National Library of Energy BETA

Sample records for bind deleted domain

  1. 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.

  2. Cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    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.

  3. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    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.

  4. 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.

  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; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    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 detection using a cellulose binding domain fusion product

    DOE Patents [OSTI]

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    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.

  8. 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.

  9. 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.

  10. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    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.

  11. Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

    SciTech Connect (OSTI)

    Yun, Ji-Hye; Lee, Won Kyung; Kim, Heeyoun; Kim, Eunhee; Cheong, Chaejoon; Cho, Myeon Haeng; Lee, Weontae

    2014-09-26

    Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.

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

    Office of Scientific and Technical Information (OSTI)

    Title: Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF Authors: Pascoe, Heath G. ; Gutowski, Stephen ; Chen, Hua ; Brautigam, Chad A. ; ...

  13. 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.

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

    DOE Patents [OSTI]

    Shoseyov, Oded

    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.

  15. 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.

  16. 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.

  17. 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.

  18. The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition

    SciTech Connect (OSTI)

    Zhang, Lei; Zhang, Qing; Yang, Yu; Wu, Chuanfang

    2014-02-14

    Highlights: • RNA recognition motif domains of RBM5 are essential for cell proliferation inhibition. • RNA recognition motif domains of RBM5 are essential for apoptosis induction. • RNA recognition motif domains of RBM5 are essential for RNA binding. • RNA recognition motif domains of RBM5 are essential for caspase-2 alternative splicing. - Abstract: RBM5 is a known putative tumor suppressor gene that has been shown to function in cell growth inhibition by modulating apoptosis. RBM5 also plays a critical role in alternative splicing as an RNA binding protein. However, it is still unclear which domains of RBM5 are required for RNA binding and related functional activities. We hypothesized the two putative RNA recognition motif (RRM) domains of RBM5 spanning from amino acids 98–178 and 231–315 are essential for RBM5-mediated cell growth inhibition, apoptosis regulation, and RNA binding. To investigate this hypothesis, we evaluated the activities of the wide-type and mutant RBM5 gene transfer in low-RBM5 expressing A549 cells. We found that, unlike wild-type RBM5 (RBM5-wt), a RBM5 mutant lacking the two RRM domains (RBM5-ΔRRM), is unable to bind RNA, has compromised caspase-2 alternative splicing activity, lacks cell proliferation inhibition and apoptosis induction function in A549 cells. These data provide direct evidence that the two RRM domains of RBM5 are required for RNA binding and the RNA binding activity of RBM5 contributes to its function on apoptosis induction and cell growth inhibition.

  19. 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

  20. 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 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, 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.

  1. 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.

  2. 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

  3. 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.

  4. Crystal Structure of 12-Lipoxygenase Catalytic-Domain-Inhibitor Complex Identifies a Substrate-Binding Channel for Catalysis

    SciTech Connect (OSTI)

    Xu, Shu; Mueser, Timothy C.; Marnett, Lawrence J.; Funk, Jr., Max O.

    2014-10-02

    Lipoxygenases are critical enzymes in the biosynthesis of families of bioactive lipids including compounds with important roles in the initiation and resolution of inflammation and in associated diseases such as diabetes, cardiovascular disease, and cancer. Crystals diffracting to high resolution (1.9 {angstrom}) were obtained for a complex between the catalytic domain of leukocyte 12-lipoxygenase and the isoform-specific inhibitor, 4-(2-oxapentadeca-4-yne)phenylpropanoic acid (OPP). In the three-dimensional structure of the complex, the inhibitor occupied a new U-shaped channel open at one end to the surface of the protein and extending past the redox-active iron site that is essential for catalysis. In models, the channel accommodated arachidonic acid, defining the binding site for the substrate of the catalyzed reaction. There was a void adjacent to the OPP binding site connecting to the surface of the enzyme and providing a plausible access channel for the other substrate, oxygen.

  5. 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.

  6. 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

  7. 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.

  8. Financial Opportunities Delete Me | Department of Energy

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

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  9. 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.

  10. 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.

  11. 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.

  12. 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.

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

    SciTech Connect (OSTI)

    Zhang, Bing; Liu, Caini; Qian, Wen; Han, Yue; Li, Xiaoxia; Deng, Junpeng

    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 protein–protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 Å 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 α-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 βC and helix αC in IL-17RA SEFIR is mostly well ordered, displaying a helix (αCC′{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 Å to accommodate the αCC′{sub ins} helix without forming any knots. Helix αC was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR–SEFIR association via helix αC 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 αC could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.

  14. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    SciTech Connect (OSTI)

    Gough, Mallory Blanthorn-Hazell, Sophee Delury, Craig Parkin, Edward

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  15. Production, purification, and characterization of a fusion protein of carbonic anhydrase from Neisseria gonorrhoeae and cellulose binding domain from Clostridium thermocellum

    SciTech Connect (OSTI)

    Liu, Zhu; Bartlow, Patrick; Dilmore, Robert M.; Soong, Yee; Pan, Zhiwei; Koepsel, Richard; Ataai, Mohammad

    2009-01-01

    Carbon dioxide capture technologies have the potential to become an important climate change mitigation option through sequestration of gaseous CO2, A new concept for CO2 capture involves use of immobilized carbonic anhydrase (CA) that catalyzes the reversible hydration of CO2 to HCO3- and H+. Cost-efficient production of the enzyme and an inexpensive immobilization system are critical for development of economically feasible CA-based CO2 capture processes. An artificial, bifunctional enzyme containing CA from Neisseria gonorrhoeae and a cellulose binding domain (CBD) from Clostridium thermocellum was constructed with a His6 tag. The chimeric enzyme exhibited both CA activity and CBD binding affinity. This fusion enzyme is of particular interest due to its binding affinity for cellulose and retained CA activity, which could serve as the basis for improved technology to capture CO2 from flue gasses.

  16. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

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

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. Amore » putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.« less

  17. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    SciTech Connect (OSTI)

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

  18. 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.

  19. 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...

  20. 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...

  1. Coupled ion Binding and Structural Transitions Along the Transport...

    Office of Scientific and Technical Information (OSTI)

    binding primes the transport domain to accept its substrate and triggers extracellular gate opening, which prevents inward domain translocation until substrate binding takes place. ...

  2. Template:PleaseDelete | Open Energy Information

    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....

  3. 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.

  4. 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.

  5. 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. ...

  6. Critical role of domain crystallinity, domain purity and domain...

    Office of Scientific and Technical Information (OSTI)

    Critical role of domain crystallinity, domain purity and domain interface sharpness for reduced bimolecular recombination in polymer solar cells Citation Details In-Document Search ...

  7. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J.; Quesada, Mark A.; Randesi, Matthew

    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.

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

    SciTech Connect (OSTI)

    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, 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

  9. 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

  10. 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.

  11. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J.; Quesada, Mark A.; Randesi, Matthew

    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.

  12. 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.

  13. 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.

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

    Office of Scientific and Technical Information (OSTI)

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

  15. 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...

  16. The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

    SciTech Connect (OSTI)

    Syeda, Farisa; Fagan, Rebecca L.; Wean, Matthew; Avvakumov, George V.; Walker, John R.; Xue, Sheng; Dhe-Paganon, Sirano; Brenner, Charles

    2015-11-30

    Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenic DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.

  17. 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.

  18. 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.

  19. 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.

  20. Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1

    SciTech Connect (OSTI)

    Katsuki, Yuko; Sakamoto, Kei; Minamizato, Tokutaro; Makino, Hatsune; Umezawa, Akihiro; Ikeda, Masa-aki; Perbal, Bernard; Amagasa, Teruo; Yamaguchi, Akira; Katsube, Ken-ichi

    2008-04-11

    CCN3/NOV activates the Notch signal through the carboxyl terminal cysteine-rich (CT) domain. CCN3 transfection to Kusa-A1 inhibited osteogenic differentiation and cell proliferation, which is accompanied by upregulation of Hes/Hey, Notch downstream targets, and p21, a CDK inhibitor. Upregulation of Hes/Hey and p21 was abrogated by the deletion of CT domain. Anti-proliferative activity of CCN3 was also abrogated by CT domain deletion whereas anti-osteogenic activity was not completely abrogated. We found that CT domain-deleted CCN3 still possesses antagonistic effect on BMP-2. These results suggest that CCN3 employs Notch and BMP pathways in anti-osteogenic activity while it inhibits cell proliferation uniquely by Notch/p21 pathway.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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, ... Figure 1. Overall structure of human TLR3 ECD. The N-terminal region is colored blue, the ...

  6. Coenzyme A Binding to the Aminoglycoside Acetyltransferase (3)-IIIb Increases Conformational Sampling of Antibiotic Binding Site

    SciTech Connect (OSTI)

    Hu, Xiaohu; Norris, Adrianne; Baudry, Jerome Y; Serpersu, Engin H

    2011-01-01

    NMR spectroscopy experiments and molecular dynamics simulations were performed to describe the dynamic properties of the aminoglycoside acetyltransferase (3)-IIIb (AAC) in its apo and coenzyme A (CoASH) bound forms. The {sup 15}N-{sup 1}H HSQC spectra indicate a partial structural change and coupling of the CoASH binding site with another region in the protein upon the CoASH titration into the apo enzyme. Molecular dynamics simulations indicate a significant structural and dynamic variation of the long loop in the antibiotic binding domain in the form of a relatively slow (250 ns), concerted opening motion in the CoASH enzyme complex and that binding of the CoASH increases the structural flexibility of the loop, leading to an interchange between several similar equally populated conformations.

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

    SciTech Connect (OSTI)

    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 the 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.

  8. 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

  9. Product Binding Varies Dramatically between Processive and Nonprocessive Cellulase Enzymes

    SciTech Connect (OSTI)

    Bu, L.; Nimlos, M. R.; Shirts, M. R.; Stahlberg, J.; Himmel, M. E.; Crowley, M. F.; Beckham, G. T.

    2012-07-13

    Cellulases hydrolyze {beta}-1,4 glycosidic linkages in cellulose, which are among the most prevalent and stable bonds in Nature. Cellulases comprise many glycoside hydrolase families and exist as processive or nonprocessive enzymes. Product inhibition negatively impacts cellulase action, but experimental measurements of product-binding constants vary significantly, and there is little consensus on the importance of this phenomenon. To provide molecular level insights into cellulase product inhibition, we examine the impact of product binding on processive and nonprocessive cellulases by calculating the binding free energy of cellobiose to the product sites of catalytic domains of processive and nonprocessive enzymes from glycoside hydrolase families 6 and 7. The results suggest that cellobiose binds to processive cellulases much more strongly than nonprocessive cellulases. We also predict that the presence of a cellodextrin bound in the reactant site of the catalytic domain, which is present during enzymatic catalysis, has no effect on product binding in nonprocessive cellulases, whereas it significantly increases product binding to processive cellulases. This difference in product binding correlates with hydrogen bonding between the substrate-side ligand and the cellobiose product in processive cellulase tunnels and the additional stabilization from the longer tunnel-forming loops. The hydrogen bonds between the substrate- and product-side ligands are disrupted by water in nonprocessive cellulase clefts, and the lack of long tunnel-forming loops results in lower affinity of the product ligand. These findings provide new insights into the large discrepancies reported for binding constants for cellulases and suggest that product inhibition will vary significantly based on the amount of productive binding for processive cellulases on cellulose.

  10. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Caroline

    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.

  11. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Caroline

    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.

  12. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Carolyn

    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.

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

    SciTech Connect (OSTI)

    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 proteins 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Structure of the cytoplasmic domain of Yersinia pestis YscD, an essential component of the type III secretion system

    SciTech Connect (OSTI)

    Lountos, George T.; Tropea, Joseph E.; Waugh, David S.

    2012-09-17

    The Yersinia pestis YscD protein is an essential component of the type III secretion system. YscD consists of an N-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). Both the cytoplasmic and the periplasmic domains are required for the assembly of the type III secretion system. Here, the structure of the YscD cytoplasmic domain solved by SAD phasing is presented. Although the three-dimensional structure is similar to those of forkhead-associated (FHA) domains, comparison with the structures of canonical FHA domains revealed that the cytoplasmic domain of YscD lacks the conserved residues that are required for binding phosphothreonine and is therefore unlikely to function as a true FHA domain.

  19. 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.

  20. 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 ;)...

  1. 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...

  2. Thermodynamics of Binding Biomass to Cellulases for Renewable Fuel |

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

    Argonne Leadership Computing Facility Thermodynamics of Binding Biomass to Cellulases for Renewable Fuel PI Name: Michael Crowley PI Email: michael.crowley@nrel.gov Institution: National Renewable Energy Laboratory Allocation Program: INCITE Allocation Hours at ALCF: 70 Million Year: 2013 Research Domain: Energy Technologies The U.S. Department of Energy (DOE) has stipulated that 30% of the gasoline demand be displaced by renewable transportation fuels from non-food feedstock by 2030. The

  3. Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

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

    Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.

    2016-01-14

    Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less

  4. Domain Dynamics in Piezoresponse Force Microscopy: Quantitative...

    Office of Scientific and Technical Information (OSTI)

    The fine structure of the hysteresis loop is shown to be related to the observed jumps in the domain geometry during domain wall propagation (nanoscale Barkhausen jumps), ...

  5. Domain Dynamics in Piezoresponse Force Spectroscopy: Quantitative...

    Office of Scientific and Technical Information (OSTI)

    The fine structure of the hysteresis loop is shown to be related to the observed jumps in the domain geometry during domain wall propagation (nanoscale Barkhausen jumps), ...

  6. Structurally Similar but Functionally Diverse ZU5 Domains in Human Erythrocyte Ankyrin

    SciTech Connect (OSTI)

    Yasunaga, Mai; Ipsaro, Jonathan J.; Mondragón, Alfonso

    2014-10-02

    The metazoan cell membrane is highly organized. Maintaining such organization and preserving membrane integrity under different conditions are accomplished through intracellular tethering to an extensive, flexible protein network. Spectrin, the principal component of this network, is attached to the membrane through the adaptor protein ankyrin, which directly bridges the interaction between {beta}-spectrin and membrane proteins. Ankyrins have a modular structure that includes two tandem ZU5 domains. The first domain, ZU5A, is directly responsible for binding {beta}-spectrin. Here, we present a structure of the tandem ZU5 repeats of human erythrocyte ankyrin. Structural and biophysical experiments show that the second ZU5 domain, ZU5B, does not participate in spectrin binding. ZU5B is structurally similar to the ZU5 domain found in the netrin receptor UNC5b supramodule, suggesting that it could interact with other domains in ankyrin. Comparison of several ZU5 domains demonstrates that the ZU5 domain represents a compact and versatile protein interaction module.

  7. 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

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

    SciTech Connect (OSTI)

    Olek, Anna T.; Rayon, Catherine; Makowski, Lee; Kim, Hyung Rae; Ciesielski, Peter; Badger, John; Paul, Lake N.; Ghosh, Subhangi; Kihara, Daisuke; Crowley, Michael; Himmel, Michael E.; Bolin, Jeffrey T.; Carpita, Nicholas C.

    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, elongated 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.

  9. 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.

  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. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

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

    Giorgio, E.; Robyr, D.; Spielmann, M.; Ferrero, E.; Di Gregorio, E.; Imperiale, D.; Vaula, G.; Stamoulis, G.; Santoni, F.; Atzori, C.; et al

    2015-02-20

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (~660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in amore » postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. Finally, this second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.« less

  12. Multifunctional cellulase catalysis targeted by fusion to different carbohydrate-binding modules

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

    Walker, Johnnie A.; Takasuka, Taichi E.; Deng, Kai; Bianchetti, Christopher M.; Udell, Hannah S.; Prom, Ben M.; Kim, Hyunkee; Adams, Paul D.; Northen, Trent R.; Fox, Brian G.

    2015-12-21

    Carbohydrate binding modules (CBMs) bind polysaccharides and help target glycoside hydrolases catalytic domains to their appropriate carbohydrate substrates. To better understand how CBMs can improve cellulolytic enzyme reactivity, representatives from each of the 18 families of CBM found in Ruminoclostridium thermocellum were fused to the multifunctional GH5 catalytic domain of CelE (Cthe_0797, CelEcc), which can hydrolyze numerous types of polysaccharides including cellulose, mannan, and xylan. Since CelE is a cellulosomal enzyme, none of these fusions to a CBM previously existed. CelEcc_CBM fusions were assayed for their ability to hydrolyze cellulose, lichenan, xylan, and mannan. Several CelEcc_CBM fusions showed enhanced hydrolyticmore » activity with different substrates relative to the fusion to CBM3a from the cellulosome scaffoldin, which has high affinity for binding to crystalline cellulose. Additional binding studies and quantitative catalysis studies using nanostructure-initiator mass spectrometry (NIMS) were carried out with the CBM3a, CBM6, CBM30, and CBM44 fusion enzymes. In general, and consistent with observations of others, enhanced enzyme reactivity was correlated with moderate binding affinity of the CBM. Numerical analysis of reaction time courses showed that CelEcc_CBM44, a combination of a multifunctional enzyme domain with a CBM having broad binding specificity, gave the fastest rates for hydrolysis of both the hexose and pentose fractions of ionic-liquid pretreated switchgrass. In conclusion, we have shown that fusions of different CBMs to a single multifunctional GH5 catalytic domain can increase its rate of reaction with different pure polysaccharides and with pretreated biomass. This fusion approach, incorporating domains with broad specificity for binding and catalysis, provides a new avenue to improve reactivity of simple combinations of enzymes within the complexity of plant biomass.« less

  13. Multifunctional cellulase catalysis targeted by fusion to different carbohydrate-binding modules

    SciTech Connect (OSTI)

    Walker, Johnnie A.; Takasuka, Taichi E.; Deng, Kai; Bianchetti, Christopher M.; Udell, Hannah S.; Prom, Ben M.; Kim, Hyunkee; Adams, Paul D.; Northen, Trent R.; Fox, Brian G.

    2015-12-21

    Carbohydrate binding modules (CBMs) bind polysaccharides and help target glycoside hydrolases catalytic domains to their appropriate carbohydrate substrates. To better understand how CBMs can improve cellulolytic enzyme reactivity, representatives from each of the 18 families of CBM found in Ruminoclostridium thermocellum were fused to the multifunctional GH5 catalytic domain of CelE (Cthe_0797, CelEcc), which can hydrolyze numerous types of polysaccharides including cellulose, mannan, and xylan. Since CelE is a cellulosomal enzyme, none of these fusions to a CBM previously existed. CelEcc_CBM fusions were assayed for their ability to hydrolyze cellulose, lichenan, xylan, and mannan. Several CelEcc_CBM fusions showed enhanced hydrolytic activity with different substrates relative to the fusion to CBM3a from the cellulosome scaffoldin, which has high affinity for binding to crystalline cellulose. Additional binding studies and quantitative catalysis studies using nanostructure-initiator mass spectrometry (NIMS) were carried out with the CBM3a, CBM6, CBM30, and CBM44 fusion enzymes. In general, and consistent with observations of others, enhanced enzyme reactivity was correlated with moderate binding affinity of the CBM. Numerical analysis of reaction time courses showed that CelEcc_CBM44, a combination of a multifunctional enzyme domain with a CBM having broad binding specificity, gave the fastest rates for hydrolysis of both the hexose and pentose fractions of ionic-liquid pretreated switchgrass. In conclusion, we have shown that fusions of different CBMs to a single multifunctional GH5 catalytic domain can increase its rate of reaction with different pure polysaccharides and with pretreated biomass. This fusion approach, incorporating domains with broad specificity for binding and catalysis, provides a new avenue to improve reactivity of simple combinations of enzymes within the complexity of plant biomass.

  14. 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 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 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.

  15. 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

  16. 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.

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

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

    scratch files will be deleted on 11/30/2015 when Edison moves Edison scratch files will be deleted on 11/30/2015 when Edison moves November 15, 2015 by Zhengji Zhao Edison is scheduled to be powered off at 7:00am PST on November 30, 2015 to move to our new CRT building. We expect Edison to be offline for up to six weeks. During the move Edison's scratch file systems will be reformatted and all data will be removed. ALL files on the /scratch1, /scratch2, and /scratch3 file systems WILL BE

  18. Pyramidal inversion domain boundaries revisited

    SciTech Connect (OSTI)

    Remmele, T.; Albrecht, M.; Irmscher, K.; Fornari, R.; Strassburg, M.

    2011-10-03

    The structure of pyramidal inversion domain boundaries in GaN:Mg was investigated by aberration corrected transmission electron microscopy. The analysis shows the upper (0001) boundary to consist of a single Mg layer inserted between polarity inverted GaN layers in an abcab stacking. The Mg bound in these defects is at least one order of magnitude lower than the chemical Mg concentration. Temperature dependent Hall effect measurements show that up to 27% of the Mg acceptors is electrically compensated.

  19. 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.

  20. Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms

    SciTech Connect (OSTI)

    Lin,S.; Huang, Y.; Lo, Y.; Lu, M.; Wu, H.

    2007-01-01

    X-linked inhibitor of apoptosis (XIAP) is a potent negative regulator of apoptosis. It also plays a role in BMP signaling, TGF-{beta} signaling, and copper homeostasis. Previous structural studies have shown that the baculoviral IAP repeat (BIR2 and BIR3) domains of XIAP interact with the IAP-binding-motifs (IBM) in several apoptosis proteins such as Smac and caspase-9 via the conserved IBM-binding groove. Here, we report the crystal structure in two crystal forms of the BIR1 domain of XIAP, which does not possess this IBM-binding groove and cannot interact with Smac or caspase-9. Instead, the BIR1 domain forms a conserved dimer through the region corresponding to the IBM-binding groove. Structural and sequence analyses suggest that this dimerization of BIR1 in XIAP may be conserved in other IAP family members such as cIAP1 and cIAP2 and may be important for the action of XIAP in TGF-{beta} and BMP signaling and the action of cIAP1 and cIAP2 in TNF receptor signaling.

  1. How Dynein Binds to Microtubules

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

    ... Drawing source: R.D. Vale, Cell 112, 467 (2003). The heart of cytoplasmic dynein is the motor domain that couples hydrolysis of ATP with conformational changes that drive motility ...

  2. Slow Dynamics of Orbital Domains in Manganite

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

    in order to study their domain motion. By using these soft x rays generated at the ALS, one of the ... we can understand the movement of the electronic domain structure. ...

  3. 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,

  4. 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.

  5. 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

  6. 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.

  7. Structural basis for DNA binding by replication initiator Mcm10

    SciTech Connect (OSTI)

    Warren, Eric M.; Vaithiyalingam, Sivaraja; Haworth, Justin; Greer, Briana; Bielinsky, Anja-Katrin; Chazin, Walter J.; Eichman, Brandt F.

    2009-06-30

    Mcm10 is an essential eukaryotic DNA replication protein required for assembly and progression of the replication fork. The highly conserved internal domain (Mcm10-ID) has been shown to physically interact with single-stranded (ss) DNA, DNA polymerase alpha, and proliferating cell nuclear antigen (PCNA). The crystal structure of Xenopus laevis Mcm10-ID presented here reveals a DNA binding architecture composed of an oligonucleotide/oligosaccharide-fold followed in tandem by a variant and highly basic zinc finger. NMR chemical shift perturbation and mutational studies of DNA binding activity in vitro reveal how Mcm10 uses this unique surface to engage ssDNA. Corresponding mutations in Saccharomyces cerevisiae result in increased sensitivity to replication stress, demonstrating the functional importance of DNA binding by this region of Mcm10 to replication. In addition, mapping Mcm10 mutations known to disrupt PCNA, polymerase alpha, and DNA interactions onto the crystal structure provides insight into how Mcm10 might coordinate protein and DNA binding within the replisome.

  8. 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.

  9. 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.

  10. 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 ...

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

    SciTech Connect (OSTI)

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

    2015-02-25

    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. Moreover, 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, furthermore, we 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. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  17. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

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

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

    2015-02-25

    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. Moreover, our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of themore » 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, furthermore, we 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. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

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

    Rosenberg, Oren S.; Dovala, Dustin; Li, Xueming; Connolly, Lynn; Bendebury, Anastasia; Finer-Moore, Janet; Holton, James; Cheng, Yifan; Stroud, Robert M.; Cox, Jeffery S.

    2015-04-09

    We report that Mycobacterium tuberculosis and Staphylococcus aureus secrete virulence factors via type VII protein secretion (T7S), a system that intriguingly requires all of its secretion substrates for activity. To gain insights into T7S function, we used structural approaches to guide studies of the putative translocase EccC, a unique enzyme with three ATPase domains, and its secretion substrate EsxB. The crystal structure of EccC revealed that the ATPase domains are joined by linker/pocket interactions that modulate its enzymatic activity. EsxB binds via its signal sequence to an empty pocket on the C-terminal ATPase domain, which is accompanied by an increasemore » in ATPase activity. Surprisingly, substrate binding does not activate EccC allosterically but, rather, by stimulating its multimerization. Thus, the EsxB substrate is also an integral T7S component, illuminating a mechanism that helps to explain interdependence of substrates, and suggests a model in which binding of substrates modulates their coordinate release from the bacterium.« less

  7. Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

    SciTech Connect (OSTI)

    Rosenberg, Oren S.; Dovala, Dustin; Li, Xueming; Connolly, Lynn; Bendebury, Anastasia; Finer-Moore, Janet; Holton, James; Cheng, Yifan; Stroud, Robert M.; Cox, Jeffery S.

    2015-04-09

    We report that Mycobacterium tuberculosis and Staphylococcus aureus secrete virulence factors via type VII protein secretion (T7S), a system that intriguingly requires all of its secretion substrates for activity. To gain insights into T7S function, we used structural approaches to guide studies of the putative translocase EccC, a unique enzyme with three ATPase domains, and its secretion substrate EsxB. The crystal structure of EccC revealed that the ATPase domains are joined by linker/pocket interactions that modulate its enzymatic activity. EsxB binds via its signal sequence to an empty pocket on the C-terminal ATPase domain, which is accompanied by an increase in ATPase activity. Surprisingly, substrate binding does not activate EccC allosterically but, rather, by stimulating its multimerization. Thus, the EsxB substrate is also an integral T7S component, illuminating a mechanism that helps to explain interdependence of substrates, and suggests a model in which binding of substrates modulates their coordinate release from the bacterium.

  8. 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...

  9. 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:

  10. 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...

  11. Development of Nonlinear SSI Time Domain Methodology

    Broader source: Energy.gov [DOE]

    Development of Nonlinear SSI Time Domain Methodology Justin Coleman, P.E. Nuclear Science and Technology Idaho National Laboratory October 22, 2014

  12. 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...

  13. Optical coherence domain reflectometry guidewire

    DOE Patents [OSTI]

    Colston, Billy W.; Everett, Matthew; Da Silva, Luiz B.; Matthews, Dennis

    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.

  14. 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.

  15. 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.

  16. EERE Web Domains, URLs, and Redirects

    Broader source: Energy.gov [DOE]

    All Office of Energy Efficiency and Renewable Energy (EERE) office and partnership websites must use domains and URLs that have been approved by the Department of Energy (DOE)’s Chief Information Office, the Office of Management and Budget (OMB), and EERE's domain policies.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Deletion of nfnAB in Thermoanaerobacterium saccharolyticum and Its Effect on Metabolism

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

    Lo, Jonathan; Zheng, Tianyong; Olson, Daniel G.; Ruppertsberger, Natalie; Tripathi, Shital A.; Guss, Adam M.; Lynd, Lee R.

    2015-06-29

    NfnAB catalyzes the reversible transfer of electrons from reduced ferredoxin and NADH to 2 NADP+. The NfnAB complex has been hypothesized to be the main enzyme for ferredoxin oxidization in strains of Thermoanaerobacterium saccharolyticum engineered for increased ethanol production. NfnAB complex activity was detectable in crude cell extracts of T. saccharolyticum. In this paper, activity was also detected using activity staining of native PAGE gels. The nfnAB gene was deleted in different strains of T. saccharolyticum to determine its effect on end product formation. In wild-type T. saccharolyticum, deletion of nfnAB resulted in a 46% increase in H2 formation butmore » otherwise little change in other fermentation products. In two engineered strains with 80% theoretical ethanol yield, loss of nfnAB caused two different responses: in one strain, ethanol yield decreased to about 30% of the theoretical value, while another strain had no change in ethanol yield. Biochemical analysis of cell extracts showed that the ΔnfnAB strain with decreased ethanol yield had NADPH-linked alcohol dehydrogenase (ADH) activity, while the ΔnfnAB strain with unchanged ethanol yield had NADH-linked ADH activity. Deletion of nfnAB caused loss of NADPH-linked ferredoxin oxidoreductase activity in all cell extracts. Significant NADH-linked ferredoxin oxidoreductase activity was seen in all cell extracts, including those that had lost nfnAB. This suggests that there is an unidentified NADH:ferredoxin oxidoreductase (distinct from nfnAB) playing a role in ethanol formation. The NfnAB complex plays a key role in generating NADPH in a strain that had become reliant on NADPH-ADH activity. Importance: Thermophilic anaerobes that can convert biomass-derived sugars into ethanol have been investigated as candidates for biofuel formation. Many anaerobes have been genetically engineered to increase biofuel formation; however, key aspects of metabolism remain unknown and poorly understood. One

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    SciTech Connect (OSTI)

    Backues, Steven K.; Bednarek, Sebastian Y.

    2010-03-19

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  13. 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.

  14. 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.

  15. Proposed docking interface between peptidoglycan and the target recognition domain of zoocin A

    SciTech Connect (OSTI)

    Chen, Yinghua; Simmonds, Robin S.; Timkovich, Russell

    2013-11-15

    Highlights: •Peptidoglycan added to zoocin rTRD perturbs NMR resonances around W115. •Simulations predict docking to a shallow surface groove near W115. •The docking interface is similar to mammalian antibody–antigen sites. •EDTA binds to a distinct surface site. -- Abstract: A docking model is proposed for the target recognition domain of the lytic exoenzyme zoocin A with the peptidoglycan on the outer cell surface of sensitive bacterial strains. Solubilized fragments from such peptidoglycans perturb specific backbone and side chain amide resonances in the recombinant form of the domain designated rTRD as detected in two-dimensional {sup 1}H–{sup 15}N correlation NMR spectra. The affected residues comprise a shallow surface cleft on the protein surface near W115, N53, N117, and Q105 among others, which interacts with the peptide portion of the peptidoglycan. Calculations with AutoDock Vina provide models of the docking interface. There is approximate homology between the rTDR-peptidoglycan docking site and the antigen binding site of Fab antibodies with the immunoglobin fold. EDTA was also found to bind to rTRD, but at a site distinct from the proposed peptidoglycan docking site.

  16. 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.

  17. Human-computer interface incorporating personal and application domains

    DOE Patents [OSTI]

    Anderson, Thomas G.

    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.

  18. 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.

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

    Office of Scientific and Technical Information (OSTI)

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

  20. Molecular functions of the TLE tetramerization domain in Wnt...

    Office of Scientific and Technical Information (OSTI)

    domain in Wnt target gene repression Citation Details In-Document Search Title: Molecular functions of the TLE tetramerization domain in Wnt target gene repression ...

  1. 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...

  2. 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...

  3. 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 ...

  4. 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...

  5. Ferroelasticity and domain physics in two-dimensional transition...

    Office of Scientific and Technical Information (OSTI)

    Accepted Manuscript: Ferroelasticity and domain physics in two-dimensional transition metal dichalcogenide monolayers Prev Next Title: Ferroelasticity and domain physics in ...

  6. 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...

  7. 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...

  8. Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains

    SciTech Connect (OSTI)

    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; Lesley, Scott A.; Elsliger, Marc-André; Deacon, Ashley M.; Wilson, Ian A.

    2015-09-15

    ABSTRACT

    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. 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 of 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.

    IMPORTANCEPeptidoglycan 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

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

    SciTech Connect (OSTI)

    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; Lesley, Scott A.; Elsliger, Marc -André; Deacon, Ashley M.; Wilson, Ian A.

    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 of 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

  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

  11. A structural model of anti-anti-[sigma];#963; inhibition by a two-component receiver domain: the PhyR stress response regulator

    SciTech Connect (OSTI)

    Herrou, Julien; Foreman, Robert; Fiebig, Aretha; Crosson, Sean

    2012-03-30

    PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.

  12. A structural model of anti-anti-[sigma] inhibition by a two-component receiver domain: the PhyR stress response regulator

    SciTech Connect (OSTI)

    Herrou, Julien; Foreman, Robert; Fiebig, Aretha; Crosson, Sean

    2012-05-09

    PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.

  13. 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.

  14. 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.

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

    SciTech Connect (OSTI)

    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 demonstrate 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.

  16. 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

  17. Critical role of domain crystallinity, domain purity and domain interface sharpness for reduced bimolecular recombination in polymer solar cells

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

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; Dubey, Ashish; Khatiwada, Devendra; Zhang, Cheng; Qiao, Qiquan

    2014-12-31

    In this study, inverted bulk heterojunction solar cells were fabricated using poly(3-hexylthiophene) (P3HT) blended with two different fullerene derivatives namely phenyl-C61-butyric acid methyl ester (PC60BM) and indene-C60 bis-adduct (IC60BA). The effects of annealing temperatures on the morphology, optical and structural properties were studied and correlated to differences in photovoltaic device performance. It was observed that annealing temperature significantly improved the performance of P3HT:IC60BA solar cells while P3HT:PC60BM cells showed relatively less improvement. The performance improvement is attributed to the extent of fullerene mixing with polymer domains. Energy filtered transmission electron microscopy (EFTEM) and x-ray diffraction (XRD) results showed that ICBAmore » mixes with disordered P3HT much more readily than PC60BM which leads to lower short circuit current density and fill factor for P3HT:IC60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC60BA whereas in P3HT:PC60BM films, annealing above 80°C leads to negligible change in crystallinity. Crystallization of P3HT also leads to higher domain purity as seen EFTEM. Further it is seen that cells processed with additive nitrobenzene (NB) showed enhanced short circuit current density and power conversion efficiency regardless of the fullerene derivative used. Addition of NB led to nanoscale phase separation between purer polymer and fullerene domains. Kelvin probe force microscopy (KPFM) images showed that enhanced domain purity in additive casted films led to a sharper interface between polymer and fullerene. Lastly, enhanced domain purity and interfacial sharpness led to lower bimolecular recombination and higher mobility and charge carrier lifetime in NB modified devices.« less

  18. 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.

  19. 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)

  20. Critical role of domain crystallinity, domain purity and domain interface sharpness for reduced bimolecular recombination in polymer solar cells

    SciTech Connect (OSTI)

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; Dubey, Ashish; Khatiwada, Devendra; Zhang, Cheng; Qiao, Qiquan

    2014-12-31

    In this study, inverted bulk heterojunction solar cells were fabricated using poly(3-hexylthiophene) (P3HT) blended with two different fullerene derivatives namely phenyl-C61-butyric acid methyl ester (PC60BM) and indene-C60 bis-adduct (IC60BA). The effects of annealing temperatures on the morphology, optical and structural properties were studied and correlated to differences in photovoltaic device performance. It was observed that annealing temperature significantly improved the performance of P3HT:IC60BA solar cells while P3HT:PC60BM cells showed relatively less improvement. The performance improvement is attributed to the extent of fullerene mixing with polymer domains. Energy filtered transmission electron microscopy (EFTEM) and x-ray diffraction (XRD) results showed that ICBA mixes with disordered P3HT much more readily than PC60BM which leads to lower short circuit current density and fill factor for P3HT:IC60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC60BA whereas in P3HT:PC60BM films, annealing above 80°C leads to negligible change in crystallinity. Crystallization of P3HT also leads to higher domain purity as seen EFTEM. Further it is seen that cells processed with additive nitrobenzene (NB) showed enhanced short circuit current density and power conversion efficiency regardless of the fullerene derivative used. Addition of NB led to nanoscale phase separation between purer polymer and fullerene domains. Kelvin probe force microscopy (KPFM) images showed that enhanced domain purity in additive casted films led to a sharper interface between polymer and fullerene. Lastly, enhanced domain purity and interfacial sharpness led to lower bimolecular recombination and higher mobility and charge carrier lifetime in NB modified devices.

  1. 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.

  2. 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.

  3. 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.

  4. Domain decomposition multigrid for unstructured grids

    SciTech Connect (OSTI)

    Shapira, Yair

    1997-01-01

    A two-level preconditioning method for the solution of elliptic boundary value problems using finite element schemes on possibly unstructured meshes is introduced. It is based on a domain decomposition and a Galerkin scheme for the coarse level vertex unknowns. For both the implementation and the analysis, it is not required that the curves of discontinuity in the coefficients of the PDE match the interfaces between subdomains. Generalizations to nonmatching or overlapping grids are made.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Deletion of the paired [alpha]5(IV) and [alpha]6(IV) collagen genes in inherited smooth muscle tumors

    SciTech Connect (OSTI)

    Zhou, J.; Mochizuki, T.; Reeders, S.T. ); Smeets, H. ); Antignac, C. ); Laurila, P. ); Paepe, A. de ); Tryggvason, K. )

    1993-08-27

    The gene encoding [alpha]6(IV) collagen, COL4A6, was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of the [alpha]5(IV) collagen gene, COL4A5. In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes. In some families, AS cosegregates with diffuse leiomyomatosis (DL), a benign smooth muscle tumor diathesis. Here it is shown that patients with AS-DL harbor deletions that disrupt both COL4A5 and COL4A6. Thus, type IV collagen may regulate smooth muscle differentiation and morphogenesis.

  12. 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.

  13. A recombination outside the BB deletion refines the location of the X-linked retinitis pigmentosa locus RP3

    SciTech Connect (OSTI)

    Fujita, R.; Bingham, E.; Forsythe, P.; McHenry, C.

    1996-07-01

    Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was though to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending {approximately}3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located {approximately}40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected male shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3. 22 refs., 3 figs., 2 tabs.

  14. 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 ...

  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

  16. 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.

  17. 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.

  18. 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...

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

  20. 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.

  1. 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.

  2. Shaping nanoscale magnetic domain memory in exchange-coupled ferromagnets

    Office of Scientific and Technical Information (OSTI)

    by field cooling (Journal Article) | SciTech Connect Shaping nanoscale magnetic domain memory in exchange-coupled ferromagnets by field cooling Citation Details In-Document Search Title: Shaping nanoscale magnetic domain memory in exchange-coupled ferromagnets by field cooling The advance of magnetic nanotechnologies relies on detailed understanding of nanoscale magnetic mechanisms in materials. Magnetic domain memory (MDM), that is, the tendency for magnetic domains to repeat the same

  3. 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

  4. 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

  5. Dental optical coherence domain reflectometry explorer

    DOE Patents [OSTI]

    Everett, Matthew J.; Colston, Jr., Billy W.; Sathyam, Ujwal S.; Da Silva, Luiz B.

    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.

  6. Structural And Functional Analysis of the Ligand Specificity of the HtrA2/OmI PDZ Domain

    SciTech Connect (OSTI)

    Zhang, Y.; Appleton, B.A.; Wu, P.; Wiesmann, C.; Sidhu, S.S.

    2009-06-04

    The mitochondrial serine protease HtrA2/Omi helps to maintain mitochondrial function by handling misfolded proteins in the intermembrane space. In addition, HtrA2/Omi has been implicated as a proapoptotic factor upon release into the cytoplasm during the cell death cascade. The protein contains a C-terminal PDZ domain that packs against the protease active site and inhibits proteolytic activity. Engagement of the PDZ domain by peptide ligands has been shown to activate the protease and also has been proposed to mediate substrate recognition. We report a detailed structural and functional analysis of the human HtrA2/Omi PDZ domain using peptide libraries and affinity assays to define specificity, X-ray crystallography to view molecular details of PDZ-ligand interactions, and alanine-scanning mutagenesis to probe the peptide-binding groove. We show that the HtrA2/Omi PDZ domain recognizes both C-terminal and internal stretches of extended, hydrophobic polypeptides. High-affinity ligand recognition requires contacts with up to five hydrophobic side chains by distinct sites on the PDZ domain. However, no particular residue type is absolutely required at any position, and thus, the HtrA2/Omi PDZ domain appears to be a promiscuous module adapted to recognize unstructured, hydrophobic polypeptides. This type of specificity is consistent with the biological role of HtrA2/Omi in mitochondria, which requires the recognition of diverse, exposed stretches of hydrophobic sequences in misfolded proteins. The findings are less consistent with, but do not exclude, a role for the PDZ domain in targeting the protease to specific substrates during apoptosis.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Structural Basis of Ubiquitin Recognition by the Ubiquitin-associated (UBA) Domain of the Ubiquitin Ligase EDD

    SciTech Connect (OSTI)

    Kozlov, G.; Nguyen, L; Lin, T; De Crescenzo, G; Park, M; Gehring, K

    2007-01-01

    EDD (or HYD) is an E3 ubiquitin ligase in the family of HECT (homologous to E6-AP C terminus) ligases. EDD contains an N-terminal ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Here, we use isothermal titration calorimetry (ITC), NMR titrations, and pull-down assays to show that the EDD UBA domain binds ubiquitin. The 1.85{angstrom} crystal structure of the complex with ubiquitin reveals the structural basis of ubiquitin recognition by UBA helices {alpha}1 and {alpha}3. The structure shows a larger number of intermolecular hydrogen bonds than observed in previous UBA/ubiquitin complexes. Two of these involve ordered water molecules. The functional importance of residues at the UBA/ubiquitin interface was confirmed using site-directed mutagenesis. Surface plasmon resonance (SPR) measurements show that the EDD UBA domain does not have a strong preference for polyubiquitin chains over monoubiquitin. This suggests that EDD binds to monoubiquitinated proteins, which is consistent with its involvement in DNA damage repair pathways.

  12. Single Molecule Kinetics of ENTH Binding to Lipid Membranes

    SciTech Connect (OSTI)

    Rozovsky, Sharon; Forstner, Martin B.; Sondermann, Holger; Groves, Jay T.

    2012-04-03

    Transient recruitment of proteins to membranes is a fundamental mechanism by which the cell exerts spatial and temporal control over proteins’ localization and interactions. Thus, the specificity and the kinetics of peripheral proteins’ membrane residence are an attribute of their function. In this article, we describe the membrane interactions of the interfacial epsin N-terminal homology (ENTH) domain with its target lipid phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2). The direct visualization and quantification of interactions of single ENTH molecules with supported lipid bilayers is achieved using total internal reflection fluorescence microscopy (TIRFM) with a time resolution of 13 ms. This enables the recording of the kinetic behavior of ENTH interacting with membranes with physiologically relevant concentrations of PtdIns(4,5)P2 despite the low effective binding affinity. Subsequent single fluorophore tracking permits us to build up distributions of residence times and to measure ENTH dissociation rates as a function of membrane composition. In addition, due to the high time resolution, we are able to resolve details of the motion of ENTH associated with a simple, homogeneous membrane. In this case ENTH’s diffusive transport appears to be the result of at least three different diffusion processes.

  13. 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.

  14. Flow cytometer measurement of binding assays

    DOE Patents [OSTI]

    Saunders, George C.

    1987-01-01

    A method of measuring the result of a binding assay that does not require separation of fluorescent smaller particles is disclosed. In a competitive binding assay the smaller fluorescent particles coated with antigen compete with antigen in the sample being analyzed for available binding sites on larger particles. In a sandwich assay, the smaller, fluorescent spheres coated with antibody attach themselves to molecules containing antigen that are attached to larger spheres coated with the same antibody. The separation of unattached, fluorescent smaller particles is made unnecessary by only counting the fluorescent events triggered by the laser of a flow cytometer when the event is caused by a particle with a light scatter measurement within a certain range corresponding to the presence of larger particles.

  15. Birefringence insensitive optical coherence domain reflectometry system

    DOE Patents [OSTI]

    Everett, Matthew J.; Davis, Joseph G.

    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.

  16. Interaction of the S100A6 mutant (C3S) with the V domain of the receptor for advanced glycation end products (RAGE)

    SciTech Connect (OSTI)

    Mohan, Sepuru K. Gupta, Arun A. Yu, Chin

    2013-05-03

    Highlights: •The halo human S100A6 (C3S) NMR chemical shifts were assigned. •The interactions between S100A6m and RAGE V domain was investigated by ITC. •The residues involved in the S100A6m–RAGE V domain binding were mapped by {sup 1}H–{sup 15}N HSQC titration. •S100A6–RAGE V domain tetrameric complex model was generated from NMR studies. •The S100A6–RAGE V domain interface regions were elucidated based on HADDOCK model. -- Abstract: S100A6 is involved in several vital biological functions, such as calcium sensing and cell proliferation. It is a homodimeric protein that belongs to the S100 protein family. The receptor for advanced glycation end products (RAGE) has been shown to play a role in the progression of various disease conditions, such as diabetes and immune/inflammatory disorders. Information regarding the association of RAGE with S100 proteins at a molecular level is useful to understand the diversity of the RAGE signaling pathways. In this report, biomolecular NMR techniques were utilized for the resonance assignment of the C3S mutation in human S100A6 and characterizing its interaction with the RAGE V domain. Further binding affinity between S100A6m and the RAGE V domain was determined by isothermal titration calorimetric studies. HADDOCK was used to generate a heterotetramer model of the S100A6m–RAGE V domain complex. This model provides an important insights into the S100–RAGE cellular signaling pathway.

  17. Glycosylation Helps Cellulase Enzymes Bind to Plant Cell Walls (Fact Sheet)

    SciTech Connect (OSTI)

    Not Available

    2012-06-01

    Computer simulations suggest a new strategy to design enhanced enzymes for biofuels production. Large-scale computer simulations predict that the addition of glycosylation on carbohydrate-binding modules can dramatically improve the binding affinity of these protein domains over amino acid mutations alone. These simulations suggest that glycosylation can be used as a protein engineering tool to enhance the activity of cellulase enzymes, which are a key component in the conversion of cellulose to soluble sugars in the production of biofuels. Glycosylation is the covalent attachment of carbohydrate molecules to protein side chains, and is present in many proteins across all kingdoms of life. Moreover, glycosylation is known to serve a wide variety of functions in biological recognition, cell signaling, and metabolism. Cellulase enzymes, which are responsible for deconstructing cellulose found in plant cell walls to glucose, contain glycosylation that when modified can affect enzymatic activity-often in an unpredictable manner. To gain insight into the role of glycosylation on cellulase activity, scientists at the National Renewable Energy Laboratory (NREL) used computer simulation to predict that adding glycosylation on the carbohydrate-binding module of a cellulase enzyme dramatically boosts the binding affinity to cellulose-more than standard protein engineering approaches in which amino acids are mutated. Because it is known that higher binding affinity in cellulases leads to higher activity, this work suggests a new route to designing enhanced enzymes for biofuels production. More generally, this work suggests that tuning glycosylation in cellulase enzymes is a key factor to consider when engineering biochemical conversion processes, and that more work is needed to understand how glycosylation affects cellulase activity at the molecular level.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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 domain’s 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.

  8. 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...

  9. Structural Basis for the Interaction between Pyk2-FAT Domain...

    Office of Scientific and Technical Information (OSTI)

    Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats Citation Details In-Document Search Title: Structural Basis for the Interaction between ...

  10. Death Domain Assembly Mechanism Revealed by Crystal Structure...

    Office of Scientific and Technical Information (OSTI)

    SciTech Connect Search Results Journal Article: Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex Citation Details In-Document ...

  11. 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...

  12. 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...

  13. Initiation factor 2 crystal structure reveals a different domain...

    Office of Scientific and Technical Information (OSTI)

    Initiation factor 2 crystal structure reveals a different domain organization from eukaryotic initiation factor 5B and mechanism among translational GTPases Citation Details ...

  14. 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...

  15. 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...

  16. 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)...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Frequency domain quantum optimal control under multiple constraints...

    Office of Scientific and Technical Information (OSTI)

    SciTech Connect Search Results Journal Article: Frequency domain quantum optimal control under multiple constraints Citation Details In-Document Search This content will become ...

  4. 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.,...

  5. 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...

  6. 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...

  7. 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...

  8. 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,...

  9. 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...

  10. 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...

  11. 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 ...

  12. Catheter guided by optical coherence domain reflectometry

    DOE Patents [OSTI]

    Everett, Matthew; Colston, Billy W.; Da Silva, Luiz B.; Matthews, Dennis

    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.

  13. 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.

  14. BPA FINAL Binding Arbitration policy | Department of Energy

    Office of Environmental Management (EM)

    BPA FINAL Binding Arbitration policy BPA FINAL Binding Arbitration policy Alternative dispute resolution (ADR) encompasses a variety of methods that parties may use to resolve disputes without litigation. Arbitration is a private, less formal process in which parties agree to submit a dispute to one or more impartial arbitrators who then render a decision or award. In non-binding arbitration a party is not required to accept the arbitrator's decision. In contrast, a decision or award in binding

  15. 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.

  16. 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.

  17. 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.

  18. Structure of the JmjC domain-containing protein NO66 complexed with ribosomal protein Rpl8

    SciTech Connect (OSTI)

    Wang, Chengliang; Zhang, Qiongdi; Hang, Tianrong; Tao, Yue; Ma, Xukai; Wu, Minhao; Zhang, Xuan Zang, Jianye

    2015-08-28

    The structure of the complex of NO66 and Rpl8 was solved in the native state and NO66 recognizes the consensus motif NHXH . Tetramerization is required for efficient substrate binding and catalysis by NO66. The JmjC domain-containing proteins belong to a large family of oxygenases possessing distinct substrate specificities which are involved in the regulation of different biological processes, such as gene transcription, RNA processing and translation. Nucleolar protein 66 (NO66) is a JmjC domain-containing protein which has been reported to be a histone demethylase and a ribosome protein 8 (Rpl8) hydroxylase. The present biochemical study confirmed the hydroxylase activity of NO66 and showed that oligomerization is required for NO66 to efficiently catalyze the hydroxylation of Rpl8. The structures of NO66{sup 176–C} complexed with Rpl8{sup 204–224} in a tetrameric form and of the mutant protein M2 in a dimeric form were solved. Based on the results of structural and biochemical analyses, the consensus sequence motif NHXH recognized by NO66 was confirmed. Several potential substrates of NO66 were found by a BLAST search according to the consensus sequence motif. When binding to substrate, the relative positions of each subunit in the NO66 tetramer shift. Oligomerization may facilitate the motion of each subunit in the NO66 tetramer and affect the catalytic activity.

  19. 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.

  20. Increased magnetic damping of a single domain wall and adjacent magnetic domains detected by spin torque diode in a nanostripe

    SciTech Connect (OSTI)

    Lequeux, Steven; Sampaio, Joao; Bortolotti, Paolo; Cros, Vincent; Grollier, Julie; Matsumoto, Rie; Yakushiji, Kay; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji; Nishimura, Kazumasa; Nagamine, Yoshinori; Tsunekawa, Koji

    2015-11-02

    Spin torque resonance has been used to simultaneously probe the dynamics of a magnetic domain wall and of magnetic domains in a nanostripe magnetic tunnel junction. Due to the large associated resistance variations, we are able to analyze quantitatively the resonant properties of these single nanoscale magnetic objects. In particular, we find that the magnetic damping of both the domains and the domain wall is doubled compared to the damping value of the host magnetic layer. We estimate the contributions to the damping arising from the dipolar couplings between the different layers in the junction and from the intralayer spin pumping effect, and find that they cannot explain the large damping enhancement that we observe. We conclude that the measured increased damping is intrinsic to large amplitudes excitations of spatially localized modes or solitons such as vibrating or propagating domain walls.

  1. 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.

  2. Polynucleotides encoding TRF1 binding proteins

    DOE Patents [OSTI]

    Campisi, Judith; Kim, Sahn-Ho

    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.

  3. Specific albumin binding to microvascular endothelium in culture

    SciTech Connect (OSTI)

    Schnitzer, J.E.; Carley, W.W.; Palade, G.E. )

    1988-03-01

    The specific binding of rat serum albumin (RSA) to confluent microvascular endothelial cells in culture derived from the vasculature of the rat epididymal fat pad was studied at 4{degree}C by radioassay and immunocytochemistry. Radioiodinated RSA ({sup 125}I-RSA) binding to the cells reached equilibrium at {approximately} 20 min incubation. Albumin binding was a slowly saturating function over concentrations ranging from 0.01 to 50 mg/ml. Specific RSA binding with a moderate apparent affinity constant of 1.0 mg/ml and with a maximum binding concentration of 90 ng/cm{sup 2} was immunolocalized with anti-RSA antibody to the outer (free) side of the enothelium. Scatchard analysis of the binding yielded a nonlinear binding curve with a concave-upward shape. Dissociation rate analysis supports negative cooperativity of albumin binding, but multiple binding sites may also be present. Albumin binding fulfilled many requirements for ligand specificity including saturability, reversibility, competibility, and dependence on both cell type and cell number. The results are discussed in terms of past in situ investigations on the localization of albumin binding to vascular endothelium and its effect on transendothelial molecular transport.

  4. An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia

    SciTech Connect (OSTI)

    Tahara, T.; Kraus, J.P.; Rosenberg, L.E. )

    1990-02-01

    Propionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionly-CoA carboxylase. Affected patients fall into two complementation groups, pccA and pccBC (subgroups B, C, and BC), resulting from deficiency of the nonidentical {alpha} and {beta} subunits of PCC, respectively. The authors have detected an unusual insertion/deletion in the DNA of patients from the pccBC and pccC subgroups that replaces 14 nucleotides in the coding sequence of the {beta} subunit with 12 nucleotides unrelated to this region of the gene. Among 14 unrelated Caucasian patients in the pccBc complementation group, this unique mutation was found in 8 of 28 mutant alleles examined. Mutant allele-specific oligonucleotide hybridization to amplified genomic DNAs revealed that the inserted 12 nucleotides do not originate in an {approx}1000-bp region around the mutation. In the course of the investigation, they identified another mutation in the same exon: a 3-bp in-frame deletion that eliminates one of two isoleucine codons immediately preceding the Msp I site. Two unrelated patients were compound heterozygotes for this single-codon deletion and for the insertion/deletion described above. They conclude that either there is a propensity for the PCC {beta}-subunit gene to undergo mutations of this sort at this position or, more likely, the mutations in all of the involved Caucasian patients have a common origin in preceding generations.

  5. 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.

  6. Reflection-Based Python-C++ Bindings

    SciTech Connect (OSTI)

    Generowicz, Jacek; Lavrijsen, Wim T.L.P.; Marino, Massimo; Mato, Pere

    2004-10-14

    Python is a flexible, powerful, high-level language with excellent interactive and introspective capabilities and a very clean syntax. As such, it can be a very effective tool for driving physics analysis. Python is designed to be extensible in low-level C-like languages, and its use as a scientific steering language has become quite widespread. To this end, existing and custom-written C or C++ libraries are bound to the Python environment as so-called extension modules. A number of tools for easing the process of creating such bindings exist, such as SWIG and Boost. Python. Yet, the process still requires a considerable amount of effort and expertise. The C++ language has few built-in introspective capabilities, but tools such as LCGDict and CINT add this by providing so-called dictionaries: libraries that contain information about the names, entry points, argument types, etc. of other libraries. The reflection information from these dictionaries can be used for the creation of bindings and so the process can be fully automated, as dictionaries are already provided for many end-user libraries for other purposes, such as object persistency. PyLCGDict is a Python extension module that uses LCG dictionaries, as PyROOT uses CINT reflection information, to allow /cwPython users to access C++ libraries with essentially no preparation on the users' behalf. In addition, and in a similar way, PyROOT gives ROOT users access to Python libraries.

  7. 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.

  8. Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata

    SciTech Connect (OSTI)

    Sampathkumar, Parthasarathy; Kim, Seung Joong; Manglicmot, Danalyn; Bain, Kevin T.; Gilmore, Jeremiah; Gheyi, Tarun; Phillips, Jeremy; Pieper, Ursula; Fernandez-Martinez, Javier; Franke, Josef D.; Matsui, Tsutomu; Tsuruta, Hiro; Atwell, Shane; Thompson, Devon A.; Emtage, J. Spencer; Wasserman, Stephen R.; Rout, Michael P.; Sali, Andrej; Sauder, J. Michael; Almo, Steven C.; Burley, Stephen K.

    2012-10-23

    The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of {approx}456 polypeptide chains contributed by {approx}30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC. Nup116 is a modular protein with N-terminal 'FG' repeats containing a Gle2p-binding sequence motif and a NPC targeting domain at its C-terminus. We report the crystal structure of the NPC targeting domain of Candida glabrata Nup116, consisting of residues 882-1034 [CgNup116(882-1034)], at 1.94 {angstrom} resolution. The X-ray structure of CgNup116(882-1034) is consistent with the molecular envelope determined in solution by small-angle X-ray scattering. Structural similarities of CgNup116(882-1034) with homologous domains from Saccharomyces cerevisiae Nup116, S. cerevisiae Nup145N, and human Nup98 are discussed.

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

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

    PDF icon Smart Grid Conceptual ActorsData Flow Diagram- Cross Domain Network Focued- Open SGSG-Network TF More Documents & Publications Report to NIST on the Smart Grid ...

  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 Print Movement is fundamental to life. It takes place even at the cellular level where cargo is continually being transported...

  11. Magnetic anisotropy and domain structure of the layered manganite...

    Office of Scientific and Technical Information (OSTI)

    1.64Mnsub 2Osub 7 Citation Details In-Document Search Title: Magnetic anisotropy and domain structure of the layered manganite Lasub 1.36Srsub 1.64Mnsub 2Osub ...

  12. The application of domain decomposition to time-domain computations of nonlinear water waves with a panel method

    SciTech Connect (OSTI)

    De Haas, P.C.A.; Zandbergen, P.J.

    1996-12-01

    In this paper an iterative domain decomposition method for the solution of Laplace`s equation is described and its effectiveness in time-domain computations of nonlinear water waves with a panel method is investigated. An important aspect of these computations is the varying shape of the free surface. The convergence of the iterative method is fast and leads to a speedup of the computations in the aforementioned application. The domain decomposition method gives a considerable reduction of memory requirements. Furthermore, it lends itself naturally for parallel computing. 18 refs., 9 figs., 2 tabs.

  13. 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.

  14. Multi-domain Job Coscheduling for Leadership Computing Systems | Argonne

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

    Leadership Computing Facility Multi-domain Job Coscheduling for Leadership Computing Systems Authors: Tang, W., Desai, N., Vishwanath, V., Buettner, D., Lan, Z. Current supercomputing centers usually deploy a large-scale compute system together with an associated data analysis or visualization system. Multiple scenarios have driven the demand that some associated jobs co-execute on different machines. We propose a multi-domain coscheduling mechanism, providing the ability to coordinate

  15. 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

  16. 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}

  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 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

  18. 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 pvmrw13_ps2_casewestern_bruckman.pdf (6.77 MB) More Documents & Publications Literature Review of the Effects of UV Exposure on PV Modules Failure Rates from Certification Testing to UL

  19. Micro- and nano-domain engineering in lithium niobate

    SciTech Connect (OSTI)

    Shur, V. Ya.; Akhmatkhanov, A. R.; Baturin, I. S.

    2015-12-15

    The physical basis of the domain engineering in ferroelectrics and its application to lithium niobate crystals were reviewed. The unified kinetic approach to the domain structure evolution in electric field was formulated and its validity for understanding the variety of observed domain evolution scenarios was demonstrated. The kinetics and statics of the domain structure in the crystals of lithium niobate family including congruent, stoichiometric, and MgO doped ones have been discussed. The main stages of the periodical poling process and related problems have been pointed out. The basic poling techniques applied for creation of the periodical domain structures in bulk crystals and waveguides were compared. The recent applications of the periodically poled lithium niobate for light frequency conversion using second harmonic generation and optical parametric oscillation, excitation of the surface acoustic waves, and generation of terahertz radiation have been discussed. The special attention has been paid for achievements in fabrication of high-power optical parametric oscillation and integrated optical devices with periodically poled lithium niobate. The future trends in periodical poling and development of the nanodomain engineering which will allow to create the nanoscale domain patterns necessary for utilization of the new nonlinear interactions were reviewed.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Binding Behavior of Dopamine Transporter Key to Understanding...

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

    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 ...

  5. 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.

  6. 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...

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

    Office of Scientific and Technical Information (OSTI)

    X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified ... LIFE SCIENCES; ALDEHYDES; CARBOXYLIC ACIDS; CRYSTAL STRUCTURE; IN VIVO; INFLAMMATION; ...

  8. Hydrodynamic and Membrane Binding Properties of Purified Rous...

    Office of Scientific and Technical Information (OSTI)

    Purified Rous Sarcoma Virus Gag Protein Citation Details In-Document Search Title: Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein ...

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

    Office of Scientific and Technical Information (OSTI)

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

  10. Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding...

    Office of Scientific and Technical Information (OSTI)

    Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding Change Mechanism Resources with Additional Information Paul D. Boyer Courtesy of UCLA 'For Paul Boyer, the Nobel Prize ...

  11. 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,...

  12. Experimental observation of the interaction of propagating spin waves with Néel domain walls in a Landau domain structure

    SciTech Connect (OSTI)

    Pirro, P.; Sebastian, T.; Leven, B.; Hillebrands, B.; Koyama, T.; Brächer, T.

    2015-06-08

    The interaction of propagating dipolar spin waves with magnetic domain walls is investigated in square-shaped microstructures patterned from the Heusler compound Co{sub 2}Mn{sub 0.6}Fe{sub 0.4}Si. Using magnetic force microscopy, the reversible preparation of a Landau state with four magnetic domains separated by Néel domain walls is confirmed. A local spin-wave excitation using a microstructured antenna is realized in one of the domains. It is shown by Brillouin light scattering microscopy that the domain structure in the remanence state has a strong influence on the spin-wave excitation and propagation. The domain walls strongly reflect the spin waves and can be used as spin-wave reflectors. A comparison with micromagnetic simulations shows that the strong reflection is due to the long-range dipolar interaction which has important implications for the use of these spin waves for exerting an all-magnonic spin-transfer torque.

  13. 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.

  14. MicroRNAs Suppress NB Domain Genes in Tomato That Confer Resistance to Fusarium oxysporum

    SciTech Connect (OSTI)

    Ouyang, Shouqiang; Park, Gyungsoon; Atamian, Hagop S.; Han, Cliff S.; Stajich, Jason E.; Kaloshian, Isgouhi; Borkovich, Katherine A.

    2014-10-16

    MicroRNAs (miRNAs) suppress the transcriptional and post-transcriptional expression of genes in plants. Several miRNA families target genes encoding nucleotide-binding site–leucine-rich repeat (NB-LRR) plant innate immune receptors. The fungus Fusarium oxysporum f. sp. lycopersici causes vascular wilt disease in tomato. Here, we explored a role for miRNAs in tomato defense against F. oxysporum using comparative miRNA profiling of susceptible (Moneymaker) and resistant (Motelle) tomato cultivars. slmiR482f and slmiR5300 were repressed during infection of Motelle with F. oxysporum. Two predicted mRNA targets each of slmiR482f and slmiR5300 exhibited increased expression in Motelle and the ability of these four targets to be regulated by the miRNAs was confirmed by co-expression in Nicotiana benthamiana. Silencing of the targets in the resistant Motelle cultivar revealed a role in fungal resistance for all four genes. All four targets encode proteins with full or partial nucleotide-binding (NB) domains. One slmiR5300 target corresponds to tm-2, a susceptible allele of the Tomato Mosaic Virus resistance gene, supporting functions in immunity to a fungal pathogen. The observation that none of the targets correspond to I-2, the only known resistance (R) gene for F. oxysporum in tomato, supports roles for additional R genes in the immune response. In conclusion, taken together, our findings suggest that Moneymaker is highly susceptible because its potential resistance is insufficiently expressed due to the action of miRNAs.

  15. 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.

  16. 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.

  17. Magnetoelectric domain wall dynamics and its implications for magnetoelectric memory

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

    Belashchenko, K. D.; Tchernyshyov, O.; Kovalev, Alexey A.; Tretiakov, O. A.

    2016-03-30

    Domain wall dynamics in a magnetoelectric antiferromagnet is analyzed, and its implications for magnetoelectric memory applications are discussed. Cr2O3 is used in the estimates of the materials parameters. It is found that the domain wall mobility has a maximum as a function of the electric field due to the gyrotropic coupling induced by it. In Cr2O3, the maximal mobility of 0.1 m/(s Oe) is reached at E≈0.06 V/nm. Fields of this order may be too weak to overcome the intrinsic depinning field, which is estimated for B-doped Cr2O3. These major drawbacks for device implementation can be overcome by applying amore » small in-plane shear strain, which blocks the domain wall precession. Domain wall mobility of about 0.7 m/(s Oe) can then be achieved at E = 0.2 V/nm. Furthermore, a split-gate scheme is proposed for the domain-wall controlled bit element; its extension to multiple-gate linear arrays can offer advantages in memory density, programmability, and logic functionality.« less

  18. 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

  19. Real-time observation of epitaxial graphene domain reorientation

    SciTech Connect (OSTI)

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

  20. 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.

  1. Babel Fortran 2003 Binding for Structured Data Types

    SciTech Connect (OSTI)

    Muszala, S; Epperly, T; Wang, N

    2008-05-02

    Babel is a tool aimed at the high-performance computing community that addresses the need for mixing programming languages (Java, Python, C, C++, Fortran 90, FORTRAN 77) in order to leverage the specific benefits of those languages. Scientific codes often rely on structured data types (structs, derived data types) to encapsulate data, and Babel has been lacking in this type of support until recently. We present a new language binding that focuses on their interoperability of C/C++ with Fortran 2003. The new binding builds on the existing Fortran 90 infrastructure by using the iso-c-binding module defined in the Fortran 2003 standard as the basis for C/C++ interoperability. We present the technical approach for the new binding and discuss our initial experiences in applying the binding in FACETS (Framework Application for Core-Edge Transport Simulations) to integrate C++ with legacy Fortran codes.

  2. 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.

  3. Seventh international conference on Domain decomposition methods in scientific and engineering computing

    SciTech Connect (OSTI)

    1993-12-31

    This report contains abstracts presented at the Seventh International Conference on Domain Decomposition Methods.

  4. 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.

  5. 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.

  6. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect (OSTI)

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  7. A nodal domain theorem for integrable billiards in two dimensions

    SciTech Connect (OSTI)

    Samajdar, Rhine; Jain, Sudhir R.

    2014-12-15

    Eigenfunctions of integrable planar billiards are studied — in particular, the number of nodal domains, ν of the eigenfunctions with Dirichlet boundary conditions are considered. The billiards for which the time-independent Schrödinger equation (Helmholtz equation) is separable admit trivial expressions for the number of domains. Here, we discover that for all separable and non-separable integrable billiards, ν satisfies certain difference equations. This has been possible because the eigenfunctions can be classified in families labelled by the same value of mmodkn, given a particular k, for a set of quantum numbers, m,n. Further, we observe that the patterns in a family are similar and the algebraic representation of the geometrical nodal patterns is found. Instances of this representation are explained in detail to understand the beauty of the patterns. This paper therefore presents a mathematical connection between integrable systems and difference equations. - Highlights: • We find that the number of nodal domains of eigenfunctions of integrable, planar billiards satisfy a class of difference equations. • The eigenfunctions labelled by quantum numbers (m,n) can be classified in terms of mmodkn. • A theorem is presented, realising algebraic representations of geometrical patterns exhibited by the domains. • This work presents a connection between integrable systems and difference equations.

  8. Modeling of Carbohydrate Binding Modules Complexed to Cellulose

    SciTech Connect (OSTI)

    Nimlos, M. R.; Beckham, G. T.; Bu, L.; Himmel, M. E.; Crowley, M. F.; Bomble, Y. J.

    2012-01-01

    Modeling results are presented for the interaction of two carbohydrate binding modules (CBMs) with cellulose. The family 1 CBM from Trichoderma reesei's Cel7A cellulase was modeled using molecular dynamics to confirm that this protein selectively binds to the hydrophobic (100) surface of cellulose fibrils and to determine the energetics and mechanisms for locating this surface. Modeling was also conducted of binding of the family 4 CBM from the CbhA complex from Clostridium thermocellum. There is a cleft in this protein, which may accommodate a cellulose chain that is detached from crystalline cellulose. This possibility is explored using molecular dynamics.

  9. Binding Preferences, Surface Attachment, Diffusivity, and Orientation of a Family 1 Carbohydrate-Binding Module on Cellulose

    SciTech Connect (OSTI)

    Nimlos, M. R.; Beckham, G. T.; Matthews, J. F.; Bu, L.; Himmel, M. E.; Crowley, M. F.

    2012-06-08

    Cellulase enzymes often contain carbohydrate-binding modules (CBMs) for binding to cellulose. The mechanisms by which CBMs recognize specific surfaces of cellulose and aid in deconstruction are essential to understand cellulase action. The Family 1 CBM from the Trichoderma reesei Family 7 cellobiohydrolase, Cel7A, is known to selectively bind to hydrophobic surfaces of native cellulose. It is most commonly suggested that three aromatic residues identify the planar binding face of this CBM, but several recent studies have challenged this hypothesis. Here, we use molecular simulation to study the CBM binding orientation and affinity on hydrophilic and hydrophobic cellulose surfaces. Roughly 43 {mu}s of molecular dynamics simulations were conducted, which enables statistically significant observations. We quantify the fractions of the CBMs that detach from crystal surfaces or diffuse to other surfaces, the diffusivity along the hydrophobic surface, and the overall orientation of the CBM on both hydrophobic and hydrophilic faces. The simulations demonstrate that there is a thermodynamic driving force for the Cel7A CBM to bind preferentially to the hydrophobic surface of cellulose relative to hydrophilic surfaces. In addition, the simulations demonstrate that the CBM can diffuse from hydrophilic surfaces to the hydrophobic surface, whereas the reverse transition is not observed. Lastly, our simulations suggest that the flat faces of Family 1 CBMs are the preferred binding surfaces. These results enhance our understanding of how Family 1 CBMs interact with and recognize specific cellulose surfaces and provide insights into the initial events of cellulase adsorption and diffusion on cellulose.

  10. Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1

    SciTech Connect (OSTI)

    Yun, Sang-Moon; Moulaei, Tinoush; Lim, Dan; Bang, Jeong K.; Park, Jung-Eun; Shenoy, Shilpa R.; Liu, Fa; Kang, Young H.; Liao, Chenzhong; Soung, Nak-Kyun; Lee, Sunhee; Yoon, Do-Young; Lim, Yoongho; Lee, Dong-Hee; Otaka, Akira; Appella, Ettore; McMahon, James B.; Nicklaus, Marc C.; Burke, Jr., Terrence R.; Yaffe, Michael B.; Wlodawer, Alexander; Lee, Kyung S.

    2009-09-14

    Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.

  11. 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.

  12. 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:...

  13. Visually Relating Gene Expression and in vivo DNA Binding Data

    SciTech Connect (OSTI)

    Huang, Min-Yu; Mackey, Lester; Ker?; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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:

  19. 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.

  20. The same pocket in menin binds both MLL and JUND but has opposite...

    Office of Scientific and Technical Information (OSTI)

    Menin binds the JUN family transcription factor JUND and inhibits its transcriptional ... A recent report on the tethering of MLL1 to chromatin binding factor lens ...

  1. 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...

  2. Domain decomposition methods for solving an image problem

    SciTech Connect (OSTI)

    Tsui, W.K.; Tong, C.S.

    1994-12-31

    The domain decomposition method is a technique to break up a problem so that ensuing sub-problems can be solved on a parallel computer. In order to improve the convergence rate of the capacitance systems, pre-conditioned conjugate gradient methods are commonly used. In the last decade, most of the efficient preconditioners are based on elliptic partial differential equations which are particularly useful for solving elliptic partial differential equations. In this paper, the authors apply the so called covering preconditioner, which is based on the information of the operator under investigation. Therefore, it is good for various kinds of applications, specifically, they shall apply the preconditioned domain decomposition method for solving an image restoration problem. The image restoration problem is to extract an original image which has been degraded by a known convolution process and additive Gaussian noise.

  3. 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.

  4. Mechanism-Based Tuning of a LOV Domain Photoreceptor

    SciTech Connect (OSTI)

    Zoltowski, B.; Vaccaro, B; Crane, B

    2009-01-01

    Phototropin-like LOV domains form a cysteinyl-flavin adduct in response to blue light but show considerable variation in output signal and the lifetime of the photo-adduct signaling state. Mechanistic studies of the slow-cycling fungal LOV photoreceptor Vivid (VVD) reveal the importance of reactive cysteine conformation, flavin electronic environment and solvent accessibility for adduct scission and thermal reversion. Proton inventory, pH effects, base catalysis and structural studies implicate flavin N5 deprotonation as rate-determining for recovery. Substitutions of active site residues Ile74, Ile85, Met135 and Met165 alter photoadduct lifetimes by over four orders of magnitude in VVD, and similar changes in other LOV proteins show analogous effects. Adduct state decay rates also correlate with changes in conformational and oligomeric properties of the protein necessary for signaling. These findings link natural sequence variation of LOV domains to function and provide a means to design broadly reactive light-sensitive probes.

  5. 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.

  6. Domain decomposed preconditioners with Krylov subspace methods as subdomain solvers

    SciTech Connect (OSTI)

    Pernice, M.

    1994-12-31

    Domain decomposed preconditioners for nonsymmetric partial differential equations typically require the solution of problems on the subdomains. Most implementations employ exact solvers to obtain these solutions. Consequently work and storage requirements for the subdomain problems grow rapidly with the size of the subdomain problems. Subdomain solves constitute the single largest computational cost of a domain decomposed preconditioner, and improving the efficiency of this phase of the computation will have a significant impact on the performance of the overall method. The small local memory available on the nodes of most message-passing multicomputers motivates consideration of the use of an iterative method for solving subdomain problems. For large-scale systems of equations that are derived from three-dimensional problems, memory considerations alone may dictate the need for using iterative methods for the subdomain problems. In addition to reduced storage requirements, use of an iterative solver on the subdomains allows flexibility in specifying the accuracy of the subdomain solutions. Substantial savings in solution time is possible if the quality of the domain decomposed preconditioner is not degraded too much by relaxing the accuracy of the subdomain solutions. While some work in this direction has been conducted for symmetric problems, similar studies for nonsymmetric problems appear not to have been pursued. This work represents a first step in this direction, and explores the effectiveness of performing subdomain solves using several transpose-free Krylov subspace methods, GMRES, transpose-free QMR, CGS, and a smoothed version of CGS. Depending on the difficulty of the subdomain problem and the convergence tolerance used, a reduction in solution time is possible in addition to the reduced memory requirements. The domain decomposed preconditioner is a Schur complement method in which the interface operators are approximated using interface probing.

  7. 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

  8. 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

  9. 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

  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 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

  11. 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

  12. 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

  13. 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

  14. Adaptive domain decomposition methods for advection-diffusion problems

    SciTech Connect (OSTI)

    Carlenzoli, C.; Quarteroni, A.

    1995-12-31

    Domain decomposition methods can perform poorly on advection-diffusion equations if diffusion is dominated by advection. Indeed, the hyperpolic part of the equations could affect the behavior of iterative schemes among subdomains slowing down dramatically their rate of convergence. Taking into account the direction of the characteristic lines we introduce suitable adaptive algorithms which are stable with respect to the magnitude of the convective field in the equations and very effective on bear boundary value problems.

  15. 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

  16. 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.

  17. 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 ...

  18. All-electron self-consistent G W in the Matsubara-time domain...

    Office of Scientific and Technical Information (OSTI)

    All-electron self-consistent G W in the Matsubara-time domain: Implementation and ... Title: All-electron self-consistent G W in the Matsubara-time domain: Implementation ...

  19. 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...

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

    Office of Environmental Management (EM)

    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 ...

  1. Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcript...

    Office of Scientific and Technical Information (OSTI)

    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 ...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. MamO Is a Repurposed Serine Protease that Promotes Magnetite Biomineralization through Direct Transition Metal Binding in Magnetotactic Bacteria

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

    Hershey, David M.; Ren, Xuefeng; Melnyk, Ryan A.; Browne, Patrick J.; Ozyamak, Ertan; Jones, Stephanie R.; Chang, Michelle C. Y.; Hurley, James H.; Komeili, Arash

    2016-03-16

    Many living organisms transform inorganic atoms into highly ordered crystalline materials. An elegant example of such biomineralization processes is the production of nano-scale magnetic crystals in magnetotactic bacteria. Previous studies have implicated the involvement of two putative serine proteases, MamE and MamO, during the early stages of magnetite formation in Magnetospirillum magneticum AMB-1. Here, using genetic analysis and X-ray crystallography, we show that MamO has a degenerate active site, rendering it incapable of protease activity. Instead, MamO promotes magnetosome formation through two genetically distinct, noncatalytic activities: activation of MamE-dependent proteolysis of biomineralization factors and direct binding to transition metal ions.more » By solving the structure of the protease domain bound to a metal ion, we identify a surface-exposed di-histidine motif in MamO that contributes to metal binding and show that it is required to initiate biomineralization in vivo. Finally, we find that pseudoproteases are widespread in magnetotactic bacteria and that they have evolved independently in three separate taxa. In conclusion, our results highlight the versatility of protein scaffolds in accommodating new biochemical activities and provide unprecedented insight into the earliest stages of biomineralization.« less

  7. Cloning, purification and preliminary crystallographic analysis of a putative DNA-binding membrane protein, YmfM, from Staphylococcus aureus

    SciTech Connect (OSTI)

    Xu, Ling; Sedelnikova, Svetlana E.; Baker, Patrick J.; Rice, David W.

    2008-07-01

    Truncation by the removal of the C-terminal hydrophobic transmembrane anchor has enabled the overexpression of a soluble domain of S. aureus YmfM in Escherichia coli, which has then been purified and subsequently crystallized. The Staphylococcus aureus protein YmfM contains a helix–turn–helix motif and is thought to be a putative DNA-binding protein which is associated with the membrane through a C-terminal hydrophobic transmembrane anchor. Truncation of the protein by the removal of this C-terminal hydrophobic segment has enabled the overexpression of a soluble domain of S. aureus YmfM (ΔYmfM) in Escherichia coli, which has been purified and subsequently crystallized. Crystals of ΔYmfM diffract to beyond 1.0 Å resolution and belong to one of the pair of enantiomorphic tetragonal space groups P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 45.5, c = 72.9 Å and one molecule in the asymmetric unit. The crystals of ΔYmfM have an unusually low V{sub M} of 1.6 Å{sup 3} Da{sup −1}, which is one of the lowest values observed for any protein to date. A full structure determination is under way in order to provide insights into the function of this protein.

  8. 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.

  9. 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, μ, and the effective warm ion-to-electron temperature ratio, τ, 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 τ and μ that support stopbands are found. It is suggested that, inter alia, the analysis should be applicable to the solar wind plasma.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Inhibition Of Call-Cell Binding By Kipid Assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. , Bargatze, Robert F.

    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.

  17. Inhibition of cell-cell binding by lipid assemblies

    DOE Patents [OSTI]

    Nagy, Jon O.; Bargatze, Robert F.

    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.

  18. 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.

  19. Modeling silver binding to gills of rainbow trout (Oncorhynchus mykiss)

    SciTech Connect (OSTI)

    Janes, N.; Playle, R.C.

    1995-11-01

    Rainbow trout (Oncorhynchus mykiss, 1--3 g) were exposed to {approximately} 1.0 {micro}M silver (Ag) ({approximately} 11 {micro}g {center_dot} L{sup {minus}1} Ag) for 2 to 3 h in synthetic soft water (Ca, Na {approximately} 300 {micro}M, pH 6.5--7.5) to which was added Ca, Na, H{sup +}, dissolved organic carbon (DOC), Cl, or thiosulfate (S{sub 2}O{sub 3}). Gills were extracted and gill Ag concentrations were measured using graphite-furnace atomic absorption spectrophotometry. The concentration of cations (Ca, Na, H{sup +}) and complexing agents (DOC, Cl, S{sub 2}O{sub 3}) needed to keep Ag off the gills were used to calculate conditional equilibrium binding constants (K) at the gills. Log K for Ag-gill binding was 10.0, with approximately 1.3 nmol Ag binding sites per fish. All experimentally determined log K values were entered into an aquatic chemistry equilibrium model, MINEQL{sup +}, to predict Ag binding at trout gills. For a series of natural waters, model-predicted gill Ag concentrations correlated well with observed gill Ag concentrations, with one exception, very hard city of Waterloo tapwater. This exception may indicate a kinetic constraint on the thermodynamic basis of the model.

  20. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1.

    SciTech Connect (OSTI)

    Avvakumov, George V.; Walker, John R.; Xue, Sheng; Li, Yanjun; Duan, Shili; Bronner, Christian; Arrowsmith, Cheryl H.; Dhe-Paganon, Sirano

    2008-11-17

    Epigenetic inheritance in mammals is characterized by high-fidelity replication of CpG methylation patterns during development. UHRF1 (also known as ICBP90 in humans and Np95 in mouse) is an E3 ligase important for the maintenance of global and local DNA methylation in vivo. The preferential affinity of UHRF1 for hemi-methylated DNA over symmetrically methylated DNA by means of its SET and RING-associated (SRA) domain and its association with the maintenance DNA methyltransferase 1 (DNMT1) suggests a role in replication of the epigenetic code. Here we report the 1.7 {angstrom} crystal structure of the apo SRA domain of human UHRF1 and a 2.2 {angstrom} structure of its complex with hemi-methylated DNA, revealing a previously unknown reading mechanism for methylated CpG sites (mCpG). The SRA-DNA complex has several notable structural features including a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. Two specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other three bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand. The structure, along with mutagenesis data, suggests how UHRF1 acts as a key factor for DNMT1 maintenance methylation through recognition of a fundamental unit of epigenetic inheritance, mCpG.

  1. Global Proteome Response to Deletion of Genes Related to Mercury Methylation and Dissimilatory Metal Reduction Reveals Changes in Respiratory Metabolism in Geobacter sulfurreducens PCA

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

    Qian, Chen; Johs, Alexander; Chen, Hongmei; Mann, Benjamin F.; Lu, Xia; Abraham, Paul E.; Hettich, Robert L.; Gu, Baohua

    2016-07-27

    Geobacter sulfurreducens PCA can reduce, sorb, and methylate mercury (Hg); however, the underlying biochemical mechanisms of these processes and interdependent metabolic pathways remain unknown. In this study, shotgun proteomics was used to compare global proteome profiles between wild-type G. sulfurreducens PCA and two mutant strains: a ΔhgcAB mutant, which is deficient in two genes known to be essential for Hg methylation and a ΔomcBESTZ mutant, which is deficient in five outer membrane c-type cytochromes and thus impaired in its ability for dissimilatory metal ion reduction. We were able to delineate the global response of G. sulfurreducens PCA in both mutantsmore » and identify cellular networks and metabolic pathways that were affected by the loss of these genes. Deletion of hgcAB increased the relative abundances of proteins implicated in extracellular electron transfer, including most of the c-type cytochromes, PilA-C, and OmpB, and is consistent with a previously observed increase in Hg reduction in the hgcAB mutant. Deletion of omcBESTZ was found to significantly increase relative abundances of various methyltransferases, suggesting that a loss of dissimilatory reduction capacity results in elevated activity among one-carbon metabolic pathways and thus increased methylation. We show that G. sulfurreducens PCA encodes only the folate branch of the Wood Ljungdahl pathway, and proteins associated with the folate branch were found at lower abundance in the ΔhgcAB mutant strain than the wild type. In conclusion, this observation supports the hypothesis that the function of HgcA and HgcB may be linked to one carbon metabolism through the folate branch of the Wood-Ljungdahl pathway by providing methyl groups required for Hg methylation.« less

  2. 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.

  3. 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

  4. Detecting Rare Events in the Time-Domain

    SciTech Connect (OSTI)

    Rest, A; Garg, A

    2008-10-31

    One of the biggest challenges in current and future time-domain surveys is to extract the objects of interest from the immense data stream. There are two aspects to achieving this goal: detecting variable sources and classifying them. Difference imaging provides an elegant technique for identifying new transients or changes in source brightness. Much progress has been made in recent years toward refining the process. We discuss a selection of pitfalls that can afflict an automated difference imagine pipeline and describe some solutions. After identifying true astrophysical variables, we are faced with the challenge of classifying them. For rare events, such as supernovae and microlensing, this challenge is magnified because we must balance having selection criteria that select for the largest number of objects of interest against a high contamination rate. We discuss considerations and techniques for developing classification schemes.

  5. Ion mobility spectrometer using frequency-domain separation

    DOE Patents [OSTI]

    Martin, Stephen J.; Butler, Michael A.; Frye, Gregory C.; Schubert, W. Kent

    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).

  6. 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.

  7. Representing ductile damage with the dual domain material point method

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

    Long, C. C.; Zhang, D. Z.; Bronkhorst, C. A.; Gray, III, G. T.

    2015-12-14

    In this study, we incorporate a ductile damage material model into a computational framework based on the Dual Domain Material Point (DDMP) method. As an example, simulations of a flyer plate experiment involving ductile void growth and material failure are performed. The results are compared with experiments performed on high purity tantalum. We also compare the numerical results obtained from the DDMP method with those obtained from the traditional Material Point Method (MPM). Effects of an overstress model, artificial viscosity, and physical viscosity are investigated. Our results show that a physical bulk viscosity and overstress model are important in thismore » impact and failure problem, while physical shear viscosity and artificial shock viscosity have negligible effects. A simple numerical procedure with guaranteed convergence is introduced to solve for the equilibrium plastic state from the ductile damage model.« less

  8. Representing ductile damage with the dual domain material point method

    SciTech Connect (OSTI)

    Long, C. C.; Zhang, D. Z.; Bronkhorst, C. A.; Gray, III, G. T.

    2015-12-14

    In this study, we incorporate a ductile damage material model into a computational framework based on the Dual Domain Material Point (DDMP) method. As an example, simulations of a flyer plate experiment involving ductile void growth and material failure are performed. The results are compared with experiments performed on high purity tantalum. We also compare the numerical results obtained from the DDMP method with those obtained from the traditional Material Point Method (MPM). Effects of an overstress model, artificial viscosity, and physical viscosity are investigated. Our results show that a physical bulk viscosity and overstress model are important in this impact and failure problem, while physical shear viscosity and artificial shock viscosity have negligible effects. A simple numerical procedure with guaranteed convergence is introduced to solve for the equilibrium plastic state from the ductile damage model.

  9. Aspen: A Domain Specific Language for Performance Modeling

    SciTech Connect (OSTI)

    Spafford, Kyle L; Vetter, Jeffrey S

    2012-01-01

    We present a new approach to analytical performance modeling using Aspen, a domain specific language. Aspen (Abstract Scalable Performance Engineering Notation) fills an important gap in existing performance modeling techniques and is designed to enable rapid exploration of new algorithms and architectures. It includes a formal specification of an application's performance behavior and an abstract machine model. We provide an overview of Aspen's features and demonstrate how it can be used to express a performance model for a three dimensional Fast Fourier Transform. We then demonstrate the composability and modularity of Aspen by importing and reusing the FFT model in a molecular dynamics model. We have also created a number of tools that allow scientists to balance application and system factors quickly and accurately.

  10. 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.

  11. 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.

  12. 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.

  13. Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-[alpha

    SciTech Connect (OSTI)

    Carter, Percy H.; Scherle, Peggy A.; Muckelbauer, Jodi K.; Voss, Matthew E.; Liu, Rui-qin; Thompson III, Lorin A.; Xu, Meizhong; Lo, Yvonne C.; Li, Zhong; Strzemienski, Paul; Yang, Gengjie; Falahatpishen, Nikoo; Farrow, Neil A.; Tebben, Andrew J.; Underwood, Denis; Trzaskos, James M.; Friedman, Steven M.; Newton, Robert C.; Decicco, Carl P.

    2010-03-05

    The binding of tumor necrosis factor alpha (TNF-{alpha}) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-{alpha} to TNFRc1 (IC{sub 50} = 50 nM) and also blocked TNF-stimulated phosphorylation of I{kappa}-B in Ramos cells (IC{sub 50} = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 {micro}M. Detailed evaluation of this and related molecules revealed that compounds in this class are 'photochemically enhanced' inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 mM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-{alpha} to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-{alpha}-TNFRc1 interaction.

  14. 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.

  15. Accurate nuclear radii and binding energies from a chiral interaction

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

    Ekstrom, Jan A.; Jansen, G. R.; Wendt, Kyle A.; Hagen, Gaute; Papenbrock, Thomas F.; Carlsson, Boris; Forssen, Christian; Hjorth-Jensen, M.; Navratil, Petr; Nazarewicz, Witold

    2015-05-01

    With the goal of developing predictive ab initio capability for light and medium-mass nuclei, two-nucleon and three-nucleon forces from chiral effective field theory are optimized simultaneously to low-energy nucleon-nucleon scattering data, as well as binding energies and radii of few-nucleon systems and selected isotopes of carbon and oxygen. Coupled-cluster calculations based on this interaction, named NNLOsat, yield accurate binding energies and radii of nuclei up to 40Ca, and are consistent with the empirical saturation point of symmetric nuclear matter. In addition, the low-lying collective Jπ=3- states in 16O and 40Ca are described accurately, while spectra for selected p- and sd-shellmore » nuclei are in reasonable agreement with experiment.« less

  16. Accurate nuclear radii and binding energies from a chiral interaction

    SciTech Connect (OSTI)

    Ekstrom, Jan A.; Jansen, G. R.; Wendt, Kyle A.; Hagen, Gaute; Papenbrock, Thomas F.; Carlsson, Boris; Forssen, Christian; Hjorth-Jensen, M.; Navratil, Petr; Nazarewicz, Witold

    2015-05-01

    With the goal of developing predictive ab initio capability for light and medium-mass nuclei, two-nucleon and three-nucleon forces from chiral effective field theory are optimized simultaneously to low-energy nucleon-nucleon scattering data, as well as binding energies and radii of few-nucleon systems and selected isotopes of carbon and oxygen. Coupled-cluster calculations based on this interaction, named NNLOsat, yield accurate binding energies and radii of nuclei up to 40Ca, and are consistent with the empirical saturation point of symmetric nuclear matter. In addition, the low-lying collective Jπ=3− states in 16O and 40Ca are described accurately, while spectra for selected p- and sd-shell nuclei are in reasonable agreement with experiment.

  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. Zheng, S.; Duan, P.

    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, Alfvén 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. 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.

  19. Structure of Concatenated HAMP Domains Provides a Mechanism for Signal Transduction

    SciTech Connect (OSTI)

    Airola, Michael V.; Watts, Kylie J.; Bilwes, Alexandrine M.; Crane, Brian R.

    2010-08-23

    HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a three-unit poly-HAMP chain from the Pseudomonas aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angle, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.

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

    SciTech Connect (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.

  1. Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding Change

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

    Mechanism Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding Change Mechanism Resources with Additional Information Paul D. Boyer Courtesy of UCLA 'For Paul Boyer, the Nobel Prize was "an unexpected pleasure." It had been 20 years since he formulated a hypothesis to describe what he calls "the most prominent chemical reaction in the whole world." It is the process by which molecules produce ATP (adenosine triphosphate), thereby transmuting light, air, water and

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  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. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  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. 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...

  4. 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...

  5. 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 ...

  6. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films

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

    Damodaran, Anoop; Okatan, M. B.; Kacher, J.; Gammer, C.; Vasudevan, Rama; Pandya, S.; Dedon, L. R.; Mangalam, R. V.; Jesse, Stephen; Balke, Nina; et al

    2016-02-15

    Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructuresmore » stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.« less

  7. TU-C-17A-05: Dose Domain Optimization of MLC Leaf Patterns for...

    Office of Scientific and Technical Information (OSTI)

    domain required multiplying the fluence with a sparse matrix. Exploiting this property made it feasible to solve the problem using CVX, a MATLAB-based convex modeling framework. ...

  8. Evolution of domain wall networks: The Press-Ryden-Spergel algorithm

    SciTech Connect (OSTI)

    Sousa, L.; Avelino, P. P.

    2010-04-15

    The Press-Ryden-Spergel (PRS) algorithm is a modification to the field theory equations of motion, parametrized by two parameters ({alpha} and {beta}), implemented in numerical simulations of cosmological domain wall networks, in order to ensure a fixed comoving resolution. In this paper we explicitly demonstrate that the PRS algorithm provides the correct domain wall dynamics in (N+1)-dimensional Friedmann-Robertson-Walker universes if {alpha}+{beta}/2=N, fully validating its use in numerical studies of cosmic domain evolution. We further show that this result is valid for generic thin featureless domain walls, independently of the Lagrangian of the model.

  9. Existence and uniqueness of domain wall solitons in a Maxwell–Chern–Simons model

    SciTech Connect (OSTI)

    Zhang, Ruifeng; College of Mathematics and Information Science, Henan University, Kaifeng 475001 ; Li, Fangfang

    2014-02-15

    We present some sharp existence and uniqueness theorems for the domain wall solutions of the basic governing equations of a self-dual Maxwell–Chern–Simons model.

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

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

    Molecular view of a polymerorganic solar film showing an interface between donor and acceptor domains. Red dots are organic fullerene molecules and blue lines represent polymer ...

  11. 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.

  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. An Analog Filter Approach to Frequency Domain Fluorescence Spectroscopy

    SciTech Connect (OSTI)

    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 entire 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.

  14. THz time-domain spectroscopy for tokamak plasma diagnostics

    SciTech Connect (OSTI)

    Causa, F.; Zerbini, M.; Buratti, P.; Gabellieri, L.; Pacella, D.; Romano, A.; Tuccillo, A. A.; Tudisco, O.; Johnston, M.; Doria, A.; Gallerano, G. P.; Giovenale, E.

    2014-08-21

    The technology is now becoming mature for diagnostics using large portions of the electromagnetic spectrum simultaneously, in the form of THz pulses. THz radiation-based techniques have become feasible for a variety of applications, e.g., spectroscopy, imaging for security, medicine and pharmaceutical industry. In particular, time-domain spectroscopy (TDS) is now being used also for plasma diagnostics in various fields of application. This technique is promising also for plasmas for fusion applications, where plasma characteristics are non-uniform and/or evolve during the discharge This is because THz pulses produced with femtosecond mode-locked lasers conveniently span the spectrum above and below the plasma frequency and, thus, can be used as very sensitive and versatile probes of widely varying plasma parameters. The short pulse duration permits time resolving plasma characteristics while the large frequency span permits a large dynamic range. The focus of this work is to present preliminary experimental and simulation results demonstrating that THz TDS can be realistically adapted as a versatile tokamak plasma diagnostic technique.

  15. 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.

    2015-10-01

    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. Furthermore, 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

  16. 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.

  17. Computational Investigation of Glycosylation Effects on a Family 1 Carbohydrate-Binding Module

    SciTech Connect (OSTI)

    Taylor, C. B.; Talib, M. F.; McCabe, C.; Bu, L.; Adney, W. S.; Himmel, M. E.; Crowley, M. F.; Beckham, G. T.

    2012-01-27

    Carbohydrate-binding modules (CBMs) are ubiquitous components of glycoside hydrolases, which degrade polysaccharides in nature. CBMs target specific polysaccharides, and CBM binding affinity to cellulose is known to be proportional to cellulase activity, such that increasing binding affinity is an important component of performance improvement. To ascertain the impact of protein and glycan engineering on CBM binding, we use molecular simulation to quantify cellulose binding of a natively glycosylated Family 1 CBM. To validate our approach, we first examine aromatic-carbohydrate interactions on binding, and our predictions are consistent with previous experiments, showing that a tyrosine to tryptophan mutation yields a 2-fold improvement in binding affinity. We then demonstrate that enhanced binding of 3-6-fold over a nonglycosylated CBM is achieved by the addition of a single, native mannose or a mannose dimer, respectively, which has not been considered previously. Furthermore, we show that the addition of a single, artificial glycan on the anterior of the CBM, with the native, posterior glycans also present, can have a dramatic impact on binding affinity in our model, increasing it up to 140-fold relative to the nonglycosylated CBM. These results suggest new directions in protein engineering, in that modifying glycosylation patterns via heterologous expression, manipulation of culture conditions, or introduction of artificial glycosylation sites, can alter CBM binding affinity to carbohydrates and may thus be a general strategy to enhance cellulase performance. Our results also suggest that CBM binding studies should consider the effects of glycosylation on binding and function.

  18. Overexpression, purification and crystallization of the two C-terminal domains of the bifunctional cellulase ctCel9D-Cel44A from Clostridium thermocellum

    SciTech Connect (OSTI)

    Najmudin, Shabir; Guerreiro, Catarina I. P. D.; Ferreira, Luís M. A.; Romão, Maria J. C.; Fontes, Carlos M. G. A.; Prates, José A. M.

    2005-12-01

    The two C-terminal domains of the cellulase ctCel9D-Cel44A from C. thermocellum cellulosome have been crystallized in tetragonal space group P4{sub 3}2{sub 1}2 and X-ray diffraction data have been collected to 2.1 and 2.8 Å from native and seleno-l-methionine-derivative crystals, respectively. Clostridium thermocellum produces a highly organized multi-enzyme complex of cellulases and hemicellulases for the hydrolysis of plant cell-wall polysaccharides, which is termed the cellulosome. The bifunctional multi-modular cellulase ctCel9D-Cel44A is one of the largest components of the C. thermocellum cellulosome. The enzyme contains two internal catalytic domains belonging to glycoside hydrolase families 9 and 44. The C-terminus of this cellulase, comprising a polycystic kidney-disease module (PKD) and a carbohydrate-binding module (CBM44), has been crystallized. The crystals belong to the tetragonal space group P4{sub 3}2{sub 1}2, containing a single molecule in the asymmetric unit. Native and seleno-l-methionine-derivative crystals diffracted to 2.1 and 2.8 Å, respectively.

  19. 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

  20. 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.

  1. Current-driven vortex domain wall motion in wire-tube nanostructures

    SciTech Connect (OSTI)

    Espejo, A. P.; Vidal-Silva, N.; López-López, J. A.; Goerlitz, D.; Nielsch, K.; Escrig, J.

    2015-03-30

    We have investigated the current-driven domain wall motion in nanostructures comprised of a pair of nanotube and nanowire segments. Under certain values of external magnetic fields, it is possible to pin a vortex domain wall in the transition zone between the wire and tube segments. We explored the behavior of this domain wall under the action of an electron flow applied in the opposite direction to the magnetic field. Thus, for a fixed magnetic field, it is possible to release a domain wall pinned simply by increasing the intensity of the current density, or conversely, for a fixed current density, it is possible to release the domain wall simply decreasing the magnetic external field. When the domain wall remains pinned due to the competition between the current density and the magnetic external field, it exhibits a oscillation frequency close to 8 GHz. The amplitude of the oscillations increases with the current density and decreases over time. On the other hand, when the domain wall is released and propagated through the tube segment, this shows the standard separation between a steady and a precessional regime. The ability to pin and release a domain wall by varying the geometric parameters, the current density, or the magnetic field transforms these wire-tube nanostructures in an interesting alternative as an on/off switch nano-transistor.

  2. Magnetic thin-film split-domain current sensor-recorder

    DOE Patents [OSTI]

    Hsieh, Edmund J.

    1979-01-01

    A sensor-recorder for recording a representation of the direction and peak amplitude of a transient current. A magnetic thin film is coated on a glass substrate under the influence of a magnetic field so that the finished film is magnetically uniaxial and anisotropic. The film is split into two oppositely magnetized contiguous domains with a central boundary by subjecting adjacent portions of the film simultaneously to magnetic fields that are opposed 180.degree.. With the split-domain sensor-recorder placed with the film plane and domain boundary either perpendicular or parallel to the expected conductive path of a transient current, the occurrence of the transient causes switching of a portion of one domain to the direction of the other domain. The amount of the switched domain portion is indicative of the amplitude of the peak current of the transient, while the particular domain that is switched is indicative of the direction of the current. The resulting domain patterns may be read with a passive magnetic tape viewer.

  3. 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.

  4. Combined state-adding and state-deleting approaches to type III multi-step rationally extended potentials: Applications to ladder operators and superintegrability

    SciTech Connect (OSTI)

    Marquette, Ian; Quesne, Christiane

    2014-11-15

    Type III multi-step rationally extended harmonic oscillator and radial harmonic oscillator potentials, characterized by a set of k integers m{sub 1}, m{sub 2}, ⋯, m{sub k}, such that m{sub 1} < m{sub 2} < ⋯ < m{sub k} with m{sub i} even (resp. odd) for i odd (resp. even), are considered. The state-adding and state-deleting approaches to these potentials in a supersymmetric quantum mechanical framework are combined to construct new ladder operators. The eigenstates of the Hamiltonians are shown to separate into m{sub k} + 1 infinite-dimensional unitary irreducible representations of the corresponding polynomial Heisenberg algebras. These ladder operators are then used to build a higher-order integral of motion for seven new infinite families of superintegrable two-dimensional systems separable in cartesian coordinates. The finite-dimensional unitary irreducible representations of the polynomial algebras of such systems are directly determined from the ladder operator action on the constituent one-dimensional Hamiltonian eigenstates and provide an algebraic derivation of the superintegrable systems whole spectrum including the level total degeneracies.

  5. Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung

    SciTech Connect (OSTI)

    Weston, A.; Willey, J.C.; Modali, R.; Sugimura, H.; McDowell, E.M.; Resau, J.; Light, B.; Haugen, A.; Mann, D.L.; Trump, B.F.; Harris, C.C. )

    1989-07-01

    Activation of protooncogens and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.

  6. 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.

  7. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOE Patents [OSTI]

    Bertozzi, Carolyn R.; Song, Jie; Lee, Seung-Wuk

    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.

  8. 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

  9. 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.

  10. Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1∙Nup98)

    SciTech Connect (OSTI)

    Quan, Beili; Seo, Hyuk-Soo; Blobel, Günter; Ren, Yi

    2014-07-01

    mRNA export factor 1 (Rae1) and nucleoporin 98 (Nup98) are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). How Rae1 functions in mRNA export and how M protein targets both Rae1 and Nup98 are not understood at the molecular level. To obtain structural insights, we assembled a 1:1:1 complex of M•Rae1•Nup98 and established a crystal structure at 3.15-Å resolution. We found that the M protein contacts the Rae1•Nup98 heterodimer principally by two protrusions projecting from the globular domain of M like a finger and thumb. Both projections clamp to the side of the β-propeller of Rae1, with the finger also contacting Nup98. The most prominent feature of the finger is highly conserved Methionine 51 (Met51) with upstream and downstream acidic residues. The complementary surface on Rae1 displays a deep hydrophobic pocket, into which Met51 fastens like a bolt, and a groove of basic residues on either side, which bond to the acidic residues of the finger. Notably, the M protein competed for in vitro binding of various oligonucleotides to Rae1•Nup98. We localized this competing activity of M to its finger using a synthetic peptide. Collectively, our data suggest that Rae1 serves as a binding protein for the phosphate backbone of any nucleic acid and that the finger of M mimics this ligand. In the context of mRNA export, we propose that a given mRNA segment, after having been deproteinated by helicase, is transiently reproteinated by Nup98-tethered Rae1. We suggest that such repetitive cycles provide cytoplasmic stopover sites required for ratcheting mRNA across the nuclear pore.

  11. 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.

  12. 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.

  13. Scaling Behavior of the First Arrival Time of a Random-Walking Magnetic Domain

    SciTech Connect (OSTI)

    Im, M.-Y.; Lee, S.-H.; Kim, D.-H.; Fischer, P.; Shin, S.-C.

    2008-02-04

    We report a universal scaling behavior of the first arrival time of a traveling magnetic domain wall into a finite space-time observation window of a magneto-optical microscope enabling direct visualization of a Barkhausen avalanche in real time. The first arrival time of the traveling magnetic domain wall exhibits a nontrivial fluctuation and its statistical distribution is described by universal power-law scaling with scaling exponents of 1.34 {+-} 0.07 for CoCr and CoCrPt films, despite their quite different domain evolution patterns. Numerical simulation of the first arrival time with an assumption that the magnetic domain wall traveled as a random walker well matches our experimentally observed scaling behavior, providing an experimental support for the random-walking model of traveling magnetic domain walls.

  14. Disparity of secondary electron emission in ferroelectric domains of YMnO{sub 3}

    SciTech Connect (OSTI)

    Cheng, Shaobo; Deng, S. Q.; Yuan, Wenjuan; Yan, Yunjie; Zhu, Jing; Li, J.; Li, J. Q.

    2015-07-20

    The applications of multiferroic materials require our understanding about the behaviors of domains with different polarization directions. Taking advantage of the scanning electron microscope, we investigate the polar surface of single crystal YMnO{sub 3} sample in secondary electron (SE) mode. By slowing down the scanning speed of electron beam, the negative surface potential of YMnO{sub 3} can be realized, and the domain contrast can be correspondingly changed. Under this experimental condition, with the help of a homemade Faraday cup, the difference of intrinsic SE emission coefficients of antiparallel domains is measured to be 0.12 and the downward polarization domains show a larger SE emission ability. Our results indicate that the total SE emission of this material can be altered by changing the ratio of the antiparallel domains, which provide an avenue for device design with this kind of materials.

  15. 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.

  16. Cable Damage Detection System and Algorithms Using Time Domain Reflectometry

    SciTech Connect (OSTI)

    Clark, G A; Robbins, C L; Wade, K A; Souza, P R

    2009-03-24

    This report describes the hardware system and the set of algorithms we have developed for detecting damage in cables for the Advanced Development and Process Technologies (ADAPT) Program. This program is part of the W80 Life Extension Program (LEP). The system could be generalized for application to other systems in the future. Critical cables can undergo various types of damage (e.g. short circuits, open circuits, punctures, compression) that manifest as changes in the dielectric/impedance properties of the cables. For our specific problem, only one end of the cable is accessible, and no exemplars of actual damage are available. This work addresses the detection of dielectric/impedance anomalies in transient time domain reflectometry (TDR) measurements on the cables. The approach is to interrogate the cable using time domain reflectometry (TDR) techniques, in which a known pulse is inserted into the cable, and reflections from the cable are measured. The key operating principle is that any important cable damage will manifest itself as an electrical impedance discontinuity that can be measured in the TDR response signal. Machine learning classification algorithms are effectively eliminated from consideration, because only a small number of cables is available for testing; so a sufficient sample size is not attainable. Nonetheless, a key requirement is to achieve very high probability of detection and very low probability of false alarm. The approach is to compare TDR signals from possibly damaged cables to signals or an empirical model derived from reference cables that are known to be undamaged. This requires that the TDR signals are reasonably repeatable from test to test on the same cable, and from cable to cable. Empirical studies show that the repeatability issue is the 'long pole in the tent' for damage detection, because it is has been difficult to achieve reasonable repeatability. This one factor dominated the project. The two-step model-based approach is

  17. 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 μm for green light second harmonic generation. Spatial distribution of the efficiency of light frequency conversion confirmed the high homogeneity of the tailored domain patterns.

  18. Deletion of a gene cluster encoding pectin degrading enzymes in Caldicellulosiruptor bescii reveals an important role for pectin in plant biomass recalcitrance

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

    Chung, Daehwan; Pattathil, Sivakumar; Biswal, Ajaya K.; Hahn, Michael G.; Mohnen, Debra; Westpheling, Janet

    2014-10-10

    A major obstacle, and perhaps the most important economic barrier to the effective use of plant biomass for the production of fuels, chemicals, and bioproducts, is our current lack of knowledge of how to efficiently and effectively deconstruct wall polymers for their subsequent use as feedstocks. Plants represent the most desired source of renewable energy and hydrocarbons because they fix CO2, making their use carbon neutral. Their biomass structure, however, is a barrier to deconstruction, and this is often referred to as recalcitrance. Members of the bacterial genus Caldicellulosiruptor have the ability to grow on unpretreated plant biomass and thusmore » provide an assay for plant deconstruction and biomass recalcitrance. Using recently developed genetic tools for manipulation of these bacteria, a deletion of a gene cluster encoding enzymes for pectin degradation was constructed, and the resulting mutant was reduced in its ability to grow on both dicot and grass biomass, but not on soluble sugars. The plant biomass from three phylogenetically diverse plants, Arabidopsis (a herbaceous dicot), switchgrass (a monocot grass), and poplar (a woody dicot), was used in these analyses. These biomass types have cell walls that are significantly different from each other in both structure and composition. While pectin is a relatively minor component of the grass and woody dicot substrates, the reduced growth of the mutant on all three biomass types provides direct evidence that pectin plays an important role in biomass recalcitrance. Glycome profiling of the plant material remaining after growth of the mutant on Arabidopsis biomass compared to the wild-type revealed differences in the rhamnogalacturonan I, homogalacturonan, arabinogalactan, and xylan profiles. In contrast, only minor differences were observed in the glycome profiles of the switchgrass and poplar biomass. In conclusion, the combination of microbial digestion and plant biomass analysis provides a new and

  19. Deletion of a gene cluster encoding pectin degrading enzymes in Caldicellulosiruptor bescii reveals an important role for pectin in plant biomass recalcitrance

    SciTech Connect (OSTI)

    Chung, Daehwan; Pattathil, Sivakumar; Biswal, Ajaya K.; Hahn, Michael G.; Mohnen, Debra; Westpheling, Janet

    2014-10-10

    A major obstacle, and perhaps the most important economic barrier to the effective use of plant biomass for the production of fuels, chemicals, and bioproducts, is our current lack of knowledge of how to efficiently and effectively deconstruct wall polymers for their subsequent use as feedstocks. Plants represent the most desired source of renewable energy and hydrocarbons because they fix CO2, making their use carbon neutral. Their biomass structure, however, is a barrier to deconstruction, and this is often referred to as recalcitrance. Members of the bacterial genus Caldicellulosiruptor have the ability to grow on unpretreated plant biomass and thus provide an assay for plant deconstruction and biomass recalcitrance. Using recently developed genetic tools for manipulation of these bacteria, a deletion of a gene cluster encoding enzymes for pectin degradation was constructed, and the resulting mutant was reduced in its ability to grow on both dicot and grass biomass, but not on soluble sugars. The plant biomass from three phylogenetically diverse plants, Arabidopsis (a herbaceous dicot), switchgrass (a monocot grass), and poplar (a woody dicot), was used in these analyses. These biomass types have cell walls that are significantly different from each other in both structure and composition. While pectin is a relatively minor component of the grass and woody dicot substrates, the reduced growth of the mutant on all three biomass types provides direct evidence that pectin plays an important role in biomass recalcitrance. Glycome profiling of the plant material remaining after growth of the mutant on Arabidopsis biomass compared to the wild-type revealed differences in the rhamnogalacturonan I, homogalacturonan, arabinogalactan, and xylan profiles. In contrast, only minor differences were observed in the glycome profiles of the switchgrass and poplar biomass. In conclusion, the combination of microbial digestion and plant biomass analysis provides a new

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  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. 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

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

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

    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. Smart Grid Conceptual Actors/Data Flow Diagram- Cross Domain Network Focued- Open SG/SG-Network TF (523.02 KB) More Documents & Publications Report to NIST on the Smart Grid Interoperability Standards Roadmap SG

  12. Domain wall motion driven by spin Hall effect—Tuning with in-plane magnetic anisotropy

    SciTech Connect (OSTI)

    Rushforth, A. W.

    2014-04-21

    This letter investigates the effects of in-plane magnetic anisotropy on the current induced motion of magnetic domain walls in systems with dominant perpendicular magnetic anisotropy, where accumulated spins from the spin Hall effect in an adjacent heavy metal layer are responsible for driving the domain wall motion. It is found that that the sign and magnitude of the domain wall velocity in the uniform flow regime can be tuned significantly by the in-plane magnetic anisotropy. These effects are sensitive to the ratio of the adiabatic and non-adiabatic spin transfer torque parameters and are robust in the presence of pinning and thermal fluctuations.

  13. 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.

  14. 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...

  15. 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.

  16. Compliant ferroelastic domains in epitaxial Pb(Zr,Ti)O{sub 3} thin films

    SciTech Connect (OSTI)

    Feigl, L.; McGilly, L. J.; Sandu, C. S.; Setter, N.

    2014-04-28

    Ordered patterns of highly compliant ferroelastic domains have been created by use of tensile strained epitaxial Pb(Zr,Ti)O{sub 3} thin films, of very low defect density, grown on DyScO{sub 3} substrates. The effect of 180° switching on well-ordered a/c 90° domain patterns is investigated by a combination of transmission electron microscopy, piezoelectric force microscopy, and X-ray diffraction. It is shown that ferroelastic a-domains, having an in-plane polarization, can be created and completely removed on a local level by an out-of-plane electric field. The modifications of the ferroelastic domain pattern can be controlled by varying the parameters used during switching with a piezoresponse force microscope to produce the desired arrangement.

  17. 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.

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

    Broader source: Energy.gov [DOE]

    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

  19. Structure of the N-terminal dimerization domain of CEACAM7 (Journal...

    Office of Scientific and Technical Information (OSTI)

    SciTech Connect Search Results Journal Article: Structure of the N-terminal dimerization domain of CEACAM7 Citation Details In-Document Search Title: Structure of the N-terminal ...

  20. Coiled-coil dimerization of the LOV2 domain of the blue-light...

    Office of Scientific and Technical Information (OSTI)

    blue-light photoreceptor phototropin 1 from Arabidopsis thaliana Citation Details In-Document Search Title: Coiled-coil dimerization of the LOV2 domain of the blue-light ...

  1. The TLR4 agonist fibronectin extra domain A is cryptic, exposed...

    Office of Scientific and Technical Information (OSTI)

    matrix cancer vaccine Citation Details In-Document Search Title: The TLR4 agonist fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer ...

  2. 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.

  3. Identification and characterization of riboflavin-binding proteins in human circulation

    SciTech Connect (OSTI)

    Innis-Whitehouse, W.S.A.

    1988-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis and binding was observed to vary over a greater than 10-fold range. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly, although FMN and photo-chemical degradation products were more tightly bound. Most of the binding occurred in the gamma-globulin fraction and was attributed to immunoglobulins because the binding proteins and immunoglobulins copurified using various methods, were removed by treatment of plasma with protein A-agarose, and were coincident upon immuno-electrophoresis followed by autoradiography to detect (2-{sup 14}C)-riboflavin. Binding differences among plasma samples were reflected in the binding recovered with the immunoglobulin fractions; however, there was not a direct relationship between the amount of immunoglobulin and the amount of (2-{sup 14}C)riboflavin bound. Hence, it appeared that the binding was due to a subfraction of immunoglobulins.

  4. Strong and Reversible Binding of Carbon Dioxide in a Green Metal...

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

    Strong and Reversible Binding of Carbon Dioxide in a Green Metal-Organic Framework Previous Next List Jeremiah J. Gassensmith, Hiroyasu Furukawa, Ronald A. Smaldone, Ross S. ...

  5. 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

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Evapotranspiration Within the Groundwater Model Domain of the Tuba City, Arizona, Disposal Site Interim Report

    SciTech Connect (OSTI)

    None, None

    2015-03-01

    The revised groundwater model includes estimates of evapotranspiration (ET). The types of vegetation and the influences of ET on groundwater hydrology vary within the model domain. Some plant species within the model domain, classified as phreatophytes, survive by extracting groundwater. ET within these plant communities can result in a net discharge of groundwater if ET exceeds precipitation. Other upland desert plants within the model domain survive on meteoric water, potentially limiting groundwater recharge if ET is equivalent to precipitation. For all plant communities within the model domain, excessive livestock grazing or other disturbances can tip the balance to a net groundwater recharge. This task characterized and mapped vegetation within the groundwater model domain at the Tuba City, Arizona, Site, and then applied a remote sensing algorithm to estimate ET for each vegetation type. The task was designed to address five objectives: 1. Characterize and delineate different vegetation or ET zones within the groundwater model domain, focusing on the separation of plant communities with phreatophytes that survive by tapping groundwater and upland plant communities that are dependent on precipitation. 2. Refine a remote sensing method, developed to estimate ET at the Monument Valley site, for application at the Tuba City site. 3. Estimate recent seasonal and annual ET for all vegetation zones, separating phreatophytic and upland plant communities within the Tuba City groundwater model domain. 4. For selected vegetation zones, estimate ET that might be achieved given a scenario of limited livestock grazing. 5. Analyze uncertainty of ET estimates for each vegetation zone and for the entire groundwater model domain.

  13. 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.

  14. 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.

  15. 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.

  16. Integrative curriculum reform, domain dependent knowing, and teachers` epistemological theories: Implications for middle-level teaching

    SciTech Connect (OSTI)

    Powell, R.R.

    1998-12-01

    Integrative curriculum as both a theoretical construct and a practical reality, and as a theme-based, problem-centered, democratic way of schooling, is becoming more widely considered as a feasible alternative to traditional middle-level curricula. Importantly for teaching and learning, domain dependence requires teachers to view one area of knowledge as fully interdependent with other areas of knowledge during the learning process. This requires teachers to adopt personal epistemological theories that reflect integrative, domain dependent knowing. This study explored what happened when teachers from highly traditional domain independent school settings encountered an ambitious college-level curriculum project that was designed to help the teachers understand the potential that integrative, domain dependent teaching holds for precollege settings. This study asked: What influence does an integrative, domain dependent curriculum project have on teachers` domain independent, epistemological theories for teaching and learning? Finding an answer to this question is essential if we, as an educational community, are to understand how integrative curriculum theory is transformed by teachers into systemic curriculum reform. The results suggest that the integrative curriculum project that teachers participated in did not explicitly alter their classroom practices in a wholesale manner. Personal epistemological theories of teachers collectively precluded teachers from making any wholesale changes in their individual classroom teaching. However, teachers became aware of integrative curriculum as an alternative, and they expressed interest in infusing integrative practices into their classrooms as opportunities arise.

  17. 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.

  18. 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.

  19. 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.

  20. Domain imaging on multiferroic BiFeO{sub 3}(001) by linear and circular dichroism in threshold photoemission

    SciTech Connect (OSTI)

    Sander, Anke; Christl, Maik; Chiang, Cheng-Tien; Alexe, Marin; Widdra, Wolf

    2015-12-14

    We demonstrate ferroelectric domain imaging at BiFeO{sub 3}(001) single crystal surfaces with laser-based threshold photoemission electron microscopy (PEEM). Work function differences and linear dichroism allow for the identification of the eight independent ferroelectric domain configurations in the PEEM images. There, the determined domain structure is consistent with piezoresponse force microscopy of the sample surface and can also be related to the circular dichroic PEEM images. Our results provide a method for efficient mapping of complex ferroelectric domains with laser-excited PEEM and may allow lab-based time-resolved studies of the domain dynamics in the future.

  1. Conformational Variability of Organophosphorus Hydrolase upon Soman and Paraoxon Binding

    SciTech Connect (OSTI)

    Gomes, Diego Eb; Lins, Roberto D.; Pascutti, Pedro G.; Lei, Chenghong; Soares, Thereza A.

    2011-12-31

    The bacterial enzyme organophosphorus hydrolase (OPH) exhibits both catalytic and substrate promiscuity. It hydrolyzes bonds in a variety of phosphotriester (P-O), phosphonothioate (P-S), phosphofluoridate (P-F) and phosphonocyanate (F-CN) compounds. However, its catalytic efficiency varies markedly for different substrates, limiting the broad-range application of OPH as catalyst in the bioremediation of pesticides and chemical war agents. In the present study, pK{sub a} calculations and multiple explicit-solvent molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of OPH bound to two substrates hydrolyzed with very distinct catalytic efficiencies: the nerve agent soman (O-pinacolyl-methyl-phosphonofluoridate) and the pesticide paraoxon (diethyl p-nitrophenyl phosphate). pK{sub a} calculations for the substrate-bound and unbound enzyme showed a significant pK{sub a} shift from standard values ({Delta}pK{sub a} = {+-} 3 units) for residues 254His and 275Arg. MD simulations of the doubly protonated 254His revealed a dynamic hydrogen bond network connecting the catalytic residue 301Asp via 254His to 232Asp, 233Asp, 275Arg and 235Asp, and is consistent with a previously postulated proton relay mechanism to ferry protons away from the active site with substrates that do not require activation of the leaving group. Hydrogen bonds between 301Asp and 254His were persistent in the OPH-paraoxon complex but not in the OPH-soman one, suggesting a potential role for such interaction in the more efficient hydrolysis of paraoxon over soman by OPH. These results are in line with previous mutational studies of residue 254His, which led to an increase of the catalytic efficiency of OPH over soman yet decreased its efficiency for paraoxon. In addition, comparative analysis of the molecular trajectories for OPH bound to soman and paraoxon suggests that binding of the latter facilitates the conformational transition of OPH from the

  2. Super-Grid Modeling of the Elastic Wave Equation in Semi-Bounded Domains

    SciTech Connect (OSTI)

    Petersson, N. Anders; Sjögreen, Björn

    2014-10-01

    Abstract

    We develop a super-grid modeling technique for solving the elastic wave equation in semi-bounded two- and three-dimensional spatial domains. In this method, waves are slowed down and dissipated in sponge layers near the far-field boundaries. Mathematically, this is equivalent to a coordinate mapping that transforms a very large physical domain to a significantly smaller computational domain, where the elastic wave equation is solved numerically on a regular grid. To damp out waves that become poorly resolved because of the coordinate mapping, a high order artificial dissipation operator is added in layers near the boundaries of the computational domain. We prove by energy estimates that the super-grid modeling leads to a stable numerical method with decreasing energy, which is valid for heterogeneous material properties and a free surface boundary condition on one side of the domain. Our spatial discretization is based on a fourth order accurate finite difference method, which satisfies the principle of summation by parts. We show that the discrete energy estimate holds also when a centered finite difference stencil is combined with homogeneous Dirichlet conditions at several ghost points outside of the far-field boundaries. Therefore, the coefficients in the finite difference stencils need only be boundary modified near the free surface. This allows for improved computational efficiency and significant simplifications of the implementation of the proposed method in multi-dimensional domains. Numerical experiments in three space dimensions show that the modeling error from truncating the domain can be made very small by choosing a sufficiently wide super-grid damping layer. The numerical accuracy is first evaluated against analytical solutions of Lamb’s problem, where fourth order accuracy is observed with a sixth order artificial dissipation. We then use successive grid refinements to study the numerical accuracy in the more

  3. 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.

  4. Superlattices assembled through shape-induced directional binding

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

    Lu, Fang; Yager, Kevin G.; Zhang, Yugang; Xin, Huolin; Gang, Oleg

    2015-04-23

    Organization of spherical particles into lattices is typically driven by packing considerations. Although the addition of directional binding can significantly broaden structural diversity, nanoscale implementation remains challenging. Here we investigate the assembly of clusters and lattices in which anisotropic polyhedral blocks coordinate isotropic spherical nanoparticles via shape-induced directional interactions facilitated by DNA recognition. We show that these polyhedral blocks—cubes and octahedrons—when mixed with spheres, promote the assembly of clusters with architecture determined by polyhedron symmetry. Moreover, three-dimensional binary superlattices are formed when DNA shells accommodate the shape disparity between nanoparticle interfaces. The crystallographic symmetry of assembled lattices is determined bymore » the spatial symmetry of the block’s facets, while structural order depends on DNA-tuned interactions and particle size ratio. Lastly, the presented lattice assembly strategy, exploiting shape for defining the global structure and DNA-mediation locally, opens novel possibilities for by-design fabrication of binary lattices.« less

  5. 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.

  6. rVISTA for Comparative Sequence-Based Discovery of Functional Transcription Factor Binding Sites

    SciTech Connect (OSTI)

    Loots, Gabriela G.; Ovcharenko, Ivan; Pachter, Lior; Dubchak, Inna; Rubin, Edward M.

    2002-03-08

    Identifying transcriptional regulatory elements represents a significant challenge in annotating the genomes of higher vertebrates. We have developed a computational tool, rVISTA, for high-throughput discovery of cis-regulatory elements that combines transcription factor binding site prediction and the analysis of inter-species sequence conservation. Here, we illustrate the ability of rVISTA to identify true transcription factor binding sites through the analysis of AP-1 and NFAT binding sites in the 1 Mb well-annotated cytokine gene cluster1 (Hs5q31; Mm11). The exploitation of orthologous human-mouse data set resulted in the elimination of 95 percent of the 38,000 binding sites predicted upon analysis of the human sequence alone, while it identified 87 percent of the experimentally verified binding sites in this region.

  7. 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

  8. Position specific variation in the rate of evolution intranscription factor binding sites

    SciTech Connect (OSTI)

    Moses, Alan M.; Chiang, Derek Y.; Kellis, Manolis; Lander, EricS.; Eisen, Michael B.

    2003-08-28

    The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Here we analyze the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikataeto study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artifacts of computational motif finding algorithms. As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative

  9. Detection of ferromagnetic domain wall pinning and depinning with a semiconductor device

    SciTech Connect (OSTI)

    Malec, Chris E.; Bennett, Brian R.; Johnson, Mark B.

    2015-12-21

    We demonstrate the detection of a ferromagnetic domain wall using a nanoscale Hall cross. A narrow permalloy wire is defined lithographically on top of a Hall cross fabricated from an InAs quantum well. The width of the Hall cross (500 nm–1 μm) is similar to the width of the ferromagnetic wire (200–500 nm), and a geometric pinning site is fabricated in the ferromagnetic wire to trap a domain wall within the area of the Hall cross. The devices provide a signal that is often the same order of magnitude as the offset Hall voltage when a domain wall is located above the Hall cross, and may be useful for memory applications. Different geometries for the Hall cross and ferromagnetic wire are tested, and radiofrequency pulses are sent into the wire to demonstrate current driven domain wall motion. Further changes to the Hall bar geometry with respect to the wire geometry are investigated by numerical computation. A large gain in signal is seen for Hall bars only slightly wider than the ferromagnetic wires as compared to those twice as wide, as well as a larger sensitivity to the exact position of the domain wall with respect to the center of the Hall cross.

  10. 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.

  11. Crystal structure studies of NADP{sup +} dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain

    SciTech Connect (OSTI)

    Kumar, S.M.; Pampa, K.J.; Manjula, M.; Abdoh, M.M.M.; Kunishima, Naoki; Lokanath, N.K.

    2014-06-20

    Highlights: • We determined the structure of isocitrate dehydrogenase with citrate and cofactor. • The structure reveals a unique novel terminal domain involved in dimerization. • Clasp domain shows significant difference, and catalytic residues are conserved. • Oligomerization of the enzyme is quantized with subunit-subunit interactions. • Novel domain of this enzyme is classified as subfamily of the type IV. - Abstract: NADP{sup +} dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP{sup +} was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH’s. And, small domain and clasp domain showing significant differences when compared to other IDH’s of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH’s. Also, helices/beta sheets are absent in the small domain, when compared to other IDH’s of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit–subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

  12. Stability of a pinned magnetic domain wall as a function of its internal configuration

    SciTech Connect (OSTI)

    Montaigne, F.; Duluard, A.; Briones, J.; Lacour, D.; Hehn, M.; Childress, J. R.

    2015-01-14

    It is shown that there are many stable configurations for a domain wall pinned by a notch along a magnetic stripe. The stability of several of these configurations is investigated numerically as a function of the thickness of the magnetic film. The depinning mechanism depends on the structure of the domain wall and on the thickness of the magnetic film. In the case of a spin-valve structure, it appears that the stray fields emerging from the hard layer at the notch location influence the stability of the micromagnetic configuration. Different depinning mechanisms are thus observed for the same film thickness depending on the magnetization orientation of the propagating domain. This conclusion qualitatively explains experimental magnetoresistance measurements.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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