data illuminate how inactivation of DLEU2 promotes cell proliferation and tumor progression through functional loss of miR-15a/miR-16-1.

  8. Wyo. Stat. 1-26 - Eminent Domain | Open Energy Information

    Open Energy Info (EERE)

    Wyo. Stat. 1-26 - Eminent Domain Jump to: navigation, search OpenEI Reference LibraryAdd to library Legal Document- StatuteStatute: Wyo. Stat. 1-26 - Eminent DomainLegal...

  9. Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Smart Grid Conceptual ActorsData Flow Diagram- Cross Domain Network Focued- Open SGSG-Network TF Smart Grid Conceptual ActorsData Flow Diagram- Cross Domain Network Focued- Open ...

  10. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Monday, 28 November 2011 14:52 Movement is fundamental to life. It...

  11. Sequestering Uranium from Seawater: Binding Strength and Modes...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl...

  12. Fragment-Based Exploration of Binding Site Flexibility in Mycobacteriu...

    Office of Scientific and Technical Information (OSTI)

    Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Citation Details In-Document Search Title: Fragment-Based Exploration of Binding Site ...

  13. Particle Communication and Domain Neighbor Coupling: Scalable Domain Decomposed Algorithms for Monte Carlo Particle Transport

    SciTech Connect (OSTI)

    O'Brien, M J; Brantley, P S

    2015-01-20

    In order to run Monte Carlo particle transport calculations on new supercomputers with hundreds of thousands or millions of processors, care must be taken to implement scalable algorithms. This means that the algorithms must continue to perform well as the processor count increases. In this paper, we examine the scalability of:(1) globally resolving the particle locations on the correct processor, (2) deciding that particle streaming communication has finished, and (3) efficiently coupling neighbor domains together with different replication levels. We have run domain decomposed Monte Carlo particle transport on up to 221 = 2,097,152 MPI processes on the IBM BG/Q Sequoia supercomputer and observed scalable results that agree with our theoretical predictions. These calculations were carefully constructed to have the same amount of work on every processor, i.e. the calculation is already load balanced. We also examine load imbalanced calculations where each domains replication level is proportional to its particle workload. In this case we show how to efficiently couple together adjacent domains to maintain within workgroup load balance and minimize memory usage.

  14. Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution

    SciTech Connect (OSTI)

    Chen, Liqing Wang, Yujun; Wells, David; Toh, Diana; Harold, Hunt; Zhou, Jing; DiGiammarino, Enrico; Meehan, Edward J.

    2006-09-01

    The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 . The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in proteinprotein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 1272, yielded crystals that diffracted to the ultrahigh resolution of 1.07 . The overall structure shows a characteristic SH3 fold consisting of two perpendicular ?-sheets that form a ?-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors.

  15. Ligand-induced conformational changes in a thermophilic ribose-binding protein

    SciTech Connect (OSTI)

    Cuneo, Matthew J.; Beese, Lorena S.; Hellinga, Homme W.

    2009-05-21

    Members of the periplasmic binding protein (PBP) superfamily are involved in transport and signaling processes in both prokaryotes and eukaryotes. Biological responses are typically mediated by ligand-induced conformational changes in which the binding event is coupled to a hinge-bending motion that brings together two domains in a closed form. In all PBP-mediated biological processes, downstream partners recognize the closed form of the protein. This motion has also been exploited in protein engineering experiments to construct biosensors that transduce ligand binding to a variety of physical signals. Understanding the mechanistic details of PBP conformational changes, both global (hinge bending, twisting, shear movements) and local (rotamer changes, backbone motion), therefore is not only important for understanding their biological function but also for protein engineering experiments. Here we present biochemical characterization and crystal structure determination of the periplasmic ribose-binding protein (RBP) from the hyperthermophile Thermotoga maritima in its ribose-bound and unliganded state. The T. maritima RBP (tmRBP) has 39% sequence identity and is considerably more resistant to thermal denaturation (appTm value is 108 C) than the mesophilic Escherichia coli homolog (ecRBP) (appTm value is 56 C). Polar ligand interactions and ligand-induced global conformational changes are conserved among ecRBP and tmRBP; however local structural rearrangements involving side-chain motions in the ligand-binding site are not conserved. Although the large-scale ligand-induced changes are mediated through similar regions, and are produced by similar backbone movements in tmRBP and ecRBP, the small-scale ligand-induced structural rearrangements differentiate the mesophile and thermophile. This suggests there are mechanistic differences in the manner by which these two proteins bind their ligands and are an example of how two structurally similar proteins utilize different mechanisms to form a ligand-bound state.

  16. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Wednesday, 29 July 2009 00:00 Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray

  17. Jamming Behavior of Domains in a Spiral Antiferromagnetic System

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Jamming Behavior of Domains in a Spiral Antiferromagnetic System Jamming Behavior of Domains in a Spiral Antiferromagnetic System Print Tuesday, 04 June 2013 13:34 This schematic of x-ray scattering is from a spiral antiferromagnet with a spin structure that gives rise to domains with jamming behavior. Using resonant magnetic x-ray photon correlation spectroscopy, this research shows that the domains of a spiral antiferromagnet enter a jammed state at the onset of long-range order. Researchers

  18. Development of Nonlinear SSI Time Domain Methodology | Department of Energy

    Office of Environmental Management (EM)

    Development of Nonlinear SSI Time Domain Methodology Development of Nonlinear SSI Time Domain Methodology Development of Nonlinear SSI Time Domain Methodology Justin Coleman, P.E. Nuclear Science and Technology Idaho National Laboratory October 22, 2014 PDF icon Development of Nonlinear SSI Time Domain Methodology More Documents & Publications 3D Site Response using NLSSI Idaho National Laboratory (INL) Seismic Initiative Non-Linear Seismic Soil Structure Interaction (SSI) Method for

  19. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen

    2000-01-01

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  20. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2006-10-17

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  1. Dental optical coherence domain reflectometry explorer

    DOE Patents [OSTI]

    Everett, Matthew J. (Livermore, CA); Colston, Jr., Billy W. (Livermore, CA); Sathyam, Ujwal S. (Livermore, CA); Da Silva, Luiz B. (Pleasanton, CA)

    2001-01-01

    A hand-held, fiber optic based dental device with optical coherence domain reflectometry (OCDR) sensing capabilities provides a profile of optical scattering as a function of depth in the tissue at the point where the tip of the dental explorer touches the tissue. This system provides information on the internal structure of the dental tissue, which is then used to detect caries and periodontal disease. A series of profiles of optical scattering or tissue microstructure are generated by moving the explorer across the tooth or other tissue. The profiles are combined to form a cross-sectional, or optical coherence tomography (OCT), image.

  2. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    SciTech Connect (OSTI)

    Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang

    2014-10-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor ? (ER?) and ER? expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17?-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ER? between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ER?. We also found that RTV directly bound to ER? and selectively inhibited the nuclear localization of ER?, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ER?-LBD like E2, which explained how ER? lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17?-estradiol in regulating ? subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ER? and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: RTV increases the thickness of rat coronary artery wall and foam cell formation. RTV downregulates the expression of ER? and ER?. RTV inhibits ER? promoter activity. RTV directly binds to ER? and the key amino acid is Leu536. RTV inhibits the nuclear translocation of ER? and GPER.

  3. Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

    SciTech Connect (OSTI)

    Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

    2011-11-25

    We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: > We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. > Cre/loxP recombination was used to modify the adenovirus genome. > A targeting ligand present on capsid protein IX was removed or replaced using recombination. > Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

  4. Binding and Recognition in the Assembly of an Active BRCA1/BARD1 Ubiquitin-Ligase Complex

    SciTech Connect (OSTI)

    Brzovic, Peter S.; Keeffe, Jennifer R.; Nishikawa, Hiroyuki; Miyamoto, Keiko; Fox, David; Fukuda, Mamoru; Ohta, Tomohiko; Klevit, Rachel E.

    2003-05-13

    BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RING/RING heterodimer. The BRCA1/BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. By using NMR spectroscopy and site-directed mutagenesis, we have mapped the binding site on the BRCA1/BARD1 heterodimer for the Ub-conjugating enzyme UbcH5c. The results demonstrate that UbcH5c binds only to the BRCA1 RING domain and not the BARD1 RING. The binding interface is formed by the first and second Zn2+-loops and central -helix of the BRCA1 RING domain, a region disrupted by cancer-predisposing mutations. Unexpectedly, a second Ub-conjugating enzyme, UbcH7, also interacts with the BRCA1/BARD1 complex with similar affinity, although it is not active in Ub-ligase activity assays. Thus, binding alone is not sufficient for BRCA1-dependent Ub-ligase activity.

  5. Inflationary power asymmetry from primordial domain walls

    SciTech Connect (OSTI)

    Jazayeri, Sadra; Akrami, Yashar; Firouzjahi, Hassan; Solomon, Adam R.; Wang, Yi E-mail: yashar.akrami@astro.uio.no E-mail: a.r.solomon@damtp.cam.ac.uk

    2014-11-01

    We study the asymmetric primordial fluctuations in a model of inflation in which translational invariance is broken by a domain wall. We calculate the corrections to the power spectrum of curvature perturbations; they are anisotropic and contain dipole, quadrupole, and higher multipoles with non-trivial scale-dependent amplitudes. Inspired by observations of these multipole asymmetries in terms of two-point correlations and variance in real space, we demonstrate that this model can explain the observed anomalous power asymmetry of the cosmic microwave background (CMB) sky, including its characteristic feature that the dipole dominates over higher multipoles. We test the viability of the model and place approximate constraints on its parameters by using observational values of dipole, quadrupole, and octopole amplitudes of the asymmetry measured by a local-variance estimator. We find that a configuration of the model in which the CMB sphere does not intersect the domain wall during inflation provides a good fit to the data. We further derive analytic expressions for the corrections to the CMB temperature covariance matrix, or angular power spectra, which can be used in future statistical analysis of the model in spherical harmonic space.

  6. EERE Web Domains and URLs | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Project Process & Approvals » EERE Web Domains and URLs EERE Web Domains and URLs For domains and URLs, all Office of Energy Efficiency and Renewable Energy (EERE) office and partnership websites must comply with the Department of Energy (DOE), the Office of Management and Budget (OMB), and the EERE domain policies. Getting Approval All domains must be approved by the Web Governance Team (WGT). For new Web projects, you'll include it on the Project Information Form, which you'll complete

  7. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    SciTech Connect (OSTI)

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Di Leo, Rosa; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H.W.; Curmi, Paul M.G.; Mabbutt, Bridget C.

    2012-02-15

    The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.

  8. Exciton binding energy in semiconductor quantum dots

    SciTech Connect (OSTI)

    Pokutnii, S. I.

    2010-04-15

    In the adiabatic approximation in the context of the modified effective mass approach, in which the reduced exciton effective mass {mu} = {mu}(a) is a function of the radius a of the semiconductor quantum dot, an expression for the exciton binding energy E{sub ex}(a) in the quantum dot is derived. It is found that, in the CdSe and CdS quantum dots with the radii a comparable to the Bohr exciton radii a{sub ex}, the exciton binding energy E{sub ex}(a) is substantially (respectively, 7.4 and 4.5 times) higher than the exciton binding energy in the CdSe and CdS single crystals.

  9. Birefringence insensitive optical coherence domain reflectometry system

    DOE Patents [OSTI]

    Everett, Matthew J. (Livermore, CA); Davis, Joseph G. (Lafayette, CA)

    2002-01-01

    A birefringence insensitive fiber optic optical coherence domain reflectometry (OCDR) system is provided containing non-polarization maintaining (non-PM) fiber in the sample arm and the reference arm without suffering from signal degradation caused by birefringence. The use of non-PM fiber significantly reduces the cost of the OCDR system and provides a disposable or multiplexed section of the sample arm. The dispersion in the reference arm and sample arm of the OCDR system are matched to achieve high resolution imaging. This system is useful in medical applications or for non-medical in situ probes. The disposable section of non-PM fiber in the sample arm can be conveniently replaced when contaminated by a sample or a patient.

  10. Stabilized sulfur binding using activated fillers

    DOE Patents [OSTI]

    Kalb, Paul D.; Vagin, Vyacheslav P.; Vagin, Sergey P.

    2015-07-21

    A method of making a stable, sulfur binding composite comprising impregnating a solid aggregate with an organic modifier comprising unsaturated hydrocarbons with at least one double or triple covalent bond between adjacent carbon atoms to create a modifier-impregnated aggregate; heating and drying the modifier-impregnated aggregate to activate the surface of the modifier-impregnated aggregate for reaction with sulfur.

  11. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  12. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  13. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  14. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  15. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  16. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  17. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stochastic Domain-Wall Depinning in Magnetic Nanowires Print Reliably controlling the motion of magnetic domain walls along magnetic nanowires is a key requirement for current technological development of novel classes of logic and storage devices, but understanding the nature of non-deterministic domain-wall motion remains a scientific challenge. A statistical analysis of high-resolution magnetic soft x-ray microscopy images by a Berkeley Lab-University of Hamburg group has now revealed that

  18. National Geothermal Data System (NGDS) Geothermal Data Domain...

    Open Energy Info (EERE)

    Geothermal Data System (NGDS) Geothermal Data Domain: Assessment of Geothermal Community Data Needs Jump to: navigation, search OpenEI Reference LibraryAdd to library Conference...

  19. Organic Solar Cells: Absolute Measurement of Domain Composition...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Organic Solar Cells: Absolute Measurement of Domain Composition and Nanoscale Size Distribution Explains Performance in Solar Cells Organic Solar Cells: Absolute Measurement of...

  20. Stochastic Domain-Wall Depinning in Magnetic Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    concept called a racetrack memory, for example, the electron spin provides the driving force that moves a domain wall (boundary between regions of different magnetization) down...

  1. Experimental measurement of stress at a four-domain junction...

    Office of Scientific and Technical Information (OSTI)

    domains in a lead zirconate titanate ceramic is analyzed using Kikuchi diffraction ... Such stress concentrations could act as nuclei for cracking of the ceramic under ...

  2. Time-Domain Electromagnetics At Kilauea East Rift Geothermal...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Kilauea East Rift Geothermal Area (Thomas, 1986) Exploration...

  3. Time-Domain Electromagnetics At Kilauea East Rift Geothermal...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Kilauea East Rift Geothermal Area (Skokan, 1974) Exploration...

  4. Time-Domain Electromagnetics At Kilauea Southwest Rift And South...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Kilauea Southwest Rift And South Flank Area (Thomas, 1986)...

  5. Time-Domain Electromagnetics At Hualalai Northwest Rift Area...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Hualalai Northwest Rift Area (Thomas, 1986) Exploration...

  6. Time-Domain Electromagnetics At Mauna Loa Northeast Rift Area...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Mauna Loa Northeast Rift Area (Thomas, 1986) Exploration...

  7. Time-Domain Electromagnetics At Glass Mountain Area (Cumming...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Glass Mountain Area (Cumming And Mackie, 2007) Exploration...

  8. Time-Domain Electromagnetics At Haleakala Volcano Area (Thomas...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Haleakala Volcano Area (Thomas, 1986) Exploration Activity...

  9. Time-Domain Electromagnetics At Truckhaven Area (Warpinski, Et...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Truckhaven Area (Warpinski, Et Al., 2004) Exploration...

  10. Time-Domain Electromagnetics At Dixie Hot Springs Area (Combs...

    Open Energy Info (EERE)

    Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Dixie Hot Springs Area (Combs 2006) Exploration Activity...

  11. Visualizing the Behavior of Polar Domains and Screening Charges...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Visualizing the Behavior of Polar Domains and Screening Charges Under Electric and Mechanical Fields Event Sponsor: Mathematics and Computing Science - LANS Seminar Start Date: Sep...

  12. Structure and Dynamics of Domains in Ferroelectric Nanostructures...

    Office of Scientific and Technical Information (OSTI)

    of ferroelectric domains in ferroelectric thin films and nanostructures by advanced transmission electron microscopy (TEM) techniques in close collaboration with phase field...

  13. Controlled Source Frequency-Domain Magnetics (Montgomery, Et...

    Open Energy Info (EERE)

    (Montgomery, Et Al., 2005) Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Controlled Source Frequency-Domain Magnetics (Montgomery, Et Al.,...

  14. Controlled Source Frequency-Domain Magnetics At Salt Wells Area...

    Open Energy Info (EERE)

    At Salt Wells Area (Montgomery, Et Al., 2005) Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Controlled Source Frequency-Domain Magnetics At...

  15. Atmospheric Correction of Satellite Signal in Solar Domain: ...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Atmospheric Correction of Satellite Signal in Solar Domain: Impact of Improved Molecular Spectroscopy A. P. Trishchenko Canada Centre for Remote Sensing Ottawa, Ontario, Canada B....

  16. Time-Domain Electromagnetics At Kilauea East Rift Geothermal...

    Open Energy Info (EERE)

    At Kilauea East Rift Geothermal Area (FURUMOTO, 1976) Exploration Activity Details Location Kilauea East Rift Geothermal Area Exploration Technique Time-Domain...

  17. Frequency-Domain Electromagnetics Survey At Kilauea East Rift...

    Open Energy Info (EERE)

    1976) Jump to: navigation, search GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Frequency-Domain Electromagnetics Survey At Kilauea East Rift Geothermal Area (FURUMOTO,...

  18. Nonlinear Time Domain Modeling and Simulation of Surface and...

    Office of Environmental Management (EM)

    Jose Abell, Kohei Watanabe, Chao Luo University of California, Davis Lawrence Berkeley National Laboratory, Berkeley DOE NPH, October 2014 PDF icon Nonlinear Time Domain...

  19. Crystal structure of a ;#8203;BRAF kinase domain monomer explains...

    Office of Scientific and Technical Information (OSTI)

    Crystal structure of a ;8203;BRAF kinase domain monomer explains basis for allosteric regulation Citation Details In-Document Search Title: Crystal structure of a ;8203;BRAF ...

  20. Catheter guided by optical coherence domain reflectometry

    DOE Patents [OSTI]

    Everett, Matthew (Pleasanton, CA); Colston, Billy W. (Livermore, CA); Da Silva, Luiz B. (Danville, CA); Matthews, Dennis (Moss Beach, CA)

    2002-01-01

    A guidance and viewing system based on multiplexed optical coherence domain reflectometry is incorporated into a catheter, endoscope, or other medical device to measure the location, thickness, and structure of the arterial walls or other intra-cavity regions at discrete points on the medical device during minimally invasive medical procedures. The information will be used both to guide the device through the body and to evaluate the tissue through which the device is being passed. Multiple optical fibers are situated along the circumference of the device. Light from the distal end of each fiber is directed onto the interior cavity walls via small diameter optics (such as gradient index lenses and mirrored corner cubes). Both forward viewing and side viewing fibers can be included. The light reflected or scattered from the cavity walls is then collected by the fibers and multiplexed at the proximal end to the sample arm of an optical low coherence reflectometer. The system may also be implemented in a nonmedical inspection device.

  1. Dual-domain lateral shearing interferometer

    DOE Patents [OSTI]

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2004-03-16

    The phase-shifting point diffraction interferometer (PS/PDI) was developed to address the problem of at-wavelength metrology of extreme ultraviolet (EUV) optical systems. Although extremely accurate, the fact that the PS/PDI is limited to use with coherent EUV sources, such as undulator radiation, is a drawback for its widespread use. An alternative to the PS/PDI, with relaxed coherence requirements, is lateral shearing interferometry (LSI). The use of a cross-grating, carrier-frequency configuration to characterize a large-field 4.times.-reduction EUV lithography optic is demonstrated. The results obtained are directly compared with PS/PDI measurements. A defocused implementation of the lateral shearing interferometer in which an image-plane filter allows both phase-shifting and Fourier wavefront recovery. The two wavefront recovery methods can be combined in a dual-domain technique providing suppression of noise added by self-interference of high-frequency components in the test-optic wavefront.

  2. Homozygous deletions on the short arm of chromosome 9 in ovarian adenocarcinoma cell lines and loss of heterozygosity in sporadic tumors

    SciTech Connect (OSTI)

    Chenevix-Trench, G.; Kerr, J.; Hurst, T.; Sanderson, B.; Coglan, M.; Ward, B.; Khoo, S.K. ); Friedlander, M.; Leary, J.

    1994-07-01

    Rat ovarian surface epithelial cells transformed spontaneously in vitro have been found to have homozygous deletions of the interferon alpha (IFNA) gene. This suggests that inactivation of a tumor-suppressor gene in this region may be crucial for the development of ovarian cancer. The authors therefore used microsatellite markers and Southern analysis to examine the homologous region in humans - the short arm of chromosome 9 - for deletions in sporadic ovarian adenocarcinomas and ovarian tumor cell lines. Loss of heterozygosity occurred in 34 (37%) of 91 informative sporadic tumors, including some benign, low-malignant-potential and early-stage tumors, suggesting that it is an early event in the development of ovarian adenocarcinoma. Furthermore, homozygous deletions on 9p were found in 2 of 10 independent cell lines. Deletion mapping of the tumors and lines indicates that the candidate suppressor gene inactivated as a consequence lies between D9S171 and the IFNA locus, a region that is also deleted in several other tumors and that contains the melanoma predisposition gene, MLM. 52 refs., 4 figs., 1 tab.

  3. X-ray crystallographic analysis of adipocyte fatty acid binding...

    Office of Scientific and Technical Information (OSTI)

    binding protein (aP2) modified with 4-hydroxy-2-nonenal Citation Details In-Document Search Title: X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) ...

  4. Thermal effects on transverse domain wall dynamics in magnetic nanowires

    SciTech Connect (OSTI)

    Leliaert, J.; Van de Wiele, B.; Vandermeulen, J.; Coene, A.; Dupré, L.; Vansteenkiste, A.; Waeyenberge, B. Van; Laurson, L.; Durin, G.

    2015-05-18

    Magnetic domain walls are proposed as data carriers in future spintronic devices, whose reliability depends on a complete understanding of the domain wall motion. Applications based on an accurate positioning of domain walls are inevitably influenced by thermal fluctuations. In this letter, we present a micromagnetic study of the thermal effects on this motion. As spin-polarized currents are the most used driving mechanism for domain walls, we have included this in our analysis. Our results show that at finite temperatures, the domain wall velocity has a drift and diffusion component, which are in excellent agreement with the theoretical values obtained from a generalized 1D model. The drift and diffusion component are independent of each other in perfect nanowires, and the mean square displacement scales linearly with time and temperature.

  5. Domain evolution and polarization of continuously graded ferroelectric films

    SciTech Connect (OSTI)

    Roytburd, A.; Roytburd, V.

    2008-01-01

    A thermodynamic analysis of graded ferroelectric films demonstrates that in the equilibrium state the films are subdivided into a single-domain band and a polydomain band which consists of wedge-shape domains. Polarization under an external electrostatic field proceeds through an inter-band boundary movement due to growth or shrinkage of the wedge domains. It is shown how the domain structure and evolution are determined by the principal characteristics of the film: the distribution of the spontaneous polarization and dielectric constant. Graded films exhibit a sharp increase of polarization with the field for weak fields, with a drop of the dielectric constant when the field is increasing. A general approach to finding the dependence of the displacement and the wedge-domain shape on the field as well as analytical solutions for the p{sup 4} Landau-Devonshire and parabolic potentials are presented.

  6. Multidomain Carbohydrate-binding Proteins Involved in Bacteroides...

    Office of Scientific and Technical Information (OSTI)

    Title: Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Authors: Cameron, Elizabeth A. ; Maynard, Mallory A. ; Smith, ...

  7. Recognition of the Activated States of G[alpha]13 by the rgRGS Domain of PDZRhoGEF

    SciTech Connect (OSTI)

    Chen, Zhe; Singer, William D.; Danesh, Shahab M.; Sternweis, Paul C.; Sprang, Stephen R.

    2009-12-01

    G12 class heterotrimeric G proteins stimulate RhoA activation by RGS-RhoGEFs. However, p115RhoGEF is a GTPase Activating Protein (GAP) toward G{alpha}13, whereas PDZRhoGEF is not. We have characterized the interaction between the PDZRhoGEF rgRGS domain (PRG-rgRGS) and the alpha subunit of G13 and have determined crystal structures of their complexes in both the inactive state bound to GDP and the active states bound to GDP {center_dot} AlF (transition state) and GTP{gamma}S (Michaelis complex). PRG-rgRGS interacts extensively with the helical domain and the effector-binding sites on G{alpha}13 through contacts that are largely conserved in all three nucleotide-bound states, although PRG-rgRGS has highest affinity to the Michaelis complex. An acidic motif in the N terminus of PRG-rgRGS occupies the GAP binding site of G{alpha}13 and is flexible in the GDP {center_dot} AlF complex but well ordered in the GTPS complex. Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity.

  8. Frequent intragenic deletion of the P gene in Tanzanian patients with Type II oculocutaneous albinism (OCA2)

    SciTech Connect (OSTI)

    Spritz, R.; Fukai, K.; Holmes, S.A.

    1995-06-01

    Type II oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which results from mutations of the P gene, is the most frequent type of albinism in African and African-American patients. OCA2 is especially frequent in Tanzania, where it occurs with an incidence of {approximately}1/1,400. We have identified abnormalities of the P gene in each of 13 unrelated patients with OCA2 from Tanzania. One of these, a deletion of exon 7, is strongly predominant, accounting for {approximately}77% of mutant alleles in this group of patients. 20 refs., 2 figs.

  9. Gene encoding herbicide safener binding protein

    DOE Patents [OSTI]

    Walton, Jonathan D.; Scott-Craig, John S.

    1999-01-01

    The cDNA encoding safener binding protein (SafBP), also referred to as SBP1, is set forth in FIG. 5 and SEQ ID No. 1. The deduced amino acid sequence is provided in FIG. 5 and SEQ ID No. 2. Methods of making and using SBP1 and SafBP to alter a plant's sensitivity to certain herbicides or a plant's responsiveness to certain safeners are also provided, as well as expression vectors, transgenic plants or other organisms transfected with said vectors and seeds from said plants.

  10. Polynucleotides encoding TRF1 binding proteins

    DOE Patents [OSTI]

    Campisi, Judith (Berkeley, CA); Kim, Sahn-Ho (Albany, CA)

    2002-01-01

    The present invention provides a novel telomere associated protein (Trf1-interacting nuclear protein 2 "Tin2") that hinders the binding of Trf1 to its specific telomere repeat sequence and mediates the formation of a Tin2-Trf1-telomeric DNA complex that limits telomerase access to the telomere. Also included are the corresponding nucleic acids that encode the Tin2 of the present invention, as well as mutants of Tin2. Methods of making, purifying and using Tin2 of the present invention are described. In addition, drug screening assays to identify drugs that mimic and/or complement the effect of Tin2 are presented.

  11. Iran Thomas Auditorium, 8600 Charged Domain Walls in Ferroelectrics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Monday, February 4, 2013 11:00 am Iran Thomas Auditorium, 8600 Charged Domain Walls in Ferroelectrics Alexander K. Tagantsev Ceramics Laboratory, Swiss Federal Institute of Technology (EPFL) Lausanne 1015, Switzerland CNMS D D I I S S C C O O V V E E R R Y Y SEMINAR SERIES Abstract: A ferroelectric domain wall can carry net bound charge depending on its orientation with respect to the direction of polarization in the adjacent domains. Many features of such walls, called charged walls, can

  12. Insights into Regulated Ligand Binding Sites from the Structure of ZO-1 Src Homology 3-Guanylate Kinase Module

    SciTech Connect (OSTI)

    Lye, Ming F.; Fanning, Alan S.; Su, Ying; Anderson, James M.; Lavie, Arnon (UNC); (UIC)

    2010-11-09

    Tight junctions are dynamic components of epithelial and endothelial cells that regulate the paracellular transport of ions, solutes, and immune cells. The assembly and permeability of these junctions is dependent on the zonula occludens (ZO) proteins, members of the membrane-associated guanylate kinase homolog (MAGUK) protein family, which are characterized by a core Src homology 3 (SH3)-GUK module that coordinates multiple protein-protein interactions. The structure of the ZO-1 SH3-GUK domain confirms that the interdependent folding of the SH3 and GUK domains is a conserved feature of MAGUKs, but differences in the orientation of the GUK domains in three different MAGUKs reveal interdomain flexibility of the core unit. Using pull-down assays, we show that an effector loop, the U6 region in ZO-1, forms a novel intramolecular interaction with the core module. This interaction is divalent cation-dependent and overlaps with the binding site for the regulatory molecule calmodulin on the GUK domain. These findings provide insight into the previously observed ability of the U6 region to regulate TJ assembly in vivo and the structural basis for the complex protein interactions of the MAGUK family.

  13. The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile

    SciTech Connect (OSTI)

    Bradshaw, William J.; Kirby, Jonathan M.; Thiyagarajan, Nethaji; Chambers, Christopher J.; Davies, Abigail H.; Roberts, April K.; Shone, Clifford C.; Acharya, K. Ravi

    2014-07-01

    The crystal structure of Cwp84, an S-layer protein from Clostridium difficile is presented for the first time. The cathepsin L-like fold of cysteine protease domain, a newly observed lectin-like domain and several other features are described. Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism.

  14. On the predictability of the orientation of protein domains joined...

    Office of Scientific and Technical Information (OSTI)

    On the predictability of the orientation of protein domains joined by a spanning alpha-helical linker Citation Details In-Document Search Title: On the predictability of the...

  15. Domain-level rocking motion within a polymerase that translocates...

    Office of Scientific and Technical Information (OSTI)

    nucleic acid An X-ray crystallographic structure is described for unliganded Vaccinia virus poly(A) polymerase monomer (VP55), showing the first domain-level structural isoforms...

  16. Dynamic domain walls in a Maxwell-dilaton background (Journal...

    Office of Scientific and Technical Information (OSTI)

    Citation Details In-Document Search Title: Dynamic domain walls in a Maxwell-dilaton background Motivated by the well-known Chamblin-Reall solutions of n-dimensional background ...

  17. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported...

  18. Antiferromagnetism and domain effects in UPdSn

    SciTech Connect (OSTI)

    Nakotte, H. [Manual Lujan Jr. Neutron Scattering Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Manual Lujan Jr. Neutron Scattering Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); [Department of Physics, New Mexico State University, Las Cruces, New Mexico 88003 (United States); Robinson, R.A.; Purwanto, A. [Manuel Lujan Jr. Neutron Scattering Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Manuel Lujan Jr. Neutron Scattering Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Tun, Z. [Chalk River Laboratories, Atomic Energy of Canada Limited, Chalk River, Ontario, K0J 1J0 (CANADA)] [Chalk River Laboratories, Atomic Energy of Canada Limited, Chalk River, Ontario, K0J 1J0 (CANADA); Prokes, K.; Brueck, E.; de Boer, F.R. [Van der Waals-Zeeman Institute, University of Amsterdam, 1018 XE Amsterdam (The Netherlands)] [Van der Waals-Zeeman Institute, University of Amsterdam, 1018 XE Amsterdam (The Netherlands)

    1998-10-01

    Neutron-diffraction experiments have been performed on a single crystal of the hexagonal noncollinear antiferromagnetic compound UPdSn as a function of temperature and magnetic field. The use of a special horizontal-field magnet (with very wide horizontal access to the neutron beams) has allowed the study of the principal magnetic Bragg reflections in all three antiferromagnetic domain pairs throughout the magnetic phase diagram for B{lt}3thinspT and T{gt}6thinspK. The data confirm a picture in which one domain pair (1) grows at the expense of the other two domain pairs (2 and 3), for fields along the [100] axis for domain 1. On the other hand, if the field is applied along the perpendicular axis, [010] for domain 1, the other two domains are preferred. These results are consistent with the picture given in a previous vertical-field study of only one magnetic reflection from one domain, in which the 3-T field-induced transition is viewed as a spin-flop transition. There is, however, a small amount of irreversible moment rotation (from {theta}=43{degree} to 48{degree}, where {theta} is the moment canting angle within the hexagonal basal plane), on passing through the spin-flop transition. This seems to be connected with whether the sample is single or multidomain. In addition, the field independence of the N{acute e}el temperature (T{sub N}=37thinspK) has been measured up to 3 T, and data on the domain kinetics are presented. {copyright} {ital 1998} {ital The American Physical Society}

  19. Nucleon transverse momentum-dependent parton distributions from domain wall

    Office of Scientific and Technical Information (OSTI)

    fermion calculations at 297 MeV pion mass (Conference) | SciTech Connect Conference: Nucleon transverse momentum-dependent parton distributions from domain wall fermion calculations at 297 MeV pion mass Citation Details In-Document Search Title: Nucleon transverse momentum-dependent parton distributions from domain wall fermion calculations at 297 MeV pion mass Lattice QCD calculations of transverse momentum-dependent parton distributions (TMDs) in a nucleon are performed based on a

  20. Death Domain Assembly Mechanism Revealed by Crystal Structure of the

    Office of Scientific and Technical Information (OSTI)

    Oligomeric PIDDosome Core Complex (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex Citation Details In-Document Search Title: Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex Authors: Park, Hyun Ho ; Logette, Emmanuelle ; Rausnser, Stefan ; Cuenin, Solange ; Walz, Thomas ; Tschopp, Jurg ; Wu, Hao [1] ;

  1. In situ measurement of increased ferroelectric/ferroelastic domain wall

    Office of Scientific and Technical Information (OSTI)

    motion in declamped tetragonal lead zirconate titanate thin films (Journal Article) | DOE PAGES DOE PAGES Search Results Publisher's Accepted Manuscript: In situ measurement of increased ferroelectric/ferroelastic domain wall motion in declamped tetragonal lead zirconate titanate thin films Title: In situ measurement of increased ferroelectric/ferroelastic domain wall motion in declamped tetragonal lead zirconate titanate thin films Authors: Wallace, M. [1] Search DOE PAGES for author

  2. Organic Solar Cells: Absolute Measurement of Domain Composition and

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Nanoscale Size Distribution Explains Performance in Solar Cells Organic Solar Cells: Absolute Measurement of Domain Composition and Nanoscale Size Distribution Explains Performance in Solar Cells Organic Solar Cells: Absolute Measurement of Domain Composition and Nanoscale Size Distribution Explains Performance in Solar Cells Print Tuesday, 22 January 2013 00:00 This front cover represents the morphology and resulting device dynamics in organic solar cell blend films of PTB7 and PC71BM, as

  3. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Monday, 28 November 2011 14:52 Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin

  4. Statistical and Domain Analytics Applied to PV Module Lifetime and

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Degradation Science | Department of Energy Statistical and Domain Analytics Applied to PV Module Lifetime and Degradation Science Statistical and Domain Analytics Applied to PV Module Lifetime and Degradation Science Presented at the PV Module Reliability Workshop, February 26 - 27 2013, Golden, Colorado PDF icon pvmrw13_ps2_casewestern_bruckman.pdf More Documents & Publications Literature Review of the Effects of UV Exposure on PV Modules Failure Rates from Certification Testing to UL

  5. Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion

    SciTech Connect (OSTI)

    Bose, Sayantan; Welch, Brett D.; Kors, Christopher A.; Yuan, Ping; Jardetzky, Theodore S.; Lamb, Robert A.

    2014-10-02

    Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 {angstrom}, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.

  6. Method and apparatus for detecting chemical binding

    DOE Patents [OSTI]

    Warner, Benjamin P.; Havrilla, George J.; Miller, Thomasin C.; Wells, Cyndi A.

    2007-07-10

    The method for screening binding between a target binder and potential pharmaceutical chemicals involves sending a solution (preferably an aqueous solution) of the target binder through a conduit to a size exclusion filter, the target binder being too large to pass through the size exclusion filter, and then sending a solution of one or more potential pharmaceutical chemicals (preferably an aqueous solution) through the same conduit to the size exclusion filter after target binder has collected on the filter. The potential pharmaceutical chemicals are small enough to pass through the filter. Afterwards, x-rays are sent from an x-ray source to the size exclusion filter, and if the potential pharmaceutical chemicals form a complex with the target binder, the complex produces an x-ray fluorescence signal having an intensity that indicates that a complex has formed.

  7. Method And Apparatus For Detecting Chemical Binding

    DOE Patents [OSTI]

    Warner, Benjamin P.; Havrilla, George J.; Miller, Thomasin C.; Wells, Cyndi A.

    2005-02-22

    The method for screening binding between a target binder and potential pharmaceutical chemicals involves sending a solution (preferably an aqueous solution) of the target binder through a conduit to a size exclusion filter, the target binder being too large to pass through the size exclusion filter, and then sending a solution of one or more potential pharmaceutical chemicals (preferably an aqueous solution) through the same conduit to the size exclusion filter after target binder has collected on the filter. The potential pharmaceutical chemicals are small enough to pass through the filter. Afterwards, x-rays are sent from an x-ray source to the size exclusion filter, and if the potential pharmaceutical chemicals form a complex with the target binder, the complex produces an x-ray fluorescence signal having an intensity that indicates that a complex has formed.

  8. Neptunium Binding Kinetics with Arsenazo(III)

    SciTech Connect (OSTI)

    Leigh R. Martin; Aaron T. Johnson; Stephen P. Mezyk

    2014-08-01

    This document has been prepared to meet FCR&D level 2 milestone M2FT-14IN0304021, Report on the results of actinide binding kinetics with aqueous phase complexants This work was carried out under the auspices of the Thermodynamics and Kinetics of Advanced Separations Systems FCR&D work package. The report details kinetics experiments that were performed to measure rates of aqueous phase complexation for pentavalent neptunium with the chromotropic dye Arsenazo III (AAIII). The studies performed were designed to determine how pH, ionic strength and AAIII concentration may affect the rate of the reaction. A brief comparison with hexavalent neptunium is also made. It was identified that as pH was increased the rate of reaction also increased, however increasing the ionic strength and concentration of AAIII had the opposite effect. Interestingly, the rate of reaction of Np(VI) with AAIII was found to be slower than that of the Np(V) reaction.

  9. Hardware device to physical structure binding and authentication

    DOE Patents [OSTI]

    Hamlet, Jason R.; Stein, David J.; Bauer, Todd M.

    2013-08-20

    Detection and deterrence of device tampering and subversion may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a binding of the hardware device and a physical structure. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generate an internal PUF value. Binding logic is coupled to receive the internal PUF value, as well as an external PUF value associated with the physical structure, and generates a binding PUF value, which represents the binding of the hardware device and the physical structure. The cryptographic fingerprint unit also includes a cryptographic unit that uses the binding PUF value to allow a challenger to authenticate the binding.

  10. Defining How Botulinum Toxin Binds to the Synaptotagmin Receptor...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    II (Syt-II) recognition domain (1) and botulinum toxin with two different neutralizing monoclonal antibodies (2). To compliment the structural work, biochemical, mutagenesis,...

  11. The Effects of Somatic Hypermutation on Neutralization and Binding...

    Office of Scientific and Technical Information (OSTI)

    Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies Citation Details In-Document Search Title: The Effects of Somatic...

  12. U-183: ISC BIND DNS Resource Records Handling Vulnerability

    Broader source: Energy.gov [DOE]

    This problem was uncovered while testing with experimental DNS record types. It is possible to add records to BIND with null (zero length) rdata fields.

  13. Developing Adnectins That Target SRC Co-Activator Binding to...

    Office of Scientific and Technical Information (OSTI)

    Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Citation Details In-Document Search Title: ...

  14. Structural and functional analysis of FIP2 binding to theendosome...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Citation Details In-Document Search Title: Structural and functional ...

  15. Assessment of current cybersecurity practices in the public domain : cyber indications and warnings domain.

    SciTech Connect (OSTI)

    Hamlet, Jason R.; Keliiaa, Curtis M.

    2010-09-01

    This report assesses current public domain cyber security practices with respect to cyber indications and warnings. It describes cybersecurity industry and government activities, including cybersecurity tools, methods, practices, and international and government-wide initiatives known to be impacting current practice. Of particular note are the U.S. Government's Trusted Internet Connection (TIC) and 'Einstein' programs, which are serving to consolidate the Government's internet access points and to provide some capability to monitor and mitigate cyber attacks. Next, this report catalogs activities undertaken by various industry and government entities. In addition, it assesses the benchmarks of HPC capability and other HPC attributes that may lend themselves to assist in the solution of this problem. This report draws few conclusions, as it is intended to assess current practice in preparation for future work, however, no explicit references to HPC usage for the purpose of analyzing cyber infrastructure in near-real-time were found in the current practice. This report and a related SAND2010-4766 National Cyber Defense High Performance Computing and Analysis: Concepts, Planning and Roadmap report are intended to provoke discussion throughout a broad audience about developing a cohesive HPC centric solution to wide-area cybersecurity problems.

  16. Real-time observation of epitaxial graphene domain reorientation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Thuermer, Konrad; Foster, Michael E.; Bartelt, Norman Charles; Rogge, Paul C.; Lawrence Berkeley National Lab.; McCarty, Kevin F.; Dubon, Oscar D.; Lawrence Berkeley National Lab.; Bartelt, Norman C.

    2015-04-20

    Graphene films grown by vapour deposition tend to be polycrystalline due to the nucleation and growth of islands with different in-plane orientations. Here, using low-energy electron microscopy, we find that micron-sized graphene islands on Ir(111) rotate to a preferred orientation during thermal annealing. We observe three alignment mechanisms: the simultaneous growth of aligned domains and dissolution of rotated domains, that is, ‘ripening’; domain boundary motion within islands; and continuous lattice rotation of entire domains. By measuring the relative growth velocity of domains during ripening, we estimate that the driving force for alignment is on the order of 0.1 meV permore » C atom and increases with rotation angle. A simple model of the orientation-dependent energy associated with the moiré corrugation of the graphene sheet due to local variations in the graphene–substrate interaction reproduces the results. This study suggests new strategies for improving the van der Waals epitaxy of 2D materials.« less

  17. Frequency-domain multiscale quantum mechanics/electromagnetics simulation method

    SciTech Connect (OSTI)

    Meng, Lingyi; Yin, Zhenyu; Yam, ChiYung E-mail: ghc@everest.hku.hk; Koo, SiuKong; Chen, GuanHua E-mail: ghc@everest.hku.hk; Chen, Quan; Wong, Ngai

    2013-12-28

    A frequency-domain quantum mechanics and electromagnetics (QM/EM) method is developed. Compared with the time-domain QM/EM method [Meng et al., J. Chem. Theory Comput. 8, 11901199 (2012)], the newly developed frequency-domain QM/EM method could effectively capture the dynamic properties of electronic devices over a broader range of operating frequencies. The system is divided into QM and EM regions and solved in a self-consistent manner via updating the boundary conditions at the QM and EM interface. The calculated potential distributions and current densities at the interface are taken as the boundary conditions for the QM and EM calculations, respectively, which facilitate the information exchange between the QM and EM calculations and ensure that the potential, charge, and current distributions are continuous across the QM/EM interface. Via Fourier transformation, the dynamic admittance calculated from the time-domain and frequency-domain QM/EM methods is compared for a carbon nanotube based molecular device.

  18. Sampling Approaches for Multi-Domain Internet Performance Measurement Infrastructures

    SciTech Connect (OSTI)

    Calyam, Prasad

    2014-09-15

    The next-generation of high-performance networks being developed in DOE communities are critical for supporting current and emerging data-intensive science applications. The goal of this project is to investigate multi-domain network status sampling techniques and tools to measure/analyze performance, and thereby provide “network awareness” to end-users and network operators in DOE communities. We leverage the infrastructure and datasets available through perfSONAR, which is a multi-domain measurement framework that has been widely deployed in high-performance computing and networking communities; the DOE community is a core developer and the largest adopter of perfSONAR. Our investigations include development of semantic scheduling algorithms, measurement federation policies, and tools to sample multi-domain and multi-layer network status within perfSONAR deployments. We validate our algorithms and policies with end-to-end measurement analysis tools for various monitoring objectives such as network weather forecasting, anomaly detection, and fault-diagnosis. In addition, we develop a multi-domain architecture for an enterprise-specific perfSONAR deployment that can implement monitoring-objective based sampling and that adheres to any domain-specific measurement policies.

  19. Domain wall and isocurvature perturbation problems in axion models

    SciTech Connect (OSTI)

    Kawasaki, Masahiro; Yoshino, Kazuyoshi; Yanagida, Tsutomu T. E-mail: tsutomu.tyanagida@ipmu.jp

    2013-11-01

    Axion models have two serious cosmological problems, domain wall and isocurvature perturbation problems. In order to solve these problems we investigate the Linde's model in which the field value of the Peccei-Quinn (PQ) scalar is large during inflation. In this model the fluctuations of the PQ field grow after inflation through the parametric resonance and stable axionic strings may be produced, which results in the domain wall problem. We study formation of axionic strings using lattice simulations. It is found that in chaotic inflation the axion model is free from both the domain wall and the isocurvature perturbation problems if the initial misalignment angle ?{sub a} is smaller than O(10{sup ?2}). Furthermore, axions can also account for the dark matter for the breaking scale v ? 10{sup 12?16}GeV and the Hubble parameter during inflation H{sub inf}?<10{sup 11?12}GeV in general inflation models.

  20. Current Domain Challenges in the Emergency Response Community

    SciTech Connect (OSTI)

    Barr, Jonathan L.; Peddicord, Annie M Boe; Burtner, Edwin R.; Mahy, Heidi A.

    2011-05-08

    This paper describes the development of a framework targeted to technology providers in order to better understand the grand domain challenges of the emergency response and management community (EM). In developing this framework, Pacific Northwest National Laboratory researchers interviewed subject matter experts (SMEs) across the EM domain and corroborated these findings with current literature. We are currently examining relationships and dependencies within the framework. A thorough understanding of these gaps and dependencies will allow for a more informed approach prioritizing research, developing tools, and applying technology to enhance performance in the EM community.

  1. Multidomain Carbohydrate-binding Proteins Involved in Bacteroides

    Office of Scientific and Technical Information (OSTI)

    thetaiotaomicron Starch Metabolism (Journal Article) | SciTech Connect Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Citation Details In-Document Search Title: Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Authors: Cameron, Elizabeth A. ; Maynard, Mallory A. ; Smith, Christopher J. ; Smith, Thomas J. ; Koropatkin, Nicole M. ; Martens, Eric C. [1] ; Danforth) [2] + Show Author

  2. Internal stress distribution for generating closure domains in laser-irradiated Fe3%Si(110) steels

    SciTech Connect (OSTI)

    Iwata, Keiji; Imafuku, Muneyuki; Orihara, Hideto; Sakai, Yusuke; Ohya, Shin-Ichi; Suzuki, Tamaki; Shobu, Takahisa; Akita, Koichi; Ishiyama, Kazushi

    2015-05-07

    Internal stress distribution for generating closure domains occurring in laser-irradiated Fe3%Si(110) steels was investigated using high-energy X-ray analysis and domain theory based on the variational principle. The measured triaxial stresses inside the specimen were compressive and the stress in the rolling direction became more dominant than stresses in the other directions. The calculations based on the variational principle of magnetic energy for closure domains showed that the measured triaxial stresses made the closure domains more stable than the basic domain without closure domains. The experimental and calculation results reveal that the laser-introduced internal stresses result in the occurrence of the closure domains.

  3. Blimp-1{delta}exon7: A naturally occurring Blimp-1 deletion mutant with auto-regulatory potential

    SciTech Connect (OSTI)

    Schmidt, Doris; Nayak, Arnab; Schumann, Julia E.; Schimpl, Anneliese; Berberich, Ingolf Berberich-Siebelt, Friederike

    2008-12-10

    Blimp-1 is a master regulator of terminal B cell differentiation and plays a pivotal role in various developmental processes. In addition to full length Blimp-1, a Blimp-1 mRNA lacking exon 7 (Blimp-1{delta}7) has been described to occur in murine B cells. The activity and function of the mutant mRNA-encoded protein (Blimp-1{delta}7), lacking three crucial zinc fingers necessary for DNA interaction, is completely unknown. Since isoforms of other prdm family proteins affect each other's functions, we wondered whether Blimp-1{delta}7 still plays a role in B cells, independent of direct DNA binding. In this study, we found that Blimp-1{delta}7 is preferentially expressed in naive CD19{sup +} B cells. A fraction of Blimp-1{delta}7 migrates to the nucleus, colocalizes with HDAC2 and is found at sites of repressed chromatin, although it does not bind to the Blimp-1 DNA consensus site. Unexpectedly, Blimp-1 and Blimp-1{delta}7 homodimerize as well as heterodimerize with each other. Ectopic expression of Blimp-1{delta}7 in WEHI 231 cells, a Blimp-1-negative murine lymphoma line, leads to cessation of proliferation and enhancement of apoptosis. Importantly, LPS-induced differentiation is suppressed in the presence of Blimp-1{delta}7. This is in agreement with our finding that Blimp-1{delta}7 interferes with endogenous Blimp-1 expression. Thus, our data suggest an auto-regulatory mechanism of Blimp-1 activation.

  4. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-[gamma]-linolenic acid

    SciTech Connect (OSTI)

    Zhang, Wei; Chakravarty, Bornali; Zheng, Fei; Gu, Ziwei; Wu, Hongmei; Mao, Jianqiang; Wakil, Salih J.; Quiocho, Florante A.

    2012-05-29

    Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the crystal structure of the hFAS TE domain covalently modified and inactivated by methyl {gamma}-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated {gamma}-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an {alpha} helix (the 'helix flap'). We then found inhibition of the TE domain activity by the PUFA dihomo-{gamma}-linolenic acid; {gamma}- and {alpha}-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-{gamma}-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.

  5. Metal binding proteins, recombinant host cells and methods

    DOE Patents [OSTI]

    Summers, Anne O.; Caguiat, Jonathan J.

    2004-06-15

    The present disclosure provides artificial heavy metal binding proteins termed chelons by the inventors. These chelons bind cadmium and/or mercuric ions with relatively high affinity. Also disclosed are coding sequences, recombinant DNA molecules and recombinant host cells comprising those recombinant DNA molecules for expression of the chelon proteins. In the recombinant host cells or transgenic plants, the chelons can be used to bind heavy metals taken up from contaminated soil, groundwater or irrigation water and to concentrate and sequester those ions. Recombinant enteric bacteria can be used within the gastrointestinal tracts of animals or humans exposed to toxic metal ions such as mercury and/or cadmium, where the chelon recombinantly expressed in chosen in accordance with the ion to be rededicated. Alternatively, the chelons can be immobilized to solid supports to bind and concentrate heavy metals from a contaminated aqueous medium including biological fluids.

  6. Linear Scaling of the Exciton Binding Energy versus the Band...

    Office of Scientific and Technical Information (OSTI)

    Linear Scaling of the Exciton Binding Energy versus the Band Gap of Two-Dimensional Materials This content will become publicly available on August 6, 2016 Prev Next Title:...

  7. Stopbands in the existence domains of acoustic solitons

    SciTech Connect (OSTI)

    Nsengiyumva, F. Hellberg, M. A. Mace, R. L.; Verheest, F.

    2014-10-15

    A fully nonlinear Sagdeev pseudopotential approach is used to study the existence domain of fast mode ion-acoustic solitons in a three-species plasma composed of cold and warm adiabatic positive ion species and Boltzmann electrons. It is shown that for appropriate values of the cold-to-warm ion charge-to-mass ratio, ?, and the effective warm ion-to-electron temperature ratio, ?, there is a range in cold to warm ion charge density ratio, f, over which a stopband in soliton speed exists. Solitons do not propagate in the stopband, although they can occur for both higher and lower speeds. The stopbands are associated with a limiting curve of the existence domain that is double-valued in speed for a range of values of f. Analytical estimates of the upper and lower limits of ? and ? that support stopbands are found. It is suggested that, inter alia, the analysis should be applicable to the solar wind plasma.

  8. Time Domain Partitioning of Electricity Production Cost Simulations

    SciTech Connect (OSTI)

    Barrows, C.; Hummon, M.; Jones, W.; Hale, E.

    2014-01-01

    Production cost models are often used for planning by simulating power system operations over long time horizons. The simulation of a day-ahead energy market can take several weeks to compute. Tractability improvements are often made through model simplifications, such as: reductions in transmission modeling detail, relaxation of commitment variable integrality, reductions in cost modeling detail, etc. One common simplification is to partition the simulation horizon so that weekly or monthly horizons can be simulated in parallel. However, horizon partitions are often executed with overlap periods of arbitrary and sometimes zero length. We calculate the time domain persistence of historical unit commitment decisions to inform time domain partitioning of production cost models. The results are implemented using PLEXOS production cost modeling software in an HPC environment to improve the computation time of simulations while maintaining solution integrity.

  9. Domain-independent information extraction in unstructured text

    SciTech Connect (OSTI)

    Irwin, N.H.

    1996-09-01

    Extracting information from unstructured text has become an important research area in recent years due to the large amount of text now electronically available. This status report describes the findings and work done during the second year of a two-year Laboratory Directed Research and Development Project. Building on the first-year`s work of identifying important entities, this report details techniques used to group words into semantic categories and to output templates containing selective document content. Using word profiles and category clustering derived during a training run, the time-consuming knowledge-building task can be avoided. Though the output still lacks in completeness when compared to systems with domain-specific knowledge bases, the results do look promising. The two approaches are compatible and could complement each other within the same system. Domain-independent approaches retain appeal as a system that adapts and learns will soon outpace a system with any amount of a priori knowledge.

  10. Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Print Sunday, 14 October 2012 00:00 The ocean is an important source of uranium if it can be extracted economically. Extraction of uranium from seawater is very challenging, not only because it is in an extremely low concentration, but also because

  11. Briefly Bound to Activate: Transient Binding of a Second Catalytic

    Office of Scientific and Technical Information (OSTI)

    Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Briefly Bound to Activate: Transient Binding of a Second Catalytic Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis Citation Details In-Document Search Title: Briefly Bound to Activate: Transient Binding of a Second Catalytic Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis We have

  12. Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium

    Office of Scientific and Technical Information (OSTI)

    tuberculosis BioA (Journal Article) | SciTech Connect Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Citation Details In-Document Search Title: Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Authors: Dai, Ran ; Geders, Todd W. ; Liu, Feng ; Park, Sae Woong ; Schnappinger, Dirk ; Aldrich, Courtney C. ; Finzel, Barry C. [1] ; Weill-Med) [2] + Show Author Affiliations (UMM) ( Publication Date: 2015-09-29 OSTI

  13. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print Wednesday, 29 March 2006 00:00 The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of

  14. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Characterization of Selective Binding of Alkali Cations with Carboxylate Print Wednesday, 24 September 2008 00:00 During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of

  15. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Wednesday, 09 December 2015 00:00 Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps

  16. Computational Biology: A Recipe for Ligand-Binding Proteins

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computational Biology: A Recipe for Ligand-Binding Proteins Authors: Ghirlanda, G. Title: Computational Biology: A Recipe for Ligand-Binding Proteins Source: Nature Year: 2013 Volume: 501 Pages: 177-178 ABSTRACT: Cellular cross-talk, enzymatic catalysis and regulation of gene expression all depend on molecular recognition. A method that allows the design of proteins with desired recognition sites could thus be revolutionary Date of online publication: Thu, 2013-09-12 Link online:

  17. Structural and functional analysis of FIP2 binding to the

    Office of Scientific and Technical Information (OSTI)

    endosome-localised Rab25 GTPase (Journal Article) | SciTech Connect Journal Article: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Citation Details In-Document Search Title: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Authors: Lall, Patrick ; Horgan, Conor P. ; Oda, Shunichiro ; Franklin, Edward ; Sultana, Azmiri ; Hanscom, Sara R. ; McCaffrey, Mary W. ; Khan, Amir R. [1] ; Cork) [2] + Show Author

  18. Structural basis for biomolecular recognition in overlapping binding sites

    Office of Scientific and Technical Information (OSTI)

    in a diiron enzyme system (Journal Article) | SciTech Connect Structural basis for biomolecular recognition in overlapping binding sites in a diiron enzyme system Citation Details In-Document Search Title: Structural basis for biomolecular recognition in overlapping binding sites in a diiron enzyme system Authors: Acheson, Justin F. ; Bailey, Lucas J. ; Elsen, Nathaniel L. ; Fox, Brian G. [1] + Show Author Affiliations UW Publication Date: 2016-01-22 OSTI Identifier: 1229904 Resource Type:

  19. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  20. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  1. Investigation of Unusual Albedos in the SGP Domain

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Investigation of Unusual Albedos in the SGP Domain Groff, David ARM SGP Duchon, Claude University Of Oklahoma Category: Atmospheric State and Surface We investigate the cause of unusually high albedos at an Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) extended facility near Morris, OK. In a previous study, daily albedos were calculated at several SGP extended facilities for 1998 and 1999 using broadband (.28 to 3 microns) pyranometers. The average daily albedo during this

  2. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  3. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  4. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  5. Dynein Motor Domain Shows Ring-Shaped Motor, Buttress

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dynein Motor Domain Shows Ring-Shaped Motor, Buttress Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported by motor proteins. These tiny machines convert the energy gained from hydrolysing ATP into a series of small conformational changes that allow them to literally "walk" along microscopic tracks. Motor proteins (in the kinesin and myosin families) have been extensively studied by x-ray crystallography, but

  6. An Unprecedented NADPH Domain Conformation in Lysine Monooxygenase NbtG Provides Insights into Uncoupling of Oxygen Consumption from Substrate Hydroxylation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Binda, Claudia; Robinson, Reeder M.; Martin del Campo, Julia S.; Keul, Nicholas D.; Rodriguez, Pedro J.; Robinson, Howard H.; Mattevi, Andrea; Sobrado, Pablo

    2015-03-23

    N-hydroxylating monooxygenases (NMOs) are involved in the biosynthesis of iron-chelating hydroxamate-containing siderophores that play a role in microbial virulence. These flavoenzymes catalyze the NADPH- and oxygen-dependent hydroxylation of amines, such as those found on the side chains of lysine and ornithine. In this work we report the biochemical and structural characterization of Nocardia farcinica Lys monooxygenase (NbtG), which has similar biochemical properties to mycobacterial homologs. NbtG is also active on D-Lys although it binds L-Lys with a higher affinity. Differently from the ornithine monooxygenases PvdA, SidA and KtzI, NbtG can use both NADH and NADPH and is highly uncoupled, producingmore » more superoxide and hydrogen peroxide than hydroxylated Lys. The crystal structure of NbtG solved at 2.4 Å resolution revealed an unexpected protein conformation with a 30° rotation of the NAD(P)H domain with respect to the FAD domain that precludes binding of the nicotinamide cofactor. This “occluded” structure may explain the biochemical properties of NbtG, specifically with regard to the substantial uncoupling and limited stabilization of the C4a-hydroperoxyflavin intermediate. We discuss the biological implications of these findings.« less

  7. V-172: ISC BIND RUNTIME_CHECK Error Lets Remote Users Deny Service...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ISC BIND RUNTIMECHECK Error Lets Remote Users Deny Service Against Recursive Resolvers V-172: ISC BIND RUNTIMECHECK Error Lets Remote Users Deny Service Against Recursive...

  8. Effect of the deletion of qmoABC and the promoter distal gene encoding a hypothetical protein on sulfate-reduction in Desulfovibrio vulgaris Hildenborough

    SciTech Connect (OSTI)

    Zane, Grant M.; Yen, Huei-chi Bill; Wall, Judy D.

    2010-03-18

    The pathway of electrons required for the reduction of sulfate in sulfate-reducing bacteria (SRB) is not yet fully characterized. In order to determine the role of a transmembrane protein complex suggested to be involved in this process, a deletion of Desulfovibrio vulgaris Hildenborough was created by marker exchange mutagenesis that eliminated four genes putatively encoding the QmoABC complex and a hypothetical protein (DVU0851). The Qmo complex (quinone-interacting membrane-bound oxidoreductase) is proposed to be responsible for transporting electrons to the dissimilatory adenosine-5?phosphosulfate (APS) reductase in SRB. In support of the predicted role of this complex, the deletion mutant was unable to grow using sulfate as its sole electron acceptor with a range of electron donors. To explore a possible role for the hypothetical protein in sulfate reduction, a second mutant was constructed that had lost only the gene that codes for DVU0851. The second constructed mutant grew with sulfate as the sole electron acceptor; however, there was a lag that was not present with the wild-type or complemented strain. Neither deletion strain was significantly impaired for growth with sulfite or thiosulfate as terminal electron acceptor. Complementation of the D(qmoABC-DVU0851) mutant with all four genes or only the qmoABC genes restored its ability to grow by sulfate respiration. These results confirmed the prediction that the Qmo complex is in the electron pathway for sulfate-reduction and revealed that no other transmembrane complex could compensate when Qmo was lacking.

  9. V-084: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Scripting, Cross-Domain Access, Clickjacking, and File Upload Attacks V-084: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain Access, Clickjacking, and File Upload ...

  10. Structure and Interactions of the CS Domain of Human H/ACA RNP...

    Office of Scientific and Technical Information (OSTI)

    Structure and Interactions of the CS Domain of Human HACA RNP Assembly Protein Shq1 Citation Details In-Document Search Title: Structure and Interactions of the CS Domain of Human...

  11. Structure of the SPRY domain of human Ash2L and its interactions...

    Office of Scientific and Technical Information (OSTI)

    Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30 Citation Details In-Document Search Title: Structure of the SPRY domain of human Ash2L and its ...

  12. f{sub K}/f{sub {pi}} in full QCD with domain wall valence quarks...

    Office of Scientific and Technical Information (OSTI)

    fsub Kfsub pi in full QCD with domain wall valence quarks Citation Details In-Document Search Title: fsub Kfsub pi in full QCD with domain wall valence quarks We ...

  13. The TLR4 agonist fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer vaccine

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Julier, Ziad; Martino, Mikaël M.; de Titta, Alexandre; Jeanbart, Laura; Hubbell, Jeffrey A.

    2015-02-24

    Fibronectin (FN) is an extracellular matrix (ECM) protein including numerous fibronectin type III (FNIII) repeats with different functions. The alternatively spliced FN variant containing the extra domain A (FNIII EDA), located between FNIII 11 and FNIII 12, is expressed in sites of injury, chronic inflammation, and solid tumors. Although its function is not well understood, FNIII EDA is known to agonize Toll-like receptor 4 (TLR4). Here, by producing various FN fragments containing FNIII EDA, we found that FNIII EDA's immunological activity depends upon its local intramolecular context within the FN chain. N-terminal extension of the isolated FNIII EDA with itsmore » neighboring FNIII repeats (FNIII 9-10-11) enhanced its activity in agonizing TLR4, while C-terminal extension with the native FNIII 12-13-14 heparin-binding domain abrogated it. We reveal that an elastase 2 cleavage site is present between FNIII EDA and FNIII 12. Activity of the C-terminally extended FNIII EDA could be restored after cleavage of the FNIII 12-13-14 domain by elastase 2. FN being naturally bound to the ECM, we immobilized FNIII EDA-containing FN fragments within a fibrin matrix model along with antigenic peptides. Such matrices were shown to stimulate cytotoxic CD8+ T cell responses in two murine cancer models.« less

  14. Nonlinear Time Domain Modeling and Simulation of Surface and Embedded NPPS

    Office of Environmental Management (EM)

    | Department of Energy Nonlinear Time Domain Modeling and Simulation of Surface and Embedded NPPS Nonlinear Time Domain Modeling and Simulation of Surface and Embedded NPPS Nonlinear Time Domain Modeling and Simulation of Surface and Embedded NPPS Boris Jeremic with contributions from Federico Pisanò, Jose Abell, Kohei Watanabe, Chao Luo University of California, Davis Lawrence Berkeley National Laboratory, Berkeley DOE NPH, October 2014 PDF icon Nonlinear Time Domain Modeling and

  15. Propagating and reflecting of spin wave in permalloy nanostrip with 360 domain wall

    SciTech Connect (OSTI)

    Zhang, Senfu; Mu, Congpu; Zhu, Qiyuan; Zheng, Qi; Liu, Xianyin; Wang, Jianbo; Liu, Qingfang

    2014-01-07

    By micromagnetic simulation, we investigated the interaction between propagating spin wave (or magnonic) and a 360 domain wall in a nanostrip. It is found that propagating spin wave can drive a 360 domain wall motion, and the velocity and direction are closely related to the transmission coefficient of the spin wave of the domain wall. When the spin wave passes through the domain wall completely, the 360 domain wall moves toward the spin wave source. When the spin wave is reflected by the domain wall, the 360 domain wall moves along the spin wave propagation direction. Moreover, when the frequency of the spin wave is coincident with that of the 360 domain wall normal mode, the 360 domain wall velocity will be resonantly enhanced no matter which direction the 360 DW moves along. On the other hand, when the spin wave is reflected from the moving 360 domain wall, we observed the Doppler effect clearly. After passing through a 360 domain wall, the phase of the spin wave is changed, and the phase shift is related to the frequency. Nevertheless, phase shift could be manipulated by the number of 360 domain walls that spin wave passing through.

  16. On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase

    SciTech Connect (OSTI)

    Brokaw, Jason B.; Chu, Jhih-wei

    2010-11-17

    We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier works of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.

  17. Impact on the steam electric power industry of deleting Section 316(a) of the Clean Water Act: Energy and environmental impacts

    SciTech Connect (OSTI)

    Veil, J.A.; VanKuiken, J.C.; Folga, S.; Gillette, J.L.

    1993-01-01

    Many power plants discharge large volumes of cooling water. In some cases, the temperature of the discharge exceeds state thermal requirements. Section 316(a) of the Clean Water Act (CWA) allows a thermal discharger to demonstrate that less stringent thermal effluent limitations would still protect aquatic life. About 32% of the total steam electric generating capacity in the United States operates under Section 316(a) variances. In 1991, the US Senate proposed legislation that would delete Section 316(a) from the CWA. This study, presented in two companion reports, examines how this legislation would affect the steam electric power industry. This report quantitatively and qualitatively evaluates the energy and environmental impacts of deleting the variance. No evidence exists that Section 316(a) variances have caused any widespread environmental problems. Conversion from once-through cooling to cooling towers would result in a loss of plant output of 14.7-23.7 billion kilowatt-hours. The cost to make up the lost energy is estimated at $12.8-$23.7 billion (in 1992 dollars). Conversion to cooling towers would increase emission of pollutants to the atmosphere and water loss through evaporation. The second report describes alternatives available to plants that currently operate under the variance and estimates the national cost of implementing such alternatives. Little justification has been found for removing the 316(a) variance from the CWA.

  18. Domain-Specific Languages for Composing Signature Discovery Workflows

    SciTech Connect (OSTI)

    Jacob, Ferosh; Gray, Jeff; Wynne, Adam S.; Liu, Yan; Baker, Nathan A.

    2012-10-23

    Domain-agnostic signature discovery entails investigation across multiple scientific disciplines. The breadth and cross-disciplinary nature of this work requires that existing executables be integrated with new capabilities into workflows, representing a wide range of user tasks. An algorithm may be written in multiple programming languages for various hardware platforms, and so workflow composition requires integrating executables from any number of remote hosts. This raises an engineering issue on how to generate web service wrappers for these heterogeneous executables and to compose them into a scientific workflow environment (e.g., Taverna). In this paper, we introduce two simple Domain-Specific Languages (DSLs) to automate these processes. Our Service Description Language (SDL) describes key elements of a signature discovery service and automatically generates its implementation code. The Workflow Description Language (WDL) describes the pipeline of services and generates deployable artifacts for the Taverna workflow management system. We demonstrate our approach with a real-world workflow composed of services wrapping remote executables.

  19. Parametric Study of the Frequency-Domain Thermoreflectance Technique

    SciTech Connect (OSTI)

    C. Xing; C. Jensen; Z. Hua; H. Ban; D. H. Hurley; M. Khafizov; J. Rory Kennedy

    2012-11-01

    Without requiring regression for parameter determination, one-dimensional (1D) analytical models are used by many research groups to extract the thermal properties in frequency-domain thermoreflectance measurements. Experimentally, this approach involves heating the sample with a pump laser and probing the temperature response with spatially coincident probe laser. Micron order lateral resolution can be obtained by tightly focusing the pump and probe lasers. However, small laser beam spot sizes necessarily bring into question the assumptions associated with 1D analytical models. In this study, we analyzed the applicability of 1D analytical models by comparing to 2D analytical and fully numerical models. Specifically, we considered a generic nlayer two-dimensional (2D), axisymmetric analytical model including effects of volumetric heat absorption, contact resistance, and anisotropic properties. In addition, a finite element numerical model was employed to consider nonlinear effects caused by temperature dependent thermal conductivity. Nonlinearity is of germane importance to frequency domain approaches because the experimental geometry is such that the probe is always sensing the maximum temperature fluctuation. To quantify the applicability of the 1D model, parametric studies were performed considering the effects of: film thickness, heating laser size, probe laser size, substrate-to-film effusivity ratio, interfacial thermal resistance between layers, volumetric heating, substrate thermal conductivity, nonlinear boundary conditions, and anisotropic and temperature dependent thermal conductivity.

  20. Example Work Domain Analysis for a Reference Sodium Fast Reactor

    SciTech Connect (OSTI)

    Hugo, Jacques; Oxstrand, Johanna

    2015-01-01

    The nuclear industry is currently designing and building a new generation of reactors that will include different structural, functional, and environmental aspects, all of which are likely to have a significant impact on the way these plants are operated. In order to meet economic and safety objectives, these new reactors will all use advanced technologies to some extent, including new materials and advanced digital instrumentation and control systems. New technologies will affect not only operational strategies, but will also require a new approach to how functions are allocated to humans or machines to ensure optimal performance. Uncertainty about the effect of large scale changes in plant design will remain until sound technical bases are developed for new operational concepts and strategies. Up-to-date models and guidance are required for the development of operational concepts for complex socio-technical systems. This report describes how the classical Work Domain Analysis method was adapted to develop operational concept frameworks for new plants. This adaptation of the method is better able to deal with the uncertainty and incomplete information typical of first-of-a-kind designs. Practical examples are provided of the systematic application of the method in the operational analysis of sodium-cooled reactors. Insights from this application and its utility are reviewed and arguments for the formal adoption of Work Domain Analysis as a value-added part of the Systems Engineering process are presented.

  1. Phylogenomic and functional domain analysis of polyketide synthases in Fusarium

    SciTech Connect (OSTI)

    Brown, Daren W.; Butchko, Robert A.; Baker, Scott E.; Proctor, Robert H.

    2012-02-01

    Fusarium species are ubiquitous in nature, cause a range of plant diseases, and produce a variety of chemicals often referred to as secondary metabolites. Although some fungal secondary metabolites affect plant growth or protect plants from other fungi and bacteria, their presence in grain based food and feed is more often associated with a variety of diseases in plants and in animals. Many of these structurally diverse metabolites are derived from a family of related enzymes called polyketide synthases (PKSs). A search of genomic sequence of Fusarium verticillioides, F. graminearum, F. oxysporum and Nectria haematococca (anamorph F. solani) identified a total of 58 PKS genes. To gain insight into how this gene family evolved and to guide future studies, we conducted a phylogenomic and functional domain analysis. The resulting genealogy suggested that Fusarium PKSs represent 34 different groups responsible for synthesis of different core metabolites. The analyses indicate that variation in the Fusarium PKS gene family is due to gene duplication and loss events as well as enzyme gain-of-function due to the acquisition of new domains or of loss-of-function due to nucleotide mutations. Transcriptional analysis indicate that the 16 F. verticillioides PKS genes are expressed under a range of conditions, further evidence that they are functional genes that confer the ability to produce secondary metabolites.

  2. Orientation-dependent binding energy of graphene on palladium

    SciTech Connect (OSTI)

    Kappes, Branden B.; Ebnonnasir, Abbas; Ciobanu, Cristian V. [Department of Mechanical Engineering and Materials Science Program, Colorado School of Mines, Golden, Colorado 80401 (United States)] [Department of Mechanical Engineering and Materials Science Program, Colorado School of Mines, Golden, Colorado 80401 (United States); Kodambaka, Suneel [Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095 (United States)] [Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095 (United States)

    2013-02-04

    Using density functional theory calculations, we show that the binding strength of a graphene monolayer on Pd(111) can vary between physisorption and chemisorption depending on its orientation. By studying the interfacial charge transfer, we have identified a specific four-atom carbon cluster that is responsible for the local bonding of graphene to Pd(111). The areal density of such clusters varies with the in-plane orientation of graphene, causing the binding energy to change accordingly. Similar investigations can also apply to other metal substrates and suggests that physical, chemical, and mechanical properties of graphene may be controlled by changing its orientation.

  3. Pathogenicity of the BRCA1 Missense Variant M1775K is Determined by the Disruption of the BRCT Phosphopeptide-Binding Pocket: a Multi-Modal Approach

    SciTech Connect (OSTI)

    Tischkowitz,M.; Hamel, N.; Carvalho, M.; Birrane, G.; Soni, A.; van Beers, E.; Joosse, S.; Wong, N.; Novak, D.; et al

    2008-01-01

    A number of germ-line mutations in the BRCA1 gene confer susceptibility to breast and ovarian cancer. However, it remains difficult to determine whether many single amino-acid (missense) changes in the BRCA1 protein that are frequently detected in the clinical setting are pathologic or not. Here, we used a combination of functional, crystallographic, biophysical, molecular and evolutionary techniques, and classical genetic segregation analysis to demonstrate that the BRCA1 missense variant M1775K is pathogenic. Functional assays in yeast and mammalian cells showed that the BRCA1 BRCT domains carrying the amino-acid change M1775K displayed markedly reduced transcriptional activity, indicating that this variant represents a deleterious mutation. Importantly, the M1775K mutation disrupted the phosphopeptide-binding pocket of the BRCA1 BRCT domains, thereby inhibiting the BRCA1 interaction with the proteins BRIP1 and CtIP, which are involved in DNA damage-induced checkpoint control. These results indicate that the integrity of the BRCT phosphopeptide-binding pocket is critical for the tumor suppression function of BRCA1. Moreover, this study demonstrates that multiple lines of evidence obtained from a combination of functional, structural, molecular and evolutionary techniques, and classical genetic segregation analysis are required to confirm the pathogenicity of rare variants of disease-susceptibility genes and obtain important insights into the underlying pathogenetic mechanisms.

  4. A probabilistic approach to microRNA-target binding

    SciTech Connect (OSTI)

    Ogul, Hasan; Umu, Sinan U.; Bioinformatics Program, Informatics Institute, Middle East Technical University, Cankaya TR-06800, Ankara ; Tuncel, Y. Yener; Akkaya, Mahinur S.

    2011-09-16

    Highlights: {yields} A new probabilistic model is introduced for microRNA-target binding. {yields} The new model significantly outperforms RNAHybrid and miRTif. {yields} The experiments can unveil the effects of the type and directions of distinct base pairings. -- Abstract: Elucidation of microRNA activity is a crucial step in understanding gene regulation. One key problem in this effort is how to model the pairwise interactions of microRNAs with their targets. As this interaction is strongly mediated by their sequences, it is desired to set-up a probabilistic model to explain the binding preferences between a microRNA sequence and the sequence of a putative target. To this end, we introduce a new model of microRNA-target binding, which transforms an aligned duplex to a new sequence and defines the likelihood of this sequence using a Variable Length Markov Chain. It offers a complementary representation of microRNA-mRNA pairs for microRNA target prediction tools or other probabilistic frameworks of integrative gene regulation analysis. The performance of present model is evaluated by its ability to predict microRNA-target mRNA interaction given a mature microRNA sequence and a putative mRNA binding site. In regard to classification accuracy, it outperforms two recent methods based on thermodynamic stability and sequence complementarity. The experiments can also unveil the effects of base pairing types and non-seed region in duplex formation.

  5. Inhibition of cell-cell binding by lipid assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Bargatze, Robert F. (Bozeman, MT)

    2001-05-22

    This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

  6. Inhibition Of Call-Cell Binding By Kipid Assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA), Bargatze, Robert F. (Bozeman, MT)

    2003-12-16

    This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

  7. Workshop on gate valve pressure locking and thermal binding

    SciTech Connect (OSTI)

    Brown, E.J.

    1995-07-01

    The purpose of the Workshop on Gate Valve Pressure Locking and Thermal Binding was to discuss pressure locking and thermal binding issues that could lead to inoperable gate valves in both boiling water and pressurized water reactors. The goal was to foster exchange of information to develop the technical bases to understand the phenomena, identify the components that are susceptible, discuss actual events, discuss the safety significance, and illustrate known corrective actions that can prevent or limit the occurrence of pressure locking or thermal binding. The presentations were structured to cover U.S. Nuclear Regulatory Commission staff evaluation of operating experience and planned regulatory activity; industry discussions of specific events, including foreign experience, and efforts to determine causes and alleviate the affects; and valve vendor experience and recommended corrective action. The discussions indicated that identifying valves susceptible to pressure locking and thermal binding was a complex process involving knowledge of components, systems, and plant operations. The corrective action options are varied and straightforward.

  8. A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1

    SciTech Connect (OSTI)

    Godwin, A.K.; Vanderveer, L.; Schultz, D.C.; Altomare, D.A.; Buetow, K.H.; Daly, M.; Getts, L.A.; Masny, A.; Rosenblum, N.

    1994-10-01

    Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans {approximately} 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene. 58 refs., 3 figs., 4 tabs.

  9. Depinning transition of a domain wall in ferromagnetic films

    SciTech Connect (OSTI)

    Xi, Bin; Luo, Meng -Bo; Vinokur, Valerii M.; Hu, Xiao

    2015-09-14

    We report first principle numerical study of domain wall (DW) depinning in two-dimensional magnetic film, which is modeled by 2D random-field Ising system with the dipole-dipole interaction. We observe non-conventional activation-type motion of DW and reveal the fractal structure of DW near the depinning transition. We determine scaling functions describing critical dynamics near the transition and obtain universal exponents establishing connection between thermal softening of pinning potential and critical dynamics. In addition, we observe that tuning the strength of the dipole-dipole interaction switches DW dynamics between two different universality classes, corresponding to two distinct dynamic regimes characterized by non-Arrhenius and conventional Arrhenius-type DW motions.

  10. Uncertainty in terahertz time-domain spectroscopy measurement

    SciTech Connect (OSTI)

    Withayachumnankul, Withawat; Fischer, Bernd M.; Lin Hungyen; Abbott, Derek

    2008-06-15

    Measurements of optical constants at terahertz--or T-ray--frequencies have been performed extensively using terahertz time-domain spectroscopy (THz-TDS). Spectrometers, together with physical models explaining the interaction between a sample and T-ray radiation, are progressively being developed. Nevertheless, measurement errors in the optical constants, so far, have not been systematically analyzed. This situation calls for a comprehensive analysis of measurement uncertainty in THz-TDS systems. The sources of error existing in a terahertz spectrometer and throughout the parameter estimation process are identified. The analysis herein quantifies the impact of each source on the output optical constants. The resulting analytical model is evaluated against experimental THz-TDS data.

  11. Time-domain reflectometry (TDR) in geotechnics: A review

    SciTech Connect (OSTI)

    Benson, C.H.; Bosscher, P.J.

    1999-07-01

    Time-domain reflectometry (TDR) is an electromagnetic geophysical technique used in the geosciences to measure water content of unfrozen and frozen soils and concentrations of inorganic solutes. In geotechnical and geological engineering, TDR is used for the same purposes, and also to measure frost depths, water levels, and displacements in soil and rock. Nevertheless, geo-engineers use TDR far less frequently than geo-scientists, primarily because they are unfamiliar with the technology. One purpose of this paper is to explain in practical terms how TDR is used in geo-engineering in each of the aforementioned applications. These descriptions reference the important publications in the literature. Another purpose is to share some of the authors' practical experience using TDR in the field.

  12. Ion mobility spectrometer using frequency-domain separation

    DOE Patents [OSTI]

    Martin, Stephen J. (Albuquerque, NM); Butler, Michael A. (Albuquerque, NM); Frye, Gregory C. (Cedar Crest, NM); Schubert, W. Kent (Albuquerque, NM)

    1998-01-01

    An apparatus and method is provided for separating and analyzing chemical species in an ion mobility spectrometer using a frequency-domain technique wherein the ions generated from the chemical species are selectively transported through an ion flow channel having a moving electrical potential therein. The moving electrical potential allows the ions to be selected according to ion mobility, with certain of the ions being transported to an ion detector and other of the ions being effectively discriminated against. The apparatus and method have applications for sensitive chemical detection and analysis for monitoring of exhaust gases, hazardous waste sites, industrial processes, aerospace systems, non-proliferation, and treaty verification. The apparatus can be formed as a microelectromechanical device (i.e. a micromachine).

  13. Depinning transition of a domain wall in ferromagnetic films

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xi, Bin; Luo, Meng -Bo; Vinokur, Valerii M.; Hu, Xiao

    2015-09-14

    We report first principle numerical study of domain wall (DW) depinning in two-dimensional magnetic film, which is modeled by 2D random-field Ising system with the dipole-dipole interaction. We observe non-conventional activation-type motion of DW and reveal the fractal structure of DW near the depinning transition. We determine scaling functions describing critical dynamics near the transition and obtain universal exponents establishing connection between thermal softening of pinning potential and critical dynamics. In addition, we observe that tuning the strength of the dipole-dipole interaction switches DW dynamics between two different universality classes, corresponding to two distinct dynamic regimes characterized by non-Arrhenius andmore » conventional Arrhenius-type DW motions.« less

  14. Investigation of dominant spin wave modes by domain walls collision

    SciTech Connect (OSTI)

    Ramu, M.; Purnama, I.; Goolaup, S.; Chandra Sekhar, M.; Lew, W. S.

    2014-06-28

    Spin wave emission due to field-driven domain wall (DW) collision has been investigated numerically and analytically in permalloy nanowires. The spin wave modes generated are diagonally symmetric with respect to the collision point. The non-propagating mode has the highest amplitude along the middle of the width. The frequency of this mode is strongly correlated to the nanowire geometrical dimensions and is independent of the strength of applied field within the range of 0.1?mT to 1?mT. For nanowire with film thickness below 5?nm, a second spin wave harmonic mode is observed. The decay coefficient of the spin wave power suggests that the DWs in a memory device should be at least 300?nm apart for them to be free of interference from the spin waves.

  15. Ion mobility spectrometer using frequency-domain separation

    DOE Patents [OSTI]

    Martin, S.J.; Butler, M.A.; Frye, G.C.; Schubert, W.K.

    1998-08-04

    An apparatus and method are provided for separating and analyzing chemical species in an ion mobility spectrometer using a frequency-domain technique wherein the ions generated from the chemical species are selectively transported through an ion flow channel having a moving electrical potential therein. The moving electrical potential allows the ions to be selected according to ion mobility, with certain of the ions being transported to an ion detector and other of the ions being effectively discriminated against. The apparatus and method have applications for sensitive chemical detection and analysis for monitoring of exhaust gases, hazardous waste sites, industrial processes, aerospace systems, non-proliferation, and treaty verification. The apparatus can be formed as a microelectromechanical device (i.e. a micromachine). 6 figs.

  16. Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

    SciTech Connect (OSTI)

    Suzuki, Nobuhiro; Yamazaki, Yasuo; Brown, R. Lane; Fujimoto, Zui; Morita, Takashi; Mizuno, Hiroshi

    2008-10-01

    The structures of pseudechetoxin and pseudecin suggest that both proteins bind to cyclic nucleotide-gated ion channels in a manner in which the concave surface occludes the pore entrance. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine-rich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinities on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn{sup 2+}-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn{sup 2+} ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn{sup 2+} binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.

  17. Unstable domains of tearing and Kelvin-Helmholtz instabilities in a rotating cylindrical plasma

    SciTech Connect (OSTI)

    Fan, D. M.; Wei, L.; Wang, Z. X., E-mail: zxwang@dlut.edu.cn; Zheng, S. [Key Laboratory of Materials Modification by Beams of the Ministry of Education, School of Physics and Optoelectronic Engineering, Dalian University of Technology, Dalian 116024 (China); Duan, P. [Department of Physics, Dalian Maritime University, Dalian 116026 (China)

    2014-09-15

    Effects of poloidal rotation profile on tearing and Kelvin-Helmholtz (KH) instabilities in a cylindrical plasma are investigated by using a reduced magnetohydrodynamic model. Since the poloidal rotation has different effects on the tearing and KH modes in different rotation regimes, four unstable domains are numerically identified, i.e., the destabilized tearing mode domain, stabilized tearing mode domain, stable-window domain, and unstable KH mode domain. It is also found that when the rotation layer is in the outer region of the rational surface, the stabilizing role of the rotation can be enhanced so significantly that the stable window domain is enlarged. Moreover, Alfvn resonances can be induced by the tearing and KH modes in such rotating plasmas. Radially wide profiles of current and vorticity perturbations can be formed when multiple current sheets on different resonance positions are coupled together.

  18. System and method for manipulating domain pinning and reversal in ferromagnetic materials

    DOE Patents [OSTI]

    Silevitch, Daniel M.; Rosenbaum, Thomas F.; Aeppli, Gabriel

    2013-10-15

    A method for manipulating domain pinning and reversal in a ferromagnetic material comprises applying an external magnetic field to a uniaxial ferromagnetic material comprising a plurality of magnetic domains, where each domain has an easy axis oriented along a predetermined direction. The external magnetic field is applied transverse to the predetermined direction and at a predetermined temperature. The strength of the magnetic field is varied at the predetermined temperature, thereby isothermally regulating pinning of the domains. A magnetic storage device for controlling domain dynamics includes a magnetic hard disk comprising a uniaxial ferromagnetic material, a magnetic recording head including a first magnet, and a second magnet. The ferromagnetic material includes a plurality of magnetic domains each having an easy axis oriented along a predetermined direction. The second magnet is positioned adjacent to the magnetic hard disk and is configured to apply a magnetic field transverse to the predetermined direction.

  19. Holographic imaging based on time-domain data of natural-fiber-containing materials

    DOE Patents [OSTI]

    Bunch, Kyle J.; McMakin, Douglas L.

    2012-09-04

    Methods and apparatuses for imaging material properties in natural-fiber-containing materials can utilize time-domain data. In particular, images can be constructed that provide quantified measures of localized moisture content. For example, one or more antennas and at least one transceiver can be configured to collect time-domain data from radiation interacting with the natural-fiber-containing materials. The antennas and the transceivers are configured to transmit and receive electromagnetic radiation at one or more frequencies, which are between 50 MHz and 1 THz, according to a time-domain impulse function. A computing device is configured to transform the time-domain data to frequency-domain data, to apply a synthetic imaging algorithm for constructing a three-dimensional image of the natural-fiber-containing materials, and to provide a quantified measure of localized moisture content based on a pre-determined correlation of moisture content to frequency-domain data.

  20. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  1. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  2. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  3. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  4. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  5. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  6. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the discovery of mixed domains of donor and acceptor molecules, many have pictured the excitons' journey as easy

  7. Modeling of leachate generation from MSW landfills by a 2-dimensional 2-domain approach

    SciTech Connect (OSTI)

    Fellner, Johann

    2010-11-15

    The flow of water through Municipal Solid Waste (MSW) landfills is highly non-uniform and dominated by preferential pathways. Thus, concepts to simulate landfill behavior require that a heterogeneous flow regime is considered. Recent models are based on a 2-domain approach, differentiating between channel domain with high hydraulic conductivity, and matrix domain of slow water movement with high water retention capacity. These models focus on the mathematical description of rapid water flow in channel domain. The present paper highlights the importance of water exchange between the two domains, and expands the 1-dimensional, 2-domain flow model by taking into account water flows in two dimensions. A flow field consisting of a vertical path (channel domain) surrounded by the waste mass (matrix domain) is defined using the software HYDRUS-2D. When the new model is calibrated using data sets from a MSW-landfill site the predicted leachate generation corresponds well with the observed leachate discharge. An overall model efficiency in terms of r{sup 2} of 0.76 was determined for a simulation period of almost 4 years. The results confirm that water in landfills follows a preferential path way characterized by high permeability (K{sub s} = 300 m/d) and zero retention capacity, while the bulk of the landfill (matrix domain) is characterized by low permeability (K{sub s} = 0.1 m/d) and high retention capacity. The most sensitive parameters of the model are the hydraulic conductivities of the channel domain and the matrix domain, and the anisotropy of the matrix domain.

  8. The Importance of Domain Size and Purity in High-Efficiency Organic...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of Domain Size and Purity in High-Efficiency Organic Solar Cells Print The efficiency of polymerorganic photovoltaic cells hinges on excitons-electronhole pairs energized by...

  9. Axial current generation by P-odd domains in QCD matter (Journal Article) |

    Office of Scientific and Technical Information (OSTI)

    SciTech Connect SciTech Connect Search Results Journal Article: Axial current generation by P-odd domains in QCD matter Citation Details In-Document Search This content will become publicly available on June 23, 2016 Title: Axial current generation by P-odd domains in QCD matter The dynamics of topological domains which break parity (P) and charge-parity (CP) symmetry of QCD are studied. We derive in a general setting that those local domains will generate an axial current and quantify the

  10. Domain walls in a Born-Infeld-dilaton background (Journal Article) |

    Office of Scientific and Technical Information (OSTI)

    SciTech Connect Domain walls in a Born-Infeld-dilaton background Citation Details In-Document Search Title: Domain walls in a Born-Infeld-dilaton background We study the dynamics of domain walls in the Einstein-Born-Infeld-dilaton theory. A dilaton is nontrivially coupled with the Born-Infeld electromagnetic field. We find three different types of solutions consistent with the dynamic domain walls. For every case, the solutions have singularity. Furthermore, in these backgrounds, we study

  11. Domain pinning near a single-grain boundary in tetragonal and...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Domain pinning near a single-grain boundary in tetragonal and rhombohedral lead zirconate titanate films Citation Details In-Document Search This content will...

  12. Polarization reversal and domain kinetics in magnesium doped stoichiometric lithium tantalate

    SciTech Connect (OSTI)

    Shur, V. Ya., E-mail: vladimir.shur@urfu.ru; Akhmatkhanov, A. R.; Baturin, I. S. [Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation); Labfer Ltd., 620014 Ekaterinburg (Russian Federation); Chuvakova, M. A. [Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation)

    2014-10-13

    The polarization reversal process has been studied in 1?mol.?% MgO doped stoichiometric lithium tantalate (LT) single crystal. The revealed stages of domain structure evolution represent (1) continuous nucleation and growth of isolated hexagonal domains with walls oriented along Y directions and (2) continuous motion of the plane domain walls stimulated by merging with isolated domains. The activation field dependence of the switching time has been revealed. The coercive field for quasi-static switching is about 150?V/mm. The bulk screening process has been analyzed. The main parameters of the switching process have been compared with other representatives of LT family.

  13. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  14. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  15. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  16. Reversible Acid Gas Capture Using CO2-Binding Organic Liquids

    SciTech Connect (OSTI)

    Heldebrant, David J.; Koech, Phillip K.; Yonker, Clement R.; Rainbolt, James E.; Zheng, Feng

    2010-08-31

    Acid gas scrubbing technology is predominantly aqueous alkanolamine based. Of the acid gases, CO2, H2S and SO2 have been shown to be reversible, however there are serious disadvantages with corrosion and high regeneration costs. The primary scrubbing system composed of monoethanolamine is limited to 30% by weight because of the highly corrosive solution. This gravimetric limitation limits the CO2 volumetric (?108 g/L) and gravimetric capacity (?7 wt%) of the system. Furthermore the scrubbing system has a large energy penalty from pumping and heating the excess water required to dissolve the MEA bicarbonate salt. Considering the high specific heat of water (4 j/g-1K-1), low capacities and the high corrosion we set out to design a fully organic solvent that can chemically bind all acid gases i.e. CO2 as reversible alkylcarbonate ionic liquids or analogues thereof. Having a liquid acid gas carrier improves process economics because there is no need for excess solvent to pump and to heat. We have demonstrated illustrated in Figure 1, that CO2-binding organic liquids (CO2BOLs) have a high CO2 solubility paired with a much lower specific heat (<1.5 J/g-1K-1) than aqueous systems. CO2BOLs are a subsection of a larger class of materials known as Binding Organic Liquids (BOLs). Our BOLs have been shown to reversibly bind and release COS, CS2, and SO2, which we denote COSBOLS, CS2BOLs and SO2BOLs. Our BOLs are highly tunable and can be designed for post or pre-combustion gas capture. The design and testing of the next generation zwitterionic CO2BOLs and SO2BOLs are presented.

  17. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of prokaryotic partition is the Escherichia coli P1 plasmid par system, which consists of a centromere

  18. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  19. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  20. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  1. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  2. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of prokaryotic partition is the Escherichia coli P1 plasmid par system, which consists of a centromere

  3. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  4. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  5. Protein Immobilization in Metal-Organic Frameworks by Covalent Binding |

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Protein Immobilization in Metal-Organic Frameworks by Covalent Binding Previous Next List Xuan Wang, Trevor A. Makal and Hong-Cai Zhou, Aust. J. Chem. 67, 1629-1631 (2014) DOI: 10.1071/CH14104 CH14104_TOC Abstract: Metal-organic frameworks (MOFs), possessing a well defined system of pores, demonstrate extensive potential serving as a platform in biological catalysis. Successful immobilization of enzymes in a

  6. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  7. Gold Binding by Native and Chemically Modified Hops Biomasses

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    López, M. Laura; Gardea-Torresdey, J. L.; Peralta-Videa, J. R.; de la Rosa, G.; Armendáriz, V.; Herrera, I.; Troiani, H.; Henning, J.

    2005-01-01

    Heavy metals from mining, smelting operations and other industrial processing facilities pollute wastewaters worldwide. Extraction of metals from industrial effluents has been widely studied due to the economic advantages and the relative ease of technical implementation. Consequently, the search for new and improved methodologies for the recovery of gold has increased. In this particular research, the use of cone hops biomass ( Humulus lupulus ) was investigated as a new option for gold recovery. The results showed that the gold binding to native hops biomass was pH dependent from pH 2 to pH 6, with a maximum percentage bindingmore » at pH 3. Time dependency studies demonstrated that Au(III) binding to native and modified cone hops biomasses was found to be time independent at pH 2 while at pH 5, it was time dependent. Capacity experiments demonstrated that at pH 2, esterified hops biomass bound 33.4 mg Au/g of biomass, while native and hydrolyzed hops biomasses bound 28.2 and 12.0 mg Au/g of biomass, respectively. However, at pH 5 the binding capacities were 38.9, 37.8 and 11.4 mg of Au per gram of native, esterified and hydrolyzed hops biomasses, respectively.« less

  8. V-058: Microsoft Internet Explorer CDwnBindInfo Object Reuse...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    8: Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote Users Execute Arbitrary Code V-058: Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote...

  9. New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities...

    Office of Scientific and Technical Information (OSTI)

    New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins Citation Details In-Document Search Title: New Insights into the RNA-Binding and E3 Ubiquitin Ligase...

  10. Plasticity of the Quinone-binding Site of the Complex II Homolog...

    Office of Scientific and Technical Information (OSTI)

    Plasticity of the Quinone-binding Site of the Complex II Homolog Quinol:Fumarate Reductase Citation Details In-Document Search Title: Plasticity of the Quinone-binding Site of the...

  11. Discovery of a new ATP-binding motif involved in peptidic azoline...

    Office of Scientific and Technical Information (OSTI)

    Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Citation Details In-Document Search Title: Discovery of a new ATP-binding motif involved in peptidic ...

  12. Time domain reflectometry development for use in geotechnical engineering

    SciTech Connect (OSTI)

    Siddiqui, S.I.; Drnevich, V.P.; Deschamps, R.J.

    2000-03-01

    This study extends the use of time domain reflectometry (TDR) in geotechnical engineering, a technique originally developed to locate faults in transmission lines. Different elements of the TDR technique are developed, including design of TDR probes, probe installation/test methodology, and relationships between TDR measured dielectric constant and water content of soil. A coaxial probe is developed that is used for measuring the dielectric constant of soil prepared in a cylindrical cell or compaction mold. A multiple-rod field probe is developed that modifies previously developed multiple-rod probes and extends their capability for measuring the in-place dielectric constant of soil. An analytical solution is developed to determine the sampling volume and spatial bias of the TDR measurement. The solution is extended to study the effect of soil disturbance and presence of air gaps due to probe insertion. Experimental results validate the solutions. New relationships are proposed between dielectric constant and water content to eliminate some of the limitations of the existing calibration relationships. Several possible applications of the developed probes, test methodology, and calibration equations for measuring water content and density of soil are illustrated.

  13. Magnetic bead detection using domain wall-based nanosensor

    SciTech Connect (OSTI)

    Corte-León, H.; Krzysteczko, P.; Schumacher, H. W.; Manzin, A.; Cox, D.; Antonov, V.; Kazakova, O.

    2015-05-07

    We investigate the effect of a single magnetic bead (MB) on the domain wall (DW) pinning/depinning fields of a DW trapped at the corner of an L-shaped magnetic nanodevice. DW propagation across the device is investigated using magnetoresistance measurements. DW pinning/depinning fields are characterized in as-prepared devices and after placement of a 1 μm-sized MB (Dynabeads{sup ®} MyOne{sup ™}) at the corner. The effect of the MB on the DW dynamics is seen as an increase in the depinning field for specific orientations of the device with respect to the external magnetic field. The shift of the depinning field, ΔB{sub dep} = 4.5–27.0 mT, is highly stable and reproducible, being significantly above the stochastic deviation which is about 0.5 mT. The shift in the deppinning field is inversely proportional to the device width and larger for small negative angles between the device and the external magnetic field. Thus, we demonstrate that DW-based devices can be successfully used for detection of single micron size MB.

  14. An Analog Filter Approach to Frequency Domain Fluorescence Spectroscopy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Trainham, Clifford P.; O'Neill, Mary D.; McKenna, Ian J.

    2015-04-24

    The rate equations found in frequency domain fluorescence spectroscopy are the same as those found in electronics under analog filter theory. Laplace transform methods are a natural way to solve the equations, and the methods can provide solutions for arbitrary excitation functions. The fluorescence terms can be modeled as circuit components and cascaded with drive and detection electronics to produce a global transfer function. Electronics design tools such as Spicea can be used to model fluorescence problems. In applications, such as remote sensing, where detection electronics are operated at high gain and limited bandwidth, a global modeling of the entiremore » system is important, since the filter terms of the drive and detection electronics affect the measured response of the fluorescence signals. The techniques described here can be used to separate signals from fast and slow fluorophores emitting into the same spectral band, and data collection can be greatly accelerated by means of a frequency comb driver waveform and appropriate signal processing of the response.« less

  15. Reversible CO Binding in Metal-Organic Frameworks | Center for Gas

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Reversible CO Binding in Metal-Organic Frameworks

  16. Iterative image-domain decomposition for dual-energy CT

    SciTech Connect (OSTI)

    Niu, Tianye; Dong, Xue; Petrongolo, Michael; Zhu, Lei

    2014-04-15

    Purpose: Dual energy CT (DECT) imaging plays an important role in advanced imaging applications due to its capability of material decomposition. Direct decomposition via matrix inversion suffers from significant degradation of image signal-to-noise ratios, which reduces clinical values of DECT. Existing denoising algorithms achieve suboptimal performance since they suppress image noise either before or after the decomposition and do not fully explore the noise statistical properties of the decomposition process. In this work, the authors propose an iterative image-domain decomposition method for noise suppression in DECT, using the full variance-covariance matrix of the decomposed images. Methods: The proposed algorithm is formulated in the form of least-square estimation with smoothness regularization. Based on the design principles of a best linear unbiased estimator, the authors include the inverse of the estimated variance-covariance matrix of the decomposed images as the penalty weight in the least-square term. The regularization term enforces the image smoothness by calculating the square sum of neighboring pixel value differences. To retain the boundary sharpness of the decomposed images, the authors detect the edges in the CT images before decomposition. These edge pixels have small weights in the calculation of the regularization term. Distinct from the existing denoising algorithms applied on the images before or after decomposition, the method has an iterative process for noise suppression, with decomposition performed in each iteration. The authors implement the proposed algorithm using a standard conjugate gradient algorithm. The method performance is evaluated using an evaluation phantom (Catphan600) and an anthropomorphic head phantom. The results are compared with those generated using direct matrix inversion with no noise suppression, a denoising method applied on the decomposed images, and an existing algorithm with similar formulation as the proposed method but with an edge-preserving regularization term. Results: On the Catphan phantom, the method maintains the same spatial resolution on the decomposed images as that of the CT images before decomposition (8 pairs/cm) while significantly reducing their noise standard deviation. Compared to that obtained by the direct matrix inversion, the noise standard deviation in the images decomposed by the proposed algorithm is reduced by over 98%. Without considering the noise correlation properties in the formulation, the denoising scheme degrades the spatial resolution to 6 pairs/cm for the same level of noise suppression. Compared to the edge-preserving algorithm, the method achieves better low-contrast detectability. A quantitative study is performed on the contrast-rod slice of Catphan phantom. The proposed method achieves lower electron density measurement error as compared to that by the direct matrix inversion, and significantly reduces the error variation by over 97%. On the head phantom, the method reduces the noise standard deviation of decomposed images by over 97% without blurring the sinus structures. Conclusions: The authors propose an iterative image-domain decomposition method for DECT. The method combines noise suppression and material decomposition into an iterative process and achieves both goals simultaneously. By exploring the full variance-covariance properties of the decomposed images and utilizing the edge predetection, the proposed algorithm shows superior performance on noise suppression with high image spatial resolution and low-contrast detectability.

  17. The domains of instability for the pulsating PG1159 stars.

    SciTech Connect (OSTI)

    Quirion, P.-O.; Fontaine, Gilles.; Brassard, Pierre; Herwig, F. H.

    2004-01-01

    The fact that we find pulsating and nonpulsating stars mixed together in the PG 1159 region of the log g - T{sub eff} diagram has been a long standing puzzle. The poor understanding of the driving mechanism in those stars has been the reason why it has taken so long to address properly this problem. Following the work of Saio (1996) and Gautschy (1997) based on the OPAL opacities, Quirion, Fontaine, & Brassard (2004) recently showed that we are now able to understand and reproduce the ranges of observed periods in the pulsating PG 1159 stars in terms of the original {kappa}-mechanism associated with the partial ionization of the K-shell electrons of C and O which, along with He, make up the composition of the envelope of those stars. Contrary to others, those three studies agree in that no composition gradients are needed between the atmospheric layers and the driving region. Furthermore, the cohabitation of pulsating and nonpulsating PG 1159 stars is naturally explained in terms of a dispersion in atmospheric parameters and in terms of a variation in surface composition from star to star. In particular, the most He-rich stars tend to be stable. We go beyond the findings discussed by Quirion et al. (2004) in this paper, and present the results of additional calculations aimed at describing better the role of the chemical composition (in particular the role of metallicity) as well as that of the stellar mass on the boundaries of the instability domain in the log g - T{sub eff} plane.

  18. Sapphire decomposition and inversion domains in N-polar aluminum nitride

    SciTech Connect (OSTI)

    Hussey, Lindsay White, Ryan M.; Kirste, Ronny; Bryan, Isaac; Guo, Wei; Osterman, Katherine; Haidet, Brian; Bryan, Zachary; Bobea, Milena; Collazo, Ramn; Sitar, Zlatko; Mita, Seiji

    2014-01-20

    Transmission electron microscopy (TEM) techniques and potassium hydroxide (KOH) etching confirmed that inversion domains in the N-polar AlN grown on c-plane sapphire were due to the decomposition of sapphire in the presence of hydrogen. The inversion domains were found to correspond to voids at the AlN and sapphire interface, and transmission electron microscopy results showed a V-shaped, columnar inversion domain with staggered domain boundary sidewalls. Voids were also observed in the simultaneously grown Al-polar AlN, however no inversion domains were present. The polarity of AlN grown above the decomposed regions of the sapphire substrate was confirmed to be Al-polar by KOH etching and TEM.

  19. Self-annihilation of inversion domains by high energy defects in III-Nitrides

    SciTech Connect (OSTI)

    Koukoula, T.; Kioseoglou, J. Kehagias, Th.; Komninou, Ph.; Ajagunna, A. O.; Georgakilas, A.

    2014-04-07

    Low-defect density InN films were grown on Si(111) by molecular beam epitaxy over an ?1??m thick GaN/AlN buffer/nucleation layer. Electron microscopy observations revealed the presence of inverse polarity domains propagating across the GaN layer and terminating at the sharp GaN/InN (0001{sup }) interface, whereas no inversion domains were detected in InN. The systematic annihilation of GaN inversion domains at the GaN/InN interface is explained in terms of indium incorporation on the Ga-terminated inversion domains forming a metal bonded In-Ga bilayer, a structural instability known as the basal inversion domain boundary, during the initial stages of InN growth on GaN.

  20. Structure of a Longitudinal Actin Dimer Assembled by Tandem W Domains: Implications for Actin Filament Nucleation

    SciTech Connect (OSTI)

    Rebowski, Grzegorz; Namgoong, Suk; Boczkowska, Malgorzata; Leavis, Paul C.; Navaza, Jorge; Dominguez, Roberto

    2013-11-20

    Actin filament nucleators initiate polymerization in cells in a regulated manner. A common architecture among these molecules consists of tandem WASP homology 2 domains (W domains) that recruit three to four actin subunits to form a polymerization nucleus. We describe a low-resolution crystal structure of an actin dimer assembled by tandem W domains, where the first W domain is cross-linked to Cys374 of the actin subunit bound to it, whereas the last W domain is followed by the C-terminal pointed end-capping helix of thymosin {beta}4. While the arrangement of actin subunits in the dimer resembles that of a long-pitch helix of the actin filament, important differences are observed. These differences result from steric hindrance of the W domain with intersubunit contacts in the actin filament. We also determined the structure of the first W domain of Vibrio parahaemolyticus VopL cross-linked to actin Cys374 and show it to be nearly identical with non-cross-linked W-Actin structures. This result validates the use of cross-linking as a tool for the study of actin nucleation complexes, whose natural tendency to polymerize interferes with most structural methods. Combined with a biochemical analysis of nucleation, the structures may explain why nucleators based on tandem W domains with short inter-W linkers have relatively weak activity, cannot stay bound to filaments after nucleation, and are unlikely to influence filament elongation. The findings may also explain why nucleation-promoting factors of the Arp2/3 complex, which are related to tandem-W-domain nucleators, are ejected from branch junctions after nucleation. We finally show that the simple addition of the C-terminal pointed end-capping helix of thymosin {beta}4 to tandem W domains can change their activity from actin filament nucleation to monomer sequestration.

  1. Analytical models of calcium binding in a calcium channel

    SciTech Connect (OSTI)

    Liu, Jinn-Liang; Eisenberg, Bob

    2014-08-21

    The anomalous mole fraction effect of L-type calcium channels is analyzed using a Fermi like distribution with the experimental data of Almers and McCleskey [J. Physiol. 353, 585 (1984)] and the atomic resolution model of Lipkind and Fozzard [Biochemistry 40, 6786 (2001)] of the selectivity filter of the channel. Much of the analysis is algebraic, independent of differential equations. The Fermi distribution is derived from the configuration entropy of ions and water molecules with different sizes, different valences, and interstitial voids between particles. It allows us to calculate potentials and distances (between the binding ion and the oxygen ions of the glutamate side chains) directly from the experimental data using algebraic formulas. The spatial resolution of these results is comparable with those of molecular models, but of course the accuracy is no better than that implied by the experimental data. The glutamate side chains in our model are flexible enough to accommodate different types of binding ions in different bath conditions. The binding curves of Na{sup +} and Ca{sup 2+} for [CaCl{sub 2}] ranging from 10{sup −8} to 10{sup −2} M with a fixed 32 mM background [NaCl] are shown to agree with published Monte Carlo simulations. The Poisson-Fermi differential equation—that includes both steric and correlation effects—is then used to obtain the spatial profiles of energy, concentration, and dielectric coefficient from the solvent region to the filter. The energy profiles of ions are shown to depend sensitively on the steric energy that is not taken into account in the classical rate theory. We improve the rate theory by introducing a steric energy that lumps the effects of excluded volumes of all ions and water molecules and empty spaces between particles created by Lennard-Jones type and electrostatic forces. We show that the energy landscape varies significantly with bath concentrations. The energy landscape is not constant.

  2. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOE Patents [OSTI]

    Bertozzi, Carolyn R. (Berkeley, CA); Song, Jie (Shrewsbury, MA); Lee, Seung-Wuk (Walnut Creek, CA)

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  3. Functionalized polymers for binding to solutes in aqueous solutions

    DOE Patents [OSTI]

    Smith, Barbara F.; Robison, Thomas W.

    2006-11-21

    A functionalized polymer for binding a dissolved molecule in an aqueous solution is presented. The polymer has a backbone polymer to which one or more functional groups are covalently linked. The backbone polymer can be such polymers as polyethylenimine, polyvinylamine, polyallylamine, and polypropylamine. These polymers are generally water-soluble, but can be insoluble when cross-linked. The functional group can be for example diol derivatives, polyol derivatives, thiol and dithiol derivatives, guest-host groups, affinity groups, beta-diphosphonic acids, and beta-diamides

  4. Breaking the ties that bind: New hope for biomass fuels

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    New hope for biomass fuels Breaking the ties that bind: New hope for biomass fuels Researchers have discovered a potential chink in the armor of fibers that make the cell walls of certain inedible plant materials so tough. April 22, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources, to plasma physics and new materials.

  5. Climate change: Clinton affirms binding emissions reduction policy

    SciTech Connect (OSTI)

    Fairley, P.

    1996-12-04

    In Australia last month President Clinton called for an international agreement to negotiate {open_quotes}legally binding commitments to fight climate change.{close_quotes} His comments affirmed the line the Administration adopted in July and lent prominence to the effort to bring about a treaty by December 1997. Environmentalists welcomed Clinton`s comments, but industry response is divided. The Global Climate Coalition (Washington), of which CMA is a member, has tried to slow negotiations by questioning the scientific consensus on climate change and suggesting {open_quotes}serious damage to the American economy{close_quotes} could result from emissions reduction.

  6. Highly-Selective and Reversible O2 Binding in

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cr3(1,3,5-benzenetricarboxylate)2 | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Highly-Selective and Reversible O2 Binding in Cr3(1,3,5-benzenetricarboxylate)2 Previous Next List Leslie J. Murray, Mircea Dinca, Junko Yano, Sachin Chavan, Silvia Bordiga, Craig M. Brown and Jeffrey R. Long, J. Am. Chem. Soc., 2010, 132 (23), pp 7856-7857 DOI: 10.1021/ja1027925 Abstract Image Abstract: Reaction of Cr(CO)6 with trimesic acid in DMF affords the metal-organic

  7. Somatic mutational analysis of FAK in breast cancer: A novel gain-of-function mutation due to deletion of exon 33

    SciTech Connect (OSTI)

    Fang, Xu-Qian; Liu, Xiang-Fan; Yao, Ling; Chen, Chang-Qiang; Gu, Zhi-Dong; Ni, Pei-Hua; Zheng, Xin-Min; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY ; Fan, Qi-Shi

    2014-01-10

    Highlights: A novel FAK splicing mutation identified in breast tumor. FAK-Del33 mutation promotes cell migration and invasion. FAK-Del33 mutation regulates FAK/Src signal pathway. -- Abstract: Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introduced into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.

  8. Domain patterning by electron beam of MgO doped lithium niobate covered by resist

    SciTech Connect (OSTI)

    Shur, V. Ya. Chezganov, D. S.; Akhmatkhanov, A. R.; Kuznetsov, D. K.

    2015-06-08

    Periodical domain structuring by focused electron beam irradiation of MgO-doped lithium niobate (MgOCLN) single crystalline plate covered by resist layer was studied both experimentally and by computer simulation. The dependences of domain size on the charge dose and distance between isolated domains were measured. It has been shown that the quality of periodical domain pattern depends on the thickness of resist layer and electron energy. The experimentally obtained periodic domain structures have been divided into four types. The irradiation parameters for the most uniform patterning were obtained experimentally. It was shown by computer simulation that the space charge slightly touching the crystal surface produced the maximum value of electric field at the resist/LN interface thus resulting in the best pattern quality. The obtained knowledge allowed us to optimize the poling process and to make the periodical domain patterns in 1-mm-thick wafers with an area up to 1 5?mm{sup 2} and a period of 6.89??m for green light second harmonic generation. Spatial distribution of the efficiency of light frequency conversion confirmed the high homogeneity of the tailored domain patterns.

  9. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  10. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  11. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  12. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  13. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print Wednesday, 26 September 2007 00:00 The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray

  14. The Importance of Domain Size and Purity in High-Efficiency Organic Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells The Importance of Domain Size and Purity in High-Efficiency Organic Solar Cells Print Wednesday, 27 March 2013 00:00 The efficiency of polymer/organic photovoltaic cells hinges on excitons-electron/hole pairs energized by sunlight-getting to the interfaces of donor and acceptor domains quickly, before recombining. At the interfaces, they become free charges that must then reach device electrodes. With the

  15. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  16. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  17. X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    X-Ray Imaging Current-Driven Magnetic Domain-Wall Motion in Nanowires Print The quest to increase both computer data-storage density and the speed at which one can read and write the information remains unconsummated. One novel concept is based on the use of a local electric current to push magnetic domain walls along a thin nanowire. A German, Korean, Berkeley Lab team has used the x-ray microscope XM-1 at the ALS to demonstrate that magnetic domain walls in curved permalloy nanowires can be

  18. V-084: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain Access,

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Clickjacking, and File Upload Attacks | Department of Energy 84: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain Access, Clickjacking, and File Upload Attacks V-084: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain Access, Clickjacking, and File Upload Attacks February 5, 2013 - 12:01am Addthis PROBLEM: RSA Archer eGRC Permits Cross-Site Scripting, Cross-Domain Access, Clickjacking, and File Upload Attacks PLATFORM: RSA Archer SmartSuite Framework version 4.x RSA Archer

  19. Axial current generation by P-odd domains in QCD matter

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Iatrakis, Ioannis; Yin, Yi; Lin, Shu

    2015-06-23

    The dynamics of topological domains which break parity (P) and charge-parity (CP) symmetry of QCD are studied. We derive in a general setting that those local domains will generate an axial current and quantify the strength of the induced axial current. Thus, our findings are verified in a top-down holographic model. The relation between the real time dynamics of those local domains and the chiral magnetic field is also elucidated. We finally argue that such an induced axial current would be phenomenologically important in a heavy-ion collisions experiment.

  20. Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain Network

    Energy Savers [EERE]

    Focued- Open SG/SG-Network TF | Department of Energy Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain Network Focued- Open SG/SG-Network TF Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain Network Focued- Open SG/SG-Network TF Smart Grid data flow diagram. PDF icon Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain Network Focued- Open SG/SG-Network TF More Documents & Publications Report to NIST on the Smart Grid Interoperability Standards Roadmap SG

  1. Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping

    SciTech Connect (OSTI)

    Henke, Paul S.; Mak, Chi H.

    2014-08-14

    The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg{sup 2+} that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

  2. The TLR4 agonist fibronectin extra domain A is cryptic, exposed...

    Office of Scientific and Technical Information (OSTI)

    fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer vaccine Citation Details In-Document Search Title: The TLR4 agonist fibronectin extra...

  3. Dynamics of spintronic materials: Exploration in the time and frequency domain

    SciTech Connect (OSTI)

    Zabel, Hartmut

    2014-12-14

    X-ray and neutron reflectivity are mature experimental techniques for the exploration of film thicknesses and interface roughnesses on the nanoscale. Combining with photon and neutron polarization, these methods can be carried forward to the analysis of magnetic thin films and magnetic domain structures. New opportunities open up when these methods are used either in the time or in the frequency domain. Then dynamical processes can be studied such as domain oscillations, domain propagation, precession of spins, and damping effects. Two methods are discussed which have been developed recently: polarized neutron reflectivity from magnetic films in an alternating magnetic field and time resolved resonant magnetic x-ray reflectivity of the free precessional dynamics in films and multilayers.

  4. Magnetic soft x-ray microscopy of the domain wall depinning process...

    Office of Scientific and Technical Information (OSTI)

    Magnetic soft x-ray microscopy of the domain wall depinning process in permalloy magnetic nanowires Citation Details In-Document Search Title: Magnetic soft x-ray microscopy of the...

  5. Analysis of electron capture process in charge pumping sequence using time domain measurements

    SciTech Connect (OSTI)

    Hori, Masahiro Watanabe, Tokinobu; Ono, Yukinori; Tsuchiya, Toshiaki

    2014-12-29

    A method for analyzing the electron capture process in the charge pumping (CP) sequence is proposed and demonstrated. The method monitors the electron current in the CP sequence in time domain. This time-domain measurements enable us to directly access the process of the electron capture to the interface defects, which are obscured in the conventional CP method. Using the time-domain measurements, the rise time dependence of the capture process is systematically investigated. We formulate the capture process based on the rate equation and derive an analytic form of the current due to the electron capture to the defects. Based on the formula, the experimental data are analyzed and the capture cross section is obtained. In addition, the time-domain data unveil that the electron capture process completes before the electron channel opens, or below the threshold voltage in a low frequency range of the pulse.

  6. Development of Gamma-Emitting Receptor Binding Radiopharmace

    SciTech Connect (OSTI)

    Reba, Richard

    2003-02-20

    The long-term objective is to develop blood-brain barrier (BBB) permeable m2-selective (relative to m1, m3, and m4) receptor-binding radiotracers and utilize these radiotracers for quantifying receptor concentrations obtained from PET or SPECT images of human brain. In initial studies, we concluded that the lipophilicity and high affinity prevented (R,S)-I-QNB from reaching a flow-independent and receptor-dependent state in a reasonable time. Thus, it was clear that (R,S)-I-QNB should be modified. Therefore, during the last portion of this funded research, we proposed that more polar heterocycles should help accomplish that. Since reports of others concluded that radiobromination and radiofluorination of the unactivated phenyl ring is not feasible (Newkome et al,,1982), we, therefore, explored during this grant period a series of analogues of (R)-QNB in which one or both of the six-membered phenyl rings is replaced by a five-membered thienyl (Boulay et al., 1995), or furyl ring. The chemistry specific aims were to synthesize novel compounds designed to be m2-selective mAChR ligands capable of penetrating into the CNS, and develop methods for efficient radiolabeling of promising m2-selective muscarinic ligands. The pharmacology specific aims were to determine the affinity and subtype-selectivity of the novel compounds using competition binding studies with membranes from cells that express each of the five muscarinic receptor subtypes, to determine the ability of the promising non-radioactive compounds and radiolabeled novel compounds to cross the BBB, to determine the biodistribution, in-vivo pharmacokinetics, and in-vitm kinetics of promising m2-selective radioligands and to determine the distribution of receptors for the novel m2-selective radioligands using quantitative autoradiography of rat brain, and compare this distribution to the distribution of known m2-selective compounds.

  7. Structure of the DUF2233 Domain in Bacteria and the Stuttering-associated

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    UCE Glycoprotein | Stanford Synchrotron Radiation Lightsource the DUF2233 Domain in Bacteria and the Stuttering-associated UCE Glycoprotein Wednesday, July 31, 2013 UCE figure DUF2233, a Domain of Unknown Function (DUF), is present in ~1200 bacterial and several viral and eukaryotic proteins. DUF2233 has been identified in proteins ranging in size from ~300-2000 residues. The 515 amino acid mammalian transmembrane glycoprotein α-N-acetylglucosamine-1-phosphodiester N-acetylglucosaminidase

  8. Phase Behavior and Domain Size in Sphingomyelin-Containing Lipid Bilayers

    SciTech Connect (OSTI)

    Petruzielo, Robin S [Cornell University; Heberle, Frederick A [ORNL; Drazba, Paul [ORNL; Katsaras, John [ORNL; Feigenson, Gerald [Cornell University

    2013-01-01

    Membrane raft size measurements are crucial to understanding the stability and functionality of rafts in cells. The challenge of accurately measuring raft size is evidenced by the disparate reports of domain sizes, which range from nanometers to microns for the ternary model membrane system sphingomyelin (SM)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol (Chol). Using F rster resonance energy transfer (FRET) and differential scanning calorimetry (DSC), we established phase diagrams for porcine brain SM (bSM)/dioleoyl-sn-glycero-3-phosphocholine (DOPC)/Chol and bSM/POPC/Chol at 15 and 25 C. By combining two techniqueswith different spatial sensitivities, namely FRET and small-angle neutron scattering (SANS),we have significantly narrowed the uncertainty in domain size estimates for bSM/POPC/Chol mixtures. Compositional trends in FRET data revealed coexisting domains at 15 and 25 C for bothmixtures, while SANS measurements detected no domain formation for bSM/POPC/Chol. Together these results indicate that liquid domains in bSM/POPC/Chol are between 2 and 7 nmin radius at 25 C: that is, domains must be on the order of the 2 6 nmF rster distance of the FRET probes, but smaller than the ~7 nm minimum cluster size detectable with SANS. However, for palmitoyl SM (PSM)/POPC/Chol at a similar composition, SANS detected coexisting liquid domains. This increase in domain size upon replacing the natural SMcomponent (which consists of amixture of chain lengths) with synthetic PSM, suggests a role for SM chain length in modulating raft size in vivo.

  9. Molecular functions of the TLE tetramerization domain in Wnt target gene

    Office of Scientific and Technical Information (OSTI)

    repression (Journal Article) | SciTech Connect Molecular functions of the TLE tetramerization domain in Wnt target gene repression Citation Details In-Document Search Title: Molecular functions of the TLE tetramerization domain in Wnt target gene repression Authors: Chodaparambil, Jayanth V. ; Pate, Kira T. ; Hepler, Margretta R.D. ; Tsai, Becky P. ; Muthurajan, Uma M. ; Luger, Karolin ; Waterman, Marian L. ; Weis, William I. [1] ; CSU) [2] ; UCI) [2] + Show Author Affiliations (Stanford) (

  10. Magnetic anisotropy and domain patterning of amorphous films by He-ion

    Office of Scientific and Technical Information (OSTI)

    irradiation (Journal Article) | SciTech Connect Magnetic anisotropy and domain patterning of amorphous films by He-ion irradiation Citation Details In-Document Search Title: Magnetic anisotropy and domain patterning of amorphous films by He-ion irradiation The magnetic anisotropy in amorphous soft magnetic FeCoSiB films was modified by He-ion irradiation. A rotation of uniaxial anisotropy depending on the applied field direction in the irradiated areas is observed by magnetometry and

  11. Crystal structure of a ;#8203;BRAF kinase domain monomer explains basis for

    Office of Scientific and Technical Information (OSTI)

    allosteric regulation (Journal Article) | SciTech Connect Crystal structure of a ;#8203;BRAF kinase domain monomer explains basis for allosteric regulation Citation Details In-Document Search Title: Crystal structure of a ;#8203;BRAF kinase domain monomer explains basis for allosteric regulation Authors: Thevakumaran, Neroshan ; Lavoie, Hugo ; Critton, David A. ; Tebben, Andrew ; Marinier, Anne ; Sicheri, Frank ; Therrien , Marc [1] ; Montreal) [2] ; BMS) [2] + Show Author Affiliations

  12. Domain pinning near a single-grain boundary in tetragonal and rhombohedral

    Office of Scientific and Technical Information (OSTI)

    lead zirconate titanate films (Journal Article) | SciTech Connect Domain pinning near a single-grain boundary in tetragonal and rhombohedral lead zirconate titanate films Citation Details In-Document Search This content will become publicly available on April 26, 2016 Title: Domain pinning near a single-grain boundary in tetragonal and rhombohedral lead zirconate titanate films Authors: Marincel, D. M. ; Zhang, H. R. ; Britson, J. ; Belianinov, A. ; Jesse, S. ; Kalinin, S. V. ; Chen, L. Q. ;

  13. Domain walls as dark energy (Journal Article) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Domain walls as dark energy Citation Details In-Document Search Title: Domain walls as dark energy No abstract prepared. Authors: Friedland, Alexander ; Murayama, Hitoshi ; Perelstein, Maxim Publication Date: 2003-01-16 OSTI Identifier: 840977 Report Number(s): LBNL--50255 R&D Project: PTHOPS; TRN: US0502453 DOE Contract Number: AC03-76SF00098 Resource Type: Journal Article Resource Relation: Journal Name: Physical Review D; Journal Volume: 66; Other Information: Journal Publication Date:

  14. Engineering of a Histone-Recognition Domain in Dnmt3a Alters the Epigenetic

    Office of Scientific and Technical Information (OSTI)

    Landscape and Phenotypic Features of Mouse ESCs (Journal Article) | SciTech Connect Engineering of a Histone-Recognition Domain in Dnmt3a Alters the Epigenetic Landscape and Phenotypic Features of Mouse ESCs Citation Details In-Document Search Title: Engineering of a Histone-Recognition Domain in Dnmt3a Alters the Epigenetic Landscape and Phenotypic Features of Mouse ESCs Authors: Noh, Kyung-Min ; Wang, Haibo ; Kim, Hyunjae R. ; Wenderski, Wendy ; Fang, Fang ; Li, Charles H. ; Dewell, Scott

  15. Diverse oligomeric states of CEACAM IgV domains (Journal Article) | SciTech

    Office of Scientific and Technical Information (OSTI)

    Connect Diverse oligomeric states of CEACAM IgV domains Citation Details In-Document Search Title: Diverse oligomeric states of CEACAM IgV domains Authors: Bonsor, Daniel A. ; Günther, Sebastian ; Beadenkopf, Robert ; Beckett, Dorothy ; Sundberg, Eric J. [1] + Show Author Affiliations Maryland Publication Date: 2016-01-19 OSTI Identifier: 1235483 Resource Type: Journal Article Resource Relation: Journal Name: Proceedings of the National Academy of Sciences of the United States of America;

  16. Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional

    Office of Scientific and Technical Information (OSTI)

    Activity (Journal Article) | SciTech Connect Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity Citation Details In-Document Search Title: Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity Authors: Hu, Tiancen ; Yeh, Jennifer E. ; Pinello, Luca ; Jacob, Jaison ; Chakravarthy, Srinivas ; Yuan, Guo-Cheng ; Chopra, Rajiv ; Frank, David A. [1] ; DFCI) [2] ; Harvard) [2] ; IIT) [2] ; BWH) [2] + Show Author Affiliations

  17. Dynamic load balancing algorithm for molecular dynamics based on Voronoi cells domain decompositions

    SciTech Connect (OSTI)

    Fattebert, J.-L.; Richards, D.F.; Glosli, J.N.

    2012-12-01

    We present a new algorithm for automatic parallel load balancing in classical molecular dynamics. It assumes a spatial domain decomposition of particles into Voronoi cells. It is a gradient method which attempts to minimize a cost function by displacing Voronoi sites associated with each processor/sub-domain along steepest descent directions. Excellent load balance has been obtained for quasi-2D and 3D practical applications, with up to 440106 particles on 65,536 MPI tasks.

  18. Dependence of effective internal field of congruent lithium niobate on its domain configuration and stability

    SciTech Connect (OSTI)

    Das, Ranjit E-mail: souvik2cat@gmail.com Ghosh, Souvik E-mail: souvik2cat@gmail.com Chakraborty, Rajib E-mail: souvik2cat@gmail.com

    2014-06-28

    Congruent lithium niobate is characterized by its internal field, which arises due to defect clusters within the crystal. Here, it is shown experimentally that this internal field is a function of the molecular configuration in a particular domain and also on the stability of that particular configuration. The measurements of internal field are done using interferometric technique, while the variation of domain configuration is brought about by room temperature high voltage electric field poling.

  19. A Linked-Cell Domain Decomposition Method for Molecular Dynamics Simulation on a Scalable Multiprocessor

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yang, L. H.; Brooks III, E. D.; Belak, J.

    1992-01-01

    A molecular dynamics algorithm for performing large-scale simulations using the Parallel C Preprocessor (PCP) programming paradigm on the BBN TC2000, a massively parallel computer, is discussed. The algorithm uses a linked-cell data structure to obtain the near neighbors of each atom as time evoles. Each processor is assigned to a geometric domain containing many subcells and the storage for that domain is private to the processor. Within this scheme, the interdomain (i.e., interprocessor) communication is minimized.

  20. Structure and Dynamics of Domains in Ferroelectric Nanostructures. In-situ TEM Studies

    SciTech Connect (OSTI)

    Pan, Xiaoqing

    2015-06-30

    The goal of this project was to explore the structure and dynamic behaviors of ferroelectric domains in ferroelectric thin films and nanostructures by advanced transmission electron microscopy (TEM) techniques in close collaboration with phase field modeling. The experimental techniques used include aberration-corrected sub-Å resolution TEM and in-situ TEM using a novel scanning tunneling microscopy (STM) - TEM holder that allows the direct observation of nucleation and dynamic evolution of ferroelectric domains under applied electric field. Specifically, this project was aimed to (1) to study the roles of static electrical boundary conditions and electrical charge in controlling the equilibrium domain structures of BiFeO3 thin films with controlled substrate constraints, (2) to explore the fundamental mechanisms of ferroelectric domain nucleation, growth, and switching under an applied electric field in both uniform thin films and nanostructures, and to understand the roles of crystal defects such as dislocations and interfaces in these processes, (3) to understand the physics of ferroelectric domain walls and the influence of defects on the electrical switching of ferroelectric domains.

  1. Post-deposition control of ferroelastic stripe domains and internal electric field by thermal treatment

    SciTech Connect (OSTI)

    Feigl, L.; Iwanowska, M.; Sandu, C. S.; Setter, N.; Janolin, P.-E.; Yamada, T.

    2015-01-19

    The dependence of the formation of ferroelastic stripe domain patterns on the thermal history is investigated by detailed piezoresponse force microscopy and X-ray diffraction experiments after and during annealing of tensile strained tetragonal Pb(Ti,Zr)O{sub 3} epitaxial thin films on DyScO{sub 3} substrates. In particular, the ferroelastic pattern is reversibly interchanged between a cross-hatched and a stripe domain pattern if the films are cooled at different rates after annealing above the formation temperature of a-domains. Different types of 180 and non-180 patterns can be created, depending on the thermal treatment. The changes in the 180 domain structure and lattice parameters are attributed to a change of oxygen vacancy concentration, which results in a modification of the internal electric field and unit cell size, causing also a shift of T{sub C}. Thermal treatment is done on rhombohedral La:BiFeO{sub 3} thin films as well. It is observed that also in these films, appropriate heat treatment modifies the domain pattern and films with a stripe domain pattern can be created, confirming the general validity of the developed model.

  2. The RCK Domain of the KtrAB K+ Transporter: Multiple Conformations of an Octameric Ring

    SciTech Connect (OSTI)

    Albright,R.; Vazquez Ibar, J.; Kim, C.; Gruner, S.; Morais-Cabral, J.

    2006-01-01

    The KtrAB ion transporter is a complex of the KtrB membrane protein and KtrA, an RCK domain. RCK domains regulate eukaryotic and prokaryotic membrane proteins involved in K{sup +} transport. Conflicting functional models have proposed two different oligomeric arrangements for RCK domains, tetramer versus octamer. Our results for the KtrAB RCK domain clearly show an octamer in solution and in the crystal. We determined the structure of this protein in three different octameric ring conformations that resemble the RCK-domain octamer observed in the MthK potassium channel but show striking differences in size and symmetry. We present experimental evidence for the association between one RCK octameric ring and two KtrB membrane proteins. These results provide insights into the quaternary organization of the KtrAB transporter and its mechanism of activation and show that the RCK-domain octameric ring model is generally applicable to other ion-transport systems.

  3. Cell-penetrating DNA-binding protein as a safe and efficient naked DNA delivery carrier in vitro and in vivo

    SciTech Connect (OSTI)

    Kim, Eun-Sung; Yang, Seung-Woo; Hong, Dong-Ki; Kim, Woo-Taek; Kim, Ho-Guen; Lee, Sang-Kyou

    2010-01-29

    Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 {mu}g of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.

  4. delete me | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    & Publications Paducah Community Relations Plan TEC Working Group Topic Groups Manual Review Key Documents EIS-0407: Amended Notice of Intent to Modify the Scope of the...

  5. U-227: bind-dyndb-ldap DN Escaping Flaw Lets Remote Users Deny Service

    Broader source: Energy.gov [DOE]

    A vulnerability has been reported in bind-dyndb-ldap, which can be exploited by malicious people to cause a DoS (Denial of Service).

  6. V-172: ISC BIND RUNTIME_CHECK Error Lets Remote Users Deny Service Against Recursive Resolvers

    Broader source: Energy.gov [DOE]

    A defect exists which allows an attacker to crash a BIND 9 recursive resolver with a RUNTIME_CHECK error in resolver.c

  7. Ultraviolet laser-induced poling inhibition produces bulk domains in MgO-doped lithium niobate crystals

    SciTech Connect (OSTI)

    Boes, Andreas, E-mail: s3363819@student.rmit.edu.au; Steigerwald, Hendrik; Sivan, Vijay; Mitchell, Arnan [School of Electrical and Computer Engineering, RMIT University, Melbourne, Victoria 3001 (Australia); ARC Center for Ultra-high Bandwidth Devices for Optical Systems (CUDOS), RMIT University, Melbourne, Victoria 3001 (Australia); Yudistira, Didit [School of Electrical and Computer Engineering, RMIT University, Melbourne, Victoria 3001 (Australia); Wade, Scott [Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122 (Australia); Mailis, Sakellaris [Optoelectronics Research Centre, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom); Soergel, Elisabeth [Institute of Physics, University of Bonn, Wegelerstr. 8, 53115 Bonn (Germany)

    2014-09-01

    We report the realization of high-resolution bulk domains achieved using a shallow, structured, domain inverted surface template obtained by UV laser-induced poling inhibition in MgO-doped lithium niobate. The quality of the obtained bulk domains is compared to those of the template and their application for second harmonic generation is demonstrated. The present method enables domain structures with a period length as small as 3??m to be achieved. Furthermore, we propose a potential physical mechanism that leads to the transformation of the surface template into bulk domains.

  8. Single-Molecule Dynamics Reveals Cooperative Binding-Folding in Protein Recognition

    SciTech Connect (OSTI)

    Wang, Jin; Lu, Qiang N.; Lu, H PETER.

    2006-07-01

    The study of associations between two biomolecules is the key to understand molecular recognition and function. Molecular function is often thought to be determined by the underlying structures. Here, combining single molecule study of protein binding with an energy landscape inspired microscopic model, we found strong evidences that bio-molecular recognition is determined by flexibilities in addition to structures. Our model is based on coarse grained molecular dynamics performed on the residue level with the energy function biased towards the native binding structure (Go model). With our model, the underlying free energy landscape of the binding can be explored. Two distinct conformational states as free energy minimum, one with partially folding of CBD and significant binding of CBD to CDC42, and another with native folding of CBD and native binding of CBD to CDC42, are clearly seen. This shows the binding process proceeds with significant interface binding of CBD with CDC42 first without complete folding of CBD. Finally binding and folding are coupled with each other cooperatively to reach the native binding state. The single molecule experimental finding of the dynamic fluctuations between the loosely bound and closely bound conformational states can be identified with theoretically calculated free energy minimum and quantitatively explained in our model as a result of binding associated with large conformational changes. Theoretical predictions have identified certain key residues for binding which are consistent with mutational experiments. The combined study provides a test ground for fundamental mechanisms as well as insights into design and further explorations on biomolecular recognition with large conformational changes.

  9. Structural studies of conformational changes of proteins upon phosphorylation: Structures of activated CheY, CheY-N16-FliM complex, and AAA {sup +} ATPase domain of NtrC1 in both inactive and active states

    SciTech Connect (OSTI)

    Lee, Seok-Yong

    2003-04-10

    Protein phosphorylation is a general mechanism for signal transduction as well as regulation of cellular function. Unlike phosphorylation in eukaryotic systems that uses Ser/Thr for the sites of modification, two-component signal transduction systems, which are prevalent in bacteria, archea, and lower eukaryotes, use an aspartate as the site of phosphorylation. Two-component systems comprise a histidine kinase and a receiver domain. The conformational change of the receiver domain upon phosphorylation leads to signal transfer to the downstream target, a process that had not been understood well at the molecular level. The transient nature of the phospho-Asp bond had made structural studies difficult. The discovery of an excellent analogue for acylphosphate, BeF{sub 3}{sup -}, enabled structural study of activated receiver domains. The structure of activated Chemotaxis protein Y (CheY) was determined both by NMR spectroscopy and X-ray crystallography. These structures revealed the molecular basis of the conformational change that is coupled to phosphorylation. Phosphorylation of the conserved Asp residue in the active site allows hydrogen bonding of the T87 O{gamma} to phospho-aspartate, which in turn leads to the rotation of Y106 into the ''in'' position (termed Y-T coupling). The structure of activated CheY complexed with the 16 N-terminal residues of FliM (N16-FliM), its target, was also determined by X-ray crystallography and confirmed the proposed mechanism of activation (Y-T coupling). First, N16-FliM binds to the region on CheY that undergoes a significant conformational change. Second, the ''in'' position of Y106 presents a better binding surface for FliM because the sidechain of Y106 in the inactive form of CheY (''out'' position) sterically interferes with binding of N16-FliM. In addition to confirmation of Y-T coupling, the structure of the activated CheY-N16-FliM complex suggested that the N16-FliM might be sandwiched between CheY and the remainder of FliM to change the direction of flagellar rotation.

  10. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    SciTech Connect (OSTI)

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  11. Ionic field effect and memristive phenomena in single-point ferroelectric domain switching

    SciTech Connect (OSTI)

    Ievlev, Anton; Morozovska, A. N.; Eliseev, E. A.; Shur, Vladimir Ya.; Kalinin, Sergei V

    2014-01-01

    Electric field induced polarization switching underpins most functional applications of ferroelectric materials in information technology, materials science, and optoelectronics. In the last 20 years, much attention has been focused on the switching of individual domains using scanning probe microscopy, both as model of ferroelectric data storage and approach to explore fundamental physics of ferroelectric switching. The classical picture of tip induced switching includes formation of cylindrical domain oriented along the tip field, with the domain size is largely determined by the tip-induced field distribution and domain wall motion kinetics. The polarization screening is recognized as a necessary precondition to the stability of ferroelectric phase; however, screening processes are generally considered to be uniformly efficient and not leading to changes in switching behavior. Here, we demonstrate that single-point tip-induced polarization switching can give rise to a surprisingly broad range of domain morphologies, including radial and angular instabilities. These behaviors are traced to the surface screening charge dynamics, which in some cases can even give rise to anomalous switching against the electric field (ionic field effect). The implications of these behaviors for ferroelectric materials and devices are discussed.

  12. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    SciTech Connect (OSTI)

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang Karam, George

    2006-11-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity.

  13. Domain-Specific Languages For Developing and Deploying Signature Discovery Workflows

    SciTech Connect (OSTI)

    Jacob, Ferosh; Wynne, Adam S.; Liu, Yan; Gray, Jeff

    2013-12-02

    Domain-agnostic Signature Discovery entails scientific investigation across multiple domains through the re-use of existing algorithms into workflows. The existing algorithms may be written in any programming language for various hardware architectures (e.g., desktops, commodity clusters, and specialized parallel hardware platforms). This raises an engineering issue in generating Web services for heterogeneous algorithms so that they can be composed into a scientific workflow environment (e.g., Taverna). In this paper, we present our software tool that defines two simple Domain-Specific Languages (DSLs) to automate these processes: SDL and WDL. Our Service Description Language (SDL) describes key elements of a signature discovery algorithm and generates the service code. The Workflow Description Language (WDL) describes the pipeline of services and generates deployable artifacts for the Taverna workflow management system. We demonstrate our tool with a landscape classification example that is represented by BLAST workflows composed of services that wrap original scripts.

  14. Lattice QCD with Domain Decomposition on Intel Xeon Phi Co-Processors

    SciTech Connect (OSTI)

    Heybrock, Simon; Joo, Balint; Kalamkar, Dhiraj D.; Smelyanskiy, Mikhail; Vaidyanathan, Karthikeyan; Wettig, Tilo; Dubey, Pradeep

    2014-12-01

    The gap between the cost of moving data and the cost of computing continues to grow, making it ever harder to design iterative solvers on extreme-scale architectures. This problem can be alleviated by alternative algorithms that reduce the amount of data movement. We investigate this in the context of Lattice Quantum Chromodynamics and implement such an alternative solver algorithm, based on domain decomposition, on Intel Xeon Phi co-processor (KNC) clusters. We demonstrate close-to-linear on-chip scaling to all 60 cores of the KNC. With a mix of single- and half-precision the domain-decomposition method sustains 400-500 Gflop/s per chip. Compared to an optimized KNC implementation of a standard solver [1], our full multi-node domain-decomposition solver strong-scales to more nodes and reduces the time-to-solution by a factor of 5.

  15. Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme Print Wednesday, 31 May 2006 00:00 The rate and intensity of calcium (Ca2+) currents that oscillate through the plasma membrane around a cell affect such diverse phenomena as fertilization, the cardiac rhythm, and even the formation of memories. How does the cell sense these digital oscillations and transduce them into a cellular signal, such as changes in

  16. Gravitational waves from domain walls in the next-to-minimal supersymmetric standard model

    SciTech Connect (OSTI)

    Kadota, Kenji; Kawasaki, Masahiro; Saikawa, Ken’ichi

    2015-10-16

    The next-to-minimal supersymmetric standard model predicts the formation of domain walls due to the spontaneous breaking of the discrete Z{sub 3}-symmetry at the electroweak phase transition, and they collapse before the epoch of big bang nucleosynthesis if there exists a small bias term in the potential which explicitly breaks the discrete symmetry. Signatures of gravitational waves produced from these unstable domain walls are estimated and their parameter dependence is investigated. It is shown that the amplitude of gravitational waves becomes generically large in the decoupling limit, and that their frequency is low enough to be probed in future pulsar timing observations.

  17. Electric field driven magnetic domain wall motion in ferromagnetic-ferroelectric heterostructures

    SciTech Connect (OSTI)

    Van de Wiele, Ben; Laurson, Lasse; Franke, Kvin J. A.; Dijken, Sebastiaan van

    2014-01-06

    We investigate magnetic domain wall (MDW) dynamics induced by applied electric fields in ferromagnetic-ferroelectric thin-film heterostructures. In contrast to conventional driving mechanisms where MDW motion is induced directly by magnetic fields or electric currents, MDW motion arises here as a result of strong pinning of MDWs onto ferroelectric domain walls (FDWs) via local strain coupling. By performing extensive micromagnetic simulations, we find several dynamical regimes, including instabilities such as spin wave emission and complex transformations of the MDW structure. In all cases, the time-averaged MDW velocity equals that of the FDW, indicating the absence of Walker breakdown.

  18. Crystal Structure of the Glutamate Receptor Glua1 N-Terminal Domain

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect the Glutamate Receptor Glua1 N-Terminal Domain Citation Details In-Document Search Title: Crystal Structure of the Glutamate Receptor Glua1 N-Terminal Domain Authors: Yao, G. ; Zong, Y. ; Gu, S. ; Zhou, J. ; Xu, H. ; Mathews, I.I. ; Jin, R. ; , Publication Date: 2013-09-13 OSTI Identifier: 1092804 Report Number(s): SLAC-REPRINT-2013-700 DOE Contract Number: AC02-76SF00515 Resource Type: Journal Article Resource Relation: Journal Name: Biochem. J.

  19. Crystal structure of the Nod1 caspase activation and recruitment domain

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Crystal structure of the Nod1 caspase activation and recruitment domain Citation Details In-Document Search Title: Crystal structure of the Nod1 caspase activation and recruitment domain Authors: Coussens, N.P. ; Mowers, J.C. ; McDonald, C. ; Nunez, G. ; Ramaswamy, S. [1] ; LRI) [2] ; Michigan-Med) [2] + Show Author Affiliations (Iowa) ( Publication Date: 2015-09-02 OSTI Identifier: 1213704 Resource Type:

  20. Cytoplasmic Domain Structures of Kir2.1 and Kir3.1 Shows Sites for

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Modulating Gating and Rectification Cytoplasmic Domain Structures of Kir2.1 and Kir3.1 Shows Sites for Modulating Gating and Rectification Scott Pegan1, Christine Arrabit2, Wei Zhou1, Witek Kwiatkowski1, Anthony Collins3, Paul Slesinger2 and Senyon Choe1 Structural Biology1 and Peptide Biology2 Laboratories, The Salk Institute, La Jolla, Ca 92037; Department of Pharmaceutical Sciences3, College of Pharmacy, Oregon State University, Corvallis, OR 97331 Figure 1. Kir2.1 cytoplasmic domain's

  1. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Wednesday, 27 August 2008 00:00 Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core.

  2. TU-C-17A-05: Dose Domain Optimization of MLC Leaf Patterns for Highly

    Office of Scientific and Technical Information (OSTI)

    Complicated 4Ï€ IMRT Plans (Journal Article) | SciTech Connect TU-C-17A-05: Dose Domain Optimization of MLC Leaf Patterns for Highly Complicated 4Ï€ IMRT Plans Citation Details In-Document Search Title: TU-C-17A-05: Dose Domain Optimization of MLC Leaf Patterns for Highly Complicated 4Ï€ IMRT Plans Purpose: Highly conformal non-coplanar 4π radiotherapy plans typically require more than 20 intensity-modulated fields to deliver. A novel method to calculate multileaf collimator (MLC)

  3. NMR studies of DNA oligomers and their interactions with minor groove binding ligands

    SciTech Connect (OSTI)

    Fagan, P A

    1996-05-01

    The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I{center_dot}C base pairs are functional analogs of A{center_dot}T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

  4. Assessing Energetic Contributions to Binding from a Disordered Region in a Protein-Protein Interaction

    SciTech Connect (OSTI)

    S Cho; C Swaminathan; D Bonsor; M Kerzic; R Guan; J Yang; C Kieke; P Anderson; D Kranz; et al.

    2011-12-31

    Many functional proteins are at least partially disordered prior to binding. Although the structural transitions upon binding of disordered protein regions can influence the affinity and specificity of protein complexes, their precise energetic contributions to binding are unknown. Here, we use a model protein-protein interaction system in which a locally disordered region has been modified by directed evolution to quantitatively assess the thermodynamic and structural contributions to binding of disorder-to-order transitions. Through X-ray structure determination of the protein binding partners before and after complex formation and isothermal titration calorimetry of the interactions, we observe a correlation between protein ordering and binding affinity for complexes along this affinity maturation pathway. Additionally, we show that discrepancies between observed and calculated heat capacities based on buried surface area changes in the protein complexes can be explained largely by heat capacity changes that would result solely from folding the locally disordered region. Previously developed algorithms for predicting binding energies of protein-protein interactions, however, are unable to correctly model the energetic contributions of the structural transitions in our model system. While this highlights the shortcomings of current computational methods in modeling conformational flexibility, it suggests that the experimental methods used here could provide training sets of molecular interactions for improving these algorithms and further rationalizing molecular recognition in protein-protein interactions.

  5. Effects of twin boundary mobility on domain microstructure evolution in magnetic shape memory alloys: Phase field simulation

    SciTech Connect (OSTI)

    Jin, Yongmei M.

    2009-02-09

    Effects of twin boundary mobility on domain microstructure evolution during magnetic field-induced deformation in magnetic shape memory alloys are studied by phase field micromagnetic microelastic modeling. The simulations show that different twin boundary mobilities lead to drastically different domain microstructures and evolution pathways, yielding very different magnetization and strain responses, even with opposite signs. The study also reveals complex domain phenomena in magnetic shape memory alloys.

  6. Method for detecting binding events using micro-X-ray fluorescence spectrometry

    DOE Patents [OSTI]

    Warner, Benjamin P. (Los Alamos, NM); Havrilla, George J. (Los Alamos, NM); Mann, Grace (Hong Kong, HK)

    2010-12-28

    Method for detecting binding events using micro-X-ray fluorescence spectrometry. Receptors are exposed to at least one potential binder and arrayed on a substrate support. Each member of the array is exposed to X-ray radiation. The magnitude of a detectable X-ray fluorescence signal for at least one element can be used to determine whether a binding event between a binder and a receptor has occurred, and can provide information related to the extent of binding between the binder and receptor.

  7. X-ray crystallographic analysis of adipocyte fatty acid binding protein

    Office of Scientific and Technical Information (OSTI)

    (aP2) modified with 4-hydroxy-2-nonenal (Journal Article) | SciTech Connect X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal Citation Details In-Document Search Title: X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal Fatty acid binding proteins (FABP) have been characterized as facilitating the intracellular solubilization and transport of long-chain fatty acyl

  8. Configuration of ripple domains and their topological defects formed under local mechanical stress on hexagonal monolayer graphene

    SciTech Connect (OSTI)

    Park, Yeonggu; Choi, Jin Sik; Choi, Taekjib; Lee, Mi Jung; Jia, Quanxi; Park, Minwoo; Lee, Hoonkyung; Park, Bae Ho

    2015-03-24

    Ripples in graphene are extensively investigated because they ensure the mechanical stability of two-dimensional graphene and affect its electronic properties. They arise from spontaneous symmetry breaking and are usually manifested in the form of domains with long-range order. It is expected that topological defects accompany a material exhibiting long-range order, whose functionality depends on characteristics of domains and topological defects. However, there remains a lack of understanding regarding ripple domains and their topological defects formed on monolayer graphene. Here we explore configuration of ripple domains and their topological defects in exfoliated monolayer graphenes on SiO?/Si substrates using transverse shear microscope. We observe three-color domains with three different ripple directions, which meet at a core. Furthermore, the closed domain is surrounded by an even number of cores connected together by domain boundaries, similar to topological vortex and anti-vortex pairs. In addition, we have found that axisymmetric three-color domains can be induced around nanoparticles underneath the graphene. This fascinating configuration of ripple domains may result from the intrinsic hexagonal symmetry of two-dimensional graphene, which is supported by theoretical simulation using molecular dynamics. Our findings are expected to play a key role in understanding of ripple physics in graphene and other two-dimensional materials.

  9. Configuration of ripple domains and their topological defects formed under local mechanical stress on hexagonal monolayer graphene

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Park, Yeonggu; Choi, Jin Sik; Choi, Taekjib; Lee, Mi Jung; Jia, Quanxi; Park, Minwoo; Lee, Hoonkyung; Park, Bae Ho

    2015-03-24

    Ripples in graphene are extensively investigated because they ensure the mechanical stability of two-dimensional graphene and affect its electronic properties. They arise from spontaneous symmetry breaking and are usually manifested in the form of domains with long-range order. It is expected that topological defects accompany a material exhibiting long-range order, whose functionality depends on characteristics of domains and topological defects. However, there remains a lack of understanding regarding ripple domains and their topological defects formed on monolayer graphene. Here we explore configuration of ripple domains and their topological defects in exfoliated monolayer graphenes on SiO₂/Si substrates using transverse shear microscope.more » We observe three-color domains with three different ripple directions, which meet at a core. Furthermore, the closed domain is surrounded by an even number of cores connected together by domain boundaries, similar to topological vortex and anti-vortex pairs. In addition, we have found that axisymmetric three-color domains can be induced around nanoparticles underneath the graphene. This fascinating configuration of ripple domains may result from the intrinsic hexagonal symmetry of two-dimensional graphene, which is supported by theoretical simulation using molecular dynamics. Our findings are expected to play a key role in understanding of ripple physics in graphene and other two-dimensional materials.« less

  10. Investigation of the mode of binding of a novel series ofN-benzyl...

    Office of Scientific and Technical Information (OSTI)

    of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select...

  11. Capture and release of acid-gasses with acid-gas binding organic compounds

    DOE Patents [OSTI]

    Heldebrant, David J; Yonker, Clement R; Koech, Phillip K

    2015-03-17

    A system and method for acid-gas capture wherein organic acid-gas capture materials form hetero-atom analogs of alkyl-carbonate when contacted with an acid gas. These organic-acid gas capture materials include combinations of a weak acid and a base, or zwitterionic liquids. This invention allows for reversible acid-gas binding to these organic binding materials thus allowing for the capture and release of one or more acid gases. These acid-gas binding organic compounds can be regenerated to release the captured acid gasses and enable these organic acid-gas binding materials to be reused. This enables transport of the liquid capture compounds and the release of the acid gases from the organic liquid with significant energy savings compared to current aqueous systems.

  12. Novel CO2 Binding Mechanism Determined via in-situ Absorption Spectroscopy

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    & Theory | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Novel CO2 Binding Mechanism Determined via in-situ Absorption Spectroscopy & Theory

  13. Metal binding in an aluminum based metal-organic framework for carbon

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    dioxide capture | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Metal binding in an aluminum based metal-organic framework for carbon dioxide capture

  14. Developing Adnectins That Target SRC Co-Activator Binding to PXR: A

    Office of Scientific and Technical Information (OSTI)

    Structural Approach toward Understanding Promiscuity of PXR (Journal Article) | SciTech Connect Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Citation Details In-Document Search Title: Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Authors: Khan, Javed A. ; Camac, Daniel M. ; Low, Simon ; Tebben, Andrew J. ; Wensel, David L. ;

  15. Discovery of a new ATP-binding motif involved in peptidic azoline

    Office of Scientific and Technical Information (OSTI)

    biosynthesis (Journal Article) | SciTech Connect Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Citation Details In-Document Search Title: Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Authors: Dunbar, Kyle L. ; Chekan, Jonathan R. ; Cox, Courtney L. ; Burkhart, Brandon J. ; Nair, Satish K. ; Mitchell , Douglas A. [1] + Show Author Affiliations (UIUC) Publication Date: 2014-11-20 OSTI Identifier: 1163365 Resource Type: Journal

  16. Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived

    Office of Scientific and Technical Information (OSTI)

    Phosphopeptide in Its Vestigial Active Site (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived Phosphopeptide in Its Vestigial Active Site Citation Details In-Document Search Title: Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived Phosphopeptide in Its Vestigial Active Site Authors: Qiu, Chen ; Lienhard, Susanne ; Hynes, Nancy E. ; Badache, Ali ; Leahy, Daniel

  17. The same pocket in menin binds both MLL and JUND but has opposite effects

    Office of Scientific and Technical Information (OSTI)

    on transcription (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription Citation Details In-Document Search Title: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is

  18. Designing artificial metal binding peptides | Center for Bio-Inspired Solar

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Fuel Production artificial metal binding peptides 24 Oct 2012 Dong Wang is a graduate student in the Department of Chemistry and Biochemistry at Arizona State University. He is working in the lab of Professor James Allen, who is leading the Subtask 2 of the Bisfuel Center (Water oxidation catalysts). Dong's research project is focused on design and characterization of artificial peptides capable of binding divalent metals with the aim to construct an efficient water oxidation catalyst that

  19. U-039: ISC Update: BIND 9 Resolver crashes after logging an error in query.c

    Broader source: Energy.gov [DOE]

    A remote server can cause the target connected client to crash. Organizations across the Internet are reporting crashes interrupting service on BIND 9 nameservers performing recursive queries. Affected servers crash after logging an error in query.c with the following message: "INSIST(! dns_rdataset_isassociated(sigrdataset))" Multiple versions are reported as being affected, including all currently supported release versions of ISC BIND 9. ISC is actively investigating the root cause and working to produce patches which avoid the crash.

  20. U-038: BIND 9 Resolver crashes after logging an error in query.c

    Broader source: Energy.gov [DOE]

    A remote server can cause the target connected client to crash. Organizations across the Internet are reporting crashes interrupting service on BIND 9 nameservers performing recursive queries. Affected servers crash after logging an error in query.c with the following message: "INSIST(! dns_rdataset_isassociated(sigrdataset))" Multiple versions are reported as being affected, including all currently supported release versions of ISC BIND 9. ISC is actively investigating the root cause and working to produce patches which avoid the crash.

  1. Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus

    SciTech Connect (OSTI)

    Borbulevych, Oleg; Kumarasiri, Malika; Wilson, Brian; Llarrull1, Leticia I.; Lee, Mijoon; Hesek, Dusan; Shi, Qicun; Peng, Jeffrey; Baker, Brian M.; Mobashery, Shahriar

    2012-10-29

    The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of {beta}-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N{sup {zeta}}-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N{sup {zeta}}-decarboxylation. This unique process, termed the lysine N{sup {zeta}}-decarboxylation switch, arrests the sensor domain in the activated ('on') state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus.

  2. Magnetic domain structure and domain-wall energy in UFe{sub 8}Ni{sub 2}Si{sub 2} and UFe{sub 6}Ni{sub 4}Si{sub 2} intermetallic compounds

    SciTech Connect (OSTI)

    Wyslocki, J.J.; Suski, W.; Wochowski, K.

    1994-03-01

    Magnetic domain structures in the UFe{sub 8}Ni{sub 2}Si{sub 2} and UFe{sub 6}Ni{sub 4}Si{sub 2} compounds were studied using the powder pattern method. The domain structure observed is typical for uniaxial materials. The domain-wall energy density {gamma} was determined from the average surface domain width D{sub s} observed on surfaces perpendicular to the easy axis as equal to 16 erg/cm{sup 2} for UFe{sub 8}Ni{sub 2}Si{sub 2} and 10 erg/cm{sup 2} for UFe{sub 6}Ni{sub 4}Si{sub 2}. Moreover, the critical diameter for single domain particle D{sub c} was calculated for the studied compounds.

  3. Oligomycin frames a common drug-binding site in the ATP synthase

    SciTech Connect (OSTI)

    Symersky, Jindrich; Osowski, Daniel; Walters, D. Eric; Mueller, David M.

    2015-12-01

    We report the high-resolution (1.9 {angstrom}) crystal structure of oligomycin bound to the subunit c10 ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c10 ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common 'drug-binding site.' We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

  4. Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs

    SciTech Connect (OSTI)

    Leung, F.C.; Bohn, L.R.; Dagle, G.E. )

    1991-04-01

    The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using {sup 125}I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

  5. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    SciTech Connect (OSTI)

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo; Tabaei, Seyed M.H. [Prostate Centre at the Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6 (Canada); Miguel-Queralt, Solange; Underhill, Caroline [Department of Obstetrics and Gynecology, University of British Columbia, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4 (Canada); Cherkasov, Artem [Prostate Centre at the Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6 (Canada)], E-mail: artc@interchange.ubc.ca; Hammond, Geoffrey L. [Department of Obstetrics and Gynecology, University of British Columbia, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4 (Canada)

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.

  6. Evidence for small-molecule-mediated loop stabilization in the structure of the isolated Pin1 WW domain

    SciTech Connect (OSTI)

    Mortenson, David E.; Kreitler, Dale F.; Yun, Hyun Gi; Gellman, Samuel H., E-mail: gellman@chem.wisc.edu; Forest, Katrina T., E-mail: gellman@chem.wisc.edu [University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2013-12-01

    Two structures of a small protein with a defined tertiary fold, the isolated Pin1 WW domain, have been determined via racemic crystallization with small-molecule additives. These additives, which are either racemic or achiral, appear to stabilize a dynamic loop region of the structure. The human Pin1 WW domain is a small autonomously folding protein that has been useful as a model system for biophysical studies of ?-sheet folding. This domain has resisted previous attempts at crystallization for X-ray diffraction studies, perhaps because of intrinsic conformational flexibility that interferes with the formation of a crystal lattice. Here, the crystal structure of the human Pin1 WW domain has been obtained via racemic crystallization in the presence of small-molecule additives. Both enantiomers of a 36-residue variant of the Pin1 WW domain were synthesized chemically, and the l- and d-polypeptides were combined to afford diffracting crystals. The structural data revealed packing interactions of small carboxylic acids, either achiral citrate or a d,l mixture of malic acid, with a mobile loop region of the WW-domain fold. These interactions with solution additives may explain our success in crystallization of this protein racemate. Molecular-dynamics simulations starting from the structure of the Pin1 WW domain suggest that the crystal structure closely resembles the conformation of this domain in solution. The structural data presented here should provide a basis for further studies of this important model system.

  7. Temperature dependence of carrier spin polarization determined from current-induced domain wall motion in a Co/Ni nanowire

    SciTech Connect (OSTI)

    Ueda, K.; Koyama, T.; Hiramatsu, R.; Kobayashi, K.; Ono, T.; Chiba, D.; Fukami, S.; Tanigawa, H.; Suzuki, T.; Ohshima, N.; Ishiwata, N.; Nakatani, Y.

    2012-05-14

    We have investigated the temperature dependence of the current-induced magnetic domain wall (DW) motion in a perpendicularly magnetized Co/Ni nanowire at various temperatures and with various applied currents. The carrier spin polarization was estimated from the measured domain wall velocity. We found that it decreased more with increasing temperature from 100 K to 530 K than the saturation magnetization did.

  8. Fast multiscale Gaussian beam methods for wave equations in bounded convex domains

    SciTech Connect (OSTI)

    Bao, Gang; Department of Mathematics, Michigan State University, East Lansing, MI 48824 ; Lai, Jun; Qian, Jianliang

    2014-03-15

    Motivated by fast multiscale Gaussian wavepacket transforms and multiscale Gaussian beam methods which were originally designed for pure initial-value problems of wave equations, we develop fast multiscale Gaussian beam methods for initial boundary value problems of wave equations in bounded convex domains in the high frequency regime. To compute the wave propagation in bounded convex domains, we have to take into account reflecting multiscale Gaussian beams, which are accomplished by enforcing reflecting boundary conditions during beam propagation and carrying out suitable reflecting beam summation. To propagate multiscale beams efficiently, we prove that the ratio of the squared magnitude of beam amplitude and the beam width is roughly conserved, and accordingly we propose an effective indicator to identify significant beams. We also prove that the resulting multiscale Gaussian beam methods converge asymptotically. Numerical examples demonstrate the accuracy and efficiency of the method.

  9. Work Domain Analysis Methodology for Development of Operational Concepts for Advanced Reactors

    SciTech Connect (OSTI)

    Hugo, Jacques

    2015-05-01

    This report describes a methodology to conduct a Work Domain Analysis in preparation for the development of operational concepts for new plants. This method has been adapted from the classical method described in the literature in order to better deal with the uncertainty and incomplete information typical of first-of-a-kind designs. The report outlines the strategy for undertaking a Work Domain Analysis of a new nuclear power plant and the methods to be used in the development of the various phases of the analysis. Basic principles are described to the extent necessary to explain why and how the classical method was adapted to make it suitable as a tool for the preparation of operational concepts for a new nuclear power plant. Practical examples are provided of the systematic application of the method and the various presentation formats in the operational analysis of advanced reactors.

  10. A Moving Window Technique in Parallel Finite Element Time Domain Electromagnetic Simulation

    SciTech Connect (OSTI)

    Lee, Lie-Quan; Candel, Arno; Ng, Cho; Ko, Kwok; ,

    2010-06-07

    A moving window technique for the finite element time domain (FETD) method is developed to simulate the propagation of electromagnetic waves induced by the transit of a charged particle beam inside large and long structures. The window moving along with the beam in the computational domain adopts high-order finite-element basis functions through p refinement and/or a high-resolution mesh through h refinement so that a sufficient accuracy is attained with substantially reduced computational costs. Algorithms to transfer discretized fields from one mesh to another, which are the key to implementing a moving window in a finite-element unstructured mesh, are presented. Numerical experiments are carried out using the moving window technique to compute short-range wakefields in long accelerator structures. The results are compared with those obtained from the normal FETD method and the advantages of using the moving window technique are discussed.

  11. Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme Print The rate and intensity of calcium (Ca2+) currents that oscillate through the plasma membrane around a cell affect such diverse phenomena as fertilization, the cardiac rhythm, and even the formation of memories. How does the cell sense these digital oscillations and transduce them into a cellular signal, such as changes in phosphorylation (addition of a phosphate group to a protein) or gene transcription? A group from the

  12. Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure of the Kinase Domain of CaMKII and Modeling the Holoenzyme Print The rate and intensity of calcium (Ca2+) currents that oscillate through the plasma membrane around a cell affect such diverse phenomena as fertilization, the cardiac rhythm, and even the formation of memories. How does the cell sense these digital oscillations and transduce them into a cellular signal, such as changes in phosphorylation (addition of a phosphate group to a protein) or gene transcription? A group from the

  13. Field-driven Polarization and Domain Dynamics of Ferroelectric/Dielectric

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Superlattices | Stanford Synchrotron Radiation Lightsource Field-driven Polarization and Domain Dynamics of Ferroelectric/Dielectric Superlattices Thursday, March 1, 2012 - 10:00am SSRL Conference Room 137-226 Paul G. Evans, Materials Science and Engineering, University of Wisconsin-Madison The atomic-scale periodicity of ferroelectric/dielectric superlattices leads to an exciting variety of structural and dynamic effects in applied electric fields. The richness of these phenomena arises in

  14. Time domain analysis of a gyrotron traveling wave amplifier with misaligned electron beam

    SciTech Connect (OSTI)

    Wang, Qiushi Peng, Shuyuan; Luo, Jirun

    2014-08-15

    This article develops a time-domain theory to study the beam-wave interaction in gyrotron traveling wave amplifier (gyro-TWA) with a misaligned electron beam. The effects of beam misalignment on the TE{sub 01} mode gyro-TWA operating at the fundamental are discussed. Numerical results show that the effect of misalignment is less obvious when the input power is larger, and the influences of misalignment on the stable gain and the stable time are basically opposite.

  15. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This alsomore » represents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.« less

  16. DNA polymerase with modified processivity

    DOE Patents [OSTI]

    Bedford, Ella; Tabor, Stanley; Richardson, Charles C.

    1999-01-01

    Chimeric DNA polymerase having a DNA polymerase domain and processivity factor binding domain not naturally associated with DNA polymerase domain.

  17. Crystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220)

    SciTech Connect (OSTI)

    Zorn, Julie A.; Wang, Qi; Fujimura, Eric; Barros, Tiago; Kuriyan, John; Boggon, Titus J.

    2015-04-02

    More than 30% of acute myeloid leukemia (AML) patients possess activating mutations in the receptor tyrosine kinase FMS-like tyrosine kinase 3 or FLT3. A small-molecule inhibitor of FLT3 (known as quizartinib or AC220) that is currently in clinical trials appears promising for the treatment of AML. Here, we report the co-crystal structure of the kinase domain of FLT3 in complex with quizartinib. FLT3 with quizartinib bound adopts an “Abl-like” inactive conformation with the activation loop stabilized in the “DFG-out” orientation and folded back onto the kinase domain. This conformation is similar to that observed for the uncomplexed intracellular domain of FLT3 as well as for related receptor tyrosine kinases, except for a localized induced fit in the activation loop. The co-crystal structure reveals the interactions between quizartinib and the active site of FLT3 that are key for achieving its high potency against both wild-type FLT3 as well as a FLT3 variant observed in many AML patients. This co-complex further provides a structural rationale for quizartinib-resistance mutations.

  18. The HPr Proteins from the Thermophile Bacillus stearothermophilus Can Form Domain-swapped Dimers

    SciTech Connect (OSTI)

    Sridharan, Sudharsan; Razvi, Abbas; Scholtz, J. Martin; Sacchettini, James C. (TAM)

    2010-07-20

    The study of proteins from extremophilic organisms continues to generate interest in the field of protein folding because paradigms explaining the enhanced stability of these proteins still elude us and such studies have the potential to further our knowledge of the forces stabilizing proteins. We have undertaken such a study with our model protein HPr from a mesophile, Bacillus subtilis, and a thermophile, Bacillus stearothermophilus. We report here the high-resolution structures of the wild-type HPr protein from the thermophile and a variant, F29W. The variant proved to crystallize in two forms: a monomeric form with a structure very similar to the wild-type protein as well as a domain-swapped dimer. Interestingly, the structure of the domain-swapped dimer for HPr is very different from that observed for a homologous protein, Crh, from B. subtilis. The existence of a domain-swapped dimer has implications for amyloid formation and is consistent with recent results showing that the HPr proteins can form amyloid fibrils. We also characterized the conformational stability of the thermophilic HPr proteins using thermal and solvent denaturation methods and have used the high-resolution structures in an attempt to explain the differences in stability between the different HPr proteins. Finally, we present a detailed analysis of the solution properties of the HPr proteins using a variety of biochemical and biophysical methods.

  19. Dopant profile modeling by rare event enhanced domain-following molecular dynamics

    DOE Patents [OSTI]

    Beardmore, Keith M. (Santa Fe, NM); Jensen, Niels G. (Davis, CA)

    2002-01-01

    A computer-implemented molecular dynamics-based process simulates a distribution of ions implanted in a semiconductor substrate. The properties of the semiconductor substrate and ion dose to be simulated are first initialized, including an initial set of splitting depths that contain an equal number of virtual ions implanted in each substrate volume determined by the splitting depths. A first ion with selected velocity is input onto an impact position of the substrate that defines a first domain for the first ion during a first timestep, where the first domain includes only those atoms of the substrate that exert a force on the ion. A first position and velocity of the first ion is determined after the first timestep and a second domain of the first ion is formed at the first position. The first ion is split into first and second virtual ions if the first ion has passed through a splitting interval. The process then follows each virtual ion until all of the virtual ions have come to rest. A new ion is input to the surface and the process repeats until all of the ion dose has been input. The resulting ion rest positions form the simulated implant distribution.

  20. Crystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220)

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zorn, Julie A.; Wang, Qi; Fujimura, Eric; Barros, Tiago; Kuriyan, John; Boggon, Titus J.

    2015-04-02

    More than 30% of acute myeloid leukemia (AML) patients possess activating mutations in the receptor tyrosine kinase FMS-like tyrosine kinase 3 or FLT3. A small-molecule inhibitor of FLT3 (known as quizartinib or AC220) that is currently in clinical trials appears promising for the treatment of AML. Here, we report the co-crystal structure of the kinase domain of FLT3 in complex with quizartinib. FLT3 with quizartinib bound adopts an “Abl-like” inactive conformation with the activation loop stabilized in the “DFG-out” orientation and folded back onto the kinase domain. This conformation is similar to that observed for the uncomplexed intracellular domain ofmore » FLT3 as well as for related receptor tyrosine kinases, except for a localized induced fit in the activation loop. The co-crystal structure reveals the interactions between quizartinib and the active site of FLT3 that are key for achieving its high potency against both wild-type FLT3 as well as a FLT3 variant observed in many AML patients. This co-complex further provides a structural rationale for quizartinib-resistance mutations.« less

  1. Modulation of FadR Binding Capacity for Acyl-CoA Fatty Acids Through Structure-Guided Mutagenesis

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Bacik, John-Paul; Yeager, Chris M.; Twary, Scott N.; Martí-Arbona, Ricardo

    2015-09-18

    FadR is a versatile global regulator in Escherichia coli that controls fatty acid metabolism and thereby modulates the ability of this bacterium to grow using fatty acids or acetate as the sole carbon source. FadR regulates fatty acid metabolism in response to intra-cellular concentrations of acyl-CoA lipids. The ability of FadR to bind acyl-CoA fatty acids is hence of significant interest for the engineering of biosynthetic pathways for the production of lipid-based biofuels and commodity chemicals. Based on the available crystal structure of E. coli bound to myristoyl- CoA, we predicted amino acid positions within the effector binding pocket thatmore » would alter the ability of FadR to bind acyl-CoA fatty acids without affecting DNA binding. We utilized fluorescence polarization to characterize the in-vitro binding properties of wild type and mutant FadR. We found that a Leu102Ala mutant enhanced binding of the effector, likely by increasing the size of the binding pocket for the acyl moiety of the molecule. Conversely, the elimination of the guanidine side chain (Arg213Ala and Arg213Met mutants) of the CoA moiety binding site severely diminished the ability of FadR to bind the acyl-CoA effector. These results demonstrate the ability to fine tune FadR binding capacity. The validation of an efficient method to fully characterize all the binding events involved in the specific activity (effector and DNA operator binding) of FadR has allowed us to increase our understanding of the role of specific amino acids in the binding and recognition of acyl-CoA fatty acids and will greatly facilitate efforts aimed at engineering tunable FadR regulators for synthetic biology.« less

  2. Beyond the detergent effect: a binding site for sodium dodecyl sulfate (SDS) in mammalian apoferritin

    SciTech Connect (OSTI)

    Liu, Renyu Bu, Weiming; Xi, Jin; Mortazavi, Shirin R.; Cheung-Lau, Jasmina C.; Dmochowski, Ivan J.; Loll, Patrick J.

    2012-05-01

    Using X-ray crystallography and isothermal titration calorimetry, we show that sodium dodecyl sulfate (SDS) binds specifically to a pre-formed internal cavity in horse-spleen apoferritin. Although sodium dodecyl sulfate (SDS) is widely used as an anionic detergent, it can also exert specific pharmacological effects that are independent of the surfactant properties of the molecule. However, structural details of how proteins recognize SDS are scarce. Here, it is demonstrated that SDS binds specifically to a naturally occurring four-helix bundle protein: horse apoferritin. The X-ray crystal structure of the apoferritinSDS complex was determined at a resolution of 1.9 and revealed that the SDS binds in an internal cavity that has previously been shown to recognize various general anesthetics. A dissociation constant of 24 9 M at 293 K was determined by isothermal titration calorimetry. SDS binds in this cavity by bending its alkyl tail into a horseshoe shape; the charged SDS head group lies in the opening of the cavity at the protein surface. This crystal structure provides insights into the proteinSDS interactions that give rise to binding and may prove useful in the design of novel SDS-like ligands for some proteins.

  3. Protein binding studies of technetium-99m-labeled phosphine and isocyanide cationic complexes

    SciTech Connect (OSTI)

    Zanelli, G.D.; Cook, N.; Lahiri, A.; Ellison, D.; Webbon, P.; Woolley, G.

    1988-01-01

    Most /sup 99m/Tc/phosphine/isocyanide complexes synthesized to date show preferential uptake by the myocardium of many animal species but not in man. A new complex has been synthesized, (/sup 99m/Tc(DEPE)2(CNR)2), +(DEPIC), where R = t - butyl isocyanide, which in three animal species images the myocardium very well, but in humans it remains primarily in the blood pool. One reason for the difference in the behavior of these complexes in different species could be the characteristics of their binding to plasma proteins. The protein binding characteristics of DEPIC and two other well-known complexes have therefore been studied. Whereas the other complexes bind nonspecifically to many proteins both in animal and human plasma, DEPIC binds almost exclusively to prealbumin in humans but nonspecifically to other proteins in the rabbit. The binding sites in human plasma appear to be those normally occupied by thyroxine on the prealbumin tetramer and these can be blocked by sodium salicylate.

  4. Magnetic domain structure in nanocrystalline Ni-Zn-Co spinel ferrite thin films using off-axis electron holography

    SciTech Connect (OSTI)

    Zhang, D.; Ray, N. M.; Petuskey, W. T.; Smith, D. J.; McCartney, M. R.

    2014-08-28

    We report a study of the magnetic domain structure of nanocrystalline thin films of nickel-zinc ferrite. The ferrite films were synthesized using aqueous spin-spray coating at low temperature (?90?C) and showed high complex permeability in the GHz range. Electron microscopy and microanalysis revealed that the films consisted of columnar grains with uniform chemical composition. Off-axis electron holography combined with magnetic force microscopy indicated a multi-grain domain structure with in-plane magnetization. The correlation between the magnetic domain morphology and crystal structure is briefly discussed.

  5. Beta-endorphin and alpha-n-acetyl beta-endorphin; synthesis, conformation and binding parameter

    SciTech Connect (OSTI)

    Lovegren, E.S.

    1986-01-01

    Beta-endorphin (EP) is a 31-residue opioid peptide found in many tissues, including the pituitary, brain and reproductive tract. Alpha-amino-acetyl beta-endorphin (AcEP) was characterized spectroscopically by proton nuclear magnetic resonance (NMR) and circular dichroism in deuterated water and trifluoroethanol (TFE). Both EP and AcEP bind to neuroblastoma N2a cells. This binding was not mediated through opiate receptors, and both peptides seemed to bind at common sites. Ovarian immunoreactive-EP levels were determined for immature and mature rates. These levels were found to be responsive to exogenous gonadotropin treatment in immature animals. A large percentage of the immunoreactive-EP is present in follicular fluid, and most of the endorphin-like peptides were acetylated, as measured by radioimmunoassay. Chromatogaphic analysis suggested at least three EP-like species: EP, a carboxy-terminally cleaved and an amino-terminally acetylated EP.

  6. T-662: ISC BIND Packet Processing Flaw Lets Remote Users Deny Service

    Broader source: Energy.gov [DOE]

    A defect in the affected BIND 9 versions allows an attacker to remotely cause the "named" process to exit using a specially crafted packet. This defect affects both recursive and authoritative servers. The code location of the defect makes it impossible to protect BIND using ACLs configured within named.conf or by disabling any features at compile-time or run-time. A remote attacker would need to be able to send a specially crafted packet directly to a server running a vulnerable version of BIND. There is also the potential for an indirect attack via malware that is inadvertently installed and run, where infected machines have direct access to an organization's nameservers.

  7. Binding of formyl peptides to Walker 256 carcinosarcoma cells and the chemotactic response of these cells

    SciTech Connect (OSTI)

    Rayner, D.C.; Orr, F.W.; Shiu, R.P.

    1985-05-01

    N-Formylmethionylleucylphenylalanine (fMLP) induces chemotaxis in leukocytes, the response being mediated by peptide binding to a receptor on the plasma membrane. In tumor cells, this peptide has been reported to induce cellular swelling and chemotaxis in vitro and to enhance the localization of circulating tumor cells in vivo. In the Boyden chamber, the authors evaluated the migratory responses of Walker carcinosarcoma 256 cells to varying concentrations of fMLP. Sigmoidal dose-response curves were obtained with the dose of chemotactic factor that elicits a half-maximal chemotactic response of 5.0 +/- 2.5 X 10(-8) M. Checkerboard analysis indicated that these responses were dependent upon a concentration gradient of fMLP with increases in migration of circa 2 to 2.5 times that of random movement. To examine the binding of fMLP, the tumor cells were incubated with 5 X 10(-9) M fML-(/sup 3/H)P in Hanks balanced salt solution. Specific binding (0.5 to 1% of total radioligand, to whole cells inhibited by 5 X 10(-6) M fMLP) approached equilibrium after 4 to 6 h at 4 degrees C and after 6 to 10 h at 22 degrees C. Autoradiographic studies demonstrated heterogeneous binding of the peptide by tumor cells and also showed its intracellular localization. In homogenates of Walker cells prepared in 0.1 M Tris HCl, pH 7.4, with 10 mM MgCl2 and bovine serum albumin (1 mg/ml), specific binding of approximately 0.5% of total fML-(/sup 3/H)P reached equilibrium after 60 min at 4 degrees C. In whole cells and homogenates, binding was reversible by addition of unlabeled fMLP.

  8. Photoelectron Spectroscopy and Theoretical Studies of Anion-pi Interactions: Binding Strength and Anion Specificity

    SciTech Connect (OSTI)

    Zhang, Jian; Zhou, Bin; Sun, Zhenrong; Wang, Xue B.

    2015-01-01

    Proposed in theory and confirmed to exist, anion? interactions have been recognized as new and important non-covalent binding forces. Despite extensive theoretical studies, numerous crystal structural identifications, and a plethora of solution phase investigations, intrinsic anion? interaction strengths that are free from complications of condensed phases environments, have not been directly measured in the gas phase. Herein we present a joint photoelectron spectroscopic and theoretical study on this subject, in which tetraoxacalix[2]arene[2]triazine 1, an electron-deficient and cavity self-tunable macrocyclic was used as a charge-neutral molecular host to probe its interactions with a series of anions with distinctly different shapes and charge states (spherical halides Cl?, Br?, I?, linear thiocyanate SCN?, trigonal planar nitrate NO??, pyramidic iodate IO??, and tetrahedral sulfate SO??). The binding energies of the resultant gaseous 1:1 complexes (1Cl?,1Br?, 1I?, 1SCN?, 1NO??, 1IO?? and 1SO??) were directly measured experimentally, exhibiting substantial non-covalent interactions with pronounced anion specific effects. The binding strengths of Cl?, NO??, IO?? with 1 are found to be strongest among all singly charged anions, amounting to ca. 30 kcal/mol, but only about 40% of that between 1 and SO??. Quantum chemical calculations reveal that all anions reside in the center of the cavity of 1 with anion? binding motif in the complexes optimized structures, where 1 is seen to be able to self-regulate its cavity structure to accommodate anions of different geometries and three-dimensional shapes. Electron density surface and natural bond orbital charge distribution analysis further support anion? binding formation. The calculated binding energies of the anions and 1 nicely reproduce the experimentally estimated electron binding energy increase. This work illustrates that size-selective photoelectron spectroscopy combined with theoretical calculations represent a powerful technique to probe intrinsic anion? interactions and has potential to provide quantitative guest-host molecular binding strengths and unravel fundamental insights in specific anion recognitions.

  9. De novo Design of an Artificial bis-[4Fe4S] Binding Protein

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    De novo Design of an Artificial bis-[4Fe4S] Binding Protein Authors: Roy, A,, Sarrou, I., Vaughn, M.D., Astashkin, A.V., and Ghirlanda, G. Title: De novo Design of an Artificial bis-[4Fe4S] Binding Protein Source: Biochemistry Year: 2013 Volume: 52 Pages: 7586-7594 ABSTRACT: In nature, protein subunits containing multiple iron-sulfur clusters often mediate the delivery of reducing equivalents from metabolic pathways to the active site of redox proteins. The de novo design of redox active

  10. Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6 Citation Details In-Document Search Title: Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6 Authors: Ahn, Victoria E. ; Chu, Matthew Ling-Hon ; Choi, Hee-Jung ; Tran, Denise ; Abo, Arie ; Weis, William I. Publication Date: 2011-11-01 OSTI Identifier: 1198118 Type: Published Article Journal Name: Developmental Cell Additional Journal Information: Journal Volume: 21;

  11. Structural Studies of Wnts and Identification of an LRP6 Binding Site

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Structural Studies of Wnts and Identification of an LRP6 Binding Site Citation Details In-Document Search Title: Structural Studies of Wnts and Identification of an LRP6 Binding Site Authors: Chu, Matthew Ling-Hon ; Ahn, Victoria E. ; Choi, Hee-Jung ; Daniels, Danette L. ; Nusse, Roel ; Weis, William I. ; , Publication Date: 2014-05-13 OSTI Identifier: 1131442 Report Number(s): SLAC-REPRINT-2014-111 DOE Contract Number: AC02-76SF00515 Resource Type:

  12. Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind

    Office of Scientific and Technical Information (OSTI)

    to Munc18a in a Closed Conformation (Journal Article) | SciTech Connect Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind to Munc18a in a Closed Conformation Citation Details In-Document Search Title: Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind to Munc18a in a Closed Conformation Authors: Colbert, Karen N. ; Hattendorf, Douglas A. ; Weiss, Thomas M. ; Burkhardt, Pawel ; Fasshauer, Dirk ; Weis, William I. Publication Date: 2014-05-13 OSTI

  13. Quantitative broadband absorption and scattering spectroscopy in turbid media by combined frequency-domain and steady state methodologies

    DOE Patents [OSTI]

    Tromberg, Bruce J.; Berger, Andrew J.; Cerussi, Albert E.; Bevilacqua, Frederic; Jakubowski, Dorota

    2008-09-23

    A technique for measuring broadband near-infrared absorption spectra of turbid media that uses a combination of frequency-domain and steady-state reflectance methods. Most of the wavelength coverage is provided by a white-light steady-state measurement, whereas the frequency-domain data are acquired at a few selected wavelengths. Coefficients of absorption and reduced scattering derived from the frequency-domain data are used to calibrate the intensity of the steady-state measurements and to determine the reduced scattering coefficient at all wavelengths in the spectral window of interest. The absorption coefficient spectrum is determined by comparing the steady-state reflectance values with the predictions of diffusion theory, wavelength by wavelength. Absorption spectra of a turbid phantom and of human breast tissue in vivo, derived with the combined frequency-domain and steady-state technique, agree well with expected reference values.

  14. Control of domain wall pinning by localised focused Ga {sup +} ion irradiation on Au capped NiFe nanowires

    SciTech Connect (OSTI)

    Burn, D. M. Atkinson, D.

    2014-10-28

    Understanding domain wall pinning and propagation in nanowires are important for future spintronics and nanoparticle manipulation technologies. Here, the effects of microscopic local modification of the magnetic properties, induced by focused-ion-beam intermixing, in NiFe/Au bilayer nanowires on the pinning behavior of domain walls was investigated. The effects of irradiation dose and the length of the irradiated features were investigated experimentally. The results are considered in the context of detailed quasi-static micromagnetic simulations, where the ion-induced modification was represented as a local reduction of the saturation magnetization. Simulations show that domain wall pinning behavior depends on the magnitude of the magnetization change, the length of the modified region, and the domain wall structure. Comparative analysis indicates that reduced saturation magnetisation is not solely responsible for the experimentally observed pinning behavior.

  15. A portable time-domain LED fluorimeter for nanosecond fluorescence lifetime measurements

    SciTech Connect (OSTI)

    Wang, Hongtao; Salthouse, Christopher D.; Qi, Ying; Mountziaris, T. J.; Chemical Engineering Department, University of Massachusetts, Amherst, Massachusetts 01003

    2014-05-15

    Fluorescence lifetime measurements are becoming increasingly important in chemical and biological research. Time-domain lifetime measurements offer fluorescence multiplexing and improved handling of interferers compared with the frequency-domain technique. In this paper, an all solid-state, filterless, and highly portable light-emitting-diode based time-domain fluorimeter (LED TDF) is reported for the measurement of nanosecond fluorescence lifetimes. LED based excitation provides more wavelengths options compared to laser diode based excitation, but the excitation is less effective due to the uncollimated beam, less optical power, and longer latency in state transition. Pulse triggering and pre-bias techniques were implemented in our LED TDF to improve the peak optical power to over 100 mW. The proposed pulsing circuit achieved an excitation light fall time of less than 2 ns. Electrical resetting technique realized a time-gated photo-detector to remove the interference of the excitation light with fluorescence. These techniques allow the LED fluorimeter to accurately measure the fluorescence lifetime of fluorescein down to concentration of 0.5 μM. In addition, all filters required in traditional instruments are eliminated for the non-attenuated excitation/emission light power. These achievements make the reported device attractive to biochemical laboratories seeking for highly portable lifetime detection devices for developing sensors based on fluorescence lifetime changes. The device was initially validated by measuring the lifetimes of three commercial fluorophores and comparing them with reported lifetime data. It was subsequently used to characterize a ZnSe quantum dot based DNA sensor.

  16. Dynamic frequency-domain interferometer for absolute distance measurements with high resolution

    SciTech Connect (OSTI)

    Weng, Jidong; Liu, Shenggang; Ma, Heli; Tao, Tianjiong; Wang, Xiang; Liu, Cangli; Tan, Hua

    2014-11-15

    A unique dynamic frequency-domain interferometer for absolute distance measurement has been developed recently. This paper presents the working principle of the new interferometric system, which uses a photonic crystal fiber to transmit the wide-spectrum light beams and a high-speed streak camera or frame camera to record the interference stripes. Preliminary measurements of harmonic vibrations of a speaker, driven by a radio, and the changes in the tip clearance of a rotating gear wheel show that this new type of interferometer has the ability to perform absolute distance measurements both with high time- and distance-resolution.

  17. Method and apparatus for monitoring the integrity of a geomembrane liner using time domain reflectometry

    DOE Patents [OSTI]

    Morrison, John L. (Idaho Falls, ID)

    2001-04-24

    Leaks are detected in a multi-layered geomembrane liner by a two-dimensional time domain reflectometry (TDR) technique. The TDR geomembrane liner is constructed with an electrically conductive detection layer positioned between two electrically non-conductive dielectric layers, which are each positioned between the detection layer and an electrically conductive reference layer. The integrity of the TDR geomembrane liner is determined by generating electrical pulses within the detection layer and measuring the time delay for any reflected electrical energy caused by absorption of moisture by a dielectric layer.

  18. Magnetic domain wall manipulation in (Ga,Mn)As nanostructures for spintronic applications

    SciTech Connect (OSTI)

    Wosinski, Tadeusz; Andrearczyk, Tomasz; Figielski, Tadeusz; Olender, Karolina; Wrobel, Jerzy

    2014-02-21

    Ring-shaped nanostructures have been designed and fabricated by electron-beam lithography patterning and chemical etching from thin epitaxial layers of the ferromagnetic semiconductor (Ga,Mn)As. The nanostructures, in a form of planar rings with a slit, were supplied with four electrical terminals and subjected to magneto-transport studies under planar weak magnetic field. Magnetoresistive effects caused by manipulation of magnetic domain walls and magnetization reversal in the nanostructures have been investigated and possible applications of the nanostructures as four-terminal spintronic devices are discussed.

  19. rbstmultiprince.f; Equivalent Dipole Polarizability Inversion of Time Domain Electromagnetic Induction Data

    Energy Science and Technology Software Center (OSTI)

    2006-10-01

    This software, rbstmultiprince.f, computes polarizations and positions from electromagnetic data and is used in conjunction with technology to detect UXO. This software was funded by the ESTCP program of the DoD. This code makes use of third party code from the 1970s and 1980s that appears to have entered the public domain and is available for free download via the website netlib.org. The code was first developed by the author while he was employed atmore »UCB and funded by the SERDP of the U.S. Army.« less

  20. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  1. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  2. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  3. Crystal Structure of a Conserved Phosphatase Domain of Non-structural

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein-3 (nsp3) from the SARS Coronavirus a Conserved Phosphatase Domain of Non-structural Protein-3 (nsp3) from the SARS Coronavirus Kumar Singh Saikatendu1, Jeremiah S. Joseph1, Vanitha Subramanian1, Benjamin W. Neuman3, Michael J. Buchmeier3, Raymond C. Stevens2 and Peter Kuhn1. 1Departments of Cell Biology, 2Molecular Biology, and 3Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 Severe Acute Respiratory Syndrome (SARS) is a

  4. High-resolution retinal imaging using adaptive optics and Fourier-domain optical coherence tomography

    DOE Patents [OSTI]

    Olivier, Scot S.; Werner, John S.; Zawadzki, Robert J.; Laut, Sophie P.; Jones, Steven M.

    2010-09-07

    This invention permits retinal images to be acquired at high speed and with unprecedented resolution in three dimensions (4.times.4.times.6 .mu.m). The instrument achieves high lateral resolution by using adaptive optics to correct optical aberrations of the human eye in real time. High axial resolution and high speed are made possible by the use of Fourier-domain optical coherence tomography. Using this system, we have demonstrated the ability to image microscopic blood vessels and the cone photoreceptor mosaic.

  5. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  6. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  7. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  8. Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Vortices Influence of Domain Wall Pinning on the Dynamic Behavior of Magnetic Vortices Print Soft magnetic, micron-sized thin-film structures with magnetic vortices are intriguing systems that may one day be used in ultrafast computer memories. In such systems, the otherwise in-plane magnetization turns perpendicular to the plane at the center of the vortex, forming the vortex core. Because such a core has two possible polarizations (up or down) and can be switched between these two states

  9. Evaluating the coherence and time-domain profile of quantum cascade laser frequency combs

    SciTech Connect (OSTI)

    Burghoff, David; Yang, Yang; Hayton, Darren J.; Gao, Jian -Rong; Reno, John L.; Hu, Qing

    2015-01-01

    Recently, much attention has been focused on the generation of optical frequency combs from quantum cascade lasers. We discuss how fast detectors can be used to demonstrate the mutual coherence of such combs, and present an inequality that can be used to quantitatively evaluate their performance. We discuss several technical issues related to shifted wave interference Fourier Transform spectroscopy (SWIFTS), and show how such measurements can be used to elucidate the time-domain properties of such combs, showing that they can possess signatures of both frequency-modulation and amplitude-modulation.

  10. Final Technical Report - Integrated Hydrogeophysical and Hydrogeologic Driven Parameter Upscaling for Dual-Domain Transport Modeling

    SciTech Connect (OSTI)

    Shafer, John M

    2012-11-05

    The three major components of this research were: 1. Application of minimally invasive, cost effective hydrogeophysical techniques (surface and borehole), to generate fine scale (~1m or less) 3D estimates of subsurface heterogeneity. Heterogeneity is defined as spatial variability in hydraulic conductivity and/or hydrolithologic zones. 2. Integration of the fine scale characterization of hydrogeologic parameters with the hydrogeologic facies to upscale the finer scale assessment of heterogeneity to field scale. 3. Determination of the relationship between dual-domain parameters and practical characterization data.

  11. Axial couplings of heavy hadrons from domain-wall lattice QCD

    SciTech Connect (OSTI)

    W. Detmold, C.J.D. Lin, S. Meinel

    2011-12-01

    We calculate matrix elements of the axial current for static-light mesons and baryons in lattice QCD with dynamical domain wall fermions. We use partially quenched heavy hadron chiral perturbation theory in a finite volume to extract the axial couplings g{sub 1}, g{sub 2}, and g{sub 3} from the data. These axial couplings allow the prediction of strong decay rates and enter chiral extrapolations of most lattice results in the b sector. Our calculations are performed with two lattice spacings and with pion masses down to 227 MeV.

  12. Protein superfamily members as targets for computer modeling: The carbohydrate recognition domain of a macrophage lectin

    SciTech Connect (OSTI)

    Stenkamp, R.E.; Aruffo, A.; Bajorath, J.

    1996-12-31

    Members of protein superfamilies display similar folds, but share only limited sequence identity, often 25% or less. Thus, it is not straightforward to apply standard homology modeling methods to construct reliable three-dimensional models of such proteins. A three-dimensional model of the carbohydrate recognition domain of the rat macrophage lectin, a member of the calcium-dependent (C-type) lectin superfamily, has been generated to illustrate how information provided by comparison of X-ray structures and sequence-structure alignments can aid in comparative modeling when primary sequence similarities are low. 20 refs., 4 figs.

  13. Coordinated Multi-layer Multi-domain Optical Network (COMMON) for Large-Scale Science Applications (COMMON)

    SciTech Connect (OSTI)

    Vokkarane, Vinod

    2013-09-01

    We intend to implement a Coordinated Multi-layer Multi-domain Optical Network (COMMON) Framework for Large-scale Science Applications. In the COMMON project, specific problems to be addressed include 1) anycast/multicast/manycast request provisioning, 2) deployable OSCARS enhancements, 3) multi-layer, multi-domain quality of service (QoS), and 4) multi-layer, multidomain path survivability. In what follows, we outline the progress in the above categories (Year 1, 2, and 3 deliverables).

  14. Structures of Minimal Catalytic Fragments of Topoisomerase V Reveals Conformational Changes Relevant for DNA Binding

    SciTech Connect (OSTI)

    Rajan, Rakhi; Taneja, Bhupesh; Mondragn, Alfonso

    2010-12-03

    Topoisomerase V is an archaeal type I topoisomerase that is unique among topoisomerases due to presence of both topoisomerase and DNA repair activities in the same protein. It is organized as an N-terminal topoisomerase domain followed by 24 tandem helix-hairpin-helix (HhH) motifs. Structural studies have shown that the active site is buried by the (HhH) motifs. Here we show that the N-terminal domain can relax DNA in the absence of any HhH motifs and that the HhH motifs are required for stable protein-DNA complex formation. Crystal structures of various topoisomerase V fragments show changes in the relative orientation of the domains mediated by a long bent linker helix, and these movements are essential for the DNA to enter the active site. Phosphate ions bound to the protein near the active site helped model DNA in the topoisomerase domain and show how topoisomerase V may interact with DNA.

  15. Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

    SciTech Connect (OSTI)

    Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.; Ellington, Andrew D.; Looger, Loren L.; Schreiter, Eric R.

    2012-09-17

    The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by {approx}70{sup o} between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.

  16. NRC staff review of licensee responses to pressure-locking and thermal-binding issue

    SciTech Connect (OSTI)

    Rathbun, H.J.

    1996-12-01

    Commercial nuclear power plant operating experience has indicated that pressure locking and thermal binding represent potential common mode failure mechanisms that can cause safety-related power-operated gate valves to fail in the closed position, thus rendering redundant safety-related systems incapable of performing their safety functions. In Generic Letter (GL) 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves,{close_quotes} the U.S. Nuclear Regulatory Commission (NRC) staff requested that nuclear power plant licensees take certain actions to ensure that valves susceptible to pressure locking or thermal binding are capable of performing their safety functions within the current licensing bases of the facility. The NRC staff has received summary information from licensees in response to GL 95-07 describing actions they have taken to prevent the occurrence of pressure locking and thermal binding. The NRC staff has developed a systematic process to help ensure uniform and consistent review of licensee submittals in response to GL 95-07.

  17. Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria

    DOE Patents [OSTI]

    DiSpirito, Alan A. (Ames, IA); Zahn, James A. (Harbor Beach, MI); Graham, David W. (Lawrence, KS); Kim, Hyung J. (St. Paul, MN); Alterman, Michail (Lawrence, KS); Larive, Cynthia (Lawrence, KS)

    2007-04-03

    A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.

  18. Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells

    SciTech Connect (OSTI)

    Tsujimoto, M.; Yip, Y.K.; Vilcek, J.

    1985-11-01

    Highly purified, Escherichia coli-derived recombinant human tumor necrosis factor (TNF) was labeled with /sup 125/I and employed to determine receptor binding, internalization, and intracellular degradation in murine L929 cells (highly sensitive to the cytotoxic action of TNF) and in diploid human FS-4 cells (resistant to TNF cytotoxicity). /sup 125/I-labeled TNF bound specifically to high-affinity receptors on both L929 and FS-4 cells. Scatchard analysis of the binding data indicated the presence of 2200 binding sites per L929 cell and 7500 binding sites per FS-4 cell. The calculated dissociation constants are 6.1 x 10/sup -10/ M and 3.2 x 10/sup -10/ M for L929 and FS-4 cells, respectively. In both L929 and FS-4 cells, incubation at 37/sup 0/C resulted in a rapid internalization of the bulk of the cell-bound TNF, followed by the appearance of trichloroacetic acid-soluble /sup 125/I radioactivity in the tissue culture medium, due to degradation of TNF. Degradation but not cellular uptake of TNF was inhibited in the presence of chloroquine (an inhibitor of lysosomal proteases) in both L929 and FS-4 cells, suggesting that degradation occurs intracellularly, probably within lysosomes. These results show that resistance of FS-4 cells to TNF cytotoxicity is not due to a lack of receptors or their inability to internalize and degrade TNF.

  19. Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

    SciTech Connect (OSTI)

    Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis; Rubin, EdwardM.; Couronne, Olivier

    2005-06-13

    Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.

  20. Improving Cyber-Security of Smart Grid Systems via Anomaly Detection and Linguistic Domain Knowledge

    SciTech Connect (OSTI)

    Ondrej Linda; Todd Vollmer; Milos Manic

    2012-08-01

    The planned large scale deployment of smart grid network devices will generate a large amount of information exchanged over various types of communication networks. The implementation of these critical systems will require appropriate cyber-security measures. A network anomaly detection solution is considered in this work. In common network architectures multiple communications streams are simultaneously present, making it difficult to build an anomaly detection solution for the entire system. In addition, common anomaly detection algorithms require specification of a sensitivity threshold, which inevitably leads to a tradeoff between false positives and false negatives rates. In order to alleviate these issues, this paper proposes a novel anomaly detection architecture. The designed system applies the previously developed network security cyber-sensor method to individual selected communication streams allowing for learning accurate normal network behavior models. Furthermore, the developed system dynamically adjusts the sensitivity threshold of each anomaly detection algorithm based on domain knowledge about the specific network system. It is proposed to model this domain knowledge using Interval Type-2 Fuzzy Logic rules, which linguistically describe the relationship between various features of the network communication and the possibility of a cyber attack. The proposed method was tested on experimental smart grid system demonstrating enhanced cyber-security.

  1. Cosmic bubble and domain wall instabilities II: fracturing of colliding walls

    SciTech Connect (OSTI)

    Braden, Jonathan; Bond, J. Richard; Mersini-Houghton, Laura

    2015-08-26

    We study collisions between nearly planar domain walls including the effects of small initial nonplanar fluctuations. These perturbations represent the small fluctuations that must exist in a quantum treatment of the problem. In a previous paper, we demonstrated that at the linear level a subset of these fluctuations experience parametric amplification as a result of their coupling to the planar symmetric background. Here we study the full three-dimensional nonlinear dynamics using lattice simulations, including both the early time regime when the fluctuations are well described by linear perturbation theory as well as the subsequent stage of fully nonlinear evolution. We find that the nonplanar fluctuations have a dramatic effect on the overall evolution of the system. Specifically, once these fluctuations begin to interact nonlinearly the split into a planar symmetric part of the field and the nonplanar fluctuations loses its utility. At this point the colliding domain walls dissolve, with the endpoint of this being the creation of a population of oscillons in the collision region. The original (nearly) planar symmetry has been completely destroyed at this point and an accurate study of the system requires the full three-dimensional simulation.

  2. Interplay between intrinsic and stacking-fault magnetic domains in bi-layered manganites

    SciTech Connect (OSTI)

    Hossain, M.A; Burkhardt, Mark H.; Sarkar, S.; Ohldag, H.; Chuang, Y.-D.; Scholl, A.; Young, A.T.; Doran, A.; Dessau, D.S.; Zheng, H.; Mitchell, J.F.; Durr, H.A.; Stohr, J.

    2012-09-11

    We present a low temperature X-ray photoemission electron microscopy study of the bi-layered manganite compound La{sub 1.2}Sr{sub 1.8}Mn{sub 2}O{sub 7} (BL-LSMO) to investigate the influence of stacking faults, which are structurally and magnetically different from the bi-layered host. In BL-LSMO small magnetic moment persists to T* = 300K, well above the Curie temperature of 120K (T{sub C}). Our magnetic images show that 3D stacking faults are responsible for the T* transition. Furthermore, close to the T{sub C}, stacking faults are well coupled to the bi-layered host with latter magnetic domains controlling the spin direction of the stacking faults. Contrary to recent reports, we find that stacking faults do not seed magnetic domains in the host via an exchange spring mechanism and the intrinsic T{sub C} of the BL-LSMO is not lower than 120K.

  3. Spatially Resolved Mapping of Electrical Conductivity around Individual Domain (Grain) Boundaries in Graphene

    SciTech Connect (OSTI)

    Li, An-Ping [ORNL; Clark, Kendal W [ORNL; Zhang, Xiaoguang [ORNL; Vlassiouk, Ivan V [ORNL; He, Guowei [Carnegie Mellon University (CMU); Feenstra, Randall [Carnegie Mellon University (CMU)

    2013-01-01

    Graphene films can now be produced on the scale of up to meters. However, all large-scale graphene films contain topological defects that can significantly affect the characteristic transport behaviors of graphene. Here, we spatially map the structures and electronic transport near specific domain and grain boundaries in graphene, and evaluate effects of different types of defect on the electronic conductivity in epitaxial graphene grown on SiC and CVD graphene on Cu subsequently transferred to a SiO2 substrate. We use a combined approach with a multi-probe scanning tunneling potentiometry to investigate both structures and transport at individual grain boundaries and domain boundaries that are defined by coalesced grains, surface steps, and changes in layer thickness. It is found that the substrate step on SiC presents a significant potential barrier for electron transport of epitaxial graphene due to the reduced charge transport from the substrate at the step edges, monolayer-bilayer boundaries exhibit a high resistivity that can change depending on directions of the current across the boundary, and the resistivity of grain boundaries changes with the transition width of the disordered region between two adjacent grains in graphene. The detailed understanding of graphene defects will provide the feedback for controlled engineering of defects in large-scale graphene films.

  4. SuperIdentity: Fusion of Identity across Real and Cyber Domains

    SciTech Connect (OSTI)

    Black, Sue; Creese, Sadie; Guest, Richard; Pike, William A.; Saxby, Steven; Stanton Fraser, Danae; Stevenage, Sarah; Whitty, Monica

    2012-04-23

    Under both benign and malign circumstances, people now manage a spectrum of identities across both real-world and cyber domains. Our belief, however, is that all these instances ultimately track back for an individual to reflect a single 'SuperIdentity'. This paper outlines the assumptions underpinning the SuperIdentity Project, describing the innovative use of data fusion to incorporate novel real-world and cyber cues into a rich framework appropriate for modern identity. The proposed combinatorial model will support a robust identification or authentication decision, with confidence indexed both by the level of trust in data provenance, and the diagnosticity of the identity factors being used. Additionally, the exploration of correlations between factors may underpin the more intelligent use of identity information so that known information may be used to predict previously hidden information. With modern living supporting the 'distribution of identity' across real and cyber domains, and with criminal elements operating in increasingly sophisticated ways in the hinterland between the two, this approach is suggested as a way forwards, and is discussed in terms of its impact on privacy, security, and the detection of threat.

  5. Discontinuous Galerkin solution of the Navier-Stokes equations on deformable domains

    SciTech Connect (OSTI)

    Persson, P.-O.; Bonet, J.; Peraire, J.

    2009-01-13

    We describe a method for computing time-dependent solutions to the compressible Navier-Stokes equations on variable geometries. We introduce a continuous mapping between a fixed reference configuration and the time varying domain, By writing the Navier-Stokes equations as a conservation law for the independent variables in the reference configuration, the complexity introduced by variable geometry is reduced to solving a transformed conservation law in a fixed reference configuration, The spatial discretization is carried out using the Discontinuous Galerkin method on unstructured meshes of triangles, while the time integration is performed using an explicit Runge-Kutta method, For general domain changes, the standard scheme fails to preserve exactly the free-stream solution which leads to some accuracy degradation, especially for low order approximations. This situation is remedied by adding an additional equation for the time evolution of the transformation Jacobian to the original conservation law and correcting for the accumulated metric integration errors. A number of results are shown to illustrate the flexibility of the approach to handle high order approximations on complex geometries.

  6. Development of time-domain differential Raman for transient thermal probing of materials

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xu, Shen; Wang, Tianyu; Hurley, David; Yue, Yanan; Wang, Xinwei

    2015-01-01

    A novel transient thermal characterization technology is developed based on the principles of transient optical heating and Raman probing: time-domain differential Raman. It employs a square-wave modulated laser of varying duty cycle to realize controlled heating and transient thermal probing. Very well defined extension of the heating time in each measurement changes the temperature evolution profile and the probed temperature field at ?s resolution. Using this new technique, the transient thermal response of a tipless Si cantilever is investigated along the length direction. A physical model is developed to reconstruct the Raman spectrum considering the temperature evolution, while taking intomoreaccount the temperature dependence of the Raman emission. By fitting the variation of the normalized Raman peak intensity, wavenumber, and peak area against the heating time, the thermal diffusivity is determined as 9.17 10??, 8.14 10??, and 9.51 10?? m/s. These results agree well with the reference value of 8.66 10?? m/s considering the 10% fitting uncertainty. The time-domain differential Raman provides a novel way to introduce transient thermal excitation of materials, probe the thermal response, and measure the thermal diffusivity, all with high accuracy.less

  7. Development of time-domain differential Raman for transient thermal probing of materials

    SciTech Connect (OSTI)

    Xu, Shen; Wang, Tianyu; Hurley, David; Yue, Yanan; Wang, Xinwei

    2015-01-01

    A novel transient thermal characterization technology is developed based on the principles of transient optical heating and Raman probing: time-domain differential Raman. It employs a square-wave modulated laser of varying duty cycle to realize controlled heating and transient thermal probing. Very well defined extension of the heating time in each measurement changes the temperature evolution profile and the probed temperature field at ?s resolution. Using this new technique, the transient thermal response of a tipless Si cantilever is investigated along the length direction. A physical model is developed to reconstruct the Raman spectrum considering the temperature evolution, while taking into account the temperature dependence of the Raman emission. By fitting the variation of the normalized Raman peak intensity, wavenumber, and peak area against the heating time, the thermal diffusivity is determined as 9.17 10??, 8.14 10??, and 9.51 10?? m/s. These results agree well with the reference value of 8.66 10?? m/s considering the 10% fitting uncertainty. The time-domain differential Raman provides a novel way to introduce transient thermal excitation of materials, probe the thermal response, and measure the thermal diffusivity, all with high accuracy.

  8. Fabrication of single crystalline, uniaxial single domain Co nanowire arrays with high coercivity

    SciTech Connect (OSTI)

    Ramazani, A. Almasi Kashi, M.; Montazer, A. H.

    2014-03-21

    Whilst Co nanorods with high coercivity were synthesized during recent years, they did not achieve the same results as for Co nanowires embedded in solid templates. In the present work, Co nanowire arrays (NWAs) with high coercivity were successfully fabricated in porous aluminum oxide template under optimum conditions by using pulsed ac electrodeposition technique. Magnetic properties and crystalline characteristics of the nanowires were investigated by hysteresis loop measurements, first-order reversal curve (FORC) analysis, X-ray diffraction (XRD), and selected area electron diffraction (SAED) patterns. Hysteresis loop measurements showed high coercivity of about 4.8 kOe at room temperature together with optimum squareness of 1, resulting in an increase of the previous maximum coercivity for Co NWAs up to 45%. XRD and SAED patterns revealed a single crystalline texture along the [0002] direction, indicating the large magnetocrystalline anisotropy. On the other hand, FORC analysis confirmed a single domain structure for the Co NWAs. In addition, the reversal mechanism of the single crystalline, single domain Co NWAs was studied which resulted in the fixed easy axis with a coherent rotation. Accordingly, these nanowires might offer promising applications in high density bit patterned media and low power logic devices.

  9. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

    SciTech Connect (OSTI)

    Simarro, Maria; Gimenez-Cassina, Alfredo; Kedersha, Nancy; Lazaro, Jean-Bernard; Adelmant, Guillaume O.; Marto, Jarrod A.; Rhee, Kirsten; Tisdale, Sarah; Danial, Nika; Benarafa, Charaf; Orduna, Anonio; Anderson, Paul

    2010-10-22

    Research highlights: {yields} Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. {yields} The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. {yields} Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.

  10. Calculation of positron binding energies using the generalized any particle propagator theory

    SciTech Connect (OSTI)

    Romero, Jonathan; Charry, Jorge A.; Flores-Moreno, Roberto; Varella, Mrcio T. do N.; Reyes, Andrs

    2014-09-21

    We recently extended the electron propagator theory to any type of quantum species based in the framework of the Any-Particle Molecular Orbital (APMO) approach [J. Romero, E. Posada, R. Flores-Moreno, and A. Reyes, J. Chem. Phys. 137, 074105 (2012)]. The generalized any particle molecular orbital propagator theory (APMO/PT) was implemented in its quasiparticle second order version in the LOWDIN code and was applied to calculate nuclear quantum effects in electron binding energies and proton binding energies in molecular systems [M. Daz-Tinoco, J. Romero, J. V. Ortiz, A. Reyes, and R. Flores-Moreno, J. Chem. Phys. 138, 194108 (2013)]. In this work, we present the derivation of third order quasiparticle APMO/PT methods and we apply them to calculate positron binding energies (PBEs) of atoms and molecules. We calculated the PBEs of anions and some diatomic molecules using the second order, third order, and renormalized third order quasiparticle APMO/PT approaches and compared our results with those previously calculated employing configuration interaction (CI), explicitly correlated and quantum Montecarlo methodologies. We found that renormalized APMO/PT methods can achieve accuracies of ?0.35 eV for anionic systems, compared to Full-CI results, and provide a quantitative description of positron binding to anionic and highly polar species. Third order APMO/PT approaches display considerable potential to study positron binding to large molecules because of the fifth power scaling with respect to the number of basis sets. In this regard, we present additional PBE calculations of some small polar organic molecules, amino acids and DNA nucleobases. We complement our numerical assessment with formal and numerical analyses of the treatment of electron-positron correlation within the quasiparticle propagator approach.

  11. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-02-05

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  12. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-05-24

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  13. High-Affinity and Cooperative Binding of Oxidized Calmodulin by Methionine Sulfoxide Reductase

    SciTech Connect (OSTI)

    Xiong, Yijia; Chen, Baowei; Smallwood, Heather S.; Urbauer, Ramona J.; Markillie, Lye Meng; Galeva, Nadezhda A.; Williams, Todd D.; Squier, Thomas C.

    2006-12-12

    Methionines play an important role in modulating protein-protein interactions associated with intracellular signaling, and their reversible oxidation to form methionine sulfoxides [Met(O)] in calmodulin (CaM) and other signaling proteins has been suggested to couple cellular redox changes to protein function changes through the action of methionine sulfoxide reductases (Msr). Prior measurements indicate the full recovery of target protein activation upon the stereospecific reduction of oxidized CaM by MsrA, where the formation of the S-stereoisomer of Met(O) selectively inhibits the CaM-dependent activation of the Ca-ATPase. However, the physiological substrates of MsrA remain unclear, as neither the binding specificities nor affinities of protein targets have been measured. To assess the specificity of binding and its possible importance in the maintenance of CaM function, we have measured the kinetics of repair and the binding affinity between oxidized CaM and MsrA. Reduction of Met(O) in fully oxidized CaM by MsrA is sensitive to protein folding, as repair of the intact protein is incomplete, with > 6 Met(O) remaining in each CaM following MsrA reduction. In contrast, following proteolytic digestion, MsrA is able to fully reduce one-half of the oxidized methionines, indicating that Met(O) within folded proteins are not substrates for MsrA repair. Further, in comparison to free Met(O), the turnover number and Km for oxidized CaM (CaMox) are substantially smaller, indicating that the binding interaction retards Msr recycling to reduce steady-state enzyme activity. Mutation of the active site (i.e., C72S) in MsrA permitted equilibrium-binding measurements using both ensemble and single-molecule measurements obtained by fluorescence correlation spectroscopy (FCS). Multiple MsrA bind tightly to CaMox (Kd = 70 +- 10 nM) with an affinity that is three orders of magnitude greater than the Michaelis constant (KM = 71 +- 8 micromolar). These results indicate that MsrA selectively reduces surface-exposed Met(O) within unstructured sequences and suggest that only a small subset of oxidized proteins are substrates for MsrA, which may selectively modulate the function of key signaling proteins as part of an adaptive response to oxidative stress.

  14. PRODUCTION PROCESS MONITORING OF MULTILAYERED MATERIALS USING TIME-DOMAIN TERAHERTZ GAUGES

    SciTech Connect (OSTI)

    Zimdars, David; Duling, Irl; Fichter, Greg; White, Jeffrey

    2010-02-22

    The results of both a laboratory and factory trial of a time-domain terahertz (TD-THz) multi-layer gauge for on-line process monitoring are presented. The TD-THz gauge is demonstrated on a two layer laminated plastic insulation material. The TD-THz gauge simultaneously measured the total and the individual layer thicknesses. Measurements were made while transversely scanning across a 12 foot wide sheet extruded at high speed in a factory environment. The results were analyzed for precision, accuracy, and repeatability; and demonstrated that the TD-THz gauge performed in an equivalent or superior manner to existing ionizing radiation gauges (which measure only one layer). Many dielectric materials (e.g., plastic, rubber, paper, paint) are transparent to THz pulses, and the measurement of a wide range of samples is possible.

  15. Method and apparatus for active tamper indicating device using optical time-domain reflectometry

    DOE Patents [OSTI]

    Smith, D. Barton (Oak Ridge, TN); Muhs, Jeffrey D. (Lenoir City, TN); Pickett, Chris A. (Clinton, TN); Earl, D. Duncan (Knoxville, TX)

    1999-01-01

    An optical time-domain reflectometer (OTDR) launches pulses of light into a link or a system of multiplexed links and records the waveform of pulses reflected by the seals in the link(s). If a seal is opened, the link of cables will become a discontinuous transmitter of the light pulses and the OTDR can immediately detect that a seal has been opened. By analyzing the waveform, the OTDR can also quickly determine which seal(s) were opened. In this way the invention functions as a system of active seals. The invention is intended for applications that require long-term surveillance of a large number of closures. It provides immediate tamper detection, allows for periodic access to secured closures, and can be configured for many different distributions of closures. It can monitor closures in indoor and outdoor locations and it can monitor containers or groups of containers located many kilometers apart.

  16. Spectral evolution of two-dimensional kinetic plasma turbulence in the wavenumber-frequency domain

    SciTech Connect (OSTI)

    Comi?el, H.; Institute for Space Sciences, Atomi?tilor 409, P.O. Box MG-23, Bucharest-M?gurele RO-077125 ; Verscharen, D.; Narita, Y.; Motschmann, U.; Deutsches Zentrum fr Luft- und Raumfahrt, Institut fr Planetenforschung, Rutherfordstr. 2, D-12489 Berlin

    2013-09-15

    We present a method for studying the evolution of plasma turbulence by tracking dispersion relations in the energy spectrum in the wavenumber-frequency domain. We apply hybrid plasma simulations in a simplified two-dimensional geometry to demonstrate our method and its applicability to plasma turbulence in the ion kinetic regime. We identify four dispersion relations: ion-Bernstein waves, oblique whistler waves, oblique Alfvn/ion-cyclotron waves, and a zero-frequency mode. The energy partition and frequency broadening are evaluated for these modes. The method allows us to determine the evolution of decaying plasma turbulence in our restricted geometry and shows that it cascades along the dispersion relations during the early phase with an increasing broadening around the dispersion relations.

  17. FETI Prime Domain Decomposition base Parallel Iterative Solver Library Ver.1.0

    Energy Science and Technology Software Center (OSTI)

    2003-09-15

    FETI Prime is a library for the iterative solution of linear equations in solid and structural mechanics. The algorithm employs preconditioned conjugate gradients, with a domain decomposition-based preconditioner. The software is written in C++ and is designed for use with massively parallel computers, using MPI. The algorithm is based on the FETI-DP method, with additional capabilities for handling constraint equations, as well as interfacing with the Salinas structural dynamics code and the Finite Element Interfacemore » (FEI) library. Practical Application: FETI Prime is designed for use with finite element-based simulation codes for solid and structural mechanics. The solver uses element matrices, connectivity information, nodal information, and force vectors computed by the host code and provides back the solution to the linear system of equations, to the user specified level of accuracy, The library is compiled with the host code and becomes an integral part of the host code executable.« less

  18. Current-driven domain wall motion enhanced by the microwave field

    SciTech Connect (OSTI)

    Wang, Xi-guang; Guo, Guang-hua Nie, Yao-zhuang; Wang, Dao-wei; Li, Zhi-xiong; Tang, Wei; Zeng, Zhong-ming

    2014-07-14

    The magnetic domain wall (DW) motion driven by a spin-polarized current opens a new concept for memory and logic devices. However, the critical current density required to overcome the intrinsic and/or extrinsic pinning of DW remains too large for practical applications. Here, we show, by using micromagnetic simulations and analytical approaches, that the application of a microwave field offers an effective solution to this problem. When a transverse microwave field is applied, the adiabatic spin-transfer torque (STT) alone can sustain a steady-state DW motion without the sign of Walker breakdown, meaning that the intrinsic pinning disappears. The extrinsic pinning can also be effectively reduced. Moreover, the DW velocity is increased greatly for the microwave-assisted DW motion. This provides a new way to manipulate the DW motion at low current densities.

  19. Non-linear Conjugate Gradient Time-Domain Controlled Inversion Source

    Energy Science and Technology Software Center (OSTI)

    2006-11-16

    Software that simulates and inverts time-domain electromagnetic field data for subsurface electrical properties (electrical conductivity) of geological media. The software treats data produced by a step-wise source signal from either galvanic (grounded wires) or inductive (magnetic loops) sources. The inversion process is carried inductive (magnetic loops) sources. The inversion process is carried out using a non-linear conjugate gradient optimization scheme, which minimizes the misfit between field data and model data using a least squares criteria.more » The software is an upgrade from the code TEM3D ver. 2.0. The upgrade includes the following components: (1) Improved (faster)memory access during gradient computation. (2) Data parellelization scheme: Multiple transmitters (sources) can be distributed accross several banks of processors (daa-planes). Similarly, the receivers of each source are also distributed accross the corresponding data-plane. (3) Improved data-IO.« less

  20. Time-Domain Reflectometry for Tamper Indication in Unattended Monitoring Systems for Safeguards

    SciTech Connect (OSTI)

    Tedeschi, Jonathan R.; Smith, Leon E.; Moore, David E.; Sheen, David M.; Conrad, Ryan C.

    2014-12-17

    The International Atomic Energy Agency (IAEA) continues to expand its use of unattended, remotely monitored measurement systems. An increasing number of systems and an expanding family of instruments create challenges in terms of deployment efficiency and the implementation of data authentication measures. Pacific Northwest National Laboratory (PNNL) leads a collaboration that is exploring various tamper-indicating (TI) measures that could help to address some of the long-standing detector and data-transmission authentication challenges with IAEAs unattended systems. PNNL is investigating the viability of active time-domain reflectometry (TDR) along two parallel but interconnected paths: (1) swept-frequency TDR as the highly flexible, laboratory gold standard to which field-deployable options can be compared, and (2) a low-cost commercially available spread-spectrum TDR technology as one option for field implementation. This report describes PNNLs progress and preliminary findings from the first year of the study, and describes the path forward.